Clinical Judgement USMLE Step 3

CLINICAL JUDGMENT
Step 3 Review
360-degree exam prep for the NEW USMLE Step 3
Strong focus on patient management
Foundational science correlations for key diseases
Typical and atypical presentations
Medical concepts interrelated by their connecting point features
Integrated CCS cases and advice
George P. Lee

USMLE Step 3 Review

Notice
Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required.The authors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide informa­ tion that is complete and generally in accord with the standards accepted at the time of publica­ tion. However, in view of the possibility of human error or changes in medical sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or
infrequently used drugs.

Clinical Judgment USMLE Step 3 Review
George P. Lee, MD
Chicago> Illinois
Me
Graw
Medical Education
New York • Chicago • San Francisco • Athens • London • Madrid • Mexico City Milan • New Delhi • Singapore • Sydney • Toronto
Hill

Clinical Judgment USMLE Step 3 Review
Copyright © 2014 by McGraw-Hill Education. All rights reserved. Printed in the United States of America. Except as permitted under the United States Copyright Act of 1976, no part of this publica­ tion may be reproduced or distributed in any form or by any means, or stored in a data base or retrieval system, without the prior written permission of the publisher.
1234567890 QVS/QVS 19 18 17 16 1514
ISBN-13\: 978-0-07-173908-5 MHID\: 0-07-173908-4
This book was set in Minion Pro Regular by MPS Limited.
Hie editors were Catherine A. Johnson and Karen G. Edmonson.
The production supervisor was Richard Ruzycka.
Project management was provided by Vipra Fauzdar at MPS Limited. The cover designer was Thomas De Pierro.
Image credit\: Biddiboo/Getty Images.
Quad Graphics Versailles was printer and binder.
This book is printed on acid-free paper.
Library of Congress Cataloging-in-Publication Data
Lee, George P. (George Park), 1972- author.
Clinical judgment USMLE Step 3 review / George P. Lee.
p.; cm.
Includes index.
ISBN 978-0-07-173908-5 (pbk.\: alk. paper)—ISBN 0-07-173908-4 (pbk.\: alk. paper)
I. Title.
[DNLM\: 1. Diagnosis—Examination Questions. 2. Diagnosis—Outlines. 3. Clinical Medicine—methods—
Examination Questions. 4. Clinical Medicine—methods—Outlines. 5. Decision Making—Examination Questions. 6. Decision Making—Outlines. 7. Decision Making, Computer-Assisted—Examination Questions. 8. Decision Making, Computer-Assisted—Outlines. 9. Judgment—Examination Questions. 10. Judgment—Outlines. WB 18.2]
RB38.25 616.07'5076—dc23
2014014055
McGraw-Hill books are available at special quantity discounts to use as premiums and sales promotions, or for use in corporate training programs. To contact a representative, please visit the Contact Us pages at www.mhprofessional.com.

To my mother andfatherfor their support, encouragement, and most importantly,for their unconditional (agape) love.

Contents
Preface........................................................................................... ix Acknowledgments....................................................................... xi Introduction............................................................................... xiii
CHAPTER 1
Allergy and Immunology.........................................................1
CHAPTER 2 Biostatistics............................................................................ 11
CHAPTER 3 Cardiology..............................................................................17
CHAPTER 4 Dermatology......................................................................... 47
CHAPTER 5 EKG......................................................................................... 57
CHAPTER 6 Endocrinology....................................................................... 65
CHAPTER 7 Ethics...................................................................................... 87
CHAPTER 8 Gastroenterology.................................................................. 93
CHAPTER 9 Gynecology......................................................................... 107
CHAPTER 10 Hematology......................................................................... 125
CHAPTER 11 Neurology...........................................................................139
CHAPTER 12 Obstetrics...........................................................................159
CHAPTER 13 Ophthalmology....................................................................193
CHAPTER 14 Orthopedics........................................................................ 203
CHAPTER 15
Otolaryngology—Head and Neck..................................... 213
CHAPTER 16 Psychiatry............................................................................ 225
CHAPTER 17 Pulmonary........................................................................... 241
CHAPTER 18
Renal and Genitourinary..................................................... 269
CHAPTER 19 Rheumatology..................................................................... 281
CHAPTER 20 Vascular................................................................................295
APPENDICES
A Pattern Recognition.................................................... 303
B Rapid-fire Clinical Judgments.................................... 313 C Factoids....................................................................... 325 D Key Lab Values............................................................ 337 E Final Pearls................................................................... 339
Index....................................................................................341
VII

Preface
Medical information is constantly growing and changing, and the nature of the USMLE Step 3 is no exception. It is nearly impos­ sible to know every single fact and concept in medicine, hence the reason for specialties and subspecialties. Therefore, the con­ cept of this book is not to necessarily memorize every single fact and concept, but rather to attain a certain skill\: clinical judgment. Once you develop and nurture your clinical judgment skills, you can position yourself at a higher percentage of answering exam questions correctly, and you will also make good decisions in your daily patient care.
The next question you have to consider is, “How do I know I’ve reached sound clinical judgment?” It is just like when the boiling point of water is reached at 100°C, the water starts to bubble. You may be at 86°C or 98°C in your preparation now, but if you continue to work hard, digest and integrate the information, and think with a critical lens, then at one point, the water will boil and you will notice that you are making good decisions on the majority of your practice questions. Remember that developing your clinical judgment skills does not come overnight. It is a process that takes time like any developing skill. Therefore, it is important to start early in your exam preparation.
Tire design of this book will enable you to see typical and atypical presentations in the Clinical Features and Pattern Recognition sections. Basic science concepts (foundational
science) are correlated with the clinical topics. The goal of the basic science concepts is to help you understand the disease in a broader context. In addition, medical information from different specialties is interrelated by the Connecting Point feature of this book. At this stage of your medical journey, you should know the basic flow of patient care\: history and physical —> diagnostic tests—>treatment.TheNextStepsectionofthisbookwillshift your thinking about patient management helping you prioritize your thoughts. (For example, in tension pneumothorax it is im­ portant to perform an immediate decompression of the lung be­ fore ordering a chest x-ray.) Finally, it is imperative to start your computer-based case simulations (CCS) preparation early, and therefore the CCS component is integrated in the majority of the chapters.
A successful outcome on Step 3 is largely determined by your preparation and attitude. Remember, by the closure of your exam preparation you may still feel that you do not know enough, but the point of this book is to develop your clinical judgment skills. It is my hope that once you achieve sound clini­ cal judgment, you will be able to pass the exam and carry over this lifelong skill into your field of practice. Good luck on the USMLE Step 3 exam!
George R Lee, M.D. Chicago, Illinois
IX

Acknowledgments
I would like to take this opportunity to thank my editor, Catherine Johnson, for all her encouragement and for believ­ ing in this project. I would also like to recognize my other edi­ tor, Karen G. Edmonson, for her counsel and her editorial skills in preparing the manuscript for production. I want to thank my production supervisor, Richard Ruzycka, for his invaluable
assistance in preparation of the book. I am also grateful to Vipra Fauzdar at MPS for her professionalism and remarkable talents for overseeing the composition of the book. Finally, I am in­ debted to my publisher, McGraw-Hill, for providing me a plat­ form to make a contribution to medicine and for their strong commitment to high quality publishing in the healthcare field.
XI

Introduction EXAM LOGISTICS
I PURPOSE
The purpose of the USMLE Step 3 exam is to assess the exam­ inee’s ability to understand and apply medical knowledge that is considered essential for the unsupervised practice of medicine. In other words, this can be a challenging test.
I GENERAL INFORMATION
For a detailed description of the USMLE Step 3 exam, includ­ ing physician tasks, objectives, content, and CCS overview, please review the USMLE Step 3 Content Description and Gen­ eral Information. It is also recommended to review the USMLE Bulletin of Information to understand eligibility, scoring, and score reporting. Finally, it is essential to review the USMLE Step 3 practice materials that are provided to you upon reg­ istration, or you can download the information by visiting www.usmle.org.
I REGISTRATION
To apply for the Step 3 exam, please follow the instructions on the Federation of State Medical Boards (FSMB) website at www .fsmb.org. Starting August 2014, the state board sponsorship for Step 3 will be discontinued.
I EXAMBREAKDOWN
The USMLE Step 3 is a 2-day examination that comprises a total of 480 multiple-choice questions and 12 CCS cases.
Day 1
• Total of 336 multiple-choice questions.
• Total of 7 blocks.
• 48 questions per block.
• 60 minutes per block. If you finish any block early, any re­ maining time may be added to your total break time.
• Total of 7 hours of testing.
• A minimum of 45 minutes break time.
• 15 minute optional tutorial. It is highly recommended to do an audio calibration and to adjust the monitor resolu­ tion to a minimum of 1024 x 768. If you finish the tutorial early, any remaining time may be added to your total break time.
• Expect the day to last <8 hours for day 1.
Day 2
• Total of 144 multiple-choice questions.
• Total of 4 blocks.
• 36 questions per block.
• 45 minutes per block. If you finish any block early, any re­ maining time may be added to your total break time.
• Total of 3 hours for the first four blocks.
• 12 CCS cases follow the multiple-choice questions with a total of 4 hours to complete all the cases.
• A minimum of 45 minutes break time.
• 15 minute optional tutorial for the CCS. If you finish the tu­ torial early, any remaining time may be added to your total break time.
• Expect the day to last <8 hours for day 2.
I PASSINGUSMLESTEP3
Passing the Step 3 exam is imperative. Consider three reasons\: (1) if you fail the exam, you might compromise your eligibil­ ity to be reappointed to the next postgraduate year position, (2) you might compromise your eligibility for state licensure based on the number of USMLE attempts and time limit for completing all Steps, and (3) “Do you really want to take another two grueling days of examinations?” For the initial medical licensure process, the following table lists the maxi­ mum number of USMLE attempts for each state. Additional postgraduate training may be required in certain states if the maximum attempts are exceeded for medical licensure. For further information regarding state-specific requirements for medical licensure, please visit www.fsmb.org.
Xlll

XiV
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Maximum Number of USMLE Attempts by State
33
USMLE Attempts
3 per Step
3atStep3 No limit No limit
3 per Step 4 per Step 3 per Step No limit
3 per Step 3atStep3 3atStep3
No limit 3atStep3
6 per Step
3 per Step
7 total at all Steps
State Alabama
Alaska
Arizona Arkansas California Colorado Connecticut Delaware Washington, DC Florida
Georgia
Hawaii Idaho Illinois Indiana Iowa
Kansas Kentucky
USMLE Attempts
10 total at all Steps
2 per Step No limit
3 per Step 4 at Step 3 No limit No limit
6 per Step 3atStep3 No limit
3 per Step
No limit
2 per Step
5 total at all Steps
3 per Step
6atStep1;6at Step 2; 3 at Step 3
No limit
4 per Step
State Louisiana
Maine Maryland Massachusetts Michigan Minnesota Mississippi Missouri Montana Nebraska Nevada
New Hampshire New Jersey New Mexico New York
North Carolina
North Dakota Ohio
USMLE Attempts
No limit at Step 1; 4 at Step 2; 4 at Step 3
3 at Step 3 4 per Step 3 at Step 3 No limit
3 per Step
3 at Step 3
3 at Step 3
3 at Step 3
4 per Step
9 total at all Steps with Step 3 in no more than 3 attempts
3 per Step 5 at Step 3 6 per Step No limit
3 per Step
3 per Step 4 per Step
State Oklahoma
Oregon Pennsylvania Puerto Rico Rhode Island South Carolina South Dakota Tennessee Texas
Utah Vermont
Virginia Washington West Virginia Wisconsin Wyoming
EXAM PREPARATION
I INTRODUCTION
usually result in a successful outcome, therefore, it is important to start early. You may have your own strategy, but make it me­ thodical and take ownership of your valuable time and efforts. The following is a recommended approach, and if you follow these 3 basic principles, then I believe that you have a higher percentage of passing Step 3.
Stage I\: Strengthen Your Knowledge Base
Physicians are trained to become highly evolved creatures of learning. Learning has transitioned from the lectures in the class­ room to the clinical wards during medical school. Once a resi­ dent, he or she has to learn under time constraints and is expected to pass Step 3 and show overall improvement in the in-training exams. Once residency is over, the practicing physician has to pass his or her specialty board, continue with lifelong learning through the Maintenance of Certification (MOC), and learn in a different setting (eg, academics, private sector). Throughout each stage of learning, the only constant is the physicians ability to un­ derstand, extract information, and apply medical knowledge. At this stage of your training and onward, time is valuable and self­ learning is imperative. Therefore, use your time wisely and care­ fully select materials that will maximize your learning potential.
I STRATEGY
From day 1 of your preparation to the last exam question, you need to take control of your destiny, which is to pass Step 3. In general, a systematic approach to your preparation will
• •
The bottom line is that you have to put in the time, there are no tricks.
Make sure that the time you put in is efficient, effective, and exciting (“Triple E’s”).
• Efficient time means mastering a chapter or section of a chapter that is related to the rotation you are on, for ex­ ample, mastering the cardiology chapter by the end of the cardiology rotation. If you have a lot of time on an elective rotation, then you should master 2 to 3 chapters. If you are on a hard rotation like ICU, then do parts of a chapter such as the “EKG Review” section. If you find pockets of time during your schedule, master another section. Re­ member that the time you put in will all add up. You don’t have to go in order, but you do have to take control of your preparation, and be sure to monitor your progress.

• Effective time means being extremely focused. For exam­ ple, after coming home from work, give your undivided attention for 1 complete hour of Step 3. On the way to work in the morning, try to remember, recite, and repeat what you learned the night before.
• The time you put in should be exciting, don’t look at it like “work.” Examples may include personalizing your prepa­ ration, summarizing tables, photocopying a table and car­ rying it with you during the day, or after seeing a patient with a certain disease making sure you read about that disease the same day.
• It is important to have good momentum in your prepara­ tion. During your preparation you want to keep pushing forward with good velocity. You can remember this con­ cept from the fact that momentum is proportional to the velocity from the equation\: momentum (p) = mass (m) x velocity (v). If you find that some sections are harder than others, then move on and take a break from that section and come back with a renewed sense of purpose and finish the section in pieces in order to maintain good momentum.
Stage II\: Transition into Questions
• After beefing up your knowledge base, it is important to ap­ ply your knowledge with questions.
• After reading all the chapters and the appendices, it is im­ portant to get your mind frame into a question mode style of thinking. It is also important to assess your timing. You have 1 minute and 15 seconds per question.
• Remember that you don’t have to do 1,000 practice questions to be successful on the exam.
• It is highly recommended to do the USMLE practice ques­ tions with the timing on. The practice questions will be simi­ lar to the actual format of the exam.
Stage III\: Final Review
• It is important to leave enough time for your final review.
• All the information must be consolidated, assimilated, and integrated.
• At this point, it is important to start firing those neurons to make hardwire connections because everything must stick.
1 THEPEDAGOGY
The following features will enhance and nurture your clinical judgment skills and maximize your ability to interrelate medical information. Once you embrace all the features of this book you will be able to have a deeper understanding of the material and ultimately success on Step 3.
Keywords Review\:
At the beginning of each chapter is a description of medical terms. Some of the terms may not be seen in the chapter, but they will be mentioned to highlight the specialty.
introduction\:
When appropriate, the introduction of each topic discusses the etiology and pathophysiology of the disease.
Clinical Features\:
Typical and atypical presentations are presented in this section. Because systemic diseases can present in a disarrayed fashion, the Clinical Features section incorporates a relative head-to-toe presentation to help you organize your thoughts.
Next Step\:
A strong focus on patient management is presented in this sec­ tion. The Next Step section provides a logical sequential ap­ proach that will help you prioritize your thoughts. By having an organized thought process, you can tackle any clinical situa­ tion in a systematic approach. During your review process, you may find steps within steps in this section, but this entire sec­ tion should be viewed as a working paradigm that ultimately incorporates the standard of care. Just like in the real world, having a working paradigm as part of your mental framework allows you to account for other factors in patient management (eg, comorbidities, available resources, insurance). Once you train your thoughts to figure out what the most important steps are in management, then you develop sharper clinical judgment skills.
Option-based Management\:
The option-based management is described in the Next Step section and provides alternatives to patient management. Remember that there is more than one way to appropriately treat a patient.
Short- and Long-term Management\:
Short- and long-term management are described in the Next Step section and mentioned in the CCS tips. By integrating this type of management, you begin to understand how to “bridge your therapy” by addressing any acute issues (eg, pain) along with long-term issues (eg, prevention). With this approach, you become more comprehensive in patient management. In addi­ tion, this style of approach will help prioritize your thoughts for the CCS cases.
Follow-Up/Disposition\:
The Follow-up section describes the follow-up care for patients for topics that would most likely be seen in the office. The Dis­ position section describes the placement of the patient that is typically seen in the emergency department. This section should engage you to think about topics that are emergent or office-based during the exam.
Pearls\:
This section provides “pearls of wisdom” for the particular topic in addition to serving as an umbrella for other features that are considered pearls (eg, caveats,foundational points, CCS tips, clin­ ical judgments, connecting points). Once you have read through the Introduction, Clinical Features, Next Step, Follow-up/ Disposition, and Pearls section for each topic, then you begin
INTRODUCTION XV

XVI CLINICAL JUDGMENT USMLE STEP 3 REVIEW
to have a broader perspective of the disease. This is where your clinical judgment begins to be refined.
Caveats\:
Caveats are presented in the Pearls section and serve to give precautions or warnings for that particular topic.
Foundational Points\:
Foundational points are presented in the Pearls section and describe a basic science concept in reference to that particular clinical topic. Foundational science concepts may also be found in the Keywords Review (eg, Allergy and Immunology).
Connecting Points\:
The beauty of medicine is that everything truly is interconnected. By connecting one seemingly unlikely piece of knowledge to an­ other piece of medical knowledge, you begin to see the sym­ phony or orchestration of the human body as a whole. One of the goals of connecting points is to strengthen your memory of one topic to another topic by “neuronal wiring.” Each connect­ ing point will have a reference for you to make another medi­ cal connection. By the end of your final review (Stage III), you should be able to move quickly and interrelate all the connect­ ing points without hesitation.
Clinical Judgments (CJ)\:
CJ questions are presented in the Pearls section. Initially, try to answer the CJ without looking at the answer.
CCS Tips\:
CCS tips are presented in the Pearls section and offer you tips on that particular topic.
CCS Cases\:
At the end of each chapter, some CCS cases will be offered. This is an opportunity for you to understand and integrate your CCS
EXAM EXECUTION
1 THEQUARTERMETHOD
It is important to be conscious about your timing during the exam. You may be a naturally slow reader or you may be a relatively fast reader, but you might get stuck on time because you spent too much time on a question or you are just plain tired. Therefore, it is essential to have landmarks. Just as a sur­ geon needs anatomic landmarks for surgery, you need to have time landmarks for the exam. The quarter method takes the time and number of questions per block and divides it by 4. Therefore, you have 4 quarters or 4 intervals for which you should be on target or may need to catch up. Every quarter should serve as a reference point. This method can be applied
preparation early. Do not wait until the last minute to prepare the CCS component of the exam. Try to get your hands on a computer and practice the CCS software with each chapter re­ view so that you can become proficient.
Pattern Recognition\:
A special section on Pattern Recognition appears as Appendix A. Both typical and atypical presentations are described, and the concept of this section is to develop your gut instinct about a disease. Although it is not recommended to memorize every feature of each disease (you might drive yourself crazy!), begin incorporating this section in Stage I of your preparation.
Rapid-fire Clinical Judgments\:
Rapid-fire clinical judgment questions appear in Appendix B. Begin incorporating this section into Stage I and Stage II ofyour preparation.
Factoids\:
Factoids are pure medical facts, and appear in Appendix C. This section should serve to strengthen your knowledge base, and you should begin incorporating this section during Stage I of your exam preparation.
Key Lab Values\:
In your last 1 to 2 days prior to the exam, you should know some basic lab values. These are presented in Appendix D. It is recom­ mended to take this extra step in learning some basic lab values to improve your efficiency with exam questions and to maintain a good rhythm during the course of each exam block.
Final Pearls\:
This section appears as Appendix E and should serve as your last piece of review prior to your examination.
to any exam, and it works well if you answer the questions in sequential order. It is recommended not to skip more than 5 questions because you have to take into account the time that you did not spend on the skipped questions. For example, if you skip 5 questions and do them at the end of the block, then you have to account for 6 minutes and 15 seconds since you have 1 minute and 15 seconds per question. If you apply the quarter method on the exam you will have a sense of control during each block. Remember, do not let the exam control you, you control the exam. The following depiction is a clock with landmarks that encompass the time remaining (Tr) and the target question (Tq). If the landmarks are hard to remem­ ber, you can always draw this picture on the dry-erase board provided on the exam. Try the quarter method during Stage II of your preparation.

60-minute block
45-minute block
Block 4
20-minute lunch break Block 5
Block 6
10-minute break Block 7
Option 3\: Day 1
Block 1
Block 2
Block 3
10-minute break Block 4
25-minute lunch break Block 5
Block 6 10-minute break Block 7
1 FUEL
Block 4
5-minute break CCSCases1-2 10-minute lunch break CCS Cases 3-6 10-minute break
CCS Cases 7-10 5-minute break
Cases 11-12
Day 2
Block 1
Block 2
Block 3 10-minute break Block 4
CCS Cases 1-2 20-minute lunch break CCS Cases 3-6 10-minute break
CCS Cases 7-10 5-minute break CCS-Cases 11-12
I THEAUDIBLEPLAN
Prior to the exam, you should devise your own plan on how to tackle the blocks and allocate your break time. Sometimes dur­ ing the exam day you have to make adjustments with your break time and the number of consecutive blocks you want to attack. It is important to have at least 2 to 3 different audible plans go­ ing into the exam. In American football, the term audible re­ fers to a change in playing tactics that is usually called by the quarterback as an adjustment to the playing situation. Similarly, you may have to adjust your tactics during the examination. By having an audible plan, you control the exam day, the day does not control you. The following are examples of an audible plan, and you may be able to allocate more time to your breaks if you finish any block or tutorial earlier.
Option 1\: Day I
Block I
Block 2
10-minute break Block 3
Block 4
25-minute lunch break Block 5
Block 6
10-minute break Block 7
Option 2\: Day 1
Block 1 5-minute break Block 2 5-minute break Block 3 5-minute break
Day 2
Block 1
Block 2
10-minute break Block 3
Block 4
10-minute break
CCS Cases 1-3 20-minute lunch break CCS Cases 4-6
CCS Cases 7-9 5-minute break CCS-Cases 10-12
Day 2
Block 1 5-minute break Block 2 5-minute break Block 3 5-minute break
The best way to achieve optimal mental capacity is to have a basal level of glucose throughout the exam day. Consider munching on snacks throughout the day rather than having a big lunch. Instead of eating a full sandwich at lunch, try eating half the sandwich at lunch and the rest of the sandwich dur­ ing your breaks. In this approach you should feel relatively light rather than bloated and still maintain a good level of glucose throughout the day. It is still crucial to stay alert and focused to­ ward the end of the day because the last block could potentially determine your destiny. If you feel a little tired at the end of the day, then consider an extra boost of energy during your break time (eg, caffeinated beverage, chocolate-covered coffee beans).
INTRODUCTION XVII

Allergy and Immunology
KEYWORDS REVIEW
CD4—CD4 is a surface marker on T cells. The CD4 molecule is closely associated with the components of theT-cell receptor (TCR), and hence, they are sometimes referred to
as co-receptors. Lck tyrosine kinase is also closely associated with the CD4 co-receptor, but on the cytoplasmic side of the T cell. The CD4 marker is necessary for interacting with cells that express MHC class II molecules that present the antigen to theT cells. Naive CD4T cells can differentiate intoT helper subsets ofTH1 orTH2 cells (see below).
CD8—CD8 is a surface marker on T cells.TheT cells are often referred to as cytotoxic T cells, and like CD4, they are associated with the TCR and Lck tyrosine kinase. The CD8 marker is necessary for interacting with cells that express MHC class I molecules that present the antigen to theT cells. Cytotoxicity occurs by two mechanisms. First, cyto- toxicT cells that have the Fas ligand (CD95L) will target cells that express the Fas molecule (CD95) and trigger apopto­ sis. Second, granules are delivered into the target cell via perforin-induced pores.
Cytokines—Proteins secreted by cells that act as signals to other cells. Consider the following\:
IL-1—Mediates inflammation; the major source is from macrophages.
IL-2—Involved inT cell proliferation.
IL-3—Enhances growth of blood cells made by the bone
marrow.
IL-4—Enhances IgE switching, enhances B-cell prolifera­ tion, and 1 inflammatory cytokines.
IL-5—Enhances IgA switching and enhances eosinophil growth.
IL-6—Enhances B andT cell proliferation and acute phase protein production.
IL-7—Enhances pre-B and pre-T cell growth. IL-8—Induces neutrophil chemotaxis. IL-9—Enhances mast cell activity.
IL-10—InhibitsTh1 cell development and suppresses macrophage function.

2
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
IL-12—Enhances Th1 cell development IL-13—Similar effects to IL-4.
IFN-gamma—Activates macrophages and increases MHC expression.
TNF (a and p)—Mediates inflammation.
Endotoxin—A toxin that is not secreted, but rather released during bacterial cell lysis. Endotoxin is present only in gram- negative bacteria except for Listeria monocytogenes (gram­ positive). The term endotoxin is used interchangeably with lipopolysaccharide (LPS). LPS is part of the outer membrane of the gram-negative cell envelope. LPS is made of three components, which include O-antigen, core polysaccharide, and lipid A (ie, lipid A is the toxic component of the LPS).
Exotoxin—A toxin that is secreted by both gram-negative and gram-positive (except Listeria monocytogenes) bacteria. Exotoxins that act on the CNS or Gl tract are referred to as neurotoxin and enterotoxin, respectively. Some exotoxins can act as superantigens (eg, TSST-1, streptococcal pyogenic exotoxins) that can bind to the MHC class II and T-cell receptor simultaneously (ie, without processing
of the toxin by an antigen-presenting cell) and thereby stimulate a subset ofT cells.
Fab (fragment antigen binding)—The "arms"of the antibody that contain both heavy and light chains. It is involved in antigen binding.
Fc (fragment crystallizable) region—The "tail" portion of an antibody that contains only heavy chains and is involved in binding to cell receptors and complement proteins.
HUMORAL-MEDIATED IMMUNODEFICIENCY
1 SELECTIVEIgADEFICIENCY
Selective IgA deficiency is the most common primary immuno­ deficiency. IgA is normally found in mucosal secretions such as in the saliva, tears, GI tract, GU tract, breast milk, and nasal and pulmonary secretions. The majority ofpatients are asymptomatic, and it is thought that the lack of symptoms may be compensated by IgM, which may perform some of the same functions as IgA. The pathogenesis of selective IgA deficiency is unknown.
Clinical Features\:
Selective IgA deficiency can occur sporadically or by familial inheritance. The majority of patients with selective IgA
HIV glycoproteins—The HIV viral envelop is studded with glycoprotein (gp)120 that is attached to transmembrane gp-41. GP-120 has high affinity to CD4 molecules. Once binding occurs between gp-120 and CD4, a conformational change occurs in the gp-41, which now mediates the fusion between the viral envelope and the target cell.
Lcktyrosine kinase—Lck tyrosine kinase is found on the cytoplasmic side of the T cell and is closely associated with the CD4 and CD8 co-receptors. Once an antigen binds to the T cell receptor, Lck tyrosine kinase is activated and initiates intracellular signaling. Lck tyrosine kinase is important for the development and function of the T cell.
Opsonization—The process of enhancing phagocytosis by having opsonins (eg, antibodies or complement fragments) bind onto antigens, marking them for an immune response.
Sphingosine kinase—An enzyme that catalyzes sphingosine to sphingosine-1-phosphate (SIP). SIP is implicated in many physiological processes such as cell survival, cellular adhesion, motility, angiogenesis, immunity, and inflammation.
TH1 cells—Th1 cells are primarily involved in immunity to intracellular pathogens, autoimmunity, pro-inflammatory response, and delayed hypersensitivity reactions. The major cytokines produced byTH1 cells include IL-2, IFN-gamma, and TNF.
Th2 cells—Th2 cells are involved in allergic diseases (IgE response) and immunity to parasitic infections. The major cytokines produced byTH2 cells include IL-4, IL-5, IL-9, IL-10, and IL-13.
deficiency are asymptomatic. The remainder ofpatients that do have clinical symptoms may present with any of the following\:
Recurrent infections—Sinopulmonary infections such as sinus­ itis, otitis media, bronchitis, or pneumonia may be recurrent GI infections due to Giardia lamblia may also be recurrent.
Autoimmune diseases—Patients can develop SLE, ITP, RA, type 1 diabetes, or Graves’ disease.
Atopic diseases—Patients can develop atopic dermatitis (eczema), allergic conjunctivitis, allergic rhinitis, asthma, or food allergies.
Anaphylactic reactions—Patients can develop an anaphylactic reaction (type 1 hypersensitivity) to blood products that contain IgA such as platelets, packed RBCs, whole blood, cryoprecipitate, FFP, IVIG, or granulocytes.
GI diseases—Crohn’s disease, ulcerative colitis, celiac dis­ ease, and nodular lymphoid hyperplasia are associated with selective IgA deficiency.

Next Step\:
Step 1) Selective IgA deficiency is a diagnosis of exclusion, particularly of other types of primary humoral immune deficiencies. The diagnosis may not be readily apparent, but a pattern of recurrent infections, chronic diarrhea, autoim­ mune disease, atopic disease, anaphylactic reactions to blood products, family history, or a combination of these problems may provide insight to a possible diagnosis of selective IgA deficiency. The best test to confirm a clinical suspicion is to obtain serum immunoglobulins of IgA, IgG, and IgM levels. Patients with selective IgA deficiency will have low IgA, normal IgG, and normal IgM levels. In addition, patients must be older than 4 years of age, since children younger than 4 years old may still be able to normalize their IgA levels.
Step 2) Further evaluation may be indicated in patients with coexisting diseases such as SLE (eg, ANA, dsDNA antibodies), ITP (eg, CBC with peripheral smear), RA (eg, anti-CCP or rheumatoid factor), type 1 diabetes (eg, Hb A1C), Graves’ dis­ ease (eg, TSH), asthma (eg, spirometry), celiac disease (eg, IgG- antigliadin antibodies or IgG-based anti-tissue transglutaminase antibodies), Crohn’s disease or ulcerative colitis (eg, colonoscopy).
Step 3) There is no therapeutic intervention to replace IgA. Patients should be educated and counseled about other associated conditions, and treatment should be offered for the coexisting diseases. In cases of recurrent infections, prophylac­ tic antibiotics may be considered in select cases to reduce the frequency of infections. The use of IVIG in patients with iso­ lated IgA deficiency (ie, without coexisting IgG subclass defi­ ciency) is controversial and is not routinely recommended.
Follow-Up\:
There are two important elements in the follow-up care. First, children younger than 4 years old should be monitored peri­ odically to see if their IgA levels normalize. Second, patients diagnosed with selective IgA deficiency should be periodically reevaluated to assess the frequency of infections and to remain vigilant about the development of associated disorders.
Pearls\:
• Medications can cause a reduction in immunoglobulins, including IgA. These medications include anticonvulsants (eg, carbamazepine, phenytoin, valproic acid), cyclosporine, captopril, sulfasalazine, D-penicillamine, and thyroxine.
• It is unlikely that children with immune defects will present with recurrent infections before the age of6 months since ma­ ternal immunoglobulins (IgG) are still present until that age.
• Patients that require transfusions should receive “washed” blood products to remove as much of the IgA and thereby reduce the risk of anaphylaxis.
• Patients diagnosed with selective IgA deficiency may have a family history of either IgA deficiency or common variable immunodeficiency (CVID).
• In a subset of patients, selective IgA deficiency can progress to common variable immunodeficiency (CVID).
• Foundational point—The five antibody isotypes include IgG, IgA, IgM, IgE, and IgD. Consider the main features of each type\:
IgG—Most abundant isotype; only isotype that can cross the placenta; major player in the secondary response to an antigen.
IgA—Principally found in secretions and a major player in mucosal immunity.
IgM—Major player in the primary response to an antigen (ie, the first antibody to appear).
IgE—Major player in type 1 hypersensitivity. Allergen-specific IgE binds to the cell surface ofmast cells and basophils. Upon re-exposure to the allergen, cross-linking of the IgE results in degranulation and secretion of the inflammatory mediators.
IgD—Function is unclear, but is usually coexpressed with IgM on the cell surface of mature B cells.
• On the CCS, obtaining serum IgA, IgG, and IgM measure­ ments will provide you with the actual value and the normal value in the practice CCS.
• On the CCS, “counsel family/patient” is available in the practice CCS.
• On the CCS, you will be evaluated on your diagnostic work-ups, appropriate treatments, monitoring the patient, sequence of actions, timing, and appropriately locating the patient to the right setting.
1 COMMONVARIABLEIMMUNODEFICIENCY
Common variable immunodeficiency (CVID) is characterized by the inability of B cells to differentiate into plasma cells that are capable of producing the various immunoglobulin isotypes (ie, hypogammaglobulinemia).The pathogenesis ofCVID is unknown.
Clinical Features\:
CVID can occur sporadically or by familial inheritance. Males and females are equally affected, and the peak of onset appears to have a bimodal distribution affecting children 1 to 5 years old and individuals 16 to 25 years old. Common variable immuno­ deficiency is truly variable in its clinical manifestations, which can make this disease hard to detect. Consider the following features\:
Recurrent infections—Sinopulmonary infections such as sinusitis, otitis media, bronchitis, pneumonia, or conjuncti­ vitis may be recurrent. GI infections due to Giardia lamblia, Cryptosporidium, or CMV. Other possible infections may include meningitis, septic arthritis, or enterovirus infections.
Autoimmune diseases—Possible autoimmune disorders include SLE, ITP, RA, diabetes, psoriasis, vitiligo, alope­ cia totalis, autoimmune hemolytic anemia, autoimmune neutropenia, pernicious anemia, or thyroid diseases.
Granulomatous diseases—Noncaseating granulomas may be found in the lungs, liver, lymph nodes, spleen, intestine, brain, skin, or conjunctivae.
CHAPTER 1 ALLERGY AND IMMUNOLOGY B

*
Growth—Failure to thrive (FTT) may be seen in children.
Malignancy—There is an increased risk of developing non- Hodgkin’s lymphoma (NHL) and gastric cancers.
CVID can also affect specific organ systems, and it may be helpful to consider them in a relative head to toe fashion\:
Pulmonary—Bronchiectasis may be the result of repeated infections.
GI—Crohn’s disease, ulcerative colitis, sprue-like disorder, malabsorption, and nodular lymphoid hyperplasia are associated with CVID.
Hepatobiliary—Primary biliary cirrhosis (PBC) may be seen. Spleen—Splenomegaly is a relatively common finding.
Lymph nodes—Lymphadenopathy may be seen in the neck, chest, or abdomen.
Next Step\:
Step 1) CVID is a diagnosis ofexclusion. The diagnosis may not be straightforward early in the course of the disease, but a com­ bination of problems may point you in that direction. The best initial test is to obtain serum immunoglobulins of IgG, IgA, and IgM levels. Patients with CVID will have low IgG in addition to a low IgA and/or low IgM levels. Patients should also be older than 4 years of age to make the diagnosis.
Step 2) The next best step in patients with low levels of immu­ noglobulins is to assess an antibody response to vaccines. The diagnosis can be established if the patient has a poor or absent response to the vaccines.
Step 3) Patients should be counseled and educated about the disease, especially younger individuals since they may be more inclined to withdraw from social activities.
Step 4) Management approach in patients with CVID is to treat any coexisting diseases and treatment with immune globulin replacement either intravenously (IVIG) or subcutaneously (SCIG). The subcutaneous route of administration may offer more convenience (ie, self-administration at home) than the intravenous route.
Follow-Up\:
Patients receiving immune globulin replacement should have trough levels of IgG every several months. Children suspected of having CVID should be monitored periodically to see if their immunoglobulin levels improve and to assess antibody titers.
Pearls\:
• Common variable immunodeficiency is a relatively common primary immunodeficiency, but not as frequent as selective IgA deficiency.
• Soon after birth, maternal IgG declines and reaches a low point at approximately 3 to 6 months of life. Meanwhile, the infant’s own endogenous IgG production begins to rise. There is a point when the infant normally has low immunoglobulin levels that is referred to as normal physiologic hypogammaglobulinemia. Prolongation of this physiologic phenomenon is referred to as transient
hypogammaglobulinemia of infancy (THI) and is usually present after the sixth month oflife. THI can be characterized by low IgG, with or without diminished values of the other isotypes. However, the IgG levels should normalize by 2 to 4 years of age. In addition, patients with THI will have ad­ equate antibody response to vaccines, usually before the im­ munoglobulin levels become normal.
• The overall B cell numbers in patients with CVID is normal or slightly reduced.
• In a subset of patients with CVID, a low CD4/CD8 T cell ratio can be observed.
• Patients diagnosed with CVID should receive age-appropri­ ate cancer screening.
• On the CCS, “IVIG” is available in the practice CCS, but not “SCIG.”
• On the CCS, you can advance the clock by selecting “On,” “In,” “With next available result,” or “Call/see me as needed.”
• On the CCS, early in your CCS preparation, you might want to stick with a particular routine that is familiar with you when you advance the clock.
0 X-LINKEDAGAMMAGLOBULINEMIA
X-linked agammaglobulinemia (XLA), also referred to as Bruton’s agammaglobulinemia, is caused by a mutation in a gene that codes for Bruton’s tyrosine kinase (BTK). BTK is a signal transduction molecule that is important in B cell development. Failure of B cell development results in diminished levels of mature B lymphocytes that can no longer generate antibody producing plasma cells.
Clinical Features\:
The clinical manifestations of XLA typically present after 3 months of age since the maternal IgG is protecting the new­ born before that time. XLA primarily affects males because the disease is an X-linked recessive trait. On physical exam, most patients will have very small tonsils, adenoids, lymph nodes, or spleen. The main feature of XLA is recurrent infections\:
Recurrent infections—Patients with XLA are suscep­ tible to encapsulated bacteria such as Streptococcus pneu­ moniae, Haemophilus influenzae, and Pseudomonas species. Other common bacteria include staphylococcus. Infection with specific viruses such as enteroviruses can also occur. The possible types of infection vary, and they may include sinusitis, otitis media, bronchitis, pneumonia, conjunctivitis, osteomyelitis, septic arthritis, sepsis, hepatitis, CNS infec­ tions, skin infections, respiratory infections, or GI infections (eg, giardia, Campylobacter, shigella, or salmonella).
Next Step\:
Step 1) The best initial step in a patient with suspected XLA (ie, male, family history, recurrent infections) is to obtain serum immunoglobulins of IgG, IgA, and IgM levels. Patients with XLA will have low IgG, IgA, and IgM levels.
Step 2) If the serum immunoglobulins are low, the next best step is obtain measurement of the B cell numbers. Patients
4
CLINICAL JUDGMENT USMLE STEP 3 REVIEW

with XLA will demonstrate less than 2% of circulating CD19+ B cells.
Step 3) If the B cell numbers are low from Step 2, XLA can be confirmed with molecular studies (ie, analysis of DNA, RNA, or protein), which will identify the mutation in the BTK gene.
Step 4) Genetic counseling should be offered to the family since the patients female family members may be carriers.
Step 5) Unfortunately, there is no cure for XLA. However, patients should be treated for any coexisting diseases (eg, infections) and treatment with immune globulin replacement via intrave­ nously (IVIG) or subcutaneously (SCIG).
Follow-Up\:
Patients on immune globulin replacement will require trough levels. Overall, patients can live a relatively normal life with im­ mune globulin therapy.
Pearls\:
• In X-linked recessive disorders, males only require one bad copy of the X chromosome to be affected, while females re­ quire two bad copies of the X chromosome.
• All female offspring of patients diagnosed with XLA will be carriers.
• All female carriers will be asymptomatic, but they have a 50% chance of transmitting the disease to each of their sons and a 50% chance that each of their daughters will be carriers.
CCS\: ANAPHYLAXIS CASE INTRODUCTION
Day 1 @ 14\:30 Emergency Room
A 12-year-old white boy is rushed to the emergency room by his mother because ofgeneralized urticaria, crampy abdominal pain, and lightheadedness for the past 45 minutes. He appears to be in mild distress.
Initial Vital Signs\:
Temperature\: 37.0°C (98.6°F)
Pulse\: 102 beats/min
Respiratory\: 32/min
Blood pressure\: 88/68 mm Hg
Height\: 162.6 cm (64.0 inches)
Weight\: 65.8 kg (145 lb; >95th percentile) BMI\: 24.9 kg/m2
• There is no male-to-male transmission in X-linked recessive inheritance.
• When a male patient is diagnosed with XLA and his mother as a carrier, look closely at the maternal uncles since they may be affected as well.
• XLA patients will have very low numbers of B cells, while CVID patients will have close to normal B cell numbers.
• XLA patients will have a poor response to vaccines (ie, low antibody titers to immunizations).
• Foundational point—CD19 and CD20 are proteins that are found on the cell surface of mature B cells.
• Foundational point—Tyrosine kinases are intracellular sig­ naling proteins that function as molecular switches turning on and off various cellular functions.
• Connecting point (pg. 163)—Know the pattern of X-linked recessive genes.
• On the CCS, “B cell count” is available in the practice CCS. • On the CCS, “Genetic counseling” is available in the practice
CCS.
• On the CCS, you are expected to know the routes of admin­ istration and frequency (ie, one time/bolus or continuous), but not the dosages or fluid rates of the medication.
• On the CCS, when you order something during the case, the “clerk” will recognize the first three characters of the order, even abbreviations (eg, CXR for chest x-ray). Be sure to try different abbreviations in the practice CCS software.
CHAPTER 1 ALLERGY AND IMMUNOLOGY 5
Initial History\:
Reason(s) for visit\: Urticaria, abdominal pain, lightheadedness.
HPI\:
A 12-year-old child is brought to the ED by his mother because of itchy “hives” distributed throughout his body, crampy abdominal pain, and lightheadedness that started 45 minutes ago. They were both at a birthday party when the symptoms started to appear. The mother recalls that her son was interacting very well with his friends at the party, but the symptoms appeared after he finished his hot dog and birthday cake with yellow frosting. The patient felt a crampy pain in his abdomen approximately 10 minutes after ingesting his food, and at the same time his friends noticed skin lesions appearing over his neck, face, and arms. His friends called his mother, who was in an adjacent room, to see him. The pa­ tient was sitting on the floor with friends by the time his mother arrived. He told his mother, “I feel a little weak and lightheaded.”

6 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
PastMedicalHistory\: Past Surgical History\:
Medications\:
Allergies\:
Vaccinations\: Development History\:
Family History\:
Review of Systems\: General\:
Skin\:
HEENT\: Musculoskeletal\: Cardiorespiratory\: Gastrointestinal\: Genitourinary\: Neuropsychiatric\:
Day 1 @ 14\:35
Physical Examination\: HEENT/Neck\:
Chest/Lungs\:
Heart/Cardiovascular\: Skin\:
First Order Sheet\:
1) Epinephrine, IM,
one time
Second Order Sheet\: 1) IV access
2) Continuous cardiac monitor, stat
None.Nohistoryofanaphylactic reactions.
Tonsillectomy at age 5.
None.
Ragweed causes sneezing, runny nose, and itchy eyes.
Up to date.
Patient’s height has been in the 90th percentile since 2 years old. His weight has been above the 95th percentile for the past 3 years. He is considered obese for his age
. group. He likes to playvideo games nonstop while eating chips and soda. He also likes to ride his bike with his father on the weekends. Father,age38,hasseasonalallergies. Mother, age 37, is healthy.
See HPI See HPI Negative Negative Negative See HPI Negative See HPI
No swelling of the lips, tongue, or uvula.
Tachypnea. Chest wall normal. Diaphragm and chest moving equally and symmetrically with respiration. No expiratory wheezes. No audible stridor. Tachycardia. SI, S2 normal. No
murmurs, rubs, gallops, or extra sounds. No JVD.
Discrete wheals located over the face and neck. White-to-pink color annular lesions over the arms. Erythematous serpiginous lesions over the legs. White oval round lesions over the trunk and back.
Note\: Epinephrine injected in the upper thigh.
Result\: Sinus tachycardia
3) Continuousblood pressure cuff, stat
4) Pulse oximetry, stat 5) EKG, 12-lead, stat
Result\:88/68mmHg
Result\: 97%
Result\: Sirius tachycardia. Other findings\: WNL
Third Order Sheet\:
1) Normal saline solution,
0.9% NaCl, IV, one time/bolus
2) Urine output, stat, ql hour
3) Diphenhydramine, IV, onetime
4) Methylprednisolone, IV, one time
Physical Examination\: Abdomen\:
Extremities/Spine\:
Neuro/Psych\:
Fourth Order Sheet\: 1) Vital signs, stat
Fifth Order Sheet\: 1) Epinephrine, IM,
one time
Normal bowel sounds; no bruits. No tenderness. No masses. No hepato- splenomegaly.
No joint deformity or warmth. No cyanosis or clubbing. No edema. Peripheral pulses 1+ (diminished). Spine exam normal.
Alert; normal neurologic exam.
Result\: 37°C, HR\: 100, RR\: 30, BP\: 90/70 mm Hg
Note\: Approximately 15 minutes has elapsed since the last dose of epinephrine.
Note\: Epinephrine injected in the lower thigh.
Actions\:
1) Reevaluate case\: In 10 minutes
Sixth Order Sheet\: 1) Vital signs, stat
Result\: 37°C, HR\: 92, RR\: 26, BP\: 115/74 mm Hg
Seventh Order Sheet\:
1) Normal saline solution,
0.9% NaCl, IV, continuous
2) Pediatric allergy medicine consult
Urine output is now available
Physical Examination\: 1) Skin\:
2) Extremities/Spine\:
Reason\: Anaphylactic reaction to unknown substance, please evaluate with skin testing. Result\: 135 mL/hr
Resolving skin lesions. Peripheral pulses 2+(normal).

Follow-Up History\:
Patient feels better. No moire lightheadedness or abdominal pain.
Respiratory—Dyspnea, cough, hoarseness, Wheezing, au­ dible stridor, feeling of throat closure, rhinorrhea, nasal congestion, sneezing, or shortness ofbreath
Cardiovascular—Hypotension, lightheadedness (second­ ary to low BP), syncope, weakness, chest tightness, chest pain, palpitations, dysrhythmia, or tachycardia
GI—Nausea, vomiting, abdominal cramps, bloating, or diarrhea
GU—Urinary incontinence, cramps
Skin—Flushing, angioedema (soft-tissue swelling), warmth, pruritus, or urticaria, which can take different shapes due to the confluence and resolution of the lesions, which are in­ tensely pruritic.
Next Step Summary\:
Step 1) Anaphylaxis is a true medical emergency, and you need to act quickly because fatalities do occur. The best initial step is to assess the Airway, Breathing, and Circulation. Securing the airway should be the top priority, and intubation should be per­ formed immediately ifthere is audible stridor or respiratory dis­ tress or arrest. In our case, the physical exam revealed no tongue swelling or stridor on the initial assessment. If the skin exam reveals an inciting antigen (eg, stinger), remove it right away or remove the offending substance. Notice that we did not need to do the full exam in the beginning of the case. You can do the rest ofthe exam while you’re waiting to see ifthe patient responds to the epinephrine. The patient should also be in the supine posi­ tion with the legs elevated (unless the patient is vomiting or in respiratory distress) to facilitate perfusion of the vital organs.
Step 2) Anaphylaxis is a clinical diagnosis. Look for a history of exposure to an inciting substance. Also, patients may have a com­ bination of organ-system involvement (eg, respiratory, cutaneous, cardiovascular, or GI). Patients with food-induced anaphylaxis tend to have more GI involvement as in this case. Since anaphylaxis is a clinical diagnosis, laboratory studies are usually not required.
Step 3) Treatment of anaphylaxis can be broken down to first- line and second-line treatments. Consider the following\:
First-line Treatments
Epinephrine—Rapid administration of epinephrine should be one of the first things you do. Epinephrine can be given subcutaneously (SubQ) or intramuscularly (IM). The pre­ ferred route of administration is intramuscularly because it provides faster absorption compared to SubQ. The way to think about anaphylaxis and an easy way to remember this is to “Stick it in IM!” The ideal injection site is the mid-outer thigh rather than the deltoid because it provides more effec­ tive peak levels of the drug. In our case, the injection site was in the upper thigh where you have to penetrate through more fat to get to the muscle, especially in an obese patient. There­ fore, the patient partially responded to the first injection. Ide­ ally, in an obese patient, the injection site should be in the lower half of the thigh or even in the calf muscle where there is better access to muscular tissue. Epinephrine injections can be given every 5 to 15 minutes. Epinephrine infusion
Actions\: 1)Change,location to ICU
Note\: Vitals are automatically ordered as q4 hrs in the practice CCS.
This case will end in the next few minutes of “real time.” You may add or delete orders at this time,
then enter a diagnosis on the following screen.
Eighth Order Sheet\:
1) Counsel patient on using epi pen
2) Advise patient, exercise 3) Allergy skin test, routine
Future date\: In 30 days
Result\: Cutaneous reaction to Yellow 5 Lake
Please enter your diagnosis\: Anaphylaxis
DISCUSSION\:
Anaphylaxis is a medical emergency. It is typically caused by re-exposure to an allergen that results in cross-linking of the IgE on presensitized mast cells and basophils, with subsequent release of various substances (eg, histamine, tryptase, chymase, heparin, platelet-activating factor, leukotrienes, prostaglandins, IL-4, IL-13).
Anaphylactic Triggers\:
Food (nuts, egg, milk, shellfish, fish, soybeans, seeds, wheat, sulfites), food additives (coloring, emulsifiers, enhancers), Hy- menoptera stings, bugs, latex, venom, vaccines, meds (NSAIDs, beta-lactam antibiotics, TMP-SMX, hormones), radiocontrast materials
Clinical Features\:
The signs and symptoms of anaphylaxis are usually sudden, with manifestations appearing within minutes to <1 hour, although a delayed presentation (several hours) can some­ times be seen. The course of anaphylaxis is typically uniphasic (occurs only once), although a biphasic course (occurring again after the initial event) or protracted course (a prolonged event ofhours to days) can occur. In some cases, a fatal reaction can occur with symptoms appearing within 25 minutes and death within the first hour. The clinical manifestations can vary, and it may be helpful to consider them in a relative head to toe fashion\:
Neurologic—Anxiety (feeling of impending doom), dizzi­ ness, or headache
Eyes—Swelling (angioedema), tearing, conjunctival injec­ tion or pruritus
Oral—Metallic taste, swelling of the lips, tongue, or uvula
CHAPTER 1 ALLERGY AND IMMUNOLOGY 7

8
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
should be considered in patients that do not respond ade­ quately (usually after the third injection) to IM epinephrine.
Oxygen-r-Provide oxygen to maintain an Sa02 of >90%. Fluids—Isotonic (6.9% NaCl) saline solution should be given as a bolus and repeated as necessary. Massive fluid shifts from intravascular to the extravascular space do occur in anaphylaxis. Be sure to monitor the urine output when giving fluids. In our case, the patient was producing an ade­ quate amount of urine. Children with oliguria will typically make less than 1 to 2 mL/kg/hr.
Second-line Treatments
Glucocorticoids—IV methylprednisolone, IV hydrocorti­ sone, or PO prednisone are acceptable choices. Glucocorti­ coids do not have an immediate effect on anaphylaxis, but the rationale for giving steroids is to prevent a biphasic or pro­ tracted anaphylactic course. Tapering is usually not required.
Antihistamines—Antihistamines are considered adjunc­ tive therapy to epinephrine. antihistamines (eg, diphen­ hydramine, cetirizine, hydroxyzine, promethazine) relieve itching and urticaria. H2 antihistamines (eg, ranitidine, ci- metidine) can be given in conjunction with an Hj antihista­ mine, but it is not required.
Bronchodilators—Nebulized albuterol is typically given to patients who are wheezing. It is considered an adjunctive therapy to epinephrine.
Step 4) Prior to discharge, the patient and family members should be educated on how to administer self-injectable epinephrine and when to inject the medication (ie, emergency action plan).
Step 5) Patients should have allergy skin testing 4 to 6 weeks following the episode. In our case, the inciting antigen was the yellow food coloring in the cake. Yellow 5 Lake (also known as tartrazine).
Disposition\:
Patients who had airway intervention, severe anaphylaxis (ie, cardiovascular or respiratory issues), or patients who do not respond promptly to epinephrine should be transferred to the ICU for further monitoring. However, patients who initially re­ spond immediately to epinephrine can be observed in the ED for several hours and then safely discharged home.
Pearls\:
• Approximately 90% of patients with anaphylaxis will have some type of skin manifestations, while 10% of patients may not have any skin findings at all.
• A reference for low systolic blood pressure in children that are 11 to 17 years old is a systolic blood pressure (SBP) <90 mm Hg.
• Caveat 1—Care must be taken when administering vaccines in patients with egg allergies. Vaccines that are egg protein based are influenza, yellow fever, MMR, and rabies.
• Caveat 2—Care must be taken when giving the appropriate diluted epinephrine solution. When giving epinephrine as
IM or SubQ, the diluted solution should be 1\:1000. When giving epinephrine as IV, the diluted solution should be more diluted to 1\:10,000 which makes sense because you are injecting it directly into the blood. If you give a 1\:1000 solution in the IV form, the patient may have arrhyth­ mias, chest pain, MI, sharp rise in BP, and even a cerebral hemorrhage.
• Caveat 3—Patients may require a second vasopressor (eg, dobutamine) to support the blood pressure, but remember to have continuous monitoring.
• Caveat 4—Patients who are on beta-blocker therapy may have a reduced bronchodilator response to the beta-adrenergic effects of epinephrine (ie, beta2 agonist effects).
• Caveat 5—Caution is warranted in two types of patients that are taking beta-blockers. First, patients that are given epinephrine can develop hypertension secondarily to an unopposed alpha-adrenergic effect of epinephrine (ie, alphaj agonist effect). Second, patients may have refrac­ tory anaphylaxis that is poorly responsive to epinephrine and fluids. In such cases, patients will actually be hypotensive and the next best step is to give IV glucagon as a bolus (over 3 to 5 minutes). If there is no response, another dose can be given as a bolus or followed by an IV infusion. Glucagon provides chronotropic and inotropic effects on the heart.
• Serum sickness is a type III hypersensitivity reaction that results from exposure to a foreign antigen or serum. One to two weeks after exposure to the inciting agent (eg, medications), patients can develop fever (which usually precedes skin findings), malaise, skin manifestations (eg, rash, edema, papules, palpable purpura), polyarthralgias, headaches, blurred vision, lymphadenopathy, or GI complaints (eg, nausea, vomiting, cramps, abdominal pain, diarrhea, bloating). Once the causative agent is removed, symptoms usually resolve within two weeks.
• Arthus reaction is a type III hypersensitivity reaction that results from local intradermal injection of foreign antigen into the skin. Several hours later, patients can develop swelling, induration, and hemorrhage followed occasionally by necrosis. On light microscope, fibrinoid necrosis of a vessel can sometimes be seen.
• Foundational point—The effects of epinephrine include alphal agonist (vasoconstriction, mucosal edema), betat agonist (t heart rate, f cardiac contractility), and beta2 agonist (bronchodilation) effects.
• Foundational point—The four types of hypersensitivity reactions can be remembered by the mnemonic ACID\:
Type I—Anaphylaxis or Allergy
Mediator\: Antibody (IgE) Antigen\: Soluble (exogenous)
MOA\:AntigenbindstoIgEonpresensitizedmastcellsand basophils
End result\: Release of vasoactive substances Reaction onset\: Immediate

Examples\: Asthma, anaphylaxis, allergic rhinitis, aller­ gic conjunctivitis, urticaria, food allergy, drug allergies (eg. urticarial rash), atopic dermatitis
Type II—Cytotoxic
Mediator\: Antibody (IgG, IgM)
Antigen\: Cell surface (Note\: Drugs can bind to cell sur­ faces and act as antigens.)
MOA\: Antibodies bind to antigens on cell surfaces
End result\: Cell lysis (via MAC) or susceptible to phagocytosis (via opsonization)
Reaction onset\: Minutes to days
Examples\: Hemolytic anemia, Rh incompatibility (eryth­ roblastosis fetalis), ITP, blood transfusion reactions, Grave’s disease, Goodpasture’s syndrome, drug reactions (eg, hemolytic anemia, thrombocytopenia, neutropenia), rheumatic fever, myasthenia gravis, pernicious anemia, pemphigus vulgaris, bullous pemphigoid, vasculitides
Type III—Immune Complex
Mediator\: Antibody (IgG, IgM)
Antigen\: Soluble (exogenous or endogenous)
MOA\: Ifantigen circulates in blood, an antibody-antigen complex can form, resulting in immune complex depo­ sition into vessel walls or tissues with subsequent com­ plement activation leading to an inflammatory reaction. If antigen is locally injected into tissue, an antibody-an­ tigen complex can form, resulting in complement activa­ tion and an ensuing local inflammatory response.
End result\: Inflammatory reaction. A systemic inflam­ matory response can result in serum sickness, while a lo­ cal inflammatory response results in the Arthus reaction.
Reaction onset\: Serum sickness occurs within weeks, but earlier (within days) if the patient was previously ex­ posed to the inciting agent. Arthus reaction occurs within hours (peaks at 4 to 10 hours).
Examples\: SLE, rheumatoid arthritis, post-streptococcal glomerulonephritis, infective endocarditis, polyarteritis nodosa, Farmer’s lung, serum sickness, Arthus reaction, drug reactions (eg, drug fever), Henoch-Schonlein pur­ pura, arthritis, glomerulonephritis, vasculitides
Type IV—Delayed Hypersensitivity
Mediators\: Not antibody mediated, but rather CD4 T cells (mainly TH1 cells) and CD8 T cells (also known as cytotoxic T cells)
Antigen\: Antigen presented by antigen-presenting cells (APC) on MHC class II molecules or on MHC class I molecules
MOA\: CD4 T cells interact with MHC class II mol­ ecules that stimulate T cells to secrete cytokines and chemokines. CD8 T cells interact with MHC class I molecules that triggers the T cell to directly kill the target cell. (Note\: MHC molecules are encoded by the HLA [Human Leukocyte Antigen] genes.)
End result\: CD4 T cells trigger an inflammatory response with macrophages as the dominant cell type recruited to the site. CD8 T cells directly cause tissue damage.
Reaction onset\: Delayed, usually after many hours to even weeks after exposure. PPD reaction peaks 48 to 72 hours after injection.
Examples\: PPD reaction, type 1 diabetes, contact dermatitis (eg, poison ivy), Hashimoto’s thyroiditis morbilliform/maculopapular eruptions, Steven-John- son syndrome, toxic epidermal necrolysis, drug reac­ tions (eg, drug rash), allograft rejection, graft versus host disease, granulomatous inflammation (eg, Crohn’s disease, sarcoidosis, schistosomiasis, leprosy, TB)
On the CCS, do not assume that any orders will be writ­ ten for you (eg, vitals) during the CCS cases.
On the CCS, “allergy skin test” is available in the practice CCS.
On the CCS, “counsel patient, use of epi pen” is available in the practice CCS.
On the CCS, you cannot order fluids as a bolus in the practice CCS, but rather in the continuous mode of fre­ quency.
On the CCS, timing is very important in anaphylaxis. Suboptimal management would include delaying treat­ ment (eg, ordering an ABG if the patient really needs to be intubated or ordering a chest x-ray when the patient really needs epinephrine, STAT).
On the CCS, poor management would include failure to monitor the patient (eg, urine output, pulse oximetry, physical exams, cardiac monitor, BP, HR, RR, or locate to a monitored setting).
On the CCS, remember to “bridge” your therapy by ad­ dressing any acute issues (eg, securing airway, anaphy­ laxis) with the long-term management of anaphylaxis (eg, allergy skin testing, instructions on how and when to use epinephrine).
CHAPTER 1 ALLERGY AND IMMUNOLOGY 9

Biostatistics
I
I
I
MEASURES OF DISEASE FREQUENCY..................1.2... Relative Risk Reduction.........
CHAPTER OUTLINE
MEASURES OF DIAGNOSTICTEST PERFORMANCE.....12 1 PRINCIPLES OF RISK........
Sensitivity...................................................1.2...........Relative Risk...................... Specificity...................................................1.2...........O.ddsRatio......................... Positive PredictiveValue......................................1.2........ Attributable Risk................. NegativePredictiveValue.....................................1.2....... AbsoluteRiskReduction........
Incidence....................................................1.2...........Number Needed to Treat........ Number Needed to Harm.......
Prevalence...................................................1.2...........
MEASURES OF QUALITY...............................1.2...... I DATA INFERENCES.......................................1.5........
Null Hypothesis................................................1.5.......... Reliability...................................................1.2............
Alternative Hypothesis.........................................1.5......... Validity......................................................1.2............
STUDY DESIGN........................................1.3........
Prospective Study............................................1.3......... Retrospective Study............................ 13 DescriptiveStudies...........................................1.3......... Observational AnalyticStudies................................1.3...... Experimental Studies.........................................1.3......... Literature Review............................................1.3......... HierarchyofEvidence........................................1.3.........
Type I Error....................................................1.5............ Type II Error...................................................1.5............
P-Value........................................................1.5............ ConfidenceInterval............................................1.6.......... Correlation Coefficient..........................................1.6........
11

12 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
MEASURES OF DIAGNOSTIC TEST PERFORMANCE
I SENSITIVITY
Sensitivity is the ability of a test to detect disease. The higher the sensitivity of a diagnostic test (eg, 99%), the more likely it will test positive for the disease with fewer false negative results (see Table 2-1).
True Positives (a)
True Positives (a)+ False Negatives (c)
Table 2-1 • Measures of Diagnostic Test Performance
I SPECIFICITY
Specificity is the ability of a test to detect the absence of dis­ ease. The higher the specificity of a diagnostic test (eg, 99%), the more likely it will test negative for the disease with fewer false positive results (see Table 2-1).
True Negatives (d)
True Negatives (d) + False Positives (b)
I POSITIVEPREDICTIVEVALUE
The positive predictive value (PPV) is the probability or likeli­ hood that a person who tested positive for the disease truly does have the disease. The higher the PPV, the more likely the person has the disease (see Table 2-1).
True Positives (a)
True Positives (a) + False Positives (b)
I NEGATIVEPREDICTIVEVALUE
The negative predictive value (NPV) is the probability or like­ lihood that a person who tested negative for the disease truly does not have the disease. The higher the NPV, the more likely the person does not have the disease (see Table 2-1).
True Negatives (d)
True Negatives (d) + False Negatives (c)
■ prevalence
Prevalence is the total number of cases, including new and old, at a given point of time or a specified time period in a popula­ tion at risk during that time.
Number of all cases at a specific point of time or interval of time Number of people at risk during that time

validity
Validity (ie, trueness) refers to a test’s ability to measure the
true intended goal. In other words, did a test measure what it claimed to measure?
Disease
Positive True positives (a) Test
Negative False
Test negatives (c)
No Disease
False positives (b)
True negatives (d)
-» PPV = a/a + b -» NPV = d/d +c
i1 Sensitivity = Specificity = a/a+c d/d+b
MEASURES OF DISEASE FREQUENCY
I INCIDENCE
The number of new cases of disease in a population at risk with­ in a specified time period.
Number of new cases in a specified time period Number of people at risk during that time period
MEASURES OF QUALITY
I RELIABILITY
Reliability (ie, reproducibility) refers to a test’s ability to mea­ sure something consistently. In other words, can a test repro­ duce the same result repeatedly?

STUDY DESIGN
I PROSPECTIVE STUDY
Prospective studies are forward-looking studies that follow subjects over time to look for a particular outcome.
I RETROSPECTIVESTUDY
Retrospective studies are backward-looking studies in which researchers try to learn what factors may have been associated with the disease or condition.
I DESCRIPTIVESTUDIES
Descriptive studies describe accounts of a particular situation, individual, or group (somewhat like a documentary). Descriptive studies do not try to answer a particular question (and therefore require no comparison groups) but rather to bring a particular event to attention in the medical literature.
Case Report
A case report is a detailed report (with clinical presentation, diagnosis, treatment, and follow-up) that usually describes an unusual medical occurrence from a single clinical event. Case reports may be the first clue in identifying a new disease or ad­ verse effect from a type of exposure.
Case Series
A case series is a group or series of case reports that describe pa­ tients with an outcome of interest (eg, an aspect of a condition or reaction to a treatment). However, there are no comparative or control groups.
I OBSERVATIONALANALYTICSTUDIES
Observational studies observe patients for a particular out­ come, but no attempt is made to affect the outcome. Unlike descriptive studies, observational studies typically use com­ parison groups.
Cohort Study
Cohort study observes a group of subjects (two or more) with a particular exposure of interest (eg, exposed vs. nonexposed) and follows these cohorts for a particular outcome of inter­ est. Data can be collected prospectively or retrospectively (ie, from past medical records). Relative risk is used to calculate the risk.
Case-Control Study
A case-control study compares a group of people with a specific disease (cases) with a group of people without the disease (control). Researchers look at the outcome of in­ terest and then work backward to the exposure of interest (the opposite of cohort study). Case-control study is per­ formed retrospectively and utilizes the odds ratio to provide anestimateoftherisk.
Cross-Sectional Study
Cross-sectional studies provide a “snapshot” or observation of a population at a given point in time. Both exposure and outcome of interest are determined simultaneously.
I EXPERIMENTALSTUDIES
Experimental studies use comparison groups (experimental vs control group) and intervene in the studies to answer a particu­ lar question.
Randomized Controlled Trial
A randomized controlled trial (RCT) is a prospective study that randomly assigns participants to a treatment group or pla­ cebo control group. In single-blind studies, only the researcher knows which group of subjects are “tested” but not the subjects. In double-blind studies, both researcher and subjects are unaware of which group the subjects are placed in. In this sense, a double-blind study provides a higher level of scientific rigor and is considered the gold standard among study design. In gen­ eral, randomized controlled trials reduce confounding variables.
I LITERATURE REVIEW
A literature review is the process of reviewing, analyzing, and summarizing the available medical literature. There are several kinds of literature review.
Meta-Analysis
Meta-analysis is the process ofpooling several studies (usually RCTs) about the same subject to draw a single conclusion based on all the statistical results of die studies, which would yield a greater statistical power when compared to a single study alone. Meta-analysis can be thought of as one large trial rather than several smaller studies.
Systematic Review
A systematic review is a comprehensive review that pools all the relevant information (published and unpublished studies) about a particular subject and draws a summary based on the information. The main difference between a meta-analysis and a systematic review is that systematic reviews do not use statis­ tical analysis to combine all the studies. In effect, a systematic review can be viewed as a “qualitative perspective,” while meta­ analysis can be viewed as a “quantitative perspective.”
I HIERARCHYOF EVIDENCE
The various types of study design can be listed in order of the level of evidence they provide for a conclusion as follows\:
1) Systematicreviewsandmeta-analysis(highestlevelofevidence)
2) Randomized controlled trials (double-blind studies provide a higher level of evidence than single-blind)
3) Cohort studies
4) Case-control studies
5) Caseseries
6) Casereports
7) Editorials(lowestlevelofevidence)
CHAPTER 2 BIOSTATISTICS 13

14 CLINICAL JUDGMENT USMLE STEP S REVIEW
PRINCIPLES OF RISK
a RELATIVERISK
Relative risk (RR), or risk ratio, tells us the probable risk of a cer­ tain event happening in one group exposed to a factor compared to another group that is not exposed to the factor. Relative risk can be expressed as the incidence among the exposed group divided by the incidence of the unexposed group. Mathematically, it can also be expressed as [a/(a+b)]/[c/(c + d)]. Relative risk is typically interpreted relative to the number one. If the relative risk is greater than one, it usually means that exposure to the factor increases the risk of that event happening. If the relative risk is less than one, it means that exposure to the factor decreases the risk of that event happening. If the relative risk equals one, there is no difference or association between the two groups in terms of that event happen­ ing. Relative risk is typically used in prospective studies (cohort or clinical studies). Consider the following examples\:
Example 1—A cohort study of exposure to cigarette smoke and the development of lung cancer.
ad/be. Similar to relative risk, odds ratio is interpreted relative to the number one. However, the relative risk cannot be used in case-control studies (ie, retrospective study), rather the odds ratio is calculated, which provides an estimate ofthe relative risk.
Example 3—A case-control study of patients with breast cancer (cases) and non-breast cancer patients (control) with exposure to heavy alcohol drinking.
Exposure (Smoke)
No Exposure
'
Disease (Lung Cancer)
a = 20 c=5
No Disease
-
Total 30
RR calculation\: (20/30)/(5/30) = 4.0
Bottom line\: RR is greater than 1, which indicates there is a risk of developing lung cancer with smoke exposure.
Example 2—A randomized controlled trial looking at the mor­ tality when comparing a new medical therapy vs a control group for the same medical condition.
New Medical Therapy
Control
Death a=25
c=50
Total b = 50 75
d = 25 75
RR calculation\: (25/75)/(50/75) = 0.5
Bottom line\: The risk ofdying from the new medical treatment is 33% (25/75) and the risk of dying in the control group is 66% (50/75). The RR is less than 1, which indicates there is a decrease risk of death in the group treated with the new medical therapy.
1 ODDS RATIO
The odds ratio (OR) tells us the odds of a certain event happening in one group compared to the odds of it occurring in another group. Mathematically, it can be expressed as (a/b)/(c/d) or
b= 10
d = 25 30
Survival
Breast Cancer
No Disease b = 3
OR calculation\: (12 x 5)/(3 x 20) = 1.0
Bottom line\: OR = 1, which indicates that there is no differ­ ence in the odds of an event happening (ie, breast cancer) when comparing the two groups (cases vs controls).
1 ATTRIBUTABLE RISK
Attributable risk (AR) is the difference in the rate of disease in exposed compared to an unexposed population.
(Incidence of disease in exposed) - (Incidence of disease in nonexposed)
1 ABSOLUTERISKREDUCTION
Absolute risk reduction (ARR), which is also known as excess risk or risk difference, looks at the difference between the control group’s event rate (CER) and the experimental group’s event rate (EER). Absolute risk reduction can be expressed as CER - EER, which is the same as [c/(c + d)] - [a/(a + b)]. ARR is used in randomized control trials.
Example 4—Using the data from example 2, what is the ARR?
ARR calculation\: (50/75) - (25/75) = 0.666 - 0.333 = 0.333
Bottom line\: The absolute risk reduction in using the new medical therapy is 33.3%.
Example 5—A randomized clinical trial demonstrated that a new NSAID on the market has lowered the number of cardiovascular events in patients with coronary heart disease from 100 per 1000 patients to 20 per 1000 patients. What is the ARR?
ARR calculation\: (100/1000) - (20/1000) = 0.1 - 0.02 = 0.08
Bottom line\: The absolute risk reduction with the new NSAID is 8%.
1 RELATIVERISKREDUCTION
Relative risk reduction (RRR) can viewed as the percent re­ duction in events in the treated group compared to the control group. Relative risk reduction can be expressed as
Exposure (Heavy EtOH)
a = 12 No Exposure c=20
Q. ii Ol

CER - EER/CER, which is the same as [c/(c + d) - a/(a + b)]/c/ (c + d), which is the same as 1 - [a/(a + b)]/[c/(c + d)], which is the same as 1 - relative risk. For board purposes, it is not impor­ tant to know every single formula, but rather to understand that there is a risk reduction in a specific event when comparing two groups (eg, treated vs control). RRR is typically used in random­ ized control trials.
Example 6—Using the data from example 2, what is the RRR?
RRR calculation\: 1 - Relative Risk = 1 - 0.5 = 0.5
Bottom line\: The relative risk reduction in using the new medical therapy is 50%. Be aware that the relative risk reduction appears to show a greater magnitude of risk re­ duction compared to the absolute risk reduction seen in example 4. Ads will sometimes use the relative risk reduc­ tion as opposed to the ARR. An easy way to remember the difference is that “absolute” will give you absolute real values while “relative” is really just relative.
0 NUMBERNEEDEDTOTREAT
Number needed to treat (NNT) tells us the number of patients who need to be treated in order to prevent one bad outcome. The ideal NNT is when it equals one because everyone ben­ efits with the treatment and no one improves with the control.
DATA INFERENCES
1 NULLHYPOTHESIS
When you think of the word null, you should think of such words as void, empty, absent, or nullify. Therefore the null hypothesis (H0) tells us that there is no difference, no association, or a void between two measured phenomena (eg, drug A showed no difference between the treatment group and control group). In the statistical world, we have to decide whether we should or should not reject the null hypothesis. Once we reach a level of statistical significance, then we can decide to either reject or accept the null hy­ pothesis.
1 ALTERNATIVE HYPOTHESIS
The alternative hypothesis (Ht) states that there is a difference or association between the two measured phenomena.
0 TYPE I ERROR
Type 1 error (also known as alpha or a) is when the null hypothesis is rejected even though the null hypothesis is true. The bottom line is that there really is no difference or no association, but we mistakenly concluded that there was an effect.
A higher NNT suggests that the therapy in question is prob­ ably not that good. NNT can be expressed as 1/absolute risk reduction.
Example 7—If the absolute risk reduction between medical therapy vs a control group for a specific medical condition is 50%. What is the NNT?
NNT calculation\: 1/0.5 = 2
Bottom line\: Need to treat 2 patients to prevent one bad outcome (which is not too bad).
1 NUMBERNEEDEDTOHARM
Number needed to harm (NNH) can be calculated in a simi­ lar fashion to NNT, but instead we are looking at harm as the outcome rather than benefit. A higher NNH suggest that the therapy in question is good because adverse events are not common, while a lower NNH suggests that adverse events are common.
Example 8—If abatacept causes severe headaches in 3 of 100 patients (ie, 3%), what is.the NNH?
NNH calculation\: 1/0.03 = 33
Bottom line\: Need to treat 33 patients to cause one patient to have a severe headache.
0 TYPE II ERROR
Type II error (also known as beta or (5) is failure to re­ ject the null hypothesis when in fact the null hypothesis is false. The bottom line is that there really is a difference or association, but we mistakenly concluded that there was no effect. Beta errors typically reflect a low power in the study.
1 POWER
Power (which equals 1 - beta) is the ability of a study to re­ ject the null hypothesis when the null hypothesis is actually false, thereby not committing a type II error. The bottom line is that you are trying to demonstrate an association if one exists. Increasing sample size will increase your power, but if the sample size is too small, the study will not be able to detect a true difference between the groups.
i p-value
P-value is the probability that any particular outcome would have occurred by chance. In scientific practice, we arbitrarily set the p < 0.05 as “statistically significant.” In other words, there is less than 5% or less than 1 in 20 probability that the findings have occurred by chance alone.
CHAPTER 2 BIOSTATISTICS 15

16 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
I CONFIDENCE INTERVAL
Confidence interval (Cl) does not imply how confident your results are, but rather a boundary of values in which the true parameter actually lies (eg, relative risk, odds ratio, absolute difference, mean). Confidence interval can be reported at any level of confidence (eg, 80%, 90%), but we usually report a 95% Cl as a high probability that the true value will be found within those boundaries. A wider confidence interval usually indicates a greater degree of uncertainty and typically reflects a smaller sample size. A narrower confidence inter­ val narrows down the boundary levels and typically reflects a larger sample size. Whenever the confidence interval over­ laps the null value (eg, RR = 1, OR = 1), you need to be more skeptical because it suggests that there might be no effect or
that there is no statistically difference between the groups studied, and therefore you may not be able to reject the null hypothesis.
1 CORRELATIONCOEFFICIENT
The correlation coefficient (r) expresses the association be­ tween two variables with regard to direction and magnitude (ie, -1 to +1). An r value of-1 indicates the strongest possible negative relationship, an r value equal to zero indicates no relationship, and an r value of+1 indicates the strongest possible positive relationship between two variables. For example, a study between lung cancer and cigarettes sales demonstrated an r value of +0.98, which signifies a strong positive relationship between lung cancer and cigarette sales.

Cardiology
CHAPTER OUTLINE
Key Findings Review...........................................1..7........ Mitral Valve Prolapse...........................................3.2.........
I
I
PRESSURE DISORDER...................................1.8...... Aortic Stenosis.................................................3.3........... Chronic Aortic Regurgitation...................................3.5........
LIPID METABOLISM DISORDER. . . . . . . . . . . . . . . . . . . . . . . . .2.2. . . . . I MYOCARDIUM DISORDER. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3.6. . . . . .
HypertrophicCardiomyopathy..................................3.6....... Hyperlipidemia................................................2..2..........
I
I CCS...............................\:.....................4..2... VALVULARDISORDERS.................................2.8....... AcutePericarditis..............................................4.2...........
Hypertension..................................................1.8...........
I CORONARYHEARTDISEASE—ACUTECORONARY
I CONGENITAL DISORDERS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3.8. . . . . .
Atrial Septal Defect.............................................3.8.........
SYNDROMES............................................2.5.........
STEMI, NSTEMI, and Unstable Angina...........................2..5.....
Ventricular Septal Defect.......................................4.0........
Mitral Stenosis.................................................2.8........... Chronic Mitral Regurgitation...................................3..0.......
KEY FINDINGS REVIEW Murmurs
| Cl'|Ck l s2 s. Si s2 S, S2
11
ill llll !h £2
Aortic Stenosis Pulmonic Stenosis HCM
Mitral Stenosis Mitral Regurgitation Tricuspid Stenosis Tricuspid Regurgitation
VSD
Mitral Valve Prolapse
Aortic Regurgitation Pulmonic Regurgitation
17
ro^ ----

18 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Aortic area
• Aortic stenosis
Left sternal border
• Aortic regurgitation
• Pulmonic regurgitation • Tricuspid regurgitation • Tricuspid stenosis •ASD, VSD, HCM
Pulmonic area
• Pulmonic stenosis •ASD
Apex
• Mitral stenosis
• Mitral regurgitation
• Mitral valve prolapse
Heart Sounds
S,—Normal mitral and tricuspid valve closure.
52— Normal aortic (A2) and pulmonic (P2) valve closure.
53— Rapidventricularfillingduringearlydiastole.Normalin children and young adults, but suggestive of an enlarged ven­ tricular chamber (eg, heart failure) in adults >40 years of age.
54— Late ventricular filling during late diastole, which corresponds to blood forced into a "stiffened" ventricle and can be seen in patients with HTN, aortic stenosis, or hypertrophic cardiomyopathy.2
S2 Splits
Physiologic (normal) split—On inspiration, A2 is separated from P2. On expiration, A2 and P2 are fused as one sound.
Wide split—On inspiration, A2 is more widely separated from P2. On expiration, A2 and P2 are fused as one sound. This condition is seen in RBBB, WPW with preexcitation
PRESSURE DISORDER
I HYPERTENSION
Hypertension can be categorized as either primary (essential) or
secondaryhypertension. Essential hypertension (no identifiable cause) accounts for approximately 95% of cases, and secondary
of the left ventricle, LV pacing, pulmonic stenosis, mitral regurgitation, pulmonary HTN with right-sided heart failure, VSD, and acute massive PE.
Fixed split—On inspiration and expiration, A2 and P2 are separated and unchanged throughout the respiratory cycle. This condition is commonly seen in ASD.
Paradoxical split—On inspiration, A2 and P2 are fused as one sound. On expiration, P2 precedes A2.This condition is seen in LBBB, WPW with preexcitation of the right ventricle, RV pacing, aortic stenosis, aortic regurgitation, HTN, PDA, and hypertrophic cardiomyopathy.
Atrial Pressure Waveforms
a wave—An upward deflection produced by atrial contraction.
c wave—An upward deflection produced by mitral or tricuspid valve closure during ventricular contraction.
v wave—An upward deflection produced by atrial filling during ventricular contraction.
hypertension (identifiable cause) accounts for 5%. In either case, hypertension is an important risk factor for the development of strokes, heart attacks, heart failure, and kidney disease.
Risk Factors for Essential HTN\:
Obesity, weight gain, inactive lifestyle, excessive alcohol intake, high sodium intake, vitamin D deficiency, family history, older age, males, African Americans, stress, depression, dyslipideinia.

------------------------------------------------------------------------------------------------------------------------------------------------------------ , Table 3-1 • Causes of Secondary Hypertension
Disorder
Neurologic
Sleep apnea
Cardiovascular
Coarctation of the aorta
Renal
Renovascular hypertension
Primary renal disease
Endocrine Cushing's syndrome
Pheochromocytoma
Primary aldosteronism
Hypothyroidism
Hyperthyroidism
Primary hyperparathyroidism
Clinical Features\:
The majority of hypertensive patients will be asymptomatic on routine screening. Patients with secondary HTN will have clini­ cal features based on their specific etiology (see Table 3-1). At some point, chronic elevations in blood pressures can result in end-organ damage. The following are targets of end-organ dam­ age (from head to toe)\:
Neurologic—Strokes, TIA, dementia
Eyes—Hemorrhages, microaneurysms, cotton-wool spots, exudates, papilledema, arteriovenous nicking, copper wiring
Next Step Initial Approach
Sleep study
Transthoracic echocardiography (TTE) and a chest MRI or CT scan
Since there is potential harm in radiologic testing, imaging studies are conducted only if there is a clinical suspicion
for renovascular disease and a corrective procedure
would be performed if renovascular disease was detected. Renal arteriography is considered the gold standard for diagnosis, but it is an invasive test. Less invasive testing may be considered prior to renal arteriography, and that may include any of the following\:
• Duplex ultrasound
• CT angiography (CTA)
• MR angiography (MRA)
Evaluate for vascular disease (eg, vasculitis), glomerular disease (eg, infections, autoimmune disease), tubulointer­ stitial disease (eg, obstruction), cystic disease (eg, polycystic kidney disease), or chronic kidney disease (estimated GFR).
Dexamethasone suppression test and a 24-hour urine free cortisol level
24-hour urinary metanephrine or catecholamine
Plasma renin level or activity (low) Plasma aldosterone (high) Aldosterone/renin ratio (high) TSH (high)
TSH (low)
Serum calcium (high) PTH (high)
Cardiac—Heart failure, LVH, MI Renal—Renal failure, nephrosclerosis
Vascular—Peripheral arterial disease, arteriosclerosis, an­ eurysm, dissection
Next Step\:
Step 1) After an initial blood pressure screen, patients should have >2 follow-up visits (spaced over one or more weeks) to ob­ tain the average of >2 blood pressure readings to classify the blood pressure severity based on the JNC 7. The following are
Clinical Clues
Loud snoring, fatigue, daytime somnolence
Coarctation after the left subclavian artery\:
• Elevated BP in the upper extremities compared to the lower extremities
• Radial-femoral pulse delay
Coarctation before the left subclavian artery\:
• Elevated BP in the right arm compared to the left arm
• Delayed pulse in the left radial and femorals compared to the right radial artery
Abdominal bruit, recurrent flash pulmonary edema, T Cr levels after initiating an ACE inhibitor or ARB, atherosclerosis (older patients), fibromuscular dysplasia (young females), abrupt onset of severe HTN after 55 years of age, unexplained atrophic kidney, unprovoked hypokalemia
Elevated creatinine level, abnormal urinalysis
Moon facies, central obesity, buffalo hump, muscle weakness
Diaphoresis, palpitations, headaches, sense of "impending doom"
Hypokalemia, metabolic alkalosis
Cold intolerance, weight gain, coarse hair Heat intolerance, weight loss, fine hair
"Bones, stones, abdominal groans, and psychic moans"
CHAPTER 3 CARDIOLOGY 19

20 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
for adults 18 years and older. If there is a disparity between the systolic and diastolic pressures, the higher number is used to determine the severity of the hypertension.
Normal BP\: systolic <120 Hg and diastolic <80 mm Hg
Pre-HTN\: systolic 120 to 139 mm Hg or diastolic 80 to 89 mm Hg
Stage 1 HTN\: systolic 140 to 159 mm Hg or diastolic 90 to 99 mm Hg
Stage 2 HTN\: systolic >160 mm Hg or diastolic >100 mm Hg
Step 2) Patients with normal blood pressures can be followed up in 2 years, and patients that have prehypertension should be counseled about lifestyle modification (see step 4) and have a follow-up visit in 1 year. Patients diagnosed with hypertension should be evaluated for end-organ damage, to identify possible secondary causes of HTN (see Table 3-1), and to identify car­ diovascular risk factors, which is based on the JNC 7\:
• Age (men >55, women >65)
• Family history ofpremature cardiovascular disease (men<55, women <65)
• T LDL (or total), or >1 HDL
• Estimated GFR <60 mL/min • Microalbuminuria
• Diabetes mellitus
• Obesity
• Weight gain
• Hypertension
• Tobacco use, particularly cigarettes
Step 3) Extensive testing for secondary hypertension is not recommended unless the clinical clues suggest the presence of secondary hypertension. However, the initial workup for all hypertensive patients should include the following\:
• CBC (hematocrit)
• Blood chemistries (K+, Ca2+, Cr, or estimated GFR)
• Fasting blood glucose or Ale
• Lipid profile (LDL, HDL, triglycerides)
• Urinalysis
• Microalbuminuria (mainly for diabetics)
• EKG
Step4)Targetbloodpressuresshouldbe<140/90mmHginallhy­ pertensive patients and <130/80 mm Hg in patients with diabetes or renal disease. The best initial treatment approach is with lifestyle modification (either alone or in concert with medications) for at least 3 to 6 months. Lifestyle modifications include the following\:
• Weight loss—For every 1 kg lost, there is a 0.5 to 2.0 mm Hg reduction in BP.
• Diet—Reduce sodium intake, adopt DASH diet (T fruits, T vegetables, low-fat dairy)
• Exercise—At least 30 min/dy for most days of the week
• Alcohol—Limit 2 drinks/dy in men and 1 drink/dy in women
• Smoking cessation—To reduce cardiovascular risk, not necessarily BP
Step 5) Pharmacologic therapy is the next best step when patients continue to have elevated blood pressures (systolic >140 and/ or diastolic >90) despite attempts with lifestyle modification. Pharmacologic therapy can be easily remembered in four broad categories by their “A, B, C, Ds” (ACE inhibitors, ARBs, Beta- blocker, Calcium channel blocker, Diuretics). For most patients, thiazide diuretics are used as initial therapy, but under special conditions (see Table 3-2), the other classes of antihypertensive agents are used as initial therapy. The following is the initial pharmacologic management for stages 1 and 2 hypertension\:
Stage 1 HTN\: Thiazide-type diuretic (eg, chlorthalidone or HCTZ)
Stage 2 HTN\: Thiazide-type diuretic + “A, B, or C”
Step 6) After initiation of lifestyle modification and drug ther­ apy, suboptimal control of hypertension can occur. Consider four different clinical scenarios\:
Drug initiation\: In a patient that does not respond to an ad­ equate dose of a drug, switching to another first-line agent should be attempted rather than adding another agent. In a patient that has a partial response with a drug but target blood pressure is not achieved, either the dose may be titrated up to the next step or a low-dose agent of another drug can be added. The goal of therapy is to maximize the response from a drug, but to minimize the side effects with lower dosages.
Pseudoresistant hypertension\: Pseudoresistant hyper­ tension refers to patients that have poorly controlled hyper­ tension that appears to be resistant to medical treatment. However, the hypertension is usually due to the following\:
• “White coat” hypertension or office hypertension • Noncompliance
• Poor BP measurement technique
Pseudohypertension\: Pseudohypertension refers to patients that have an overestimation of their blood pressure readings because ofthe inability ofthe blood pressure cuffto adequately compress against a calcified or stiffened brachial artery. The elderly are particularly prone to this condition and are inad­ vertently being overdosed on antihypertensive agents result­ ing in orthostatic hypotension and other side effects.
Resistant hypertension\: Resistant hypertension refers to patients that cannot meet target blood pressures despite the useofthreedifferentclassesofantihypertensives(oneofwhich should be a diuretic), or blood pressure that is controlled with >4 drugs. Important aspects to consider are reversible factors that are associated with elevated blood pressures\:
Lifestyle—Physical inactivity, high salt intake, or heavy alcohol intake
Suboptimal therapy—Ineffective drugs, inadequate dosing, or inappropriate combinations
Secondary HTN—Identifiable secondary causes of hy­ pertension (see Table 3-1)
Medications—Glucocorticoids, NSAIDs, COX-2 in­ hibitors, OCPs (mainly estrogen), decongestants, diet pills, erythropoietin, tacrolimus, cyclosporine,

Table 3-2 • Antihypertensive Drug Profiles
Drugs
ACEIs
• Benazepril • Captopril • Lisinopril
ARBs
• Candesartan • Losartan
• Valsartan
Beta-blockers
• Atenolol
• Metoprolol • Propranolol
CCBs
Dihydropyridines
• Amlodipine • Nifedipine
Nondihydropyri- dines
• Diltiazem • Verapamil
Diuretics
Thiazides
• Chlorthalidone • HCTZ
Loops
• Furosemide • Bumetanide
Aldosterone antagonists
Side Effects
Cough, angioedema, hyperkalemia, worsening renal function with RAS
Angioedema, hyperkalemia, worsening renal function with RAS
Bradycardia, bronchospasm, fatigue, Raynaud's syndrome, masking hypoglycemic symptoms, associated with new-onset diabetes
Dihydropyridines
• Peripheral edema
• Reflex tachycardia
Nondihydropyridines
• Peripheral edema • AV blocks
• Bradycardia
Hypokalemia, hyperuricemia, hyperglycemia, increase in cholesterol
Hyperkalemia, gynecomastia, irregular
Avoid in These Conditions
• Pregnancy
• Intolerable cough • Hx of angioedema • Hyperkalemia
• Poor renal function
• Pregnancy
• Hxofangioedema • Hyperkalemia
• Poor renal function
• Asthma
• COPD
• 2° or 3° AV blocks
• Sick sinus syndrome • Severe bradycardia
• Severe PAD
• Depression
• Raynaud's syndrome • Uncompensated HF
Dihydropyridines
• Hypotension • PostMl
• Systolic HF
Nondihydropyridines • Hypotension
• 2° or 3° AV blocks
• Sick sinus syndrome • WPW syndrome
• Systolic HF
• Hypokalemia
• Gout
• Cautious use in diabetics • Severe dyslipidemia
• Hyperkalemia • Renal failure
Preferred Agents in These Conditions
• Diabetes
• Systolic HF
• Diastolic HF
• Stable angina • UA/NSTEMI
• STEMI
• LV dysfunction
• Intolerable cough from using ACEIs
• Atrial fibrillation • Stable angina
• UA/NSTEMI
• STEMI
• LV dysfunction
• Hyperthyroidism • Essential tremor • Migraine
• Compensated HF
In all CCBs\:
• Bronchospastic disease when BBs would be contraindicated.
• Raynaud's syndrome • Migraine
• Atrial fibrillation (only
nondihydropyridines)
• Systolic HF
• Osteoporosis (only
thiazides) • Edema
• Primary aldosteronism • Hypokalemia
Agents Shown to be Beneficial (Based on Clinical Trials) in These Conditions
• Diabetes
• HF
• Post-MI
• High coronary disease
risk • CKD
• Recurrent stroke prevention
• Diabetes • HF
• CKD
• Diabetes
. HF
• Post-MI
• High coronary disease
risk
In all CCBs\:
• Diabetes
• High coronary disease
risk
• Diabetes
• HF
• High coronary disease
risk
• Recurrent stroke
prevention
• HF
• Post-MI
• Spironolactone menses
ACEIs—angiotensin converting enzyme inhibitors, ARBs—angiotensin receptor blockers, AV—atrioventricular, BBs—beta-blockers, CCBs—calcium channel blockers, CKD—chronic kidneydisease, HCTZ—hydrochlorothiazide, HF—heart failure, Hx—history, LV—left ventricular, Ml—myocardialinfarction, NSTEMI—non-STsegmentelevation Ml, PAD—peripheral arterialdisease,RAS—renalarterystenosis,STEMI—STsegmentelevationMl,UA—unstableangina, WPW—Wolff-Parkinson-White
carbamazepine, clozapine, antidepressants, methylphe- nidate, metoclopramide
Illicit drugs—Cocaine, amphetamines, anabolic ste­ roids, PCP, ketamine, narcotic withdrawal
Natural compounds—Ephedra, ma huang, licorice, bitter orange
Follow-Up\:
Once antihypertensive agents are initiated, patients should be seen at monthly intervals or until blood pressure goals are achieved. Thereafter, patients can be seen every 3 to 6 months. Serum potassium and creatinine levels should be checked at least 1 or 2 times per year.
CHAPTER 3 CARDIOLOGY 21

22 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Pearls\:
• Prehypertension is not considered a disease category, but rather identifies those that are at risk of developing hypertension.
• Reduction in blood pressure is the major determinant in reducing cardiovascular risk, not the type of medication.
• Under the age of 50, the diastolic blood pressure is a better predictor of cardiovascular risk.
• After the age of 50, the systolic blood pressure becomes the better predictor of cardiovascular risk.
• In the presence of microalbuminuria, diabetics have an in­ creased risk of cardiovascular disease.
• Hypertension can result in left ventricular hypertrophy (LVH), which is usually characterized by concentric hyper­ trophy. LVH is associated with cardiovascular risk, and regression of LVH (via weight loss, salt restriction, and i BP) can lower the risk of a cardiovascular event.
• Blood pressure can rise transiently with each cigarette, but ha­ bitual smokers generally have lower blood pressures compared to nonsmokers. Smoking cessation should be advised for car­ diovascular risk reduction, not to lower the blood pressure.
• African Americans respond particularly well to thiazides and calcium channel blockers, but less so with ACEIs and beta-blockers. However, ACEIs and beta-blockers should still be used under specific indications (eg, diabetes/ACEIs, post-MI/beta-blockers).
• Elderly patients respond well to thiazides and calcium chan­ nel blockers, but they do not tolerate aggressive diuretic or beta-blocker therapy.
• Alpha-blockers (eg, doxazosin, prazosin, terazosin) are not con­ sidered first-line antihypertensive drugs, especially since they are associated with an increased risk of heart failure. However, alpha-blockers can be considered in older hypertensive men with concurrent prostatism that are not at high cardiovascular risk. Alpha-blockers should be discontinued in patients that have postural hypotension, which is a side effect of the medication.
• Calcium channel blockers (ie, verapamil, diltiazem, nifedip­ ine) are generally avoided in patients with coexisting systolic heart failure because these agents have negative inotropic properties. Patients with Systolic heart failure have a “Sissy” heart or a weakened floppy/dilated heart that can’t pump well, and giving a negative inotropic agent will cause further clinical deterioration. However, amlodipine and felodipine are better tolerated and appear safer since they have almost no negative inotropic properties. In patients that have sys­ tolic heart failure with coexisting angina or hypertension, a
LIPID METABOLISM DISORDER
1 HYPERLIPIDEMIA
Hyperlipidemia is characterized by elevated lipoprotein particles in the plasma. Total serum cholesterol consists of LDL (60%-70%), HDL (20%-30%), and VLDL (10%-15%).
beta-blocker or ACE inhibitor would be the preferred agents since they have been shown to improve survival.
• Treatment options for renovascular hypertension include an­ tihypertensive medications, percutaneous transluminal renal angioplasty (PTRA) ± stent, or surgical revascularization. Al­ though ACEIs and ARBs can worsen renal function (1GFR, TCr) in patients with renal artery stenosis (RAS), it is not a contraindication to use in RAS as long as the renal function is carefully monitored. In fact, ACEIs and ARBs are fairly effec­ tive in controlling hypertension in these patients, but therapy should be discontinued if creatinine levels rise significantly.
• Foundational point—Hypertension is associated with two types of vascular pathology, (1) hyaline arteriolosderosis, which is more common in the elderly and in diabetics (vessels consist of hyaline thickening), and (2) hyperplastic arteriolo- sclerosis, which is associated with acute or severe elevations in blood pressures (vessels consist of an onion-skin, concentric thickening).
• Foundational point—Sarcomeres are arranged in parallel instead of in series in concentric hypertrophy.
• Connecting point (pg. 76)—Know the management of Cushing’s syndrome.
• Connecting point (pg. 78)—Know the management of pheochromocytoma.
• Connecting point (pg. 72)—Know the management of hypothyroidism.
• Connecting point (pg. 68)—Know the management of hyperthyroidism.
• Connecting point (pg. 73)—Know the management of primary hyperparathyroidism.
• Connecting point (pg. 58)—Know the pattern of LVH on EKG.
• On the CCS, remember to "counsel” all your hypertensive patients.
• On the CCS, remember to encourage lifestyle modifications. The practice CCS does have “weight loss diet,” “low sodium diet,” “advise patient exercise program,” “advise patient limit alcohol intake,” and “advise patient no smoking.”
• On the CCS, when you place a patient on an antihyperten­ sive medication, be sure to select the “continuous” mode of frequency, which takes into account the periodic adminis­ tration (eg, q6 hours).
• On the CCS, office-based cases will usually require you to relocate patients back home, therefore become comfortable relocating patients prior to your Step 3 exam.
Chylomicrons (formed from dietary fat) and VLDL are both triglyceride-rich lipoproteins. An increase in cholesterol levels, particularly LDL, is a significant risk factor for coronary heart disease (CHD).
Modifiable Risk Factors\:
Smoking, overweight, obesity, physical inactivity, high-fat diet, diabetes, hypertension.

Clinical Features\:
Hyperlipidemic patients will be asymptomatic on routine screening. Accumulation of cholesterol is usually deposited in the vascular system (atherosclerosis), eyes, tendons, joints, or skin. Consider the possible clinical manifestations of hyperlipidemia, which can be due to acquired or familial disorders\:
1) Arcus senilis—An opaque ring-like deposit on the periph­ eral cornea.
2) Lipemia retinalis—Retinal blood vessels that take on a creamy appearance.
3) Xanthomas—Yellowish plaques or nodules that can be seen over skin, tendons (tendinous xanthoma), joints (tuberous xanthoma), or the inner canthus ofthe eyelids (xanthelasma).
Next Step\:
Step 1) Patients should be screened with a fasting lipid profile (ie, total cholesterol, LDL, HDL, triglyceride). There are two dif­ ferent recommendations on screening, so be aware of both\:
Adult Treatment Panel (ATP) III—Screening should occur in all persons >20 years of age at least every 5 years.
US Preventive Services Task Force (USPSTF)—Screening should occur in men >35 years of age. Women should be screened >45 years of age who are at risk for coronary heart disease (eg, smokers, obese, HTN, DM, Hx of CHD, family Hx of heart disease).
Step 2) Patients should have a risk assessment to help guide management. The following major risk factors for CHD should be counted\:
1) Age\: Men >45 years, women >55 years
2) Family Hx of premature CHD\: Male first-degree relative <55 years, female first-degree relative <65 years
3) Cigarettesmoking
4) Hypertension\: >140/90 mm Hg or on antihypertensive
medication
5) Low HDL\: <40 mg/dL, but if HDL is >60 mg/dL then one risk factor is negated from the total count of risk factors.
Table 3-3 • Clinical Management of the Different Risk Categories
Risk Category 0-1 Risk factor 2+ Risk factors
CHD or CHD risk equivalent (10-year risk >20%)a
Step 3) Identify patients that have established CHD (eg, MI, stable angina, unstable angina, Hx of coronary procedures) or CHD risk equivalents that are not part of the total count of risk factors in step 2. The following are CHD risk equivalents\:
• Diabetes
• Abdominal aortic aneurysm (AAA)
• Peripheral arterial disease
• Carotid artery disease (ie, >50% stenosis or symptomatic patients such as strokes or TIAs that originate from the carotids)
• Renal artery disease due to atherosclerosis
• Multiple risk factors that confer a >20% risk of a CHD event in 10 years (You won’t be able to calculate this on the boards since you need the Framingham risk tables.)
Step 4) Determine the risk category (see Table 3-3), which is based on the ATP III.
Step 5) Initiate therapeutic lifestyle changes (either alone or in concert with medications) for at least 3 months in patients that are not at LDL goal (see Table 3-3). Therapeutic lifestyle changes (TLC) includes the following\: i saturated fats, i cho­ lesterol, consider plant stanols/sterols and viscous fiber, T physi­ cal activity, weight control.
Step 6) Consider adding a lipid-lowering agent if LDL is not at goal despite TLC. Statins are the preferred agents because they are the only class of drugs to show improvements in mortality for primary prevention (ie, prevent new onset CHD) and sec­ ondary prevention (ie, prevent recurrent CHD in a person with established CHD). However, consider the other classes of lipid lowering drugs in Table 3-4.
Step 7) Concerns may arise during the clinical management of hyperlipidemia. Consider four different clinical scenarios\:
Myopathy—Myopathy can occur after the initiation of statins. Manifestations of myopathy can range from myal­ gias (± creatine kinase elevations) to myositis or to rhab- domyolysis (± acute renal failure from the myoglobinuria). Patients that are susceptible to statin-induced myopathy are those with liver disease, renal disease, hypothyroidism, or concomitant use with other drugs (eg, azole antifungals,
INITIATE TLC Based CONSIDER Drug Therapy Based on the LDL Level on the LDL Level (After TLC)

160 >190
160 (if 10-year risk <10%)a
Goal LDL (mg/dL)
<160
<130 >130
<100 >100 <70 (Optional for very high risk)b
130 (if 10-year risk 10%-20%)a
130 (Initiate drug therapy +TLC) 100-129 (Consider drug therapy)
‘ThepercentriskofaCHDeventin 10yearsrequirestheFraminghamrisktables,whichyouprobablywon'tbeable tocalculateontheboards,butitisgoodtobeawareofthe LDL ranges.
"Very high risk patients include those that have coronary heart disease (CHD) + DM, CHD + acute coronary syndrome, CHD + metabolic syndrome, or CHD + poorly controlled risk factors (eg, persistent smoking)
CHAPTER 3 CARDIOLOGY 23

24 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Table 3-4 • Lipid-lowering Drug Profiles Major Lipid
Drugs
HMG CoA reductase inhibitors (statins)
• Atorvastatin • Fluvastatin
• Simvastatin • Rosuvastatin
Bile acid sequestrants (resins)
• Cholestyramine • Colestipol
• Colesevelam
Nicotinic acid (niacin)
Fibrates
• Gemfibrozil • Fenofibrate
Cholesterol inhibitor
• Ezetimibe
Indications
To lower LDL (Considered first-line agents in LDL reduction)
To lower LDL
Favorable effects on
all lipids, but long-term use is limited by side effects
To lowerTG
To lower LDL
Effects
Side Effects
Avoid in These Conditions
Pregnancy (Category X), breast-feeding, active or chronic liver disease, unexplained persistent T in transaminases, or coadministration with macrolides (eg, erythromycin), antifungals (eg, itraconazole), HIV protease inhibitors (eg, telaprevir), or cyclosporine
Precautions\:
• Caution with concomitant use with nicotinic acid or fibrates Biliary obstruction, elevated triglycerides >200 mg/dL
Precautions\:
• Resins can interfere with absorption of warfarin, digoxin, and fat-soluble vitamins; however, they can be taken
1 hour before or 4 hours after administration of the resin.
Active or chronic liver disease, severe gout, unexplained persistent T in transaminases, arterial hemorrhage, or active peptic ulcer
Precautions\:
• Cautious use in diabetics
• Caution with concomitant use with statins
(rhabdomyolysis)
• Flushing and pruritus can be attenuated if aspirin or
NSAID is taken 30 minutes before dosing
Severe renal or hepatic disease, gallbladder disease, PBC, and repaglinide should not be used concurrently with gemfibrozil
Precautions\:
• Caution with concomitant use with statins (rhabdomyolysis)
• Caution with concomitant use with sulfonylureas (hypoglycemia)
• Caution with concomitant use with warfarin (T anticoagulation)
Unexplained persistent T in transaminases, or active liver disease plus coadministration with a statin
LDL 44 • Myopathy hdlT • TTransaminases TG i
LDLi • Abdominal pain hdlT • Bloating
TG T or • Nausea
no effect • Constipation
ldlT • Flushing hdlT • Pruritus TG i • Acanthosis
nigricans
• Hyperpigmentation • Hyperglycemia
• Hyperuricemia
• Gout
• TTransaminases
• i Platelets
• Peptic ulcer
LDLi • Dyspepsia
hdlT
tg44
• Cholelithiasis • Myopathy
• Hepatitis
LDL i • TTransaminases
hdlT
TG4
• Upper respiratory infections
LDL—low density lipoprotein, HDL—high-densitylipoprotein, PBC—primary biliarycirrhosis, TG—triglyceride
macrolides, HIV protease inhibitors, cyclosporine, gemfi­ brozil). Patients that complain of muscle weakness, brown urine, or muscle pain should be advised to call their phy­ sician. A creatine kinase should be obtained to document the myopathy, and discontinuation of the statin is recom­ mended if myopathy is suspected.
Statin-induced transaminase elevations—Patients should have a baseline LFT prior to initiating a statin. If patients develop an increase in transaminases after starting a statin, a repeat LFT should be obtained to confirm the elevation and then monitored frequently until the LFTs normalize. Statins should be discontinued if the AST/ALT is persis­ tently elevated 3 times the upper limit of normal.
Metabolic syndrome—Patients with the metabolic syn­ drome are at risk of CHD. The first-line strategy is to change their lifestyle, particularly increasing physical activity and reducing weight. The components of the metabolic syn­ drome are as follows, and the ATP III criteria use the pres­ ence of any three of the five traits\:
1) Abdominal obesity\: Men >40 inches (102 cm), Women >35 inches (88 cm)
2) HDL\:Men<40mg/dL,Women<50mg/dL 3) Triglycerides >150 mg/dL
4) Blood pressure >130/85 mm HG
5) Fasting glucose >110 mg/dL

Elevated triglycerides—Elevated triglycerides are asso­ ciated with an increased risk for CHD. Acquired causes of elevated triglycerides include obesity, physical inactiv­ ity, smoking, excessive alcohol intake, high-carb diets, type 2 diabetes, hypothyroidism, renal failure, nephrotic syndrome, pregnancy, or drugs (eg, beta-blockers, gluco­ corticoids, cyclosporine, retinoids, protease inhibitors, estrogens, tamoxifen). The first-line strategy is to change the patients’ lifestyle (eg, smoking cessation, t physical activity, 1 alcohol intake). Patients that have high tri­ glycerides (>500 mg/dL) are at risk of acute pancreatitis, in which case lifestyle changes plus drug therapy can be considered. Fibrates are the most effective, and bile acid sequestrants should be avoided.
Follow-Up\:
After initiating drug therapy, patients should be seen in 6 to 8 weeks for a repeat lipid profile. If there are any adjustments to the drug regimen, then the patient should be seen again in another 6 to 8 weeks. Once the patient is at goal, he or she can be seen every 4 to 6 months. Routine creatine kinase (CK) or LFTs are not necessary unless clinically indicated.
Pearls\:
• For every 10% reduction in cholesterol, there is an 11% reduction in total mortality risk and a 15% reduction in cor­ onary heart disease mortality.
• An easy way to remember an ideal cholesterol level is to keep your “highs high” (ie, T high-density lipoprotein) and your “lows low” (ie, 1 low-density lipoprotein).
• Most statins can be taken at any time of day, but in particular, simvastatin should be taken in the evening because it has a
CORONARY HEART DISEASE—ACUTE CORONARY SYNDROMES
I STEMI, NSTEMI, AND UNSTABLE ANGINA
Acute coronary syndromes (ACS) represent a continuum of clinical presentations that ranges from unstable angina (UA) through non-ST elevation myocardial infarction (NSTEMI), and to ST elevation myocardial infarction (STEMI). There are varying degrees of coronary artery obstruction in which a com­ plete occlusion is the typical cause for a STEMI, but a partial occlusion is the typical cause for UA and NSTEMI.
Clinical Features\:
Unstable angina—UA can present as either rest angina (>20 minutes), new-onset exertional angina, or previously diagnosed angina that takes on a crescendo pattern (increasing
relatively short half-life and most of the cholesterol synthesis occurs at night.
• Nicotinamide is also referred to as niacin, but it does not have any lipid lowering properties.
• Homocysteine appears to be associated with an increased risk for CHD, however it is not considered a “major” risk factor, and therefore, routine measurement or treatment of homocysteine levels is not recommended.
• Secondary causes of dyslipidemia include hypothyroidism, diabetes, nephrotic syndrome, chronic renal failure, obstruc­ tive biliary disease, and drugs (eg, corticosteroids, anabolic steroids, progestins, HIV protease inhibitors).
• If secondary dyslipidemia is suspected, a blood sample should also be sent for a TSH, Ale, UA (proteinuria), creati­ nine, and alkaline phosphatase.
• Foundational point—Statins inhibit the enzyme HMG CoA reductase, which plays a role in the rate-limiting step in cho­ lesterol biosynthesis.
• Foundational point—Atherosclerotic plaques consists of a lipid-rich core within the intima covered by a fibrous cap.
• Connecting point (pg. 81)—Metabolic syndrome can be seen in type 2 diabetes.
• Connecting point (pg. 121)—Metabolic syndrome can be seen in PCOS.
• On the CCS, remember to "counsel” all your hyperlipidemic patients.
• On the CCS, remember to encourage therapeutic lifestyle changes. The practice CCS does have “diet low fat,” “diet low cholesterol,” “diet high fiber? “advise patient exercise program,” and “weight loss diet” (recommend if patient is overweight).
severity, frequency, or duration). Clinical manifestations are similar to those of a STEMI (see next).
NSTEMI—Symptoms typically present at rest and are charac­ teristically more intense and prolonged. Clinical manifestations of a NSTEMI can also resemble those of a STEMI (see next).
STEMI—The classic presentation is retrosternal chest pain that radiates to the arms, neck, or back. Patients may not be able to precisely locate the pain, but may describe the pain as “heavy, pressure, aching, or discomfort,” which reflects visceral pain (somatic pain is described as sharp with precise location). Patients can experience sympathetic (eg, cool, clammy hands and diaphoresis) and parasympathetic effects (eg, weakness, nausea, vomiting). If the MI results in LV dysfunction, patients may have pulmonary rales, tachy­ pnea, hypotension (due to ventricular or valve dysfunction), S3, S4, paradoxical S2 (LBBB), or a systolic murmur (ventral septal rupture, papillary muscle dysfunction, or a flail mitral leaflet). If the MI results in RV dysfunction, patients may have JVD, hypotension, right-sided S3, or Kussmaul sign (T JVP with inspiration).
CHAPTER 3 CARDIOLOGY 25

26 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Next Step\:
Step 1) Access and stabilize Airway, Breathing, and Circulation.
Step 2) Establish IV access.
Step 3) Place monitoring equipment on patient\: pulse oximetry, continuous blood pressure cuff, continuous cardiac monitoring, 12-lead EKG. The EKG will give a clue to which anatomic part of the heart might be affected (see Table 3-5) and will help guide initial management of ACS (see step 7).
Step 4) Intervene with MONA\:
Morphine (IV)—Every 5 to 15 minutes (PRN) to alleviate
chest pain or anxiety. Oxygen—Maintain O., saturation >90%.
Nitroglycerin (sublingual)—Every 5 minutes for a maxi­ mum of 3 doses.
Aspirin (chewed and swallowed)—If unable to take orally, then rectal suppository.
Step 5) Perform a targeted history and physical. A focused physical exam may include general appearance, HEENT/neck, lung exam, heart exam, abdomen, and extremities.
Step 6) Obtain portable CXR (<30 minutes) and laboratory studies\: CBC, electrolytes, cardiac enzymes (eg, troponin-I), coagulation studies (eg, PTT, PT/INR), lipid profile.
Step 7) In the early stages of management, your clinical suspi­ cion for ACS and the initial 12-lead EKG will guide treatment approach. The cardiac enzymes are not useful in the early stages of patient care because in some patients it can take 4 to 6 hours (12 hours for all patients) for the cardiac enzymes to rise after an ML However, for board purposes, you should be able to differentiate between unstable angina, NSTEMI, and STEMI.
Unstable angina—No elevations in cardiac enzymes, and EKG may or may not show T wave inversions, ST depres­ sion, or transient ST elevation.
NSTEMI—Elevation in cardiac enzymes, which distin­ guishes this condition from UA, and EKG may or may not show T-wave inversions, ST depression, or transient ST elevation.
STEMI—Elevation in cardiac enzymes, and EKG will show new ST segment elevations in at least >2 contiguous leads or a new LBBB that is consistent with the presentation of ACS.
The ST segment elevations start at the ) point with eleva­ tions >1 mm in all leads except V, and V3, where elevations are >1.5 mm in all women, or >2 mm in men >40 years, or >2.5 mm in men <40 years.
Step 8) Therapeutic interventions consist ofreperfusion therapy (PCI or fibrinolysis), anti-ischemic therapy (beta-blockers and nitrates) and antithrombotic therapy which consists of antiplatelets (eg, aspirin, thienopyridines [clopidogrel, prasug- rel, ticlopidine], GPIIb/IIIa inhibitors [abciximab, eptifibatide, tirofiban]), and anticoagulation (eg, unfractionated heparin, LMWH, fondaparinux, bivalirudin). Consider the clinical man­ agement in the following three scenarios\:
Initial EKG Normal + Initial Enzymes Normal
1) Perform serial EKGs and serial cardiac enzymes.
2) Ifserialtestresultsarenegativeandthereisnofurtherchest discomfort, then consider stress testing. If cardiac enzymes are positive or there is recurrent chest pain, then treat as UA/NSTEMI.
STEMI
1) Select the reperfusion strategy without waiting for the results of the initial cardiac enzymes. Consider the 2 types of reperfusion therapies\:
Percutaneous coronary intervention (PCI)—PCI is the preferred approach if performed expeditiously (goal of door-to-balloon in <90 minutes). If long delays are antici­ pated (>120 minutes), then fibrinolytic therapy should be considered.
Fibrinolysis—If fibrinolysis (eg, streptokinase, alteplase, reteplase) is the treatment of choice, therapy should be per­ formed expeditiously (goal ofdoor-to-needle in <30 minutes). Fibrinolysis is usually considered if symptom onset is <12 hours, PCI is unavailable, or no contraindications exist. Absolute contraindications to fibrinolysis include\: active bleeding, Hx of intracranial hemorrhage, intracranial malignancy, ischemic stroke in the preceding 3 months, facial trauma/closed head injury in the preceding 3 months, cere­ bral vascular malformation, or suspected aortic dissection.
2) Startanti-ischemictherapy\:IVnitroglycerincanbegivenif patient has persistent chest pain despite 3 doses ofsublingual

nitroglycerin, and give a beta-blocker (eg, metoprolol) if the patient does not have bradycardia, AV blocks, overt heart failure, or reactive airway disease.
3) Start anticoagulation (eg, IV heparin).
4) Startantiplatelettherapy\:Aspirin(addclopidogrelifPCIis planned).
5) Inititatereperfusiontherapy.
No ST Elevation (UA/NSTEMI)
1) Startanti-ischemictherapy\:IVnitroglycerinifthereisper­ sistent chest pain and a beta-blocker if not contraindicated.
2) Start anticoagulation (eg, IV heparin).
3) Startantiplatelettherapy\:
Aspirin + clopidogrel (if noninvasive testing is selected), or
Aspirin + clopidogrel or GP Ilb/IIIa inhibitor (if angiogra­ phy is selected)
4) Decide which management strategy fits the patient. Consider the following\:
Immediate angiography—Patients in this category usu­ ally have very high risk features such as cardiogenic shock, hemodynamic instability, sustained arrhythmias, heart fail­ ure, new mitral regurgitation, new ventricular septal rupture, or persistent chest pain despite optimal medical therapy.
Early angiography—Angiography is usually performed within a 24-hour period as the anti-ischemic and an­ tithrombotic therapies are intensified. Patients in this category have high risk features, but they appear more stable. High risk features include elevated cardiac enzymes, prior CABG, prior PCI within 6 months, LVEF <40%, new ST segment depression on admission, or a high TIMI score.
Noninvasive testing—Patients in this category do not have high risk features. Patients can undergo stress testing (only if there is no recurrent chest pain and they have been clini­ cally stable for 12 to 24 hours) or an echo to evaluate for LV function. If there are high risk findings on the stress test or echo (eg, LVEF <40%), patients should be referred for diagnostic angiography with intent to perform revascular­ ization if needed.
Step 9) A predischarge assessment of the LV function with an echocardiography should be performed since there is an in­ crease in mortality in the long-term with patients that have LV systolic dysfunction.
Step 10) Discharge medications in patients treated for a STEMI, UA, or NSTEMI include the following\:
Aspirin is recommended indefinitely. Clopidogrel for 1 month to 1 year.
Beta-blocker is recommended indefinitely, CCBs if beta- blockers are contraindicated.
Statin (eg, atorvastatin).
ACEIs (or ARB if ACEI intolerant) in patients with heart failure, LVEF <40%, diabetes, HTN, and anterior MI in STEMI patients.
Disposition\:
Patients in the emergency room that are treated for a STEMI or UA/NSTEMI should be admitted to the hospital. Patients that are eventually released from the hospital should have close follow-up to reinforce secondary preventive measures. Low-risk patients can be seen in 2 to 6 weeks and higher-risk patients should be seen within 14 days.
Pearls\:
• Women, elderly, and diabetic patients may present with “atypical” symptoms such as nausea, vomiting, weakness, syncope, palpitations, or dyspnea.
• Troponins can exist as I, T, or C. Only I and T are heart- specific, but C is expressed in heart and skeletal muscle.
• Troponins I or T is considered the marker of choice for the diagnosis ofMI and much preferred over CK-MB because of their greater specificity and sensitivity.
• Creatine kinase (CK) can exist as MM, BB, or MB. All forms are distributed in different tissues, but there is more dis­ tribution of CK-MB in the heart. Specificity decreases in CK-MB in the setting of muscle injury, muscle disease, or surgery.
• Troponins (I or T) can rise as early as 2 to 3 hours after the onset of an acute MI and can persist for 10 to 14 days, permitting a late diagnosis.
• CK-MB can rise as early as 4 to 6 hours after the onset of an acute MI, but returns to baseline within 24 to 48 hours.
• Myoglobin and lactate dehydrogenase (LDH) are biomarkers for cardiac injury, but both lack specificity for the heart, and therefore, they are not routinely performed since troponins are more specific.
• Clopidogrel is an acceptable alternative to aspirin in patients that are intolerant to aspirin.
• A PPI should be given to patients with a history of GI bleed­ ing that are concurrently taking aspirin or clopidogrel.
• Caveat 1—Nitrates can cause hypotension and therefore should be avoided in patients taking a phosphodiesterase-5 inhibitor (eg, sildenafil, tadalafil, vardenafil) for erectile dysfunction, se­ vere aortic stenosis, low blood pressures, or right ventricular infarction (ie, patients rely on preload for cardiac output).
• Caveat 2—The initial EKG is often nondiagnostic in patients with ACS, therefore repeat EKGs at 10-minute intervals in patients with suspicion for ACS.
• Caveat 3—Fibrinolytic therapy is non-diagnostic recom­ mended in patients with UA or NSTEMI.
• Caveat 4—Patients should avoid caffeine for 12 hours or theophylline for 48 hours if the vasodilator stress agents are used for stress testing since caffeine and theophylline can attenuate the effects of the vasodilatation.
• Caveat 5—All nonaspirin NSAIDs should be withheld in the management of ACS since there is an increased risk of cardiovascular events with its use.
• Stress (exercise or pharmacologic) testing can be assessed by EKG, echocardiography, or radionuclide imaging.
CHAPTER 3 CARDIOLOGY 27

28 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Exercise EKG is often the initial test for patients that can ex­ ercise adequately and to risk-stratify patients with suspected coronary heart disease.
• Stress imaging (echocardiography or nuclear studies) is the preferred modality if the patient had a prior revasculariza­ tion, is on digoxin, or the resting EKG shows a LBBB, LVH, ventricular preexcitation, paced ventricular rhythm, or a ST segment depression >1 mm.
• Pharmacologic stress agents include an adrenergic agonist (eg, dobutamine) or vasodilator stress agents (eg, adenosine, dipyr­ idamole, regadenoson) that can increase coronary blood flow.
• Dobutamine should not be used in patients with severe hyper­ tension, aortic dissection, significant LV outflow tract obstruc­ tion, unstable angina, recent MI, or ventricular arrhythmias.
• Adenosine, dipyridamole, and regadenoson should be avoided in patients with bronchospastic airway disease, sick sinus syndrome, high degree AV blocks, hypotension, or pa­ tients receiving oral dipyridamole for medical therapy.
• Stress (exercise or pharmacologic) nuclear studies require a radioactive tracer that uses either thallium or technetium (Tc) based agents.
• Benzodiazepines should be used early in the care of cocaine- related myocardial ischemia, but beta-blockers should be avoided because of concerns for unopposed alpha-adrenergic stimulation.
• Inferior Mis are frequently associated with right ventricular infarctions because they are usually supplied by the same right coronary artery. Patients may present with hypoten­ sion, and treatment consists of a fluid challenge with normal saline to maintain adequate right ventricular preload.
• UA/NSTEMI patients that have multivessel disease after di­ agnostic angiography can be considered for a CABG or multi­ vessel PCI. In general, indications for a CABG in UA/NSTEMI patients are similar to those of stable angina, which include (1) left main coronary artery stenosis, (2) >70% stenosis
VALVULAR DISORDERS
0 MITRALSTENOSIS
Mitral stenosis is characterized by blood-flow obstruction from the left atrium to the left ventricle. The most common cause of mitral stenosis is rheumatic fever, and less commonly from congenital stenosis, mitral annular calcification, and large veg­ etations seen in endocarditis.
Clinical Features\:
Murmur Type\: Diastolic murmur (between S2 and S^.
Heart Sounds\: A loud St can be heard after closure of the ste­ notic mitral value in systole. As the mitral value opens in S2, an “opening snap” (OS) can be heard that is thought to represent tensing of the chordae tendineae in combination with opening
ofthe proximal LAD and proximal left circumflex artery, (3) severe 3-vessel disease, (4) multivessel disease + DM, or (5) multivessel disease + poor LV function.
• CABG is infrequendy performed in patients with a STEMI because ofthe relative quickness in reperfusion with either PCI or fibrinolysis; however, an urgent CABG can be considered in patients that are not candidates for PCI or fibrinolysis.
• Agents that reduce mortality include beta-blockers, ACEIs, aspirin, clopidogrel, prasugrel, and statins.
• There is no proven benefit (and there is potentially harm) in using fibrinolysis in patients with UA/NSTEMI.
• On the CCS, after the initial management in patients with a STEMI or UA/NSTEMI, remember to transfer the patient to the ICU setting for monitored care (ie, coronary care unit).
• On the CCS, remember to implement a course of action before a cardiology consultant is able to see your patient.
• On the CCS, if you want to order a stress test, type in “stress” in the order menu and then select your choice.
• On the CCS, be aware that a “PCI” is not the same as “coro­ nary angiography” (mainly diagnostic) but rather the same terminology as a “coronary angioplasty” (ie, stent placement).
• On the CCS, you cannot order “fibrinolysis” or “throm- bolytics” in the practice CCS, but rather the specific drugs (eg, streptokinase, alteplase, reteplase).
• On the CCS, with each CCS case you should be cognizant about monitoring the patient. Examples of monitoring param­ eters include repeat vital signs, physical exams, neuro checks, urine outputs, labs, pulse oximetry, cardiac monitoring, BP monitoring, fetal heart rate, or a monitored setting (eg, ICU).
• On the CCS, after managing a case on ACS, remember to “counsel family/patient,” “advise patient, no smoking,” “cardiac rehabilitation program,” “advise patient, exercise program,” “diet low fat,” “diet low sodium,” “advise patient, relaxation techniques,” and “vaccination, influenza.”
of the stenotic leaflets. After the opening snap, a mid to late diastolic, low-frequency decrescendo murmur (ie, “diastolic rumble”) can be best heard at the apex with the patient in the left lateral decubitus position in held expiration using the bell of the stethoscope. The diastolic rumble represents turbulent flow of blood through the stenotic valve. The intensity of the murmur will change upon different maneuvers (see Table 3-6).
Clinical Progression\: As the left atrial pressures become higher due to the stenosis, the size of the left atrium can become large enough to compress the recurrent laryngeal nerve causing hoarse­ ness. In addition, patients are more likely to develop atrial fibril­ lation due to left atrial enlargement. It should also be noted that an embolic event is often associated with atrial fibrillation. As the blood flow begins to back up and cause increasing pressures in the pulmonary vasculature, the patient may experience dyspnea. In some cases, the bronchial vein will rupture into the lung paren­ chyma resulting in hemoptysis. Over time, chronic pulmonary

Table 3-6 • Changes in the Intensity of Murmurs from Bedside Maneuvers
Maneuver
Standing (-1- preload)
Valsalva
(-1 preload) Squat (tpreload,
t afterload) Handgrip
(t afterload) Inspiration
(T blood to RV, -l blood to LV) Expiration
(4 blood to RV, t blood to LV)
Mitral Mitral Stenosis Regurgitation
4 4 4 4 4 T
t t 4 4
T T
Mitral Valve Prolapse
Early click, longer murmur
Early click, longer murmur
Delayed click, shorten murmur
Delayed click, shorten murmur
Aortic Stenosis 4
4 T4
Aortic
Regurgitation HCM
4 t 4 T T 4
VSD 4
t
HCM—hypertrophiccardiomyopathy, LV—leftventricle,RV—rightventricle, VSD—ventralseptaldefect
Note\: Left-sided murmurs (ie, mitral, aortic) and left-sided gallops (ie, SJ,S4) are typically louder during expiration. Right-sided murmurs (ie, tricuspid, pulmonic) and right-sided gallops (ie, Ss,St) are usuallylouderduring inspiration.
hypertension will lead to right-sided heart failure resulting in T
JVP, hepatomegaly, and lower extremity edema.
Severity\: Normal mitral valve area is between 4 and 6 cm2 with a mean gradient between the 2 chambers of 0 mm Hg and a pulmonary artery systolic pressure (PASP) less than 30 mm Hg. The severity of the stenosis is classified as mild stenosis (valve area >1.5 cm2, mean gradient <5 mm Hg, PASP <30 mm Hg), moderate stenosis (valve area 1.0-1.5 cm2, mean gradient 5-10 mm Hg, PASP 30-50 mm Hg), and severe stenosis (valve area <1 cm2, mean gradient >10 mm Hg, PASP >50 mm Hg).
Next Step\:
Step 1) The best initial test is with a transthoracic echocar­ diography (TTE) with color flow Doppler imaging that can assess the severity of the stenosis, valve area, valve morphology, associated valve lesions, mean gradients, estimated PASP, and suitability for percutaneous mitral balloon valvotomy (PMBV). Other adjunctive testing may include the following\:
EKG—In the presence of left atrial enlargement, a large P wave that is broad and notched (M shaped) can be seen in lead II, also referred to as “P-mitrale.” A biphasic P wave with a promi­ nent negative component in the terminal portion ofthe P wave in lead V, is also consistent with left atrial enlargement. In the presence of pulmonary hypertension with subsequent right ventricular hypertrophy (RVH), a tall R wave can be seen in lead Vj usually with a right axis deviation.
Chest x-ray—Enlargement of the left atrium may produce a double shadowing of the cardiac silhouette (“double den­ sity”), upward displacement of the left mainstem bronchi,
and straightening of the left heart border. Kerley A, B, and C lines can sometimes be appreciated with increasing pul­ monary congestion.
Transesophageal echocardiography (TEE)—TEE is more invasive compared to the TTE, but it provides superior visualization of the posterior cardiac structures. The main indi­ cations for a TEE are equivocal information based on the TTE or to detect the presence of left atrial thrombi before DC car­ dioversion or percutaneous mitral balloon valvotomy (PMBV).
Cardiac catheterization—Cardiac catheterization is an inva­ sive test that can be used when the severity of the stenosis is still in question after echocardiography. Catheterization can pro­ vide information on the hemodynamics within the valve area.
Step 2) The clinical management for mitral stenosis can be best summarized into patients that are asymptomatic or symptomatic.
Asymptomatic\: Patients with moderate to severe mitral steno­ sis (valve area <1.5 cm2) plus evidence of pulmonary hyperten­ sion (PASP >50 mm Hg at rest or >60 mm Hg with exercise) can undergo percutaneous mitral balloon valvotomy (PMBV).
Symptomatic\: Patients with moderate to severe mitral stenosis (valve area <1.5 cm2) can undergo PMBV, but pharmacologic therapy may be appropriate to stabilize the patient or optimize loading conditions prior to intervention. The following condi­ tions may require medical attention before intervention\:
Pulmonary congestion—Diuretics (usually loop diuretics) and sodium restriction.
Systolic heart failure—Digoxin can be used as an inotropic agent in patients with decreased ventricular contractility.
CHAPTER 3 CARDIOLOGY
29
4 T4T 4 4
T t

30
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Atrial fibrillation—Hemodynamically unstable patients re­ quire immediate electrical cardioversion. Hemodynamically stable patients may require rate control with beta-blockers (eg, metoprolol), calcium channel blockers (eg, verapamil, diltiazem), or less preferably with digoxin. In addition, long­ term anticoagulation is recommended in patients with a left atrial thrombus, prior embolic event, or atrial fibrillation that is persistent, paroxysmal, or permanent. Warfarin can be used with a target INR of 2.5 with a range of 2.0 to 3.0.
Step 3) Patients with rheumatic mitral stenosis should receive prophylactic antibiotics for secondary prevention of rheumat­ ic fever. It should be noted that if patients have acute rheumatic fever, a full course of therapeutic antibiotics should be given prior to initiating prophylactic antibiotics. Acceptable prophy­ lactic antibiotics include benzathine penicillin G (intramuscu­ lar), penicillin V (oral), or sulfadiazine (oral).
Follow-Up\:
A TTE should be performed anytime there is a change in clinical status. Patients that are stable and asymptomatic but have mild stenosis should have an echo every 3 to 5 years, with moderate stenosis every 1 to 2 years, and with severe stenosis every year.
Pearls\:
• Routine infective endocarditis prophylaxis is no longer rec­ ommended in patients with common valvular disease (eg, aortic or mitral valve disease, mitral valve prolapse with regurgitation) except in patients with a previous episode of infective endocarditis or prosthetic materials used in heart repair. Amoxicillin or ampicillin can be used in these high-risk patients that require prophylaxis for dental, oral, or upper respiratory tract procedures. Routine infective endo­ carditis prophylaxis is not indicated in patients undergoing GI (eg, colonoscopy) or GU (eg, cystoscopy) procedures unless the patient has an ongoing GI or GU infection. If a patient has an ongoing infection, then amoxicillin or ampi­ cillin are acceptable antibiotics prior to the procedure.
• A percutaneous mitral balloon valvotomy (PMBV) involves threading a catheter from the femoral vein into the right atrium and into the left atrium through a transseptal puncture and then across the mitral valve. A balloon is inflated and deflated to open the fused commissures.
• When PMBV is indicated, it is generally performed on patients with rheumatic mitral stenosis.
• Surgical intervention is preferred over PMBV in the setting of persistent left atrial thrombus despite anticoagulation, moderate to severe mitral regurgitation, unfavorable mitral valve morphology, mitral annular calcification, or congenital mitral stenosis.
• An open surgical commissurotomy allows direct visualiza­ tion of the mitral valve and is often indicated when a valve is not amenable to PMBV.
• Mitral valve replacement (MVR) is considered the last alter­ native for treating mitral stenosis and is often indicated when a valve is not amenable to PMBV or open commissurotomy.
• The effects of pregnancy, especially an increase in heart rate and cardiac output, can cause mitral stenosis to mani­ fest in previously asymptomatic patients or exacerbate existing symptoms. In most pregnant patients, mitral stenosis is due to rheumatic fever. Patients with mild to moderate mitral stenosis can be medically managed and PMBV reserved for severe symptoms that are refractory to medical management. It should be noted that warfarin is contraindicated, especially in the first trimester, because of teratogenicity; instead, heparin should be used for hos­ pitalized patients.
• A prominent “a” wave can be seen in the right atrial pressure waveform in patients with pulmonary hypertension with right ventricular hypertrophy.
• Connecting point (pg. 58)—Know right axis deviation and right ventricular hypertrophy (RVH).
• Connecting point (pg. 223)—Know how to treat pharyngitis due to group A streptococcus (GAS).
• On the CCS, a “TTE” and a “TEE” are both available in the practice CCS.
• On the CCS, a “percutaneous mitral balloon valvotomy (PMBV)” is not available in the practice CCS, but if you type in “mitral” in the order menu, a list of mitral valve procedures are available including “mitral valve balloon valvuloplasty.”
• On the CCS, once you demonstrate your skills sufficiently and have met the exam objectives, the CCS case will most likely end early.
0 CHRONICMITRALREGURGITATION
Mitral regurgitation (MR) is characterized by the failure of the mitral valve to close during systole resulting in a portion of the stroke volume being ejected back into the left atrium. Primary causes of MR that involve the valve apparatus are trauma, rheu­ matic heart disease, infective endocarditis, mitral annular cal­ cification, congenital malformation, or mitral valve prolapse. Secondary (functional) causes of MR include ischemic heart disease (left ventricular remodeling), hypertrophic cardiomy­ opathy, or dilated cardiomyopathy.
Clinical Features\:
Murmur Type\: Systolic murmur (between Sj and S2) Heart Sounds\:
Sj—Soft Sj reflecting the failure of the mitral valve to close.
S2—Wide split S2 can be due to early (shortened ejection time) and/or late P2 (presence of pulmonary hypertension).
Sj—Sj gallop is usually seen in chronic MR, which reflects the increase in blood return to the left ventricle in early diastole (Sj is a normal finding in young adults and children).
Murmur sound—A high-frequency pansystolic/holosys- tolic murmur (ie, “blowing” quality) can be best heard over the apex with the patient in the left lateral decubitus position using the diaphragm of the stethoscope. The murmur will

classically radiate to the left axilla or subscapular region. The intensity of the murmur will change upon different maneu­ vers (see Table 3-6).
Clinical Progression\: As blood flows in a retrograde fashion from the left ventricle to the left atrium during systole, the left atrium enlarges and becomes more compliant in the gradual development ofchronic mitral regurgitation (MR). Because ofthe atrial enlarge­ ment, the left atrial pressures are reduced and pulmonary conges­ tion becomes less common. However, left atrial enlargement can predispose the patient to the development of atrial fibrillation with subsequent thromboembolism. In addition to left atrial enlargement, the left ventricle also undergoes compensatory dila­ tation (ie, compensated phase). Over time, the chronic volume overload results in eccentric hypertrophy. As a result of an in­ crease in end-diastolic volume, the stroke volume increases, which translates into a preserved cardiac output (Frank-Starling mecha­ nism). At some point, the myocardium begins to weaken and can no longer compensate for the regurgitation (the transitional phase). Eventually, the forward output deteriorates and signs and symptoms of heart failure develop (the decompensated phase).
Severity\: For board purposes, the following is a general guide­ line for classifying the severity of MR seen in adults\: mild (LA and LV size normal, regurgitant fraction <30%, regurgitant orifice area <0.2 cm2), moderate (LA and LV size normal to dilated, regurgitant fraction 30%-49%, regurgitant orifice area 0.2-0.39 cm2), and severe (LA and LV dilated, regurgitant frac­ tion >50%, regurgitant orifice area >0.4 cm2).
Next Step\:
Step 1) The best initial test is with a transthoracic echocardiogra­ phy (TTE). Ifthe information provided by the TTE is suboptimal, the next best step is with a transesophageal echocardiography (TEE). A cardiac catheterization can be considered if the infor­ mation on TTE or TEE is equivocal or mechanical intervention is being considered in patients at risk of coronary artery disease. Other adjunctive testing may include the following\:
EKG—EKG may demonstrate “P-mitrale” (ie, left atrial enlargement), tall R wave in lead Vt with right axis devia­ tion (ie, RVH), or a tall R wave in lead Vs or V6 with a deep S wave in lead Vt (ie, LVH).
Chest x-ray—Enlargement of the left atrium (ie, double density, left bronchi upward displacement, left heart border straightened), enlargement of the left ventricle (ie, cardiac silhouette displaced to the left), or concomitant enlarge­ ment of both the atrium and ventricle (ie, cardiomegaly) can be seen.
Step 2) The clinical management for mitral regurgitation can be best summarized into patients that are asymptomatic or symptomatic. The recommendations for mitral valve surgery are based on the American College of Cardiology/American Heart Association (ACC/AHA) guidelines.
Asymptomatic\:
1)Severe chronic MR + Dysfunctional LV (EF <60% and/or end-systolic dimension >40 mm) —> Mitral valve surgery
2) SeverechronicMR+PreservedLVfunction(EF>60%and end-systolic dimension <40 mm) + Good chance of suc­ cessful repair —» Mitral valve surgery
3) Severe chronic MR + Preserved LV function + New-onset atrial fibrillation —> Mitral valve surgery + Maze procedure (several cuts in the left atrium to disrupt electrical pathways)
4) Severe chronic MR + Preserved LV function + Pulmonary HTN (PASP >50 mm Hg at rest or >60 mm Hg during exercise) —» Mitral valve surgery
Symptomatic\:
1) MedicalTherapy
• Vasodilators are not typically recommended in patients with asymptomatic chronic MR.
• Short-term vasodilator therapy (eg, IV nitroprusside) may be beneficial in patients with severe symptomatic chronic MR.
• Long-term vasodilator therapy (eg, oral hydralazine) is typically reserved for symptomatic patients who are not candidates for surgery.
• Patients with secondary (functional) MR with systolic heart failure should receive an ACE inhibitor (or ARB), diuretic, beta-blocker, and an aldosterone antagonist. It is important to optimize medical therapy since the long­ term benefit of mitral valve surgery for severe secondary MR is still inconclusive.
2) Surgery
• Severe chronic MR + NYHA Class II-IV (see Pearls) + LV dysfunction that is not severe (EF >30% and/or end- systolic dimension < 55 mm) —> Mitral valve surgery
• Severe primary chronic MR (ie, not secondary MR) + NYHA Class III-IV (see Pearls) + Severe LV dysfunction (EF <30% and/or end-systolic dimension >55 mm) + Good chance of successful repair —» Mitral valve surgery
Step 3) Patients with rheumatic mitral regurgitation should receive prophylactic antibiotics for secondary prevention of rheumatic fever.
Follow-Up\:
A TTE should be performed anytime there is a change in clini­ cal status. Patients that are asymptomatic but have moderate MR should have an echo every year, and those with severe MR should have an echo every 6 to 12 months. Patients that have mild MR should be seen every year, but an echo is not necessary unless there is a change in clinical status.
Pearls\:
• Routine infective endocarditis prophylaxis is no longer recommended in patients with common valvular disease, in­ cluding mitral regurgitation, unless the patient had a previous episode of infective endocarditis or prior prosthetic repair.
• New York Heart Association (NYHA) functional classifica­ tion summarized\:
CHAPTER 3 CARDIOLOGY 31

32 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Class I—Cardiac disease without physical limitation.
Class II—Slight limitation of physical activity, but comfort­ able at rest.
Class III—Marked limitation of physical activity, but com­ fortable at rest.
Class IV—Discomfort with any physical activity, and symp­ toms may be present at rest.
• Consider three types of holosystolic murmurs\:
1) VSD
2) Tricuspidregurgitation—Typicallyassociatedwith pulmonary HTN
3) Mitral regurgitation—Characteristically seen in chronic MR
• Consider three types of early systolic murmurs\:
1) VSD—AssociatedwithlargeVSDswithpulmonary HTN or small muscular VSDs
2) Tricuspidregurgitation—Typicallywithoutpulmonary HTN
3) Mitralregurgitation—CharacteristicallyseeninacuteMR
• If atrial fibrillation is encountered, rate control and antico­ agulation may be warranted.
• The pulmonary capillary wedge pressure (PCWP) is an indi­ rect measurement of the left atrial pressures.
• Concentric hypertrophy is seen in conditions with chronic pressure overload such as aortic stenosis or hypertension.
• In general, mitral valve repair is preferred over mitral valve replacement.
• Two types of mitral valve replacement can be performed, ei­ ther with a mechanical valve (requires lifelong warfarin) or a bioprosthetic valve (limited “shelf” life due to degeneration).
• The bell of the stethoscope is used to detect low-frequency sounds, and the diaphragm is used to detect high-frequency sounds.
• Although there are a lot of details in this topic, it should be noted that once you understand the details you will have a better global (broader) understanding of mitral regurgitation and your overall clinical judgment will be sharper.
• Foundational point—Sarcomeres that are arranged in series (resulting in elongation of the heart) instead of in parallel are seen in eccentric hypertrophy.
• Foundational point—The Frank-Starling principle explains that the greater the end-diastolic volume (ie, t muscle fiber stretch), the greater the stroke volume or cardiac output. At the same token, a reduced end-diastolic volume (eg, dehy­ dration) would result in a reduced stroke volume.
• CJ\: A 51 -year-old man presents with sudden severe dyspnea, tachycardia, hypotension, pallor, and diaphoresis. Heart exam reveals an early systolic murmur ending before S2 that can be heard along the left sternal border. EKG shows no sig­ nificant abnormalities, CXR shows pulmonary edema, and a TTE shows a flail mitral leaflet. What are your next steps? Answer\: The patient has acute mitral regurgitation (MR). Causes of acute MR include trauma, infective endocarditis,
or MI, which can cause a papillary muscle rupture, chordae tendineae rupture, or a flail leaflet. In cases when the left atrium has not compensated, the regurgitant blood flow will cause high pressures that will eventually be transmitted to the pulmonary circulation resulting in rapid pulmonary edema. In cases when acute MR is superimposed on chronic MR, the presentation may not be so dramatic. In either case, the left atrial pressure waveform will have a prominent “v” wave, which is often referred to as a “cv” wave because the v wave merges with the preceding c wave. The corresponding “cv” wave reflects the increasing left atrial filling during systole. Surgical intervention is the definitive treatment, however, prior to surgery, the patient may need to be medically man­ aged. If the patient is normotensive, then IV nitroprusside can be used to reduce the afterload and improve forward output. However if the patient is hypotensive, then adminis­ tration of an inotropic agent (eg, dobutamine) or intraaortic balloon pump (LABP) should be inserted in conjunction with the nitroprusside.
• On the CCS, ifyour CCS case ends early, any remaining real time will not be added to other CCS cases.
1 MITRALVALVEPROLAPSE
Mitral valve prolapse (MVP) is a common valvular disorder that affectsapproximately0.6%to2.4%ofthepopulationintheUnited States. MVP can be characterized by the billowing of the mitral leafletsintotheleftatriumduringsystole.PrimarycausesofMVP include familial or sporadic cases. Secondary causes of MVP can be associated with connective tissue disorders (eg, Ehlers-Danlos syndrome, osteogenesis imperfecta, Marfan syndrome) or a se­ quel to acute rheumatic fever, endocarditis, trauma, or myocardial infarction (ie, chordae tendineae or papillary muscle rupture). MVP is a common cause of mitral regurgitation (MR) and typi­ cally a common cause of MR seen in pregnant women.
Clinical Features\:
Murmur Type\: Systolic murmur (between St and S2).
Heart Sounds\: The classic auscultatory finding is a midsystolic “click” (single or multiple), which is thought to represent the sud­ den tensing of the chordae tendineae with billowing of the mitral leaflet into the left atrium. In some patients, the click is followed by a late systolic murmur (early in the disease) that crescendos into S2. Ifthere is a flail leaflet or severe prolapse, a holosystolic murmur will be heard instead. The click and murmur can be best heard over the cardiac apex using the diaphragm ofthe stethoscope with bed­ side maneuvers altering the sound pattern (see Table 3-6).
Clinical Presentation\: MVP occurs more frequently in women than in men. Most patients with MVP are asymptomatic. How­ ever, another group of patients have MVP syndrome, which includes MVP plus nonspecific symptoms such as palpitations, chest pain, anxiety, dizziness, dyspnea, fatigue, or exercise in­ tolerance. Although the validity of MVP syndrome is still in question, it is important to be aware of the condition for board purposes. On physical exam, common associated conditions in­ clude scoliosis, pectus excavatum, and low BMI.

Next Step\:
Step 1) The clinical examination is the best initial test. Upon auscultatory findings on exam, MVP can be con­ firmed with 2D-echocardiography that demonstrates the valve prolapse of >2 mm above the mitral annulus in long axis views (parasternal and apical 3-chamber). The EKG and CXR are usually normal unless the patient has developed chronic mitral regurgitation.
Step 2) Consider the clinical management of MVP\:
Asymptomatic—Provide reassurance. Patients that have mild to moderate MR with normal LV function can par­ ticipate in all competitive sports. However, patients with severe MR or LV dysfunction should be restricted to less competitive sports.
Autonomic dysfunction—Patients that have palpitations, chest pain, or anxiety may respond to beta-blockers. In addition, they should be counseled to avoid alcohol, caffeine, and tobacco. A 24-hour Holter monitor may be beneficial to detect supraventricular or ventricular arrhythmias.
Mitral regurgitation—Indications for mitral valve surgery in patients with MVP are the same as those for other primary causes of MR (see step 2 in Chronic Mitral Regurgitation section).
Infective endocarditis prophylaxis—Routine infective endo­ carditis prophylaxis is no longer recommended in patients with common valvular disorders, including MVP even with mitral regurgitation, unless the patient had a previous episode of in­ fective endocarditis or prior prosthetic repair.
Step 3) Patients with MVP due to rheumatic disease should receive prophylactic antibiotics for secondary prevention of rheumatic fever.
Follow-Up\:
Patients with MVP that are asymptomatic and without mitral regurgitation should be seen for a clinical exam every 3 to 5 years, but should be seen earlier anytime there is a change in clinical status.
Pearls\:
• The association between sudden cardiac death (SCD) and MVP is still unclear. However, patients that do survive a sud­ den cardiac arrest (SCA) through appropriate intervention may require an implantable cardioverter-defibrillator (ICD).
• The association between cerebral vascular events and MVP continues to be controversial. Different societies have dif­ fering recommendations on antithrombotic therapy, but the common agreement is (1) aspirin is recommended in pa­ tients with unexplained TIAs, and (2) anticoagulation (war­ farin) is recommended if aspirin is ineffective (ie, recurrent TIAs) or there is established systemic embolism.
• The prevalence of panic disorder in patients with MVP is no different than in patients without MVP.
• On the CCS, the final diagnosis and reasons for your consult are not used in evaluating your performance.
1 AORTICSTENOSIS
Aortic stenosis (AS) can be characterized by the obstruction of blood flow across the aortic valve. Three main causes ofvalvular AS are congenital (unicuspid or bicuspid valve), calcific (due to age-related degenerative changes), and rheumatic disease (usu­ ally coexisting with mitral valve disease).
Clinical Features\:
Murmur Type\: Systolic murmur (between St and S2). Heart Sounds\:
Sj—Usually normal.
S2—Soft Aj (reflecting the immobile aortic valve) followed by a P2. With increasing severity ofthe AS, a delayed aortic valve clo­ sure can cause the P2 to precede the \ resulting in a paradoxical split S2. As the aortic valve becomes more stenotic, the \ may disappear, resulting in a single S2 (ie, just a P2).
S.—S. can be heard, which reflects atrial contraction into a 44
stiffened ventricle (ie, LV hypertrophy).
Murmur sound—A systolic crescendo-decrescendo “ejec­ tion” murmur (ie, “harsh” quality) can be best heard over the right second intercostal space with radiation that is trans­ mitted equally over both carotid arteries. In elderly patients, the murmur may radiate to the apex instead of the carotids, which may be misinterpreted as mitral regurgitation (Gal- lavardin phenomenon). On palpation ofthe carotid artery, a diminished and delayed (parvus et tardus) carotid upstroke is a classic finding in severe aortic stenosis, but may be masked in elderly patients who have stiffened carotid ves­ sels. The intensity ofthe murmur will change upon different maneuvers (see Table 3-6).
Clinical Progression\: As the aortic orifice area becomes smaller and a pressure gradient begins to develop, the outflow obstruc­ tion leads to an increase in left ventricular systolic pressures. The left ventricle is able to compensate by increasing the wall thickness (ie, concentric hypertrophy). The wall thickness can now reduce the wall stress (Laplace’s law) and ventricular func­ tion can be preserved with the patient being asymptomatic for a prolonged period. At some point, the left ventricular func­ tion becomes maladaptive and LV function begins to decline. Patients with advanced aortic stenosis can present with the classic symptoms, which can be easily remembered by the mnemonic “SAD” or Syncope, Angina, and Dyspnea (ie, heart failure).
Severity\: In adults, the normal aortic valve area is between 3 and 4 cm2 with a mean gradient <5 mm Hg and an aortic jet velocity of <2 in/sec. The severity of the stenosis can be classified as mild stenosis (valve area >1.5 cm2, mean gradient <25 mm Hg, aortic jet velocity <3 m/sec), moderate stenosis (valve area 1.0-1.5 cm2, mean gradient 25-40 mm Hg, aortic jet velocity 3-4 m/sec), severe stenosis (valve area <1 cm2, mean gradient >40 mm Hg, aortic jet velocity >4 m/sec), and critical aortic stenosis (valve area <0.75 cm2 and/or aortic jet velocity >5 m/sec). It should be noted that there is variability between symptoms and the severity of the stenosis (eg, patients classified with severe stenosis may have little to no symptoms and vice versa).
CHAPTER 3 CARDIOLOGY 33

34 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Next Step\:
Step 1) The best initial test is with a transthoracic echocar­ diography (TTE). The TTE may also detect concurrent mitral valve disease and aortic regurgitation that can be seen with AS. The transesophageal echocardiography (TEE) is not routinely used, but would be the next best step if TTE does not provide adequate information. A cardiac catheterization can be consid­ ered if there is a discrepancy between the clinical and echocar- diographic findings. In addition, coronary angiography becomes fairly important in patients with aortic stenosis since there is a higher prevalence of coronary artery disease (CAD). Patients who have signs and symptoms of coronary artery disease who are about to undergo valve surgery should have a coronary an­ giography. Also, patients that are >35 years old with risk factors for CAD should undergo a coronary angiography prior to valve surgery. Other adjunctive testing may include the following\:
EKG—EKG may be completely normal or may reveal left ventricular hypertrophy (LVH) and sometimes left atrial hypertrophy.
Chest x-ray—CXR may be completely normal early in the disease, but later show rounding of the LV apex suggesting LVH. Another key finding is dilatation of the aortic root and/or ascending aorta, which may suggest that the patient has bicuspid aortic valves. It is important to be aware of such findings since dilatation ofthe aorta can lead to dissec­ tion or aneurysm formation. Therefore, a CT or MRI may be necessary to better visualize the aorta since echocardiog­ raphy may be limited in its assessment. However, it should be noted that a TTE is the best initial test in patients with known bicuspid aortic valves to evaluate the aortic root and ascending aorta.
Step 2) The clinical management for aortic stenosis can be best summarized into patients that are asymptomatic or symptomatic.
Asymptomatic\: It is generally recommended that asymptomatic patients with isolated severe aortic stenosis should not undergo routine prophylactic valve replacement. However, the ACC/ AHA guidelines do support surgery if the patient has severe AS with a LVEF of <50%, or a patient with moderate to severe AS who will undergo a concurrent CABG, aortic surgery, or other valve surgery at the same time.
Symptomatic\: Aortic valve replacement (AVR) is indicated when patients become symptomatic since the survival time is limited after the onset of symptoms and there is an increased risk of sudden cardiac death (especially in symptomatic severe AS). Pharmacologic therapy should be limited prior to surgery since it can potentially destabilize the patient.
Step 3) Patients with rheumatic aortic stenosis should receive prophylactic antibiotics for secondary prevention of rheumatic fever.
Follow-Up\:
A TTE should be performed anytime there is a change in clini­ cal status. Patients with mild AS should receive an echo every 3 to 5 years, those with moderate AS every 1 to 2 years, and those with severe AS every year. In addition, the ACC/AHA
recommends monitoring dilatation of the aortic root or ascend­ ing aorta (diameter >40 mm) every year with echocardiography, cardiac MRI, or CT.
Pearls\:
• Routine infective endocarditis prophylaxis is no longer
recommended in patients with common valvular disease, including AS, unless the patient had a previous episode of infective endocarditis or prior prosthetic repair.
• Exercise testing is not recommended in patients with symp­ tomatic AS.
• Atrial fibrillation is not a common event in isolated aortic stenosis. If atrial fibrillation is present, it is usually associated with heart failure.
• If atrial fibrillation is encountered, the management is simi­ lar to patients without AS.
• Percutaneous aortic balloon valvotomy is not considered an al­ ternative to aortic valve replacement (AVR), but it can be used as a bridge to AVR or as a palliative measure in critically ill patients.
• If a patient has a contraindication to warfarin or does not want to take anticoagulation, consider a bioprosthetic valve over a mechanical valve.
• Both aortic and pulmonic valves are normally tricuspid.
• Patients with congenitally deformed aortic valves can have normal functioning valves at birth, but over time the aortic valve can develop fibrocalcific changes that can lead to pro­ gressive stenosis.
• Aortic stenosis due to a congenital cause is typically seen in younger patients.
• Aortic stenosis due to rheumatic disease is not as common in the United States, but is common worldwide.
• Aortic stenosis due to age-related degenerative calcific changes (also known as “senile” or sclerocalcific AS) is now considered the most common cause of adult aortic stenosis in the United States.
• Aortic valve sclerosis can be defined as thickening of one or more leaflets without impairment ofthe leaflet motion. On echo, the leaflets may show thickening and calcification, but the flow velocities are essentially normal. Aortic valve sclerosis can prog­ ress to aortic stenosis (not in all individuals), which is an im­ portant marker for an increased risk of atherosclerotic disease. Therefore, it is important to identify any cardiovascular risks in these patients (ie, age, sex, smoking, hyperlipidemia, HTN, DM).
• Aortic valve sclerosis is commonly found in the elderly and may present without a murmur or may have a midsystolic ejection murmur.
• Caveat 1—Diuretics should be used with caution (ie, avoid overdiuresis) since a decrease in preload may affect the cardiac output.
• Caveat 2—Vasodilators (eg, hydralazine, nitroglycerin) should be used with caution since they can cause hypotension.
• Caveat 3—Positive inotropic agents (eg, dobutamine) should be used with caution since they can cause stress on the heart (ie, myocardial ischemia).

• Caveat 4—Beta-blockers should be avoided in heart failure or symptomatic AS since a decrease in contractility can cause more stress on the already overloaded left ventricle.
• Patients that present with signs and symptoms of heart failure are the most worrisome since the approximate median survival time after the onset of symptoms is the following (in decreasing order of survival time)\: angina (5-year survival time) >syncope (3-year survival time) >heart failure (2-year survival time).
• Patients with aortic stenosis have an increased risk of bleed­ ing from the skin, mucosa, and GI (ie, bleeding from the an- giodysplasia).
• The increase risk of bleeding is now thought to be due to an acquired von Willebrand syndrome that results in the me­ chanical disruption of the von Willebrand multimers as they pass through the stenotic valve.
• Foundational point—Laplace’s law explains that the wall stress is proportional to the intraventricular pressure and radius of the ventricle, but inversely related to the wall thickness.
• Connecting point (pg. 132)—Acquired von Willebrand dis­ ease can be seen in other conditions.
• On the CCS, type in “aortic” in the order menu and notice the options available to you.
• On the CCS, you will be given a 2-minute warning toward the end of your case to finalize care for your patient. If you use all 2 minutes to add or delete orders, you may not be able to type in your final diagnosis. You should still attempt to enter a diagnosis even though it is not part ofyour evaluation performance.
I CHRONICAORTICREGURGITATION
Aortic regurgitation (AR), also known as aortic insufficiency, can be characterized by the retrograde diastolic blood flow from the aorta into the left ventricle. Causes of AR can be due to valvular abnormalities or dilatation of the aortic root. Consider the following causes\:
Valvular\: Congenital (bicuspid), endocarditis, rheumatic fever, RA, fenfluramine-phentermine
Aorta\: HTN, syphilis (aortitis), Marfan syndrome, ankylosing spondylitis, reactive arthritis
Clinical Features\:
Murmur Type\: Diastolic murmur (between S2 and Sj). Heart Sounds\:
52—Soft A2, but with severe AR; A2 is usually absent.
53—S3 gallop is usually seen in the presence of LV dysfunction.
Murmur sound—A high-frequency decrescendo murmur (ie, “blowing” quality) can be best heard along the left sternal border (usually due to valvular disease), at the third and fourth intercostal space using the diaphragm ofthe stethoscope. Ifthe murmur is barely audible, it can be appreciated by having the patient sit up, lean forward, and hold his or her breath on expira­ tion. Ifthe murmur is heard best along the right sternal border, it suggests that the AR is due to an aortic root abnormality.
If a murmur is heard at the apex (using the bell of the stethoscope), consider an Austin Flint murmur, which is a low-frequency rumbling mid-diastolic murmur that is thought to represent turbulent flow as a result of mitral leaflet displace­ ment from the aortic regurgitant jet flow. The intensity of the murmur will change upon different maneuvers (see Table 3-6).
Clinical Progression\: Since the LV must pump the normal blood volume from the left atrium plus the regurgitant volume, the LV compensates gradually through dilatation and eccen­ tric hypertrophy. The left atrium can also accommodate the increase in LV diastolic pressure by enlarging its chamber and reducing the likelihood of pulmonary congestion. Therefore, patients will remain asymptomatic for a prolonged period. As a result of LV dilatation, a higher stroke volume will be pumped out during systole (ie, higher systolic pressure), but at the same time a larger amount of regurgitant blood flow will occur dur­ ing diastole (ie, lower diastolic pressure), which ultimately leads to a widened pulse pressure. At some point, the LV function deteriorates and symptoms of heart failure develop.
Clinical Presentation\: The widened pulse pressure, which is manifested as marked distention and quick collapse on palpa­ tion of the peripheral arteries (eg, carotid or radial artery), is known as the “water-hammer” or Corrigan’s pulse. Most of the widened pulse pressure accounts for other physical findings, which include (from head to toe)\:
Head—Head bobbing (de Musset’s sign). Eyes—Retinal artery pulsations (Becker’s sign).
Lips—Pulsations can be seen on the lips or fingernails with light pressure applied to the nail tip (Quincke’s sign).
Liver—Pulsation of the liver (Rosenbach’s sign).
Spleen—Pulsation of the spleen (Gerhard’s sign).
Femoral artery—“Pistol-shot” sound over the femoral artery (Traube’s sign) and a to-and-fro murmur over the femoral artery with light compression (Duroziez’s sign).
Uvula—Pulsation of the uvula (Muller’s sign).
Popliteal artery—Popliteal systolic pressure 60 mm Hg higher than brachial systolic pressure (Hill’s sign).
Severity\: For board purposes, the following is a general guide­ line for classifying the severity of the AR seen in adults\: mild (LV size normal, regurgitant fraction <30%, regurgitant orifice area <0.1 cm2), moderate (LV size normal to dilated, regurgi­ tant fraction 30%-49%, regurgitant orifice area 0.1-0.29 cm2), and severe (LV size dilated, regurgitant fraction >50%, regurgi­ tant orifice area >0.3 cm2).
Next Step\:
Step 1) The best initial test is with a transthoracic echocar­ diography (TTE). If the information provided by the TTE is suboptimal, the next best step is with a transesophageal echocardiography (TEE). A cardiac catheterization can be considered when there is a discrepancy between clinical and echocardiographic findings, or when the patient is about to undergo valve surgery but has risk factors for coronary artery disease. Other adjunctive testing may include the following\:
CHAPTER 3 CARDIOLOGY 35

36
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
EKG—EKG may show signs of LVH and sometimes left atrial hypertrophy.
Chest x-ray—On frontal view, the apex may be displaced inferiorly and to the left (advanced AR). Other possible findings include a dilated aortic root and/or ascending aorta (consider AR due to bicuspid aortic valve) and evidence of heart failure.
Exercise stress testing—Exercise stress testing may be per­ formed in patients to assess functional status prior to athletic activity or in patients with equivocal symptoms.
Step 2) The clinical management for aortic regurgitation can be best summarized into patients that are asymptomatic or symptomatic. The following recommendations are based on the American College of Cardiology/American Heart Association (ACC/AHA) guidelines.
Asymptomatic\:
1) Severe AR + Not candidates for surgery + LV dysfunction —> Chronic vasodilator therapy
2) Severe AR + Concurrent CABG, aortic or valve surgery at the same time -4 AVR
3) Severe AR + LV dysfunction at rest (EF < 50%) —> AVR
4) SevereAR+NormalLVfunction(EF>50%)+LVdilatation (end-systolic dimension >55 mm or end-diastolic dimen­ sion >75 mm) -4 AVR
Symptomatic\:
1) SevereAR+Notcandidatesforsurgery-4Chronicvasodi­ lator therapy
2) Severeheartfailuresymptoms+SevereLVdysfunction+Be­ fore proceeding with AVR -4 Short-term vasodilator therapy
3) SevereAR(irrespectiveofEF)—>AVR
Step 3) Patients with rheumatic aortic regurgitation should receive prophylactic antibiotics for secondary prevention of rheumatic fever.
Follow-Up\:
A TTE should be performed anytime there is a change in clinical status. As a general guideline, patients with mild AR (with­ out LV dysfunction and dilatation) should have yearly clinical exams with routine echo every 2 to 3 years. Patients with mod­ erate AR (without LV dysfunction and dilatation) should have yearly clinical exams with routine echo every 1 to 2 years. Those with severe AR (without LV dysfunction but with LV dilatation) require more frequent assessments such as clinical exams every
MYOCARDIUM DISORDER
I HYPERTROPHICCARDIOMYOPATHY
Hypertrophic cardiomyopathy (HCM) is frequently referred to as hypertrophic obstructive cardiomyopathy (HOCM) or idiopathic hypertrophic subaortic stenosis (IHSS). HCM is distinct from
6 months and echo every 6 to 12 months. In addition, the ACC/ AHA recommends monitoring dilatation of the aortic root or ascending aorta (diameter >40 mm) every year with echocar­ diography, cardiac MRI, or CT.
Pearls\:
• Routine infective endocarditis prophylaxis is no longer recommended in patients with common valvular disease, including chronic AR, unless the patient had a previous epi­ sode of infective endocarditis or prior prosthetic repair.
• The prognosis in patients with AR is mainly determined by the presence of symptoms, LV function, and LV size.
• On EKG, right atrial hypertrophy is characterized by a bi- phasic P wave with a prominent positive deflection in the initial portion of the P wave in lead Vr
• CJ\: A 42-year-old man presents to the ED with blunt trauma to the chest. The patient presents with dyspnea, tachycardia, and hypotension. On cardiac exam, a low-pitched early diastolic murmur can be heard along the left sternal border in the third intercostal space. A soft A2 with an accentuated P2 (ie, pres­ ence of pulmonary hypertension) as well as an S3 can also be appreciated. A bedside TTE suggests an acute aortic regurgi­ tation. What are your next steps? Answer\: Patients with acute AR require emergent aortic valve replacement or repair. In the interim, treat pulmonary edema with oxygen and respiratory failure with intubation (ie, high diastolic LV pressure transmit­ ted to left atrium and lungs since the LV is relatively noncom- pliant). The patient may need to be temporarily stabilized in the ICU with IV vasodilators (eg, nitroprusside) and positive inotropic agents (eg, dobutamine or dopamine) to facilitate forward flow. Intraaortic balloon pump (IABP) is contraindi­ cated in patients with acute AR since the balloon will worsen the regurgitant flow. Causes of acute AR include trauma, aor­ tic dissection, and endocarditis. Clues to endocarditis would be the presence offevers, chills, and a murmur heard along the left sternal border. Clues to an aortic dissection would include a “ripping” pain in the back or chest, greater than 20 mm Hg blood pressure difference between the left and right arm, and murmur heard along the right sternal border. Patients suspect­ ed of having an aortic dissection should have either a TEE or CT to make the diagnosis. In general, patients with an acute AR will not have a widened pulse pressure seen in chronic AR.
• On the CCS, once you receive the 2-minute warning to­ ward the end of the case, you will not be able to relocate the patient, perform physical exams, make follow-up appoint­ ments, or view pending results.
secondary hypertrophy (due to HTN or aortic stenosis) in that (1) Myocytes have a disorganized arrangement (unlike the or­ derly and enlarged myocytes seen in secondary hypertrophy) and (2) HCM can occur as a familial disease with autosomal dominant inheritance, or sporadically. HCM can have different morpholo­ gies (eg, septal, apical, or biventricular hypertrophy) with the end result of having diastolic dysfunction (ie, impaired filling).

Clinical Features\:
Murmur Type\: Systolic murmur (between S, and S2). Heart Sounds\:
S2—Normally a physiologic split, but with severe outflow obstruction, a paradoxical split can be heard.
S4—S4is a common finding.
Murmur sound—A harsh systolic crescendo-decrescendo murmurcanbebestheardalongtheleftlowersternalborder, and sometimes it can radiate to the apex or base of the heart (usually not into the carotids). Unlike aortic stenosis, palpa­ tion of the carotid artery will reveal a brisk upstroke in the carotid pulse during early systole but then quickly decline in midsystole as a result ofthe outflow obstruction. In addition, the pulse is frequently biphasic or bifid (pulsus bisferiens). If a holosystolic blowing murmur is heard at the apex, then mitral regurgitation has developed from the outflow obstruction. The intensity of the murmur will change upon different maneuvers (see Table 3-6).
Clinical Progression\: Some patients will develop HCM without an outflow tract obstruction. However, these patients will still develop increasing LV diastolic pressures (due to a stiff ventri­ cle), which can eventually be transmitted back to the pulmonary vasculature and manifest as dyspnea. In other patients, outflow tract obstruction can accompany HCM with the systolic ante­ rior motion (SAM) of the mitral leaflet against a hypertrophied septum. As a result of an improperly closed mitral valve during systole, mitral regurgitation can develop with subsequent devel­ opment of dyspnea and atrial fibrillation. In a minority of pa­ tients, heart failure can develop in the late stages of the disease.
Clinical Presentation\: HCM can occur at any age, and clinical manifestations can vary. However, features of HCM (similar to aor­ tic stenosis) can be easily remembered by the mnemonic “SAAAD”\:
Syncope—Syncope can be due to the outflow tract obstruc­ tion or arrhythmias.
Arrhythmias—Supraventricular (eg, atrial fibrillation, atrial flutter) and ventricular arrhythmias (eg, ventricular fibrillation, which can cause sudden cardiac death) can result in palpitations.
Asymptomatic—Some patients may have minor to no symptoms. There is no strong correlation between the severity of the obstruction and symptoms.
Angina—Even in the absence of CAD, angina may be due to an increase in myocardial 02 demand and/or a decrease in myocardial 0 2 supply.
Dyspnea—Dyspnea is a common finding that can be due to diastolic dysfunction (ie, impaired diastolic relaxation), outflow obstruction with mitral regurgitation, or less com­ monly from heart failure, which may present as paroxysmal nocturnal dyspnea and orthopnea.
Next Step\:
Step 1) The best initial tests are with a transthoracic echocar­ diography (TTE) and EKG. If information on the TTE is incon­ clusive, then a transesophageal echocardiography (TEE) would be the next best step to help guide management decisions. Cardiac
catheterization is usually unnecessary, but in the uncommon cir­ cumstances where there is a discrepancy between clinical findings and echocardiography, cardiac catheterization may be beneficial. The following are possible findings on the TTE and EKG\:
TTE—Diastolic dysfunction, LVH with an increase in sep­ tal wall thickness, systolic anterior motion of the mitral valve, mitral regurgitation, increase in the LV outflow tract gradient, small LV cavity, or a “ground-glass” appearance of the hypertrophied myocardium.
EKG—EKG findings may include any of the following\: LVH, left atrial enlargement, left axis deviation, prominent Q waves mimicking an MI in the inferior (II, III, aVF) and lateral leads (I, aVL, V4-V6), diffuse T-wave inversion in the precordial leads, or arrhythmias during ambulatory (Holter) monitoring.
Other adjunctive testing may include the following\:
Chest x-ray—Chest x-ray is usually normal or may show mild to moderate enlargement of the cardiac silhouette.
Exercise stress testing—Exercise stress testing may be reasonable to assess functional capacity, SCD risk stratifica­ tion (EKG monitoring), or to assess an inducible LV outflow obstruction (echocardiography monitoring) in patients without LV outflow obstruction at rest.
Step 2) The clinical management for HCM can be best sum­ marized into patients that are asymptomatic or symptomatic.
Asymptomatic\: Routine pharmacologic therapy (eg, beta- blockers, calcium channel blockers) and septal reduction therapy is not recommended in asymptomatic patients.
Symptomatic\: Symptomatic patients can undergo phar­ macologic therapy and/or surgery. Consider the following conditions\:
Syncope—The next best step to manage patients with syn­ cope is (1) order an echocardiography to evaluate for an obstruction, and/or (2) Holter monitor to evaluate for ar­ rhythmias. Patients that continue to have syncope despite optimal medical therapy and known outflow tract obstruc­ tion are candidates for septal reduction therapy. However, if syncope cannot be explained by a specific cause, it is considered a risk factor for sudden cardiac death (SCD). Therefore, the next best step is to consider an implantable cardioverter defibrillator (ICD).
Sudden cardiac death (SCD)—Patients that survive an SCD through appropriate intervention should have a thor­ ough evaluation for the possible cause (eg, EKG, Holter monitor, echo) and should be treated appropriately. Since patients that survive an SCD are at risk of another SCD event, patients should receive prophylactic ICD placement. In addition, patients are advised to avoid competitive sports and strenuous exercise.
Acute hypotension—HCM patients with an outflow tract obstruction can sometimes present with acute hypotension. In these patients, the first step is to elevate their legs. The next step is to administer IV fluids. Patients who do not respond to fluids should then receive IV phenylephrine (alpha-1 agonist).
CHAPTER 3 CARDIOLOGY 37

38
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Atrial fibrillation—If atrial fibrillation is encountered, patients can be managed with either rate control (eg, beta- blockers or calcium channel blockers) or rhythm control (eg, amiodarone or disopyramide with ventricular rate­ controlling agent). If patients continue to have persistent or recurrent atrial fibrillation, then radiofrequency ablation or surgical maze procedure (only if the patient is undergoing concurrent cardiac surgery) can be performed. Anticoagu­ lation is recommended in patients with persistent, paroxys­ mal, or chronic atrial fibrillation with HCM.
Angina or dyspnea—The following is the next step treat­ ment approach for angina or dyspnea\:
Step 1) The best initial therapy is with a negative inotropic agent such as low-dose beta-blocker or verapamil.
Step 2) If no response, titrate to a higher dose.
Step 3) If no response, switch to the other drug (ie, beta- blocker or verapamil).
Step 4) If no response, add disopyramide (class la anti- arrhythmic agent) to either beta-blocker or verapamil.
Step 5) If symptoms are refractory despite medical therapy and the patient has known outflow tract ob­ struction (ie, provokable or at rest), then consider a septal myectomy, septal (alcohol) ablation, or dual­ chamber pacing.
Step 3) Since SCD has been associated with strenuous exercise, patients with HCM should be counseled to avoid competitive or high-intensity sports.
Step 4) First-degree relatives ofan affected HCM patient should be screened for possible genetic inheritance with a thorough history, physical, echo, and EKG.
Disposition/Follow-Up\:
A TTE should be performed anytime there is a change in clinical status. First-degree relatives ofan affected individual should con­ tinue to have periodic surveillance since delayed-onset HCM can occur and first-degree family members are still at risk of SCD. Patients who present with syncope in the emergency department with suspected HCM should be admitted to the hospital for fur­ ther workup (eg, Holter monitor, echo, stress test).
Pearls\:
• Routine infective endocarditis prophylaxis is no longer rec­ ommended in patients with HCM, unless the patient had a previous episode of infective endocarditis or prior pros­ thetic heart repair.
CONGENITAL DISORDERS
1 ATRIALSEPTALDEFECT
Atrial septal defect (ASD) is a common congenital heart anom­ aly that is characterized by an interatrial septal defect that
• Caveat 1—Avoid diuretics, digoxin, and vasodilators (eg, nitroglycerin, ACE inhibitors, ARBs) in patients with HCM and significant LV outflow tract obstruction (remember patients can still have HCM without obstruction).
• Caveat 2—The calcium channel blockers (eg, nifedipine, verapamil, diltiazem) have vasodilatory properties that can cause hypotension. Therefore, calcium channel blockers should be avoided or used with caution in HCM patients with outflow tract obstruction.
• Caveat 3—Beta-blockers and verapamil should be used with caution in patients with sinus bradycardia.
• Caveat 4—Digoxin should be avoided in the management of atrial fibrillation since it has a positive inotropic effect that could worsen the outflow tract obstruction.
• Caveat 5—Be aware of volume status in patients with HCM since volume depletion can exacerbate the outflow tract obstruction, which may lead to worsening of symptoms.
• The Valsalva maneuver decreases preload, which makes the LV cavity smaller and allows the anterior mitral leaflet to come closer to the hypertrophied septum creating greater obstruction and increasing the intensity of the murmur.
• Competitive athletes that train with high intensity can develop “athlete’s heart,” which may resemble HCM. However, several distinctions should be made\: (1) There is no impair­ ment in diastolic filling (remember, they are athletes), (2) left atrium is usually normal, (3) LV wall thickness is usually symmetric, and (4) EKG findings usually reveal only LVH.
• The “SAD” (syncope, angina, dyspnea/heart failure) seen in aortic stenosis reflects end-stage disease. Patients can remain as­ ymptomatic for a period oftime before they encounter the clas­ sic symptoms of aortic stenosis. The “SAAAD” seen in HCM reflects a varied presentation that can occur at any one time.
• SCD is a major cause of mortality in patients with HCM. The incidence of SCD in children with HCM is as high as 6% per year, and it is 2% to 4% per year in adults.
• A prominent “a wave” may be seen on inspection of the neck veins.
• A double or triple apical impulse can be appreciated over the cardiac apex.
• Connecting point (pg. 163)—Know the inheritance pattern of autosomal dominant genes.
• On the CCS, be aware that in some CCS cases you will have to recognize when to refrain from further evaluation or treatment since the examination is assessing your clinical judgment.
results in a left-to-right shunt (ie, acyanotic lesion). Septal tissue is absent in ASDs, which distinguishes this condition from a patent foramen ovale (PFO). ASDs can be an isolated disease or associated with other congenital lesions such as transposition of the great arteries, tricuspid atresia, tricuspid regurgitation, mitral regurgitation, or a VSD. There are four types of ASDs to consider, and it may be helpful to consider them in their

relative anatomic location from a superior to inferior direction within the interatrial septum\:
1) Sinus venosus defect—These are uncommon defects, and there are two types. The superior sinus venosus defect is located below the orifice of the SVC, and the inferior sinus venosus defect is located above the orifice of the IVC. Both types of sinus venosus defects can have anomalous pulmo­ nary venous connections (eg, pulmonary veins connecting into the right atrium, SVC, or IVC).
2) Ostium secundum defect—This type is the most common defect and is located in the midseptum. This defect is more common in females than in males and is associated with mitral valve prolapse. Ostium secundum defects should not be confused with a PFO.
3) Ostium primum defect—This type of defect is located near the base of the interatrial septum or adjacent to the AV valves. This defect is associated with AV valve anomalies and is commonly seen in Down syndrome.
4) Coronary sinus defect—This is an uncommon defect that can be characterized by the absence of the wall between the coronary sinus and the left atrium. Many patients will also have a persistent left SVC that drains into the left atrium.
Clinical Features\: Heart Sounds\:
Sj—Sj can be normal or split with accentuation of the second component (tricuspid closure).
S2—Wide, fixed splitting is usually seen with larger left- to-right shunts with normal pulmonary arterial pressures, which is thought to reduce the respiratory variation.
S4—A right-sided S4 can be heard if right ventricular hyper­ trophy (RVH) develops.
Murmur sound—There is no murmur at the site of the ASD because of an insufficient pressure gradient between the two atria. However, murmur sounds can be heard with larger left-to-right shunts that create more blood flow across the tricuspid valve (mid-diastolic murmur heard over the lower left sternal border) and across the pulmonary valve (systolic crescendo-decrescendo ejection murmur heard over the second intercostal space at the upper left sternal border). If an ostium primum defect or an ostium secundum defect is present, then a murmur sound of a mitral regurgitation or mitral valve prolapse may be heard respectively.
Clinical Progression\: Patients with small ASDs (<8 mm in diam­ eter) will typically have spontaneous closure while they are infants. It is uncommon to have spontaneous closure while they are chil­ dren or adults. Patients with moderate to large ASDs will tend to have an increase in their left-to-right shunting as they age, and therefore, they will usually be symptomatic before the age of 40. In some cases, if significant pulmonary vascular disease develops over time, the direction of the shunt may reverse, causing a right-to-left shunt and manifesting as Eisenmenger syndrome, which is gener­ ally an irreversible condition. In this condition, blood bypasses the
lungs and results in delivery of deoxygenated blood to the rest of the body, which will usually manifest as cyanosis and clubbing.
Clinical Presentation—The presentation usually depends on the size of the defect. Consider the following sizes\:
Small ASDs—Small ASDs maybe undetected during the first two years of life because the patient may be asymptomatic and have unimpressive auscultatory findings.
Moderate to large ASDs—Common manifestations in­ clude dyspnea, fatigue, and exercise intolerance. In child­ hood, patients may also present with recurrent respiratory infections. In adults, symptoms of heart failure are more prevalent by the fourth or fifth decades of life. Patients may also have palpitations associated with the heart failure, which may be due to atrial arrhythmias (eg, atrial fibrilla­ tion, atrial flutter) caused by right atrial enlargement.
Next Step\:
Step 1) A transthoracic echocardiography (TTE) is used to confirm the diagnosis of an ASD. If the image quality is sub- optimal on TTE, the next best step is with a transesophageal echocardiography (TEE). The TEE may be particularly useful in the diagnosis of a sinus venosus defect because it may poten­ tially identify an anomalous pulmonary venous connection. A cardiac catheterization is not routinely performed to make the diagnosis. However, it maybe useful if there are equivocal clini­ cal findings, measure pulmonary vascular resistance (PVR), or to perform a transcatheter closure for small to moderate secun­ dum ASDs. Other adjunctive testing may include the following\:
EKG—EKG findings may include any of the following\: left axis deviation, right axis deviation, RVH, first degree AV block, prolonged PR interval, atrial arrhythmias, or an rsR‘ pattern (RBBB) in lead V,, which is thought to be related to RVH rather than a circuitry conduction problem.
Chest x-ray—With significant amount of left-to-right shunting, the right atrium and ventricle are usually enlarged. In addition, there is usually an increase in pulmonary vascular markings with a prominent pulmonary artery.
Step 2) Consider the clinical management of ASD\:
“Wait and See Approach”\: A wait and see approach can be attempted in infants with an ostium secundum defect that is less than 8 mm since most defects will spontaneously close by 2 years of age. A wait and see approach can also be attempted in infants with larger secundum defects who are asymptomatic since there is still a possibility of spontaneous closure by 2 years of age.
ASD Closure\: ASD closure can be accomplished through sur­ gery or by percutaneous transcatheter closure. Transcatheter closure has the advantage of avoiding cardiopulmonary bypass, but the procedure is only amenable to ostium secundum de­ fects. Sinus venosus, ostium primum, and coronary sinus de­ fects should be surgically repaired. The following are indications and contraindications for ASD closure\:
Indications—ASD closure is recommended in patients with either (1) evidence of right atrial and right ventricular
CHAPTER 3 CARDIOLOGY 39

40
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
enlargement with or without symptoms, or (2) significant left-to-right shunting that correlates to a pulmonary- to-systemic flow ratio (Qp/Qs) >2\:1.
Contraindications—ASD closure is not recommended in patients with severe irreversible pulmonary hypertension and in patients with insignificant left-to-right shunts.
Follow-Up\:
A TTE should be performed anytime there is a change in clini­ cal status. Patients that do not meet the indications for an ASD closure should be seen for a clinical exam and echocardiogra­ phy at least every 2 to 3 years.
Pearls\:
• Routine infective endocarditis prophylaxis is no longer recom­ mended in patients with an ASD unless the ASD is repaired with prosthetic materials. Ifprosthetic materials are used, then for the first 6 months after the repair, prophylactic antibiotics are recommended for dental, oral, or respiratory procedures.
• Infective endocarditis prophylaxis is also recommended in patients undergoing dental, oral, or respiratory procedures who have a repaired ASD with a residual defect adjacent to or at the site of prosthetic materials.
• Patients with an ASD will have an increase in oxygen satura­ tion in the right atrium compared to the SVC or IVC.
• Paradoxical embolization occurs when an embolus origi­ nates from the venous system and crosses a PFO or ASD that eventually enters the arterial system, which could potentially cause a stroke. The embolus usually crosses the PFO or ASD when there is a transient right-to-left shunt gradient (eg, Val­ salva maneuver, repetitive coughing) and does not necessar­ ily have to occur with a chronic right-to-left shunt gradient (eg, Eisenmenger syndrome). An ASD closure is usually con­ sidered in the presence of a paradoxical embolism.
• Patients with an intracardiac shunt (eg, ASD, VSD, PFO, PDA) should avoid scuba diving because of the risk of para­ doxical embolism and decompression illness.
• Pregnant women with uncomplicated ASDs typically do well during their pregnancy; however, complications to consider are arrhythmias, paradoxical embolization, and an increase in the left-to-right shunting in the presence of acute blood loss.
• Pregnancy is contraindicated in women who have developed Eisenmenger syndrome.
• On the CCS, “Atrial septal defect repair” is available in the practice CCS, but be sure to order a cardiac surgery consult prior to the repair.
• On the CCS, prior to a surgical procedure, preoperative care may include a CBC, BMP, type and crossmatch, and coagula­ tion studies (PT, PTT).
1 VENTRICULARSEPTALDEFECT
Ventricular septal defect (VSD) is the most common congenital heart anomaly. VSD is characterized by a left-to-right shunt (ie, acyanotic lesion) with oxygenated blood still reaching the rest
of the body. VSD can be an isolated disease or associated with other congenital heart defects such as tetralogy of Fallot, trans­ position of the great arteries, PDA, ASD, or atrioventricular ca­ nal defects. Consider four types of VSDs\:
1) Membranousdefect—Thisisthemostcommontypeofde­ fect. When the defect extends into the muscular septum, it is referred to as perimembranous VSD. Aortic regurgitation with aortic valve prolapse is associated with this defect.
2) Muscular defect—This type of defect can close spontane­ ously. When there are multiple defects, the septum is often referred to as “Swiss cheese.”
3) Subpulmonic defect—This type of defect is usually asso­ ciated with aortic regurgitation caused by prolapse of the right aortic cusp of the aortic valve.
4) Inlet defect—This type of defect is associated with ASDs and Down syndrome. Inlet defects generally do not close spontaneously.
Clinical Features\:
Murmur Type\: Systolic murmur with or without diastolic murmur.
Heart Sounds\:
S2—A normal physiologic split is usually heard with small VSDs. In larger VSDs, the pulmonary arterial pressures can increase, which may result in a narrow split S2 with a louder P2 component. If there is pulmonic stenosis or concomitant RBBB (eg, complication from corrective sur­ gery), then there may be a delayed P2, which can result in a wide split S2.
Murmur sound—A harsh holosystolic murmur can be best heard along the left lower sternal border and is sometimes accompanied by an apical mid-diastolic flow rumble which is thought to represent increasing blood flow across the mitral valve. If there is a large VSD with pulmonary hypertension, the shunting effect (ie, blood flow across the defect) may end before systole, and thus, it may be referred to as an early systolic murmur. An early systolic murmur can also occur in small muscular VSDs in the absence of pulmonary hypertension since the defect can close soon after the start of systole. The inten­ sity of the murmur will change upon different maneuvers (see Table 3-6).
Clinical Progression\: Patients with small VSDs will typically have spontaneous closure within the first two years of life. Small VSDs can persist into adulthood but are usually benign, although they can develop aortic regurgitation and endocar­ ditis. Moderate VSDs may diminish in size over time and can spontaneously close, but less often than small VSDs. Patients with moderate VSDs can be asymptomatic or they can develop heart failure in childhood. Large VSDs usually do not close spontaneously, and parents seek medical attention early in life. The left-to-right shunt becomes prominent, which can result in volume overload in the right ventricle, pulmonary vasculature, left atrium, and left ventricle with subsequent development of heart failure by 3 to 4 weeks of age. If significant pulmonary

vascular resistance increases over time, the shunt can reverse to a right-to-left shunt and manifest as Eisenmenger syndrome.
Clinical Presentation—The presentation usually depends on the size of the defect. Consider the following sizes\:
Small VSDs—Patients are usually asymptomatic with nor­ mal feeding and weight gain.
Moderate to large VSDs—Patients may show signs of heart failure such as tachypnea, tachycardia, and hepatomegaly. Poor feeding with poor weight gain and growth may also be apparent. Diaphoresis (T sympathetic tone) and fatigue usually accompanies the feeds.
Next Step\:
Step 1) A transthoracic echocardiography (TTE) is used to confirm the diagnosis of a VSD. If the image quality is sub- optimal on TTE, the next best step is with a transesophageal echocardiography (TEE).The TEE may be particularly useful in visualizing aortic valve prolapse compared to the TTE. The TEE is also used intraoperatively to assess the surgical closure. A cardiac catheterization is infrequently performed, but it may beneficial to guide perioperative management, accurately assess hemodynamic status, measure pulmonary vascular resistance (PVR), or unravel equivocal clinical findings. Other adjunctive testing may include the following\:
EKG—With small VSDs, the EKG is usually normal. In moderate to large VSDs with a significant amount of left- to-right shunting, left atrial enlargement and LVH can be seen with increasing blood return to the left part of the heart. If pulmonary vascular disease develops, RVH may also be apparent.
Chest x-ray—With small VSDs, the CXR is usually normal. In moderate to large VSDs with a significant amount of left- to-right shunting, there is usually an increase in pulmonary vascular markings with a prominent pulmonary artery.
Step 2) The clinical management of VSD depends on several factors such as the size of the VSD, presence of pulmonary hy­ pertension, likelihood of spontaneous closure, and likelihood of a successful surgical repair. Consider the clinical management ofVSD\:
Small VSD\: Asymptomatic patients do not require medical or surgical intervention. During the first year of life, the pa­ tient should have regularly scheduled follow-ups, and some physicians will elect to repeat an echocardiogram after the first year.
Moderate to large VSDs\: Medical or surgical intervention is usually indicated when there is significant amount of left- to-right shunting causing symptoms. Consider the following\:
Heart failure—The best initial pharmacologic therapy is with a diuretic (eg, furosemide) to relieve pulmonary congestion. An ACE inhibitor (eg, captopril, enalapril) can be used to reduce systemic vascular resistance and thus, ultimately reduce the left-to-right shunt. Digoxin is sometimes used to,enhance contractility when diuresis or afterload reduction fails to relieve symptoms.
Poor weight gain—Infants have a high metabolic demand and require a certain amount of calories per day. Infants with a VSD may be tired with each feeding and therefore unable to meet their caloric requirements. Increasing the caloric density of the formula with each feeding may be successful. Infants should be monitored for their growth at least every 2 weeks. If infants cannot meet their nutritional requirements and growth is subpar, surgical repair is most likely to occur.
VSD Closure\: VSD closure can be accomplished through surgery or by percutaneous transcatheter closure. Transcath­ eter closure can be performed on muscular VSDs and certain membranous VSDs. The following are indications and con­ traindications for VSD closure\:
t Indications—VSD closure is recommended in infants when
patients continue to have symptoms despite optimal medi­ cal therapy, pulmonary-to-systemic flow ratio (Qp/Qs) >2\:1 with elevated pulmonary arterial pressures, or in the pres­ ence of aortic regurgitation, which is seen in membranous and subpulmonic defects. VSD closure is recommended in adults when patients have a history of infective endocardi­ tis, or pulmonary-to-systemic flow ratio (Qp/Qs) >2\:1 with evidence of LV volume overload.
Contraindications—VSD closure is not recommended in patients with severe irreversible pulmonary hypertension.
Follow-Up\:
Patients with small VSDs and those who underwent cardiac surgical repair for a VSD require long-term follow-up.
Pearls\:
• Routine infective endocarditis prophylaxis is no longer recommended in patients with a VSD unless the VSD is repaired with prosthetic material. If prosthetic material is used, then for the first 6 months after the repair, prophylactic antibiotics are recommended for dental, oral, or respiratory procedures.
• Infective endocarditis prophylaxis is also recommended in patients undergoing dental, oral, or respiratory procedures who have a repaired VSD with a residual defect adjacent to or at the site ofprosthetic materials.
• Increasing the afterload (ie, handgrip or squat) will increase the effect ofthe left-to-right shunt, thereby increasing the in­ tensity of the murmur.
• Remember to keep a watchful eye on patients with a VSD and a narrow split S2 with marked accentuation of the P2 component because they are indications of increasing pul­ monary arterial pressures, which may limit the patients’ ability to undergo corrective surgical repair.
• In patients that developed right ventricular hypertrophy (RVH), a prominent “a” wave may be seen on jugular venous inspection.
• Pregnant women with small VSDs usually complete their pregnancy without complications.
CHAPTER 3 CARDIOLOGY 41

42 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Pregnant women with moderate to large VSDs are at higher risk of developing complications.
• Pregnancy is contraindicated in women who have developed Eisenmenger syndrome.
• Patients with a VSD will have an increase in oxygen satura­ tion in the right ventricle compared to the right atrium.
• On the CCS, patients that present to the office or ED with heart failure symptoms should initially be admitted to the hospital and managed on the inpatient unit.
CCS\: ACUTE PERICARDITIS CASE INTRODUCTION
Day 1 @ 10\:00 Emergency Room
A 42-year-old man from India comes to the emergency room because of chest pain.
Initial Vital Signs\:
Temperature\: 38.3°C (101°F) Pulse\: 85 beats/min Respiratory\: 16/min
Blood pressure\: 128/85 mm Hg Height\: 185.4 cm (73.0 inches) Weight\: 79.3 kg (175 lb)
BMI\: 23.1 kg/m2
Initial History\:
Reason(s) for visit\: Chest pain
HPI\:
A 42-year-old man, who recently immigrated from India, is complaining of sudden chest pain for the past two days. The chest pain is a sharp retrosternal pain that radiates to the tra­ pezius ridges. Coughing, inspiration, or lying supine aggravates the pain, but it is alleviated when sitting up and leaning forward. He rates his pain as a 5 on a 10-point scale. The patient states that he had a cough, runny nose, and a sore throat 1 week ago that has since resolved. He denies chills, shortness of breath, nausea, vomiting, abdominal pain, or any recent trauma.
• On the CCS, it is appropriate to consult a pediatric car­ diologist in a patient with a VSD. Although the consult­ ant may not say anything useful on the CCS exam, you are expected to implement a course of action (eg, echo, EKG, CXR).
• On the CCS, “VSD repair” is available in the practice CCS, but be sure to order a cardiac surgery consult prior to the repair.
• On the CCS, if the patient is not feeding well, be sure to or­ der a “calorie count” or “dietary intake.”
Past Medical History\: Past Surgical History\:
Medications\: Allergies\: Vaccinations\:
History of peptic ulcer disease None
None
None
BCG vaccination
Family History\: Social History\:
Review of Systems\:
General\:
Skin\:
HEENT\: Musculoskeletal\: Cardiorespiratory\: Gastrointestinal\: Genitourinary\: Neuropsychiatric\:
Day 1 @ 10\:00
First Order Sheet\:
1) IV access
2) Pulse oximetry, stat
3) Continuous cardiac monitor, stat
4) Continuous blood pressure cuff, stat
5) 12-lead EKG, stat
Father, age 65, had a heart attack at age 60. Mother, age 63, is healthy. Smokes one pack per day x 20 years; denies drinking or drugs, married with two children, computer engineer, enjoys playing cricket
See HPI Negative See HPI See HPI See HPI Negative Negative Negative
Result\: 94%
Result\: Regular sinus
Result\: 128/85 mm Hg Result\: Diffuse ST-segment
elevations with upward concavity. Reciprocal ST-segment depressions in aVR and V,. PR segment elevation in aVR, but PR segment depressions in other leads. Q waves absent.

Second Order Sheet\: -
1) Morphine, IV, one time
2) Oxygen, inhalation, continuous
3) Nitroglycerin, sublingual, onetime
4) Aspirin, oral, one time
Follow-Up History\:
Patient feels Only partial relief and rates his pain as 4/10.2 Physical Examination\:
3) Troponin I, serum, '■ Stat
4) ESR, stat
5) PT/INR, stat
6) PTT, stat
7) Blood culture, stat
8) Interferon gamma release assay
9) Chest x-ray, portable, stat
10) Echocardiography, stat
Fourth Order Sheet\:
1) Indomethacin, oral, continuous
2) Colchicine, oral, continuous
3) Omeprazole, oral, continuous
Actions\:
1) Change location to inpatient unit
Follow-Up History\:
Result\: 0.1 ng/mL(nl\: 0-0.6) - • /' ;
Result\: 45 mm/hour (nl\: 0-15) Result\: PT-9.2 seconds (nl\:
<12), INR-i 6 (nl\: 1.0-1.3) Result\: 25 seconds (nl\: <28)
Result\: No growth Result\: Latent TB not
detected
Result\: Lungs dear, normal cardiac silhouette
Result\: 5 mm of echo-free space. LVEF 60%
General appearance\: HEENT/Neck\:
Chest/Lungs\:
Heart/Cardiovascular\:
Abdomen\:
Extremities/Spine\:
Third Order Sheet\: 1) CBC with
differential, stat 2) BMP, stat
Well nourished, well devel­ oped; in no acute distress. Normocephalic. EOMI, . PERRLA. Hearing normal. Ear, nose, mouth normal. Pharynx normal Neck supple; trachea midline; no masses or bruits; thyroid normal.
Chest wall normal. Diaphragm and chest moving equally and symmetrically with respira­ tion, but chest pain is elicited upon inspiration. Auscultation and percussion normal. Pericardial friction rub heard along the left sternal border. The intensity of the rub can be better appreciated with
the patient leaning forward or resting his elbows on his knees. No reproducible chest pain on palpation of the ante­ rior chest. No JVD.
Normal bowel sounds; no bruits. No tenderness or masses. No abnormality
on percussion. No rebound. No guarding. No hepatosplenomegaly.
No joint deformity or warmth. No cyanosis or clubbing. No edema. Peripheral pulses normal. Spine exam normal. No paraspinal tenderness.
Result\: WBC 12,500, H/H15/45%, Pit 250,000, Dif­ ferential normal
Result\: GlulOO, Urea 15, Na 140, K 4.0, Cl 100, HC03 23, Cr l,Ca 9.1
Note\: Vitals are automatically ordered for you in the practice CCS.
Patient feels better and rates his pain as 2/10.
Fifth Order Sheet\:
1) Check blood pressure 2) Check cardiac monitor
Result\: 128/85 mm Hg Result\: Regular sinus
This case will end in the next few minutes of “real time.” You may add or delete orders at this time,
then enter a diagnosis on the following screen.
Sixth Order Sheet\:
1) Cancel supplemental oxygen
2) ESR, routine
Future date\: In 14 days 3) Counselfamily/patient
4) Advise patient, no smoking
5) Advise patient, side effects of medication
Result\: 8 mm/hour (nl\: 0-15)
Please enter your diagnosis\:
Acute Pericarditis
DISCUSSION\:
Acute pericarditis refers to inflammation of the pericardium, whichconsistsofthevisceralandparietalpericardium.Mostcases
CHAPTER 3 CARDIOLOGY 43

44 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
of acute pericarditis are idiopathic in nature, but most likely of viral origin. Other causes of acute pericarditis includes bacterial infections, fungal infections, TB, inflammatory conditions (eg, RA, SLE, IBD, scleroderma, rheumatic fever), metabolic con­ ditions (eg, uremia, hypothyroidism), cardiac conditions (eg, Dressler’s syndrome, aortic dissection), radiation-induced, neo­ plastic disease, drug-induced (eg, hydralazine, procainamide, isoniazid, minoxidil, doxorubicin), iatrogenic, or trauma.
Clinical Features\:
Patients with acute pericarditis may present in different ways depending on the etiology. For example, malignancy (eg, weight loss, lymphadenopathy), infections (eg, fever, leukocytosis), SLE (eg, arthritis, photosensitivity), Crohn’s disease (eg, abdominal pain, nonbloody diarrhea), or TB (eg, night sweats, cough). In addition to the specific manifestations of the underlying cause, the vast majority of patients will also present with chest pain. The pain is typically an acute onset, but it can be gradual. The pain is precordial or retrosternal that radiates to the back, neck, shoulder, arm, or to the trapezius ridge. The pain is usually characterized as sharp and pleuritic. Lying flat often aggravates the pain, but sitting up and leaning forward relieves the pain by reducing the pressure on the parietal pericardium. Sometimes patients may complain of dysphagia due to an irritation ofthe esophagus from the posterior pericardium. An associated condition that is usually seen with viral etiologies is a “flulike” illness prior to the onset of acute peri­ carditis. On physical exam, the presence of a pericardial friction rub is pathognomonic for acute pericarditis. The rub is best heard with the diaphragm of the stethoscope applied between the left lower sternal border and the cardiac apex with the patient leaning forward in suspended respiration. Cardiac tamponade can some­ times develop in patients with a neoplastic etiology, trauma, or from an iatrogenic cardiac perforation. Clues to look for in cardi­ ac tamponade include Beck’s triad (ie, hypotension, JVD, muffled heart sounds) and pulsus paradoxus (ie, systolic blood pressure decreases more than 10 mm Hg on inspiration).
Next Step Summary\:
Step 1) In this patient that presented with chest pain, the ini­ tial clinical management focused on ruling out a myocardial infarction or ischemia. However, consider your differential di­ agnosis in this patient, which should include a pulmonary em­ bolism, aortic dissection, costochondritis, peptic ulcer disease, or esophageal spasm.
Step 2) The diagnosis of acute pericarditis is usually based on the clinical history (ie, pleuritic chest pain with improvement by sitting up and leaning forward), physical exam (ie, pericar­ dial friction rub), and EKG changes. Consider all the following possible options in evaluating a patient with suspected acute pericarditis, but use your clinical judgment on what tests are appropriate for that given patient.
CBC—Leukocytosis may be present with an infectious or inflammatory etiology.
BMP—Keep a watchful eye on an elevated BUN as a cause for uremic pericarditis.
Troponins—Elevated troponins can be seen with inflam­ mation that has reached the myocardium, and the patient is then considered to have myopericarditis rather than peri­ carditis only.
ESR or CRP—These are markers of inflammation, but not specific for acute pericarditis.
Coags—PT and PTT will give you an idea if there is a risk for hemorrhagic pericarditis or tamponade.
Blood cultures—Recommended in patients with fever >38°C (100.4°F) or suspected bacterial etiology.
Interferon gamma release assay (IGRA)—Unlike a PPD, a false positive test will not occur when using an IGRA in a BCG-vaccinated patient If a patient did not receive a BCG vaccination and comes from an endemic area where TB is high (eg, India), a PPD is acceptable to use on the CCS. In this case, the patient immigrated from an area where TB is endemic and therefore a potential cause for TB pericarditis.
ANA or rheumatoid factor—Consider these tests in patients with suspected rheumatologic diseases.
Viral culture—Not recommended since it is low-yield and does not alter management.
HIV serology—Order if clinically indicated.
CXR—Typically normal in acute pericarditis, but an enlarged cardiac silhouette suggests a pericardial effusion (ie, 200 mL needed before silhouette enlarges).
Echocardiography—Recommended in all patients sus­ pected of having pericardial disease as it can detect a car­ diac tamponade or large pericardial effusions (ie, echo-free space >20 mm). Although a pericardial effusion supports the diagnosis of pericarditis (ie, inflammation-induced effusion), the absence of an effusion does not exclude the diagnosis.
Pericardiocentesis—Not routinely performed in acute pericarditis with small or moderate sized effusions, unless there is a cardiac tamponade, large effusions despite medi­ cal therapy, or suspected bacterial or neoplastic pericarditis.
EKG—There are four stages in the EKG changes of acute pericarditis that include\: Stage 1) diffuse ST elevation with reciprocal ST depression; PR elevation and depressions (see first order sheet); Stage 2) return to isoelectric; Stage 3) diffuse T-wave inversions; and then Stage 4) return to isoelectric or continue with T-wave inversions indefinitely.
Step 3) Treatment of acute pericarditis is focused on treating the underlying cause (eg, TB pericarditis requires antitubercu­ lous therapy). Most patients with idiopathic or presumed viral pericarditis (such as in our CCS patient) will respond to medical management, which includes the following\:
NSAIDs—Ibuprofen or indomethacin can be used for the duration of the patient’s symptoms, which is typically 1 to 2 weeks, but be aware that NSAIDs do not alter the course of the disease. NSAIDs and glucocorticoids should be avoided in patients following an acute MI since they can interfere with healing and remodeling.

Aspirin—Aspirin is the preferred agent following an acute MI.
Glucocorticoids—Glucocorticoids (eg, prednisone) can be considered in patients that have a contraindication to NSAIDs or are refractory to a regimen of NSAIDs + colchicine. Glucocorticoids should be avoided in patients following an acute MI and in patients with purulent bacterial pericarditis (these patients require drainage and antibiotics, not steroids).
Golchicine—Colchicine can be added to any of the above three regimens as it is considered an adjunctive therapy to NSAIDs, aspirin, or glucocorticoids. Colchicine is thought to prevent recurrences, and it is fairly well tolerated in pa­ tients. Duration of therapy is typically 3 months or longer.
Proton pump inhibitors (PPIs)—PPIs (eg, omeprazole, lansoprazole) offer GI protection, and it is reasonable to give PPIs in patients with a history of peptic ulcer disease, age >65 years, high-dose NSAIDs, or concurrent use with aspirin, anticoagulants, or glucocorticoids. In this particu­ lar case, a PPI was given to the patient since he had a history of peptic ulcer disease.
Disposition\:
Most patients who present with acute pericarditis in the emer­ gency department do not require admission to the hospital. However, patients should be admitted if they have any of the following\:
• Cardiac tamponade
• Large pericardial effusion (ie, echo-free space >20 mm)
• Temperature >38°C (100.4°F)
• Elevated troponins (ie, suggesting myopericarditis)
• Immunosuppressed
• Concurrently taking anticoagulants
• NSAID drug failure
• Recent trauma
• Subacute onset
Pearls\:
• The EKG changes seen in acute pericarditis differs from acute MI in that (1) Q waves are generally absent in acute pericarditis (unless the inflammation has reached the myo­ cardium), (2) ST elevations have a concave shape (convex shape in STEMI), (3) widespread ST elevations in pericardi­ tis (remember the pericardium surrounds the entire heart),
and (4) reciprocal ST depressions are limited to aVR and in acute pericarditis.
• Early repolarization (normal variant) can also have wide­ spread ST-segment elevations, but differ from acute pericar­ ditis in that (1) the evolution of ST-T wave changes is absent in early repolarization, and (2) the ratio of ST amplitude to T-wave amplitude seen in lead V6 is <0.25 in early repolariza­ tion, but a ST/T ratio >0.25 suggests acute pericarditis.
• Electrical alternans can be seen in pericardial effusions or cardiac tamponade, which can be characterized by the beat- to-beat alternations of the QRS complex (ie, alternating between a reduced QRS amplitude and an increased QRS amplitude complex). The alternating pattern is thought to be due to shifting of the heart, back and forth, within the pericardial fluid.
• When a pericardial effusion is present, the echocardiography can identify echo-free fluid in the pericardial space.
• The normal thickness of the pericardial layers is less than 2 mm on echocardiography.
• Patients with uremic pericarditis respond well to dialysis.
• Post-infarct pericarditis can occur in the first few days after an MI. Consistent with the diagnosis is the presence of pleu­ ritic chest pain and pericardial friction rub, and the EKG may show an atypical ST-T wave evolution because of changes seen in the MI. Anticoagulation is typically held if a peri­ cardial effusion develops or effusion size increases. Routine NSAID treatment is avoided, but when symptomatic, aspirin is the preferred agent.
• Postcardiac injury (Dressler’s syndrome) occurs weeks to months after an acute MI and is thought to be immune medi­ ated. Consistent with the diagnosis is the presence of pleuritic chest pain, pericardial friction rub, fever, leukocytosis, and pulmonary infiltrates. Patients generally respond to NSAIDs.
• Connecting point (pgs. 252, 253)—Familiarize yourself with IGRA and know the treatment for TB.
• On the CCS, “interferon gamma release assay (IGRA)” is not recognized in the practice CCS.
• On the CCS, if you want to taper a medication (eg, predni­ sone), just discontinue the medication (ie, the CCS has done it for you without any patient problems on the actual CCS exam).
• On the CCS, do not assume that any orders will be written for you (eg, vitals) during the CCS cases.
• On the CCS, remember to order things that are pertinent and appropriate for the patient since unnecessary testing or treatments would be considered suboptimal management.
CHAPTER 3 CARDIOLOGY 45

Color Plate 1
FIGURE 4-1 • Infantile hemangioma. A segmental plaquelike lesion over the right side of the face. The lesion has a crimson color with a soft appearing texture. Involution is apparent over the forehead. The lesion on the upper eyelid and the medial canthus is impairing proper function of the lid, and this indicates that vision might be impaired in the future. In this patient, treatment was indicated. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick's ColorAtlas ofSynopsis ofClinical Dermatology. 6th ed. New York\: McGraw-Hill; 2009\:196.)

Color Plate 2
FIGURE 4-2 • Malassezia furfur on KOH preparation. Examination of both round yeast and elongated pseudohyphae reveals the characteristic "spaghetti and meatballs" pattern. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick's ColorAtlas ofSynopsis ofClinicalDermatology. 6th ed. New York\: McGraw-Hill; 2009\:735.)

Color Plate 3
FIGURE 4-3 • Kerion. An extremely painful, boggy, purulent inflammatory nodule on the scalp of this 4-year-old child with tinea capitis. The lesion drains pus from multiple openings, and there is a retroauricular, tender lymphadenopathy. Infection was due to a zoophilic dermatophyte, Trichophyton verrucosum, that was contracted from an infected rabbit. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick's ColorAtlas ofSynopsis ofClinicalDermatology. 6th ed. New York\: McGraw-Hill; 2009\:713.)

Color Plate 4
FIGURE 4-4 • Squamous cell carcinoma in situ (bowen's disease). A large, sharply demarcated, scaly, erythematous plaque simulating a psoriatic lesion. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick's ColorAtlas ofSynopsis ofClinical Dermatology. 6th ed. New York\: McGraw-Hill; 2009\:279.)

Color Plate 5
t ......................,......... . -
FIGURE 4-5 • Keratoacanthoma. A keratoacanthoma is seen on the face of a woman. Note the telangiectasias and central keratin core. (Reproduced with permissionfrom UsatineRP,etal.TheColorAtlasofFamilyMedicine.2nded.NewYork\:McGraw-Hill;2013\:977.)
- 4-"Jt
.

Color Plate 6
FIGURE 4-6 • Basal cell carcinoma. A. Rodent ulcer—A rolled, pearly border surrounds an ulcer with yellow necroses and a tiny black crust. B. Superficial BCC—A solitary, flat, bright red lesion with a slightly elevated rolled border that can be detected with "side lighting." C. Sclerosing BCC—A scarlike lesion
on the nose with ill-defined margins. D. Pigmented BCC—An irregular pitch-black plaque with a central area of regression. This pigmented BCC is clinically indistinguishable from superficial spreading melanoma. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick's ColorAtlas ofSynopsis ofClinical Dermatology. 6th ed. New York\: McGraw-Hill; 2009\:290,291,292,295.)

Color Plate 7
CD
FIGURE 4-7 • Melanoma. A. Superficial spreading—Depicted is a flat plaque that demonstrates asymmetry, irregular borders, and color variegation
(tan, brown, black, and red). Note the partially crusted nodule, which indicates a transition into the vertical growth phase. B. Nodular—A discrete darkly pigmented papule. This lesion has been present for less than 1 year. C. Lentigo maligna—An irregularly shaped, flat macular lesion with color variegation (tan, brown, black) that represents an in situ melanoma. D. Acral lentiginous—A lesion on the heel that reveals color variegation (brown, gray, black) and a nodular component that is hyperkeratotic, reddish, and ulcerated. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick's ColorAtlas ofSynopsis ofClinical Dermatology. 6th ed. New York\: McGraw-Hill; 2009\: 313,319, 322, 325.)

Color Plate 8
FIGURE 6-2 • Proliferative diabetic retinopathy. Proliferative retinopathy displaying yellow exudates, scattered hemorrhages, and neovascular vessels proliferating from the optic disc, requiring urgent panretinal laser photocoagulation. (Reproduced with permission from Lango DL, Fauci AS, Kasper DL, et al. Harrison's Principles ofInternal Medicine. 18th ed. New York\: McGraw-Hill, www.accessmedicine.com.)

Color Plate 9
FIGURE 9-1 • Leiomyomas. Uterine fibroids can be classified by their location. Subserosal myomas grow near the uterine serosa. Submucous myomas are adjacent to the endometrium. Intramural myomas are within the uterine walls. Cervical myomas are located in the cervix. Pedunculated myomas have an attached stalk. Infrequently, myomas can be found in the broad ligament, ovary, fallopian tube, vagina, and vulva. (Reproduced with permission from Hoffman BL, Schorge JO, Schaffer Jl, et al. Williams Gynecology. 2nd ed. New York\: McGraw-Hill, www.accessmedicine.com.)
Pedunculated serosal
Pedunculated submucous
Intramural Submucous
Intraligamentary Cervical

Color Plate 10
FIGURE 9-2 • Peau d' orange. Note the texture of the skin, which appears as an "orange peel.'The skin is thickened with enlarged pores secondary to lymphedema. (Reproduced with permission from Usatine RP, Smith MA, Mayeaux EJ Jr, et al. The ColorAtlas ofFamily Medicine. 2nd ed. New York\: McGraw-Hill; 2013\:553.)

Color Plate 11
FIGURE 13-1 • Retinal detachment. Depicted is a superior retinal detachment with billowing or elevation of the retina with folds that can produce an inferior scotoma. Also, note that the fovea was spared, which led to normal visual acuity in this patient. (Reproduced with permission from Hauser SL, Josephson SA, et al. Harrison's Neurology in Clinical Medicine. 2nd ed. New York\: McGraw-Hill; 2010\:183.)

Color Plate 12
FIGURE 13-2 • Macular degeneration. A. Dry ARMD—Depicted are soft yellow drusen that are beginning to coalesce. B. Wet ARMD—A clearly
evident subretinal hemorrhage over the macula may not always be present as in this case. However, further investigation with a fluorescein angiogram revealed leakage of fluorescein dye (hyperfluorescence) into the subretinal space of the macula in this patient. (Reproduced with permission from Gerstenblith AT, Rabinowitz MP, et al. The Wills Eye Manual\: Office and Emergency Room Diagnosis and Treatment of Eye Disease. 6th ed. Philadelphia, LWW; 2012\:323-324.)

Color Plate 13
FIGURE 15-1 • Acute tympanic membrane perforation. Note the clean-cut margins of the perforation, which is commonly seen in traumatic cases. Also examine the hyperemic tympanic membrane, which suggests an acute process. (Photo Contributor\: Richard A. Chole, MD, PhD. Reproduced with permission from Knoop KJ, et al. The Atlas ofEmergency Medicine. 3rd ed. McGraw-Hill, www.accessmedicine.com.)

Color Plate 14
FIGURE 18-1 • Urinary crystals. A. Calcium oxalate—Envelope-shaped crystals with a prominent"X"crossing at the center. B. Calcium phosphate— Needle-shaped crystals. C.Triple phosphate—"Coffin lid''appearance. D. Uric acid—Rosette formation. E. Cystine—Hexagonal plates. (Reproduced with permission from Mundt LA, Shanahan K. Graff. Textbook ofUrinalysis and Body Fluids. 2nd ed. Philadelphia, LWW; 2011\:66,67, 76,123,133.)

Color Plate 15
FIGURE 19-1 • Heliotrope rash. Note the reddish-purple rash over the upper eyelid with edema over the lower lids. The purplish hue is likened to the flower Heliotropium peruvianum. This patient developed severe muscle weakness of the shoulder girdle and presented with a lump in the breast that proved to be carcinoma. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick's ColorAtlas ofSynopsis ofClinicalDermatology. 6th ed. New York\: McGraw-Hill; 2009\:371.)

Color Plate 16
FIGURE 19-2 • Gottron papules. A raised, erythematous, scaly eruption can be seen over the dorsa of the hands and fingers, especially over the metacarpophalangeal and interphalangeal joints. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick's ColorAtlas ofSynopsis ofClinical Dermatology. 6th ed. New York\: McGraw-Hill; 2009\:372.)

Dermatology
CHAPTER OUTLINE
Keywords Review.........................................4..7........I INFECTIONS.............................................5.0......... I INFLAMMATORYCONDITIONS........................4..7... TineaVersicolor................................................5.0...........
AcneVulgaris................................................4.7...........DermatophyteInfections.......................................5.0........
I VASCULAR DISORDERS...............................4..8...... I NEOPLASMS............................................5.1.........
Infantile Hemangioma.......................................4..8.......
KEYWORDS REVIEW
Macule—A flat spot without skin elevation or depression.
Patch—A flat spot without skin elevation or depression, but larger than a macule.
Papule—A solid elevation of the skin.
Nodule—A solid elevation of the skin that is deeper and larger than a papule.
Plaque—A well-defined plateaulike elevation of the skin.
INFLAMMATORY CONDITIONS
I ACNEVULGARIS
The pathogenesis of acne vulgaris is not fully understood, but it is thought that follicular keratinization obstructs
Squamous Cell Carcinoma......................................5.1........ Basal Cell Carcinoma...........................................5.2.......... Melanoma.....................................................5.4...........
Wheal—A transient pinkish plaque with varying sizes and shapes.
Vesicle—A circumscribed elevation of the skin filled with fluid.
Bulla—A circumscribed elevation of the skin filled with fluid, but larger than a vesicle.
Pustule—A circumscribed elevation of the skin filled with pus. Paronychia—Inflammation of the nail fold.
sebum secretion resulting in keratin plugs or comedo­ nes. Androgens have been implicated in increasing sebum production, which provides a medium for the bacterium Propionibacterium acnes to grow within the follicle. Subse­ quently, P. acnes triggers an inflammatory response to the pilosebaceous units.
47

48 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Clinical Features\:
Lesions can occur on the face, neck, chest, back, or upper arms. Comedones are usually the earliest manifestation of acne. The comedones can be open (blackheads) or closed (whiteheads). Although there is no universal classification system for describ­ ing acne, the following has been provided as a guideline for board purposes. Mild acne can generally be characterized by comedones, papules, and pustules. Moderate acne can be char­ acterized by comedones, inflammatory papules and pustules, ± nodules. Severe acne is generally characterized by comedo­ nes, numerous inflammatory papules, pustules, nodules, and scarring. Nodules and pseudocysts can coalesce to form linear mounds (ie, sinus tracts) resulting in nodulocystic acne, which is considered severe acne.
Next Step\:
Step 1) Acne vulgaris is a clinical diagnosis. However, you have to consider hyperandrogenism ifthe patient presents with a com­ bination of acne, acanthosis nigricans, menstrual irregularity, or virilization. In these types of cases, the next best step is to order total testosterone, free testosterone, and DHEA-S levels. It is also imperative to ask the patient what type of medications he or she is taking since some drugs can cause acne. Some of the more no­ table agents that can cause acne include lithium, phenytoin, glu­ cocorticoids, isoniazid, azathioprine, and vitamins B2, B6, and B12.
Step 2) Treatment for acne vulgaris can be managed by the following\:
Mild Acne
Option 1\: For comedonal acne, patients can be treated with topical retinoids (eg, tretinoin, adapalene, tazarotene) since these meds aim to normalize follicular keratinization.
Option 2\: In the presence of papules and pustules, treat the patient with a topical retinoid + topical benzoyl peroxide + topical antibiotic (eg, clindamycin, erythromycin, sulfaceta­ mide, dapsone).
Moderate Acne
Option 1\: Topical retinoid + topical benzoyl peroxide + oral antibiotic (eg, tetracycline, doxycycline, minocycline, erythromycin, azithromycin, clindamycin, TMP-SMX).
Severe Acne
Option 1\: Oral isotretinoin is used in patients with cystic or nodulocystic acne. It can also be used in patients who have acne that is resistant to other therapies, including systemic antibiotics.
VASCULAR DISORDERS
I INFANTILEHEMANGIOMA
Infantile hemangiomas are the most common vascular tumors of infancy. Infantile hemangiomas are benign, and they can be characterized by a proliferation and an involution phase.
Prior to using isotretinoin, patients should have a pregnancy test since the drug is a teratogenic (category X). The patient should also be on birth control while taking the medication.
Step 3) Patients that improve with therapy can use topical reti­ noids for long-term maintenance therapy.
Follow-Up\:
Oral antibiotics should be used for a limited time (ie, <4 months). Oral isotretinoin can be given over a 4- to 6-month course.
Pearls\:
• It is still unclear if diet and stress contribute to the develop­ ment of acne.
• Side effects of isotretinoin include hypertriglyceridemia, hepatotoxicity, idiopathic intracranial hypertension (pseu­ dotumor cerebri), myalgias, visual changes, cheilitis, and dry skin.
• Caveat 1—Avoid using a tetracycline derivative (eg, doxycy­ cline, tetracycline, minocycline) in conjunction with isotreti­ noin since isotretinoin and the tetracycline derivatives can both cause pseudotumor cerebri.
• Caveat 2—Tazarotene is contraindicated in pregnant women since it is also a category X drug, however, adapalene is a category C drug.
• Caveat 3—Minocycline, doxycycline, and tetracycline can cause photosensitivity, and patients should be advised about sun protection.
• Caveat 4—Avoid using minocycline, doxycycline, or tetra­ cycline during pregnancy or in children since it can cause discoloration of the teeth and reduced bone growth.
• Benzoyl peroxide is an antimicrobial agent and is comedo- lytic. It is often used in conjunction with a topical or oral antibiotic to reduce the emergence of antibiotic resistance.
• Antibiotics are used to treat against Propionibacterium acnes with the aim of reducing the inflammatory response that comes along with the bacteria.
• Foundational point—Propionibacterium acnes is a gram­ positive, catalase-positive rod that can produce propionic acid, acetic acid, and lactic acid.
• Connecting point (pg. 121)—Know the clinical features and management of PCOS.
• Connecting point (pg. 165)—Take a look at the pregnancy drug ratings.
Clinical Features\:
Infantile hemangiomas are usually not present at birth but oc­ cur within the first few days to months after birth. The earliest sign will be an area of blanching with telangiectasias that will progress to a reddish macule. The lesion will enter the prolifer­ ating phase, which occurs during the first year. Rapid growth can be seen during the first 6 months of life and will slow down

by the end of the first year. The color of the lesion can be bright red, crimson, deep purple, or a halo of white speckles (vascular blanching). The lesion can be soft, rubbery, firm, compressible, or ulcerated. The lesion can be superficial and take the appear­ ance of a nodule, papule, or plaque. The lesion can also be sub­ cutaneous with a normal appearing overlying skin, or it can take on a bluish hue appearance ± telangiectatic patch. More commonly, the lesion can appear with both superficial and sub­ cutaneous components. The lesion can be solitary, multiple, or segmental (see Figure 4-1 and Color Plate 1). Hemangiomas tend to appear on the head and neck, but they can occur on the trunk, legs, lumbosacral area, mucous membranes, and even in internal organs. Following the proliferating phase is the involu­ tion phase, which can be characterized by a color change of the skin lesion, the lesion shrinks, and the consistency of the lesion becomes softer. Unfortunately, most of the skin lesions do not return to “normal skin” but will have residual effects such as dis­ coloration, scarring, atrophy, redundant skin, or telangiectasias. Approximately 50% of patients will have complete involution by 5 years, 70% by 7 years, and 90% by 9 years.
Next Step\:
Step 1) Diagnosis of infantile hemangiomas is made clinically. If the diagnosis is still in question after a thorough history and physical, then a biopsy can be performed for definitive diagnosis.
Step 2) Imaging is sometimes performed under special cir­ cumstances. Ultrasound is usually performed in infants <6 months with >5 small multiple cutaneous lesions to look for
hemangiomas in the internal organs (ie, gastrointestinal, liver, and brain). MRI is usually performed in patients that have hem­ angiomas in the lumbosacral area to look for spinal dysraphism or genitourinary anomalies.
Step 3) In the majority of uncomplicated infantile hemangio­ mas, there is no need for intervention unless vital structures are compromised. Under special circumstances a consultation should be requested\:
Pediatric ophthalmologist—If a hemangioma affects the periorbital area, especially when it involves the upper eyelid, then the vision might be compromised and a consultation would be prudent.
Pediatric otolaryngologist—If a hemangioma affects the “beard” distribution (ie, preauricular skin, mandible, lower lip, chin, and anterior neck), the patient may have hoarse­ ness, stridor, and cough. These are symptoms that an airway hemangioma may be present, and early consultation is warranted.
Plastic surgeon—When there is a risk of disfigurement or scarring at such locations as the nose, lip, and ear, an excision can be considered, but the outcome of the surgery must be weighed into consideration. In most cases, surgery should only be considered on involuted lesions and not proliferating lesions since they have the potential to bleed.
Follow-Up\:
Educating parents about the clinical course of infantile hemangiomas is important. Although there may be residual skin changes, it is important to discuss the realistic outcome with any type of intervention.
Pearls\:
• Medical and surgical intervention for infantile hemangioma may include pulsed dye laser, excisional surgery, intralesional steroids, systemic steroids, interferon-alpha, vincristine, and propranolol.
• Congenital hemangiomas are benign vascular tumors that grow in utero and are fully developed by birth.
• Complications of hemangiomas include airway obstruction, visual impairment, ulceration, bleeding, and high-output cardiac failure (secondary from hepatic or large cutaneous hemangiomas).
• Patients that have a segmental facial hemangioma should be aware of the PFIACES syndrome because the segmental lesion is one ofthe hallmarks ofthe syndrome. Ifthe syndrome is present, then a cardiac, dermatologic, neurologic, and ophthalmologic workup is necessary. PFIACES stands for\:
P—Posterior fossa malformations
H—Hemangiomas (usually a segmental lesion on the face) A—Arterial anomalies
C—Cardiac anomalies
E—Eye and endocrine abnormalities
S—Sternal cleft and/or supraumbilical raphe
FIGURE 4-1 • Infantile hemangioma. A segmental plaquelike lesion over the right side of the face. The lesion has a crimson color with a soft appear­ ing texture. Involution is apparent over the forehead. The lesion on the upper eyelid and the medial canthus is impairing proper function of the
lid, and this indicates that vision might be impaired in the future. In this patient, treatment was indicated. (Reproduced with permission from Wolff K, Johnson RA.Fitzpatrick'sColorAtlasofSynopsisofClinicalDermatology.
6th ed. New York\: McGraw-Hill; 2009\:196.)
CHAPTER 4 DERMATOLOGY 49

50 CLINICAL JUDGMENT U5MLE STEP 3 REVIEW
INFECTIONS
I TINEAVERSICOLOR
Tinea versicolor, also known as pityriasis versicolor, is a noncontagious, superficial fungal infection caused by a saprophyte in the genus Malassezia. Although there are other Malassezia (formerly known as Pityrosporum) species that can cause tinea versicolor, Malassezia furfur has been synonymous with this disease. Malassezia furfur was previously known as Pityrosporum ovale and Pityrosporum orbiculare.
Clinical Features\:
The affected skin may have several (versi-) shades of color. The skin may be hypopigmented, hyperpigmented, or have a salmon-color appearance. In light-skinned individuals, lesions may appear hypopigmented on tanned skin. In darker-skinned individuals, lesions may appear as dark brown macules. The lesions may appear as well-marginated, oval-to-round macules. Sometimes the macules can coalesce forming irregularly shaped patches. Most often, the infection has a tendency to affect sebum-rich areas or oily skin. However, lesions can be seen on the face, neck, upper arms, axilla, upper trunk, abdomen, groin, or thighs. Sometimes a fine scale can be appreciated over the skin lesion. In most cases, patients will be asymptomatic, but some will complain of mild pruritus.
Next Step\:
Step 1) Tinea versicolor is a clinical diagnosis. However, a con­ firmatory test with KOH scraping of the scale will demonstrate clusters of oval budding yeasts cells and branching hyphae in the classic “spaghetti and meatballs” appearance (see Figure 4-2 and Color Plate 2).
Step 2) Treatment involves topical or systemic therapy. Initially, topical therapy should be attempted first unless there is treat­ ment failure with topicals or recurrent or widespread infection, in which case systemic therapy would be more appropriate.
Topical therapy—Selenium sulfide, “azole” antifungals (eg, ketoconazole, clotrimazole, econazole) or terbinafine can be applied for 2 weeks.
Systemic therapy—-Oral “azole” antifungals such as keto­ conazole, fluconazole, or itraconazole can be used. Oral terbinafine and griseofulvin should be avoided since they are both ineffective in this condition.
Follow-Up\:
Patients should be aware that discoloration of the skin may persist for 1 to 2 months even after successful therapy. Although recurrence is not uncommon, physicians should think about immunosuppression in the individual.
Pearls\:
• Tinea versicolor is not a dermatophyte infection.
• Tinea versicolor is a very superficial fungal infection local­ ized to the stratum corneum, unlike the dermatophytes, which can go deeper into the epidermis.
• AWoodslampwillrevealayellow-greenfluorescenceofthe lesion in the dark.
• Hepatotoxicity has been associated with systemic “azole” antifungals.
• Tinea versicolor has a predisposition for warm tropical climates.
I DERMATOPHYTE INFECTIONS
Dermatophyte infections are fungal infections that can break down keratin and therefore affect the skin, nails, and hair. Three common dermatophytes include Trichophyton, Microsporum, and Epidermophyton.
Clinical Features\:
Tinea capitis—Tinea capitis is commonly seen in children. Clinical presentation can vary, but common symptoms include pruritus, scaling, and bald spots. Sometimes a sharply defined area of alopecia can be seen that appears as a “gray patch.” Tinea capitis can also present as diffuse, poorly circumscribed patches of alopecia that on close inspection appear as “black dots” because of broken hair shafts. Scalp lesions can also appear as cup-shaped yellow crusts. In some cases, an immune response to the fungal infection will result in a kerion, which is mani­ fested as a raised, boggy, red, painful, purulent lesion ± posterior cervical lymphadenopathy (see Figure 4-3 and Color Plate 3).
Tinea corporis—Tinea corporis usually presents as a pruritic, erythematous, scaly lesion that expands peripherally with raised advancing borders while clearing centrally, resulting in a ring- shaped lesion. Tinea corporis can be contracted from con­ taminated soil, animals, skin-to-skin contact such as wrestlers (ie,tineacorporisgladiatorum),orfromautoinoculation (eg, tinea capitis to tinea corporis).
Tinea cruris—Also known as jock itch. Similar presentation to tinea corporis, but will affect the inner thighs, groin, and some­ times the buttocks and perineum area. The infection will usually spare the scrotum and penis. Consider candidal intertrigo when it affects the scrotum and penis along with satellite papules or
FIGURE 4-2 ♦ Malassezia furfur on KOH preparation. Examination of
both round yeast and elongated pseudohyphae reveals the characteristic "spaghetti and meatballs" pattern. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick's ColorAtlas ofSynopsis ofClinical Dermatology.
6th ed. New York\: McGraw-Hill; 2009\:735.)

FIGURE 4-3 • Kerion. An extremely painful, boggy, purulent inflammatory nodule on the scalp of this 4-year-old child with tinea capitis. The lesion drains pus from multiple openings, and there is a retroauricular, tender lymphadenopathy. Infection was due to a zoophilic dermatophyte, Tricho­ phyton verrucosum, that was contracted from an infected rabbit. (Repro­ duced with permission from Wolff K, Johnson RA. Fitzpatrick's ColorAtlas of Synopsis ofClinicalDermatology. 6th ed. New York\: McGraw-Hill; 2009\:713.)
pustules. Tinea cruris can be contracted by autoinoculation or by fomites (eg, towels, bedsheets).
Tinea pedis—Also known as athlete's foot. Clinical presenta­ tion can vary, but most commonly, patients will complain of pruritus. The lesion can affect the interdigital area, which can be wet (ie, macerated ± ulceration) or dry (ie, scaling). Sometimes painful bullae or vesicles can be found on the plantar surface or toes. Another presentation includes diffuse scaling to hyper­ keratosis with distinct areas of erythema on the plantar surface and lateral borders of the feet, which is notably referred to as the moccasin type.
Tinea unguium—Also known as dermatophytic onychomyco­ sis. However, onychomycosis can also be caused by molds and yeast with Candida albicans as a common cause of fingernail onychomycosis with paronychia. Clinical presentation for der­ matophytic onychomycosis can vary, but look for a discolor­ ation of the nail plate, which can be brown, yellow, or a chalky white appearance.
Next Step\:
Step 1) Diagnosis of the tinea infections is by KOH prepara­ tion with hyphae and/or spores visible under microscope. If the diagnosis is still in question, a culture can be performed for definitive diagnosis.
Step 2) Treatment involves topical or systemic therapy. Initially, topical therapy should be attempted first in tinea corporis,
NEOPLASMS
I SQUAMOUSCELLCARCINOMA
Squamous cell carcinoma (SCC) is the second most common skin cancer after basal cell carcinoma.
cruris, and pedis unless there is treatment failure with topicals or extensive disease, in which case systemic therapy would be more appropriate.
Topical therapy—Tinea corporis, cruris, and pedis can be treated with topical ketoconazole, clotrimazole, econazole, miconazole, oxiconazole, sertaconazole, sulconazole, ter- binafine, naftifine, butenafine, ciclopirox, or tolnaftate. Do not use topical nystatin for dermatophytic infections, but it is okay to use for candidal infections.
Systemic therapy—Tinea capitis should be treated with oral griseofulvin, terbinafine, itraconazole, or fluconazole. Tinea unguium should be treated with either oral terbinafine or itraconazole with a duration of 6 weeks for fingernails or
12 weeks for toenails.
Follow-Up\:
Patients who develop a kerion and are appropriately treated with an antifungal medication should see improvement of the kerion (ie, treat the underlying infection).
Pearls\:
• Avoid using topical steroids for tinea corporis, cruris, and pedis because it can alter the clinical presentation such as decreased erythema with poorly defined borders; this condi­ tion is then referred to as tinea incognito.
• Erythrasma can present similarly to tinea cruris and tinea pedis; however, a Wood’s lamp will demonstrate the charac­ teristic coral red fluorescence in erythrasma.
• Hepatotoxicity has been associated with oral “azoles,” griseo­ fulvin, and terbinafine.
• When dermatophytes infect beyond the epidermis into the dermis, a deep folliculitis can occur that is referred to as Majocchi’s granuloma. Papules, pustules, or nodules can be present. It is most commonly seen in women who frequently shave their legs, immunocompromised individuals, or those who apply topical steroids on the skin.
• ID reactions (ie, dermatophytid reactions) are an immune response to dermatophytic infections. They can be charac­ terized by pruritic, papulovesicular eruptions occurring at distant sites from the original fungal infection. The lesions are devoid of any organisms at the distant site, and patients usually improve when the original fungal infection is treated appropriately.
Clinical Features\:
Squamous cell carcinoma has a predilection for the scalp, face (forehead, nose, cheeks, ears, outside border of the lower lip), upper chest, upper back, dorsal aspects of the hands and fore­ arms, genital area, and shins. Clinical presentation can vary but can be best characterized when the lesion is in situ or invasive\:
CHAPTER 4 DERMATOLOGY 51

52 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
FIGURE 4-4 • Squamous cell carcinoma in situ (Bowen's Disease).
A large, sharply demarcated, scaly, erythematous plaque simulating a psoriatic lesion. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick's ColorAtlas ofSynopsis ofClinical Dermatology. 6th ed. New York\: McGraw-Hill; 2009\:279.)
SCC in situ (Bowen’s disease)—Lesions are confined to the epidermis without invasion into the dermis layer. Lesions are typically presented as a sharply defined, scaly patch or plaque ± hyperkeratosis. The color can range from pink to red (see Figure 4-4 and Color Plate 4). Lesions tend to grow slowly, and once it becomes invasive, a nodular lesion usually appears within the plaque. When in situ lesions affect the penis, the lesion is referred to as erythroplasia of Queyrat. Patients are usually asymptomatic with in situ lesions.
SCC invasive—Invasive lesions can be a papule, nodule, or plaque that can be scaly, crusted, or ulcerated with heaped- up edges. Lesions can be further characterized by their dif­ ferentiation. Well-differentiated lesions are usually harder and have hyperkeratosis. Poorly differentiated lesions are usually softer, fleshy, and friable without hyperkeratosis. Patients are also asymptomatic but rapidly evolving lesions can be painful.
Next Step\:
Step 1) Confirm the diagnosis with a biopsy (ie, “tissue is the issue”).
Step 2) Surgical excision is the most common form of treat­ ment. Prevention is also an important part of skin cancer management, which should include sunscreens and protective clothing.
Follow-Up\:
The overall 5-year cure rate is >90% for primary cutaneous squamous cell carcinoma.
Pearls\:
• Risk factors for SCC include sun exposure, ionizing radia­ tion, immunosuppression, arsenic exposure, industrial car­ cinogens, and actinic keratosis.
FIGURE 4-5 • Keratoacanthoma. A keratoacanthoma is seen on the face of a woman. Note the telangiectasias and central keratin core. (Reproduced with permission from Usatine RP, et al. TheColorAtlasofFamilyMedicine. 2nd ed. New York\: McGraw-Hill; 2013\:977.)
• Actinic keratosis typically presents as yellowish-brown hy- perkeratotic scales on a red-tinged background of macules on sun-exposed skin. Removing the scales can be quite painful for the patient. Although the progression from actinic kera­ tosis to SCC is fairly low, for lesions that grow rapidly, ulcer­ ate, or for which the diagnosis is uncertain, a biopsy should be performed. Avoid prolonged sun exposure and wear sunscreens. Treatment includes cryotherapy, photodynamic therapy, topical 5-FU, or topical imiquimod.
• A keratoacanthoma is most likely a variant of SCC and presents as a rapidly growing nodule that appears domed­ shaped with central hyperkeratosis (see Figure 4-5 and Color Plate 5). Shedding or removal of the central keratotic plug results in a craterlike appearance. Regression of the lesion begins within a few months and can take as long as 1 year. Since keratoacanthomas can be indistinguishable from SCC, a biopsy is often recommended. Treatment is by excision.
• Hyperkeratosis can result in a hornlike projection of the skin. Hyperkeratosis can be seen in actinic keratosis, kerato­ acanthoma, SCC in situ, and invasive SCC. A biopsy should be taken because of the possibility of invasive SCC at the base of the horn.
• Verrucous carcinoma is a subtype of SCC and is characteris­ tically presented as “cauliflower-like” lesions.
• SCC rarely metastasizes; approximately 5% to 10% ofpatients with SCC will develop regional to distant metastasis.
• Foundational point—Histologically, invasive squamous cell carcinoma may demonstrate keratin production (“keratin

FIGURE 4-6 • Basal cell carcinoma. A. Rodent ulcer—A rolled, pearly border surrounds an ulcer with yellow necroses and a tiny black crust. B. Superficial BCC—A solitary, flat, bright red lesion with a slightly elevated rolled border that can be detected with "side lighting." C. Sclerosing BCC—A scarlike lesion on the nose with ill-defined margins. D. Pigmented BCC—An irregular pitch-black plaque with a central area of regression. This pigmented BCC is clinically indistinguishable from superficial spreading melanoma. (Reproduced with permission from WolffK,Johnson RA.Fitzpatrick'sColorAtlasofSynopsisofClinicalDermatology.6thed.NewYork\:McGraw-Hill; 2009\:290,291,292,295.)
pearls”) and intercellular attachment sites (desmosomes or “intercellular bridges”).
• Connecting point (pg. 260)—Know the other histologic features from different neoplasias.
I BASALCELLCARCINOMA
Basal cell carcinoma (BCC) is the most common skin cancer.
BCC develops from the basal layer of the epidermis.
Clinical Features\:
Basal cell carcinoma has a predilection for the scalp, face (medial and lateral canthi, nasolabial fold, ears), and trunk. BCC typically
grows slowly, and patients are often asymptomatic. Consider four different types of BCC (see Figure 4-6 and Color Plate 6)\:
Nodular—Most common type of BCC, which typically presents as a smooth, “pearly” nodule or papule with tel- angiectasias. If untreated, nodular BCC can ulcerate into a “rodent ulcer,” called this because the appearance of the le­ sion is like something that has been gnawed on by a rodent.
Superficial—These lesions tend to occur on the trunk as solitary or multiple lesions. They typically present as a red, scaly, patch or plaque with threadlike borders.
Sclerosing (morpheaform)—These lesions can present as a scarlike, flesh-colored, lesion with ill-defined borders.
CHAPTER 4 DERMATOLOGY 53

54 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Pigmented—These lesions are often confused with melano­ ma since they may appear as a brown-black plaque or nodule.
Next Step\:
Step 1) Confirm the diagnosis with a biopsy (ie, “tissue is the issue”).
Step 2) Surgical excision is the most common form of treat­ ment. Prevention is also an important part of skin cancer management, which should include sunscreens and protective clothing.
Follow-Up\:
The prognosis for patients with BCC is excellent; however, significant morbidity can occur if the lesion is left untreated.
Pearls\:
• Risk factors for BCC include sun exposure, ionizing radia­ tion, immunosuppression, arsenic exposure, and basal cell nevus syndrome.
• Basal cell nevus syndrome is an autosomal dominant disorder that results in multiple BCCs along with other numerous anomalies such as frontal bossing, palmar and plantar pitting, intracranial calcification, rib anomalies, and odontogenic (bone) keratocysts.
• Xeroderma pigmentosum is an autosomal recessive disease that results in the inability to repair damaged DNA caused by ultraviolet light. Consequently, patients can develop basal cell carcinoma, squamous cell carcinoma, melanoma, or neurologic and ocular conditions.
• Treatment options for BCC can also include cryotherapy, electrodesiccation and curettage, topical 5-FU, imiquimod, photodynamic therapy, radiation, or Mohs surgery.
• Mohs surgery is the best approach when there is concern for recurrence or for cosmetic reasons (eg, tissue sparing). In the Mohs surgery, tissue is resected at oblique angles and evalu­ ated under the microscope, providing excellent evaluation of the peripheral margins while minimizing the amount of tissue needed to be resected.
• There are no known “in situ” lesions in BCC compared to SCC.
• There is no hyperkeratosis in BCC compared to SCC.
• BCC very rarely metastasizes; approximately <0.5% of pa­ tients with BCC will develop regional or distant metastasis.
• Foundational point—Histologically, the tumor cells of nod­ ular BCC are arranged in a characteristic palisading pattern at the periphery. The stroma tends to shrink away from the tumor nests creating a cleft (ie, retraction artifact).
• Foundational point—Mutations in the tumor suppressor gene, patched 1 (PTCH1), has been identified as one of the cause for the development of BCC.
I MELANOMA
Melanoma is the fifth most common cancer in men and sev­ enth most common cancer in women in the United States. Most
melanomas have a characteristic horizontal (ie, radial) growth before transitioning to a vertical growth pattern with further in­ vasion into the dermis.
Risk Factors\:
UVA and UVB radiation exposure (especially intense intermit­ tent exposure), family history, personal history of melanoma, tanning beds, psoralen+UVA radiation therapy (PUVA), typical nevi (>50), dysplastic nevi (>5), congenital nevi, eye color (blue, green, hazel), hair color (red, blond), T freckles, sunburns in childhood or adolescence.
Clinical Features\:
Therearefourmajorsubtypesofinvasivemelanomas.Indescend­ ing order of frequency, these melanomas include (see Figure 4-7 and Color Plate 7)\:
Superficial spreading—This type of lesion is the most com­ mon. It can occur anywhere on the body but has a predilec­ tion for the back in both men and women and on the legs of women. Radial growth is fairly slow with up to a period of 2 years before switching to vertical growth. The lesion can take on a variety of colors, along with irregular borders and asymmetry. The presence of a nodule usually indicates progression into the vertical growth phase.
Nodular—These lesions do not have a radial growth phase but begin their growth in the vertical direction, making the prognosis very concerning. These lesions grow fairly rapidly within a period of 1 to 2 years. Lesions appear as dome­ shaped nodules with minimal variation in color and have more of a uniform blue-black appearance. For unknown rea­ sons, there is a high frequency ofthis type in Japanese people.
Lentigo maligna—This lesion typically occurs on sun- exposed areas such as the head, neck, and dorsa of the hands. These lesions begin as in situ lesions. Lentigo ma- lignas are very-slow-growing lesions that can take up to 20 years before transforming into an invasive lesion. Ini­ tially, the lesions start out as a brown-tan macule that develops into a larger, darker, asymmetric lesion. The pres­ ence of a nodule or papule often indicates the transition into the vertical growth phase, and then the term lentigo maligna melanoma is used.
Acral lentiginous—These lesions are the least common of the melanomas, but commonly occur in Asians and dark- skinned individuals. They can occur on the palms of the hands, soles of the feet, under the nails, and on mucosal surfaces. The lesions begin with radial growth that may go unnoticed for several years before transitioning to vertical growth where nodules usually appear.
Next Step\:
Step 1) The ABODE mnemonic (Asymmetry, Border irregular­ ities, Color variegation, Diameter >6 mm, Evolving) can assist with the initial clinical diagnosis.
Step 2) A full-thickness, narrow-margin excisional biopsy should be performed on any suspicious lesion to confirm the diagnosis.

CD
FIGURE 4-7 • Melanoma. A. Superficial spreading—Depicted is a flat plaque that demonstrates asym­ metry, irregular borders, and color variegation (tan, brown, black, and red). Note the partially crusted nodule, which indicates a transition into the vertical growth phase. B. Nodular—A discrete darkly pigmented papule. This lesion has been present for less than 1 year. C. Lentigo maligna—An irregularly shaped, flat macular lesion with color variegation (tan, brown, black) that represents an in situ melanoma. D. Acral lentiginous— A lesion on the heel that reveals color variegation (brown, gray, black) and a nodular component that is hyperkeratotic, reddish, and ulcerated. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick's ColorAtlas ofSynopsis ofClinical Dermatology. 6th ed. New York\: McGraw-Hill; 2009\: 313, 319,322,325.)
It is not recommended to perform a shave biopsy because the Breslow depth is the most important prognostic parameter in the evaluation of a melanoma.
Step 3) Surgical therapy with a wide local excision is the pri­ mary form of treatment for cutaneous malignant melanomas. Prevention with sunscreens and protective clothing is an im­ portant part of skin cancer management since patients that de­ velop melanomas are at risk of developing another melanoma in the future.
Follow-Up\:
The prognosis depends on the thickness of the lesion. For example, a thickness >3.6 mm correlates to an 8-year surviv­ al rate of 33.3%. When there is lymph node involvement, the
5-year survival rate is approximately 30% to 45%. With distant metastases, the 5-year survival rate diminishes to <10%.
Pearls\:
• Melanomas can arise from in situ lesions from the subtypes of superficial spreading, lentigo maligna, and acral lentigi­ nous but not from nodular.
• Melanomas metastasize more frequently compared to SCC or BCC.
• Foundational point—Serum S-100 is a tumor marker for melanoma. Serum levels of this protein are correlated with the stage of the disease. S-100 is not specific for melanoma since it can also be found in schwannomas, neurofibromas, and different cell types (eg, macrophages, adipocytes).
CHAPTER 4 DERMATOLOGY 55

CHAPTER OUTLINE
I EKG REVIEW...........................................5.7.......I.. AV NODE................................................5.9..........
Rate........................................................5.7...........F..irst-DegreeAVBlock..........................................5.9........ Rhythm.....................................................5.7............Second-Degree AVBlock—Type I...............................6.0..... IntervalsandComplexes.....................................5.7........ Second-DegreeAVBlock—TypeII..............................6.0...... AxisDeviation...............................................5.8.......... Third-DegreeAVBlock.........................................6.1.........
Atrial Enlargement..........................................5.8.........
Ventricular Hypertrophy.....................................5.8........ Infarcts.....................................................5.8............
I VENTRICLES............................................6.3.......... I ATRIA.................................................5..8..........TorsadesDePointes...........................................6.3..........
Multifocal Atrial Tachycardia..................................5.8......
EKG REVIEW
I RATE
Step 1) Find an R wave that lands on a heavy black line.
Step 2) From there, count the sequence “300-150-100-75-60-50” for each ofthe large boxes (ie, 5 small squares) until the next R wave is seen. Note that the next R wave may not fall exactly on another heavy black line, and therefore, you have to approximate the heart rate from the last two numbers that were counted from your sequence.
Pearl\:
• Bradycardia (<60 bpm), tachycardia (>100 bpm), parox­ ysmal tachycardia (150-250 bpm), flutter (250-350 bpm), fibrillation (350-450 bpm).
Ventricular Fibrillation.........................................6..4........
I RHYTHM
Sinus rhythm should have the following components\:
1) P wave before QRS.
2) The presence of a QRS after every P wave. 3) Upright P wave in leads I, II, aVF, V4-V6. 4) Negative P wave in aVR.
5) Heart rate between 60 and 100 bpm.
I INTERVALSANDCOMPLEXES
P wave\: <3 small boxes (<0.12 seconds), and amplitude <2.5 small boxes (<0.25 mV)
PR interval\: 3 to 5 small boxes (0.12-0.20 seconds) QRS complex\: <2.5 small boxes (<0.10 seconds)
I ACCESSORY PATHWAY..................................6.2.......
Wolff-Parkinson-White........................................6.2.........
57

58 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
QT interval\: QT interval depends on the heart rate (ie, corrected QT or QTc). For example, a faster heart rate can result in a shorter QT. The QTc in men is <0.44 seconds, and the QTc in women is <0.45 to 0.46 seconds. A simple method to detect a normal QT interval when the heart rate is within normal range (60-100 bpm) is to visually compare the R-R interval length to the QT interval length. If the QT interval appears less than half of the R-R interval, then you have a normal QT.
Pearl\:
• One small box (1 mm) going horizontally represents 0.04 seconds, and one large box (5 small squares) represents 0.2 seconds. One small box (1 mm) going vertically represents 0.1 millivolt (mV), and one large box (5 small squares) rep­ resents 0.5 millivolts (mV).
8 AXIS DEVIATION
Axis deviation represents the net direction of the electrical cur­ rents generated during ventricular depolarization. Consider the following\:
Normal axis (-30° to 90°)\: Net positive (ie, upright) QRS deflection in both leads I and II.
Left axis (-30° to -90°)\: QRS in lead I is net positive, but QRS in lead II is net negative.
Right axis (90° to 180°)\: QRS in lead I is net negative, but QRS in aVF is net positive.
Extreme axis (180° to -90°)\: Net negative (ie, downward) QRS deflection in both leads I and II.
Pearl\:
• For causes of left axis deviation, think of LVH, left bundle branch block, inferior MI, pregnancy, and hyperkalemia. For causes of right axis deviation, think of RVH, right bundle branch block, and lateral wall MI. It should be noted that the word “net” refers to the overall direction of the QRS complex (eg, upward deflection > downward deflection).
I ATRIAL ENLARGEMENT
Left atrial enlargement (LAE)\: A broad notched P wave in lead II and/or a diphasic P wave in lead Vj with a prominent negative component in the end portion of the diphasic wave.
ATRIA
1 MULTIFOCALATRIALTACHYCARDIA
Multifocal atrial tachycardia (MAT) is the result of multiple ectopic foci generating impulses. These areas of automa- ticity can lead to an elevated heart rate that exceeds 100
Right atrial enlargement (RAE)\: Increased P wave amplitude in lead II (P >2.5 mm) and/or in lead Y l (P >1.5 mm).
8 VENTRICULAR HYPERTROPHY
Left ventricular hypertrophy (LVH)\: A pattern recognition of a left axis deviation, left atrial abnormalities (eg, biphasic P wave, P wave >3 small boxes), widened QRS (>2.5 small boxes), increased voltage of the QRS complex (ie, tall R waves in lead V5 or V6, deep S wave in Vx or V2), or ST-T wave changes (eg, T wave inversions, ST depressions).
Right ventricular hypertrophy (RVH)\: A pattern recognition of a right axis deviation, right atrial enlargement, prominent R wave in lead Vj (R > S wave), or ST-T wave changes (eg, T wave inversions, ST depressions).
Pearl\:
• For causes of LVH, think of aortic stenosis, aortic regurgi­ tation, mitral regurgitation, hypertrophic cardiomyopathy, and dilated cardiomyopathies. For causes of RVH, think of pulmonary stenosis, pulmonary HTN, cor pulmonale, and lung diseases.
8 INFARCTS
Injury to the myocardial tissue secondary to an occluded artery can be identified on specific EKG leads that are associated with the anatomic regions of the heart (see Table 3-5).
Pearls\:
Hyperkalemia—Peaked T waves, P wave flattens, and QRS widens.
Hypokalemia—U waves occur after the T wave, which is best seen in leads V4-V6, T wave flattens or inverted.
Hypercalcemia—Shortened QT interval secondary to shortened ST segment.
Hypocalcemia—Prolonged QT interval.
Hypothermia—Osborne wave, which is an elevation of the J point (ie, sits between the QRS and ST segment).
Digoxintoxicity—Digoxintoxicitycancausealmostanyarrhyth­ mia (eg, asystole, PVCs, AV blocks, ventricular fibrillation).
beats per minute (bpm). The cause of MAT is related to the underlying illness. Common underlying illnesses associ­ ated with MAT include COPD, acute respiratory failure, pulmonary embolism, pneumonia, sepsis, coronary artery disease, heart failure, valvular heart disease, hypertension, right atrial enlargement, hypokalemia, hypomagnesemia, hypoxia, and medications (eg, theophylline, aminophylline, isoproterenol).

FIGURE 5-1 • Multifocal atrial tachycardia. Reproduced with permission from Loscalzo J, et al. Harrison's Cardiovascular Medicine. New York\: McGraw-Hill; 2010\:508.
EKG Features\:
(1) P waves have at least 3 different morphologies (eg, in­ verted, biphasic, upright), (2) Atrial rate >100 bpm, (3) P-P, P-R, and R-R intervals vary, and (4) A flat isoelectric base­ line between the P waves distinguishes MAT from atrial fi­ brillation (AF). See Figure 5-1.
Next Step Treatment\:
Step 1) Treat the underlying illness.
Step 2) Pharmacologic therapy can be considered for acute heart rate control. Rate control therapy with either a cal­ cium channel blocker (IV verapamil) or with a beta-blocker (IV metoprolol) has been used. Verapariiil is the preferred agent over metoprolol in patients with bronchospasms or COPD since there are concerns of bronchoconstriction if a beta-blocker is used. However, neither agent should be
AV NODE
1 FIRST-DEGREEAVBLOCK
First-degree AV block is a delay in the impulse between the atria and ventricles. The site of conduction delay usually occurs in the AV node if the QRS duration is normal.
EKG Features\:
PR interval >5 small boxes (>0.20 seconds) that does not vary. See Figure 5-2.
Next Step Treatment\:
Step 1) No pacemaker is required in most patients.
used in the presence of a second- or third-degree AV block or sinus node dysfunction unless a pacemaker has been implanted.
Disposition\:
Admit patients to the hospital for further cardiac monitoring if acute heart rate control was attempted in the ED.
Pearls\:
• DC cardioversion is ineffective.
• The use of antiarrhythmic drugs is questionable.
• The clinical manifestations of MAT typically correlate with the underlying illness.
• OntheCCS,ifyou’regoingtogivethepatientintravenous rate control, be sure to have the appropriate monitoring (eg, cardiac monitor, blood pressure monitor, pulse oximetry).
Follow-Up\:
Patients with an isolated first-degree AV block have a good prognosis, but patients with coexistent coronary artery disease should be closely observed since they are at higher risk of mor­ bidity and mortality.
Pearls\:
• Atrioventricular blocks can be the result of reversible causes (eg, T vagal tone, beta-blockers, calcium channel blockers, digoxin) or structural causes (eg, MI, myocarditis, catheter ablation).
• On the CCS, when placing an order for an EKG test, there are different types to choose from (eg, 12-lead, ambulatory, monitor, rhythm strip, and EKG stress test). The EKG 12-lead
CHAPTER 5 EKG 59

60
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Figure 5-2 • First-degree AV block. Reproduced with permission from Jones SA. ECG Success\: Exercises in ECG Interpretation. Philadelphia\: FA Davis Company; 2008\:56.
will give you the most useful information in terms of rhythm, axis, intervals, and interpretation.
1 SECOND-DEGREEAVBLOCK—TYPEI
Second-degree AV block is a result of intermittent failure of atrial impulses reaching the ventricles. Second-degree AV block type I (Mobitz type I or Wenckebach block) typically occurs within the AV node and is associated with a normal QRS inter­ val. Rarely, does type I progress to a complete heart block.
EKG Features\:
Progressive prolongation of the PR interval preceding a non- conducted P wave (ie, no QRS complex). See Figure 5-3.
Next Step Treatment\:
Step 1) The clinical management for Mobitz type I can be sum­ marized into patients that are asymptomatic or symptomatic.
Asymptomatic\: No specific therapy.
Symptomatic\:
1) Identify any reversible causes (eg, meds, MI, T vagal tone), if none found, then ...
2) IVatropine,q5minutes,nottoexceed3.0mg.
3) If atropine is unsuccessful, consider transcutaneous pacing (ie, temporary pacing).
Disposition\:
Admit patient to the hospital for further cardiac monitoring and consultation with a cardiologist for a permanent pacemaker
in patients with symptomatic bradycardia without a reversible etiology.
Pearls\:
• In approximately 90% of patients, the right coronary artery (RCA) supplies the AV node. Therefore, an obstruction in the RCA can result in an inferior MI and a Mobitz type I block.
• There is a higher risk in mortality in patients with an inferior MI and an associated Mobitz type I block.
• Connecting point (pg. 26)—Know the associated leads for an inferior MI.
• On the CCS, “transcutaneous pacemaker, temporary” and “pacemaker, permanent” are both available in the practice CCS.
1 SECOND-DEGREEAVBLOCK—TYPEII
Second-degree AV block type II (Mobitz type II) typically oc­ curs below the AV node (infranodal) and frequently progresses to a complete heart block.
EKG Features\:
A fixed PR interval prior to and after a nonconducted P wave (ie, no QRS complex). Patients with type II blocks typically do not have a normal QRS duration, but rather a wide QRS inter­ val which is indicative of a block in the infranodal system (eg, bundle of His, bundle branches). See Figure 5-4.
Next Step Treatment\:
Step 1) Identify any reversible causes (eg, meds, MI, t vagal tone).
Step 2) Similar to Mobitz type I, symptomatic bradycardia with signs of hypoperfusion may require atropine and transcutaneous pacing.
lizi- ttfit■;;\:ttSTit?ffiftttiittit??[f?fi?i\: ttitipxr.ffj?t\:;1f.jfiPHlittttilIff?ttTTriit?ftffit
l?i?♦4>t Ht'IT jjtt\: f??fft?ttfH?Elttit£idc«r StTUTtfl?jXlXilil tt ttitIfEl?imtiftt? ifffitItiltt it?pjf?H?ik ff?ftt ttiixl•itT
XTT-I
It!KSttft?ttss
'tt ■Si ft? ft?
it?
it lit
+m i tnr
$ E lip P T-H* Iff? fpt t
T-ITt fititittffif
tt tj? iti tt-HE
Bt 1
tt iij\: iff!
Tfrt
tt Hr\:
at
fit fit -gr{- tt Sh i?i! if?;
tt iff? tii tt iti
iti
Tltt tt
iltT
iiif
-i+*f 4-H-t SE 'tot E*r fit tii irtr t?i fit fit ffj? -Erf
iff? \:S±Sii it? iii?
it?
tt' Iff? IXIX
til tlf fit iit
li \:i
if jtf tt f.;t ft\: ffif
tt1 6?i±t
E Iff?tt tt tt ftp til tttt tiU
fit \:rr.
ini
Figure 5-3 • Second-degree AV block—Type I. Reproduced with permission from Jones SA. ECG Success\: Exercises in ECG Interpretation. Philadelphia\: F.A. Davis Company; 2008\:57.
St'} SH tt f.TTT
f?g fSTtt Ttixfff? tt

Figure 5-4 • Second-degree AV block—Type II. Reproduced with permission from Jones SA. ECGSuccess\: Exercises in ECG Interpretation. Philadelphia\: F.A. Davis Company; 2008\:57.
Step 3) If no reversible causes are found, then the next best step is to implant a permanent pacemaker in almost all patients with a Mobitz type II block.
Disposition\:
Admit symptomatic patients to the hospital for further mon­ itoring since patients with Mobitz type II blocks can have syncopal attacks (Stokes-Adams attacks).
Pearls\:
• Mobitz type I and Mobitz type II cannot be differentiated on EKG in the presence of a 2\:1 block. In a 2\:1 block, every other P wave is not conducted.
• On the CCS, when you order a consult, remember that you are functioning as a primary care physician and not the specialist.
I THIRD-DEGREEAVBLOCK
Third-degree AV block (complete heart block) results in no AV conduction. The escape rhythm that controls the ventricles can occur at any level below the region of the conduction block.
EKG Features\:
There is complete dissociation between the P waves and QRS complexes. If a third-degree AV block occurs within the AV node or bundle of His, the escape rhythm will usually have a narrow QRS complex. If the escape rhythm originates distal to the block (eg, ventricles), the QRS complex will usually be wider and rates will be slower (eg, <40 bpm). See Figure 5-5.
Next Step Treatment\:
Step 1) Identify any reversible causes (eg, meds, MI, T vagal tone) and remove the offending agent.
Step 2) Short-term management\: Unstable patients (symp­ tomatic bradycardia) should be managed with (1) Airway, Breathing, Circulation, (2) monitoring equipment (eg, blood pressure, cardiac monitor, pulse oximetry), (3) oxygen (if hy­ poxemic), (4) IV access, and 5) 12-lead EKG. Unstable patients should initially be treated with IV atropine (q5 minutes, 3 mg maximum). If atropine is ineffective, prepare for transcutane­ ous pacing. Acceptable alternatives to temporary pacing are IV infusions of either dopamine or epinephrine. If transcutaneous pacing or the above medications are ineffective, consider trans­ venous pacing.
Step 3) Long-term management\: If no reversible causes are found, then the next best step is to implant a permanent pace­ maker in almost all patients with a third-degree AV block.
Disposition\:
Hemodynamically unstable patients may require the ICU. He- modynamically stable patients can be sent to the telemetry floor.
Pearls\:
• Some patients may respond favorably to atropine, which is indicative of an abnormal conduction in the AV node. The more distal the conduction block is from the AV node (ie, less vagal activity), the less the response with atropine.
• As a result of the slow rate in third-degree AV blocks, pa­ tients can experience lightheadedness or syncope.
• On the CCS, telemetry is also known as cardiac monitor in the practice CCS. If you want future results from the cardiac monitor, you have to type in “check cardiac monitor” in the order form.
• On the CCS, “pacemaker, temporary, transvenous” is avail­ able in the practice CCS.
Figure 5-5 • Third-degree AV block. Reproduced with permission from Jones SA. ECG Success\: Exercises in ECG Interpretation. Philadelphia\: F.A. Davis Company; 2008\:58.
CHAPTER 5 EKG 61

62 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• On the CCS, suboptimal management includes delaying transcutaneous pacing in patients with symptomatic brady- cardia and signs of poor perfusion.
ACCESSORY PATHWAY
1 WOLFF-PARKINSON-WHITE
Wolff-Parkinson-White (WPW) is characterized by a ventricu­ lar preexcitation via an accessory pathway. Patients can have a symptomatic arrhythmia (WPW syndrome), or they can be as­ ymptomatic but have the classic EKG pattern (WPW pattern). WPW syndrome can be associated with other conditions such as atrial fibrillation, atrial flutter, sudden cardiac death (SCD), and AVRT, also known as atrioventricular reentrant tachycardia (orthodromic or antidromic).
EKG Features\:
A shortened PR interval that is usually <3 small boxes (<0.12 seconds) secondary to a rapid conduction through the acces­ sory pathway. A slurred upstroke of the QRS, also known as the delta wave, secondary to a slowed ventricular activation, which can result in a widened QRS complex. See Figure 5-6.
Next Step Treatment\:
Step 1) The clinical management for patients who are asymp­ tomatic but have the WPW pattern on EKG is usually obser­ vation. The management approach for WPW syndrome can be summarized into short-term or long-term management.
•
On the CCS, remember to “bridge” your therapy by treating any acute issues (symptomatic bradycardia) with the long-term man- agement of a third-degree AV block (permanent pacemaker).
■r
-— . A J A -A rtf"*»trrv—Vikr-'r\p/—Ap I
- .. M*=JJt\: 1
a7Tt-- Vi
Short-term Management\:
Hemodynamically unstable—Electrical cardioversion.
Atrial fibrillation—IV procainamide, amiodarone, or ibutilide.
AVRT (Orthodromic)—Attempt vagal maneuvers first; if no success, then IV adenosine, verapamil, or esmolol (short-acting beta-blocker).
AVRT (Antidromic)—IV procainamide.
Long-term Management\:
Catheter ablation is considered a first-line therapy for patients with WPW syndrome and associated conditions (eg, AVRT, atrial fibrillation, atrial flutter).
Disposition\:
Patients treated in the ED for symptomatic arrhythmias should be admitted to the hospital for further monitoring and consulta­ tion with a cardiologist.
Pearls\:
• Orthodromic AVRT is characterized by an antegrade conduction through the AV node to the ventricles, but a retrogradeconduction(backtotheatria)viaanaccessorypath­ way. This results in a narrow QRS complex with tachycardia.
\JA t i _
■t~k j1-1” I
VA 1
.. .... .
■
_1' AAA1.IA
vt
J AJlAJ-J1*
‘1 aVL
1
— 1
-j- -) -
As
JL-Ja 1 \: it
Al
f-
F\: J- -
A
1
/\ ^/La
- -H-- -
"ifV=— -\Q-j- y «==
A;=U ^V\: ”\: "D
II t - -
A A Jl\ A J
\
V<>Y *J\«■
1 n^
^l^-J L
jfV._J i-A
I
^V..F
/y-.
JA —J Av
Figure 5-6 • Wolff-Parkinson-White EKG pattern. Reproduced with permission from Tmtinalli JE, et al. Emergency Medicine\: A Comprehensive Study Guide. 7th ed. New York\: McGraw-Hill; 2011\:986.

• Antidromic AVRT is characterized by an antegrade conduc­ tion through the accessory pathway, but a retrograde con­ duction via the AV node. This results in a wide QRS complex with tachycardia.
• Avoid using AV nodal blocking drugs (eg, beta-blockers, cal­ cium channel blockers, adenosine, digoxin) in atrial fibril­ lation or atrial flutter since using these drugs can promote conduction through the accessory pathway.
• Patients with the WPW syndrome may develop palpitations, chest pain, dizziness, lightheadedness, or syncope.
• Patients with sudden cardiac death usually die from ven­ tricular fibrillation (VF), which is usually generated from an episode of atrial fibrillation (AF —»VF -» SCD).
• WPW syndrome is associated with Ebstein’s anomaly of the tricuspid valve.
VENTRICLES
1 TORSADESDEPOINTES
Torsades de pointes is a distinct form of polymorphic ventricu­ lar tachycardia that is associated with a prolonged QT interval. The presence of a prolonged QT increases the risk of developing torsades de pointes because it is often triggered by a ventricular premature complex (VPC) during the prolonged repolarization period. QT prolongation may be congenital (eg, Romano-Ward syndrome) or acquired. Consider the following acquired causes\:
Acquired long QT—Hypokalemia, hypomagnesemia, hypo­ calcemia, hypothyroidism, tricyclic antidepressants, anti- psychotics (eg, haloperidol, thioridazine, phenothiazines), antibiotics (eg, erythromycin, clarithromycin, azithromycin, levofloxacin, moxifloxacin, gatifloxacin), antifungals (eg, pentamidine, voriconazole), antiarrhythmics (eg, quinidine, procainamide, amiodarone, ibutilide, sotalol), AV blocks, MI, cocaine, ondansetron, organophosphate insecticides, intracranial disease, liquid protein diets, anorexia nervosa.
EKG Features\:
Torsades de pointes literally has a “twisting of the points” appearance. The ventricular rate is usually >150 complexes per minute. In the following figure, the tachycardia is preceded by a short R-R interval followed by a long R-R interval with a
• Patients with only the WPW pattern on EKG may have the abnormality disappear over time.
• Electrophysiologic study (EPS) is not required to make the diagnosis ofWPW, but can be used in equivocal cases.
• On the CCS, the vagal maneuver, “massage carotid” is avail­ able in the practice CCS.
• On the CCS, “electrophysiologic testing” is available in the practice CCS.
• On the CCS, “synchronous cardioversion” is available in the practice CCS.
• On the CCS, remember to “bridge” your therapy by treat­ ing any acute issues (eg, termination of the tachycardia) with the long-term management of WPW syndrome (eg, prevention).
ventricular premature complex (VPC) falling during repolariza­ tion. The arrow denotes the R on T phenomenon (ie, ventricu­ lar depolarization occurring at the end of repolarization). See Figure 5-7.
Next Step Treatment\:
Step 1) Withdraw any offending agents and correct electrolyte abnormalities.
Step 2) The clinical management for torsades de pointes can be summarized into short-term or long-term management.
Short-term Management\:
Hemodynamically unstable—Electrical cardioversion Acquired long QT
Figure 5-7 • Torsades de pointes. Reproduced with permission from Fuster V, et al. Hurst's The Heart. New York\: McGraw-Hill; 2011\:2109.
• •
•
•
IV magnesium sulfate is a first-line therapy to treat and prevent recurrence.
Temporary pacemaker can shorten the QT interval and is usually tried after an unsuccessful attempt with mag­ nesium sulfate.
IV isoproterenol (given as a continuous infusion) can also shorten the QT interval and can be given as an interim agent until pacing is available.
Congenital long QT
Beta-blockers (eg, propranolol) are the cornerstone for treatment in symptomatic patients.
CHAPTER 5 EKG 63

64
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
r3±St
4 4
|-t
t
V t\
§@Hit --rti-
U_U~
■it
;i4±\:ti±± -i±L-ttj±
•■4-fcfc
r\:\:yft ♦1- •-*- -f• i-"rirr-f\:•—
Ivtt
\:j1Tf it
\:n±r.
ilfitttSSSt iti®ssTfil-If sss
it SI
*\:d\:t± ztrtt •\: '•\: TP4
Si Sit
i.i
-tit- A\:1\: Pit'ft
-nil f-H- — i-f-4- -ftrl
pitVi\: <PJ/ 5-Lit<br />—
^4 yi- \: t
•rrK vi>V
-f-t-*—
*H-^r
\:\:ll
t\:ErSi WiSpxitiiItfiVrn\IT -i-y-H-
nr
TtN\: -r ■T-T- . 4—
ft WAZ\/4-■Vy
-tf-4-
Figure 5-8 • Ventricular fibrillation. Reproduced with permission from Stone KC, Humphries RL. Current Diagnosis and Treatment\: Emergency Medicine. 6th ed. New York\: McGraw-Hill; 2008\: Figure 33-19.
Long-term Management\:
Acquired long QT—Identify the precipitating factor. Pa­ tients with AV blocks or symptomatic bradycardia may benefit from a permanent pacemaker.
Congenital long QT—Beta-blockers, avoid strenuous ac­ tivity, and consider an implantable cardioverter defibrilla­ tor (ICD) in patients who are remain symptomatic despite beta-blocker therapy.
Disposition\:
Patients treated for acute management of torsades de pointes should be admitted to the hospital for further monitoring.
Pearls\:
• Torsades de pointes can be sustained, nonsustained, or it can degenerate into ventricular fibrillation.
• Consider torsades de pointes as the “sitting duck” of arrhyth­ mias since a prolonged QT is vulnerable to the firing of a depolarization from a PVC onto a T wave (repolarization) that can trigger the “twisting of the points.”
• On the CCS, “ICD” is available in the practice CCS.
• On the CCS, remember to “bridge” your therapy by treating any acute issues (eg, tachycardia) and addressing any chronic issues (eg, prolonged QT).
1 VENTRICULARFIBRILLATION
Ventricular fibrillation (VF) results in disorganized electri­ cal activity that leads to irregular ventricular contraction and, subsequently, into cardiac arrest (absent pulse). A com­ mon cause for VF is due to coronary artery disease with re­ sultant MI. Other causes of VF include long QT syndrome, short QT syndrome, myocarditis, valvular heart disease, di­ lated cardiomyopathies, hypertrophic cardiomyopathy, con­ genital heart disease, WPW syndrome (AF —» VF —» SCD), antiarrhythmics, electrolyte abnormalities, and acid-base abnormalities.
EKG Features\:
The rhythm appears to have a chaotic irregular appearance without recognizable P waves, QRS complexes, or T waves. At the onset of VF, high amplitude fibrillatory waves may be seen and are referred to as coarse VF (type I VF). Later, the fibrilla­ tory waves may be of low amplitude (small undulations) and are referred to as fine VF (type II VF). Fine VF may be very difficult to distinguish from asystole. In the following figure.
after 6 beats, the sinus rhythm degenerates into ventricular fibrillation. See Figure 5-8.
Next Step Treatment\:
(The following steps are based on the ACLS guidelines.)
Step 1) CPR until defibrillator arrives.
Step 2) Asynchronous cardioversion (monophasic 360 Joules or diphasic 200 Joules).
Step 3) Resume CPR and obtain IV/IO access.
Step 4) If a shockable rhythm is present, then defibrillate.
Step 5) Resume CPR, deliver IV epinephrine q3-5 minutes or IV vasopressin x 1 can replace the first or second dose of epi­ nephrine. During this step, consider intubation.
Step 6) If a shockable rhythm is present, then defibrillate.
Step 7) Resume CPR, deliver IV amiodarone in patients that are unresponsive to defibrillation, CPR, and epinephrine. If amiod­ arone is unavailable, you can use IV lidocaine. During this step, treat any reversible causes (eg, hypovolemia, hypoxia, hydrogen ions, hypo-/hyperkalemia, hypothermia, tension pneumotho­ rax, tamponade, toxins, thrombosis coronary or pulmonary).
Disposition/Follow-Up\:
Patients with a successful reversion should be transferred to the ICU. The long-term follow-up plan for patients with corrected reversible causes of VF should be considered for an implantable cardioverter defibrillator (ICD).
Pearls\:
• Vigilance should be taken within the next several hours (<5 hours) in patients with an acute MI since VF usually strikes during that window.
• Early defibrillation is key to patient survival.
• In VF, you want to use unsynchronized cardioversion because you do not want to delay the machine from sensing a QRS complex, which is seen in synchronous cardioversion.
• On the CCS, “defibrillation” is available in the practice CCS, which is synonymous with unsynchronized cardio­ version.
• On the CCS, in patients with VF, look for the patient with no pulse, unresponsiveness, and agonal gasps.
• On the CCS, this case is an emergency, move the simulated time judiciously.
• On the CCS, this is a type of case in which you’ll be judged on your timing, sequence of actions, and appropriateness of your actions.
1-

Endocrinology
CHAPTER OUTLINE
Keywords Review..............................................6.5.......... Tertiary Hyperparathyroidism...................................7.5.......
I
I
I
PITUITARY DISORDERS................................6.6......
Hypoparathyroidism...........................................7.5..........
I ADRENAL DISORDERS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7.6. . . . . . . Acromegaly.................................................6..6..........
Prolactinoma................................................6.7...........Cushing's Syndrome............................................7.6.........
Pheochromocytoma...........................................7.8..........
DiabetesMellitusType2........................................8.1........
I CCS.....................................................8.3............
DKA...........................................................8.3.............
of the skin, also described as an "orange-peel" appearance, over the lower legs.
Renal osteodystrophy—Renal bone disease that is seen in patients with chronic kidney disease as a result of derangements in electrolytes and endocrine function (eg, PTH). Examples of renal osteodystrophy include osteitis fibrosa cystica, osteomalacia, and adynamic bone disease.
THYROID DISORDERS.................. 68
Thyrotoxicosis...............................................6..8.......... Hypothyroidism..............................................7.1.......... Diabetes MellitusType 1........................................7.9........
PARATHYROID DISORDERS............................7.3.....
Primary Hyperparathyroidism................................7.3...... Secondary Hyperparathyroidism..............................7.4.....
KEYWORDS REVIEW
Acroparesthesia—Paresthesia in the extremity.
Calciphylaxis—Systemic calcification of the arteries that can lead to tissue ischemia and necrosis.
Hyperhidrosis—Excessive sweating.
Hyperprolactinemia—Elevated levels of prolactin in the blood.
Pretibial myxedema—An infiltrative dermopathy seen in Grave's disease that will present as a nonpitting induration
I GLUCOSE HOMEOSTASIS DISORDERS...................7.9...
65

66 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
PITUITARY DISORDERS
8 ACROMEGALY
Acromegaly is a disease that results from hypersecretion of growth hormone (GH). Hypersecretion is most commonly due to an anterior pituitary somatotroph adenoma. The term acromegaly is used when hypersecretion of GH occurs after the epiphyseal plates have closed. The term pituitary gigantism is used when hypersecretion of GH occurs before the epiphyseal plates have closed (results in disproportionately long arms and legs).
Clinical Features\:
Acromegaly is an insidious disease. The clinical presentation of acromegaly can be best understood by either “on-site” or “off-site” effects.
On-Site Effects (Direct Tumor Effects)
Neurologic—Headaches, cranial nerve palsies, visual defects (bitemporal hemianopsia), pituitary damage (ie, T ACTH, i LH, i FSH, i TSH, T prolactin)
Off-Site Effects (Distant Effects due to Excess GH/IGF-1) Consider the effects from a relative head to toe fashion\:
Head—Frontal bossing, coarse facial features, prognathism, sleep apnea (central and obstructive), macroglossia, dental malocclusion, enlarged salivary glands
Neck—Thyroid enlargement (visceromegaly), diffuse or multinodular goiter, deepened voice
Cardiac—Cardiomyopathy, HTN, CHF, LVH, hypertri­ glyceridemia, arrhythmias, valvular heart disease
Renal—Enlargedkidneys,ireninlevels.Taldosteronelevels, hypercalciuria, hyperphosphatemia
Hepatic—Hepatosplenomegaly
GI—Colonic polyps, colonic diverticula, adenocarcinoma
Pancreas—Diabetes mellitus, insulin resistance, hyperinsu- linemia
Prostate—Enlarged prostate
Reproduction—Menstrual irregularities, galactorrhea, i libido, impotence
Skin—Oily texture, hyperhidrosis, body odor, skin tags, women can have hirsutism, acanthosis nigricans
Musculoskeletal—Large hands and feet, T ring size, hy­ pertrophic arthropathy (eg, spine, hips, knees, ankles), acroparesthesia secondary to nerve entrapment (eg, carpal tunnel syndrome), proximal muscle weakness
Next Step\:
Step 1) The best initial test is obtaining serum IGF-I. A normal IGF-I concentration indicates that the patient does not have acromegaly.
Step 2) Ifserum IGF-I levels are high or equivocal, then the next best step is to obtain a serum GH level after administering oral glucose (ie, oral glucose tolerance test). In normal individuals, GH
is suppressed to <1 ng/mL after a 75 gram oral glucose load, but in patients with acromegaly the GH levels are inadequately sup­ pressed (ie, GH concentration usually cannot go below 2 ng/mL after a 75 gram glucose load).
Step 3) Identify the tumor with a brain MRI if the GH level is elevated after OGTT. In some cases, a pituitary adenoma may not be identified, and the next thing you have to consider is an ectopic secretion of GH or an ectopic secretion of GHRH. In such cases, consider further imaging (chest, abdomen) or biochemical testing for GHRH levels.
Step 4) The goal of therapy is to control the levels of GH and IGF-I. Consider the following treatment modalities\:
Surgical Intervention
Transsphenoidal surgery—Surgical resection is the treat­ ment of choice for most patients, especially in the presence of a mass effect (eg, bitemporal hemianopsia). The cure rate is approximately 70% for microadenomas and less than 50% for macroadenomas (size >10 mm).
Medical Intervention
Somatostatin analogs (eg, octreotide, lanreotide)—Inhibit GH secretion and are considered the best option if the adenoma does not look resectable or if the risks outweighs the benefit of surgery. Somatostatin analogs can cause nausea, abdominal discomfort, flatulence, fat malabsorption, and diarrhea. Octreotide and lanreotide can be both given as SubQ or IM (depot injection).
Dopamine agonists (eg, cabergoline, bromocriptine)— Inhibits GH secretion but not as well as the somatostatin analogs. However, these agents would be a good choice to consider for patients that cosecrete prolactin since dopa­ mine reduces prolactin secretion. Dopamine agonists can also be added as a combination therapy with other soma­ tostatin analogs. Administer orally.
GH receptor antagonist (eg, pegvisomant)—Pegvisomant blocks the binding of endogenous GH resulting in a decrease in IGF-I. The use of pegvisomant has been associated with an increase in serum GH concentration. Pegvisomant can be considered if somatostatin analogs and dopamine agonists are ineffective. Pegvisomant can also be added as a combination therapy with other somatostatin analogs. Side effects include elevated liver enzymes and lipohypertrophy. Administer SubQ.
Radiation Intervention
Radiation therapy—Used as an adjuvant therapy or contra­ indication to surgery. Radiation is mainly considered when surgery or medical treatments have been ineffective.
Follow-Up\:
Patients are followed up and monitored periodically with the clinical assessment, serum IGF-I levels, MRI (if pituitary adeno­ ma was seen on initial MRI), and colonoscopy (remember pa­ tients have a risk for colonic polyps). Patients with acromegaly have an increased risk in mortality, and most die from cardio­ vascular disease. Therefore, it is important to periodically assess and treat any cardiovascular issues.

Pearls\:
• IGF-I is GH dependent (ie, GH stimulates the secretion of IGF-I).
• IGF-I binding protein-3 (IGFBP-3) is also GH dependent and is a major IGF-I binding protein in serum. The levels of IGFBP-3 are also elevated in acromegaly, but there is considerable overlap with normal levels, which makes this measurement of limited value.
• Children with pituitary gigantism tend to have rapid weight gain along with an accelerated linear growth pattern since the epiphyseal plates have not closed.
• Adults with acromegaly do not become taller since the epiphyseal plates have closed. Instead, patients may experi­ ence hypertrophic arthropathy.
• Once treatment is initiated and serum IGF-I levels return to normal, patients may continue to have symptoms and bony abnormalities may persist.
• Complications of transsphenoidal surgery include central diabetes insipidus, CSF leak, and meningitis.
• One of the advantages of medical intervention (somatostatin analogs, dopamine agonists, GH receptor antagonist) is that it does not cause hypopituitarism, unlike surgery or radiation therapy.
• Foundational point—Approximately 40% of somatotroph adenomas have a mutation in the alpha subunit of the stimulatory GTP binding protein. The result is an increase in adenylyl cyclase activation (T cAMP), which can increase GH secretion.
• CJ\: In the office, you decide to obtain serum GH levels in addition to the serum IGF-I. Is that acceptable? Answer\: Obtaining measurements of serum GH levels is not recom­ mended because of the wide fluctuation in GH levels during a 24-hour period. IGF-I does not have as wide a variability in serum levels as GH.
• On the CCS, if a pituitary adenoma is found on MRI, remember to consult with a neurosurgeon.
• On the CCS, when you order labs during the CCS case, the nor­ mal reference values will be provided next to the actual values.
• On the CCS, in almost every case and probably in the real clinical world, you have to consider “bridging your therapy.” Ask yourself, “Do I have to treat any acute issues and address any long-term (chronic) issues?” This style ofthinking is comprehensive and will gain you points on the exam. 1
D PROLACTINOMA
Prolactinoma is a pituitary lactotroph adenoma that secretes excessive amounts of prolactin. The adenoma may be referred to as a microadenoma (<1 cm) or a macroadenoma (>1 cm).
Clinical Features\:
Both men and women may experience a local mass effect from the adenoma (eg, visual field defects, headaches). However, men and women may present with different signs and symptoms from the hyperprolactinemia. Consider the following\:
Women—In a young adolescent, delayed puberty may occur (eg, late menarche). In a reproductive-aged female, patients may present with menstrual irregularities, infertility, galactorrhea, vaginal dryness, hot flashes, or decrease bone mineral density.
Men—In a prepubescent boy, hyperprolactinemia can result in small testicles. In an adult, patients may present with impotence, 1 libido, infertility, or less commonly gynecomastia and galactorrhea.
Next Step\:
Step 1) The best initial step is to determine the serum prolactin level. If the value is elevated, this will support the suspicion of hyperprolactinemia. It should be noted that normal prolactin levels should be less than 20 ng/mL and values greater than 100 ng/mL are usually associated with a macroadenoma.
Step 2) Determine the etiology of the hyperprolactinemia (see Table 6-1). For example, order a qualitative (3-HCG in a reproductive-aged female, TSH plus T4 level for hypothyroid­ ism, LFTs for liver disease, BUN/Cr for renal insufficiency, or determine if there is a medication-induced hyperprolactinemia.
Step 3) Once the secondary causes of hyperprolactinemia have been excluded, the next best step is to order a brain MRI to evaluate for a pituitary adenoma. Be aware that not all micro­ adenomas will show up on imaging, and they may lead to a diagnosis of idiopathic hyperprolactinemia.
Step 4) First-line treatment for any size lactotroph adenoma are the dopamine agonists (eg, bromocriptine, cabergoline) since they will decrease the size of the adenoma and secretion of the prolactin. Transsphenoidal surgery is considered if dopa­ mine agonists have been unsuccessful, the size of the adenoma persists despite medical therapy, or there is drug intolerance. Radiation therapy is regarded as a second-line treatment, but is considered in patients that do not respond to drugs or surgery.
Follow-Up\:
Once the patient is treated for a prolactinoma, the follow-up consists of clinical assessments, serum prolactin levels, and imaging of the pituitary.
Pearls\:
• Prolactin has an inhibitory effect on GnRH resulting in infertility. Therefore, treating the patient with a dopamine agonist (ie, inhibits prolactin) will help patients with hyper­ prolactinemic anovulation.
• Prolactinomas can potentially increase in their size during pregnancy because of the elevated estrogen levels during pregnancy.
• The mechanism of elevated prolactin levels secondary to hypo­ thyroidism is unclear. However, thyrotropin-releasing hormone (TRH) has been implicated as a cause for elevated prolactin.
• If the cause of hyperprolactinemia is due to hypothyroidism, treat the hypothyroidism and the elevated prolactin levels should normalize.
• Hyperprolactinemia can recur after surgery or discontinua­ tion of the dopamine agonists.
CHAPTER 6 ENDOCRINOLOGY 67

68 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Table 6-1 • Causes of Hyperprolactinemia Physiologic
Pregnancy (T estrogen causes T prolactin) Nipple stimulation
Stress
Sleep
Exercise Medical
Neurologic—Prolactinoma, hypothalamic-pituitary stalk damage (e.g. trauma, tumor, surgery, sarcoidosis), seizures, acromegaly (GH can be cosecreted with prolactin)
Thyroid—Hypothyroidism
Chest wall—Chest wall injury (e.g. burns, herpetic infection, trauma, surgery) can cause an increase in prolactin
Renal—Chronic renal failure
Hepatic—Cirrhosis
Idiopathic—Unknown cause for some patients
Medications—Antipsychotics
Haloperidol Chlorpromazine Prochlorperazine Thioridazine Fluphenazine Risperidone
\: Olanzapine
Antidepressants
Amitriptyline Clomipramine
Antihypertensives
Verapamil Methyldopa Reserpine
Gl Meds
Metoclopramide Cimetidine
Opiates
Morphine Codeine
• Foundational point—Lactotroph adenomas are mainly composed of chromophobic or weakly acidophilic cells.
• Connecting point (pg. 108)—Elevated prolactin levels can cause primary and secondary amenorrhea.
• CJ\: A 27-year-old woman is in her first trimester of preg­ nancy and is experiencing visual problems. An MRI was ordered and confirms the presence of a macroadenoma with a size of 12 mm. What is your next step? Answer\: Macroadenomas have a higher propensity to enlarge during pregnancy compared to microadenomas. In this case, the patient should initially be treated with a dopamine agonist
THYROID DISORDERS
I THYROTOXICOSIS
Thyrotoxicosis is a condition of excess quantities of endogenous or exogenous thyroid hormones. Hyperthyroidism can lead to thyrotoxicosis, but should not be synonymous with thyrotoxico­ sis. Hyperthyroidism (ie, excessive thyroid function) is charac­ terized by the excess synthesis and secretion of thyroid hormone and can be divided into primary hyperthyroidism (eg, Graves disease, toxic multinodular goiter, toxic adenoma, metastatic follicular thyroid carcinoma) and secondary hyperthyroidism
(eg, bromocriptine). If the patient does not respond to medical therapy and vision is compromised, the next best step is to consider transsphenoidal surgery for surgical decompression.
• On the CCS, when rescheduling a patient to come back for an office visit, weekend schedule appointments will be defaulted to the following Monday.
• On the CCS, remember to ‘advise patient, side effects of medication” since dopamine agonists can cause nausea, constipation, nasal stuffiness, postural hypotension, Raynaud phenomenon, and dizziness.
(eg, TSH-secreting pituitary adenoma, hCG-secreting tumor). Other causes of thyrotoxicosis include exogenous causes (eg, excess ingestion of thyroid hormones) or thyroid inflammation damage leading to release of thyroid hormones (eg, subacute thyroiditis, silent thyroiditis).
Clinical Features\:
The signs and symptoms of thyrotoxicosis can vary (see Table 6-2). Consider the following clinical manifestations in a relative head to toe fashion\:
Psychiatric—Anxiety, irritability, depression, psychosis, nervousness, insomnia, emotional lability

Table 6-2 • Thyrotoxicosis Causes and Treatment
Name
Graves'disease (Hyperthyroid)
Toxic adenoma (Hyperthyroid)
Toxic multinodular (Plummer's disease)
Subacute thyroiditis (de Quervain's)
Silent
thyroiditis (Subacute lymphocytic thyroiditis)
Iodine-induced (eg, contrast, amiodarone)
Struma ovarii (Teratoma made up of thyroid)
Metastatic follicular thyroid carcinoma
Thyrotoxicosis factitia
MOA
TSH receptor antibodies activate the receptor
Clinical Features
• Diffusely nontender
enlarged gland • Exophthalmos • Pretibial
myxedema
Discrete nodule Hot nodule
or hyperfunc­ tional
nodule will produce symptoms
Multiple nodules
Enlarged thyroid
Painful
Slightly enlarged gland
Painless
Look for nodular goiter
Pelvic mass
Bone and lung involvement
Diagnostic Clues
i TSH, FT3 and FT4 can be normal to f
TSI-positive TBII-positive
(see Pearls section)
i TSH, FT3 and FT4 can be normal to f
i TSH, FT3 and FT4 can be normal to f
3 phases (Thyrotoxic -> Hypothyroid -4 Recovery)
In thyrotoxic phase\: i TSH, FT3 and
FT4 can be normal tot
Also has 3 phases. In thyrotoxic phase\:
i TSH, FT3 and FT4 can be normal to T
• T Anti-TPO • tAnti-TG
-l TSH, T FT4, and/or TFT3,
T TSH, T ft4, and/or TFT3
U/S-ovarian mass
T3-toxicosis (Ttsh,T ft3, normal FT4)
i TSH,FT3 and FT4 can be normal to f
• i thyroglobulin
RAIU
T Diffuse uptake
T Single nodule
uptake but rest of gland is suppressed
t
Patchy uptake; both hot or cold nodule may be seen
1
i
1
i
l
Next Step Treatment
Symptomatic -4 (3-blocker + PTU
or MMI
Definitive Tx-> RAI or surgery
Large obstructive goiter-> Consider surgery
Symptomatic -> (3-blocker + PTU or MMI
Definitive Tx -> RAI or surgery
Symptomatic -4 (3-blocker + PTU or MMI
DefinitiveTx-> RAI or surgery
Step 1) Try NSAIDs
Step 2) Try glucocorticoids (eg, prednisone) if NSAIDs are ineffective.
Asymptomatic —>
Observe
Symptomatic -4 (3-blocker
Remove the offending agent.
Definitive Tx -4 Sur­ gical resection of the ovarian tumor
• Surgery+RAI+ Thyroid hormone replacement
Autonomous • production •
Autonomous • production
T preformed release • of hormone 2° to • inflammation due to
a possible virus
T preformed release • of hormone 2° to inflammation •
• Considered a variant of
Hashimoto's thyroiditis
T hormone release •
•
•
•
Extrathyroidal •
Extrathyroidal •
Exogenous •
• No goiter
i• Reduce or
discontinue thyroid hormones.
Symptomatic
MMI—methimazole;MOA—mechanismofaction;RAI—radioactiveiodine;RAIU—radioactiveiodineuptake;TBII—thyrotropin-bindinginhibitoryimmunoglobulin;TG—thyroglobulin; TPO—thyroidperoxidase; TSI—thyroid-stimulating immunoglobulin; U/S—ultrasound
CHAPTER 6
ENDOCRINOLOGY 69

70
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Neurologic—Heat intolerance, tremor, cognitive dysfunction
Ocular—Staring gaze, lid lag, diplopia, proptosis (exoph­ thalmos)
Respiratory—Dyspnea secondary to respiratory muscle weakness
Cardiovascular—Tachycardia, systolic HTN, widened pulse pressure, atrial fibrillation
GI—Weight loss despite an increase in appetite, frequent bowel movements, diarrhea
Genitourinary—Urinary frequency, amenorrhea, oligo­ menorrhea, erectile dysfunction, i libido
Musculoskeletal—Osteoporosis, fatigue, weakness
Dermatologic—Warm and moist skin, sweating, fine hair, onycholysis, pretibial myxedema
Hematologic—Normochromic, normocytic anemia Metabolic—Impaired glucose tolerance, low HDL levels
Next Step\:
Step 1) The best initial screening test is serum TSH level. If TSH level is low, order an unbound free T4 (FT4) and free T3 (FT3). If TSH is low and both FT4 and FT3 are high, thyrotoxi­ cosis is confirmed. In some cases, when TSH is low but FT4 is elevated and FT3 is normal, it is considered a T4 toxicosis. When you have T4 toxicosis, you should think of T4 ingestion, nonthy- roidal illness, excess iodine, and amiodarone therapy (ie, inhib­ its conversion from T4 to T3). On the contrary, with a low TSH, but FT3 is elevated and FT4 is normal, then it is considered a T3 toxicosis. With T3 toxicosis, you should think of Graves’ disease, toxic adenoma, nodular goiter, and increased conversion from T4 to T3 (ie, T3 is the more active thyroid hormone). Finally, if you have a low TSH but normal FT4 and FT3, then the patient has subclinical hyperthyroidism.
Step 2) If the etiology of thyrotoxicosis is unclear even after a clinical assessment and laboratory testing, the next best step is with scintigraphy, also referred to as radioactive iodine uptake (RAIU). RAIU uses either 123I or technetium-99m. It should be noted that measuring thyrotropin receptor antibodies is not routinely performed, but should be considered if RAIU is contraindicated. See Table 6-2 for the clinical clues for each type of thyrotoxicosis.
Step 3) The next step treatment involves medical therapy, radia­ tion, or surgery. Consider the following\:
Medical Intervention
Beta-blockers—^-blockers (eg, propranolol, atenolol, meto- prolol) are used to treat hyperadrenergic symptoms such as tachycardia, tremulousness, palpitations, anxiety, and heat intolerance. It should be noted that beta-blockers can be coadministered with thionamides.
Thionamides—Thionamides (eg, propylthiouracil [PTU], methimazole [MMI]) decrease the synthesis of thyroid hor­ mones. Thionamides are considered the best initial therapy for children and adolescents.
Iodine—Iodine elixirs (eg, potassium iodide) and iodin- ated contrast agents (eg, iopanoic acid, sodium ipodate) can inhibit the peripheral conversion of T4 to T3. However, this type of medical therapy is considered second-line therapy and not available in the United States.
Radiation Ablation
Radioactive Iodine Therapy—Radiation ablation involves administering the radioactive iodine orally in a dose of l31I to destroy the thyroid tissue within 6 to 20 weeks.
Surgical Intervention
Surgery—Subtotal or total thyroidectomy is a definitive form of treatment, but it is not considered first-line treat­ ment because of the success with medications and radioac­ tive iodine therapy. However, surgery is considered when there is an obstructive goiter, intolerance to meds or radio­ active therapy, or severe ophthalmopathy.
Follow-Up\:
Patients taking thionamides should have a thyroid function test every 4 to 6 weeks until levels are stabilized. Patients who under­ went radioactive iodine therapy will have destruction of their thyroid tissue within 2 to 5 months, and it is important to check thyroid function every 4 to 6 weeks because at some point they can be hypothyroid and may need thyroid hormone replace­ ment. Thyroid function test should be obtained in 4 to 8 weeks postoperatively in patients who underwent a thyroidectomy.
Pearls\:
• Antibodies against thyroid peroxidase (TPO) and thyroglob- ulin (TG) are fairly nonspecific.
• Thyrotropin-binding inhibitory immunoglobulin (TBII) and thyroid-stimulating immunoglobulin (TSI) are assays that are used to detect TSH receptor antibodies (TSHR-Ab) that can be seen in Graves’ disease.
• Conditions that can increase the levels of hCG include hydatidiform mole, hyperemesis gravidarum, and choriocar­ cinoma. Elevated hCG levels can stimulate TSH receptors and thereby cause thyrotoxicosis.
• Graves’ disease is characterized by hyperthyroidism, Graves’ ophthalmopathy, goiter, and dermopathy.
• Clinical manifestations in elderly patients may appear more atypical. For example, they may appear apathetic, absence of tremor and tachycardia, constipation, and toxic multinodular goiter appears to be more common.
• Caveat 1—Pregnancy and breastfeeding is a contraindica­ tion to RAIU.
• Caveat 2—Methimazole and propylthiouracil can both cause agranulocytosis and hepatitis, therefore order baseline labs before initiating thionamides.
• Caveat 3—Thionamides can cross the placenta during preg­ nancy, but they have been given during pregnancy. Remember they are a category D drug.

Caveat 4—Radiation therapy and surgery can both lead to hypothyroidism.
Caveat 5—Patients that have a relative contraindication to beta-blockers can be given a selective beta 1-blocker (eg, metoprolol, atenolol).
Caveat 6—Radioactive iodine therapy can actually make Graves’ ophthalmopathy worse.
Caveat 7—After radioactive iodine therapy, patients should wait at least 6 months prior to conception.
Caveat 8—Always check an hCG in a reproductive female before administering radioactive iodine.
Foundational point—T4 is converted to the more active form T3 by the enzyme deiodinase.
Foundational point—T4 (thyroxine) is produced solely by the thyroid. T3 (triiodothyronine) can be produced by the thyroid, but also by other tissues (ie, peripheral conversion).
Foundational point—Thyroglobulin (Tg) is a thyroid protein that is produced in the thyroid follicular cell and is predominantly found in the lumen of the thyroid follicles. Tg is involved in the biosynthesis of T4 and T3 in the thyroid gland.
Foundational point—Thyroxine-binding globulin (TBG) is one of three carrier proteins that carry T4 and T3 in the bloodstream.
Foundational point—T3 resin uptake (T3RU) is used to estimate free T4 by measuring unbound TBG. T3RU is some­ times ordered with the total T4 to take into account abnor­ malities in protein binding such as an increase or decrease in thyroxine-binding globulin (TBG) levels.
Foundational point—TBG levels are lowered in chronic liver failure, chronic renal failure, and glucocorticoid use, which may result in low total T4 and high T3RU.
Foundational point—Estrogen, pregnancy, and OCPs can increase TBG levels and may show high total T4 and low T3RU.
Foundational point—A high T3RU and high total T4 is sug­ gestive of hyperthyroidism, while a low T3RU and low total T4 is suggestive of hypothyroidism.
Foundational point—Methimazole blocks the oxidation of iodine in the thyroid gland, which inhibits the ability of iodine to combine with tyrosine and thereby form T4 and T3.
Foundational point—Propylthiouracil blocks the oxidation of iodine, but also the conversion of T4 to T3.
CJ\: A 45-year-old man is undergoing l31I radiation. He has two small children at home. Is it okay for him to play with them? Answer\: Avoid contact with children and pregnant women for one week and avoid using utensils and other dishes while on treatment. Also, no sex!
On the CCS, ordering “antibody thyroid, serum” will give you antibody results of both thyroid peroxidase and thyro­ globulin in the practice CCS software.
• On the CCS, ordering “1123 uptake, thyroid” and “1131” are available in the practice CCS, but remember one is for imag­ ing (1123) and the other one is for treatment (1131).
• On the CCS, remember to “advise patient, side effects of medication” which is available in the practice CCS.
• On the CCS, remember to “bridge” your therapy. For example, if a hyperthyroid patient presents with hyperadrenergic symp­ toms (eg, tremors, palpitations), treat the acute issues with a beta-blocker and the long-term management (eg, hyperthy­ roidism) with thionamides, radioactive ablation, or surgery.
1 HYPOTHYROIDISM
Hypothyroidism can be characterized by the inadequate production of thyroid hormone. Iodine deficiency remains the most common cause of hypothyroidism worldwide. In iodine- sufficient areas, chronic autoimmune (Hashimoto’s) thyroiditis remains the most common cause of hypothyroidism. The cause of hypothyroidism can be understood at the level of the thyroid gland (primary), pituitary (secondary), or hypothalamus (tertiary). Consider the following etiologies\:
Primary
Autoimmune—Hashimoto’s thyroiditis
Drugs—Lithium, amiodarone, thionamides, interferon alpha
Iodine—Iodine excess and deficiency can both cause hypo­ thyroidism
Iatrogenic—Neck radiation, thyroidectomy, radioactive iodine
Transient—Subacute thyroiditis, silent thyroiditis, postpar­ tum thyroiditis
Secondary
Sheehan’s syndrome, panhypopituitarism, pituitary adenoma, drugs that i TSH (eg, dopamine, octreotide, glucocorticoids), infiltrative diseases (eg, hemochromatosis), trauma, tumor, radiation
Tertiary
Infiltrative diseases (eg, sarcoidosis), trauma, tumor, radiation
Clinical Features\:
The clinical manifestations of hypothyroidism can vary. It may be helpful to think from a relative head to toe fashion\:
Psychiatric—Depression, i concentration, forgetfulness, emotional lability
Neurologic—Cold intolerance, cognitive dysfunction, i DTRs, nerve entrapment syndromes
ENT—Decreased hearing, macroglossia, hoarseness, peri­ orbital edema, goiter, fullness in throat
Respiratory—Dyspnea on exertion, respiratory muscle weakness
CHAPTER 6 ENDOCRINOLOGY 71

72
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Cardiovascular—Bradycardia, diastolic HTN, pericardial Pearls\:
effusions
GI—Weight gain, constipation
Reproduction—Menorrhagia, impaired fertility
Musculoskeletal—Myalgia, arthralgia, paresthesia, muscle weakness, fatigue
Dermatologic—Dry skin, coarse hair, hair loss, brittle nails, myxedema (nonpitting edema)
Hematologic—Normochromic, normocytic anemia, per­ nicious anemia
Metabolic—Hyperlipidemia, hyperhomocysteinemia, hy­ perprolactinemia, hyponatremia
Next Step\:
Step 1) The best initial test is a serum TSH level. If TSH level is elevated, ofder an unbound free T, (FT4). Since approximately 25% of patients with hypothyroidism will have a normal free T3 (FT3), a routine FT3 is generally not indicated. An elevated TSH and a low FT, confirms the diagnosis of hypothyroidism. In some cases, the TSH level can be low, normal, or slightly high, and now you have to consider a central cause (ie, 2° or 3° hypothyroidism). The next best step is to order a FT, (see Table 6-3). Finally, if there is an elevated TSH but a normal FT4, the patient has subclinical hypothyroidism. It should be noted that since most cases of hypothyroidism are due to Hashi­ motos thyroiditis in iodine-sufficient areas, ordering a thyroid peroxidase antibodies (TPO-Ab) is generally not indicated since most will be positive for the antibodies. However, a TPO-Ab can be ordered in a patient with lab values that are not suggestive of hypothyroidism but the patient has a goiter, or in a patient with subclinical hypothyroidism.
Step 2) The treatment of choice for hypothyroidism is with synthetic thyroxine (T,), also known as levothyroxine. Other formulations that exist include liothyronine (T3) and liotrix (mixture of T, and T3 in a 4\:1 ratio).
Follow-Up\:
Once thyroid replacement is initiated, the patient should be seen every 6 to 8 weeks until TSH levels normalize. There­ after, patients can be seen every 6 to 12 months for a TSH checkup.
• Hashimotos thyroiditis is characterized by the destruction of thyroid cells from an autoimmune process. There are two forms to consider. First, goitrous thyroiditis (presence of a goiter), and second, atrophic thyroiditis (decrease in thy­ roid tissue), which can be seen in the later stages of the disease.
• Although antibodies against thyroid peroxidase and thy- roglobulin are nonspecific, the presence of both antibodies suggests Hashimotos.
• Hashimotos thyroiditis may be associated with other au­ toimmune diseases such as SLE, Sjogren’s syndrome, RA, DM type 1, vitiligo, pernicious anemia (may present as Bp deficiency), celiac disease, and Addisons disease.
• Hypothyroidism during pregnancy may have several important consequences such as spontaneous abortions, preeclampsia, placental abruption, low birth weight, and cognitive impairment.
• Levothyroxine is a category A drug that is safe to use during pregnancy but may require an increase in dosage during pregnancy.
• Foundational point—Iodine deficiency can not only cause hypothyroidism, but excess iodine can do it as well. Excess iodine inhibits organification (ie, oxidation) of iodide, and thereby, synthesis of T , and T3 (WolfT-Chaikoff effect).
• Connecting point (pg. 68)—Hypothyroidism can result in hyperprolactinemia.
• CJ\: In the ED, a patient with a history of long-standing untreated hypothyroidism and recurrent infections presents with hypotension, bradycardia, hypothermia, and altered mental status. Labs were drawn and revealed hyponatremia, hypoglycemia, normal TSH level, and low FT4 levels. Myxedema coma is suspected. What is your next step? Answer\: Once you suspect myxedema coma on presentation, you should consider (1) intubation if breathing is compromised, (2) fluids to support the pres­ sure (remember not to give a diluted solution since they can be hyponatremic), (3) consider empiric antibiotics, (4) IV levothyroxine (T,) plus IV liothyronine (T3), and (5) stress-dose glucocorticoids (eg, IV hydrocortisone) since you do not know if a hypopituitarism is causing both secondary hypothyroidism and concurrent adrenal insufficiency. Give the stress-dose steroids until adrenal insufficiency has been ruled out (eg, cortisol level, ACTH stimulation test).
• On the CCS, once hypothyroidism is confirmed on initial serum levels, consider ordering a “lipid profile” to look for T LDL and i HDL levels. In most cases, it is the routine cho­ lesterol screening that suggests hypothyroidism.
• On the CCS, “levothyroxine,” “liothyronine,” and “liotrix” are available in the practice CCS.
• On the CCS, you are expected to advance the clock to “make things happen” such as changes to the patients condition, test results, procedures, or an effect on treatment that you ordered.
Table 6-3 • Hypothyroidism Patterns
Hypothyroidism
Primary
Secondary-"Central" (TSH deficiency)
Tertiary-"Central" (TRH deficiency)
Subclinical
TSH
Low, normal, or slightly T
Low, normal, or slightly T
T
Free T4
FT4—free thyroxine; TRH—thyrotropin releasing hormone; TSH—thyroid-stimulating hormone
T
i
Low to low-normal Low to low-normal Normal

PARATHYROID DISORDERS
I PRIMARYHYPERPARATHYROIDISM
Primary hyperparathyroidism is characterized by excessive PTH secretion resulting in hypercalcemia (see Table 6-4). The etiology can be due to a single adenoma (approximately 85% of cases), multiple gland hyperplasia (15% of cases), or parathyroid carcinoma (1% of cases). Several other causes are neck irradiation, MEN 1 (ie, “Triple Ps”—Parathyroid tumor, Pituitary tumor, Pancreatic tumor), and MEN 2A (ie, parathy­ roid tumor, pheochromocytoma, medullary thyroid cancer).
Clinical Features\:
Patients may be asymptomatic, but the clinical manifesta­ tions vary. Remember the mnemonic for hypercalcemia is “bones, stones, abdominal groans, and psychic moans.” Con­ sider the following clinical manifestation in a relative head to toe fashion\:
Psychiatric—Depressed mood, lethargy Neurologic—Confusion, cognition dysfunction Cardiovascular—HTN, bradycardia, short QT interval
Renal—Nephrolithiasis, polyuria, polydipsia, T- GFR, hy- percalciuria, hypophosphatemia, hypomagnesemia, neph- rocalcinosis
GI—Abdominal pain, nausea, vomiting, peptic ulcer, pan­ creatitis, constipation, anorexia
Musculoskeletal—Bone pain, muscle weakness, osteopo­ rosis, osteopenia, osteitis fibrosa cystica
Next Step\:
Step 1) The best initial step is to order a serum calcium level to determine if hypercalcemia exists.
Step 2) If calcium levels are elevated, the next best step is to or­ der an intact PTH level because if it’s elevated, then you know it must be due to a PTH-mediated phenomenon (eg, parathyroid adenoma, MEN 1, 2A). If the PTH level is low, then the hyper­ calcemia is most likely due to a PTH-independent phenomenon (eg, malignancy, T vitamin D, T vitamin A, lithium, thiazides, granulomatous diseases).
Table 6-4 • Calcium Disorders
Disorder
Primary hyperparathyroidism
Familial hypocalciuric hypercalcemia (FHH) Vitamin D deficiency
Renal failure
Tertiary hyperparathyroidism Hypoparathyroidism Pseudohypoparathyroidism
Step 3) If the calcium levels are elevated with an elevated intact PTH, the next thing you have to consider is familial hypocalciuric hypercalcemia (FHH), which presents similarly to primary hyperparathyroidism. The next best step is to order a 24-hour calcium urine excretion because the key difference between primary hyperparathyroidism and FHH is the amount ofcalcium in the urine. Remember FHH has the word “hypocalciuric” in the disorder, therefore a urine calcium level <100 mg/24 hr is most likely FHH, while a urine calcium level >250 mg/24 hr is most likely primary hyperparathyroidism (see Table 6-4).
Step 4) Treatment for primary hyperparathyroidism may in­ clude observation, surgery (parathyroidectomy), and medica­ tions. Consider the following\:
Parathyroidectomy
• Surgery should be considered in patients that are symptomatic.
• Surgery should be considered in patients with severe hyper­ calcemia (eg, >15 mg/dL).
• Surgery can be considered in patients that are asymptomatic and who meet the guidelines from the Third International Workshop on Asymptomatic Primary Hyperparathyroidism\:
Age <50 years
Serum calcium 1 mg/dL above the upper limit of normal Cr clearance reduced to <60 mL/min
T-score <-2.5 at the lumbar spine, hip, femoral neck, radius
Observation
• Observation can be considered in patients who want to avoid surgery.
• Observation can be considered in patients who do not meet the above guidelines.
Medications
Intact PTH t
Normal to T T
T
t 4 T
Serum Ca
t
T Normal to i i
t
-l
i
Serum P04
i Normal to i Normal to i
T Normal to T t
t
Key Findings
Urine Ca >250 mg/24 hr
Urine Ca <100 mg/24 hr
■l 25-OHD
•T 1,25-OHD
History of secondary hyperparathyroidism 1,25-OHD can be low to normal Shortened fourth and fifth metacarpals
•
•
Bisphosphonates—Bisphosphonates (eg, alendronate) in­ hibit bone resorption and can be given to patients with os­ teopenia or osteoporosis who are unable to have surgery.
Calcimimetics—Calcimimetics (eg, cinacalcet) increases the sensitivity of the calcium-sensing receptor and thereby low­ ers PTFI secretion. Cinacalcet is an option for patients with severe hypercalcemia who are not candidates for surgery.
CHAPTER 6 ENDOCRINOLOGY 73

74 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Follow-Up\:
Asymptomatic patients who do not undergo surgery are typi­ cally followed up with serum calcium levels, creatinine levels, and bone density. Patients with MEN 1 or MEN 2A should have genetic counseling since both conditions are inherited in an autosomal dominant pattern.
Pearls\:
• Almost all patients with hypercalcemia will have an elevated free (ionized) calcium level. However, abnormal albumin levels can influence the total calcium level since calcium binds to albumin. In such cases of hypoalbuminemia (eg, liver disease, malnutrition) or hyperalbuminemia (eg, severe dehydration), a corrected total calcium should be performed. In the majority of cases, the initial diagnostic approach for determining primary hyperparathyroidism is with a serum total calcium in the presence of a normal albumin level. A free (ionized) calcium can be added as an adjunct in patients with abnormal albumin levels.
• Patients with primary hyperparathyroidism can have lower levels of 25-OHD and slightly higher levels of 1,25-OHD.
• Foundational point—Familial hypocalciuric hypercalce­ mia (FHH) is due to an inactivating mutation for a gene that codes for the calcium-sensing receptor that is expressed in many tissues (eg, parathyroid, kidney, intestine).
• Foundational point—PTH increases serum calcium levels by (1) bone resorption, (2) reabsorption of calcium in the distal tubule, (3) increasing the synthesis of calcitriol in the proximal tubules by stimulating the enzyme 1-alpha hydroxylase to convert calcidiol (25-OHD) to calcitriol (1,25-OHD), which is the more active form of vitamin D, and (4) increase intestinal calcium absorption that is mediated by 1,25-OHD.
• CJ\: In the ED, a 52-year-old man presents with confu­ sion, severe abdominal pain, HR 55 bpm, BP 160/92, and serum total calcium level of 15 mg/dL. What is your next step? Answer\: Unstable symptomatic patients with severe hypercalcemia (ie, >14 mg/dL) should be treated accordingly\:
Step 1) Administer isotonic fluids such as normal saline (0.9% NaCl) to expand intravascular volume.
Step 2) Administration of salmon calcitonin (IM or SubQ), which is effective within 2 hours.
Step 3) Administration of a bisphosphonate such as IV zoledronic acid or IV pamidronate. The maximal effect of a bisphosphonate can take several days after administration. Step 2 and step 3 are “bridging” the therapeutic effects since one medication works faster than the other.
• Connecting point (pg. 282)—Know the bone mineral density scores.
• On the CCS, “Calcitonin-Salmon therapy” is available in the practice CCS.
• On the CCS, “genetics counseling” is available in the practice CCS.
• On the CCS, “ionized calcium, serum” is available in the practice CCS.
• •
•
1
On the CCS, a “24-hour urine calcium” is available in the practice CCS.
On the CCS, remember to “bridge” your therapy by treating any acute issues of hypercalcemia with the long-term man­ agement of hypercalcemia.
On the CCS, remember to order medications by generic or trade names, not by the class of medications (eg, “beta-blockers”).
SECONDARY HYPERPARATHYROIDISM
Secondary hyperparathyroidism is characterized by an excess secretion of PTH in response to hypocalcemia. Secondary hyperparathyroidism is seen in patients with renal failure, vitamin D deficiency, or with inadequate calcium intake.
Clinical Features\:
Since the PTH levels are elevated, one of the functions of PTH is bone resorption. Naturally, patients are prone to develop renal bone disease, also referred to as renal osteodystrophy. Patients can develop osteomalacia, osteitis fibrosa cystica, mixed osteodystrophy, or adynamic bone disease. Therefore, patients will complain of musculoskeletal problems such as bone pain, muscle pain, or weakness.
Next Step\:
Step 1) Initial laboratory testing should include an intact PTH, serum calcium, serum phosphate, and 25-hydroxyvitamin D levels. See Table 6-4 for expected findings.
Step 2) X-rays may be warranted in patients who complain of bone pain to rule out fractures or other pathological diseases secondary to renal osteodystrophy.
Step 3) Medical therapy is the cornerstone for treating second­ ary hyperparathyroidism, but surgery (parathyroidectomy) is considered in cases of fractures, bone pain, or calciphylaxis. Consider the following treatment approach\:
For Hyperphosphatemia
• Dietary phosphate restriction
• Phosphate binders (eg, calcium carbonate, calcium acetate, sevelamer)
For Hypocalcemia
• Provide calcium supplementation, but keep in mind in pro­ longed disease, patients can develop hypercalcemia.
For Elevated PTH
• Calcimimetics (eg, cinacalcet) to reduce the secretion of PTH.
Vitamin Deficiency
• Vitamin D replacement, but treat the hyperphosphatemia first because raising the calcium levels before treating the hyperphosphatemia can result in calciphylaxis.

Follow-Up\:
Once medical therapy is initiated, patients are followed up with the clinical assessment, PTH, calcium, phosphate, and 25-OHD.
Pearls\:
• 25-hydroxyvitamin D (25-OHD) is the “inactive” form of vitamin D produced in the liver before it becomes hydroxyl- ated to the "active” form of 1,25-OHD in the kidney, with subsequent actions to T Ca absorption in the intestines and to 1 Ca and phosphate excretion in the kidneys.
• CJ\: Why are serum phosphate levels higher in renal failure than in vitamin D deficiency? Answer\: Serum phosphate levels will tend to be higher in renal failure than in vitamin D deficiency because of poor renal clearance of phosphate.
• On the CCS, ifyou want to order vitamin D2 therapy, it will be recognized as either “vitamin D, therapy” or “ergocalciferol.”
• On the CCS, if you want to order vitamin D3 therapy, it will be recognized as either “vitamin D3” or “cholecalciferol.”
• On the CCS, if you want to know the 25-hydroxyvitamin D level, it will be recognized as “vitamin D 25-OH, serum, total” on the practice CCS.
8 TERTIARYHYPERPARATHYROIDISM
Tertiary hyperparathyroidism is characterized by excessive PTH secretion that is no longer responsive to medical therapy.
Clinical Features\:
Patients will have signs and symptoms of hypercalcemia. Pa­ tients may also have renal bone disease and calciphylaxis.
Next Step\:
Step 1) Initial laboratory testing should include an intact PTH, serum calcium, serum phosphate, and 25-hydroxyvitamin D levels. See Table 6-4 for expected findings.
Step 2) X-rays may be warranted in patients who complain of bone pain to rule out fractures or other pathological diseases secondary to renal osteodystrophy.
Step 3) Treatment is based on a subtotal or total parathyroid­ ectomy with autotransplantation of the parathyroid tissue into the forearm.
Follow-Up\:
Obtain serum calcium, phosphate, and PTH levels postoperatively.
Pearls\:
• CJ\: Two days postoperatively from a parathyroidectomy, the patient develops tetany and complains of tingling of the fingers. What syndrome is associated with this scenario? Answer\: Hungry bone syndrome is a complication after a parathyroidectomy. Hungry bone syndrome is a result of a precipitous fall in the calcium, phosphate, and magnesium levels. Literally, the bone is hungry to uptake calcium, phos­ phate, and magnesium secondary to an abrupt decrease in PTH. Correct the electrolyte abnormalities.
• On the CCS, “parathyroidectomy” is recognized in the prac­ tice CCS.
• On the CCS, if you require a consult during the case, a reason for the consultation in 10 words or less is required.
8 HYPOPARATHYROIDISM
Hypoparathyroidism is characterized by low levels of circulat­ ing PTH resulting in a state of hypocalcemia. Consider the following etiologies of hypoparathyroidism\:
Acquired—Parathyroid surgery, neck radiation, hyper/ hypomagnesemia, Wilson’s disease, hemochromatosis, sar­ coidosis, carcinoma.
Autoimmune—Polyglandular autoimmune syndrome type 1 (ie, hypoparathyroidism, candidiasis, adrenal insufficiency).
Genetics—Di George syndrome (ie, CATCH —> Cardiac abnormality (TOF), Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia from failure ofthe parathyroid glands to develop).
Clinical Features\:
Patients will have signs and symptoms of hypocalcemia. The classic Trousseau’s sign (ie, carpopedal spasm elicited by inflat­ ing a blood pressure cuff) and Chvostek’s sign (ie, tapping on the zygoma or the area of the facial nerve to elicit facial spasms) may be present. Consider the following clinical manifestations in a relative head to toe fashion\:
Psychiatric—Anxiety, depression, emotional lability
Neurologic—Tetany, paresthesias (eg, fingers, toes, peri­ oral), seizures, muscular twitching, ectopic calcifications (basal ganglia), T deep tendon reflexes, parkinsonism
ENT—Papilledema, dental hypoplasia
Respiratory—Laryngospasm, bronchospasm, hyperventi­ lation (respiratory alkalosis)
Cardiovascular—Prolonged QT, arrhythmia Dermatologic—Dry skin, brittle nails
Next Step\:
Step 1) Initial laboratory testing should include an intact PTH, serum calcium, serum phosphate, serum magnesium, and 25-hydroxyvitamin D levels. See Table 6-4 for expected findings.
Step 2) Short-term management\: Acute symptomatic hypo- calcemic patients should be treated with IV calcium gluconate. Care must be taken in patients receiving digitalis since hyper­ calcemia may precipitate an arrhythmia or digitalis toxicity.
Step 3) Long-term management\: The goal of long-term therapy is to address any symptoms and to maintain calcium levels within normal range. Patients can be given calcium supplements (eg, calcium carbonate, calcium citrate) and vitamin D. It should be noted that vitamin D supplements (cholecalciferol or ergocalciferol) are acceptable choices, but the preferred vitamin D is the active vitamin D (1,25-OHD),
CHAPTER 6 ENDOCRINOLOGY 75

76 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
calcitriol. Remember, in the absence of PTH, patients cannot convert 25-OHD to 1,25-OHD, therefore, giving calcitriol will bypass that requirement.
Follow-Up\:
Monitor electrolytes to maintain a near-normal calcium level and to prevent hypercalciuria (ie, risk for stone formation).
Pearls\:
• Pseudohypoparathyroidism is characterized by a resistance or insensitivity to circulating PTH (see Table 6-4).
• Patients with hypoparathyroidism can have concurrent hypomagnesemia. In the presence of hypomagnesemia, hypocalcemia can be difficult to treat, therefore treat the hypomagnesemia before or in conjunction with the hypo­ calcemia.
ADRENAL DISORDERS
I CUSHING'SSYNDROME
Cushings syndrome is a constellation ofvarious clinical findings from prolonged exposure to elevated glucocorticoids. Cushings syndrome can be due to an ACTH-secreting pituitary tumor (Cushings disease), ACTH-secreting ectopic tumor (nonpi- tuitary), cortisol-secreting adrenal adenoma or carcinoma, or exogenous glucocorticoids.
Clinical Features\:
The characteristic features are central obesity, buffalo hump, moon facies, peripheral muscle wasting, and proximal weakness. How­ ever, the presentation can vary, and it may be helpful to consider the clinical manifestations in a relative head to toe fashion\:
Psychiatric—Emotionally labile, depression, i cognition Neurologic—Headaches, visual disturbances from pitu­
itary tumors
Cardiovascular—I-ITN
GI—Weight gain
Genitourinary—Oligomenorrhea, amenorrhea, impotence, polyuria, polydipsia, kidney stones
Musculoskeletal—Osteoporosis, avascular necrosis
Dermatologic—Abdominal striae, ecchymoses, hyperpig­ mentation, supraclavicular fat pads, hirsutism, poor wound healing, acne
Metabolic—Glucose intolerance Next Step\:
Step 1) The initial tests to order are the 24-hour urine cortisol level to determine if there is truly an excess cortisol secretion and an overnight low-dose dexamethasone suppression test to assess the function of the hypothalamic-pituitary-adrenal axis
• In the presence of alkalosis, calcium has a higher affinity to bind with albumin, thereby lowering ionized calcium and precipitating symptoms of hypocalcemia.
• On the CCS, sometimes you will be given preexisting medi­ cations at the beginning of the case. You have to determine whether to discontinue them or allow them to be active throughout the case. Think about whether or not the medi­ cation is affecting the patient’s current condition, and if there will be a potential for a drug-drug interaction with future medications you order during the case.
• On the CCS, for any patient presenting with an arrhythmia, be sure to monitor the patient (ie, telemetry, cardiac moni­ tor) when correcting the calcium levels.
• On the CCS, remember to “bridge” your therapy by treating any acute issues of hypocalcemia with the long-term man­ agement of hypocalcemia.
(see Figure 6-1). It should be noted that if two tests are abnor­ mal, then it rules in the diagnosis of Cushing’s syndrome, but not the etiology.
Step 2) If there are two abnormal tests, the next thing you have to consider is the level of the ACTH. Determining the ACTH level will help delineate the cause into an ACTH-independent or ACTH-dependent condition. Remember that an ACTH- dependent cause would be a condition where ACTH is needed to drive the elevated cortisol level. An ACTH-independent condition does not need ACTH to elevate the cortisol level; the lesion itself is producing the cortisol.
Step 3) Further testing with imaging to localize the etiology and high-dose dexamethasone suppression test (8 mg) to differentiate between pituitary and ectopic causes of Cushing’s syndrome are usually pursued (see Figure 6-1).
Step 4) Treatment of Cushing’s syndrome depends on the etiol­ ogy. Consider the following\:
Cushing’s Disease
• Transsphenoidal surgery is considered the treatment of choice.
• Pituitary irradiation is considered in patients who refuse sur­ gery or when surgery is not successful.
• Bilateral adrenalectomy is considered second-line treatment.
Ectopic ACTH Tumor
• Surgical removal of the tumor.
• If the mass is not identified, then control the hypercorti- solism with adrenal enzyme inhibitors (eg, ketoconazole, flu­ conazole, etomidate, metyrapone) until the culprit is found.
Adrenal Tumor
• Adrenalectomy is the treatment of choice.
Exogenous Glucocorticoids
• Gradual withdrawal of glucocorticoids.

FIGURE 6-1 • Cushing's syndrome evaluation.
Follow-Up\: •
Patients who undergo surgery should have stress doses of glucocorticoids intraoperatively and immediately postop- eratively.
Patients who undergo transsphenoidal surgery for Cushing’s disease require lifelong glucocorticoid therapy.
Patients who undergo bilateral adrenalectomy require lifelong glucocorticoid and mineralocorticoid therapy.
Finding the cause of Cushing’s syndrome is important since hypercortisolism can lead to significant morbidity.
Pearls\:
• Exogenous administration of glucocorticoids is the most common cause of Cushing’s syndrome.
• •
Suspect Cushing’s syndrome
I
Overnight low-dose (1 mg) dexamethasone suppression test
Serum cortisol not suppressed Serum cortisol suppressed (Abnormal result) (Normal physiology)
1I
24-hour urine free cortisol 24-hour urine free cortisol
IJ
Elevated (Abnormal)
_L
Cushing’s syndrome
Low ACTH
I
Adrenal MRI or CT
J Adrenal tumor
Summary
• ACTH-independent
• Low ACTH
• Adrenal lesion on imaging
Levels within normal range
Two negative tests, unlikely Cushing’s syndrome
Plasma ACTH levels
Serum cortisol suppressed
1
MRI pituitary
1 Cushing’s disease
Summary
• ACTH-dependent
• Elevated ACTH
• Cortisol suppressed (High dexamethasone)
• Pituitary adenoma
• Elevated ACTH gradient on petrosal sinus sampling
Serum cortisol not suppressed
1
High-ACTH
High-dose (8 mg) dexamethasone suppression test
r
CT chest
Ectopic ACTH tumor
Summary
• ACTH-dependent
• Elevated ACTH
• Cortisol not suppressed (High dexamethasone)
• Rnd the tumor, most are located in the chest
CHAPTER 6 ENDOCRINOLOGY 77

78 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Petrosal sinus sampling with corticotropin-releasing hor­ mone (CRH) stimulation can be performed in patients that do not have a clear pituitary lesion on MRI. This test can help differentiate an ectopic ACTH tumor from Cushing’s disease. An elevated plasma ACTH gradient (central to peripheral) is diagnostic for Cushing’s disease.
• CJ\: A 20-year-old woman with Cushing’s disease refuses transsphenoidal surgery and pituitary irradiation because of fear of brain complications. She instead consents for a bilat­ eral adrenalectomy. Over the course of the year, she notices visual disturbances, headaches, and hyperpigmentation of the skin. What syndrome is associated with a bilateral adrenalec­ tomy? Answer\: Patients who undergo bilateral adrenalectomy can develop Nelson’s syndrome, which is characterized by an enlargement of a pituitary adenoma causing a local mass effect and the development of hyperpigmentation of the skin secondary to an increase in ACTH levels from a suppressed negative feedback because of inadequate cortisol levels. Trans­ sphenoidal surgery or irradiation are the treatments of choice.
• On the CCS, “dexamethasone suppression test” is recog­ nized in the order menu, but the results will only provide you with the low-dose dexamethasone in the practice CCS.
• On the CCS, when you have a patient with multiple prob­ lems, try to select the most appropriate physical exam that will potentially give you relevant results. Remember that unnecessary parts of the physical exam can cost you time and potentially deduct from your score.
I PHEOCHROMOCYTOMA
Pheochromocytoma is a catecholamine-secreting tumor. The tumor is composed of chromaffin cells and arises from the adrenal medulla. A chromaffin cell tumor outside of the adrenal medulla such as the sympathetic ganglion is more appropriately called a paraganglioma, although it may still be referred to as an extra-adrenal pheochromocytoma.
Clinical Features\:
The classic presentation is diaphoresis, headaches, palpitations, and hypertension (episodic or sustained). However, patients can still be asymptomatic with only an incidental finding of the tumor. The presentation for pheochromocytoma is variable, and it is important to consider the other clinical findings in a relative head to toe fashion\:
Neurologic—Tremor, anxiety (“impending doom”), visual disturbances
Cardiovascular—Chest pain, arrhythmias, myocarditis, postural hypotension
GI—Nausea, epigastric pain, weight loss, constipation Dermatologic—Pallor, flushing spells
Next Step\:
Step 1) Biochemical testing with a 24-hour urine collection for fractionated catecholamines and metanephrines. Alternatively, plasma fractionated metanephrine can also be measured since it has a high sensitivity but rather poor specificity. It should be
noted that there is no consensus as to the “best diagnostic test” for pheochromocytoma.
Step 2) If biochemical testing is elevated, further investigation to locate the tumor with either an adrenal/abdominal CT or MRI should be performed.
Step 3) If CT or MRI are negative but clinical suspicion is still high (ie, clinical symptoms, positive biochemical tests), then the next best step is to order a 123-I-meta-iodobenzylguanidine (MIBG) scintigraphy (ie, a test that uses a radioactive tracer that is picked up by adrenergic tissue).
Step 4) Once pheochromocytoma is confirmed, a preoperative preparation with medication is important. Start with an alpha-blocker first with the preferred agent, phenoxybenza- mine, to control the blood pressure. Other alpha-1 blockers that can be used are prazosin, doxazosin, or terazosin. Typically, an alpha-blocker is used for 10 to 14 days preoperatively. Once adequate alpha blockade is achieved, then a beta-blocker (eg, propranolol) should be initiated.
Step 5) Surgical resection by a laparoscopic approach is the preferred procedure.
Follow-Up\:
Patients with MEN 2A, MEN 2B, and Von Hippel-Lindau disease should have genetic counseling.
Pearls\:
• Patients may have elevated glucose levels because of an increase in catecholamine release.
• Rules of 10 for pheochromocytoma\: 10% malignant, 10% bilat­ eral, 10% extra-adrenal, 10% familial, 10% found in children.
• Pheochromocytoma can occur sporadically or they can be associated with familial syndromes.
• Familial syndromes\:
MEN 2A—Pheochromocytoma, medullary thyroid CA, Hirschsprung’s, hyperparathyroidism (look for T calcium levels). Associated with mutations in the ref proto-oncogene. MEN 2B—Pheochromocytoma, medullary thyroid CA, Hirschsprung’s, intestinal ganglioneuromas, marfanoid hab­ itus. Associated with mutations in the ret proto-oncogene. Von Hippel-Lindau disease—Pheochromocytoma, heman­ gioblastomas, clear cell renal cell carcinoma
• Concurrent illnesses and medications (eg, TCAs, psychoactive meds, decongestants, acetaminophen, amphetamines, benzo­ diazepines, alcohol, labetalol, clonidine, levodopa) can alter the interpretation of the biochemical lab measurements.
• Metabolites of catecholamine include metanephrine, normetanephrine, and vanillylmandelic acid (VMA).
• Foundational point—The adrenal gland is composed of the adrenal cortex or GFR, which stands for the outermost layer, zona Glomerulosa (secretes aldosterone), then zona Fascicu- lata (secretes glucocorticoids), and then the innermost layer zona Reticularis (secretes androgens). After the cortex is the inner portion of the adrenal gland, the adrenal medulla, which secretes catecholamines.

• CJ\: In the office, you have been taking the necessary steps in preparing your patient for a laparoscopic adre­ nalectomy secondary to a pheochromocytoma. However, you’ve been treating your patient with a beta-blocker first instead of an alpha-blocker. Is that acceptable? Answer\: Beta blockade should not be administered before alpha blockade because there can be a paradoxical increase in blood pressure in the presence of an unopposed alpha- adrenergic stimulation from the catecholamine-secreting tumor.
GLUCOSE HOMEOSTASIS DISORDERS
I DIABETESMELLITUSTYPE1
Type 1 diabetes mellitus (T1DM) is characterized by a deficiency in insulin production secondary to destruction of the beta cells in the islets of Langerhans of the pancreas through an autoimmune (type 1A) or nonautoimmune/idiopathic process (type IB).
Clinical Features\:
Type 1 diabetes typically presents in childhood. Consider the following clinical manifestations ofT1DM\:
• Polyuria
• Polydipsia (secondary from T serum osmolality and fluid loss)
• Polyphagia
• Weight loss (mainly from fluid loss and increased catabolism)
• Abdominal pain
• Fatigue
• Blurred vision (secondary from the hyperosmolar state of the lens and refractive index changes from the vitreous and aqueous humor)
• Children can initially present with DKA in some cases
• On the CCS, if you order a 24-hour urine catecholamine in the practice CCS, you will get results of all the catechol­ amines (eg, epinephrine, norepinephrine, dopamine).
• On the CCS, a “24-hour urine metanephrine, total” is avail­ able in the practice CCS.
• On the CCS, “MIBG scan, pheochromocytoma” is recog­ nized in the practice CCS.
• On the CCS, in acute cases, remember to do targeted physical exams.
Next Step\:
Step 1) Diagnosis of diabetes mellitus requires at least one of the following criteria\:
• Fasting glucose >126 mg/dL (fasting for at least 8 hours)
• Random glucose >200 mg/dL with symptoms (eg, polyuria, polydipsia, or weight loss)
• 2-hour plasma glucose >200 mg/dL after a 75 gm glucose load (test known as oral glucose tolerance test, OGTT)
• Glycated hemoglobin A1C >6.5%
Step 2) Repeat any one of the criteria above on a different day to confirm diabetes mellitus, unless there is no doubt that hyper­ glycemia is present on testing.
Step 3) Insulin therapy is the treatment of choice for T1DM (see Table 6-5). Multiple insulin regimens exist, but one com­ mon example is the basal/bolus insulin therapy, which includes a premeal injection of a rapid- or short-acting insulin to cover spikes in glucose from the meals along with a once-a-day injec­ tion of a long-acting insulin to cover basal requirements. An alternative to frequent injections is a continuous subcutaneous insulin infusion using a rapid- or short-acting insulin by an external pump, which offers a more flexible lifestyle.
Step 4) The following are the glycemic recommendations for diabetic adults from the American Diabetes Association (ADA)\:
CHAPTER 6 ENDOCRINOLOGY 79

80 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Table 6-6 • Diabetic Health Maintenance Microvascular Prevention
Retinopathy Nephropathy
Neuropathy
Patients with T1 DM should have an eye exam within 5 years after the onset of diabetes and then annually. Patients with T2DM should have an eye exam at initial diagnosis and then annually.
Patients with T1 DM should have a urine microalbumin test within 5 years after the onset of diabetes and then annually. Patients with T2DM should have urine microalbumin test at initial diagnosis and then annually.
Patients with T1 DM and T2DM should have annual serum creatinine levels.
Patients withT1 DM and T2DM should have distal symmetric polyneuropathy (DPN) screen at diagnosis and then annually. T1 DM patients should be screened for autonomic neuropathy 5 years after the diagnosis, but T2DM should
be screened at diagnosis. Macrovascular Risk Reduction
Blood pressure Lipids
Aspirin
Smoking Vaccinations Influenza Pneumococcal
| Miscellaneous Foot care
A1C
• Keep A1C <7.0
• Preprandial plasma glucose between 70 and 130 mg/dL
• Postprandial plasma glucose of <180 mg/dL (1-2 hours after the beginning of a meal).
Follow-Up\:
Routine diabetic care as recommended by the ADA is an essen­ tial component to the patient’s health (see Table 6-6).
Pearls\:
• A few weeks after initiating insulin therapy, patients may require less exogenous insulin because of the “honeymoon phase,” which can last up to several months. During this phase, any remaining functional beta cells are still able to secrete endogenous insulin. It is important to monitor blood glucose during this phase to prevent a hypoglycemic episode. As exogenous insulin requirements increase, the honeymoon phase is coming to its end.
• Associated autoimmune disorders with T1DM include au­ toimmune thyroiditis, celiac disease, Addisons disease, and polyglandular autoimmune syndrome type 2.
• Improving glycemic control improves the risk of microvas- cular complications, which include retinopathy, nephropa­ thy, and neuropathy in both type 1 and type 2 diabetes.
Check at every office visit with goal of <130/80.
Check annually with goal of LDL <100 mg/dL, Trigs <150 mg/dL, HDL >40 mg/dL.
Aspirin is a key component in mitigating the inflamed and hypercoaguable vascular system (endothelial dysfunction) as
a result of diabetes. Start aspirin 75-162 mg/dy in patients who have diabetes in men >50 years old or women >60 years old who have one additional risk factor such as HTN, dyslipidemia, family history of CHD, or smoking.Those who have aspirin allergy may use clopidogrel. In patients with known cardiovascular disease start aspirin, statin, and ACE 1 if no contraindication exists.
Advise smoking cessation at every visit.
Annually in patients >6 months of age.
Diabetic patients >2 years old, and one-time revaccination >64 years old if they were immunized when they were less than 65 years old and the vaccine was given more than 5 years ago.
Visual inspection at every office visit and annual comprehensive foot exam to identify risk factors predictive of ulcers and amputations.
Check every 3 months after initial diagnosis and when changing medication therapy, and then every 6 months once controlled, with goal of <7%.
• Diabetic retinopathy is a chronic complication of diabetes that is classified as proliferative or nonproliferative diabetic retinopathy. The hallmark ofproliferative retinopathy is the for­ mation of new blood vessels (neovascularization) arising from the disc and/or retinal vessels (see Figure 6-2 and Color Plate 8).
FIGURE 6-2 • Proliferative diabetic retinopathy. Proliferative retinopathy displaying yellow exudates, scattered hemorrhages, and neovascular vessels proliferating from the optic disc, requiring urgent panretinal laser photocoagulation. (Reproduced with permission from Lango DL,
Fauci AS, Kasper DL, et al. Harrison's Principles ofInternal Medicine. 18th ed. New York\: McGraw-Hill, www.accessmedicine.com.)

• • •
•
•
•
•
•
Nonproliferative diabetic retinopathy is characterized by die absence of neovascularization but the presence of any of the following\: microaneurysm, exudates (eg, yellow lipid), cot­ ton wool spots (ie, nerve fiber layer infarcts, which have a dull white appearance), hemorrhages, dilated or tortuous vessels.
Not all patients with nonproliferative retinopathy will go on to develop proliferative retinopathy.
Insulin injections may be given in the abdomen, outer thigh, back of arm, and buttock region.
Insulin injection at the site of the abdomen has the quickest absorption compared to the thigh, arm, or buttocks and would be an ideal site prior to meals.
Lipohypertrophy is tissue scar formation from repeated injections in the same area. This can lead to poor insulin absorption and possible depot formation that can then randomly release insulin.
Urine dipstick is not sensitive enough to detect moderately increased albuminuria (formerly called microalbuminuria), which is in the range of 30 to 300 mg/dy. Instead, a 24-hour urine collection (which is more cumbersome) or a urine albumin- to-creatinine ratio (also referred to as spot urine) can be used.
Somogyi phenomenon is the notion that nocturnal hy­ poglycemia due to an increased dose of insulin at bedtime would lead to morning hyperglycemia secondary to release of stress or counterregulatory hormones from the hypogly­ cemic state.
Dawn phenomenon is the notion that morning hyperglyce­ mia is not due to nocturnal hypoglycemia, but rather from natural overnight release of hormones (eg, growth hormone, cortisol, glucagon, epinephrine).
On the CCS, “spot urine, microalbumin” and “microalbumin, 24-hour urine” are available in the practice CCS. The two
Table 6-7 • Comparison Between Type 1 and Type 2 Diabetes Mellitus
orders are different, and the results will give you values with their normal reference ranges.
• On the CCS, if you ever get stuck in a case, let the order menu help you. For example, if your case is diabetes, type in “diabetes” in the order sheet and a drop-down menu will help you order other important diabetic care such as diabetic teaching, diabetic foot care counseling, or diabetic diet.
• On the CCS, remember to always counsel your diabetic, hypertensive, asthmatic, and hyperlipidemic patients.
I DIABETES MELLITUSTYPE 2
Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance in the peripheral tissue and insufficient amounts of insulin production from the beta cells of the pancreas (see Table 6-7).
Clinical Features\:
Clinical manifestations of T2DM typically present well after the onset of the disease, and many patients will even have estab­ lished cardiovascular complications at the time of diagnosis. The classic presentation seen in T1DM may also be present (eg, polyuria, polydipsia, polyphagia), but they may appear to be less acute. Patients with type 2 diabetes who are in chronic hyper­ glycemia may also be predisposed to poor wound healing and recurrent infections (particularly yeast). Several risk factors for T2DM will help differentiate from TlDM, including\:
Features Age of onset
Body habitus Etiology
Endogenous insulin levels/C-peptide levels
Genetic predisposition HLA association Autoimmune association
Type 1
Typically <30 years old, particularly in childhood or adolescence
Thin
Destruction of beta cells
Low to absent once all beta cells destroyed
Moderate Yes
Yes (eg, hypothyroid, celiac disease, Addison's, polyglandular autoimmune type 2)
Rapid
DKA
Retinopathy, nephropathy, neuropathy Insulin agents
Onset of symptoms
Acute complications
Chronic complications
Medical therapy DKA—diabeticketoacidosis;HHNS—hyperosmolarhyperglycemicnonketoticstate;HLA—human leukocyteantigen
• • • •
Age >45 years
Family history of diabetes
History of gestational diabetes History of impaired glucose tolerance
Type 2
Typically >40 years old
Obese
Insulin resistance and insufficient amounts of insulin production from beta cells
Present, but can become relatively deficient once insulin production slows down
Strong
No
None known
Insidious
HHNS, but sometimes DKA Retinopathy, nephropathy, neuropathy Oral agents and sometimes insulin
CHAPTER 6 ENDOCRINOLOGY 81

82 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• History of cardiovascular disease (CVD)
• Obesity
• Sedentary lifestyle
• Conditions associated with insulin resistance (acanthosis nigricans, polycystic ovary syndrome, HTN (>140/90), dyslipidemia (T trigs, 4- HDL)
• Ethnicity (African American, Hispanic, Native American, Asian) Next Step\:
Step 1) Diagnosis for T2DM is the same as for T1DM (refer to T1DM section).
Step 2) The best initial therapy is lifestyle modification, which includes diet, exercise, and smoking cessation. If lifestyle measures fail to achieve the targeted blood glucose goal within 2 to 3 months, medical therapy with metformin should be initiated if there are no contraindications (eg, hypersensitivity to metformin, Cr >1.5 mg/dL in males, Cr >1.4 mg/dL in females). Key features of metformin are that it does not cause weight gain, rarely causes hypoglycemia, but can cause lactic acidosis (see Table 6-8).
Step 3) If glycemic control is not achieved with metformin even at the recommended maximum dosage, add a different class of an antidiabetic oral agent. One c—ommon combination is to add
Table 6-8 • Oral Antidiabetic Agents
Agents
Sulfonylureas
Glyburide
Glipizide
Glimepiride
Meglitinides
Repaglinide Nateglinide
MOA
T insulin release
T insulin release
Advantages
• Considered first-line agents when there is a contraindication to metformin.
• Targets postprandial glucose since they are rapid-acting agents that mimic physiological insulin secretion.
• Useful in patients with irregular or erratic eating habits.
• Targets postprandial glucose. • Weight neutral.
4- Trigs, T HDL
Disadvantages
• Weight gain
• Hypoglycemia
• Weight gain
• Hypoglycemia
• Flatulence
• Diarrhea
• Abdominal pain
• Can cause elevated serum transaminases
(AST, ALT).
. T ldl
• Weight gain
• Edema
• Bone fractures
• Contraindicated in patients with NYHA
Class III and IV CHF.
• Do not use in patients with liver disease. • Can cause elevated serum transaminases
(AST, ALT).
• Lactic acidosis
• Do not use when Cr >1.5 mg/dL in males,
or Cr >1.4 mg/dL in females.
• Do not use immediately after radiocon­
trast procedures.
• Do not use in patients with hepatic
insufficiency.
• Do not use in patients with
decompensated CHF.
• Can cause 4-vitamin B12 levels. • May cause Gl discomfort.
a-Glucosidase Inhibitors
Acarbose Miglitol
Thiazolidinediones
Rosiglitazone Pioglitazone
i Biguanide Metformin
Delays carbohydrate absorption in
the gut.
4- hepatic glucose
production
T peripheral glucose
uptake (insulin sensitivity)
•l hepatic glucose • production
Does not induce weight gain and may actually cause weight loss, preferred agent for obese patients.
T peripheral glucose uptake (insulin sensitivity)
4- intestinal glucose absorption
• Minimal risk of hypoglycemia.
CHF—congestiveheartfailure;Cr—creatinine;MOA—mechanism ofaction;NYHA—New YorkHeartAssociation

a sulfonylurea to metformin. However, it is important to know the drug profile of each antidiabetic agent to assist in your clini­ cal judgment on the board exam (see Table 6-8).
Step 4) If glycemic control is still not achieved with dual oral agents, some clinicians may add a third agent if the patient is close to the targeted blood glucose, or they may add insulin to the regimen.
Follow-Up\:
Patients should initially be seen every 3 months until Hb A1C is <7% and then at least every 6 months thereafter. As with TIDM, routine diabetic care is important (see Table 6-6).
Pearls\:
• ACE inhibitors and ARB have renal protective effects in pa­ tients with diabetes.
• Patients with the metabolic syndrome have a higher risk of developing T2DM.
• CJ\: A 45-year-old man with T2DM has elevated blood glu­ cose despite being on metformin and glipizide. His primary care physician decided to add insulin to his regimen, and in the following week, the patient became unconscious at his home. His wife immediately took a blood glucose reading of 19 mg/dL. What is the best treatment to reverse his hypo­ glycemia? Answer\: Glucagon intramuscularly or subcutane­ ously in an unconscious patient. Conscious patients who are
CCS\: DKA
CASE INTRODUCTION
Day 1 @ 16\:00 Emergency Room
A 22-year-old Hispanic man presents to the emergency depart­ ment because of severe abdominal pain, nausea, and vomiting.
Initial Vital Signs\:
Temperature\: 37.0°C (98.6°F) Pulse\: 102 beats/min Respiratory\: 30/min
Blood pressure\: 107/70 mm Hg Height\: 175.3 cm (69 inches) Weight\: 75 kg (165 lb)
BMI\: 24.4 kg/m2
Initial History\:
Reason(s) for visit\: abdominal pain, nausea, vomiting.
able to take oral intake can consume juices, glucose tablets, or a snack.
• Connecting point (pg. 24)—Know the components of the metabolic syndrome.
• On the CCS, when ordering an oral antidiabetic agent, be sure to give the specific name of the medication.
• On the CCS, “counsel patient/family.”
• On the CCS, “advice patient, no smoking.”
• On the CCS, “advise patient, side effects of medication.”
• On the CCS, a sample checklist of items for the physical examination in a diabetic patient should include the following\:
Neuro/Psych—Assesss for peripheral sensation, or signs of neuropathy.
HEENT/Neck—Assess the fundus of the eye, also assess for the thyroid.
Chest/Lungs—Assess for coexisting respiratory conditions. Heart/Cardiovascular—Assess for signs of cardiovascular
disease.
Abdomen—Assess for hepatomegaly (usually due to fatty liver).
Skin—Look at the injections sites and look for signs of acan­ thosis nigricans.
Extremities/Spine—Check for peripheral pulses and foot examination.
CHAPTER 6 ENDOCRINOLOGY 83
HPI\:
A 22-year-old college student has been experiencing diffuse ab­ dominal pain for the past several hours. He states the abdominal pain is 7/10 in severity, with no aggravating or alleviating fac­ tors. He has nausea with five episodes of nonbloody, nonbilious emesis over the past 6 hours. In addition, he has been drinking more water than usual and has been urinating more frequently. The patient states that he was diagnosed with type 1 diabetes 12 years ago and admits that he has not been compliant with his insulin medication. He has visited the emergency department twice this year for the same condition.
Type 1 diabetes diagnosed at age 10. Tonsillectomy at age 9.
Medications\:
Allergies\: None
Past Medical History\: Past Surgical History\:
Lispro, Glargine

84 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Vaccinations\: Family History\:
Social History\:
Review of Systems\: General\:
HEENT\: Musculoskeletal\: Cardiorespiratory\: Gastrointestinal\: Genitourinary\: Neuropsychiatric\:
Day 1 @ 16\:07
Physical Examination\: General appearance\: HEENT/Neck\:
Chest/Lungs\: Heart/Cardiovascular\: Abdomen\:
Neuro/Psych\:
First Order Sheet\:
1) IV access
2) Continuous cardiac monitor, stat
3) Continuous blood pressure cuff, stat
4) Pulse oximetry, stat
5) Finger-stick glucose, stat
6) Urinalysis, stat
Up to date
Father, age 50, and mother, age 48, are healthy. No siblings. Unde has history of type I diabetes.
Smokes half pack per day x 3 years; drinks on the weekends with room­ mates; admits to occasional cocaine use with fraternity friends and re­ cent use within the last two days; single; no children; full-time college student; enjoys playing baseball and going to movies.
See HPI Negative Negative Negative See HPI See HPI Negative
Patient is in pain and uncomfortable. Normocephalic. EOMI, PERRLA.
“Fruity” breath smell. Dry oral mucosa and nasal mucosa; septum
midline. Trachea midline; no masses or bruits; thyroid normal. Tachypneic, deep labored respira-
tions (Kussmaul respirations). Tachycardia. No murmurs, rubs, gallops, or extra sounds. No JVD. Normal bowel sounds; diffuse ten­ derness on palpation. No rebound or guarding. No hepatosplenomegaly. Awake, but inattentive. Normal motor, sensory, and cranial nerve exams. No focal deficits.
Result\: Sinustachycardia Result\: 107/70 mm Hg
Result\: 98% Result\: 650 mg/dL
Result\: Glucose-positive, Ketones- positive, Nitrite-negative, Leukocyte esterase-negative, Microscopic exam-unremarkable
Second Order Sheet\: 1) NS, 0.9% NaCl, IV,
continuous
2) Ondansetron, TV, one time
Third Order Sheet\: 1) BMP, stat
2) CBC with differential, stat
3) ABG, stat
4) 12-LeadEKG,stat
5) Urine culture, routine
x,
6) Blood culture, routine
Fourth Order Sheet\:
1) KCX, IV, continuous
Note\: Patient is tachycardic, hypotensive, and signs
of dehydration -¥ Start fluids.
Result\: Glu-650, Urea-17, Na-132, K-3.0, Cl-100, HC03-12, Cr-1, Ca-9
Result\: WBC-10,000, H/H-14/42%, Plt-300,000, Differential-normal
Result\: pH-7.25, pC02- 25 mm Hg, pOz-85 mm Hg,HC03-12,02 sat.-97%
Result\:Rhythm-sinus tachycardia, Axis- +30 degrees, P-waves- wnl, QRS complexes- wnl, ST-T waves- wnl, Other findings- wnl, Interpretation- sinus tachycardia
Result\: No growth Result\: No growth
Note\: Patient’s potassium level is low, and the only real indication to delay insulin therapy is if the potassium is below
3.3 mEq/L since insulin can drive the potassium into the cell and thereby exacerbate the hypokalemia.
Note\: Vitals are automati­ cally ordered for you in the practice CCS.
Result\: Glu-650, Urea-17, Na-132, K-3.4, Cl-100, HC03-12, Cr-1, Ca-9
Actions\:
1) Change location to ICU
Fifth Order Sheet\: 1) NPO
2) Bedrest
3) Urine output, q8 hrs, stat
4) BMP, routine, q2 hr, stat

Sixth Order Sheet\: 1) Insulin, Regular,
IV, continuous
Seventh Order Sheet\:
1) Vital signs, stat
2) Check cardiac monitor, stat
3) Venous pH
Follow-Up History\:
Patient is feeling a little bit better.
BMP result is now available
Result\: 37.0°C, HR-95, RR-25, BP-120/78
Result\: Regular sinus
Result\: 7.33
Note\: Obtaining a venous pH is less painful than the ABG, and still provides the acid-base status. The venous pH is approximately 0.03 lower than the arterial pH.
This case will end in the next few minutes of “real tune.” You may add or delete orders at this time,
then enter a diagnosis on the following screen.
Tenth Order Sheet\:
1). Counsel patient/family
2) Diabeticteaching
3) Diabetic diet
4) Advise patient, no smoking
5) Advise patient, no illegal drug use
Please enter your diagnosis\: DKA
DISCUSSION\:
DKA is characterized by the triad ofhyperglycemia (>200 mg/ dL), ketosis (presence ofketone bodies), and metabolic acidosis (pH <7.3, plasma bicarbonate <15 mEq/L). Precipitating factors include acute illness, noncompliance with meds, illicit drugs (eg, cocaine), medications (eg, lithium, thiazides, steroids, antipsy- chotics), infection, surgery, or new-onset diabetes. In this case, both noncompliance and probably drugs such as cocaine might have precipitated the event. One simple way to manage DKA patients is to first correct intravascular volume, then potassium levels, and finally sugar levels in this particular order because hydration is important in the early stages of management, and administering insulin depends on the potassium level. You can remember this simple format by the word DKA or “D” for dehy­ dration, “K” for potassium, and “A” for azucar (sugar in Spanish).
“D”—Fluid replacement is important early in the management of DKA patients. DKA patients can lose up to 6 liters of fluid, while patients who are in hyperosmolar hyperglycemic nonke­ totic state (HHNS) can lose up to 9 liters of total water. It is recommended to initially treat with an isotonic solution such as normal saline to establish intravascular repletion. However, it is important not to replace the water deficit too quickly as it can cause cerebral edema. Once the patient is stabilized and corrected sodium levels are either normal or elevated, switch to a less isotonic solution such as one-half normal saline. If the corrected sodium is still hyponatremic, continue with the iso­ tonic solution. Once glucose levels are between 200 and 250 mg/ dL, switch intravenous fluids to dextrose 5% in one-half normal saline to prevent hypoglycemia. Keep in mind that the CCS will not require you to know the rate or the amount of fluids to give.
“K”—Patients may initially present with hypokalemia or hyper­ kalemia. In either case, there is a total body deficit ofpotassium. Hyperkalemia can be explained by a deficiency in insulin (ie, insulin promotes potassium cell uptake). Acidosis or the H+/ K+ shift plays a minor role in hyperkalemia, probably since hy­ perkalemia can still be seen in HHNS where there is no aci­ dosis. Hypokalemia can be explained by urinary excretion due to osmotic diuresis and the need to balance electroneutrality since negative ketoacid anions are being excreted along with the
Result\: Glu-450, Urea-17, Na-135, K-3.5, Cl-100, HC03-19, Cr-1, Ca-9
Note\: Anion gap is beginning to close from 20 to 16
Eighth Order Sheet\:
1) D/C, Normal saline,
0.9%, IV
2) 1/2 NS, 0.45%, IV, continuous
Note\: Click the item on the order sheet to cancel the order.
Note\: One-half normal saline can be used if the corrected serum sodium is normal or elevated. How­ ever, if the corrected serum sodium is still low, continue with normal saline. To cor­ rect for the sodium value, add 1.6 mEq to the sodium for every 100 mg/dL of glucose over 100 mg/dL.
BMP result is now available
Result\: Glu-210, Urea-,17, Na-135, K-3.6, Cl-100, HC03-24, Cr-1, Ca-9
Ninth Order Sheet\:
1) D/C, 1/2 NS, 0.45%,
IV, continuous
2) Dextrose 5% in 0.45% saline, IV, continuous
3) Insulin, Regular, Sub Q, one time
Note\: The metabolic acidosis has improved with anion gap of 11.
CHAPTER 6 ENDOCRINOLOGY 85

86 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
positive K+. If the potassium level is <3.3 mEq/L, continue to hydrate the patient and replace the potassium (eg, KC1). Once the potassium is >3.3 mEq/L, insulin can be administered.
“A”—Treatment ofelevated “azucar” levels is with insulin. Regu­ lar insulin is the preferred agent. Again, dosage is not required on the CCS. If the initial potassium level is less than 3.3 mEq/L, it is not recommended to initiate insulin therapy since the insu­ lin will drive the potassium into the cell. At a potassium level of 3.3 and above, an insulin drip can be started and should be done in a monitored setting such as the ICU. When the anion gap (ie, serum Na+ - [Cl- + HC03-]) is less than 15, the transition from intravenous insulin to subcutaneous insulin should begin. Once the subcutaneous insulin is given, the overlap of the insulin drip should continue for at least 1 to 2 hours.
Pearls\:
esterase and nitrites were negative, the white count was within normal range, and there were no elevated bands (“left shift”).
• Foundational point—There is a total of 3 ketone bodies produced during DKA. The major circulating ketoacid is the beta-hydroxybutyric acid. The other ketoacid is acetoacetic acid and a neutral ketone called acetone.
• Foundational point—Nitroprusside tablets can only detect acetoacetic acid and acetone but not the beta-hydroxybutyric acid.
• On the CCS, perform a focused physical examination. In any acute cases that require immediate attention, a complete physi­ cal examination would be considered suboptimal management.
• On the CCS, become comfortable relocating patients to different settings (practice with the CCS software).
• On the CCS, the diagnosis is sometimes clearly evident in the HPI. It is your workup, the sequence of your actions, appropriateness of your medical decisions, and efficiency that will score you points on the examination.
• On the CCS, ordering “continuous blood pressure cuff” and “continuous cardiac monitoring” will keep the cuff and leads on the patient throughout the case. When you want future results, you have to type in “check blood pressure” or “check cardiac monitor” in the order sheet.
• On the CCS, continuous cardiac monitoring is the same as telemetry or EKG monitor. Remember, it is important to monitor the patient in this type of case.
• On the CCS, if your advancing the time to fast during the case, sometimes a “PATIENT UPDATE” screen may appear which is usually indicative of a “warning sign” (ie, slow down and reevaluate what you’re doing).
• On the CCS, when you transfer a patient to the ICU or inpatient unit, the vitals will be ordered for you. However, you should not assume any orders will be written for you during the CCS cases.
HHNS
Typically >30 years old
Insidious
Uncommon
Yes, occurs with increasing plasma osmolality. Typically >320 mOsm/kg
Typically >600 mg/dL and can exceed 1,000 mg/dL Yes

15 mEq/L
No
7.30 9 liters
• •
•
• •
•
Monitor glucose levels every hour and electrolyte levels every 2 hours until stable.
The use ofbicarbonate is controversial, and therefore, it is not routinely used in DKA management, however, bicarbonate is sometimes given when the pH is <6.9.
The metabolic acidosis caused by the ketoacids results in a compensatory hyperventilation (Kussmauls respiration) to blow offthe C02, which results in a fall in the pC02.
DKA patients often have elevated amylase and lipase levels even though they do not have pancreatitis.
The management of DKA and HHNS is essentially the same, which is to give fluids, insulin, and electrolyte correction. How­ ever, the clinical features are slightly different (see Table 6-9).
In this particular CCS case, the clinical judgment was not to give empiric antibiotics because the precipitating factor for DKA was the recent drug use and noncompliance with medica­ tion. In addition, the patient did not have a fever, the leukocyte
Table 6-9 • Comparison Between DKA and HHNS
Features Age
Onset of symptoms Abdominal pain Neurologic symptoms Plasma osmolality Plasma glucose
Total body deficit of potassium (K+) Plasma bicarbonate
Ketone bodies
pH
Total water lost
DKA
Typically <30 years old
Rapid
Common
Yes, occurs with increasing plasma osmolality. Typically <320 mOsm/kg
Typically <600 mg/dL but as high as 800 mg/dL Yes
<15 mEq/L
Yes
<7.35
6 liters
DKA—diabeticketoacidosis, HHNS—hyperosmolarhyperglycemic nonketoticstate

Ethics
CHAPTER OUTLINE
1 PRINCIPLES OF MEDICAL ETHICS........................8.7. 1 INFORMED CONSENT.......................................8.7 B COMPETENCY...............................................8..8 1 CONFIDENTIALITY..........................................8.8
PRINCIPLES OF MEDICAL ETHICS
Autonomy—The patient has the right to refuse or accept medical treatment.
Beneficence—Acting in the best interest of or benefit to the patient.
INFORMED CONSENT
Informed consent is an agreement or authorization to perform a specific intervention. The patient must understand the follow­ ing even if it requires translation into another language\:
• Diagnosis, if known
• Proposed intervention
• Risk and benefits of the intervention
• Consequence of not receiving the intervention
1 M A L P R A C T I C E . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8. 9 1 REPORTABLE DISEASES....................................8.9 1 PHYSICIAN'S RESPONSIBILITIES............. ...........9.0.. 1 END-OF-LIFE CONCERNS..................................9.0
Nonmaleficence—Do no harm to the patient.
Justice—The decision to be fair and equal with the distribu­ tion of health-care resources to patients (eg, who gets an organ transplantation).
Truthfulness—Full disclosure and honesty to patients.
• Alternatives
• Risk and benefits of the alternatives
Clinical Judgment\:
• Patient speaks and understands a different language —» Get a translator to explain everything and document it in the chart.
• A procedure was performed on a patient, but afterward the patient found out there could have been an alternative option —» The physician is liable for not explaining other alterna­ tives prior to the procedure.
87

88 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• A patient who was fully alert and conscious discussed and documented with his or her physician about not performing a specific intervention two days ago in the office. The follow­ ing day the patient becomes unconscious and the health-care proxy wants the specific intervention performed —> Honor the request of the patient.
• A pregnant woman is informed about the risk and bene­ fit about a particular medical treatment. The benefit out­ weighs the risk of the proposed treatment and without the treatment the fetus would be in jeopardy. The patient initially refuses the medical treatment —» Continue to edu­ cate and counsel the patient about the intervention without coercion.
• An unconscious patient needs a specific intervention but the health-care proxy is in another state —■> Telephone consent is acceptable as long as a second witness speaks with the health-care proxy and is documented in the chart.
• An unconscious patient arrives in the ER and requires blood —> Give blood in life-threatening cases in which the patient is unknown to you and no health-care proxy is available.
COMPETENCY
Competency is a legal term based on a court’s decision to de­ termine if a patient can comprehend and make rational deci­ sions. Capacity is a clinical evaluation made by a physician that is based on the patient’s ability to understand and make reasonable decisions. In most cases, patients that are minors (ie, <18 years old) do not have the capacity to understand their medical condition and therefore require parental consent. How­ ever, the following are exceptions to parental consent\:
• Emancipated minor (ie, married, raising children, self- supporting, or serving in the military)
• Contraception
• Prenatal care
• Treatment for STDs
• Treatment for drug and alcohol abuse
• Treatment for psychiatric illness
CONFIDENTIALITY
Physicians are expected to maintain and respect patient privacy. The exceptions to break confidentiality include\:
• Patient waiver
• Court orders
• Threat to self-harm (eg, suicide)
• Threat to others in violence (eg, child abuse, elder abuse, or homicidal potential)
• A child comes into the ER and requires urgent treatment but the parents refuse —> Treat —»Then seek a court order.
• A child needs a specific intervention in a nonurgent case and the parents refuse —> Inquire about the parents’ concerns —»If parents are still refusing —» Get a court order before treatment.
• A 14-year-old girl is in her first trimester of pregnancy and requests an abortion —» Some states require parental con­ sent, while other states do not. In some cases, a minor can ask a judge to excuse her from getting permission in those states that require parental consent, which is referred to as “judicial bypass.” —» For board purposes, the key element is to have a nonjudgmental discussion with the minor ofall the options regarding pregnancy. It is also important to explore if she is willing to inform her parents, since some adoles­ cents will disclose the information to their parents on their own. For those who are hesitant, you can schedule another follow-up visit to continue the discussions, or you can offer your assistance by being present during the discussion with her parents. It should be noted that there is no legal require­ ment to notify the father of the baby prior to the abortion.
Clinical Judgment\:
• An 80-year-old man has dementia and does not have the ca­ pacity to make decisions. The patient is in need of a specific medical intervention —» Look for advance directives —»If no advance directives —> Contact the health care proxy.
• A schizophrenic patient is compliant with his medications and appears to have no impairment in reasoning or making decisions -» Patient can accept or refuse treatment.
• A suicidal patient is refusing medical treatment —» The pa­ tient does not have the capacity to make sound decisions.
• A patient consented to a written DNR order but recently changed her decision by verbalizing it to her physician —> Make sure that the patient has the mental capacity to un­ derstand her decision, and after a full discussion change the DNR status. Also document the discussion in the chart.
• A 30-year-old patient who has the capacity to understand and make decisions refuses blood for religious reasons (eg, Jehovah’s witness) —> Honor the request of the patient.
• Threat to the public (eg, impaired airplane pilot)
• Threat to others by transmitting infectious diseases
Clinical Judgment\:
• Family members want to know the result of a biopsy test be­ fore the patient -» Disclose only to the patient unless the pa­ tient waived his rights to privacy.
• The patient’s urologist wants to have medical records from the patient’s primary care physician —> Patient must sign a release form.

• Law enforcement comes to your office without a court order and is requesting information about a patient —> Without a court order, no information should be given.
• A newly diagnosed HIV patient does not want to tell his or her partner —> Encourage the patient to tell the partner. Ultimately, the partner will have to be told even if it means breaking confidentiality.
MALPRACTICE
Lawsuits are generally successful if all four Ds have been com­ mitted. The four Ds of malpractice are duty, deviation, dam­ age, and direct causation. In other words, did the physician have a duty to the patient in which there was negligence or de­ viation from the standard of care that resulted in damage to the patient directly caused by deviating from the standard of care?
Clinical Judgment\:
• Your wife’s best friend called you to obtain medical advice over the phone. The next few weeks she took your advice, and she became extremely ill and had to go to the hospi­ tal because of your advice. She now wants to sue you —»
REPORTABLE DISEASES
Reporting certain infectious diseases to the state health depart­ ments or national agencies (eg, CDC) are important for the greater public health. They permit surveillance on disease occurrence and assist with disrupting the spread of transmissible diseases to the public. The following is a list ofreportable diseases\:
• A teenage girl comes to your office and is accompanied by her parent —» Politely ask the parent to step outside the room so that a private interview can occur. Most teenagers do not feel comfortable discussing sexual matters in front of their parents. Maintaining a good rapport with the teenager is important in developing trust. Assure her that these discussions are confiden­ tial unless violence, infectious disease, or self-harm are involved.
Unlikely she’ll win because there was never a doctor- patient relationship and therefore no duty to your wife’s best friend.
• A patient has been prescribed Drug A for a cardiovascu­ lar problem. Drug A has been around for many years and is considered the standard of care for the specific cardiovascu­ lar problem. The patient has also been prescribed Drug B for a GI problem. Drug B has been around for many years and is considered the standard of care for the GI problem. New clinical findings now show that there are adverse interactions in the concomitant use of Drug A and Drug B. The patient is experiencing the adverse side effects and wants to sue —» Unlikely the patient will win since the physician never devi­ ated from the standard of care at the time of prescribing either medication.
AIDS
Anthrax
Botulism
Brucellosis
Chancroid
Chickenpox Chlamydia trachomatis Cholera Cryptosporidiosis Dengue
Diphtheria Encephalitis (Eastern
virus, St. Louis virus) Encephalitis (Western
virus, West Nile virus) Encephalitis (California
virus)
Giardiasis
Gonorrhea Haemophilus influenza.
invasive
Hansen’s disease (leprosy) Hemolytic uremic
syndrome
Hepatitis A, B, C
HIV infection Legionellosis Listeriosis
Lyme disease
Malaria
Measles Meningococcal disease Mumps
Pertussis
• •
A 35-year-old man has genital herpes —» Not a reportable disease.
A newly diagnosed HIV patient does not want to tell his or her partner —¥ Encourage the patient to tell the partner. Ultimately the Department of Health will contact the patient’s partner, but they may not disclose the patient’s name to the partner.
Plague
Poliomyelitis Poliovirus infection,
nonparalytic Psittacosis
Q fever Rabies
Rocky Mountain spotted fever
Rubella Salmonellosis Shigellosis Smallpox Streptococcus
pneumoniae, invasive Syphilis
Clinical Judgment\:
Tetanus Tuberculosis Tularemia Typhoid fever Varicella Vibriosis Yellow fever
CHAPTER 7 ETHICS 89

90 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
PHYSICIAN'S RESPONSIBILITIES
Child Abuse
• Any child abuse that is suspected should be reported to the De­ partment of Children and Family Services. Do not let the child go back home until a full evaluation is conducted by the agency.
Elder Abuse
• Any person over the age of 60 who has been subjected to abuse, neglect, or financial exploitation should be reported to the Department of Aging.
Domestic Violence
• Ask the patient if there is domestic abuse in the relationship in a nonthreatening approach. Reporting to law enforcement or protection agencies is not the role of a physician, unless there is potential for homicide. In addition, ask if there is any child abuse in the home as well. Otherwise, offer supportive counseling and referral to support services.
Impairment
• Impairedmedicalstudent—»ReporttoDean.
• Impaired resident —> Report to residency director.
• Impaired licensed physician —>Report to state licensing board.
END-OF-LIFE CONCERNS
Brain Death
• The irreversible cessation of cerebral and brainstem func­ tions. When considering the diagnosis ofbrain death, at least 4 important elements should be assessed\: (1) Absence of cerebral function. There is no spontaneous movement, no purposeful movement, no response to painful stimuli, deeply comatose, absence of seizures, and the absence of decorti­ cate or decerebrate posturing. However, spinal cord reflexes may still be present in some cases; (2) Absence of brain­ stem function. Absent corneal, pupillary, oculocephalic (doll’s eyes), oculovestibular (caloric response), cough, suck­ ing, and gag reflexes. There is no facial movements, loss of eye movements, and the pupils are dilated or midposition; (3) Destruction of the medulla. The presence of apnea as demonstrated by the apnea test. Apnea is confirmed if there is no spontaneous respiration in the presence of elevated PaC02 (>60 mm Hg) that serves as a stimulus for respiratory activity in the medullary centers; (4) Exclusion of reversible medical conditions that may confound the clinical as­ sessment (eg, hypothermia, hypotension, electrolyte abnor­ malities, acid-base abnormalities, shock, drug intoxication, neuromuscular blockade).
Sexual Relations
• Refrain from any sexual or romantic relationships with a pa­ tient even after the medical relationship between the doctor and patient ends.
Truth Telling
• Tactful honesty is very important.
• If a physician made a mistake, it is important to be forthright about the error.
• If a patient wants to know about his or her medical illness, it is important to inform the patient and not withhold infor­ mation. However, you can ask the patient how much he or she wants to know since some patients do not want to know all the facts of their illness.
Physician Rights
• Physicians have the right not to accept a new patient into their office. However, if a physician decides that he or she no longer wants to provide medical treatment to a current patient, then the treating physician should continue the care until the patient finds another physician. It is impor­ tant not to suddenly abandon the patient, but to help and guide the patient until he or she finds the best physician for him or her.
Organ Donation
• Organ donation may be refused if the family objects to donation even if the patient has an organ donor card.
Euthanasia
• Euthanasia is the deliberate act of ending a person’s life, which is ethically unacceptable. Euthanasia can take several forms\:
Voluntary active euthanasia—The physician intentionally and directly causes death of a patient at the patients request (eg, administering a lethal dose of a drug), which is not legal in the United States.
Involuntary active euthanasia—The physician intentionally and directly causes death of a patient without the patient’s request, which is not legal in the United States.
Passive euthanasia—The physician withholds life-sustaining medicaltreatment(eg,nutrition,ventilation)withtheproxy’sor patients’ consent, which is legal and ethical in the United States.
Physician-assisted Suicide
• The physician provides the means or imparts information to enable a patient to end his or her life. Only Oregon and Washington State have legalized physician-assisted suicide.

Advance Directives
• In the event that a patient cannot make decisions for himself or herself, an advance directive is a way to communicate the patients wishes. Advance directives can take several forms\:
Living will—A document that states the patients specific instructions on medical intervention in the event that the patient loses his or her capacity to make decisions.
Health-care proxy—Also known as durable power of attor­ ney, a health-care proxy is appointed and documented by the patient to make decisions for the patient in the event that the patient loses his or her capacity to make decisions. The health­ care proxy should make decisions based on what the patient would want and not what the health-care proxy would want.
Do not resuscitate (DNR)—Do not perform cardiopulmo­ nary resuscitation in the event that the patient experiences cardiac arrest. However, in the event that the validity of the DNR order is in doubt or the patient’s best interest is in question without a DNR order, then the next best step is to initiate resuscitative measures.
Do not intubate (DNI)—Neither an endotracheal tube nor an esophageal obturator airway can be placed to secure the airway or to assist in ventilation.
Palliative Care
• The means of providing relief from pain and suffering and encouraging dignity and autonomy to the dying patient. Caution must be taken from providing active euthanasia or physician-assisted suicide. Not uncommonly, palliative care medicine will encounter the “principle of double effect” in which an intended action (eg, pain relief) may cause an unintended effect (eg, death). For example, a terminal pa­ tient may require a significant amount of pain medication to relieve pain, but at the potential consequence of respira­ tory depression, which would hasten the patient’s death. The most important element in the double effect is that the inten­ tion of the action (ie, giving pain meds to relieve pain, not to cause death) is for good, even if the bad effect (death) is expected.
Hospice Care
• In hospice care, patients have 6 or less months to live as cer­ tified by a physician, and palliative care is instituted instead of curative treatments. Hospice care can be given in a hos­ pital, nursing home, private home, or any other hospice care facility.
CHAPTER 7 ETHICS 91

Gastroenterology
KEYWORDS REVIEW
Endoscopic ultrasound (EUS)—EUS is a technique that combines endoscopy with ultrasound to evaluate a variety of lesions within the gastrointestinal tract. EUS can serve as a diagnostic and therapeutic procedure (eg, draining procedure).
ERCP—Endoscopic retrograde cholangiopancreatography
is a technique that combines endoscopy with fluoroscopic imaging to evaluate the biliary and pancreatic ductal system. Contrast material is injected into the ductal system followed by fluoroscopic imaging to produce either a cholangiogram or a pancreatogram. ERCP can serve as a diagnostic and therapeutic procedure (eg, stent placement).
MRCP—Magnetic resonance cholangiopancreatography is a noninvasive technique that is used to assess the intrahepatic duct, extrahepatic bile duct, and pancreatic duct. No contrast material or intervention (eg, stone extraction) is used with this technique.
Phlegmon—A walled-off inflammatory mass without bacterial infection.
Pyrosis—Heartburn.
Sinus tract—An abnormal channel that allows the escape of fluid. Sinus tracts can give rise to fistulas, but not all fistulas are derived from sinus tracts.
93

94 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
ESOPHAGUS
1 BARRETT'SESOPHAGUS
Barrett’s esophagus is a condition in which there is a metaplastic change from stratified squamous epithelium to columnar epithe­ lium in the distal esophagus. GERD is the most common cause of Barrett’s esophagus, and it is thought that the metaplastic colum­ nar epithelium is more resistant to the acid damage compared to squamous epithelium. The overall risk of esophageal adenocar­ cinoma in Barrett’s esophagus is approximately 0.5% per year, or in other words, 1 in 200 patients per year.
Risk Factors\:
Older age (>50 years old), male, white race, high BMI, smokers, chronic GERD, hiatal hernia.
Clinical Features\:
There are no symptoms or physical findings that are characteris­ tic of Barrett’s esophagus other than those that would be found in patients with GERD such as heartburn, dysphagia, or regur­ gitation.
Next Step\:
Step 1) Patients suspected of having Barrett’s esophagus based on multiple risk factors require an upper endoscopy with biopsy ofthe distal esophagus to confirm the diagnosis. Mucosal biopsies should show the presence of specialized intestinal metaplasia (also known as specialized columnar epithelium) from the columnar-lined distal esophagus.
Step 2) Precancerous changes seen on biopsy that are graded as “low-grade dysplasia” or “high-grade dysplasia” should be confirmed by a second pathologist who is, ideally, an expert in esophageal histopathology.
Step 3) Treatment of Barrett’s esophagus is the following\:
GERD—GERD therapy should continue as it is for patients without Barrett’s esophagus.
Eradication therapy—Patients with confirmed high-grade dysplasia may undergo various types of eradication therapy
STOMACH
1 PYLORICSTENOSIS
Pyloric stenosis, also known as infantile hypertrophic pyloric stenosis (IHPS), is characterized by hypertrophy of the mus­ cular layers of the pylorus, which can lead to gastric outlet obstruction. The etiology of pyloric stenosis is unknown, but it is thought to be multifactorial.
Clinical Features\:
Pyloricstenosisclassicallypresentsbetween3to6weeksoflife.The condition is characterized by nonbilious, projectile vomiting soon
such as endoscopic mucosal resection, radiofrequency ablation, photodynamic therapy, or alternatively an esopha­ gectomy (higher morbidity). The choice oftreatment usually depends on the patient’s comorbidities, local expertise, and the patient’s functional fitness.
Follow-Up\:
The following endoscopic surveillance intervals are recom­ mended by the American Gastroenterological Association (AGA)\:
No dysplasia\: 3 to 5 years
Low-grade dysplasia\: 6 to 12 months
High-grade dysplasia in the absence of eradication therapy\: 3 months
Pearls\:
• There is no association between H pylori infection and GERD since the organism does not infect the esophagus.
• There are 3 types of columnar epithelium to consider, they include cardia-type epithelium, gastric-fundic-type epithe­ lium, and specialized intestinal metaplasia. Only specialized intestinal metaplasia has a clear association with carcinoma.
• The specialized intestinal metaplasia comprise a collection of columnar cell types such as goblet cells, intestinal-like cells, and gastric-type cells.
• The AGA notes that the use ofproton pump inhibitors (PPIs) in patients with Barrett’s esophagus solely to reduce the risk of progression to dysplasia or cancer is indirect and has not been proven in a long-term controlled trial.
• The AGA recommends against attempts to eliminate esophageal acid exposure for the prevention of esophageal adenocarcinoma. Examples of such attempts include antire­ flux surgery, PPI doses greater than once daily, or esophageal pH monitoring to titrate PPI dosing.
• On the CCS, if you order “Endoscopy, upper gastrointes­ tinal” in the practice CCS, the evaluation will not provide biopsy results. Therefore, you will need to order “Biopsy, esophagus” to confirm the diagnosis of Barrett’s esophagus.
after a feeding. On physical examination, a firm, nontender, mobile “olive” can be felt immediately after emesis at the lateral edge of the rectus abdominis muscle in the right upper quadrant. Prior to emesis, peristaltic waves may be seen moving from the patients left to right as the peristalsis is trying to overcome the obstruction. As a result of improper feeding, patients may have various degrees of dehydration. The following are signs to look for\:
Mild dehydration—Heart rate normal, respirations normal, palpable pulses present, fontanel normal, skin turgor nor­ mal, mucous membrane moist.
Moderate to severe dehydration—Tachycardia, respira­ tions deep and rapid, palpable pulses decreased, fontanel depressed, skin turgor reduced, mucous membranes dry.

Next Step\:
Step 1) Definitive diagnosis is commonly made with an ultrasound, although an upper gastrointestinal (UGI) contrast study can also make the diagnosis.
Step 2) Prior to any type of surgical correction, the patients fluid status and electrolytes should first be corrected. The classic electrolyte finding in pyloric stenosis is a hypochloremic, hypokalemic, metabolic alkalosis (T HC03).
Treatment for Mild Dehydration with Normal Electrolytes • Treat with maintenance fluids (eg, D5 0.25% NaCl + KC1).
Treatment for Moderate to Severe Dehydration
• Treat with higher concentrations of NaCl (ie, one-half normal saline to normal saline)
• Consider a bolus of fluids initially.
• Make sure the kidneys are functioning properly before administrating KC1.
Step 3) Definitive treatment for pyloric stenosis is with a surgical pyloromyotomy.
Follow-Up\:
Up to 80% of patients will regurgitate after surgery; however, this issue should not delay feedings.
Pearls\:
• Up to 30% of patients with pyloric stenosis will be firstborn males.
INTESTINES—INFLAMMATORY BOWEL DISEASE
S CROHN'SDISEASE
Crohn’s disease (CD) is a chronic, transmural inflammatory process that can lead to progressive fibrosis, stricturing, or per­ forating disease. Crohn’s disease can affect any part of the gas­ trointestinal tract from the mouth to the anus. In descending order of frequency, the following are locations of gastrointesti­ nal tract involvement\: ileocecal region (ileocolitis) > terminal ileum only (ileitis) > colon only > mouth or gastroduode­ nal area > esophagus. The etiology of Crohn’s disease is still unknown.
Clinical Features\:
The onset of symptoms in Crohn’s disease is typically insidi­ ous. Most patients will have recurring episodes of abdomi­ nal pain, nonbloody diarrhea, weight loss, fever, and fatigue interspersed with periods of remission. As with ulcerative colitis, extraintestinal manifestations are frequently encoun­ tered with Crohn’s disease (see Table 8-1). However, consider the clinical manifestations of Crohn’s disease based on the
• Become familiar with the equivalent fractions and per­ centages\: one-quarter normal saline (0.22% NaCl), one- third normal saline (0.3% NaCl), one-half normal saline (0.45% NaCl), and normal saline (0.9% NaCl).
• Most patients with pyloric stenosis are “chloride responsive” and can be treated by replacing the chloride through saline solution and KC1, which in turn will enhance renal bicarbon­ ate excretion.
• Failure to correct the alkalosis prior to surgery can lead to postoperative apnea.
• Administering oral erythromycin, especially in the first 2 weeks of life, has been associated with pyloric stenosis.
• Hypokalemia is typically seen in patients who have been vomiting for a period of time (ie, >3 weeks).
• No single sign is pathognomonic in the upper GI contrast study, but possible findings include the “beak” sign (tapered pyloric canal), “shoulder” sign (dilated prepyloric antrum), "string” sign (narrowed pyloric lumen), or “double-track” sign (2 tracks of barium as a result of a compressed pyloric mucosa).
• On the CCS, prior to the exam day, type in “fluids” in the order menu, and become familiar with the different types of fluids and when you would want to use them.
• On the CCS, informed consent is assumed for any procedure that you order. In addition, consent is also given for any child or infant in the cases.
following affected gastrointestinal location in a superior to inferior direction\:
Esophagus—Dysphagia, odynophagia
Stomach—Upper abdominal pain, symptoms of gastric outlet obstruction due to fibrotic strictures
Intestines—Small bowel or colonic obstruction, periumbil­ ical pain, RLQ pain, steatorrhea, phlegmon, malabsorption, “bile salt” diarrhea, constipation secondary from an ob­ struction, abscess, sinus tracts, fistulas (ie, bowel to bowel, bowel to bladder, bowel to vagina, or bowel to skin)
Perianal—Perianal fistulas, fissures, perirectal abscess, anal stenosis, hemorrhoids
Next Step\:
Step 1) The diagnosis of Crohn’s disease is based on a com­ patible clinical picture along with supportive endoscopic or imaging studies.
Endoscopy
Colonoscopy—Colonoscopy with biopsy can increase the diagnostic accuracy. To establish a diagnosis in the ileocecal region, a colonoscopy with a terminal ileum intubation (ie, ileoscopy) should be performed. Endoscopic findings may reveal a “cobblestone” appearance, focal ulcerations, linear
CHAPTER 8 GASTROENTEROLOGY 95

96 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Table 8-1 • Extraintestinal Manifestations Seen in Crohn's Disease and Ulcerative Colitis
System
Neurologic Ocular
Oral
Cardiac Respiratory Hepatobiliary
Renal Musculoskeletal Dermatologic Hematologic
.
Manifestations
Peripheral neuropathy, myelopathy, myasthenia gravis, pseudotumor cerebri Episcleritis, anterior uveitis
Aphthous ulcers
Pericarditis, myocarditis, endocarditis
Pulmonary fibrosis, vasculitis, bronchitis, bronchiectasis, interstitial lung disease, BOOP
Cholelithiasis, cholangiocarcinoma, primary sclerosing cholangitis (PSC), pericholangitis, autioimmune hepatitis, fatty liver
Calcium oxalate and uric acid kidney stones, hydronephrosis, amyloidosis
Arthritis (eg, sacroiliitis, ankylosing spondylitis, peripheral arthritis), osteoporosis
Erythema nodosum, pyoderma gangrenosum
Vitamin B12 deficiency, folate deficiency, iron deficiency, anemia of chronic disease, autoimmune hemolytic anemia, thromboembolism
ulcers, stellate ulcers, serpiginous ulcers, aphthous ulcers (not just the mouth), normal rectum, normal vascular pattern ad­ jacent to affected tissue, discontinuous lesions (“skip lesions”), edema, strictures, or pseudopolyps. Histological findings may reveal crypt abscesses, crypt atrophy, mixed acute and chron­ ic inflammation, noncaseating granulomas, or deep fissures.
Esophagogastroduodenoscopy (EGD)—EGD is effective when there is gastroduodenal involvement. EGD is also helpful in differentiating Crohn’s disease from other gastro­ intestinal diseases (eg, peptic ulcer disease).
Capsule (“pill”) endoscopy—The indications for capsule endoscopy are still evolving, however it is being used more frequently in patients with Crohn’s disease with suspected small bowel involvement. Capsule endoscopy should not be used in patients with suspected strictures since it can lead to an obstruction.
Imaging Studies
Upper GI series—An upper GI series with small bowel follow-through (SBFT) is typically the initial test to evaluate the small intestines. Possible findings may include ulcer­ ations, abscess formation, “string” sign (luminal narrow­ ing), fistulas, bowel wall thickening, segmental stricturing, nodularity, or cobblestone appearance.
Barium enema—Barium enema can be performed to evaluate the lower bowel, but it should be considered as an alternative when colonoscopy cannot be performed.
Adjunctive Studies
CBC—Leukocytosis may be detected due to an abscess, chronic inflammation, or steroid treatment. Anemia may also be detected due to iron deficiency, vitamin B|2 deficiency, or folate deficiency.
CMP—Hypoalbuminemia is common in Crohn’s patients. Liver function tests may be elevated due to PSC or perichol­ angitis.
ESR or CRP—Typically elevated in patients with Crohn’s disease.
ASCA—Usually positive in Crohn’s disease. p-ANCA—Usually negative in Crohn’s disease.
Stool for occult blood—Frequently test positive, but typi­ cally no gross blood is seen.
Stool culture, bacterial—Normal flora.
Stool for white cells—Leukocytes may be seen, indicative
of gut inflammation.
Stool for ova and parasites—Negative.
Stool for C difficile toxin assay—Negative.
Stool fat, 72-hour—Usually elevated in patients with bacterial overgrowth or bile acid malabsorption.
Step 2) The goal of therapy is to achieve remission and maintain remission. Consider the different stages of treatment\:
Active Disease
Glucocorticoids—Prednisone may be used for a short course of therapy for active disease. Budesonide is another glucocor­ ticoid that appears to be less effective than conventional glu­ cocorticoids, but has the advantage of inducing less systemic side effects because of a high first-pass hepatic metabolism.
5-Aminosalicyclic acid (ASA)—The use of 5-ASA deriva­ tives for Crohn’s disease is controversial. Although some authorities continue to use 5-ASA in the management of Crohn’s, it should be noted that there is a clearer therapeutic benefit for patients with ulcerative colitis.
Antibiotics—Similar to 5-ASA agents, the utility of antibi­ otics is not well established. Aside from treating an abscess or a wound infection related to Crohn’s disease, the use of metronidazole or the combination of metronidazole and ciprofloxacin are still used to treat active Crohn’s disease.
Refractory Disease
Immunomodulators—Azathioprine (AZA) or 6-mercap- topurine (6-MP) are used in patients that are refractory to steroid therapy or as a steroid-sparing agent in attempt to with­ draw steroids from steroid-dependent patients. Methotrexate

(MTX) is an alternative drug for patients that have contrain­ dications or do not respond to AZA or 6-MP therapy.
Biologic therapies—Anti-TNF therapies such as infliximab, adalimumab, and certolizumab pegol are typically used in Crohn’s patients that are refractory to conventional treatment.
Surgery—Surgery is considered in patients that have symp­ toms refractory to optimal medical therapy or development of a complication related to Crohn’s disease.
Severe Disease
Hospitalize—Patients with severe disease will typically have persistent symptoms despite optimal medical therapy as an outpatient. Patients should be admitted to the hospital for bowel rest, intravenous glucocorticoids (eg, prednisolone), and parenteral nutrition. Broad-spectrum antibiotics (IV met­ ronidazole + IV ciprofloxacin) should be added in patients with fevers, elevated white count, fulminant features (ie, abruptly occurring symptoms), or any indication of toxicity.
Maintenance Therapy
Immunomodulators—AZA, 6-MP, and MTX are used for maintenance remission.
Biologic therapies—The anti-TNF agents are used for maintenance remission.
Glucocorticoids—Conventional glucocorticoids are not effe­ ctive in maintaining remission; however, budesonide has been approved for maintenance remission for up to 3 months.
Step 3) The risk of colon cancer in Crohn’s disease and ulcer­ ative colitis appears to be equivalent for a similar extent and duration of disease. Therefore, in patients with Crohn’s colitis, surveillance colonoscopy is typically started after 8 years of dis­ ease followed by annual examinations.
Follow-Up;
Patients with mild to moderate active Crohn’s disease can be man­ aged as an outpatient with close follow-up with their physician.
Pearls\:
• Microscopic GI bleeding can occur, but there is usually no gross bleeding.
• Be aware that extraintestinal manifestations may be the ini­ tial complaint in patients with inflammatory bowel disease.
• Thiopurine methyltransferase (TPMT) genotype or pheno­ type testing is recommended before the initiation of AZA or 6-MP therapy to prevent unwanted toxicities and to make the appropriate empiric dose adjustments.
• On pathological examination of diseased bowel in Crohn’s disease, sometimes mesenteric fat will wrap around the bow­ el surface (“creeping fat”).
• Since transmural inflammation can reach the serosal level, the inflammation itself can promote adhesion of the bowel surface to the mesentery.
• Endoscopy is considered a primary tool in the diagnosis of inflammatory bowel disease because it allows for direct
visualization and targeted biopsies, which usually leads to a definitive diagnosis. However, an endoscopy should not be performed if there is a toxic megacolon, severe acute colitis, or a patient cannot undergo adequate bowel preparation.
• The terminal ileum is the site for bile salt and vitamin B12 absorption.
• “Bile salt” diarrhea occurs when bile salts are not absorbed at the terminal ileum because of disease or resection in that region, which results in bile salts entering the colon causing a secretory diarrhea.
• Patients with bile salt diarrhea may benefit from bile acid sequestrants (eg, cholestyramine, colestipol).
• Steatorrhea may be the result of bacterial overgrowth or bile acid malabsorption (hence elevated stool fat content in the 72-hour collection).
• Avoid antidiarrheal agents (eg, loperamide) in patients with active colitis since they can precipitate a toxic megacolon.
• Infliximab has been approved for fistulizing Crohn’s disease.
• Foundational point—Azathioprine (AZA) is an immuno­ suppressant agent that is first converted to 6-mercaptopurine (6-MP) and eventually into a nucleotide, thioinosinic acid. The nucleotide analogs can inhibit enzymes involved in purine metabolism and have a cytotoxic effect on lymphoid cells.
• Connecting point (pg. 289)—Biologic agents are also used in patients with rheumatoid arthritis. Prior to treatment, remember to perform latent TB screening with a PPD.
• Connecting point (pg. 252)—Know the management for a positive PPD.
• On the CCS, “advise patient, medication compliance.”
• On the CCS, “advise patient, side effects of medication.”
• On the CCS, try to practice the CCS on a computer with each chapter you review so that you can become familiar with the possible options in that particular field.
1 ULCERATIVECOLITIS
Ulcerative colitis (UC) is a chronic inflammatory condition that involves the mucosal layer of the colon that can lead to diffuse friability and erosions with bleeding. The rectum is vir­ tually always involved and extends proximally in a continuous retrograde fashion. Approximately 50% of patients will have disease confined to the rectosigmoid region (proctosigmoid­ itis), 30% extend to the splenic flexure (left-sided colitis), and 20% extend beyond the splenic flexure and even up to the cecum (pancolitis). Similar to Crohn’s disease, the etiology of ulcerative colitis is unknown (see Table 8-2).
Clinical Features\:
The clinical course of ulcerative colitis is of a chronic intermit­ tent exacerbation interspersed with periods of remission. In some patients, the first attack is followed by a prolonged period of inactivity. Possible clinical findings may include abdominal pain, bloody diarrhea, weight loss, fever, tenesmus, passage of
CHAPTER 8 GASTROENTEROLOGY 97

—98 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Table 8-2 • Distinctive Features of Inflammatory Bowel Disease (IBD)
Features
Etiology
Age of onset
Ethnicity
Genetics
Smoking
Appendectomy
Perianal involvement
Rectal involvement
Colon involvement
Terminal ileum involvement
Distribution
Segmental colitis
Depth of inflammation
Granulomas
Ulcers
Pseudopolyps
"Cobblestone" appearance
Mesenteric encased bowel ("Creeping fat")
Crypt abscess Crypt atrophy Fistulas Strictures
Gross blood Mucus
Bloody diarrhea Bile salt diarrhea
Severe abdominal pain
Extraintestinal manifestations
Risk of colon cancer ASCA
p-ANCA
Fecal leukocytes Recurrence after surgery 5-ASA agents Methotrexate
Crohn's Disease (CD) Unknown
Bimodal (15-40 and 50-80)
Jewish > Non-Jewish
First-degree relative may have either CD or UC Increases risk
Appears to increase the risk of developing CD Yes, approximately 30% of patients
Spared
Usually
Common
Skip lesions
Yes
Transmural
Noncaseating granulomas Yes
Yes Yes
Yes
Yes
Yes
Yes Common No Sometimes No
If there is diseased or resected terminal ileum
Common Yes
Yes
Positive
Negative
Yes
Yes
Used, but controversial Used
Ulcerative Colitis (UC) Unknown
Bimodal (15-40 and 50-80)
Jewish > Non-Jewish
First-degree relative may have either CD or UC Decreases risk
Appears to be protective against the development of UC No
Almost always
Always
Sometimes ("Backwash ileitis")
Continuous
No
Mucosal, sometimes submucosal No
Yes
Yes
No
No
Yes
Yes
No Sometimes Yes
Yes Yes
Rare, unless there is diseased terminal ileum from "backwash ileitis"
Sometimes Yes
Yes
Negative
Positive
Yes
No
Clear therapeutic benefit Not supported

mucus, anemia, tachycardia, or red blood on rectal examina­ tion. As with Crohns disease, extraintestinal manifestations are encountered in ulcerative colitis (see Table 8-1). However, consider the severity of the disease in ulcerative colitis\:
Mild disease—Clinical findings may include\: <4 bowel movements per day, small amounts of blood in the stool, no fevers, no weight loss, no tachycardia.
Moderate disease—Clinical findings may include\: 4 to 6 bowel movements per day, moderate amounts of blood in the stool, low-grade fevers, some weight loss, heart rate in the upper limit of normal, mild anemia.
Severe disease—Clinical findings may include\: >6 bowel movements per day, large amounts of blood in the stool, fevers, weight loss, tachycardia, hypovolemia, anemia.
Next Step\:
Step 1) The diagnosis of ulcerative colitis is based on a compatible clinical picture along with endoscopy.
Endoscopy
Flexible sigmoidoscopy—In patients with an acute flare, flexible sigmoidoscopy can provide an adequate diagnosis since it can assess the disease activity (see endoscopic find­ ings in Colonoscopy section) and exclude other diagnosis (eg, infectious or ischemic colitis).
Colonoscopy—Colonoscopy with biopsy can make the definitive diagnosis in equivocal cases, but it should not be performed during an acute flare or in severe disease since it may precipitate a toxic megacolon or cause a per­ foration. Endoscopic findings may reveal an erythematous mucosa, granular surface, friability, spontaneous bleeding, erosions, pseudopolyps, purulent exudates, edema, loss of normal vascular pattern, continuous and circumferen­ tial involvement, or ulcerations extending into the sub­ mucosa in more severe disease. Histologic findings may reveal crypt abscesses, crypt atrophy, or diffuse mixed inflammation.
Adjunctive Studies
Plain abdominal x-ray—Colonic dilatation may be seen in patients with severe colitis.
CT abdomen—Bowel wall thickening may be seen but is nonspecific.
Barium enema—Not commonly used since the advent of flexible sigmoidoscopy and colonoscopy. Findings may reveal pseudopolyps, collar button ulcers (ie, penetration through the mucosa), or loss of haustra (lead-pipe appear­ ance). Barium enema should be avoided in patients with severe disease since it may precipitate a toxic megacolon.
CBC—Leukocytosis, anemia, and thrombocytosis may be present.
CMP—Hypoalbuminemia is often found in extensive dis­ ease. LFTs may be elevated due to PSC or pericholangitis.
ESR or CRP—Elevated, which usually correlates with disease activity.
ASCA—Usually negative in ulcerative colitis. p-ANCA—Usually positive in ulcerative colitis.
Stool for occult blood—Positive, and on examination, gross blood with mucus is usually seen.
Stool culture, bacterial—Normal flora.
Stool for white cells—Fecal leukocytes are usually present. Stool for ova and parasites—Negative.
Stool for C difficile toxin assay—Negative.
Step 2) Therapy is based on the severity and extent of the disease. Consider the different stages of treatment\:
A—Active Disease
Proctitis (rectum)
Mild to moderate disease\:
Option 1\: 5-ASA suppository
Option 2\: Hydrocortisone foam (rectal) Option 3\: Hydrocortisone suppository
Severe disease —> Hospitalize Fulminant disease Hospitalize
Proctosigmoiditis (rectum + sigmoid) Mild to moderate disease\:
Option 1\: 5-ASA enema
Option 2\: Hydrocortisone enema Severe disease —» Hospitalize Fulminant disease —» Hospitalize
Left-sided colitis or pancolitis
Mild to moderate disease\:
Oral 5-ASA + Suppository (5-ASA or steroid) + Enema (5-ASA or steroid)
Severe disease —> Hospitalize Fulminant disease —» Hospitalize
B—Refractory Disease
Glucocorticoids—Oral steroids (eg, prednisone) are usu­ ally considered when there is an inadequate response to maximal tolerated dosage of 5-ASA agents. Once remission is achieved, a gradual taper can begin.
Azathioprine (AZA) or 6-mercaptopurine (6-MP)— AZA or 6-MP is usually considered in patients who are ste­ roid dependent and/or steroid refractory. The onset of full activity for both AZA and 6-MP can take up to 3 to 6 months. TPMT testing should be performed before therapy.
Infliximab—Infliximab is an available option for patients who are not responding to corticosteroids, AZA, or 6-MP, but have reservations about undergoing surgery or want to avoid the side effects of cyclosporine (eg, neurotoxic, neph­ rotoxic, hypertension, T risk of skin cancer).
Cyclosporine—Cyclosporine (calcineurin inhibitor) has a rapid onset of action and is considered a last-ditch effort for
CHAPTER 8 GASTROENTEROLOGY 99

100
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
medical intervention. It is an option for patients who have Follow-Up\:
failed intravenous steroids, but do not want to have surgery. Cyclosporine is usually given as an intravenous infusion,
and then can be switched to PO for outpatient use for a few
months, but not for long-term maintenance. Pearls\:
Surgery—Surgery is an option for patients that have failed cyclosporine, infliximab, or intravenous steroids. Unlike Crohn’s disease, a colectomy can lead to a cure in ulcerative colitis.
C—Severe Disease
Severe disease\: Patients with severe disease have the potential to progress to toxic megacolon or fulminant colitis. The follow­ ing actions should take place\:
1) Hospitalizethepatient
2) NPO, IV fluids, electrolyte correction
3) Intravenous glucocorticoids (eg, prednisolone)
4) Consider surgery or IV cyclosporine in patients who do respond to IV steroids after 7 to 10 days.
Acute severe (fulminant) disease\: Patients with fulminant disease will have a rapid progression of severe toxic symptoms (eg, rapid weight loss, fever, severe bloody diarrhea, peritoneal signs), which can progress to toxic megacolon or bowel perfora­ tion. The following actions should take place\:
1) Hospitalizethepatient.
2) NPO, IV fluids, electrolyte correction.
3) Nasogastric suction if obstruction or toxic megacolon is suspected.
4) Abdominalx-rays.
5) Intravenous glucocorticoids (eg, prednisolone).
6) Broad-spectrum antibiotics are usually given in patients with fever, leukocytosis, elevated bands, peritoneal signs, or suspicion for toxic megacolon. Recommended antibiotics include\:
IV metronidazole (covers anaerobes) + IV ciprofloxacin (covers gram-negatives).
7) Consider surgery in patients who fail to improve in 48 to 72 hours to prevent a perforation.
D—Maintenance Therapy
Proctitis\: 5-ASA suppository; avoid IV and PO steroids to prevent systemic side effects
Proctosigmoiditis\: 5-ASA enema; avoid IV or PO steroids to prevent systemic side effects
Left-sided colitis and pancolitis\: Oral 5-ASA ± 5-ASA enema; avoid IV or PO steroids to prevent systemic side effects
Steroid-dependent colitis\: 6-MP, AZA, or infliximab (for those who responded to induction therapy)
Step 3) Since patients are at risk of colon cancer, a colono­ scopic surveillance should start after 8 years of disease and then annually.
• “Backwash ileitis” refers to the presence of inflammation at the terminal ileum in patients with ulcerative colitis that have pancolitis.
• “Backwash ileitis” can be differentiated from Crohn’s ileocolitis by obtaining a colonoscopy with ileoscopy and biopsy (ie, gran­ ulomatous inflammation should be seen in Crohn’s disease).
• The 5-ASA agents include sulfasalazine, mesalamine, bal- salazide, and olsalazine.
• Sulfasalazine is the original drug in the 5-ASA class, but it has unfavorable side effects such as nausea, vomiting, headache, dys­ pepsia, pruritus, fever, rash, male infertility, and agranulocytosis.
• Mesalamine is better tolerated and has fewer adverse effects than sulfasalazine.
• All the 5-ASA agents can be given orally, but mesalamine can also be given as an enema or as a suppository.
• Suppositories are generally effective in the rectum, but en­ emas can reach the sigmoid colon and potentially up to the splenic flexure.
• Hydrocortisone is available in PO, IV, IM, enemas, supposi­ tories, and foams.
• Patients with toxic megacolon (ie, colonic dilatation >6 cm) are managed the same as fulminant disease. In addition, nasogastric suction should be initiated and patients should roll side to side intermittently to help redistribute the gas.
• Antidiarrheals should not be used during acute flares or se­ verely ill patients.
• Patients with ulcerative colitis are at risk of colon cancer, but it also appears that having concomitant primary sclerosing cholangitis (PSC) increases the risk of colon cancer.
• Pseudopolyps are commonly seen in patients with long­ standing disease and are the result of epithelial regeneration.
• Pseudopolyps are commonly seen in ulcerative colitis, but they are not specific for the disorder.
• Periappendiceal inflammation (“cecal patch”) can sometimes be seen in patients with ulcerative colitis but may not be con­ tiguous with the disease.
• Most of the studies on serologic markers have revolved around antibodies to the yeast Saccharomyces cerevisiae (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (p-ANCA).
• A colonoscopy can assess the disease activity as well as the extent of the disease in ulcerative colitis.
• Foundational point—Sulfasalazine is a sulfa drug that is poorly absorbed in the small intestine, but when it reaches the colon the intestinal bacteria splits the drug into sulfa- pyridine (antibacterial) and 5-aminosalicylic acid (anti­ inflammatory). The 5-ASA (ie, mesalamine) is the active component of sulfasalazine. It should be noted that balsala- zide and olsalazine are prodrugs that are also converted to the active form of 5-ASA (ie, mesalamine) by colonic bacteria.
Patients that are receiving AZA or 6-MP require weekly blood moni­ toring for the first month to minimize the dose-dependent toxicides.

• On the CCS, ifyou want to order mesalamine as an enema or suppository, it will only be recognized as “rectal” under the route of administration.
PANCREAS
I PANCREATICPSEUDOCYST
Pancreatic pseudocysts are localized fluid collections of pancre­ atic enzymes that are encased by fibrous and granulation tissue (ie, no epithelial lining, hence “pseudo” cyst). Pancreatic pseu­ docysts are seen following acute pancreatitis, chronic pancreati­ tis, or blunt trauma (frequently associated with children).
Clinical Features\:
There are no signs or symptoms that are pathognomic for pan­ creatic pseudocysts. Pseudocysts should be considered in pa­ tients with a history of pancreatitis or trauma that present with persistent abdominal pain, abdominal mass, or anorexia. The clinical progression of the pseudocyst can be affected by many factors. Consider the following\:
Infection—An infected pseudocyst can lead to fever, leuko­ cytosis, or a tender epigastric mass.
Expansion—Abdominal pain, abdominal mass, abdominal fullness.
Obstruction—Biliary or duodenal obstruction can lead to jaundice, scleral icterus, nausea, or vomiting.
Fistulization—Fistulization into the abdomen (ie, ascites) or chest (ie, pleural effusions).
Rupture—Rupture of the pseudocyst can result in perito­ neal signs.
Erosion—Erosion into an adjacent vessel can result in a “pseudoaneurysm.” If there is a communication between the pseudocyst and the pancreatic duct, blood may now flow through the ampulla of Vater and into the GI tract (ie, hemosuccus pancreaticus), which may be the cause of unexplained anemia. If there is no communication between the pseudocyst and the pancreatic duct, the pseudocyst will simply enlarge and cause abdominal pain.
Next Step\:
Step 1) After a careful clinical assessment, especially in a patient with a history of pancreatitis or trauma with persistent abdominal pain, the first-line imaging modality is an abdominal CT scan. However, consider the features of the following imaging modalities\:
Ultrasound
• Ultrasound has a sensitivity of 75% to 90%.
• Overlying bowel gas can decrease the sensitivity.
• Useful in distinguishing solid from cystic masses.
• Visualization is limited by patients habitus.
• Technique is highly operator dependent.
•
On the CCS, if you need a consult during the case, type in “consult” in the order menu and a robust list of consults are available for you to choose.
CHAPTER 8 GASTROENTEROLOGY 101
CT Scan
• CT scan has a sensitivity of 90% to 100%.
• CT scan can provide information of the surrounding anat­ omy such as pancreatic duct dilatation, common bile duct dilatation, calcifications, pseudoaneurysm, and extension of the pseudocyst.
• CT scans cannot differentiate pseudocysts from pancreatic cystic neoplasms.
MRCP
• MRCP is not routinely performed as the initial diagnos­ tic test because CT scans provides most of the diagnostic information.
ERCP
• ERCP is not necessary to establish a diagnosis of a pancreatic pseudocyst, but it may be useful in planning a strategy for drainage.
Endoscopic Ultrasound (EUS)
• EUS is often performed when there is diagnostic uncer­ tainty because it provides high-quality images due to the close proximity of the ultrasound transducer to the area of interest, and the lesion can be sampled through fine needle aspiration (EUS-FNA), which can then be ana­ lyzed for cytology, molecular markers, or tumor markers (eg, CEA level).
• EUS is helpful in planning pseudocyst drainage sites since it can detect small portal collaterals (eg, gastric varices) that would otherwise not be detected by other means, which would potentially reduce the risk of bleeding.
Step 2) Management of pancreatic pseudocysts involves obser­ vation or intervening with some type of draining procedure.
No Intervention
• Most pseudocysts will resolve with supportive care.
• Medical supportive care may include analgesics, antiemetics, IV fluids, and TPN or nasoenteral feeding if the patient cannot tolerate oral intake.
Intervention
• Indications to intervene are the presence of symptoms or complications of the pseudocyst such as infection, bleeding, or gastric outlet or biliary obstruction.
• Drainage ofthe pseudocyst can be accomplished by surgery, endoscopy, or percutaneous catheter drainage using CT or US guidance.

102 CLINICAL JUDGMENT U5MLE STEP 3 REVIEW
Follow-Up\:
Patients that have stents in place for drainage or are being ob­ served are usually monitored by simple palpation on daily exam and serial CT scans to observe for resolution of the pseudocyst.
Pearls\:
• Pancreatic pseudocysts can be single or multiple.
• Pancreatic pseudocysts may have communication or no communication with the pancreatic ductal system.
• Pancreatic cysts may be associated with von Hippel-Lindau disease or polycystic kidney disease.
• Although larger-sized pseudocysts are prone to cause more symptoms and complications, the size or duration of the pseudocyst (ie, greater than 6 cm or longer than 6 weeks) is not an indication to intervene.
• To date, there are no randomized comparative studies be­ tween endoscopic, surgical, and percutaneous drainage. Therefore, the type of drainage procedure is often based on local expertise.
• Pancreatic abscess is a liquid collection of pus that can be formed secondary to an infected pseudocyst.
• Pancreatic abscesses should be drained, usually by surgery or percutaneous techniques.
• Amylase levels are usually high within the pseudocyst, but low in pancreatic cystic neoplasms.
• There are 4 main subtypes of pancreatic cystic neoplasms, which include serous cystic tumors, mucinous cystic neo­ plasms, intraductal papillary mucinous neoplasms, and solid
CCS\: EARLY GASTRIC CANCER CASE INTRODUCTION
Day 1 @ 14\:00 Office
A 50-year-old Asian man comes to the office because of mild epigastric pain.
Initial Vital Signs\:
Temperature\: 37.0°C (98.6°F)
Pulse\: 68 beats/min, regular rhythm Respiratory\: 18/min
Blood pressure\: 120/75 mm Hg Height\: 162.6 cm (64.0 inches) Weight\: 81.8 kg (180 lb)
BMI\: 30.9 kg/m2
Initial History\:
Reason(s) for visit\: Epigastric pain
pseudopapillary neoplasms. Of the four subtypes, serous cystadenomas have little to no malignant potential.
• History and imaging features of pancreatic cystic neo­ plasms that might be worrisome include no history of pan­ creatitis or trauma, dilated pancreatic duct or branches, solid component, mural nodularity, septated cyst, macro- septation, multiloculated microcystic appearance, grape­ like clusters, honeycomb pattern, external lobulation, or central scar.
• CJ\: A 50-year-old man with known pancreatic pseudocyst has sudden abdominal pain, presence of abdominal bruit, a slight drop in blood pressure, and is stool hemoccult positive with an unexplained GI bleed. How do you manage this patient? Answer\: The first step in this patient, who has a pseudoaneurysm, is to stabilize him (eg, fluids). Ultimately, the patient needs to have a mesenteric angiography, which can confirm the diagnosis, and at the same time, perform an embolization of the bleeding vessel. It should be noted that any patient with suspected pseudoaneurysm should not undergo endoscopic drainage unless arterial embolization is performed first.
• On the CCS, “angiography, mesenteric” is available in the practice CCS.
• On the CCS, remember to monitor your patients (eg, physical exam) after any kind of treatment.
• On the CCS, suboptimal management would be to make an incorrect diagnosis, since erroneously treating a pan­ creatic cystic neoplasm as a pseudocyst can lead to serious problems.
HPI\:
The patient, a 50-year-old grocery store manager, has been experiencing mild epigastric pain without radiation for the past 4 months. The pain is described as a “gnawing pain” that occurs shortly after meals. He rates his pain as a 5 on a 10-point scale. He has not taken any over-the-counter medications to alleviate his pain. He has tried drinking warm milk and hot tea without success. Lying down on the couch or bending over does not exacerbate the pain. He continues to have a normal appetite without early satiety. He denies having fevers, chills, dysphagia, regurgitation, bloody stools, passage of mucus, or unintended weight loss. He denies any trauma or recent travel.
Past Medical History\: None Past Surgical History\: None Medications\: None

Allergies\: Vaccinations\: Family History\:
Social History\:
None
Up to date
Father died of gastric cancer at age 58. Mother, age 75, has hyper­ tension. One sister, age 48, is healthy. Smokes one pack per day x 30 years; drinks 5 to 6 beers after work and drinks whiskey and vodka on the weekends; denies use of illegal drugs; eats a high- salt diet with low vegetables; eats a sufficient amount of cured meats; married; three children; works as a full-time grocery store manager; enjoys hosting dinner parties for friends and family.
See HPI Negative Negative Negative Negative See HPI Negative Negative
Well nourished, well developed; in no apparent distress.
Normal turgor. No lesions. Hair and nails normal.
No lymphadenopathy. Normocephalic. EOMI, PERRLA. Hearing normal. Ear, nose, mouth normal. Pharynx normal. Neck supple; trachea midline; no masses or bruits; thyroid normal.
Chest wall normal. Diaphragm and chest moving equally and symmetri­ cally with respiration. Auscultation and percussion normal.
SI and S2 normal. No murmurs, rubs, gallops, or extra sounds. No JVD. Normal bowel sounds; no bruits. Tenderness in the epigastric area. No masses. No abnormality on percussion. No rebound. No guarding. No rigidity. No hernias. No hepatosplenomegaly. Normal sphincter tone. No masses. No occult blood; stool brown.
2)BMP,routine
3) Lipase, serum, routine
4) Amylase, serum, routine
5) H.pyloriantibody, serum, routine
6) Stoolforoccultblood,routine
Second Order Sheet\:
1) Consult, gastroenterology,
routine
2) EGDwithbiopsy,routine
Result\: Glu-90,Urea-10, Na-141, K-3.9, Cl-101, HC03-23, Cr-l.O, Ca-9.2
Result\: 0.50 U/mL (nl\: 0.10-1.00)
Result\: 100 U/L(nL 25-125)
Result\: IgGantibody- Positive, IgA antibody-
Positive
Result\: Negative
Reason\: EGD with biopsy to rule out cancer and
H. pylori
Result\:Endoscopic examination shows an ulcerated circumferential mass measuring 30 mm in the antrum of the stomach without active bleeding. Esophageal and duodenal mucosa normal. Pathology results will be reported in approximately 24 hours.
Result\: H. pylori detected
Review of Systems\: General\:
Skin\:
HEENT\: Musculoskeletal\: Cardiorespiratory\: Gastrointestinal\: Genitourinary\: Neuropsychiatric\:
Day 1 @ 14\:10
Physical Examination\: General appearance\:
Skin\:
Lymph nodes\: HEENT/Neclc
Chest/Lungs\:
Heart/Cardiovascular\: Abdomen\:
Rectal\:
3)
H. pylori stain gastric biopsy, routine
First Order Sheet\:
1) CBC with differential, routine
Actions\:
1) Changelocationtooffice
Fourth Order Sheet\:
1) Advise patient, cancer diagnosis
2) CT,abdomen/pelvis, with contrast, routine
Result\:Nofocaldefectseen in the liver, spleen, kidneys, and pancreas. Gallbladder appears normal. No para­ aortic adenopathy
Result\: WBC-9,000, H/H-14/45%, Pit-150,000, Differential-WNL
Third Order Sheet\:
1) Lansoprazole, oral, continuous
CHAPTER 8
GASTROENTEROLOGY 103
2) Amoxicillin, therapy, oral, continuous
3) Clarithromycin, oral, continuous
4) Advisepatient,sideeffectsofmedication
Actions\:
1) Change location to home
Gastric mucosa biopsy result is now available
(24 hours later)\:
Presence of intestinal-type gastric adenocarcinoma at the level of the submucosa without invasion into the muscularis propria.

104 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
3) Chest x-ray, PA/lateral, routine
4) PET scan, routine
5) LFT, routine
6) PT/INR, routine
7) PTT, routine
Result\: Normal findings
Result\: No abnormal metabolic activity
Result\: AST-35, ALT-15, Albu­ min-4.0, T Bil-0.9, Direct Bil-0.2, Total protein-7.2, Aik Phos-72
Result\: PT-7 seconds (nl\: <12), INR-1.0 (nl\: 1.0-1.3)
Result\: 22 seconds (nl\: <28)
Risk Factors\:
H. pylori, high salt intake, low intake offruits and vegetables, di­ etary nitrates, obesity, smoking, EBV infection, gastric surgery, gastric ulcers, blood group A, pernicious anemia, family history, hereditary diffuse gastric cancer (HDGC), heavy alcohol drink­ ing (moderate alcohol drinking has no dear association with an increased risk for gastric cancer)
Clinical Features\:
Patients with early gastric cancer may be completely asymp­ tomatic, and if they are symptomatic, the symptoms are usu­ ally nonspecific. Since gastric cancers and gastric ulcers share a common risk factor (H. pylori), some patients will have mani­ festations of a gastric ulcer. It should be noted that duodenal ulcers have not been shown to increase the risk of gastric can­ cers. Although the clinical history cannot accurately differen­ tiate gastric from duodenal ulcers, the following findings may be suggestive of either gastric or duodenal ulcers. A “gnawing” or “burning” sensation may occur after meals in both gastric and duodenal ulcers. Gastric ulcer pain typically occurs shortly after meals, but 2 to 5 hours later in patients with duodenal ulcers. Approximately two-thirds of duodenal ulcers and one- third of gastric ulcers and nonulcer dyspepsia (NUD) will have nocturnal pain with awakenings during sleep. Duodenal ulcers are usually relieved with food or antacids, while in gastric ul­ cers, antacids usually provide minimal relief and food precipi­ tates the pain.
In more advanced, invasive gastric cancers, patients may present with “alarm features” such as unexplained weight loss, recurrent vomiting, hematemesis, melena, anemia, dysphagia, odynopha­ gia, abdominal mass, jaundice, early satiety, bloating, or family history of gastric cancer. In addition, physical exam may reveal hepatomegaly, left-sided supraclavicular lymph node (Vir­ chow’s nodes), periumbilical nodule (Sister Mary Joseph node), left axillary node (Irish node), a mass in the cul-de-sac on rec­ tal exam (Blumer’s shelf), or ovarian metastasis (Krukenberg’s tumor). Paraneoplastic syndromes can also be seen in advanced disease such as acanthosis nigricans, seborrheic keratoses, der- matomyositis, Trousseau’s syndrome, or microangiopathic he­ molytic anemia.
Next Step Summary\:
Step 1) In a patient with multiple risk factors for gastric cancer but without “alarm” symptoms, there are two considerations for the workup\: (1) determine if H. pylori is present so that you can appropriately treat it, and (2) determine if there is an ulcer that might be malignant. Consider the following strategies in this patient with epigastric pain not caused by NSAIDs.
Option 1\: Empirically treat with antisecretory therapy (eg, PPIs, H2 antagonists).
Caveat 1\: This may delay the diagnosis of H. pylori, delay the diagnosis of gastric cancer, and have potentially false negative results with further diagnostic testing for H. pylori if antisecre­ tory products are taken.
Fifth Order Sheet\:
1) Consult,generalsurgery,routine
Reason\: Biopsy confirms gastric adenocarcinoma, T1 lesion, in the lower two-thirds of the stomach.
General surgery consult recommendations\: After discussion with the patient regarding alternative treatments, risks and ben­ efits with surgery, the patient agrees with surgery. A subtotal gastrectomy is scheduled for tomorrow morning. Thank you for the consult.
This case will end in the next few minutes of “real time ” You may add or delete orders at this time,
then enter a diagnosis on the following screen.
Sixth Order Sheet\:
1) Urea breath test, routine
Future date\: In 60 days
2) Counselfamily/patient
3) Advise patient, no smoking
4) Advise patient, no alcohol
5) Low sodium diet
Result\: No radiolabeled carbon dioxide detected.
Please enter your diagnosis\: Early Gastric Cancer (EGC)
DISCUSSION\:
Gastric cancer is a very common cancer worldwide. Rates are highest in Asia, South America, and Eastern Europe, but lowest in North America. Approximately 85% of gastric cancers are adenocarcinomas, and 15% are due to leiomyosarcomas, gastro­ intestinal stromal tumors (GIST), and lymphomas (eg, MALT lymphomas). Adenocarcinomas can be subdivided into diffuse type and intestinal type. Intestinal type is the more common type of adenocarcinoma, and is typically seen in older people and males. Diffuse type (infiltrative type) is not as common, but typically seen in younger people and affects both sexes equally. Early gastric cancer refers to invasion of the lesion no deeper than the submucosa, irrespective of the lymph node status.

Option 2\: Empirically treat for H. pylori.
Caveat 2\: This may delay the diagnosis of gastric cancer.
Option $\: Test for H. pylori, and if\:
Positive —» Treat for H. pylori
Negative Trial of PPI for 4 to 6 weeks
Caveat 3\: This may delay the diagnosis of gastric cancer
Option 4\: Go straight to endoscopy (EGD)
Caveat 4\: This may be too invasive as the initial test in a patient with only “mild epigastric pain” without alarm symptoms.
Option 5\: Noninvasive testing for H. pylori (eg, serologic test­ ing) followed by endoscopy with biopsy if the test is positive.
Caveat 5\: This may not be cost effective.
Keep in mind that not every option will be suitable for all patients. However, in this particular CCS case, the judgment was made to undergo an EGD after a positive result from serologic testing. In this approach, a biopsy can rule out cancer, but at the same time confirm the diagnosis ofH. pylori. Remember, an endoscopy should not be used solely to establish the H. pylori status, but in this case, it was used for multiple reasons (eg, presence ofulcer, cancer, H. pylori).
Step 2) Treat the H. pylori infection with the following\: First-linecombination\: PPI (eg, omeprazole)+amoxicillin+
clarithromycin X 10 to 14 days
Penicillin allergic\: PPI (eg, pantoprazole)+metronidazole+
clarithromycin x 10 to 14 days
Failed treatment\: PPI (eg, rabeprazole) + metronidazole + tetracycline + bismuth x 10 to 14 days
Step 3) Stage the gastric cancer once it has been confirmed on biopsy. Staging can assess the extent of the disease and deter­ mine management options. Labs and imaging are typically used in the staging process. Consider a chest CT instead of a chest x-ray in patients with a proximal gastric cancer. Endoscopic ultra­ sound (EUS) can be used to assess the depth ofinvasion ofthe gas­ tric cancer, but is usually performed in patients with early disease without evidence of distant metastasis. Similarly, a staging lapa­ roscopy can be considered in patients without distant metastasis, but is usually performed in patients with more advanced disease.
Step 4) Treatment of early gastric cancers can be accomplished by either endoscopic resection or surgery.
Endoscopic Resection
• Typically reserved for patients with tumor confined to the mucosa, no lymph node involvement, size <2 cm without ulceration, and intestinal-type adenocarcinomas.
Surgery
• Typically reserved for patients with tumor extending into the submucosa, lymph node involvement, size >3 cm with ulcer­ ations, or diffuse-type adenocarcinomas.
• A total gastrectomy is typically reserved for patients with le­ sions located in the upper one-third of the stomach. •
• A subtotal gastrectomy is typically reserved for patients with lesions located in the lower two-thirds ofthe stomach.
Follow-Up\:
Patients who had treatment for early gastric cancer have a good prognosis with a 5-year survival rate greater than 90%. Patients should continue to have follow-up visits every 3 to 6 months for the first year. Patients treated for H. pylori should have nonin­ vasive testing (eg, urea breath test or stool antigen) to confirm eradication. Testing should be postponed for at least 4 weeks after treatment of the infection to prevent false-negative results.
Pearls\:
• Dietary nitrates (cured meats, food additives, contaminated water) can be converted to nitrites and eventually into N-nitroso compounds (contains -NO group). It is theN-nitroso compounds that have been associated with gastric cancer risk.
• A penetrating posterior gastric ulcer can result in pancreatitis, which can cause pain that radiates to the back.
• Signs and symptoms suggestive of GERD include pyrosis, regurgitation, dysphagia, or discomfort after bending over or lying supine.
• Gastric metastasis can occur in the liver, lymph nodes, lung, ovaries, peritoneum, bone, CNS, or soft tissues.
• Although there is a clear association between H. pylori and gastric adenocarcinomas, only a small percentage of patients will actually develop gastric cancer.
• H. pylori can increases the risk of mucosa-associated lym­ phoid tissue (MALT) lymphomas.
• Serological testing for antibodies against H. pylori is a non­ invasive and cost-effective initial test. However, it should not be used to confirm eradication because the antibodies can persist for several years. Another caveat is that a positive result cannot differentiate between active infection and past exposure. The overall sensitivity is high (90%-100%), but specificity is variable (75%-95%).
• Urea breath test and stool antigen assay for H. pylori are non­ invasive tests that have fairly high sensitivity and specificity (>90%). Either test can be used for initial diagnosis or con­ firming eradication following therapy. In contrast to serolog­ ical testing, neither test is affected from previous exposure.
• Urease testing is an invasive test for detecting H. pylori because it requires a gastric biopsy from the EGD. Urease testing has near equivalent sensitivity and specificity com­ pared to histology (>90%).
• Histology is also an invasive test that permits additional information on biopsy other than the presence of H. pylori such as MALT lymphoma or intestinal metaplasia.
• Since the stool antigen test, urea breath test, biopsy urease test, and histology depends on the H. pylori load, prior treatment with antibiotics, bismuth, and antisecretory therapy
CHAPTER 8 GASTROENTEROLOGY 105

106 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
can decrease the sensitivity of all the tests and lead to false negative results. Therefore, patients should be off antibiotics and bismuth for at least 4 weeks, and PPIs for at least 2 weeks to reduce the chance of false negative results.
Avoid using the stool antigen test and biopsy urease test in patients with a GI bleed since results can be affected.
In a patient with early gastric cancer with a positive serology (ie, IgG) for H. pylori, but a negative biopsy for H. pylori, the patient should still be treated for the infection because the onset of gastric cancer can actually decrease the H. pylori load and, hence, the sensitivity of the biopsy.
Tumor markers such as CEA or CA-125 are not typically used in the staging, unless the patient will undergo neoad­ juvant therapy.
Diffuse type gastric cancers are highly metastatic and carry a poor prognosis. This type has a tendency to invade the gastric wall, which results in a very rigid-appearing stomach termed linitis plastica or “leather bottle.”
Foundational point—Histologically, diffuse-type gastric car­ cinomas can result in signet ring cells where abundant mu­ cin formation within the tumor cells pushes the nucleus to the periphery creating an appearance of a finger hole with the nucleus mimicking the face of a ring.
• On the CCS, if you forget the name of a test, let the order menu assist you. For example, typing in “H. pylori” in the order menu will provide you a list of different tests.
• On the CCS, failure to obtain a biopsy in a patient with a nonbleeding gastric ulcer, especially in the presence of mul­ tiple risk factors for gastric cancer, would be considered sub- optimal management.
• On the CCS, failure to detect H. pylori and appropriately treat the infection with a first-line medication would be considered suboptimal management.
• On the CCS, in most cases the consultants offer very little assistance. However, in some cases, if you have enough information (ie, thorough workup), the consultants may be helpful.
• On the CCS, as you read the HPI it may be helpful to jot down a couple of differential diagnoses on the dry-erase board provided to you in the exam. As you refer to your notes, it may be helpful to order tests based on the chief complaint and your differentials. Remember that a thorough methodical workup will probably not deduct from your score, but keep in mind that you want to order your tests as “appropriate” as possible.

Gynecology
CHAPTER OUTLINE
Keywords Review...............................................1.0.7
1 OVARIES.....................................................1.0.8. Ovarian Torsion...............................................1.0.8.
1 UTERUS...........................................................1.0.9. Leiomyoma....................................................1.0.9. Adenomyosis.............................
1 CERVIX.......................................................I.l.l. Cervical Dysplasia.......................
KEYWORDS REVIEW
Colposcopy—A diagnostic procedure that uses a magnifying instrument (colposcope) to examine the cervix, vagina, and in some cases the vulva. Once acetic acid is applied to the cervix, the solution will highlight areas of tissue abnormality. The colposcope (ie, standing microscope), which does
not touch the patient, will be able to magnify the tissue of interest and help guide directed biopsies.
Dyschezia—Painful or difficult defecation. Dyspareunia—Painful or difficult sex. Hematochezia—Passage of bloody stools.
Hematocolpos—Sequestration of menstrual blood in the vagina, which is usually due to an imperforate hymen or other obstruction.
1 VAGINA/VULVA..............................................1..14 Bacterial Vaginosis..............................................1.14 Trichomoniasis...................................................1.14 Candida Vulvovaginitis...........................................1.15
1 BREAST........................................................1..16 Breast Cancer...................................................1.16
1 ENDOCRINE DISORDERS.....................................1..20 Endometriosis........................................................1.20 Polycystic Ovarian Syndrome...................................1.21
Hypomenorrhea—Reduction in menstrual flow or duration occurring at regular cycle intervals.
Loop electrosurgical excision procedure (LEEP)—A thin wire loop that uses electric current to remove a cone-shaped segment of the cervix.
Menometrorrhagia—Excessive uterine bleeding at regular and irregular intervals.
Menorrhagia—Also referred to as hypermenorrhea. Heavy or prolonged menstrual flow occurring at regular cycle intervals.
Metrorrhagia—Intermenstrual bleeding (ie, irregular intervals).
107

108 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Oligomenorrhea—Infrequent menses with intervals that vary from 35 days to 6 months.
Polymenorrhea—Abnormally frequent menstruation occurring at regular intervals of 21 days or less.
Primary amenorrhea—Absence of menses by age 15 in the presence of normal growth and secondary sexual characteristics. The cause is usually due to genetic or anatomic abnormalities.
Primary dysmenorrhea—Painful menstruation with no identifiable pelvic pathology. Instead, there is excessive endometrial prostaglandin F2 alpha that can cause uterine contractions and Gl symptoms (eg, nausea, vomiting, diarrhea). NSAIDs (prostaglandin synthetase inhibitors) can provide symptomatic relief.
Secondary amenorrhea—Absence of menses for more than 3 cycle intervals or 6 months in an individual who was
OVARIES
H OVARIANTORSION
Ovarian torsion refers to the rotation of the ovary around the supporting ligaments, most commonly the suspensory ligament of the ovary (ie, infundibulopelvic ligament) and the ovarian ligament. When the fallopian tube twists along with the ovary, it is referred to as adnexal torsion.
Risk Factors\:
Large ovarian cysts or tumors (especially size >5 cm), pregnancy, ovulation induction, congenitally elongated fallopian tubes, elongated utero-ovarian ligaments.
Clinical Features\:
The classic presentation ofovarian torsion is an acute, severe, uni­ lateral, lower abdominal and pelvic pain. The pain can be charac­ terized as sharp, stabbing, or crampy and may radiate to the back, pelvis, or thigh. Exertion such as exercise may be a precipitating factor. Associated features include nausea, vomiting, and fever. If fever is present, it suggests adnexal necrosis, which is a late find­ ing. On examination, a tender adnexal mass may sometimes be felt that is a result of an edematous and cyanotic ovary secondary to an obstruction of the lymphatic and venous outflow. Atypical presentations do occur, and features may include a mild pain, bi­ lateral involvement, no tenderness, no adnexal mass, or intermit­ tent episodes of pain. It is thought that the previous episodes of pain are attributable to partial torsion with spontaneous reversal.
Next Step\:
Step 1) Ovarian torsion is a gynecologic emergency. Provide an­ algesics for pain control and antiemetics (eg, ondansetron) for nausea and vomiting.
Step 2) Obtain both transvaginal and transabdominal ultra­ sound with color Doppler flow to get good visualization of the
previously menstruating. Pregnancy is the most common cause, but other causes can occur along the hypothalamic (eg, exercise, stress, trauma, tumor)-pituitary (eg, pituitary adenomas, infarcts)-ovarian (eg, PCOS, premature ovarian insufficiency) axis. Other endocrine disorders (eg, hypothy­ roidism, hyperthyroidism, diabetes mellitus) and anatomic abnormalities (eg, Asherman's syndrome) can result in secondary amenorrhea.
Secondary dysmenorrhea—Painful menstruation with an attributable pelvic pathology. It may be due to abnormali­ ties in the ovaries (eg, ovarian cysts), uterus (eg, leiomyomas, adenomyosis, endometriosis, endometrial polyps, IUD, PID), or cervix (eg, cervical stenosis).
Virilization—Masculinization, particularly in a female or prepubertal boy.
pelvic structures. It should be noted that an abnormal color Doppler flow suggests an ovarian torsion, but a normal color Doppler flow study does not rule out an ovarian torsion. Initial testing should also include the following\:
P-hCG—Rule out a pregnancy or ectopic pregnancy.
CBC—Check for anemia secondary to hemorrhage and leukocytosis secondary to an infection from the necrosis.
BMP—Check the electrolytes.
Step 3) The clinical management of suspected ovarian torsion is to proceed with surgery. At the time of surgical evaluation, the definitive diagnosis can be made by visualizing the rotated ovary. The surgeon may then untwist the vascular pedicle, per­ form a possible ovarian cystectomy if a benign mass is present, or perform a salpingo-oophorectomy in the presence of a ne­ crotic ovary or suspected malignancy.
Disposition\:
After initial management in the ED, patients with suspected ovarian torsion should be sent to surgery for definitive diagnosis and therapeutic treatment.
Pearls\:
• Ovarian torsion is more common on the right side than the. left side, which may confuse you with appendicitis.
• Differential diagnosis includes appendicitis, ectopic pregnancy, tubo-ovarian abscess, and small intestinal obstruction.
• Ovarian torsion can occur at any age (eg, fetus, neonates, prepubertal girls, reproductive years, postmenopausal).
• Ovarian torsion can recur.
• With early diagnosis and treatment, the prognosis of the af­ fected ovary improves.
• Foundational point—Compression of the ovarian vessels ini­ tially affects the lymphatic and venous outflow because they have fairly thin walls. This results in ovarian congestion and cyanosis.

Further progression eventually interrupts the arterial vessel (ie, muscular walls), which can lead to ovarian hypoxia causing in­ tense pelvic pain. Without intervention, the ovary can undergo necrosis, infarction, and possibly hemorrhage.
On the CCS, “ovarian artery Doppler” is available in the practice CCS.
On the CCS, if you suspect ovarian torsion, do not delay treatment, since that would be considered suboptimal man­ agement (eg, ordering an MRI).
On the CCS, poor management would include the failure to order a pelvic ultrasound.
UTERUS
I LEIOMYOMA
Leiomyoma (fibroids or myomas) is a benign smooth muscle neoplasm that is the most common pelvic tumor in women. The etiology is unclear.
Risk Factors\:
Increased risk—Early menarche, blacks, elevated BMI, early pregnancy (first trimester), reproductive-aged female, increas­ ing age (high prevalence in the fifth decade)
Decreased risk—Smoking, increased parity, postmenopausal Clinical Features\:
Patients can be asymptomatic, especially if the myomas are small. Symptomatic patients typically complain of bleeding, pain, pres­ sure sensation, or infertility. The severity of the symptoms is usually dictated by the number, size, and location of the myoma (see Figure 9-1 and Color Plate 9). Bleeding typically presents as
Pedunculated
Pedunculated submucous
Intramural Submucous
Intraligamentary Cervical
FIGURE 9-1 • Leiomyomas. Uterine fibroids can be classified by their location. Subserosal myomas grow near the uterine serosa. Submucous myomas are adjacent to the endometrium. Intramural myomas are within the uterine walls. Cervical myomas are located in the cervix. Pedunculated myomas have an attached stalk. Infrequently, myomas can be found in the broad ligament, ovary, fallopian tube, vagina, and vulva. (Reproduced with permission from Hoffman BL, Schorge JO, Schaffer Jl, et al. Williams Gynecology. 2nd ed. New York\: McGraw-Hill, www.accessmedicine.com.)
On the CCS, if your ob-gyn consultant agrees with surgery, remember to order the pre-op work up (eg, blood type and crossmatch, PT/INR, PTT).
On the CCS, your simulated timing will be important in this type of case.
On the CCS, if you’re not sure what type of surgical pro­ cedure the patient should have, type in the word “laparo­ scopic” and a menu of different procedures will be available to you.
menorrhagia. Menorrhagia is often accompanied by pain (dys­ menorrhea). Acute pelvic pain is uncommon, unless there is a de­ generating myoma or torsion of a pedunculated tumor. Enlarged myomas can compress nearby pelvic organs such as the rectum (constipation), bladder (urinary frequency, incontinence), and infrequently, the ureter (hydronephrosis). Distortion of the uter­ ine cavity, especially with submucous leiomyomas, can result in infertility. Upon bimanual pelvic examination, an enlarged, firm, asymmetrical, irregular contoured uterus may be felt. A single mass or multiple masses may also be appreciated on exam.
Next Step\:
Step 1) In a reproductive-aged woman with uterine enlarge­ ment, order a (3-hCG level to rule out a pregnancy. In a post­ menopausal woman with uterine bleeding and a rapidly growing enlarging uterine mass, a workup to rule out a uterine leiomyo­ sarcoma (ie, aggressive uterine cancer) should be performed.
Step 2) Diagnosis of a leiomyoma is based on the clinical evalu­ ation and most commonly with the transvaginal ultrasound. Leiomyomas can vary in their echogenicity from hypo- to hy- perechoic on ultrasound findings. Submucosal leiomyomas may be diagnosed by saline infusion sonography or hysteros- copy which both provide better visualization of the mass within the endometrial cavity. MRI’s are not routinely performed, but may be considered in patients with distorted anatomy or sur­ gical planning. Hysterosalpingography (HSG) is a radiologic procedure that uses radio-opaque material to characterize the contour of the uterus. HSG is often used to determine tubal pa­ tency in an infertile woman.
Step 3) The clinical management of leiomyomas can vary. Con­ sider the following approaches\:
Observation
There are two populations to consider for expectant manage­ ment. First, in a reproductive-aged woman with small, asymp­ tomatic myomas. Second, in a perimenopausal woman who is close to menopause since the condition usually improves with lower levels of estrogen.
Pharmacologic Therapy
NSAIDs—NSAIDs can be useful for patients with painful menses, but not for reducing the bulk of the myoma.
CHAPTER 9 GYNECOLOGY 109

110
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
GnRH agonist—GnRH agonist (ie, leuprolide) induces a hypogonadal state. It can reduce the uterine size within 3 months, and it can improve anemia. GnRH agonist should not be used as a form of long-term management, but rather as a preoperative medication for 3 to 6 months prior to sur­ gery and in conjunction with iron supplements. Side effects include amenorrhea, hot flashes, bone loss, insomnia, and myalgias. Due to the side effects of GnRH agonist, add-back therapy with low-dose estrogen-progestin (eg, conjugated estrogen plus medroxyprogesterone acetate) is often adminis­ tered to counter the side effects, especially bone loss and vaso­ motor symptoms. Leuprolide is administered as a onetime IM injection every month or every 3 months (ie, higher dosage).
Interventional Procedures
Hysterectomy—Hysterectomyisconsidereddefinitivetherapy. It is ideal in patients who have completed their childbearing and who are refractory to other forms of treatment.
Myomectomy—Myomectomy is ideal in patients who have not completed their childbearing and want to retain their uterus. The disadvantage of myomectomy is the formation of adhesions and leiomyoma recurrence. Additionally, there is a risk ofuterine rupture with subsequent pregnancy, and there­ fore, patients are usually advised to undergo a C-section.
Uterine artery embolization (UAE)—UAE is an alterna­ tive to surgery in symptomatic patients that are refractory to medical management. UAE can alleviate leiomyoma-related symptoms and induce shrinkage of the myoma. Although UAE can preserve the uterus, it is not ideal for patients that have not completed their childbearing since pregnancy- related complications have been associated following UAE.
Follow-Up\:
Asymptomatic patients with small myomas can be followed-up every 6 months for a pelvic exam to reassess the rate of growth.
Pearls\:
• Following discontinuation of GnRH agonists, normal men­ ses resume, leiomyomas regrow, and uterine volume returns to the original size.
• Most women, not all, that are in menopause typically have shrinkage of their leiomyomas.
• Low-dose oral contraceptives do not cause leiomyomas to grow.
• Parasitic myomas are considered a subserosal variant. In this type, a pedunculated subserosal myoma can attach itself into the peritoneal cavity and derive blood supply from another organ (eg, omentum). Subsequently, the parasitic myoma may or may not detach itself from the parent myometrium.
• Foundational point—Leiomyoma cells have a high density of estrogen receptors on the cell surface.
• Foundational point—On cut section of a leiomyoma, a characteristic "whorled” pattern of smooth muscle bundles can be seen.
• Foundational point—On histology, smooth muscle cells are elongated with an eosinophilic cytoplasm and an oval or
cigar-shaped nucleiis. Mitotic activity is uncommon in leio­ myoma, but it is frequently present in leiomyosarcoma.
• Foundational point—An outer connective tissue surrounds a leiomyoma, which serves as a cleavage plane for the sur­ geon to easily shell out the mass, unlike adenomyomas, which are not easily excised because they lack a good cleav­ age plane.
• On the CCS, “transvaginal ultrasound,” “saline infused so­ nogram of uterus,” “hysterosalpingography,” and “hysteros- copy” are available in the practice CCS. Ifyou decide to order a hysterosalpingography or hysteroscopy, an ob-gyn consult is required.
• On the CCS, ifyou order “OCP,” you will be required to pick the strength (eg, low, medium, high) of the OCR
• On the CCS, if a patient presents with menorrhagia, remem­ ber to order a CBC to check for anemia and a TSH to rule out hypothyroidism.
• On the CCS, even if you made the correct management de­ cisions during the CCS case, you may still receive no credit for those decisions if you placed them in the wrong sequence of actions (eg, ordering a hysterectomy before a transvaginal ultrasound).
1 ADEN0MY0SIS
Adenomyosis is characterized by the presence of ectopic endo­ metrial glands and stroma deep within the myometrium. The myometrium reacts to the ectopic tissue by hyperplasia and hy­ pertrophy resulting in a diffusely enlarged uterus or in a focal circumscribed nodule, also referred to as an adenomyoma. The etiology is unknown.
Risk Factors\:
Parity (opposite of leiomyoma), increasing age (usually seen in the fourth or fifth decade), uterine trauma.
Clinical Features\:
Patients can be asymptomatic. Symptomatic patients typically complain of menorrhagia and secondary dysmenorrhea. Infre­ quently, patients may complain of dyspareunia or infertility. On pelvic examination, diffuse adenomyosis will present as a uni­ formly enlarged uterus or “globular” enlargement. The uterus will be symmetrical in shape and will generally not exceed a 12-week size gestation. A focal adenomyosis (adenomyoma) is typically confined to a discrete area and results in an asym­ metrical uterus. The uterus is usually tender immediately before and during menstruation.
Next Step\:
Step 1) In a reproductive-aged woman with uterine enlarge­ ment, order a J3-hCG level to rule out a pregnancy. In a post­ menopausal woman with uterine bleeding, the initial evaluation may begin with an endometrial biopsy and/or transvaginal ul­ trasound to rule out a malignancy.
Step 2) Diagnosis of an adenomyosis is based on the clini­ cal evaluation and transvaginal ultrasound (TVUS) or MRI.

However, MRI is more accurate and it can differentiate between focal and diffuse adenomyosis. MRI can also delineate between a leiomyoma and adenomyosis. The transvaginal ultrasound is operator dependent, but results will typically demonstrate het­ erogeneity in the myometrium and hypoechoic cysts (ie, endo­ metrial cystic glands) or hypoechoic nodules (ie, adenomyoma).
Step 3) Hysterectomy is considered definitive treatment. It is ideal in patients who have completed their childbearing and who have significant symptoms. Unfortunately, there are no superior med­ ical treatments for adenomyosis. NSAIDs, estrogen-progestin contraceptives, and progestin-only (eg, levonorgestrel-releasing IUD) therapies are used for menorrhagia and dysmenorrhea.
Follow-Up\:
Symptomatic patients may require ongoing follow-ups, unless they decide to undergo a hysterectomy.
Pearls\:
• Diffuse adenomyosis is more common than focal adenomyosis.
• The clinical presentation of focal adenomyosis can resemble leiomyomas.
CERVIX
0 CERVICALDYSPLASIA
Cervical dysplasia is a precancerous condition in which abnor­ mal cell growth occurs within the cervix. The transformation zone (TZ) is an area of active cell division that poses a high risk for neoplasia. This area represents a transition of stratified squa­ mous epithelium to columnar epithelium. The position of the TZ can change based on the womans age, hormonal status (eg, pregnancy, menopause, hormonal contraception), vaginal pH, or prior cervical procedures. Cervical dysplasia usually causes no symptoms and is often discovered by routine screening.
Risk Factors\:
HPV 16 and 18, cigarette smoking, immunosuppression (eg, HIV, immunosuppressive therapy), sex at a young age, multiple sexual partners.
Cytological and Histological Features\:
The Pap smear allows for cytologic evaluation while colposcopy- directed biopsies are often used for histologic examination.
Squamous Cell Abnormalities
Low-grade squamous intraepithelial lesion (LSIL)—The risk of invasive cervical cancer is low in this category and is consistent with mild dysplasia, HPV, and CIN 1.
High-grade squamous intraepithelial lesion (HSIL)—The risk of invasive cervical cancer is fairly high in this category and is consistent with moderate to severe dysplasia, carci­ noma in situ (CIS), and CIN 2 or CIN 3.
• Adenomyosis can also occur in patients with leiomyomas and endometriosis.
• Definitive diagnosis is made from histologic exam of the uterus following a hysterectomy.
• Needle biopsy is not routinely performed in the evaluation of adenomyosis.
• Adeno- means gland in Greek. Therefore, it is easy to remember that the gland tissue is in reference to the endo­ metrial glands.
• Foundational point—Adenomyosis is derived from the ba- salis layer of the endometrium.
• Foundational point—The endometrial glands and stroma found in the myometrium rarely undergo the same prolifera­ tive and secretory changes of a normal uterine endometrium during the menstrual cycle.
• Foundational point—On cut section of the uterus, there is a spongy appearance with focal areas of hemorrhage.
• OntheCCS,ifyouordersomethingthatistrulynotindicated and it poses a threat to your patient, you will lose points (eg, ordering a laparoscopic ovarian biopsy for an adenomyoma).
Atypical squamous cell—cannot exclude a high-grade lesion (ASC-H)—Findings indicate a concern for a signifi­ cant lesion, but not conclusively. There is still a potential risk for malignant disease in this category.
Atypical squamous cell of undetermined significance (ASC-US)—ASC-US is the most common type of cervical cytologic abnormality. Consider this type as a “gray zone” category because it has some features associated with squa­ mous lesions, but it does not fit the criteria for squamous intraepithelial lesion (SIL).
Histologic Abnormalities
CIN 1—A low-grade lesion that exhibits koilocytotic atypia (HPV viral cytopathic effect). There are mild cellular changes in the lower one-third of the epithelium.
CIN 2—A high-grade lesion with progressive atypia seen in the basal two-thirds of the epithelium.
CIN 3—A high-grade lesion with severe cellular changes of more than two-thirds of the epithelium and usually lacks squamous maturation throughout the thickness of the epithelium.
Next Step\:
Step 1) Cervical cancer screening guidelines are based on sev­ eral organizations (eg, USPSTF, ACS, ASCCP, ASCP, ACOG) with slight differences in their screening parameters. It should be noted that the recognition of HPV in cervical cancer has led to the incorporation of HPV screening in women 30 to 65 years old. The following screening parameters are based on the
CHAPTER 9 GYNECOLOGY 111

112 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
above organizations and should be served as a basis for board examination\:
21 years old\: Initiate screening (no earlier), regardless of age of sexual initiation
21-29 years\: Cytology every 3 years
30-65 years\: Cytology + HPV testing every 5 years or
cytology alone every 3 years

65 years\: Not indicated if high risk is absent and 3 con­ secutive negative cytology results or 2 consecutive negative co-tests in the past 10 years
Step 2) The cervical cytology results is an initial assessment to detect abnormal cervical cells. The Pap smear is not used to establish a diagnosis nor initiate treatment. Consider the following cervical cellular abnormalities and the associated clinical management\:
LSIL
21-24 years old\: LSIL —» Repeat Pap test in 1 year. If repeat shows HSIL or ASC-H perform colposcopy, but if repeat shows LSIL or ASC-US repeat Pap test in 1 year.
25-29 years old\: LSIL —> Colposcopy. >30 years old\:
LSIL + HPV (+) —» Colposcopy
LSIL + HPV (-) —» Repeat Pap + HPV in 1 year or colposcopy
LSIL —> Colposcopy
Pregnant\: LSIL —> Colposcopy without endocervical curet­ tage (ECC). Only biopsy if you suspect a high-grade lesion.
HSIL
21-24 years old\: HSIL —> Colposcopy (Do not do LEEP). £25 years old\: HSIL-* Colposcopy or immediate LEEP.
Pregnant\: HSIL -» Colposcopy without ECC or LEEP. Only biopsy if you suspect a high-grade lesion.
ASC-H
21-24 years old\: ASC-H —» Colposcopy. £25 years old\: ASC-H Colposcopy.
Pregnant\: ASC-H —» Colposcopy without ECC. Only bi­ opsy if you suspect a high grade lesion.
ASC-US
21-24 years old\: ASC-US —» HPV testing now or repeat Pap test in 1 year. If results show HSIL or ASC-H, perform colposcopy, but if results show HPV (+), LSIL, or ASC-US, repeat Pap in 1 year.
£25 years old\: ASC-US —» HPV testing now or repeat Pap test in 1 year. If results show ASC-US, ASC-H, HSIL, LSIL, or HPV (+), perform colposcopy, but if results show HPV (-), retest in 3 years with Pap test + HPV.
Pregnant\: ASC-US —> Colposcopy without ECC. Only bi­ opsy if you suspect a high-grade lesion.
Step 3) Upon confirmed CIN 1, CIN 2, or CIN 3 via colposcopy- directed biopsies, observation or treatment may be recom­ mended. Consider the following CINs\:
CIN 1 with Prior Low-grade Lesions (LSIL or ASC-US)
21-24 years old\: Repeat Pap test in 1 year. If results show HSIL or ASC-H, perform colposcopy, but if results show LSIL or ASC-US, repeat Pap in 1 year.
£25 years old\: Repeat Pap + HPV in 1 year. If results show HPV (+), ASC-US, ASC-H, or HSIL, perform colposcopy, but if results show HPV (-) and a normal Pap test, resume screening in 3 years.
Persistent CIN 1 £2 years\: Observation or treatment (exci­ sion or ablation).
Pregnant\: No excision or ablation, reevaluate 6 weeks post­ partum.
CIN 1 with Prior High-grade Lesions (HSIL or ASC-H)
21-24 years old\: Pap test + colposcopy every 6 months for 2 years.
£25 years old\: Repeat Pap + HPV at 12 and 24 months or diagnostic excisional procedure.
Persistent CIN 1 £2 years\: Observation or treatment (exci­ sion or ablation).
Pregnant\: No excision or ablation, reevaluate 6 weeks post­ partum.
CIN 2 or CIN 3
Treat\: Excision or ablation.
Young women who have not finished childbearing\: Ob­ servation (Pap + colposcopy) or treatment.
Pregnant\: Reevaluate 6 weeks postpartum or Pap test + col­ poscopy without ECC. Only biopsy if you suspect invasive cancer.
Follow-Up\:
Patients with CIN 2 or CIN 3 who have been treated (excision or ablation) should have follow-up testing with a Pap smear plus HPV testing in 12 and 24 months.
Pearls\:
• CIN 1 is typically caused by the low-risk HPV types and is not considered precancerous unless the lesion has been pres­ ent for >2 years. CIN 1 is considered a transient HPV infec­ tion that usually regresses over several months.
• CIN 2 and 3 are true precancerous lesions.
• A higher “CIN” number reflects a high-grade lesion; this can easily be remembered in that the higher the “sin” the greater the risk of malignant disease.
• There are over 100 genotypes of HPV. The “high-risk” types that can cause cervical cancer include HPV 16 and 18, which

are the major types. HPV 31, 33, 35,45, 52, and 58 can also cause cervical cancer. The "low-risk” types that can cause be­ nign condylomatous genital warts are HPV 6 and 11.
Smoking and coexistent HPV infection have a synergistic ef­ fect on cervical cancer and CIN formation.
Most of the screening recommendations incorporate HPV testing after 30 years of age because prior to 30 years old, most of the HPV infections are transient.
Bivalent (types 16, 18) HPV vaccine is available under the trade name Cervarix and should be used for females only.
Quadrivalent (types 6, 11, 16, 18) HPV vaccine is available under the trade name Gardasil and is used for females and males. In males, HPV vaccine can be effective in preventing genital warts and anal intraepithelial neoplasia in men who have sex with men (MSM).
HPV vaccines do not remove preexisting HPV infections.
HPV vaccines are most effective when females or males have not been infected with the HPV infection (ie, before their first sexual encounter). However, females and males can still be vaccinated even if they have been sexually active or are posi­ tive for HPV infection, presence of genital warts, abnormal Pap tests in females, or anal intraepithelial neoplasia in males.
HPV vaccination is not recommended for pregnant women until more information is available on its safety even though the drug rating in pregnancy is a category B.
HPV vaccination is recommended for patients who are im­ munocompromised.
HPV vaccines can be given as early as 9 years of age, but the recommended age is 11 or 12 years old. Catch-up vaccina­ tions may be given to patients 13 to 26 years of age who have not been vaccinated. It is a 3-dose series that can be given at 0,2, and 6 months of follow-up visits.
A Pap smear involves the direct transfer of cervical cells onto a microscope slide for evaluation. Liquid-based cytol­ ogy involves the transfer of the cervical cells to a liquid vial. The cells are then place in a monolayer onto a glass slide for evaluation. Either procedure is acceptable, and there is no significant advantage ofliquid-based testing compared to the conventional Pap smear.
The cervical screening recommendations for patients that have undergone a hysterectomy for a benign disease vary from different organizations. In general, patients in this category are at lower risk of cervical cancer, especially if the cervix was removed. A collective summary and agreement of the rec­ ommendations from the various organizations propose that screening is not indicated if the patient had no history of CIN 2, CIN 3, or cervical cancer. Screening recommendations will vary based on evidence of adequate negative prior screening.
Ablation modalities are used for treatment, but excisional modalities are used for treatment plus diagnostic informa­ tion (eg, inadequate colposcopy, recurrent CIN 2, 3).
Ablation therapies include cryotherapy, C02 laser, cold coagulation, and electrocoagulation diathermy.
• Excisional therapies can be performed using a scalpel (cold knife conization), laser, or electrosurgery (ie, LEEP). The procedure involves a cone-shaped biopsy (cervical conization) that includes the entire transformation zone. Unfortunately, excisional therapies frequently result in cervi­ cal stenosis compared to ablation therapies.
• Patients with a history of cervical conization are at risk of future second trimester pregnancy loss.
• Glandular cells on cytology usually derive from the endometrium or endocervix. Glandular cells can be catego­ rized as atypical glandular cells (AGC)-endocervical, en­ dometrial, or not otherwise specified (NOS). There is also a category of AGC favoring neoplastic-endocervical or not otherwise specified (NOS).
• CJ\: A 35-year-old woman underwent a Pap smear that dem­ onstrated AGC-endocervical cells on cytology. What is your next step? Answer\: All AGC categories except endometrial cells should undergo a colposcopy with endocervical sampling. In addition, all women >35 years old or at risk for endometrial hyperplasia (eg, late menopause, early menarche, unopposed estrogen use, tamoxifen use, nulliparity, PCOS, postmenopausal with uterine bleeding) should undergo endometrial sampling. Patients with AGC-endometrial cells are managed differently. The initial workup requires endometrial sampling plus endo­ cervical sampling. If the results are negative for any premalig- nant lesion, then the next best step is to perform a colposcopy.
• Foundational point—Most women are born with columnar epithelium on the face of the cervix. The columnar cells are replaced by squamous epithelium via squamous metapla­ sia during the time of menarche, when the vagina becomes fairly acidic. The squamous epithelium is more resistant to the acidic environment.
• Foundational point—During colposcopy, acetic acid is ap­ plied to the cervix. It is thought that the acetic solution causes dehydration of squamous cells but not columnar cells. This results in an increased nuclear density or nuclear-cytoplasm ratio in the squamous cells, which would be more prominent in actively dividing cells (eg, dysplastic cells, metaplastic cells). Essentially, the acetic solution causes an increased light reflectivity in the abnormal tissue and thus creates a vi­ sual contrast from the normal tissue.
• Foundational point—During colposcopy, ifno lesion is seen with acetic acid, an iodine solution is applied to the cervix. Normal mature squamous cells contain a large amount of glycogen, and when iodine is applied, it will be taken up and stained a dark brown color.' Rapidly dividing cells contain little glycogen, and when iodine is applied, it will not be taken up and these cells will stain a light yellow.
• On the CCS, “Gardasil” is available in the practice CCS, but not “Cervarix.”
• On the CCS, if you’re not sure on the type of diagnostic ex­ cisional procedure to perform (eg, laser, LEEP, cold knife conization), type in “cervical” in the order menu and select from the list.
CHAPTER 9 GYNECOLOGY 113

114 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
VAGINA/VULVA
1 BACTERIALVAGINOSIS
Bacterial vaginosis is characterized by a shift in normal vagi­ nal flora from a hydrogen peroxide-producing lactobacilli to an increasing number of anaerobes, particularly Gardnerella vagi­ nalis, Prevotella species, and Mobiluncus species. An inflamma­ tory response is lacking in bacterial vaginosis, hence the term vaginosis rather than vaginitis.
Risk Factors\:
Sexual activity, douching
Clinical Features\:
Patients can be asymptomatic. Symptomatic patients typically complain of a “fishy” or “musty” vaginal odor, particularly after sex or during menses. It is thought that following intercourse, the alkaline semen releases aromatic amines. Patients usually do not complain of vaginal pruritus, dysuria, or dyspareunia. On examination, the vaginal discharge has a thin, gray-white appearance that adheres to the vaginal walls. Typically, there is little evidence of inflammation of the vaginal walls. In some cases, not all, patients may have a frothy discharge.
Next Step\:
Step 1) The diagnosis of bacterial vaginosis is based on the Am- sel criteria, which require at least 3 of the following 4 findings\:
• Vaginal pH >4.5 (normal pH values are from 3.8 to 4.5)
• Presence of a thin, gray-white, homogenous discharge
• Fishy odor upon adding KOH to vaginal discharge (positive whiff test)
• Presence of clue cells (>20% seen on the wet smear)
Step 2) The goal of treatment is to shift the high concentration of anaerobes back to the dominant lactobacilli. Metronidazole and clindamycin are good agents against anaerobes, and over time, the hope is for the regeneration of normal vaginal flora. Consider the following regimens\:
Option 1\: Metronidazole (oral) X 7 days
Option 2\: Metronidazole (intravaginal gel) x 5 days Option 3\: Clindamycin (intravaginal cream) x 7 days Option 4\: Clindamycin (vaginal suppository) X 3 days Option 5\: Clindamycin (oral) x 7 days
Follow-Up\:
Patients do not require a follow-up if symptoms resolve with antibiotic therapy.
Pearls\:
• Gardnerella vaginalis is actually part of the normal vaginal flora, but its concentrations increase in bacterial vaginosis.
• Male sexual partners of affected women do not have to be treated.
• Asymptomatic women do not have to be treated.
• Vaginal culture has no role in the evaluation and diagnosis of bacterial vaginosis since the organisms you culture will be part of the normal vaginal flora.
• Infected pregnant patients with bacterial vaginosis are at risk of premature rupture of membranes, preterm delivery, and endometritis.
• There is no effective treatment in replacing lactobacilli.
• In the absence of lactobacilli, the vaginal pH rises creating an environment for anaerobes to grow and Gardnerella vaginalis to adhere to vaginal epithelial cells (clue cells).
• Foundational point—Clue cells represent vaginal epithelial cells studded with coccobacilli.
• On the CCS, “vaginal pH” and “Whiff test” are available in the practice CCS.
• On the CCS, “metronidazole” and “clindamycin” are avail­ able in the practice CCS with both oral and vaginal routes of administration.
1 TRICHOMONIASIS
Trichomoniasis is the most common nonviral, nonchlamydial STD in women. Trichomoniasis is caused by a flagellated pro­ tozoan, Trichomonas vaginalis, which is primarily transmitted through sexual intercourse.
Risk Factors\:
Sexual activity with an infected partner, history of STDs, mul­ tiple partners.
Clinical Features\:
The clinical presentations are different for women and men. Consider the following\:
Women—Patients may complain of copious, malodorous vaginal discharge. Patients may also have vaginal pruritus, burning, dysuria, dyspareunia, and postcoital bleeding. On examination, the vaginal discharge may be green-yellow, white, or gray. In some cases, not all, patients may have a frothy discharge. Edema and erythema may be present in the vagina and vulva. Punctate hemorrhages (“strawberry cervix”) may be seen on the vagina or cervix, but this find­ ing is uncommon.
Men—Men can be asymptomatic (carrier state). However, untreated men can develop signs and symptoms of urethri­ tis, which may include dysuria, pruritus, burning, or a dis­ charge that is mucoid or mucopurulent. Patients may also have findings consistent with epididymitis, prostatitis, or balanoposthitis.
Next Step\:
Step 1) The clinical features of trichomoniasis are not sufficient to make the diagnosis. The diagnosis can be confirmed by ex­ amining the motile trichomonads on saline wet mount. Con­ sider the following adjunctive tests that can be used to support the diagnosis.

• Vaginal pH between 5.0 and 7.0.
• Increased numbers of PMNs on saline microscopy.
• Fishy odor upon adding KOH to vaginal discharge (positive whiff test).
• Cultures can be performed in the absence of a motile tricho- monad on saline microscopy, but with a high clinical suspi­ cion for trichomoniasis.
• Molecular testing for DNA, RNA, or antigen comes in rapid diagnostic kits that can be useful when cultures and saline microscopy are unavailable.
Step 2) Treatment involves both symptomatic and asymptom­ atic women and men. Both sexual partners should be treated simultaneously and should abstain from sexual intercourse until after treatment and until they are asymptomatic. Con­ sider the following regimens with the 5-nitroimidazole drugs\:
Option 1\: Metronidazole (oral) x 1 day (ie, single dose with 2 grams)
Option 2\: Metronidazole (oral) x 7 days (ie, 500 mg BID) Option 3\: Tinidazole (oral) x 1 day (ie, single dose with
2 grams)
Follow-Up\:
No follow-up is necessary for both patient and partner if they are asymptomatic after therapy. Keep in mind that since trichomo­ niasis is associated with STDs, patients should have the appro­ priate testing to rule out other sexually transmitted infections.
Pearls\:
• Neither a frothy discharge nor a positive whiff test (amine odor test) is pathognomonic for bacterial vaginosis or trichomoniasis.
• Wet mount microscopy is not effective in diagnosing tricho­ monas in men. Men should have either a culture or nucleic acid amplification test to make the diagnosis.
• Systemic therapy with the 5-nitroimidazole agents are the choice of therapy compared to topical therapy because the drug can reach the hidden reservoirs such as the Skene’s gland and Bartholin’s gland, which can be a cause of recur­ rence other than not treating the sexual partner.
• Infected pregnant women with trichomoniasis are at risk of premature rupture of membranes, preterm delivery, and in­ trauterine infections.
• Foundational point—The trophozoite, Trichomonas vaginalis, replicates by binary fission.
• On the CCS, “Trichomonas vaginal smear” and “wet mount, vaginal secretions” are both available in the practice CCS, and they are considered the same order.
• On the CCS, remember to “advise patient, sexual partner needs treatment.”
• On the CCS, remember to “advise patient, no intercourse.”
• On the CCS, remember to “advise patient, medication
adherence.”
• On the CCS, remember to “advise patient, side effects of medication” since metronidazole and tinidazole can cause
nausea, vomiting, metallic taste, and a disulfiram-like reac­ tion if alcohol is consumed.
• On the CCS, remember to “advise patient, no alcohol.”
• On the CCS, you do not have to know the drug doses on the exam, but you should know the duration of treatment.
1 CANDIDAVULVOVAGINITIS
Candida vulvovaginitis is a fungal infection that is caused by Candida albicans in the majority of cases. Nonalbicans species such as Candida glabrata and Candida parapsilosis can also cause infection, but they generally produce milder symptoms. Candida vulvovaginitis is not considered an STD.
Risk Factors\:
Broad-spectrum antibiotics, immunosuppression (eg, HIV, glu­ cocorticoids, chemotherapy), diabetes mellitus, high dose estro­ gen, pregnancy.
Clinical Features\:
The predominant symptom is pruritus. Patients may also have burning, dysuria, and dyspareunia. On examination, there may be vulvar erythema, edema, and excoriations. The vagina can appear erythematous. Patients may have no discharge, or they may have a thick, white, clumpy “cottage cheese” discharge that usually has no odor. The speculum exam usually reveals a nor­ mal cervix. Candida vulvovaginitis can be classified as a compli­ cated or uncomplicated infection. Features of an uncomplicated infection include signs and symptoms that are mild to moderate, sporadic, nonrecurrent, and infection with Candida albicans. Features of a complicated infection include signs and symptoms that are severe, recurrent (>4 infections per year), comorbid conditions (eg, diabetes), and infection that is nonalbicans (eg, Candida glabrata).
Next Step\:
Step 1) The clinical diagnosis of Candida vulvovaginitis should be confirmed with further testing. The diagnosis can be con­ firmed with a wet mount of the discharge and adding 10% KOH to the prep, which will dissolve the epithelial cells leaving be­ hind the hyphae, pseudohyphae, or buds. Consider the follow­ ing adjunctive tests that can be used to support the diagnosis.
• Vaginal pH between 4.0 and 4.5 (ie, basically a normal pH).
• Negative whiff test (no odor).
• Cultures can be performed in recurrent infections or the ab­ sence of hyphae, pseudohyphae, or buds on KOH prep but with a high clinical suspicion for Candida vulvovaginitis.
Step 2) Treatment of Candida vulvovaginitis is based on an un­ complicated or complicated infection. Consider the following\:
Uncomplicated Infections
Option 1\: Fluconazole (oral) x 1 day
Option 2\: Clotrimazole (intravaginal cream) X 3 to 7 days Option 3\: Miconazole (intravaginal cream) x 3 to 7 days Option 4\: Terazol (intravaginal cream) x 3 to 7 days
CHAPTER 9 GYNECOLOGY 115

116 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Complicated Infections
Option 1\: Fluconazole (oral) x total of 2 doses on day 1 and
then on day 3
Option 2\: Clotrimazole (intravaginal cream) x 7 to 14 days
Follow-Up\:
Patients with comorbid conditions (eg, poorly controlled diabe­ tes, HIV) may require a follow-up if symptoms persist. Patients may require risk factor modification (eg, improve glycemic control) and cultures if not previously performed. It should be noted that Candida species other than Candida albicans are often resistant to azole-based antifungal agents.
Pearls\:
• Sexual partners of affected women do not have to be treated.
BREAST
I BREASTCANCER
Breast cancer is the second leading cause of cancer death in women in the United States. Most breast cancers arise from malignant proliferation of the epithelial cells lining the ducts or lobules of the breast. Breast cancer can be classified as invasive or noninvasive (in situ) which depends on whether the cancer cells have infiltrated surrounding tissue or are confined by their natural boundaries, respectively (see Table 9-1).
fable 9-1 • Histologic Types of Breast Cancer
Type High Yield Features Noninvasive Disease
• Low-dose estrogen oral contraceptives do not appear to in­ crease the risk of Candida vulvovaginitis.
• Caution is advised in using boric acid for recurrent Candida vulvovaginitis. Boric acid can lead to a fatal outcome if ingested. Since it can be toxic if absorbed sys- temically, the medication is encapsulated and given via suppository.
• Foundational point—Candida glabrata generally does not form hyphae or pseudohyphae, but rather buds on KOH prep.
• On the CCS, “Candida smear, vaginal secretions” and “wet mount, vaginal secretions” are both available in the practice CCS, but they are considered two distinct orders.
• On the CCS, you should be able to know when to use the “continuous” or “one time/bolus” mode of frequency when prescribing a medication.
Risk Factors\:
Early menarche (<12 years old), late menopause (>55 years old), advancing age, nulliparity, late age of first term pregnancy (>30 years old), oral contraceptive (current or prior use), cur­ rent use of hormone replacement therapy (estrogen + proges­ tin), family history of breast cancer (first-degree relatives, and the risk is even higher with additional first-degrees affected or an earlier diagnosis of breast cancer in the first-degrees), breast- ovarian cancer syndrome defined by BRCA1 and BRCA2 genes, personal history of invasive breast cancer, personal history of noninvasive breast cancer (DCIS or LCIS), personal history of
Ductal carcinoma in situ (DCIS)
Lobular carcinoma in situ (LCIS)
• Confined to the mammary ducts.
• Divided into comedo and noncomedo subtypes.
• Prognosis is worse for comedo types.
• Considered a precursor to invasive ductal carcinoma.
• Fivefold risk for invasive breast cancer.
• Subsequent invasive breast cancer is usually in the ipsilateral breast.
• May be detected as an incidental finding.
• Considered a marker for increased risk of breast cancer rather than a direct precursor lesion.
• White women >black women
• Average age at diagnosis is in the mid 40s.
• The risk of subsequent invasive breast cancer is approximately
1% per year.
• Subsequent invasive breast cancer occurs in 25%-35% of women
with LCIS.
• Subsequent invasive breast cancer can be ductal or lobular in origin.
• Subsequent invasive breast cancer can be ipsilateral or contralateral.
• May be detected as an incidental finding.
Foundational Points
• Histologically, comedo DCIS typically have central necrosis in the duct, which can calcify.
• LCIS usually presents in the terminal ducts or ductules (acini).
• Signet-ring cells that contain mucin are frequently present.

Table 9-1 • (Continued)
Type
Invasive Disease
Infiltrating ductal •
Foundational Points
• Histologically, tumor cells can be seen in nests or cords that infiltrate the stroma.
• Associated with E-cadherin mutations.
• Signet-ring cells are common. • Usually ER-positive.
• Histologically, the presence of malig­ nant intraepithelial adenocarcinoma cells (Paget cells) within the epidermis of the nipple.
• Histologically, dermal lymphatic invasion by malignant cells.
High Yield Features
Most common invasive lesion (70%-80%).
carcinoma •
• Tendency to metastasize via lymphatics.
Tumor is usually hard (scirrhous carcinoma).
Infiltrating lobular • carcinoma •
Paget's disease of • the breast •
Inflammatory • breast cancer •
benign breast disease (ie, atypical hyperplasia or proliferative le­ sions with atypia), dense breast tissue compared to women of the same age category, tall women, obesity in postmenopausal women (BMI >30 kg/m2), alcohol (>2 drinks/dy), ionizing ra­ diation to the chest (especially at a young age).
Clinical Features\:
Patients may be asymptomatic, especially in the early stages of breast carcinomas or in DCIS and LCIS. In advanced lesions, a breast mass may be apparent. The classic presentation may be described as a hard, irregular, fixed breast mass with skin tether­ ing. Metastatic lesions may present with bone pain, coughing or shortness of breath (lung involvement), nausea and jaundice (liver involvement), headache and altered cognition (brain involve­ ment), or lymphadenopathy. Paget’s disease of the breast, which is the presence ofmalignant cells within the epidermis ofthe nipple that can spread to the areola, may present as a scaly, ulcerated, oozing, erythematous, raw lesion involving the nipple and areola. Bloody discharge may be present. Paget’s disease is usually unilat­ eral, but bilateral cases have been reported. Inflammatory breast cancer (IBC), which is the presence of malignant cells within the dermal lymphatics, may present with the classic peau d’orange (see Figure 9-2 and Color Plate 10). IBC may also appear as an “in­ flamed breast” that has a pink-red or purplish hue discoloration of the skin, a warm breast, nipple crusting, and nipple retraction may be present. Since IBC is an aggressive cancer, there is usually lymph node involvement and metastases at the time ofpresentation.
Next Step\:
Step 1) Breast cancer screening recommendations with mam­ mography vary from several different organizations. The overall consensus is that screening should definitely begin by 50 to 69 years of age. The controversy lies within routine screening at 40 to 49 years of age, >70 years of age, and the frequency of screening.
Second most common type of invasive breast cancer (5%-10%).
Seen in older women.
• Tend to be bilateral.
• Tend to be multicentric.
• Metastasize to odd places (eg, ovary, uterus, meninges, Gl tract).
Accounts for approximately 1%-3% of breast cancers.
Associated with an underlying in situ lesion (usually DCIS) and/or invasive breast cancer (usually HER2-positive) 85%-88% of the time.
Accounts for <2% of invasive breast cancers.
Aggressive cancer.
• High risk for metastases.
• Black women >white women
• Early age of diagnosis in women, but older age of diagnosis in men.
CHAPTER 9 GYNECOLOGY 117
In this area ofcontroversy, cancer screening should be individual­ ized, with shared decision-making, and risk and benefits should be discussed. The efficacy of breast self-examination (BSE) is unproven, and the clinical breast examination (CSE) is not stan­ dardized. Patients with known genetic predisposition for BRCA1 or BRCA2 mutation should be referred to genetic counseling.
Step 2) The screening mammography provides two views of the breast, and if a suspicious lesion is seen, a diagnostic mam­ mography that provides supplemental views may be able to characterize the lesion better. In addition, the ultrasound may be ordered to differentiate between a cyst and a solid mass. A malignant lesion on ultrasound will typically demonstrate irregular borders, solid mass, and internal echoes.
FIGURE 9-2 • Peau d' orange. Note the texture of the skin, which appears as an "orange peel."The skin is thickened with enlarged pores secondary to lymphedema. (Reproduced with permission from Usatine RP, Smith MA, Mayeaux EJ Jr, et al. The ColorAtlas ofFamilyMedicine. 2nd ed. New York\: McGraw-Hill; 2013\:553.)

118 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Step 3) Tissue is the issue. There are many types of biopsy pro­ cedures (eg, FNA, core needle biopsy, stereotactic, MRI-guided, wire localization, excisional, incisional, skin punch biopsy), and the choice is dependent on the treating physician. However, it should be noted that additional biopsies are required for Paget’s disease (biopsy of the nipple), inflammatory breast cancer (full thickness skin biopsy), and metastases (biopsy of a metastatic lesion). Once the tissue is obtained, the pathologist will look for histologic evidence of malignant disease and assay for estrogen (ER) and progesterone (PR) receptors and human epidermal growth factor 2 (HER2) receptor expression (see Table 9-1). Consider the following common biopsy procedures\:
Fine needle aspiration biopsy (FNA)—FNA involves a syringe and a needle that essentially draws out the tissue specimen. Unfortunately, FNA cannot differentiate between in situ lesions and invasive cancer.
Core needle biopsy (CNB)—Core needle biopsy can be performed instead of the FNA, and the advantage of CNB is that it can differentiate between in situ and invasive cancer.
Excisional biopsy—Excisional biopsy can be performed as the initial procedure, but it can also be performed ifthe core needle biopsy is negative or nondiagnostic but the clinical suspicion is high.
Step 4) When 3 assessments (ie, clinical examination, radiographic evaluation, needle biopsy) are used to diagnosis breast cancer, it is referred to as the triple test, and when all three parameters are posi­ tive, it is said to be concordant. Patients should proceed to a staging workup to assess the extent of the disease. Typically, patients are staged preoperatively (clinical stage) and postoperatively (patho­ logic stage). Patients should initially have laboratory studies (eg, CBC, LFTs, alkaline phosphatase). There are no standardized im­ aging studies, but evaluation for bone, lungs, and liver may be pur­ sued for patients suspected of metastases or locally advanced breast cancers (eg, PET scan, CT, CXR, liver ultrasound, bone scan).
Step 5) The treatment approach to patients with breast cancer vary. Consider the following\:
Lobular Carcinoma In Situ (LCIS)
Step 1) If LCIS is identified on core needle biopsy, the next best step is to perform an excisional biopsy to exclude an associated malignancy.
Step 2) Since LCIS is not viewed as a direct precursor to breast cancer, but rather as a marker of increased risk for invasive breast cancer, it is not necessary to perform a local excision with negative margins. Instead, treatment options include surveillance, chemoprevention with tamoxifen, or bilateral prophylactic mastectomy.
Ductal Carcinoma In Situ (DCIS)
Step 1) Breast-conserving therapy (wide excision with neg­ ative margins + radiation). Axillary staging is generally not indicated in DCIS.
Step 2) ER-positive patients can be treated with tamoxifen for 5 years. ER-negative patients should have counseling on the use of tamoxifen since the benefits are unclear in this group of patients.
Early Stage Breast Cancer
Patients in this category can have a tumor size that can poten­ tially be >5 cm, but there is definitely no evidence of tumor extension to the chest wall or skin, fixed or matted nodes, or metastases.
Step 1) Preoperatively, in a clinically detected axillary node, an FNA or core biopsy should be taken from the node. If the node is positive, then an axillary node dissection is under­ taken at the time of surgery. If the node is negative, then a sentinel lymph node dissection (ie, injecting a dye and radio­ active tracer near the lesion, which will identify one or more sentinel lymph nodes) is undertaken at the time of surgery.
Step 2) Breast-conserving therapy (BCT) or mastectomy ± radiation. The following are absolute contraindications for BCT\:
• Pregnancy
• Prior radiation to the affected breast
• Persistent positive margins
• Diffuse malignant microcalcifications on mammography
• Multicentric disease (ie, >2 tumors outside the breast quadrant from the primary tumor)
Step 3) Adjuvant systemic therapy may be given. Consider the following\:
Chemotherapy—Considered in patients that are node­ positive, tumor size >1 cm, node-negative of tumor size >0.5 cm plus hormone receptor-negative, node­ negative of tumor size >0.5 cm plus HER2-positive, or node-negative of tumor size >0.5 cm plus triple­ negative breast cancer (ie, ER/PR-negative and HER2- negative).
Biologic therapy—Patients should be given trastuzumab as an IV infusion for patients that are HER2-positive.
Hormonal therapy—ER/PR-positive breast cancers may be given tamoxifen for premenopausal women (preferred approach) or an aromatase inhibitor (eg, letrozole, anastrozole, exemestane) for postmenopausal women (ie, improves survival outcomes compared to tamoxifen).
Locally Advanced Breast Cancer
Patients in this category can have a tumor size that can poten­ tially be >5 cm, may or may not have tumor extending to the chest wall or skin, may or may not have fixed or matted nodes, and definitely no evidence of metastases.
Step 1) Neoadjuvant (preoperative) chemotherapy should be given to patients with locally advanced disease. Trastu­ zumab may be added to the chemotherapy in patients that are HER2-positive.
Step 2) Surgery with either a mastectomy or breast-conserv­ ing surgery (ie, lumpectomy), which depends on the treat­ ment response from the neoadjuvant therapy and patient preference.
Step 3) Postoperative radiation therapy.

Step 4) Adjuvant systemic therapy may be given. Adjuvant (postoperative) chemotherapy is generally not given if neo­ adjuvant chemotherapy was administered. Biologic therapy (eg, trastuzumab) may be resumed postoperatively for 1 year in patients that are HER2-positive, and hormonal therapy may be given to patients that are hormone receptor-positive.
Metastases
Treatment is not aimed at a curative attempt but rather to im­ prove the quality of life since the median survival is approxi­ mately 2 years. Patients have been treated with chemotherapy, hormonal therapy, biologies, surgical intervention (eg, thora­ centesis for a pleural effusion), and bisphosphonates (eg, zole- dronic acid) for bony metastases.
Paget Disease of the Breast
Treatment approach is similar to any other invasive breast cancer. Mastectomy has been the traditional standard treat­ ment, but breast-conserving therapy (ie, removal of the lesion plus nipple areolar complex + radiation) is gaining wider acceptance. Patients with an underlying DCIS do not have to undergo axillary node investigation, but patients with an un­ derlying invasive cancer that is node-negative should undergo a sentinel lymph node biopsy, while those with a node-positive should undergo axillary node dissection.
Inflammatory Breast Cancer
Step 1) Neoadjuvant chemotherapy and add trastuzumab to the chemotherapy if HER2-positive.
Step 3) Mastectomy (ie, usually modified radical mastec­ tomy that includes axillary dissection since sentinel node biopsy is contraindicated in this breast cancer).
Step 4) Postoperative radiation therapy.
Step 5) Adjuvant biologic therapy (eg, trastuzumab) may be resumed postoperatively for 1 year in patients that are HER2-positive, and adjuvant hormonal therapy may be given to patients that are hormone receptor-positive.
Follow-Up\:
The cornerstone of surveillance includes the clinical examina­ tion and mammography. Asymptomatic cancer survivors do not require an aggressive surveillance that includes laboratory testing (eg, CBC, tumor markers) and radiographic imaging (eg, CXR, ultrasound, PET scans, CT). The 5-year survival rates for early stage breast cancer (stage I-IIB) range from 70% to 95%, local advanced breast cancer (stage IIIA-IIIB) range from 48% to 52%, and metastases (stage IV) is 18%. The 5-year survival for Pagets disease of the breast range from 20% to 60% with an associated palpable mass and 75% to 100% without a palpable mass. The 5-year survival rate for inflammatory breast cancer ranges from 30% to 55%, which is noticeably worse compared to noninflammatory advanced breast cancer.
Pearls\:
• Common sites for breast cancer metastases involve the bone, liver, and lungs. Less than 5% of cases will have CNS involve­ ment as the first site of metastases.
• Premenopausal woman with a BMI >30 kg/m2 have a lower risk of breast cancer.
• MRI is not routinely used as a screening modality for breast cancer. The indications for breast MRI are still evolving; however, it is being used as an adjunct to mammography in patients that are at high risk for breast cancer (eg, BRCA mutation). Because of the high cost, MRI is typically used in select cases (eg, patient with axillary adenopathy with an occult tumor).
• The goal of neoadjuvant therapy is to improve surgical outcomes.
• Breast irradiation is contraindicated in pregnancy.
• Patients that generally have an unfavorable prognosis include black women >white women, young or old age at diagnosis, HER2 overexpression in the untreated, nodal involvement, or metastases.
• In the first 5 years following initial diagnosis of breast cancer, it appears that ER-negative cancers have a higher rate of re­ currence compared to ER-positive cancers.
• There is a higher risk of recurrence in patients who receive only breast-conserving surgery (eg, lumpectomy) without radiation compared to breast-conserving therapy (BCT).
• The breast-cancer survival rate is nearly equivalent in pa­ tients receiving breast-conserving therapy (ie, lumpectomy + radiation) or total mastectomy.
• Simple mastectomy involves removal of the entire breast without removal of the axillary contents or pectoral muscles.
• Modified radical mastectomy involves removal of the breast, underlying fascia ofthe pectoralis major muscle, and axillary contents, but sparing the pectoralis major muscle.
• Radical mastectomy involves removal ofthe breast, pectoralis major and minor muscles, and axillary contents.
• Tamoxifen is a selective estrogen receptor modulator (SERM) that is an estrogen receptor antagonist on tumor cells in the breast. However, it may act as an estrogen agonist on the uterus.
• Tamoxifen is approved for breast cancer treatment and breast cancer prevention in premenopausal and postmenopausal women at high risk.
• Tamoxifen can reduce the risk of developing hormone receptor-positive breast cancer in both premenopausal and postmenopausal women, but does not affect improved survival rates.
• Tamoxifen is associated with an increased risk of endome­ trial cancer, thromboembolic events, hot flashes, vaginal dis­ charge, cataracts, sexual dysfunction, and liver dysfunction, but a protective effect on bone mineral density (BMD) in postmenopausal women.
• Tamoxifen is contraindicated in patients on warfarin therapy and in patients with DCIS or high risk for breast cancer who have a history of thromboembolism. Tamoxifen should also be avoided in pregnancy (category D).
• Raloxifene is a SERM that is an estrogen receptor antagonist on the breast and uterus, but has estrogenic effects on the bone (T bone density) and lipids (i LDL).
CHAPTER 9 GYNECOLOGY 119

120 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Raloxifene is approved for postmenopausal osteoporosis and breast cancer prevention in postmenopausal women at high risk for invasive breast cancer.
• Raloxifene can reduce the risk of developing hormone receptor-positive breast cancer, but does not affect improved survival rates.
• Raloxifene is associated with hot flashes and thromboembolic events, but no increased risk in endometrial cancer.
• Raloxifene is contraindicated in patients with a history of thromboembolic disorders.
• Aromatase inhibitors (eg, letrozole, anastrozole, exemestane) lead to a reduction in circulating estrogen by inhibiting the peripheral conversion of androgens to estrogens.
• Aromatase inhibitors are approved for breast cancer treat­ ment but not for breast cancer prevention.
• Aromatase inhibitors demonstrate improved outcomes in hormone receptor-positive postmenopausal women com­ pared to tamoxifen.
• Aromatase inhibitors are associated with an increased risk of fractures, decrease bone mineral density (osteoporosis), hypercholesterolemia, hot flashes, and cardiac events (eg, MI, angina).
• Aromatase inhibitors are associated with a lower risk of endometrial cancer and venous thrombosis compared to tamoxifen.
• Aromatase inhibitors are contraindicated in pregnancy (category X).
ENDOCRINE DISORDERS
I ENDOMETRIOSIS
Endometriosis is characterized by the presence of endometrial glands and stroma at extrauterine sites. The ectopic implants can occur at almost any place within the body. The ovaries are the most common site, but other locations include the anterior and posterior cul-de-sac, posterior broad ligaments, uterosac- ral ligaments, uterus, fallopian tubes, sigmoid colon, appendix, round ligaments, vagina, cervix, cecum, abdominal scars, kid­ ney, ureter, and bladder. The etiology is unclear.
Risk Factors\:
Increased risk—Early menarche, nulliparity, late menopause, prolonged menses, short menstrual cycles, family history (first- degree relatives)
Decreased risk—Late menarche, increased parity Clinical Features\:
Approximately one-third of patients will be asymptomatic. Symptomatic patients may present with a pattern recognition of secondary dysmenorrhea, deep dyspareunia, subfertility, heavy or irregular bleeding, chronic fatigue, or back pain. Keep
Trastuzumab is a monoclonal antibody that binds to extracellular HER2 protein, which then mediates antibody- dependent cellular cytotoxicity in cells that overexpress HER2.
Trastuzumab is approved for breast cancer treatment in pa­ tients that are HER2-positive.
Adding trastuzumab to adjuvant chemotherapy has been shown to have a survival benefit in HER2-positive patients.
Trastuzumab is associated with cardiomyopathy (ie, CHF and decreased left ventricular ejection fraction [LVEF]).
There are no contraindications to use trastuzumab.
Common chemotherapy agents used in breast cancer include doxorubicin, cyclophosphamide, and paclitaxel.
Ovarian function cessation is an alternative to tamoxi­ fen therapy in women who defer the risks associated with tamoxifen. Ovarian cessation can be accomplished by ovar­ ian ablation (eg, oophorectomy or pelvic radiation) or ovar­ ian suppression via GnRH agonists (eg, goserelin) with the end goal of reducing estrogen levels. When considering childbearing, ovarian suppression would be the better choice for women who want to continue to have children, while ovarian ablation would be acceptable for women who have completed childbearing.
On the CCS, remember to order an oncology consult if you’re going to use chemotherapy. You are managing the pa­ tient through the eyes of a primary care physician.
On the CCS, upon establishing a diagnosis of breast cancer, remember to “advise patient, cancer diagnosis.”
in mind that the cyclic pain that the patient feels is correlated with menses. Since endometriosis can affect almost any organ, clinical manifestations can vary such as the gastrointestinal tract (eg, dyschezia, hematochezia, diarrhea, constipation, abdominal pain, bloating) or the urinary tract (eg, dysuria, hematuria, urinary frequency). On examination, possible findings include tender nodules along the uterosacral ligament or posterior cul-de-sac. Thickening of the uterosacral ligaments. The uterus may be painful upon movement, and it may be fixed in the retro- verted position. The ovaries may be enlarged, tender, and fixed. Prior surgical scars may be tender at the time of menstruation.
Next Step\:
Step 1) A presumptive clinical diagnosis of endometriosis can be initially managed with empiric medical therapy. It should be noted that the primary modality for diagnosing endome­ triosis is by direct visualization of the implants via laparoscopy. However, since the procedure is invasive, it is often limited in the initial management. Asymptomatic patients can be man­ aged expectantly. NSAIDs and/or oral estrogen-progestin contraceptives can be attempted for mild pelvic pain for 3 to 6 months.
Step 2) Patients that continue to have pain despite NSAIDs or OCPs can be managed with other hormonal therapies. Consider the following\:

GnRH agonists—Leuprolide can be given as an IM injec­ tion once a month or every 3 months (ie, higher dosage) for a 6-month course of treatment. Retreatment can be extended to another 6-month course of treatment if add- back therapy with estrogen-progestin is given. Alternatives to leuprolide include nafarelin, which is administered intra- nasally, or goserelin, which is administered SubQ every 28 days for a maximum treatment duration of 6 months.
Progestins—Progestins induce decidualization and atrophy of the endometrial tissue. Medroxyprogesterone can be given as an IM injection every 3 months for up to 12 months, or norethindrone acetate can be administered orally for 6 to 9 months.
Steroid analogue—Danazol has antigonadotropic activ­ ity. It suppresses FSH and LH, which causes atrophy of the endometrial tissue. It is administered orally and can be given for up to 9 months. Since there are adverse side ef­ fects (eg, acne, oily skin, hirsutism, weight gain, hot flashes, depression, emotional lability, breast atrophy), it has fallen out of favor as a first-line agent.
Step 3) Patients that are refractory to medical management are candidates for a diagnostic laparoscopy and therapeutic treatment. Upon laparoscopy, the diagnosis can be confirmed by visualizing the implants and obtaining a biopsy. The classic lesions are described as a “powder-burn” or “gunshot” lesions. However, the lesions can vary in their color from blue-black, red, white, brown, yellow, clear, or pink. Surgery can be divided into conservative (eg, lysis of adhesions, implant resection) or definitive (eg, TAH-BSO). Definitive surgical therapy would be ideal in patients that have completed their childbearing and who continue to have unbearable symptoms despite other forms of treatment.
Follow-Up\:
Endometriosis is typically a chronic and progressive disease that can cause significant morbidity. Patients may require ongoing follow-ups since the duration of medical therapy is restricted (eg, GnRH agonists, progestins, danazol) except for oral con­ traceptives. In addition, patients that elect to do conservative surgery may have recurrence of their endometriosis, and post­ operative adhesion formation can occur.
Pearls\:
• Most patients with endometriosis have elevated CA-125 levels.
• The degree of visible endometriosis is not correlated with the severity of symptoms.
• Patients with endometriosis are not completely infertile. Problems with fertility may be attributable to pelvic adhe­ sions, distorted anatomy, or endometriomas. Management of subfertility involves a multi-interventional approach (eg, clomiphene, in vitro fertilization, intrauterine insemination, expectant management, surgery).
• Medical treatment of minimal to mild endometriosis does not lead to a higher rate of pregnancy compared to expectant management.
• Symptoms of endometriosis often improve during preg­ nancy and menopause. However, symptoms can recur after menopause, but most are related to postmenopausal hor­ mone replacement therapy.
• Endometriomas refers to ovarian endometriosis that becomes cystic. The cysts contain a brown thick fluid, sometimes re­ ferred to as a “chocolate cyst.” Patients can be asymptomatic, or the cysts can be painful with the potential to rupture.
• Imaging studies are not very helpful in the primary diagno­ sis of endometriosis. Ultrasound may be helpful in detecting an endometrioma. CT scans and MRI are not routinely per­ formed because of nonspecific findings on CT and the ques­ tionable cost-effectiveness of an MRI.
• Foundational point—On histology, the two major findings are the presence of endometrial glands and endometrial stroma. Sometimes, hemosiderin-laden macrophages may be present.
• On the CCS, if you decide to treat with oral contraceptives for endometriosis, an acceptable option is with the “OCP, low estrogen/low progestin” in the continuous mode offrequency.
I POLYCYSTICOVARIANSYNDROME
Polycystic ovarian syndrome (PCOS) is characterized by a complex, diverse group of disorders of uncertain etiology. The principal features include hyperandrogenism, menstrual dys­ function, ovarian abnormalities, and metabolic abnormalities.
Risk Factors\:
Family history (first-degree relatives), diabetes mellitus type 1 and type 2, insulin resistance, antiepileptics (eg, valproic acid).
Clinical Features\:
Patients with PCOS can present with a variety of clinical mani­ festations. Consider the following\:
Hyperandrogenism—Patients can develop hirsutism (ex­ cessive hair) along the upper lip, chin, periareolar, or linea alba. Excessive androgen can also result in male pattern baldness (ie, androgenetic alopecia), acne, voice deepening, clitoromegaly, or increased muscle mass.
Menstrual dysfunction—Patients can develop secondary amenorrhea, oligomenorrhea, anovulation, or ovulation- related infertility. Menstrual irregularities frequently pres­ ent at the time of menarche (ie, teenage years).
Ovarian abnormalities—Polycystic ovaries with multiple peripheral follicles may be seen in patients with PCOS, but not all patients.
Metabolic abnormalities—Patients may develop type 2 diabetes, hyperinsulinemia, insulin resistance, acanthosis nigricans (possible sign of insulin resistance), dyslipidemia, metabolic syndrome, or obesity (approximately 50% of patients with PCOS are obese).
Sleep apnea—Sleep apnea is a common finding in PCOS. Patients should be asked about excessive daytime somnolence.
CHAPTER 9 GYNECOLOGY 121

122 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Next Step\:
Step 1) The Rotterdam criteria can be used to make the diagno­ sis of PCOS. It requires 2 out of 3 of the following\:
• Oligo-ovulation and/or anovulation
• Clinical and/or biochemical signs of hyperandrogenism
• Polycystic ovaries (by transvaginal ultrasound)
Step 2) Disorders that mimic PCOS should be excluded; this principal is based on the NIH criteria. Consider the following adjunctive testing to rule out other conditions\:
TSH—Rule out thyroid disorders
P-hCG—Rule out pregnancy in a female with amenorrhea or oligomenorrhea
Serum prolactin level—Rule out hyperprolactinemia as a cause of menstrual irregularities
Serum IGF-1—Rule out acromegaly as cause of menstrual irregularities or hirsutism
24-hour urine cortisol level + low-dose dexamethasone suppression test—Rule out Cushing’s syndrome
Total and free testosterone level—Elevated levels indicate androgen excess
Serum DHEA-S level—Elevated levels suggests an adrenal androgen-secreting tumor
Serum 17-hydroxyprogesterone level—Elevated levels suggest nonclassic (late-onset) congenital adrenal hy­ perplasia secondary to 21-hydroxylase deficiency, which typically presents with hirsutism, acne, and menstrual irregularities.
ACTH (cosyntropin) stimulation test—Elevated 17- hyroxyprogesterone confirms the diagnosis of nonclassic congenital adrenal hyperplasia.
Step 3) Once the other disorders are excluded, the next best step is to assess the patient’s risk for diabetes and dyslipidemia.
Fasting lipid profile—Patients typically demonstrate a high LDL, low HDL, and high triglycerides.
Two-hour OGTT—A 75-gram oral glucose tolerance test should be performed. A fasting glucose or hemoglobin A1C are acceptable alternatives.
Step 4) Treatment of PCOS depends on the specific clinical problem that the patient presents. Consider the following\:
Hyperandrogenism
Step 1) Estrogen-progestin contraceptives are consid­ ered first-line agents for patients that do not want to be­ come pregnant. The estrogen component can increase sex-hormone binding globulin (SHBG) levels, which can ultimately decrease free testosterone levels.
Step 2) Patients that do not respond to OCPs in 6 months may add an antiandrogen to the regimen such as spirono­ lactone or finasteride.
Menstrual Dysfunction
Patients with anovulation, oligomenorrhea, or amenorrhea are at risk of endometrial cancer because of chronic unopposed estrogen. Endometrial protection should include progestin to prevent endometrial hyperplasia. Consider the following options\:
Option 1\: Estrogen-progestin contraceptives can provide endometrial protection, contraception, and reduce symp­ toms of hyperandrogenism.
Option 2\: Progestin-only (eg, medroxyprogesterone ace­ tate) can be given to patients that have a contraindication to estrogen-progestin contraceptives. It may be given intermit­ tently as an oral administration for 7 to 10 days every 1 to 2 months. However, it will not provide contraception in this format of administration. Neither will it provide relief of hy­ perandrogenism since it lacks the estrogen component, but it will provide endometrial protection.
Anovulatory Infertility
Step 1) Weight loss.
Step 2) If no response, clomiphene citrate.
Step 3) If no response, consider exogenous gonadotropins, laparoscopic ovarian surgery, or metformin in patients with coexisting glucose intolerance.
Obesity
Diet, exercise, and weight loss.
Type 2 Diabetes Mellitus
Management is similar to patients without PCOS.
Dyslipidemia
Management is similar to patients without PCOS (see Table 3-3).
Follow-Up\:
PCOS is a complex disorder that usually requires ongoing follow-ups for complications and sequelae associated with the condition. Patients that were initially negative for impaired glucose tolerance or type 2 diabetes should be periodically re­ assessed. Unfortunately, there is no consensus on monitoring endometrial hyperplasia, but physicians should be cognizant of any abnormal uterine bleeding. Finally, physicians should also be aware of any eating disorders, depression, or anxiety, which patients with PCOS are prone to experience.
Pearls\:
• Patients with PCOS have low levels of sex hormone binding globulin (SHBG) secondary from hyperandrogenism and hyperinsulinemia.
• Patients with PCOS are at risk of developing gestational dia­ betes during pregnancy.
• OCPs can decrease luteinizing hormone (LH) secretion re­ sulting in a decrease in ovarian androgen secretion.

Patients with PCOS typically have elevated LH levels and an FSH that may be normal or low, which can lead to an elevated LH\:FSH ratio greater than 3\:1. It is unnecessary to order an LH nor an LH\:FSH ratio in the diagnostic evaluation of PCOS.
Normal LH levels do not exclude the diagnosis of PCOS.
Foundational point—Elevated levels of LH can induce secretion of androstenedione from ovarian theca cells. Androstenedione is a precursor to testosterone. Once it is converted to testosterone, the testosterone can be converted to the more potent androgen dihydrotestosterone (DHT) by the enzyme 5tx-reductase.
Foundational point—Finasteride is a 5a-reductase inhibitor.
Foundational point—On cut section of a polycystic ovary, the ovary is usually enlarged, there is a dense stroma, and follicular cysts are arranged along the periphery of the ovary.
Connecting point (pg. 68)—Know the other causes of hy­ perprolactinemia.
• Connecting point (pg. 66)—Know the management of ac­ romegaly.
• Connecting point (pg. 76)—Know the workup for Cushing’s syndrome.
• Connecting point (pg. 79)—Know how to make the diagno­ sis of diabetes mellitus.
• Connecting point (pg. 23,24)—Know how to manage a pa­ tient with hyperlipidemia and know the components of the metabolic syndrome.
• On the CCS, this type of case would be a complicated case, but remember that a thorough and comprehensive ap­ proach does not necessarily reduce your score unless you order something that poses a risk to your patient. Keep in mind that there are multiple correct algorithms to achiev­ ing a good score, but you want to try to manage your patients by ordering relevant items based on the history, physical exam, patient updates, or updated lab or imaging findings.
CHAPTER 9 GYNECOLOGY 123

Hematology
KEYWORDS REVIEW
Acanthocytes—Also referred to as spur cells, which are spiculated red cells with irregular projections of varying sizes distributed throughout the cell and seen in liver disease and abetalipoproteinemia.
Anisocytosis—Variation in the size of red blood cells as seen on peripheral blood smear.
Aplastic anemia—Aplastic anemia can be characterized as bone marrow failure resulting in pancytopenia and bone marrow hypocellularity.
Basophilic stippling—Blue granules seen in the RBC repre­ senting ribosomal precipitates that occur in lead poisoning, thalassemias, and alcohol abuse.
Bite cells—The appearance of a "bite" on the RBC due to the removal of Heinz bodies by spleen phagocytes.
Echinocytes—Also referred to as burr cells, spiculated red cells with more uniform, evenly spaced projections compared to acanthocytes, seen in liver disease and end-stage renal disease.
Heinz bodies—Denatured hemoglobin found in RBCs, commonly seen in patients with G6PD deficiency following oxidative stress.
Hemosiderin—The intracellular storage of iron as opposed to circulating in the blood.
Howell-Jolly bodies—Cytoplasmic inclusions within RBCs representing nuclear remnants that are normally removed by the spleen. Howell-Jolly bodies are often found after a splenectomy or splenic dysfunction.
Hypochromic—Pertaining to low hemoglobin content in the RBCs.
125

126 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
MCHC—Mean corpuscular hemoglobin concentration reflects the hemoglobin concentration per given volume of RBCs. A low MCHC will usually have cells that are hypochromic, normal MCHC levels will have cells as normochromic, and elevated MCHC levels will have cells as hyperchromic.
Poikilocytosis—Variation in red blood cell shapes such as a spur cell, target cell, sickle cell, or schistocyte.
Rouleaux—RBCs "stacking" on top of each other as seen in the peripheral blood smear of multiple myeloma patients.
RPI—Reticulocyte production index is a doubly corrected reticulocyte count, which corrects for the anemia and reticulocyte maturation time. An RPI value close to 1.0 is considered normal.
Schistocyte—Fragmented helmet-shaped RBCs seen in microangiopathic hemolytic anemia, artificial heart valves, and malignant hypertension.
ANEMIA
1 OVERVIEWOFANEMIA
Anemia is an important indicator of disease. There are a variety of underlying causes and several ways to classify anemia. It may be helpful to broadly divide anemia into problems of production or problems of destruction and accelerated blood loss (hemorrhage). See Figure 10-1.
B IRON-DEFICIENCYANEMIA
A finding of iron-deficiency anemia can be due to an increase in iron loss (eg, blood loss from menses, GI tract, or blood donation), decrease in iron intake (eg, inadequate diet, mal­ absorption, iron sequestration such as pulmonary hemosidero­ sis), or an increase in demand for iron (eg, pregnancy, infancy, adolescence).
Clinical Features\:
Patients with iron-deficiency anemia may present with the ane­ mia itself such as fatigue, pallor, reduced exercise tolerance, or poor feeding (infants). Commonly associated signs and symp­ toms of iron-deficiency anemia include\:
Neurologic—Behavioral and neurodevelopmental distur­ bances seen in the young.
Mouth—Fissures at the corner of the mouth (cheilosis or angular stomatitis).
Tongue—Glossitis will present as a smooth tongue.
Nails—Koilonychia will present as spooning of the finger­ nails.
Sideroblastic anemia—Production of ringed sideroblasts (ie, a ring of iron deposits along the nucleus of an erythroblast as seen with Prussian blue stain) from the bone marrow which can be due to acquired or congenital causes.
Smudge cells—When fragile lymphocytes are smeared on a glass slide, the cells appear "smudged "which is characteris­ tic of chronic lymphoid leukemia (CLL).
Spherocyte—RBCs that are sphere-shaped without central pallor, commonly seen in hereditary spherocytosis or autoimmune hemolytic anemia.
Target cell—RBCs with a central hyperchromic density with a halo of pallor that appears as a "bull's-eye," commonly seen in thalassemia, iron deficiency, liver disease, post splenectomy, and hemoglobinopathies (eg, Hb D).
Tear-shaped RBC—Also referred to as a dacrocyte, can be seen in myelofibrosis, myelodysplastic syndromes, severe iron deficiency, thalassemias, and hemolytic anemias.
Pica—Patients may have an unusual appetite for certain substances such as ice (pagophagia), dirt (geophagia), hair (trichophagia), or starch (amylophagia).
Next Step\:
Step 1) Diagnosis of iron-deficiency anemia is primarily a labo­ ratory diagnosis. Order a CBC, which will also include the MCV, MCHC, and RDW, but not the reticulocyte count. In addition, or­ der an iron panel, which will include serum iron, total iron binding capacity (ie, transferrin), and ferritin levels (see Table 10-1).
Step 2) Management of iron-deficiency anemia is to identify and treat the underlying cause of the iron-deficiency anemia. First-line treatment for iron-deficiency anemia is with oral iron therapy (eg, ferrous sulfate). With the appropriate dosage, the re­ ticulocyte count should increase within 4 to 7 days after starting therapy, and the hemoglobin level should increase 1 g/dL every 2 to 3 weeks while on iron therapy. Intravenous iron therapy should be limited to patients with intolerance to oral iron, refractory to oral iron, dialysis patients, and patients with inflammatory bowel disease. In the pediatric population, ifthe anemia is not severe (ie, Hb <7) and a presumptive diagnosis of iron-deficiency anemia is made along with laboratory studies indicating a microcytic ane­ mia, a therapeutic trial of iron therapy can be started.
Follow-Up\:
It can take up to 2 to 4 months for iron stores to return back to baseline while on oral iron therapy. Deciding to continue for another 3 to 6 months of iron therapy should be individualized with each patient. Children on a therapeutic trial of iron should be seen in 4 weeks. If the microcytic anemia fails to respond to iron therapy, further workup is warranted (eg, stool hemoccult, reticulocyte count, peripheral blood smear, vitamin B12 levels, folate levels, Hb electrophoresis).

Pearls\:
•
Serum ferritin is the most useful indicator of iron-deficiency anemia because it has a very high sensitivity and specific­ ity. However, interpretation should be adjusted accordingly in the setting of infectious or inflammatory conditions because ferritin is an acute-phase reactant. In some cases, a C-reactive protein (CRP) is added to the order to validate the results of the ferritin levels.
Microcytic
(MCV < 80)
• Iron deficiency
• Thalassemia
• Hemoglobinopathy
• Anemia of chronic disease
• Sideroblastic anemia
• Copper deficiency • Zinc poisoning
• Lead poisoning
Red cell morphology
Normocytic
(MCV 80-100)
• Iron deficiency (early)
• Malignancy/ marrow infiltration
• Anemia of chronic disease
• Aplastic anemia
• Chronic renal failure
• HIV infection
Macrocytic
(MCV > 100)
• Vitamin B12 deficiency
• Folate deficiency
Immune
Autoimmune
Alloimmune
Drug-induced
Hemolysis
• Hereditary spherocytosis
• Elliptocytosis Enzymopathy
• G6PD deficiency
• Pyruvate kinase deficiency
Hemoglobinopathy
• Sickle cell
• S-p thalassemia
Hemorrhage
Subacute blood loss
Extrinsic
Microangiopathy • HUS
• TTP
• DIC
• Artificial heart valve
Liver disease Hypersplenism Burns Infections
• Malaria
• Bartonella • Babesia
Agents
• Nitrites
• Snake bites • Aniline dyes • Dapsone
Production problem
Inappropriately low reticulocytes (Reticulocyte production index [RPI] < 2.5)
Destruction problem
Appropriately elevated reticulocytes (Reticulocyte production index [RPI] > 2.5)
FIGURE 10-1 • Overview of anemia.
• Iron absorption occurs at the level of the duodenum and proximal jejunum.
• Iron absorption is reduced in the presence of tannates (eg, tea), phytates (eg, bran, cereal, oats, rye liber), phosphates, and medications (eg, proton pump inhibitors, antacids, his­ tamine H2 blockers).
• Iron absorption is enhanced in the presence of ascorbic acid, meat, fish, and poultry.
• Plummer-Vinson syndrome, also referred to as Paterson- Kelly syndrome, can be characterized by iron-deficiency anemia, and esophageal webs causing dysphagia.
• Drugs—zidovudine, hydroxyurea,
methotrexate, • azathioprine,
• Myelodysplasia • Fanconi anemia • Hypothyroidism • Down syndrome • Liver disease
• Alcoholism
Intrinsic
Table 10-1 • Laboratory Differentiation from Iron-deficiency Anemia
Parameter Serum Iron
Serum Ferritin
TIBC (Transferrin)
% Transferrin Saturation
Iron-deficiency Anemia of Anemia Chronic Disease
4 4
4 Normal to high t Normal to low 4 Normal to low
Sideroblastic Anemia
Normal to high Normal to high Normal Normal to high
Thalassemia
Normal to high Normal to high Normal Normal to high
Anemia
• • •
Fetal Rh
incompatibility Membranopathy
CHAPTER 10 HEMATOLOGY 127
Nonimmune

128 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Transferrin is a protein that binds to iron and circulates in the plasma. The TIBC is a laboratory test that indirectly measures the transferrin.
• Serum transferrin receptor (sTfR) is a protein released into cir­ • culation, with elevated levels are seen in iron-deficient states.
• Protoporphyrin is involved in the intermediate steps to heme synthesis. Elevated levels of protoporphyrin are seen in iron deficiency and lead poisoning. •
• Red cell volume distribution width (RDW) is a measure of
the variation in RBC size (anisocytosis). An elevated RDW is commonly seen in deficiencies in iron, vitamin Bp, and folate. •
• The Mentzer index (ie, MCV/RBC count) is sometimes used to differentiate between iron-deficiency anemia and thalassemia. A Mentzer index >13 suggests iron-deficiency • anemia, while a value <13 suggests a thalassemia.
• Iron-deficiency anemia during pregnancy is mainly due
to plasma volume expansion relative to hemoglobin mass. • Although most prenatal vitamins contain iron, sometimes
iron is given in the second or third trimester to augment maternal hemoglobin.
determine if the child (<1 years old) is consuming whole cow’s milk because it can cause intestinal bleeding and it is low in iron content.
On the CCS, if you want the iron panel, you have to order it separately such as “Iron, serum with/TIBC” and “Ferritin, serum.” The practice CCS software does not recognize “iron panel” in the order menu.
On the CCS, the practice CCS software will recognize an order for “reticulocyte count” but does not recognize “reticu­ locyte production index (RPI).”
On the CCS, the “CBC with differential” will provide you results of the CBC, WBC differential, and peripheral blood smear.
On the CCS, consider a stool hemoccult in an adult since the premise of iron deficiency in an adult is a GI bleed until proven otherwise.
On the CCS, any child who presents with iron deficiency should have a blood lead level to screen for lead toxicity if it was not already completed by routine screening.
• Connecting point (pg. 186)—Part of the presumptive diagnosis in children with iron-deficiency anemia is to
HEMOGLOBINOPATHIES
I ALPHATHALASSEMIA
Alpha (a) thalassemia is due to a deletion or mutation in one or more of the four alpha globin genes (ie, aa/aa). This results in an underproduction of alpha globin chains, but a relative excess of gamma (y)-globin chains in the fetus and newborn and beta ((3)-globin chains in children and adults.
Clinical and Hematologic Features\:
The signs, symptoms, and test results will differ, depending on how many alpha alleles are affected\:
1 alpha defect (-a/aa)—Also referred to as a silent carrier, alpha thalassemia minima, or alpha thalassemia-2 trait. These patients will be asymptomatic and hematologically are normal. Hemoglobin electrophoresis will be normal (ie, normal levels of HbA, HbA2, HbF).
2 alpha defects (cis deletion aa/—, or trans deletion a-/ a-)—Also referred to as alpha thalassemia minor or alpha thalassemia-1 trait. Asians will commonly carry the cis de­ letion, while people of African origin will carry the trans de­ letion. Most patients will have mild anemia with the blood smear demonstrating microcytosis, hypochromia, and target cells. Hemoglobin electrophoresis will be normal.
3 alpha defects (a-/—)—Also referred to as hemoglo­ bin H (HbH) disease, which is composed of 4 beta chains
• On the CCS, remember to “advise patient, side effects of medication” since oral iron can cause nausea, vomiting, GI upset, constipation, and diarrhea.
forming an unstable tetramer. In the later stages of eryth- ropoiesis, HbH will precipitate and form inclusion bodies within the red blood cells, which will result in moderate to severe chronic hemolytic anemia. Other findings may include variable bony changes, splenomegaly, and neo­ natal jaundice. Hemoglobin electrophoresis will typically demonstrate a higher percentage of Hb Barts (y4) at birth, but a higher percentage of HbH ((3 ,) in older children and adults.
4 alpha defects (— /— )—-Also referred to as alpha thalas­ semia major or hydrops fetalis with Hb Barts. At tliis point, there are no alpha chains. Instead, there is an excess of gamma (y) globin chains forming tetramers or Hb Barts (y4) that will have such a high oxygen affinity that it shifts the oxygen dissociation curve to the left. As a result, almost no oxygen is delivered to the fetus, which causes asphyxia, massive total body edema (hydrops fetalis), high-output congestive heart failure, and death in utero or shortly after birth. Hemoglobin electrophoresis will show the presence of Hb Barts (y4), HbH ((34), Hb Portland (Z2y2) and the complete absence of HbA, HbA2, and HbF.
Next Step\:
Step 1) Diagnosis of alpha thalassemia is usually one of exclu­ sion. However, begin with laboratory testing such as a CBC and ferritin levels (see Table 10-1). Alpha thalassemia is commonly mistaken for iron-deficiency anemia, and it is important to dif­ ferentiate the two conditions because supplemental iron therapy

can cause iron overload resulting in secondary hemochromato­ sis in patients with alpha thalassemia. Other diagnostic testing includes a peripheral blood smear and staining with a supravi­ tal dye such as brilliant cresyl blue to detect inclusion bodies as seen in HbH disease.
Step 2) Hemoglobin electrophoresis may be helpful when alpha thalassemia is still suspected.
Step 3) There is no specific therapy for silent carriers or alpha thalassemia minor. Alpha thalassemia major is incompatible with extrauterine life. Similar to G6PD deficiency, HbH disease may have exacerbations of hemolytic anemia when exposed to oxidant stress such as infection or drugs (eg, sulfa). During these periods, transfusions may be required along with iron chelation (eg, deferoxamine). In time, patients with HbH dis­ ease may require a splenectomy if transfusion requirements are increased or ifthere is excessive anemia.
Step 4) Genetics counseling should be offered. Follow-Up\:
Patients undergoing chronic transfusion therapy should have close follow-up to ensure that the patient is not iron overloaded.
Pearls\:
• Foundational point—Hemoglobin F (ie, (X2y2) is the pre­ dominant hemoglobin during fetal development and decreases significantly after 6 months of life. It is only 1% to 2% of the hemoglobin in adults.
• Foundational point—Hemoglobin A (ie, a2(32) is the pre­ dominant form of hemoglobin in adults and children >6 months of life.
• Foundational point—Hemoglobin A2 (ie, a282) is com­ posed of two alpha chains and two delta chains. It is a minor component of hemoglobin and is <3% of the total hemoglo­ bin found in adults.
• Foundational point—Fetal hemoglobin has a higher affinity for oxygen and will therefore shift the oxygen-hemoglobin dissociation curve to the left.
• Connecting point (pg. 176)—Fetal hydrops can also be seen in rhesus incompatibility.
• Connecting point (see next section)—HbH disease can resemble beta thalassemia intermedia.
• On the CCS, when you order “hemoglobin electrophoresis” in the practice CCS, you will get results of the HbA, HbA2, HbS, and HbF.
a BETATHALASSEMIA
Beta (|3) thalassemia is due to a mutation or rarely a deletion of one or both of the two beta globin genes (ie, p/(i). This re­ sults in an underproduction of beta globin chains, but a relative excess ofunstable alpha globin chains. The severity ofthe anemia depends on whether there is complete absence of beta globin chains (p°) or decreased production of beta globin chains (|3+), as well as the gene dosage (ie, homozygous or heterozygous).
Beta thalassemia is commonly found in those of Mediterranean, African, and Asian descent.
Clinical and Hematological Features\:
The signs, symptoms, and test results will differ depending on the quantity and severity of affected beta globin alleles.
Beta thalassemia minor—Also referred to as (3-thalassemia trait. These patients have one normal beta globin allele and onedefectivebetaglobinallele(eg,p/p°orp/p+).Themajority of these heterozygotes will be asymptomatic. Hematologi- cally, they will have a normal RDW, and the peripheral blood smear may demonstrate microcytosis, hypochromia, target cells, tear-shaped RBC, or basophilic stippling. Hemoglobin electrophoresis will classically reveal a predominant HbA, elevated HbA2, and occasional elevations of HbF.
Beta thalassemia intermedia—Beta thalassemia interme­ dia refers to a group of patients with a clinical severity that falls between beta thalassemia minor and beta thalassemia major. The genotype in this category is very heterogeneous because patients in this group can have mild forms of homozygosity (eg, p+/p+)to severe forms ofheterozygosity (eg, p/p° or P/P+). Patients may not have any symptoms until after the first year of life, when they may have mod­ erate anemia with occasional blood transfusions (not nec­ essarily regular blood transfusions). Some of the clinical features include skeletal changes, hepatosplenomegaly, leg ulcers, thrombosis, gallstones, osteoporosis, or pulmonary hypertension.
Beta thalassemia major—Also referred to as Cooley’s anemia, this is the most severe form of beta thalassemia. At this point, there are no beta globin chains produced (ie, p°/p°) or very small amounts produced (ie, p+/p+). In addition, there is an excess of insoluble aggregates of alpha globin chains that precipitate within the cell (Heinz bodies) that ultimately lead to increased hemolysis and ineffective erythropoiesis. Symptoms do not appear in the first 6 month of life because ofthe presence ofHbF. After 6 months, HbA would normally take over, but because there are no beta globin chains patients begin to experience pallor, irritability, jaundice, abdominal swelling due to hepatosplenomegaly, and growth retardation. Soon thereafter, ineffective erythropoi­ esis causes bone marrow expansion to occur which results in “chipmunk facies,” frontal bossing, prominent malar emi­ nences, and “hair-on-end” or “crew haircut” appearance on skull x-ray. Bone changes also occur on long bones, pelvis, and vertebrae. Ineffective erythropoiesis can also result in extramedullary hematopoiesis with a mass that can potentially cause a spinal cord compression. After the age of 10, patients will have complications related to chronic iron overload. Common manifestations include diabetes, heart failure, bronzing of the skin, hypothyroidism, and hypogonadism (ie, delayed onset of primary and secondary sexual development). Patients who have not been transfused regularly will typically die before the third decade of life, and most deaths are due to cardiac-related complications. Hema- tologically, the peripheral blood smear will be similar to beta
CHAPTER 10 HEMATOLOGY 129

130
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
thalassemia minor with the addition of increased nucleated RBCs and the presence of inclusion bodies (Heinz bodies), which can be appreciated at this stage with a supravital dye. Patients may have findings of hemolysis, which include T LDH, T indirect bilirubin, and i haptoglobin. Hemoglobin electrophoresis will reveal absent to severely reduced HbA, variable levels of HbA2, and elevated levels of HbF.
Next Step\:
Step X) Diagnosis of beta thalassemia minor may not always be apparent on routine CBC and can commonly be mistaken for iron-deficiency anemia. It should be noted that the MCV of beta thalassemia minor ranges from 55 to 75 £L, with a hematocrit al­ most always >30%. However, in iron deficiency an MCV is rarely <80 fL until the hematocrit is <30%. Obtaining iron studies (see Table 10-1) is helpful in differentiating between the two condi­ tions and to avoid unnecessarily administrating iron supplements to patients with beta thalassemia. Diagnosis of beta thalassemia intermedia is often made clinically. Patients in this category should be able to maintain a hemoglobin >6 to 7 g/dL at the time of diag­ nosis and do not require regular blood transfusions. The diagnosis of beta thalassemia major is often made earlier because the signs and symptoms are presented earlier. Laboratory studies showing signs of hemolysis, abnormalities on the peripheral blood smear, and staining of inclusion bodies will begin to make the diagnosis of beta thalassemia major apparent.
Step 2) Hemoglobin electrophoresis is used to confirm the diagnosis of beta thalassemia. Bone marrow examination is usually not needed to make the diagnosis, but examination will reveal marked erythroid hyperplasia.
Step 3) Treatment of beta thalassemia is as follows\:
Beta Thalassemia Major
• Blood transfusions are given on a regular basis. Before the first transfusion, hepatitis B vaccination is given and red blood cell antigen typing is carried out.
• Iron chelation therapy (eg, deferoxamine) along with care­ ful administration of vitamin C (improves iron chelation) is inevitable in this group of patients.
• Hematopoietic cell transplantation (HCT) should be considered in a select group of patients for the possibility of a cure.
• Splenectomy is usually required if the transfusion require­ ments increase >50% or there is growth retardation or symp­ tomatic splenomegaly.
BLEEDING DISORDERS
1 HEMOPHILIA
Hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) are X-linked recessive disorders that occur almost exclusively in males since they have only one X chromosome.
• Vaccinations with pneumococcal and Haemophilus vaccines should be given before a splenectomy is anticipated.
• Prophylactic antibiotics with penicillin are given to sple- nectomized patients.
• Folic acid supplementation. Beta Thalassemia Intermedia
• Blood transfusions may be occasionally given when patients become symptomatic (ie, usually Hb <7 g/dL) at such times as an aplastic crisis from parvovirus B19 infections. Eventually, the majority of patients will need chronic blood transfusions by their third or fourth decade of life, which would then classify them as beta thalassemia major.
• Iron chelation therapy may be needed when serum ferritin levels exceed 300 |ig/L or there is evidence of iron deposition into organs from imaging.
• Splenectomy, vaccinations, prophylactic antibiotics, and folic acid may be needed for the same reasons as beta thalassemia major.
Beta Thalassemia Minor
• There is no specific therapy for beta thalassemia minor.
Step 4) Genetic counseling should be offered since beta thalas­ semia is inherited in an autosomal recessive manner.
Follow-Up\:
Patients affected with beta thalassemia major need close monitoring that includes assessment of growth and develop­ ment, ophthalmologic and audiologic exams, cardiac, thyroid, pituitary, and gallbladder evaluations, bone densitometry to assess for osteoporosis, and serum evaluations of ferritin, LFTs, and assessment of glucose intolerance.
Pearls\:
• Iron overload can still occur in patients with beta thalas­ semia intermedia even without blood transfusions because of increased intestinal absorption of iron secondary to inef­ fective erythropoiesis.
• On the CCS, in nonacute cases, you will be required to advance the time and schedule appointments for the patient; therefore, be sure to have enough practice with the CCS software to be able to advance the time, and yet be aware of the “Simulated time” and “Real time.”
Clinical Features\:
Patients will usually have a family history of hemophilia. Another indicator is excessive bleeding at the time of a circum­ cision. Hemophilia A and hemophilia B (ie, Christmas disease) are clinically indistinguishable other than therapy. Although bleeding can occur anywhere, common sites for bleeding are into the joints, muscle, and GI tract. However, consider the

overall picture ofthe signs and symptoms, which include from a relative head to toe fashion\:
Neurologic—Headache, vomiting, lethargy, stiff neck, intracranial hemorrhage (neonates).
Head and Neck—Epistaxis, oral bleeding from dental procedures, hemoptysis.
GI—Hematemesis, melena, abdominal pain. Genitourinary—Hematuria, circumcision bleeding. Joints—Hemarthrosis.
Muscle—Hematoma formation can occur in any of the muscles, with the iliopsoas as the most concerning because of the potential for large volume of blood loss and compression of the femoral nerve.
Bone—Pseudotumors may form in bones as a result of unresolved hematomas.
Dermatologic—Excessive bruising.
Next Step\:
Step 1) Diagnosis of hemophilia can be made by the clinical evaluation and laboratory testing. Expected lab findings include a normal platelet count, a normal PT (ie, extrinsic cascade), and elevated activated partial thromboplastin time (ie, intrin­ sic cascade). However, patients that have mild hemophilia (see below) may have normal aPTTs.
Step 2) A mixing study will help determine if the elevated aPTT is due to a clotting factor deficiency or an inhibitor of a factor (ie, IgG antibody). When the patient’s blood is mixed with normal blood and the PTT does not correct, then it is most likely an inhibitor and a workup with an inhibitor assay such as the Bethesda assay should be pursued. When the patient’s blood is mixed with normal blood and the PTT does correct, then it is most likely a clotting factor deficiency and a workup with factor VIII and IX assays should be pursued. For both hemophilia A and B, the severity of the hemophilia is based on the assay in which severe hemophilia is considered when there is <1% normal factor, moderate hemophilia is 1% to 5% normal factor, and mild hemophilia is >5% normal factor.
Step 3) Treatment for hemophilia A or B is with recombinant factor VIII or recombinant factor IX, respectively. Treatment for patients that have inhibitors is more difficult to manage. Since inhibitors are less commonly seen in hemophilia B compared to hemophilia A, further discussion will be based on hemophilia A. Patients that have low-titer inhibitors (ie, low responders) respond well to high doses of factor VIII. Patients that have high-titer inhibitors (ie, high responders) or demonstrate an anamnestic response can be treated with activated prothrombin complex concentrates (aPCC) or with a bypassing agent such as activated Factor VII (FVIIa).
Step 4) Genetic counseling should be offered to families with a newborn who has hemophilia, especially if there was no family history.
Disposition\:
Admit patients from the ED if the patient is bleeding from the head and neck area or retroperitoneum (eg, iliopsoas bleeds).
Pearls\:
• Hemophilia A affects 1 in 5000 males, which is more com­ mon than hemophilia B affecting 1 in 25,000 to 35,000 males.
• Cryoprecipitate (ie, factor VIII, factor XIII, vWF, fibrinogen) is no longer used to treat hemophilia A because of concerns of blood-borne infections such as HIV and hepatitis C.
• Plasma-derived products emerged to reduce the risk of viral transmission, but viruses such as hepatitis A and parvovirus still pose a threat.
• Recombinant products are well-refined products that further reduce the risk of blood-borne infections, but their cost remains fairly high.
• aPCC have been associated with thrombosis, myocardial infarction, and DIC.
• Patients with mild hemophilia A can be treated with desmo­ pressin (DDAVP) because it transiently increases the levels of factor VIII and vWF factor.
• Antifibrinolytics such as e-aminocaproic acid and tranexam- ic acid are used to treat oral mucosal hemorrhage. These agents should be avoided in the presence of hematuria because they can cause obstructive uropathy.
• Avoid NSAIDs and aspirin for pain control; instead use acetaminophen.
• Patients should be treated with factor replacement therapy if they are going to have a central line or any other invasive procedure.
• Female carriers can have variable levels of factor VIII or IX and experience mild bleeding. Female carriers will transmit the disease to half of their sons, and half of their daughters will be carriers.
• Connecting point (pg. 163)—X-linked recessive disorders will show no male-to-male transmission.
• CJ\: A patient is being treated with factor replacement ther­ apy at therapeutic doses for a GI bleed, but the therapy does not seem to help. What do you think is wrong? Answer\: Patients that fail to respond to factor replacement therapy most likely have an inhibitor problem rather than a factor deficiency.
• On the CCS, the practice CCS does not recognize “mixing study.”
• On the CCS, both “plasma factor VIII” and "plasma factor IX” levels are available in the practice CCS.
• On the CCS, ordering “factor VIII, therapy” in the practice CCS will automatically be converted to “antihemophilic factor, therapy.”
• On the CCS, if you want to order factor IX therapy, it will be viewed as “factor IX complex” in the practice CCS.
1 VONWILLEBRANDDISEASE
Von Willebrand disease (vWD) is the most common inherited bleeding disorder. Von Willebrand factor (vWF) serves two important roles. First, in the event ofvascular injury, vWF binds
CHAPTER 10 HEMATOLOGY 131

132 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
to the exposed subendothelium and subsequently binds to platelets through the Gp Ib-IX platelet receptor. Second, vWF binds and protects factor VIII from proteolysis within the plasma, thereby increasing the half-life of factor VIII. In essence, von Willebrand disease can affect both the platelet function and coagulation pathway. There are three inherited types and one acquired type of von Willebrand disease.
Type 1—An autosomal dominant disease that can be character­ ized as a partial quantitative vWF deficiency. Type 1 is the most common type.
Type 2—Mainly an autosomal dominant disease, but several subtypes can be autosomal recessive. There are 4 subtypes which include 2A, 2B, 2M, and 2N. Type 2 vWD can be characterized as a qualitative vWF deficiency.
Type 3—An autosomal recessive disease that can be character­ ized as complete vWF deficiency. Type 3 is a rare disease.
Acquired vWD—Occurs by several different mechanisms, but can be seen in patients with multiple myeloma, Waldenstroms macro- globulinemia, polycythemia vera, MGUS, CML, CLL, SLE, valvular heart disease, and Wilms tumor. Acquired vWD is a rare disease.
Clinical Features\:
In most cases ofvWD, symptoms are mild. A family history may be present, but not always (especially with acquired vWD). A medication history of taking aspirin or NSAIDs may precipitate a bleed that would normally not occur. A history of prolonged bleeding during specific events such as dental extractions, ton­ sillectomy, childbirth, or other medical procedures are clues that something is wrong. Common sites of bleeding include mucous membranes (eg, nosebleeds, gingival bleeds), uterus (eg, men­ orrhagia), and skin (eg, bruising). In types 2N and 3, factor VIII is appreciably low and will present similarly to hemophilia A, which includes joint bleeding, soft tissue bleeds, and hematuria. Although type 3 is fairly rare, it is a severe form and patients will present earlier in life such as at the time of a circumcision.
Next Step\:
Step 1) Diagnosis of vWD can be made by the clinical evalua­ tion and laboratory testing. Initial lab testing should include a CBC, PT, and PTT. Expected findings include a normal platelet count, a normal PT, and a normal to elevated PTT. Certainly types 2N and 3 will have elevated PTT (ie, intrinsic cascade) because their factor VIII is significantly low.
Step 2) If the PTT is elevated or if all the initial lab tests are normal but there is suspicion for vWD, then order a screening test that includes a vWF antigen test, vWF activity test (ie, ristocetin cofactor test), and a factor VIII activity test (ie, FVIII coagulant assay). See Table 10-2 for expected results.
Step 3) If the vWD screening test demonstrates an abnormal result or if the lab tests are normal but there is still suspicion for vWD, then repeat the initial screening tests and refer to a specialist for further specialized vWD studies.
Step 4) Treatment of vWD is based on three approaches. First, promoting release of vWF into circulation from endothelial cells via desmopressin (DDAVP). Second, replacement of vWF with plasma-derived, viral-inactivated vWF concentrates. Third, controlling hemostasis with antifibrinolytics.
Table 10-2 • Expected vWDScreening Results
Type
Type 1 Type 2A Type 2B Type 2M Type 2N Type 3
—
•tor normal
•f or undetectable
Desmopressin (DDAVP)
Ristocetin Cofactor Activity
Factor VIII Activity
-l or normal i i or undetectable 1
vWF Antigen i1i l1 i ii i ii i
• DDAVP is a synthetic derivative of vasopressin.
• DDAVP is used in type 1 and in some patients with type 2.
• DDAVP can worsen thrombocytopenia seen in type 2B patients.
• DDAVP is not recommended in type 3 because it does not increase vWF levels.
• DDAVP can cause tachyphylaxis and water retention leading to hyponatremia.
Plasma-Derived vWF Concentrates
• Humate-P and Alphanate are trade names that are FDA ap­ proved for treatment of vWD.
• Humate-P and Alphanate contain both factor VIII and vWF.
• Humate-P or Alphanate are used in patients who no longer respond to DDAVP, require long periods of DDAVP, type 3 patients, some type 2 patients, and those with significant bleeding or those having major surgery.
• Cryoprecipitate is no longer recommended because of concerns ofviral transmission.
Antifibrinolytics
• e-aminocaproic acid or tranexamic acid are particularly use­ ful in mucocutaneous bleeds.
• Antifibrinolytics can be used as monotherapy or adjunctive therapy to other medications.
• Both agents are contraindicated in patients with upper uri­ nary bleeding because it can cause ureteral obstruction.
Follow-Up\:
Patients diagnosed with type 1 and most type 2s should be tested with DDAVP to assess their response with the medication.
Pearls\:
• Patients with blood type O have vWF levels that are 30% lower compared to the other blood types.
• Factor VIII and vWF are both acute phase reactants that can be elevated in times of stress, pregnancy, exercise, inflamma­ tion, and the use of estrogen or oral contraceptives.
• Patients with menorrhagia who do not want to become pregnant can use oral contraceptives for therapy, but those

who want to become pregnant are treated with DDAVP, antifibrinolytics, or vWF concentrates.
• On the CCS, “von Willebrand factor antigen, plasma,” “ristocetin cofactor,” and “coagulation factor VIII, plasma” are available in the practice CCS.
• Ristocetin is an antibiotic that is off the market because it causes thrombocytopenia, but now used in assays. In the presence of • vWF factors, adding ristocetin will cause platelets to agglutinate.
• Bleeding time is not routinely performed because of the wide • variation of the test, but for board purposes bleeding time
tosomal dominant disorders.
NEOPLASIA
1 MULTIPLE MYELOMA
Multiple myeloma is a malignant proliferation of plasma cells. The plasma cells can overproduce M proteins (ie, IgG, IgM, IgA, IgE, or IgD) depending on their heavy chain class and ultimately causing hyperviscosity. Myeloma cells can produce abnormal light chain proteins (ie, K-kappa or A-lambda) that can cause end-organ damage. Finally, myeloma cells can secrete cytokines that can stimulate osteoClast activity (ie, “bone-Crushing cells”) while suppressing osteoblast activity (ie, “bone-forming cells”). The end result of osteoclast activity can be bone lesions, hyper­ calcemia, and osteoporosis. The etiology of multiple myeloma is still not fully understood.
Clinical Features\:
Multiple myeloma is a disease of older adults with the median age at diagnosis of 68 years. Men are more likely to have the disease compared to females, and blacks are twice as likely as whites to have multiple myeloma. Multiple myeloma can pres­ ent in a variety of ways, and it can best be remembered by the mnemonic “TIN-CRAB.”
Thickened blood—Hyperviscosity can cause headaches, blurry vision, retinopathy, fatigue, sensory loss, stroke, myocardial infarction, heart failure, or Raynaud phenomenon. One of the causes of hyperviscosity can be cryoglobulinemia, which is the presence of cryoglobulins (ie, immunoglobulins that can undergo reversible precipitation at low temperatures) in the serum.
Infection—Abnormal humoral immunity and leukopenia can cause recurrent infections. Common organisms include Staphy­ lococcus aureus, Streptococcus pneumoniae, and Klebsiella pneu­ moniae in the lungs and E coli and other gram-negative bugs in the urinary tract.
Neurologic—Spinal cord compression can occur from a ver­ tebral fracture or a plasmacytoma. As a result, patients can ex­ perience back pain, radiculopathy, or loss of bowel and bladder control. Patients with multiple myeloma can have peripheral neuropathy due to the infiltration of amyloid into peripheral nerves. Carpal tunnel syndrome is a common peripheral neu­ ropathy seen in patients with multiple myeloma.
.
On the CCS, both “DDAVP” and “desmopressin” are available in the practice CCS.
On the CCS, both trade names for “Humate-P” and “Alphanate” are available in the practice CCS.
On the CCS, “aminocaproic acid” is available, but “tranexamic acid” is not available in the practice CCS.
can be normal to elevated in vWD.
• • Connecting point (pg. 162)—Be familiar with the other au­
CHAPTER 10 HEMATOLOGY 133
Calcium—Hypercalcemia can occur from the breakdown of bone. Patients can experience confusion, depression, polydip­ sia, nausea, or lethargy.
Renal—Renal failure is seen in almost 25% of patients with multiple myeloma, and at least 50% of patients with multiple myeloma have some type of renal pathology. The most common renal dysfunction is the “myeloma kidney,” which is a light chain cast nephropathy seen in the tubules. Other pathologies are Fanconi’s syndrome in the tubules, amyloidosis in the glomeruli, and interstitial nephritis in the interstitium.
Anemia—Approximately80%ofpatientswithmultiplemyeloma will have a normocytic, normochromic anemia. The anemia may be due to tumor cell replacement in the bone marrow and inhibition ofhematopoiesis by factors released by the tumor cell. Patients will usually experience weakness, pallor, and malaise.
Bone—Bone pain is a common presenting symptom. The pain is usually in the back, chest, or ribs and less frequently in the arms and legs. The pain of multiple myeloma is precipitated by movement. The pain is usually not worse at night, compared to metastatic carcinoma where it is worse at night. The bone lesions are lytic lesions, and persistent localized pain usually signifies a pathologic fracture. Patients can actually lose height if there is a vertebral collapse from the fracture.
Next Step\:
Step 1) Routine laboratory testing in patients who initially pres­ ent with multiple myeloma may show the following\:
CBC with peripheral smear—Anemia, Rouleaux formation CMP—T BUN, T Cr, T calcium, normal alkaline phospha­ tase (ie, no osteoblastic activity)
ESR—Elevated Uric acid—Elevated
Urinalysis—± protein (ie, UA will pick up albumin in urine, not Bence Jones protein).
Step 2) Further diagnostic testing should be conducted in pa­ tients with initial lab findings and overall clinical picture of multiple myeloma.
SPEP (Serum protein electrophoresis) with immunofixa- tion—SPEP screens for the presence of monoclonal (M) proteins (also referred to as paraprotein). Immunofixation

134
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
confirms the presence of M proteins and identifies the sub- type of protein.
UPEP (urine protein electrophoresis) with immunofixa- tion—UPEP can detect M protein, but it can also identify elevated light chains (k or \), which is also referred to as Bence Jones protein.
Bone marrow aspiration and biopsy—Smears will appear with a preponderance of plasma cells with an eccentric nucleus.
Skeletal survey—Plain radiograph is the modality of choice, and lytic lesions will appear as “punched-out” lesions. MRI is the preferred technique in patients with spinal cord compres­ sion or soft tissue plasmacytomas. Nuclear bone scans are not recommended because there is no osteoblastic activity.
Step 3) Diagnosis can now be made if all three of the following criteria are met\:
1) PresenceofserumorurinaryMprotein.
2) Presenceofbonemarrowplasmacellsorplasmacytoma.
3) Presence of end-organ damage (C-T calcium, R-renal fail­
ure, A-anemia, B-bone lesions).
Step 4) Once the diagnosis is made, the patient is staged. The International Staging System (ISS) is a common staging system that incorporates serum albumin and serum (32-microglobulin. Lower albumin levels and higher p2-microglobulin are indica­ tors of a poor prognosis. But know that the {J2-microglobulin is the single most useful and important predictor of survival.
Step 5) Patients that are asymptomatic may not require any treatment. However, once the patient becomes symptomatic and the disease becomes more progressive, therapeutic inter­ vention is usually required. Treatment and management of mul­ tiple myeloma is as follows\:
Multiple myeloma—Patients are evaluated on whether or not they are stem cell transplant candidates. Patients that are not candidates tend to have comorbidities such as NYHA III or IV, or are older and inactive and probably would not be able to withstand treatment. Patients that are not transplant candi­ dates usually undergo a treatment of melphalan, prednisone, and thalidomide (MPT). Patients that are candidates for trans­ plant can undergo vincristine, doxorubicin (Adriamycin), or dexamethasone (VAD), or they can undergo thalidomide plus dexamethasone. Patients that are candidates for transplant should not be treated with melphalan because it can cause stem cell damage and collection for stem cells will be diminished.
Thickened blood—Patients that are symptomatic from the hyperviscosity should be treated with plasmapheresis regardless of the viscosity level.
Infections—The use of prophylactic antibiotics is contro­ versial, but initiate empiric antibiotics if an infection is suspected. Pneumococcal, Haemophilus, and influenza vaccines should be given despite a suboptimal response. Patients with serious recurrent infections may need IVIG.
Neurologic—Spinal cord compression is a medical emergency, and any patient suspected of having a spinal
cord compression should have an emergency MRI. Initial treatment may include dexamethasone, while definitive therapy may include surgery or radiation therapy.
Calcium—Hypercalcemia can initially be treated with normal saline and steroids (eg, dexamethasone). Also add intravenous bisphosphonates (eg, zoledronic acid, pami- dronate) because it can inhibit osteoclast activity and pro­ vide secondary prevention in bony complications.
Renal—Treat the underlying cause of the renal pathol­ ogy. In general, patients should be well hydrated to excrete light chains and calcium. Avoid nephrotoxic agents such as NSAIDs and radiocontrast dye.
Anemia—Patients with significant symptoms should be treated with irradiated, leukoreduced blood transfusions. Erythropoietin therapy is also given to patients with hemo­ globin <10 g/dL.
Bone—Bone pain can be controlled with opiates, and bone disease can be managed with radiation therapy, surgical procedures (eg, vertebroplasty, kyphoplasty), and intrave­ nous bisphosphonates (eg, zoledronic acid, pamidronate).
Follow-Up\:
One of the ways to determine the response of chemotherapy is to assess the M protein levels via SPEP or UPEP.
Pearls\:
• The approximate survival rate in patients with multiple myeloma is 3 years.
• Smoldering multiple myeloma is also referred to as asymp­ tomatic multiple myeloma and can be diagnosed if serum M protein is >3 g/dL and/or bone marrow plasma cells >10%, and there is no end organ damage.
• Monoclonal gammopathy of undetermined significance (MGUS) can be diagnosed if serum M protein is <3 g/dL, bone marrow plasma cells <10%, and there is no end organ damage.
• Although multiple myeloma arises de novo, it appears that MGUS can progress to multiple myeloma with a risk of progression of approximately 1% per year.
• Patients with smoldering multiple myeloma or MGUS usu­ ally require no therapy.
• Connecting point (pg. 73)—Review the clinical features sec­ tion on hypercalcemia.
• On the CCS, the practice CCS recognizes “SPEP,” “UPEPT and “bone marrow biopsy” in the order menu.
• On the CCS, immunofixation will be recognized as either “serum immunoelectrophoresis” or “urine immunoelectro- phoresis” in the practice CCS.
• On the CCS, the practice CCS does not recognize “beta 2 microglobulin.”
• On the CCS, remember to “bridge” your therapy by address­ ing any acute issues (eg, spinal cord compression) and ad­ dressing the long-term care (eg, chemotherapy).

CCS\: G6PD DEFICIENCY CASE INTRODUCTION
Day 1 @ 11\:00 Office
A 20-year-old Greek man comes to the office because of weak­ ness, back pain, dark urine, and jaundice.
Initial Vital Signs\:
Temperature\: 37.0°C (98.6°F) Pulse\: 92 beats/min, regular rhythm Respiratory\: 17/min
Blood pressure\: 116/75 mm Hg Height\: 182.9 cm (72.0 inches) Weight\: 77 kg (170 lb)
BMI\: 23.1 kg/m2
Initial History\:
Reason (s) for visit\: Weakness, back pain, dark urine, jaundice
HPI\:
A 20-year-old college student presents to the office with weak­ ness, back pain, dark urine, and “yellowing of the skin.” He de­ nies any sick contacts, travel, or trauma. He cannot recall any precipitating events, other than 4 days ago when he opened up a sealed container that contained strong vapors of mothballs. After removing his coat jacket from the sealed container and wearing the jacket, he noticed that he started to feel weak and had back pain several hours later. Approximately 2 days later, he noticed brownish-red urine and yellowing of his skin. The only other time that he had similar symptoms was when he con­ sumed fava beans 15 years ago, but no further workup was done because of insurance reasons.
Review of Systems\:
General\:
Skin\:
HEENT\: Musculoskeletal\: Cardiorespiratory\: Gastrointestinal\: Genitourinary\: Neuropsychiatric\:
Day 1 @ 11\:10
Physical Examination\: General appearance\: Skin\:
Lymph nodes\: HEENT/Neck\:
Chest/Lungs\:
Heart/Cardiovascular\: Abdomen\:
Extremities/Spine\:
Neuro/Psych\:
First Order Sheet\:
1) CBC with differential, stat
Past Medical History\: Past Surgical History\:
Medications\: Allergies\: Vaccinations\: Family History\:
Social History\:
Neonatal hyperbilirubinemia treated with phototherapy.
None
None
None
Up to date
Father, age 48, and mother, age 45, are both healthy. One older brother is healthy and one younger sister is healthy. An uncle (mothers side) has a blood disorder.
Does not smoke, drink, or do drugs. Single, no children. Full-time college student. Plays collegiate golf.
See HPI
See HPI See HPI See HPI Negative Negative See HPI Negative
Appears uncomfortable.
Jaundice. Pallor.
No lymphadenopathy. Norinocephalic. Scleral icterus; Pale conjunctivae. EOMI, PERRLA. Hearing normal. Ears, nose, mouth normal. Pharynx normal. Neck supple; trachea midline; no masses or bruits; thyroid normal.
Chest wall normal. Diaphragm moving equally and symmetrically with respiration. Auscultation and percussion normal.
SI, S2 normal. No murmurs, rubs, gallops, or extra sounds. No JVD. Normal bowel sounds; no bruits. No tenderness. No masses. No hernias. No hepatosplenomegaly.
No joint deformity or warmth. No cyanosis or clubbing. No edema. Peripheral pulses normal. Spine examination normal. No paraspinal tenderness.
Mental status normal. Cranial nerve and sensory examination normal. Motor strength 4/5 throughout. Cerebellar function normal. Deep tendon reflexes normal. Gait normal.
CHAPTER 10
HEMATOLOGY 135
Result\: WBC-8000, H/H-7/35%, Plt-250,000, Differential-WNL MCV-85, MCHC-37% (nl\: 31-36%), RDW-12% (nl\: 11.5-13.6)

136 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
2) Peripheralsmear,stat
3) BMP, stat
4) Reticulocyte count, blood, stat
5) LDH> serum, stat 6) LET,stat
7) PT/INR, stat 8) PTT, stat
9) Urinalysis, stat
Results\:Presenceofbite cells and spherocytes. Normochromic normocytic erythrocytes; leukocytes and platelets normal in number and morphology.
Result\: Glu-100, Urea-14, Na-140, K-4.9, Cl-102, HC03-25, Cr-1, Ca-9.5
Result\: 4% (nl\: 0.5-1.5)
Result\: 500IU/L (nl\: 45-90)
Result\:AST-50,ALT-20, Alb-5, Protein-7, AlkP-65, Total Bil-4.0 (nl\: 0.1-1.0), Direct Bil-0.3 (nl\: 0-0.3)
Result\: 9 seconds (nl\: <12 seconds), INR-1.0
Result\: 25 seconds (nl\: <28 seconds)
Result\: Appearance- brownish-red, Bilirubin­ positive
Vitalsignisnowavailable
Urine output is now available
Fourth Order Sheet\: 1) H/H, routine
Result\:37°C,HR-88, RR-16, BP-120/78 Result\: Voiding adequate amounts.
Result\: Hemoglobin-13.5 g/ dL, Hematocrit-41%
Actions\:
1) Change location to inpatient unit
Please enter your diagnosis\: G6PD Deficiency
DISCUSSION\:
G6PD deficiency is the most common enzymopathy. It is an X-linked recessive disorder commonly affecting persons of Mediterranean, Middle Eastern, African, and Asian descent. The importance of G6PD is that it ultimately defends against oxidant injury within the blood cell. G6PD catalyzes NADP to its reduced form of NADPH. NADPH is an important cofactor in maintaining elevated levels ofthe reducing agent, glutathione (GSH), and thereby protecting the cell from oxidant injury. In the event that GSH is absent or very low, such as in G6PD de­ ficiency, oxidants can accumulate within the cell and denature hemoglobin and form precipitates of inclusion bodies (Heinz bodies). The precipitates can eventually damage the membranes and cause intravascular hemolysis. Extravascular hemolysis can also occur outside the vascular compartment, and destruc­ tion can occur in the spleen, liver, and bone marrow. As the inclusion-bearing red cell passes through the spleen, the mac­ rophages remove the Heinz bodies, which gives the cell a “bite cell” appearance on peripheral smear.
Clinical Features\:
The majority of patients with G6PD deficiency will remain asymptomatic throughout their life. The two main clinical presentations that can occur in G6PD deficiency are acute he­ molytic anemia and neonatal hyperbilirubinemia. The four triggers that can cause an acute hemolytic anemia are (1) infec­ tions, (2) fava beans, (3) DKA, and (4) agents (see Table 10-3). Once exposed to the offending trigger, patients will start to
Second Order Sheet\: 1) IV access
2) NS, 0.9% NaCl, IV, continuous
3) Vital signs, q8 hrs
4) Urine output, routine, q8hrs
5) Type and crossmatch, blood, stat
6) Transfuse, packed RBC’s, routine
Result\: O+
Follow-Up History\:
“Hey Doc, I’m starting to feel better.”
Third Order Sheet\:
1) Haptoglobin, serum, routine
2) Coombs’ test, direct, routine
3) G6PD, blood, quantitative, routine
4) Heinz body stain, routine
Result\: 20 mg/dL (nl\: 30-175)
Result\: Negative
Result\: 12.5 U/g Hb (nl\: 10.0-14.2)
Result\: Inclusion bodies detected.
This case will end in the next few minutes of“real time.” You may add or delete orders at this time,
then enter a diagnosis on the following screen.
Fifth Order Sheet\:
1) G6PD, blood, quantitative,
routine
Future date\: In 90 days
2) Hemosiderin stain, urine, routine
Future date\: In 7 days
3) Counsel family/patient, routine
Result\: 12.0 U/g Hb (nl\: 10.0-14.2)
Result\: Positive

Table 10-3 • Triggering Agents of Acute Hemolytic Anemia in Persons with G6PD Deficiency
a better assessment. The following list describes issues to think about during the case\:
Intravascular hemolysis—RBCs will release LDH, AST, hemoglobin, and potassium into circulation. Free hemo­ globin will be bound to haptoglobin, and any remaining free hemoglobin will be filtered through the kidneys and appear as dark urine caused by the hemoglobinuria. As the hemoglobin passes through the renal tubules, some of the hemoglobin is taken up by the renal tubular cells and then broken down, and the iron is then stored as hemo­ siderin in the renal tubular cells. Approximately, one week later, the renal tubular cells will slough off and the iron can be detected by a Prussian blue stain and test positive for hemosiderinuria.
Extravascular hemolysis—The presence of bite cells on peripheral smear is an indication of extravascular hemo­ lysis. The loss of membrane from the bite cells can induce further damage resulting in spherocytes. The presence of spherocytes is also an indication of extravascular hemolysis.
G6PD Deficiency assessment—The G6PD blood quantity level is falsely negative in this case. It is the older erythro­ cytes that have been hemolyzed, and thereby does not truly reflect the steady state. The normal value in this case reflects the reticulocytes and young erythrocytes that have normal or near-normal enzyme activity.
Rule out liver and biliary disease—The LFTs show a normal ALT but a modest increase in AST, most likely from the red blood cells. An elevated total bilirubin but a normal direct bilirubin indicates a problem with excess unconju­ gated bilirubin (ie, indirect bilirubin) most likely from the hemolytic anemia and not from an intrinsic liver disease problem. The indirect bilirubin can also be calculated by Indirect = Total - Direct. An indirect value >1.2 mg/dL and a direct bilirubin value <20% of the total bilirubin should make you think about excess unconjugation.
Rule out a coagulopathy—Both PT and PTT are within normal range.
Rule out autoimmune hemolytic anemia—Direct Coombs test was negative in this case.
Step 3) Prevent another episode by identifying and avoiding the triggering factor.
Follow-Up\:
Patients should have a repeat G6PD level 3 months from the hemolytic episode because at that time, the patient will be in a steady-state condition with a true reflection of the red blood cells at different ages.
Pearls\:
• Both G6PD Mediterranean and G6PD A- variant are at risk of developing neonatal hyperbilirubinemia.
• Neonatal hyperbilirubinemia will usually not present at birth, but rather in 2 to 3 days after birth.
Agents
Naphthalene Henna Primaquine Dapsone Nitrofurantoin Nalidixic acid Sulfamethoxazole Sulfacetamide Sulfanilamide
Phenazopyridine Methylene blue
Purpose
Used in mothballs
Used in body art and hair dyes
Antimalarial
Antibiotic used to treat leprosy
Antibiotic used to treat UTIs
Antibiotic used to treat UTIs
Antibiotic (part of theTMP-SMX)
Antibiotic used to treat acne or conjunctivitis Antifungal used to treat vulvovaginitis
from C albicans
Urinary analgesic
Antidote to treat cyanide poisoning and drug-induced methemoglobinemia
feel weak and may have abdominal or back pain. After 2 to 4 days from exposure, they will develop a sudden onset ofjaun­ dice, pallor, and dark urine. The hemolytic episode is self­ limited even in the presence of the offending trigger because it is thought that the older erythrocytes (ie, greatest enzyme deficiency) have been hemolyzed, but the younger erythrocytes and reticulocytes (ie, near-normal enzyme activity) can sustain oxidative damage. There are several different variants of G6PD deficiency, but the two most common types include\:
G6PD Mediterranean—Commonly affects people from Greek, Italian, Arabic, and Jewish (Kurdish) descent. Clas­ sified as a class II variant and according to the World Health Organization is described as severe enzyme deficiency, but with intermittent hemolysis associated with infection, drugs, or chemicals. Favism is more likely to occur in this variant. Symptoms of favism typically begin within 24 hours of fava bean ingestion, and symptoms include fever, chills, headache, nausea, and back pain, which is then followed by jaundice and hemoglobinuria.
G6PD A- variant—Commonly affects people of African descent. Classified as a class III variant and according to the World Health Organization is described as moderate enzyme deficiency (10%-60% of normal), but with intermit­ tent hemolysis usually associated with infection, drugs, or chemicals. Favism is not as common in this group.
Next Step Summary\:
Step 1) When an acute hemolytic anemia develops, no treat­ ment is needed in most cases. However, in this case, the patients overall clinical condition appeared severe enough to warrant a blood transfusion (ie, symptomatic, vitals starting to become unstable, Hb of 7).
Step 2) The presence ofjaundice, dark urine, and symptoms of anemia should make you think about a hemolytic process. Sev­ eral laboratory studies were ordered during the CCS to give you
CHAPTER 10 HEMATOLOGY 137

138 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Neonatal hyperbilirubinemia may require phototherapy or exchange transfusion.
• Severe neonatal jaundice can result in kemicterus.
• Acute hemolytic anemia can also occur in a G6PD deficient baby who is ingesting oxidizing drugs from a woman who is breastfeeding (see Table 10-3).
• Splenomegaly may not always be present in G6PD deficient patients.
• In the presence of many spherocytes, the MCHC can be elevated.
• Reticulocytosis should be seen within 5 days after a hemo­ lytic episode.
• The presence of Heinz bodies can be detected with a supra­ vital dye, but will disappear within 4 days after the hemolytic episode.
• Fava beans are also referred to as broad beans, pigeon beans, haba beans, bell beans, fever beans, horse beans, silkworm beans, tick beans, field beans, or English dwarfbeans.
• Foundational point—G6PD deficiency involves the pen­ tose phosphate pathway (also referred to as the hexose
• • •
•
•
monophosphate shunt. The pathway ultimately produces NADPH, which then can convert oxidized glutathione to reduced glutathione. The reduced glutathione can now protect the cell from oxidant injury (eg, H20 2).
Connecting point (pg. 194)—Sulfacetamide may be used to prevent an infection in corneal abrasions.
Connecting point (pg. 48)—Sulfacetamide is used to treat mild acne.
On the CCS, in this case the mother is most likely an X-linked carrier of the disease and her brother (patient’s uncle) probably has the disease.
On the CCS, the complete metabolic panel (CMP) will give you the total bilirubin level, but not the direct bilirubin level. Therefore, order the LFT to give you both total and direct bilirubin levels to assess the indirect bilirubin.
On the CCS, be sure that whenever you provide treatment for the patient, you follow up with the appropriate monitor­ ing parameters (eg, vitals, blood work, imaging).

Neurology
CHAPTER OUTLINE
Keywords Review..............................................1..3.9.....
I MOVEMENT DISORDER...................................1..5.0...
Huntington's Disease...........................................1.5.0....
I NEOPLASM.................................................1.5.1......
Meningioma...................................................1.5..1.....
I TRAUMA....................................................1.5.2......
Epidural Hematoma............................................1.5..2... Subdural Hematoma...........................................1.5.3....
DEGENERATIVE DISEASE..................................1.4.0...
Multiple Sclerosis..............................................1.4.0.....
SPINAL DISEASE...........................................1.4.2.....
Lumbar Spinal Stenosis........................................1.4..2...
CEREBROVASCULAR DISEASES...........................1.4.3.
1 I I
KEYWORDS REVIEW___________________
Ischemic Stroke................................................1.4.3.....
TransientIschemicAttack......................................1.4..7.. I CCS..........................................................1.5..4....... Intracerebral Hemorrhage.....................................1..4.8... Subarachnoid Hemorrhage.....................................1.5.4...
Abulia—Inability to make decisions or act.
Agnosia—Inability to recognize and interpret sensory impressions from the visual, auditory, olfactory, gustatory, or tactile senses.
Agraphia—Inability to write.
Anisocoria—Unequal size of the pupils (eg, uncal herniation with CN III compression), which usually indicates a lesion
in the efferent fibers innervating the pupillary sphincter muscles.
Anosognosia—Unaware or denial that a neurological deficit is occurring.
Apractagnosia—Inability to use objects (eg, pencil to draw) or to perform motor activities (eg, assembling a model airplane).
Apraxia—Inability to carry out learned purposeful movements.
Bradykinesia—Slowness of muscular movements.
Choreoathetosis—A condition characterized by choreic (rapid, jerky) and athetoid (slow, writhing) movements.
Color anomia—Inability to identify the name of colors, but can distinguish between colors.
Desiccation—Drying out or dehydration.
139

140 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Dyspraxia—Partial loss of the ability to perform coordinated movements.
Dystonia—Sustained, involuntary muscular contractions that cause uncontrollable repetitive movements or distorted postures.
Homonymous hemianopsia—A visual field deficit affecting the right or left half of the visual field of both eyes. For exam­ ple, a patient with a left homonymous hemianopsia will not be able to see on the left visual field (ie, temporal side of the left eye and nasal side of the right eye).
Hypesthesia—Decreased sensitivity to stimuli, also known as hypoesthesia.
Myoclonus—A brief, shocklike, involuntary contraction of a muscle or group of muscles.
Oscillopsia—Oscillating vision or the sensation that objects are moving back and forth.
Romberg's test—Mainly a test of proprioception or the integrity of the dorsal columns. To maintain balance, you need two of the three parameters (ie, vision, vestibular function,
DEGENERATIVE DISEASE ,
B MULTIPLESCLEROSIS
Multiple sclerosis (MS) is a demyelinating disorder that results in variable neurologic dysfunction. Although the etiology ofMS is unknown, the primary mechanism involves inflammation, demyelination, and axon degeneration.
Clinical Features\:
Multiple sclerosis usually affects more women than men, and the mean age of onset is between 20 and 40 years of age. The neurologic manifestations of MS can vary, and there is no single clinical feature that is pathognomonic for MS. It may be helpful to consider the features of MS in a relative head to toe fashion\:
Psych—Depression, euphoria, mood swings
Brain—Seizures, cognitive dysfunction (eg, dementia, 4 concentration, 4 memory), vertigo, tremors, gait imbalance (due to cerebellar or corticospinal tract lesions), cerebellar dysarthria (scanning speech)
Face—Facial weakness (ipsilateral taste sensation is pre­ served), facial myokymia (twitching), facial paresthesia, trigeminal neuralgia
Ocular—Nystagmus, diplopia, optic neuritis (eye pain fol­ lowed by central scotoma), Marcus Gunn pupil, internucle- ar ophthalmoplegia (INO), ocular dysmetria
Spine—Lhermittes sign (electric shock radiating down the spine and sometimes into the legs upon neck flexion), acute transverse myelitis
Bowel—Constipation, incontinence
proprioception). A positive Romberg test occurs when patients sway after closing their eyes with their feet together.
Paraparesis—Partial paralysis of the lower extremity. Paraplegia—Paralysis of the lower extremity and lower trunk.
Prosopagnosia—Inability to recognize familiar faces, even the patient's own face.
Scanning speech—A type of ataxic dysarthria in which words are broken into separate syllables (ie, noticeable pauses between syllables).
Scotoma—An area of depressed vision in the visual field, but surrounded with normal vision.
Spondylolisthesis—The anterior or posterior displacement of a vertebra with respect to an adjacent vertebra.
Spondylolysis—A defect or crack at the pars interarticularis that can sometimes lead to spondylolisthesis.
Spondylosis—Degenerative spinal changes.
Tactile aphasia—Inability to name objects by tactile sensation.
Bladder—Urinary urgency, incontinence
Sexual dysfunction—Erectile dysfunction, 4 vaginal lubri­
cation, 4 libido
Motor symptoms—Spasticity, hyperreflexia, paraparesis, paraplegia, Babinski sign (reflecting upper motor neuron lesion), T deep tendon reflexes
Sensory symptoms—Pain at any location that can change with time, paresthesias, 4 vibration and position sense (pos­ terior column pathways), 4 pain sensation and light touch (spinothalamic tract)
Systemic—Fatigue
In addition to the above clinical features, MS also displays three unique characteristics (heat sensitivity, paroxysmal symptoms, and disease patterns). The neurologic signs and symptoms can be worsened with increasing body temperature or heat sensitivity (Uhthoff sign). For example, after a hot shower a patient may have urinary urgency. Patients with MS can also have paroxysmal symptoms of motor and sensory dysfunction (eg, ataxia, paresthesia, flashing lights), but these attacks do not represent true exacerbations. The paroxysmal symptoms can last for a few seconds to several minutes and can occur multiple times a day lasting for several weeks to months. Paroxysmal symptoms may be precipitated by sen­ sory stimuli, movement, or hyperventilation. Patients with MS can also have different disease patterns, which can sometimes confuse the clinical picture. Consider the following different types of disease patterns\:
Relapsing-remitting MS—Accounts for about 85% of cases and is characterized by discrete relapses (attacks) followed by periods of remission with either full recovery or residual

deficits. However, there is no functional decline between the attacks.
Primary progressive MS—Accounts for about 10% ofcases and is characterized by a steady functional decline from the onset with occasional plateaus, but without acute attacks.
Secondary progressive MS—Initially starts as a relapsing- remitting pattern, but then changes to a steady functional decline with or without attacks or plateaus. Secondary progressive MS causes the most neurological disability, and patients with the relapsing-remitting MS are at risk of developing secondary progressive MS.
Progressive-relapsing MS—Accounts for about 5% of cases and is characterized by a steady functional decline from the onset with superimposed attacks upon the declining course.
Next Step\:
Step 1) Multiple sclerosis is a clinical diagnosis. Patients should have >2 symptomatic episodes that suggest white matter pathol­ ogy in >2 distinct locations in the CNS. The attacks (paroxys­ mal episodes excluded) should last for more than 24 hours, and the episodes should be separated by at least I month or more. No single test is diagnostic, but rather supportive. Consider the following ancillary tests\:
MRI—MRI is the best initial test and the procedure of choice for supporting the diagnosis of MS.
CSF analysis—CSF analysis via lumbar puncture may re­ veal a normal CSF pressure, normal or slightly elevated CSF protein, clear CSF fluid, and cell pleocytosis (t normal cell
count). Patients with MS may also have an increase in intra­ thecal production of IgG, which would demonstrate as an oligodonal banding (OCB) on gel electrophoresis. How­ ever, these findings are not specific for MS since OCBs can be found in other chronic CNS infections.
Evoked potentials—Evoked potentials (EPs) are not spe­ cific for MS, but any delays in latencies are suggestive of de- myelination. The three most common EPs are visual (VEP), somatosensory (SSEP), and brainstem auditory (BAEP). At this time, the American Academy of Neurology does not recommend BAEP for diagnostic purposes.
Step 2) Treatment for multiple sclerosis mainly involves phar­ macologic therapy. Unfortunately, the treatments for primary or secondary progressive MS are less well established com­ pared to the relapsing-remitting disease. Consider the following treatments for the following conditions\:
Acute attacks—The preferred treatment is with IV methyl- prednisolone for 3 to 7 days ± oral prednisone taper. Plas­ mapheresis (plasma exchange) can be considered for the relapsing forms of MS if patients have a contraindication or are refractory to glucocorticoid treatment.
Relapsing-remitting MS (RRMS)—The disease modifying agents are used for the relapsing forms of MS. The following are FDA approved drugs for treatment of RRMS\:
• Interferon beta-lb—First agent approved for use in MS. IFN beta-lb can induce flulike symptoms. Administer SubQ.
• Interferon beta-la—Similar effect and side effect as IFN beta-lb. Administer SubQ or IM.
• Glatiramer acetate—Similar to interferon betas, glat- iramer is also considered a first-line agent. Side effects include injection site inflammation, flulike syndrome, chest pain, and anxiety. Administer SubQ.
• Natalizumab—Typically reserved for patients with ac­ tive RRMS that are refractory to interferon betas and glatiramer. Natalizumab can result in progressive mul­ tifocal leukoencephalopathy (PML) due to an oppor­ tunistic infection with the JC virus. Administer as IV infusion.
• Mitoxantrone—Approvedtouseinpatientswithrelapsing- remitting and secondary progressive MS. Mitoxantrone should not be used as a first-line agent, but rather for those who have failed other therapies. Mitoxantrone is associated with cardiac toxicity, acute leukemia, amenorrhea, and is a pregnancy category D drug (ie, positive fetal risk). Admin­ ister as IV infusion.
• Teriflunomide—Approved for relapsing forms of MS. Associated with hepatotoxicity and is a pregnancy cat­ egory X drug (ie, contraindicated in pregnancy). Admin­ ister orally.
• Fingolimod—Approved for relapsing forms of MS. As­ sociated with VZV infections, macular edema, cardiac adverse effects, and pulmonary dysfunction. Fingolimod is contraindicated in patients with prolonged QT at base­ line, sick sinus syndrome, 2° or 3° AV blocks, treatment with la or III antiarrhythmics, or recent (past 6 months) TIA, stroke, MI, unstable angina, or decompensated HF. Administer orally.
• Specific symptoms in MS—The following symptoms may be ameliorated by different therapies\:
• Depression—SSRIs (eg, sertraline) or second-line agents such as tricyclics (eg, amitriptyline).
• Cognitive dysfunction—No proven pharmacologic therapy to be of benefit. Mainly supportive.
• Seizures—Antiepileptic drugs.
• Gait imbalance—Potassium channel blocker (eg,
dalfampridine).
• Optic neuritis—IV methylprednisolone is the pre­ ferred approach. Oral prednisone has a risk of recur­ rent optic neuritis.
• Constipation—Increase fluid intake and consider stool softeners or laxatives.
• Urinary urgency—Oxybutynin or tolterodine.
• Erectile dysfunction—PDE-5 inhibitors (eg, silde­
nafil, tadalafil).
• Spasticity—Baclofen, dantrolene, or tizanidine.
• Fatigue—Amantadine, methylphenidate, or SSRIs.
• Heat sensitivity—Air conditioning and heat avoidance.
• Paroxysmal symptoms—Low-dose anticonvulsants (eg, carbamazepine, gabapentin).
CHAPTER 11 NEUROLOGY 141

142 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Follow-Up\:
Patients with MS should be seen once a year at a minimum and more frequently when treated with disease modifying drugs.
Pearls\:
• Whites, especially from Northern Europe, are at higher risk of developing MS compared to Asians and Africans.
• Patients that develop the relapsing form of MS typically have a better prognosis compared to the progressive disease.
• Some studies have found that there are fewer attacks during pregnancy (especially the third trimester), but an increase in attacks in the first 3 months postpartum. However, it is agreed that pregnancy does not affect the disease course of MS, and at the same time, MS does not affect the course of pregnancy, with the exception of treating with certain dis­ ease modifying drugs that are known teratogens.
• MRIT1-weighted images can sometimes demonstrate hypo- intense lesions that can appear as “black holes” that represents axonal damage.
• Some patients with MS can have Charcot’s triad, which con­ sists of nystagmus, dysarthria (scanning speech), and inten­ tion tremor.
• Internuclear ophthalmoplegia (INO) is a conjugate lateral gaze disorder caused by a lesion in the medial longitudi­ nal fasciculus (MLF) of the brainstem. Upon horizontal gaze, there is impaired adduction of the affected eye that is ipsilateral to the MLF lesion, and at the same time, there is nystagmus of the contralateral eye that is in abduction. The cumulative effect is horizontal diplopia while looking to one side. Convergence is preserved. When bilateral INO is present, it is suggestive of multiple sclerosis (not pathog­ nomonic), and vertical nystagmus is usually seen upon upward gaze.
• Marcus Gunn pupil is a relative afferent pupillary defect that can be seen in patients with optic neuritis and other optic nerve disorders. When light is directed in the affected eye with the afferent pupillary defect, a mild constriction will occur in both pupils (direct and consensual reflex), hence a “rela­ tive defect.” When light is directed in the unaffected eye, both pupils constrict normally. In either case during illumination, both pupil sizes are the same because of an intact efferent pathway (unlike anisocoria). During the swinging flashlight maneuver, a penlight is rapidly moved between the left and right pupil, and if an afferent pupillary defect is present, the
SPINAL DISEASE
1 LUMBARSPINALSTENOSIS
Lumbar spinal stenosis (LSS) refers to narrowing ofthe spinal canal that can lead to neural compression on a single intervertebral disk level or on multiple levels. The most common cause of LSS is due
pupils will constrict normally but will also appear to dilate (ie, consider a normal constriction relative to a soft constriction).
• Progressive multifocal leukoencephalopathy (PML) is a pro­ gressive demyelinating disease affecting the white matter at multiple locations. PML typically results from reactivation of the JC virus in immunosuppressed individuals. Symptoms include visual disturbances, hemiparesis, ataxia, limb clumsi­ ness, altered mental status, and sometimes seizures. Patients taking natalizumab for MS should discontinue the medication.
• Acute transverse myelitis is characterized by an inflammato­ ry process that results in spinal cord injury in 1 or 2 segments of the cord. In MS, there is partial rather than total cord in­ volvement in the transverse plane. Patients will present with sudden onset of symptoms below the level of the lesion. Common findings include lower extremity weakness, sensory disturbances, and sphincter (rectal and bladder) dysfunction.
• Acute disseminated encephalomyelitis (ADEM) should be part of the differential diagnosis and is characterized by mul­ tifocal demyelinating lesions in the CNS that are frequently seen in the setting of postvaccination or a viral infection. ADEM takes on a self-limited and monophasic course.
• Clinically isolated syndrome (CIS) is characterized by a single attack that is congruent with MS. CIS can take a self­ limited course or disseminate into the diagnosis of MS.
• Once you understand this topic, you will have a better and broader understanding of MS that will sharpen your overall clinical judgment.
• On the CCS, if you decide to order a lumbar puncture, you also need to order the specific components of the CSF analy­ sis (eg, CSF protein, CSF cell count, or CSF immunoelectro- phoresis, which has the IgG and oligoclonal banding).
• On the CCS, remember to “advise patient, side effects of medication” if you decide to treat an MS patient.
• On the CCS, remember to always “bridge” your therapy. MS is a good example because in some cases you have to treat specific symptoms while treating acute exacerbations and at the same time treating the chronic or remitting portion of the disease. Other good examples of “bridging your therapy” (ie, addressing the acute stage along with the chronic stage of the disease) is with rheumatoid arthritis, gout, multiple myeloma, PTSD, panic disorder, nephrolithiasis, Meniere’s disease, anaphylaxis, hyperthyroidism, primary hyperpara­ thyroidism, hypoparathyroidism, third degree AV block, WPW, and torsades de pointes.
to degenerative changes in the lumbar region or spondylosis. Other causes ofLSS are acquired factors (eg, trauma, neoplasms, spondylo­ listhesis) or congenital conditions (eg, achondroplasia, spina bifida).
Clinical Features\:
Patients with degenerative arthritis LSS are typically older peo­ ple (>50 years). The classic presentation is bilateral neurogenic claudication or pseudoclaudication. Patients may report pain

in the buttock, lower back, or radiating leg pain (unilateral or bilateral), or they may complain of numbness, tingling, or weak­ ness in the legs, and not uncommonly, they may complain of a combination of everything. Symptoms are usually exacerbated by standing, walking, walking downhill, or maintaining spinal extension (eg, riding a bike in the extended position). However, climbing stairs or walking uphill does not exacerbate neuro­ genic claudication. Symptoms are often relieved by sitting, lying supine, or maintaining a flexed position (eg, leaning on a shop­ ping cart). If there are unilateral radicular symptoms (eg, focal sensory loss, pain, or weakness), then consider the possibility of stenosis at the neural foramen or lateral recess. However, since the degenerative-type LSS affects multiple levels, it is not un­ common to have polyradiculopathy. On neurologic examina­ tion, patients with LSS usually have a normal exam with normal peripheral pulses and skin exam (ie, no pallor). In a small subset of patients, patients may have a positive (abnormal) Romberg test, wide-based gait, or a positive straight leg raise test.
Next Step\:
Step 1) The diagnosis of LSS is based on a thorough clinical assessment and neuroimaging. The imaging of choice for LSS is an MRI.
Step 2) The initial management approach is with conservative treatment such as pharmacologic therapy (eg, NSAIDs, analge­ sics) and physical therapy.
Step 3) When patients continue to have disabling symptoms despite conservative therapy, then surgical intervention is con­ sidered. The surgical procedure is usually a decompressive lami­ nectomy ± lumbar fusion.
Follow-Up\:
Patients that decide to undergo surgery should continue to fol­ low up with their primary care physician since approximately 25% of patients may develop recurrent stenosis after 5 years of the initial surgery.
Pearls\:
• Spinal stenosis can also occur at the cervical and thoracic levels.
• There is no strong correlation between the severity of the ste­ nosis and the severity of the symptoms.
CEREBROVASCULAR DISEASES
I ISCHEMICSTROKE
A stroke is characterized by a sudden neurologic deficit that results from inadequate blood flow (ischemic stroke) or from brain hemorrhage (intracerebral or subarachnoid). Ischemic strokes result from embolism, thrombosis in situ, or systemic hypoperfusion. Approximately 80% of strokes are ischemic and 20% are hemorrhagic.
• As we age, there is disc desiccation with loss of disc height, and it is thought that the stress placed on the surrounding structures leads to segmental instability and therefore a com­ pensatory change (eg, facet joint hypertrophy, osteophyte formation) that results in narrowing of the spinal canal and neural foramina.
• Epidural steroid injections are used to treat patients with LSS, but because of the limited evidence-based information, epidural injections is not routinely recommended.
• Vascular claudication is a result of peripheral vascular dis­ ease and can be easily confused with neurogenic claudica­ tion since both disorders are typically seen in the elderly population.
• Vascular claudication is exacerbated by walking (either up­ hill, straight, or downhill), and biking (either in the flexed or extended position). Symptoms are relieved by standing, sitting, or lying supine. Spinal flexion does not alleviate the pain, and spinal extension does not exacerbate the pain. In other words, when the patient is in the quiet state or “just chillin,” then symptoms are not exacerbated.
• The terminal portion of the spinal cord has a tapered conical shape structure, the conus medullaris, that usually sits be­ tween T12 and L2 vertebral levels.
• Infrequently, compression of the conus medullaris (conus medullaris syndrome) or lumbosacral nerve roots (cauda equina syndrome) can be a complication of LSS. Patients may complain of motor and sensory abnormalities in the lower extremities and bowel and bladder dysfunction. Patients that present with rapidly progressive symptoms may require an emergent MRI and urgent surgical con­ sultation.
• Connecting point (pg. 299)—Know how to manage periph­ eral arterial disease (PAD).
• On the CCS, "physical therapy” is available in the practice CCS.
• On the CCS, if you feel that you’ve completely managed the patient and the case does not end, you can advance the simulated time by selecting the “Call/see me as needed” option. The patient will then be sent home and the case will advance to the next pending result, patient update, or to the end of the case.
Risk Factors\:
Hypertension, diabetes mellitus, smoking, hyperlipidemia, atrial fibrillation, endocarditis, valvular disease, carotid stenosis, TIAs, cardiac structural anomalies, oral contraceptives, illicit drugs.
Clinical Features\:
Symptoms of ischemic stroke can be abrupt and maximal at onset, which would suggest an embolic stroke. Neurologic symptoms that are progressive with a waxing and waning pattern may suggest thrombosis, hypoperfusion, or recurrent emboli.
CHAPTER 11 NEUROLOGY 143

144 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
FIGURE 11-1* Cerebral vasculature. Arteries of the anterior (white) and posterior (purple) cerebral circulation in relation to the circle of Willis. (Reproduced with permission from Aminoff MJ, et al. Clinical Neurology. 6th ed. NewYork\: McGraw-Hill; 2005\:288.)
There are various stroke syndromes that typically correlate with compromise to a specific arterial supply (see Figure 11-1). Consider the following, and keep in mind that not all patients will present the same\:
Anterior cerebral artery—Contralateral hemiplegia and hemisensory loss (lower extremity > upper extremity and face); urinary incontinence; abulia; gait apraxia; dyspraxia ofleft limb; tactile aphasia in left limb; or grasp and sucking reflexes
Anterior choroidal artery—The anterior choroidal artery is a branch from the internal carotid artery. Features include contralateral hemiplegia, homonymous hemianopsia, and hemihypesthesia.
Middle cerebral artery (MCA)—Contralateral hemiplegia and hemisensory loss (upper extremity and face > lower extremity); homonymous hemianopsia; gaze preference toward the side ofthe lesion; dominant hemisphere (Brocas aphasia, Wernickes aphasia); nondominant hemisphere (neglect, anosognosia, apractognosia); and proximal MCA give rise to penetrating vessels (lenticulostriate arteries) that can result in lacunar strokes (see below).
Posterior cerebral artery (PCA)—Homonymous hemi­ anopsia; visual hallucinations; achromatopia (color blindness); color anomia; third nerve palsy; prosop­ agnosia; memory impairment; verbal dyslexia without agraphia (non-dominant hemisphere); choreoathetosis; sensory loss; contralateral hemiplegia (ie, cerebral pe­ duncle affected)
Basilar artery—The superior cerebellar artery (SCA) is a branch of the basilar artery (see Figure 11-1) and oc­ clusion of the SCA results in nausea, vomiting, ipsilateral
cerebellar ataxia, dysarthria (slurred speech), or contralat­ eral loss of pain and temperature. The anterior inferior cer­ ebellar artery (AICA) is also a branch of the basilar artery and occlusion of the AICA can produce nausea, vomiting, ipsilateral cerebellar ataxia, facial weakness, vertigo, tin­ nitus, unilateral deafness, nystagmus, Horners syndrome, conjugate lateral gaze paresis, or contralateral loss of pain and temperature. Basilar artery occlusion that results in bilateral ventral pontine damage can cause the “locked- in syndrome” that manifest as quadriplegia, spared con­ sciousness, and preserved vertical eye movements and blinking. Occlusion of the rostral section of the basilar artery is typically due to an embolism and the syndrome is referred to as “top-of-the-basilar syndrome.” Manifes­ tations include oculomotor and pupillary abnormalities, memory impairment, abulia, or hypersomnolence. Finally, occlusion of the lower basilar artery can be responsible for the medial medullary syndrome (see below).
Vertebralartery—Occlusionofthevertebralarteryorlower basilar artery can result in the medial medullary syndrome, which consists of ipsilateral paralysis with atrophy of half the tongue, contralateral paralysis of arm and leg (sparing the face), and contralateral impairment of tactile and pro­ prioceptive senses over half of the body. Lateral medullary syndrome (Wallenberg syndrome) can also occur, which is the result of an occlusion of the vertebral artery (majority of cases) or posterior inferior cerebellar artery (PICA), which is a branch of the vertebral artery (see Figure 11-1). Manifestations of the Wallenberg syndrome include vertigo, nausea, vomiting, nystagmus, diplopia, oscillopsia, Horners syndrome, loss of taste, dysphagia, hoarseness, paralysis of vocal cord, i gag reflex, hiccup, numbness of ipsilateral arm, trunk, or leg, ataxia of limbs, falling to side of lesion, ipsilateral pain, numbness, and impaired sensation over half the face, and contralateral impairment of pain and thermal senses over half the body (sometimes the face). The poste­ rior inferior cerebellar artery (PICA) is also responsible for cerebellar infarctions. Common findings include occiput headaches, gait ataxia, vomiting, truncal dysfunction, hypo­ tonia, or ipsilateral body tilt upon sitting or standing.
Internal carotid artery (ICA)—Not only does the ICA per­ fuse the brain, but also the optic nerve and retina through the ophthalmic artery, which is branch of the ICA. The cen­ tral retinal artery is a branch of the ophthalmic artery that runs within the dural sheath of the optic nerve and emerges at the optic disc. For that discussion, patients with internal carotid disease (eg, carotid occlusion or small emboli to the central retinal artery) can present with transient monocular blindness (amaurosis fugax) prior to the onset of a stroke. Patients may complain ofblurring, fogging, “graying,” dim­ ming, or a wedge of visual loss in one eye. At other times, patients may complain of a curtain or shade coming across the visual field in the affected eye. In most cases, symptoms are of short duration (a few minutes).
Common carotid artery—Atheromatous plaques can develop in the common carotids and result in occlusion of the vessel. Signs and symptoms of an occluded common

carotid can be similar to signs and symptoms of an occluded ICA. Auscultation of the carotids may reveal a carotid bruit, which would suggest stenosis of the carotid artery.
Lacunar strokes—Lacunar strokes are small vessel strokes due to an occlusion of small penetrating vessels that arise from larger arteries at acute angles (eg, MCA, circle of Willis, basilar artery, vertebral arteries). Lacunar strokes are non- cortical infarcts that usually affect the basal ganglia, pons, and subcortical white matter (eg, internal capsule). Mani­ festations can include a pure motor hemiparesis (no sensory deficit), pure sensory stroke (no motor deficit), ataxic hemi­ paresis, sensorimotor stroke (both motor and sensory deficit present), or dysarthria-clumsy hand syndrome.
Next Step\:
Step 1) Patients suspected of having a stroke require an urgent evaluation because time is of the essence. The best first step is to assess Airway, Breathing, and Circulation.
Step 2) Place monitoring equipment on patient\: pulse oximetry (check for hypoxia), continuous blood pressure cuff, continuous cardiac monitoring, and 12-lead EKG.
Step 3) Provide supplemental oxygen to maintain O, saturation >94% (do not give if nonhypoxic).
Step 4) Establish IV access with laboratory studies (eg, CBC, BMP, PT/INR, PTT, troponins, lipid profile) and in select
patients order toxicology screen, blood alcohol level, HCG, or ABG (if hypoxia is suspected).
Step 5) Finger-stick glucose. Treat hypoglycemia (glucose <60 mg/dL) with slow IV push of 25 mL of 50% dextrose to reach normoglycemia. Oral glucose should be avoided because you want to keep the patient NPO. In addition, oral glucose takes longer to achieve normoglycemia compared to IV. Treat­ ing hypoglycemia is important right away because it is one of the exclusion criteria for IV fibrinolysis (see Table 11-1).
Step 6) Perform a focused history and physical. In addition, the NIH stroke scale can be performed at this time.
Step 7) Order an emergent noncontrast CT or MRI to exclude intracerebral hemorrhage and to determine hypodensity (on CT) or hyperintensity (on MRI). In most cases, a noncontrast CT is sufficient to make management decisions. Determining hypodensity is important on CT because it is part of the exclu­ sion criteria for IV fibrinolysis (see Table 11-1). The goal of CT initiation is <25 minutes, and CT interpretation should be done in <45 minutes from the time of entering the ED.
Step 8) Determine ifthe patient is a candidate for fibrinolytic thera­ py since the goal oftherapy (door-to-drug) should be <60 minutes. The inclusion and exclusion criteria to receive IV recombinant tis­ sue plasminogen activator (rtPA) are based on the guidelines from the American Heart Association/American Stroke Association (see Table 11-1). Consider the following two scenarios\:
Table 11-1 • AHA/ASA Criteria for IV rtPA in Acute Ischemic Stroke within 4.5 Hours
Indications (All Three Must Apply)
1) Diagnosis of ischemic stroke causing measurable neurologic deficit.
2) Onset of symptoms within 3-4.5 hours; if the exact time is not known, then use the last time the patient was known to be normal. 3) Age >18 years.
Major Contraindications (Any of the Following)
Vitals
Elevated BP (systolic >185 or diastolic >110)
History
Hx of stroke or significant head trauma within the previous 3 months
Hx of arterial puncture at noncompressible site in previous 7 days
Hx of previous intracranial hemorrhage
Recent intracranial or intraspinal surgery
Intracranial neoplasm, AV malformation, or aneurysm
Clinical picture
Symptoms suggestive of subarachnoid hemorrhage
Active internal bleeding
Bleeding diathesis
Labs
Platelets <100,000/mm3
Blood glucose <50 mg/dL
Anticoagulant use with INR >1.7 or PT >15 seconds
Heparin use within 48 hours resulting in T PTT (greater than upper limit of normal)
Direct thrombin inhibitor use or direct factor Xa inhibitor use with T lab tests (eg, PTT, INR, platelets) Imaging
CT showing multilobar infarction (hypodensity > one-third cerebral hemisphere)
CHAPTER 11 NEUROLOGY 145

146 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Candidate for Fibrinolytic Therapy
• Hold all anticoagulants and antiplatelets for 24 hours.
• Hypoglycemia should be treated (see step 5).
• Elevated BP (>185/110) should be treated with IV labetalol or IV nicardipine, and ifunable to go below 185/110 mm Hg, then do not administer rtPA.
• If all criteria are met (see Table 11-1), administer IV alteplase (rtPA) followed by a transfer to a stroke unit or ICU.
Noncandidate for Fibrinolytic Therapy
• Administer aspirin followed by a transfer to a stroke unit or ICU
Step 9) Continue with supportive care; further investigation may be considered to determine the cause of the stroke. Con­ sider the following\:
Blood pressure—Patients receiving IV fibrinolysis should have their BP checked every 15 minutes for the first 2 hours with a goal BP of <180/105. If elevated, IV labetalol or IV nicardipine can be given.
Neuro checks—Patients receiving IV fibrinolysis should have neuro assessments at least every 15 minutes during and after fibrinolytic therapy for at least the first 2 hours.
Hyperglycemia—Hyperglycemia is not uncommon in acute ischemic strokes and is associated with a worse out­ come during the first 24 hours after a stroke compared to normoglycemic patients with a stroke. Treat hyperglyce­ mia to a level within 140 to 180 mg/dL, and remember to monitor glucose levels with Accu-Cheks.
Hyperthermia—Temperatures >38°C should be investi­ gated and treated with antipyretics.
Fluid status—Euvolemic patients can be given mainte­ nance fluids, and hypovolemic patients should be given normal saline.
Cardiac monitoring—Monitor for at least 24 hours after a stroke to detect atrial fibrillation or other arrhythmias.
Ancillary testing—Other testing may be considered to search for the cause of the stroke such as carotid doppler ul­ trasound, TEE, TTE, CTA, MRA, or blood tests in younger patients without a clear underlying cause (eg, protein C, protein S, factor V Leiden, ANA, anti-double stranded DNA [anti-dsDNA] antibodies).
Step 10) Encourage secondary prevention, which may include any of the following\:
Lifestyle modification—Smoking cessation, reduce heavy alcohol intake, and encourage physical activity (if able to perform).
Hypertension—Reduce blood pressure in patients who had an ischemic stroke or TIA and are beyond the first 24 hours.
Hyperlipidemia—Initiate a statin in patients who have evidence of atherosclerosis, LDL >100 mg/dL, and who are without known CHD.
Diabetics—Maintain glycemic control and keep BP <130/80.
Noncardioembolic strokes—Patients with noncardioem- bolic strokes should be given either aspirin alone, clopidogrel alone, or aspirin + dipyridamole. Do not give aspirin and clopidogrel together because it can increase the risk ofhemor­ rhage. Tidopidine is another antiplatelet agent that is used to prevent recurrence, but it is not a first-line agent and is gener­ ally reserved for patients who are intolerant ofaspirin or clop­ idogrel. Also, remember not to give aspirin within 24 hours ofIV rtPA therapy, but it should be given within 48 hours after a stroke (ie, it decreases mortality if given within 48 hours).
Cardioembolic strokes—Anticoagulation with warfarin should be given to patients with atrial fibrillation (parox­ ysmal or permanent), mechanical prosthetic heart valves, rheumatic valve disease, or in patients with an LV thrombus in the setting of an acute MI.
Disposition\:
Patients generally have better outcomes in a stroke unit where there aresystemsofstrokeprotocolsinplaceandwheredeliveryofcareis more efficient. Remember to obtain a CT or MRI at 24 hours after fibrinolytic therapy before starting antiplatelets or anticoagulants.
Pearls\:
• Systemic hypoperfusion typically causes diffuse global cerebral deficits; common causes are cardiac arrest, PE, or acute MI.
• Thrombosis and embolism typically cause focal deficits.
• A rim of ischemic tissue that surrounds the core of infarcted tissue is referred to as the ischemic penumbra, which even­ tually can infarct if blood flow is not restored. Therefore, the goal is to “save the penumbra!”
• The medial and lateral medullary syndromes contain a num­ ber of signs and symptoms, and not all patients will present the same, but you should be able to “feel the pattern” of the manifestations (ie, pattern recognition becomes essential).
• The NIH stroke scale (NIHSS) is a validated scale that is composed of 11 items with a total score from 0 to 42 with a higher number indicating impairment.
• Patients that are within 3 hours of a stroke with a NIHSS score >22 generally have a poor prognosis.
• The CHADS2 score (CHF, HTN, Age >75 years, DM, prior Stroke or TIA) estimates the risk of a stroke in patients with nonvalvular atrial fibrillation and helps determine if anti­ thrombotic therapy (ie, anticoagulant or antiplatelet therapy) is recommended. Each component is worth 1 point except for S, which is worth 2 points, for a total maximum score of 6 points. A score of 0 points indicates low risk and anti­ thrombotic therapy is not necessary, but some physicians will give aspirin even though the benefit has not been proven in this category. A score of 1 point reflects intermediate risk, and either warfarin or aspirin can be given. A score >2 points reflects relatively higher risk, and oral anticoagulant therapy (eg, warfarin, dabigatran, Rivaroxaban) is generally recom­ mended over antiplatelet therapy (eg, aspirin).
• Hypodensity seen on CT can potentially increase the risk of hemorrhage when fibrinolytic therapy is given.

Obtain a lumbar puncture after a nondiagnostic CT (ie, nega­ tive finding for blood) for suspected subarachnoid hemorrhage.
The use of emergent anticoagulation (eg, LMWH, UFH) is not recommended to prevent recurrent stroke.
Anticoagulation is not recommended within 24 hours of IV rtPA therapy.
An emergent carotid endarterectomy (CEA) in patients with acute ischemic stroke remains to be defined (ie, do not pick this on the test).
Be aware that patients with hypertension or diabetes are pre­ disposed to lacunar strokes because of small vessel disease.
Foundational point—Lipohyalinosis can be seen in small vessel occlusion resulting in lacunar strokes. It is thought that lipohyalinosis is the result of hypertension.
Foundational point—Broca’s aphasia (nonfluent aphasia) is when speech is nonfluent, but comprehension for spoken language is intact (except for grammar). The impairment can be due to an occlusion (ie, embolism) of the superior division of the middle cerebral artery resulting in an infarction in the Brocas area (expressive language) of the dominant hemi­ sphere located in the frontal lobe of the brain.
Foundational point—Wernicke’s aphasia (fluent aphasia) is when speech is fluent, but comprehension for spoken and writ­ ten language is not intact The spoken language is usually mean­ ingless, contains neologisms, and may have a pattern of a “word salad.” The impairment can be due to an occlusion (ie, embolism) of the inferior division of the middle cerebral artery resulting in an infarction in the Wernicke’s area (receptive language) of the dominant hemisphere located in the temporal lobe of the brain.
Connecting point (pg. 23)—Know the management of hy­ perlipidemia.
On the CCS, “NIH stroke scale” is available in the practice CCS.
On the CCS, "dextrose 50%” is available in the practice CCS.
On the CCS, “alteplase” and “rtPA” are both available in the practice CCS, and if you order rtPA it will be converted to alteplase on the order sheet.
On the CCS, ifyou decide to treat with rtPA, be sure to enter it in the continuous mode of frequency because the protocol recommends 10% of the rtPA should be given as a bolus over 1 minute and then infused over 60 minutes.
On the CCS, “nicardipine” is not available in the practice CCS, but “labetalol” is available. If you need to treat the hy­ pertension, order IV labetalol as a one time/bolus and check the blood pressure. The AHA/ASA recommends that you can repeat the bolus one more time if elevated BP persists.
On the CCS, assume that consent is given to you for any pro­ cedure or treatment, and if not, you will be notified.
On the CCS, you should able to order a noncontrast head CT within 25 minutes of the simulated time.
On the CCS, suboptimal management would include order­ ing any test or procedure (eg, vascular imaging, TEE) that would delay treatment. Remember you want to give IV fibri­ nolysis within 60 minutes or less of the simulated time.
I TRANSIENTISCHEMICATTACK
Transient ischemic attack (TLA) was originally defined as a tran­ sient neurologic deficit that resolved arbitrarily in <24 hours. However, the American Heart Association and American Stroke Association (AHA/ASA) has endorsed a new defini­ tion that a TLA is a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. The new tissue-based definition as opposed to the time-based definition reflects the fact that the end point is tissue injury rather than time since even a small amount of time (eg, <1 hour) of transient neurologic symptoms can result in infarction.
Clinical Features\:
TIAs can occur by the same mechanism (ie, embolism, thrombosis, hypoperfusion) and can affect the same vascular territories as ischemic stroke (see Clinical Features in Ischemic Stroke topic). TIAs can precede, accompany, or follow (rarely) a stroke or occur independently without leading to a stroke. Large artery low flow TIAs (ie, true TIAs) are brief (lasting just a few minutes to a few hours), stereotyped, and recurrent. Embolic TIAs are typically prolonged (lasting several hours) compared to true TIAs. Lacunar TIAs can precede lacunar strokes and can be characterized by their brief, repetitive motor or sensory deficits. On neurologic examination, patients can be completely normal between attacks. A classic ocular attack is amaurosis fugax (see ICA discussion under Clinical Features in the Ischemic Stroke topic).
Next Step\:
Step 1) Any patient suspected of having a stroke requires a prompt evaluation. Remember that embolic TIAs can have a prolong episode (hours) of focal neurologic symptoms, and if you’re evaluating that patient during that time you cannot be 100% sure that it is an embolic TLA or an ischemic stroke. For that reason, initially treat TIAs with urgent care and consider your first step by accessing Airway, Breathing, and Circulation.
Step 2) Place monitoring equipment on patient\: pulse oximetry (check for hypoxia), continuous blood pressure cuff, continuous cardiac monitoring, and 12-lead EKG.
Step 3) Provide supplemental oxygen ifhypoxemic.
Step 4) Establish IV access with laboratory studies (eg, CBC, BMP, PT/INR, PTT, troponins, lipid profile) and in select pa­ tients order toxicology screen, blood alcohol level, HCG, or ABG (ifhypoxia suspected).
Step 5) Finger-stick glucose; treat if indicated.
Step 6) Perform a targeted history and physical. In addition, the NIH stroke scale can be performed at this time.
Step 7) Order an emergent noncontrast CT or MRI. The AHA/ ASA guidelines recommend that patients with TIAs should have neuroimaging within 24 hours of symptom onset and that MRI with diffusion-weighted imaging (DWI) is the preferred modality, but head CT is acceptable if MRI is not available.
Step 8) Further investigation of the underlying cause should be considered.
CHAPTER 11 NEUROLOGY 147

148
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Neurovascular assessment—The AHA/ASA recommends that noninvasive imaging (eg, CTA, MRA, transcranial Dop­ pler ultrasound) of the cervical vessels should be routinely performed. Noninvasive imaging can also be performed to assess the intracranial vasculature if knowledge of an intra­ cranial stenosis or occlusion would alter management. To confirm an intracranial stenosis, a catheter angiography is the procedure of choice because it is more accurate than noninvasive imaging.
Carotid ultrasound (CUS)—A carotid ultrasound can be considered to assess the carotids especially if a carotid bruit was heard on physical exam.
Echocardiography—A transthoracic echocardiography (TTE) can be considered in patients without a clear un­ derlying cause. A transesophageal echocardiography (TEE) provides superior visualization of the posterior cardiac struc­ tures compared to the TTE and can be considered in patients with valvular disease, PFOs, or aortic arch atherosclerosis.
Blood Tests—Younger patients without clear vascular risk factors may have further blood workup, which may include protein C, protein S, factor V Leiden, ANA, or anti-double stranded DNA.
Step 9) The goal in treating patients with TIAs is to ameliorate any existing deficit and to prevent future strokes. However, pa­ tients with rapidly improving symptoms should not be given IV fibrinolytic therapy. Since approximately 4% to 10% of pa­ tients will have a stroke within the first two days after a TLA, it is important to emphasize stroke prevention treatment. The following preventive measures are based on the AHA/ASA guidelines and are the same as for ischemic stroke\:
Modifiable risk factors—Smoking cessation, reduce heavy alcohol intake, and encourage physical activity (if able to perform).
Treatable risk factors—Reduce blood pressure in patients who had an ischemic stroke or TLA and are beyond the first 24 hours; initiate a statin in patients who have evidence of atherosclerosis, LDL >100 mg/dL, and who are without known CHD; diabetics should maintain good glycemic control and keep BP <130/80.
Noncardioembolic TIAs—Patients with noncardioembolic TIAs should be given either aspirin alone, clopidogrel alone, or aspirin + dipyridamole. Do not give aspirin and clopi­ dogrel together because it can increase the risk of hemor­ rhage. Ticlopidine is another antiplatelet agent that is used to prevent recurrence, but it is not a first-line agent and is generally reserved for patients who are intolerant of aspirin or clopidogrel.
Cardioembolic TIAs—Anticoagulation with warfarin should be given to patients with atrial fibrillation (parox­ ysmal or permanent), mechanical prosthetic heart valves, rheumatic valve disease, and in patients with an LV throm­ bus in the setting of an acute MI.
Carotid endarterectomy (CEA)—CEA is recommend­ ed in patients with a recent TLA or ischemic stroke (past 6 months) that have severe carotid stenosis that is >70%,
and the estimated risk of perioperative morbidity and mor­ tality is <6%. CEA is not indicated when carotid stenosis is <50%. Between 50% and 69% stenosis, the indication is not as clear because it depends on various factors (eg, comor­ bidities, age, sex, estimated risk). The timing of CEA is also less clear, but some authorities recommend waiting between 2 and 6 weeks. Remember that an urgent CEA is not well established and not a good choice to pick on the exam.
Disposition\:
The ABCD2 score (Age, Blood pressure, Clinical features, Du­ ration of symptoms, and Diabetes) is a tool that can estimate the risk of an ischemic stroke in patients who present acutely after a TIA. The AHA/ASA guidelines state that it is reasonable to hospitalize patients with a TIA who present within 72 hours of the event and either have an ABCD2 score >3, an ABCD2 score 0 to 2 and uncertainty that diagnostic workup can be com­ pleted within 2 days as an outpatient, or an ABCD2 score 0 to 2 and other evidence that the event was caused by focal ischemia. Once the patient is in the hospital, it is also reasonable to place the patient in a telemetry unit or on Holter monitoring if the underlying cause is still unknown.
Pearls\:
• In light of the new definition of a TIA, TLA essentially does not result in acute infarction, but ischemic strokes do result in infarction of CNS tissue leaving persistent neurologic deficits.
• Diffusion-weighted MRI imaging (DWI) can detect early ischemia and has a high sensitivity and specificity for detect­ ing early infarction.
• Carotid angioplasty and stenting (CAS) is an alternative to CEA, but CEA is still considered gold standard.
• On the CCS, patients that have a carotid artery stenosis >70% should have a “vascular surgery consult.”
• On the CCS, most patients with TIAs that are seen in the ED or in the office should be hospitalized because of the op­ portunity to give IV fibrinolysis if a stroke does occur and to assess any other stroke risk factors.
1 INTRACEREBRALHEMORRHAGE
Intracerebral hemorrhage (ICH) is the second most common cause of stroke. Hypertension is the most common underly­ ing cause of spontaneous ICH. Other causes of ICH include amyloid angiopathy, arteriovenous malformations, vasculitis, coagulopathies, CNS infections, trauma, tumors, and drugs (cocaine, amphetamines, anticoagulants, thrombolytics).
Risk Factors\:
Hypertension, older age, alcohol abuse, illicit drugs (ie, sympa- thomimetics).
Clinical Features\:
The neurologic symptoms are usually of a gradual onset (ie, minutes to hours), unlike a subarachnoid hemorrhage where symptoms are abrupt. Symptoms alone in ICH may be

indistinguishable from ischemic stroke. In addition, neurologic deficits vary depending on the site of hemorrhage. Consider the following locations in a relative superior to inferior direction\:
Lobar hemorrhage—Lobar hemorrhages have a higher association with seizures. Consider the following lobes\: frontal lobe (frontal headaches, contralateral hemipa- resis), temporal lobe (aphasia), parietal lobe (contra­ lateral hemisensory loss), occipital lobe (homonymous hemianopsia)
Putamenal hemorrhage—The putamen is the most com­ mon location for hypertensive hemorrhage. Features in­ clude contralateral hemiparesis, contralateral sensory loss, homonymous hemianopsia, or gaze palsy. With larger hem­ orrhages, stupor and coma ensue.
Thalamic hemorrhage—Contralateral hemiparesis, con­ tralateral sensory loss, transient homonymous hemi­ anopsia, vertical gaze palsy, eyes that are down and in (ie, looking at nose), miotic pupils, eyes unreactive to light, aphasia (dominant hemisphere), or neglect (nondominant hemisphere).
Pontine hemorrhage—Deep coma with quadriplegia, de­ cerebrate rigidity, pinpoint pupils reactive to light, absent horizontal eye movements, or ocular bobbing.
Cerebellar hemorrhage—Vomiting, occipital headaches, gait ataxia, vertigo, gaze palsy, or facial weakness. Stupor and coma ensue in the presence of brainstem compression.
Next Step\:
Step 1) ICH is a medical emergency, and it is important to as­ sess Airway, Breathing, and Circulation.
Step 2) Place monitoring equipment on patient\: pulse oximetry, continuous blood pressure cuff, continuous cardiac monitoring, and 12-lead EKG.
Step 3) Provide supplemental oxygen if hypoxemic.
Step 4) Establish IV access with laboratory studies (eg, CBC, BMP, PT/INR, PTT, troponins, lipid profile) and in select patients order toxicology screen, blood alcohol level, HCG, or ABG (ifhypoxia suspected).
Step 5) Finger-stick glucose; treat if indicated
Step 6) Perform a targeted history and physical. In addition, the NIH stroke scale can be performed at this time.
Step 7) Order an emergent noncontrast CT or MRI. Patients that have a cerebellar hemorrhage >3 cm in diameter who are dete­ riorating, or those who have a brainstem compression, and/or those who have a hydrocephalus from ventricular obstruction require an urgent surgical removal of the hemorrhage.
Step 8) Change location to ICU and manage acute ICH in a monitored setting.
Step 9) Treat the following components of acute ICH\:
Hyperglycemia—Target glucose levels in patients with ICH is yet to be defined, but treatment with insulin to maintain normoglycemia is reasonable. Remember to monitor glu­ cose levels with Accu-Cheks.
Fever—Look for the underlying cause (eg, abscess) and treat with antipyretics.
Seizures—Routine prophylactic antiepileptics are not rec­ ommended, but if a seizure does occur, treat with a benzo­ diazepine (eg, IV lorazepam) for rapid control followed by a loading dose of either IV fosphenytoin or phenytoin to prevent recurrence.
Anticoagulant-associated ICH—Stop all anticoagulants and antiplatelet therapy. Short-term reversal of warfarin- associated ICH can be accomplished by either FFP, pro­ thrombin complex concentrates (PCC), or recombinant fac­ tor Vila (rFVIIa). Long-term reversal ofwarfarin-associated ICH can be achieved with intravenous infusion ofvitamin K. There is no standardized protocol to reverse anticoagulation, but a recommended approach is to administer vitamin K as a slow intravenous infusion in conjunction with FFP plus PCC. In this approach, you bridge the short-term reversal with the long-term reversal. Heparin-associated ICH can be reversed with an intravenous infusion ofprotamine sulfate.
Elevated intracranial pressure (ICP)—ICP can result in a midline shift with subsequent neurologic dysfunction. Sim­ ple measures to lower ICP may include elevating the head of the bed to 30 degrees and providing appropriate anal­ gesia and sedation. More aggressive approaches include os­ motic therapy (eg, mannitol, hypertonic saline), barbiturate anesthesia, neuromuscular blockade, or ventriculostomy. Glucocorticoids are not used to lower ICP in patients with ICH. Hyperventilation (PaC02 of25-30 mm Hg) is not rou­ tinely performed because the effects are rapid and transient.
Blood pressure control—The management of blood pres­ sure is still inconclusive, and the AHA/ASA guidelines acknowledge that the evidence for the efficacy of BP man­ agement in ICH is currently incomplete. However, the guidelines state that it is probably safe to acutely lower the systolic BP to 140 mm Hg when the presenting systolic BP is between 150 and 220 mm Hg. IV labetalol, nicardipine, or hydralazine are suggested agents for the boards.
Step 10) Encourage secondary prevention such as smoking ces­ sation, reduce heavy alcohol intake, quit illicit drugs, low-fat diet, reduce sodium intake, regular exercise, and a goal blood pressure of <140/90 or <130/80 in patients with diabetes or chronic kidney disease.
Disposition\:
All patients with ICH should be monitored and managed in the ICU.
Pearls\:
• Anticoagulant-associated ICH and amyloid angiopathy are usually lobar hemorrhages.
• Hyperglycemia is a common finding in patients with acute strokes and is usually associated with poor outcomes.
• When there is a suspicion for structural lesions (eg, vascular malformations, tumors) based on radiologic or clinical find­ ings, further evaluation can be made by contrast CT, contrast
CHAPTER 11 NEUROLOGY 149

150 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
MRI, magnetic resonance angiography (MRA), contrast CT angiography (CTA), CT venography, or magnetic resonance ve­ nography.
• Surgical hematoma evacuation for supratentorial ICH re­ mains controversial.
• In general, a lumbar puncture is not recommended in patients with ICH because it may induce a cerebral hernia­ tion or aggravate a midline shift.
• Patients with acute ICH should have pneumatic compression stockings to prevent venous thromboembolism (VTE).
• It can take >6 hours to reverse anticoagulation with vitamin K.
• The AHA/ASA does not routinely recommend rFVIIa as the sole agent for treating anticoagulation reversal in patients
MOVEMENT DISORDER
I HUNTINGTON'SDISEASE
Huntingtons disease (HD) is an autosomal dominant inherited disorder that results in expansion of a CAG trinucleotide repeat in the huntingtin gene located on the short arm of chromo­ some 4. The major pathology in HD is atrophy of the caudate nucleus and putamen.
Clinical Features\:
Huntington’s disease is a chronic progressive disease that can start as early as 2 years old to 80 years old, but typically be­ gins in the fourth or fifth decade. HD can be characterized by abnormal movements, psychiatric symptoms, and cognitive deterioration.
Movements—In the early stages, patients may appear fidg­ ety or restless. Eventually, choreiform movements (ie, rap­ id, involuntary, arrhythmic movements) are pronounced and involve most of the musculature. In advancing disease, the chorea is gradually replaced with spasticity, bradyki- nesia, myoclonus, dystonia (eg, abnormal postures), or a parkinsonian akinetic-rigid state. Other movement abnor­ malities that may be present in HD include oculomotor dysfunction, dysarthria, dysphagia, gait disturbances, or hyperreflexia.
Psychiatric—Patients can have depression with suicide ten­ dencies, delusions, hallucinations, irritability, or paranoia at any point during the disease.
Cognitive—Patients can develop dementia, lack insight of their cognitive deficits, and may have difficulty with con­ centration.
Next Step\:
Step 1) The diagnosis of HD is based on typical clinical features and a family history of genetically proven HD. In the absence of a family history of HD, patients can undergo genetic testing
with ICH. In addition, rFVIIa has been associated with thromboembolic events.
• On the CCS, “FFP” and “PCC” are both available on the practice CCS, but not “rFVIIa.”
• On the CCS, PCC is also known as factor IX complex and if you order “PCC” in the practice CCS, the order will be con­ verted to “factor IX complex” on the order sheet.
• On the CCS, ICH is a neurologic emergency, and therefore, your timing and sequence of actions will play an important part of your evaluation.
• On the CCS, if there are any CCS cases in which you de­ termine the patient may have an adverse or fatal outcome, remember to obtain an “advance directive,” which is available in the practice CCS.
to confirm or exclude the diagnosis of HD. Neuroimaging (eg, brain MRI) is no longer used to confirm the diagnosis of HD, but can still support the diagnosis by showing atrophy of the caudate nucleus.
Step 2) There is no cure for Huntington’s disease, and treatment is focused on symptom control and supportive care, which re­ quires a multidisciplinary approach. Dopamine-blocking agents (eg, tetrabenazine) may control the chorea, antipsychotics (eg, quetiapine) may help with the psychosis, antidepressants (eg, SSRIs) can assist with depression, but there is no effective therapy for dementia.
Follow-Up\:
Genetic counseling is recommended for patients and their families.
Pearls\:
• If HD presents before age 20, the patient is considered to have juvenile HD (Westphal variant), and clinical features can be characterized by parkinsonism (eg, rigidity), seizures, cerebellar ataxia, and little to no chorea.
• Some patients may be mistakenly diagnosed with a psychiatric illness when in fact they have HD.
• Foundational point—The CAG trinucleotide repeat en­ codes for polyglutamine tracts in the protein products (ie, longer polyglutamine tracts with more CAG repeats). CAG trinucleotide repeats can be seen in other disorders (eg, spinobulbar muscular atrophy) other than Huntington’s disease.
• Foundational point—In Huntington’s disease, the CAG tri­ nucleotide repeat mutation gives rise to a mutant huntingtin protein (with polyglutamine expansion) that is toxic to the neurons, and aggregation of the mutant protein is the patho­ logic hallmark of the disease.
• Foundational point—Anticipation can be seen in Hunting­ ton’s disease. Anticipation is a genetic terminology that ex­ plains that the genetic condition becomes more severe and

appears earlier as the disease is passed down to following generations.
Foundational point—Neurotransmitters, GABA and ace­ tylcholine, are reduced in the basal ganglia in patients with Huntington’s disease.
NEOPLASM
i MENINGIOMA
Meningiomas are one of the most common primary brain tu­ mors that are predominately benign and are typically attached to the dura (extradural is uncommon). Meningiomas can be seen in patients with neurofibromatosis type 2 (NF2), and there is a clear association in patients exposed to radiation fol­ lowed by a latency period before the development of the tumor.
Clinical Features\:
Meningiomas are typically slow-growing lesions that present in older adults and are more common in women compared to men. Patients with NF2 typically have multiple meningiomas, and they develop the tumors at an earlier age. Most individuals with meningiomas are asymptomatic, but depending on the size and location, symptoms may vary. Consider the following locations and possible effect\:
Cerebral convexities—Seizures Subfrontal—Mental status changes
Intraventricular (eg, choroid plexus)—Obstructive hydro­ cephalus
Posterior cranial fossa—Headaches, cranial nerve palsies, brain herniation
Parasagittal frontoparietal—Extremityweakness or numbness Parasellar—Visual field defects, panhypopituitarism Occipital—Hemianopsia
Optic nerve sheath—Unilateral visual loss
Olfactory groove—Anosmia
Cerebellopontine angle—Sensorineural hearing loss, vertigo
Cavernous sinus—Cranial nerve III, IV, Vj, V2, and VI deficits
Spine—Brown-Sequard syndrome (ie, hemisection of the spinal cord) that presents with weakness, loss of vibration and proprioception ipsilateral to the lesion, but contralateral loss of pain and temperature.
Next Step\:
Step 1) The best initial approach in a patient suspected ofhaving a meningioma is with imaging studies. The preferred modality is with a contrast-enhanced (gadolinium) MRI, although a contrast-enhanced CT is also acceptable. The most accurate test is with tissue biopsy, but in some cases obtaining tissue is not feasible because of the risk of further neurologic damage.
Connecting point (pg. 162)—Be familiar with the other au­ tosomal dominant disorders.
On the CCS, “genetics counseling” is available in the practice CCS.
Step 2) Complete surgical resection is the preferred approach because it is curative. However, in cases when the tumor is not surgically resectable, radiation therapy is the treatment of choice.
Follow-Up\:
Patients who undergo treatment should have surveillance with an MRI in the postoperative period and then annually to detect any recurrence.
Pearls\:
• To date, there is no association between cell phone use and meningiomas.
• Malignant meningiomas can occur, but they are rare tumors.
• Patients with NF2 also commonly have vestibular schwan­ nomas.
• Brown-Sequard syndrome can also be seen with spinal trau­ ma, spinal cord tumors, disc herniation, infarctions, infec­ tions, or hematomas.
• Brown-Sequard syndrome involves one-half of the spinal cord and affects the dorsal column, corticospinal tract, and spinothalamic tract.
• Sometimes a meningioma will show a “tail” adjacent to the tumor mass (dural tail sign) on contrast-enhanced MRI that represents dural thickening (keep in mind that this is not pathognomonic).
• Older patients with comorbidities that are found to have an incidental finding of a small asymptomatic meningioma can be initially followed radiologically.
• Stereotactic radiotherapy uses precise and focused radiation delivered to a tumor with the goal of minimizing injury to adjacent structures.
• Foundational point—Psammomatous meningioma is one of many subtypes of meningioma. Histologically, it is char­ acterized by numerous cellular whorls with psammoma bodies (laminated calcific concretions). Psammoma bodies can also be seen in other carcinomas (eg, papillary thyroid carcinoma, papillary renal cell carcinoma, papillary serous carcinoma of the ovary).
• Connecting point (pg. 162)—Be familiar with the other au­ tosomal dominant disorders.
• On the CCS, “radiation therapy” and “stereotactic radiother­ apy” are both available in the practice CCS, and if you order stereotactic radiotherapy, it will be converted to radiation therapy on the order sheet.
CHAPTER 11 NEUROLOGY 151

152 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
On the CCS, if you decided to use radiation therapy on a patient, remember to order a “radiation therapy consult,” but keep in mind that the practice CCS does not recognize “ra­ diation oncologist” under the consults.
TRAUMA
I EPIDURAL HEMATOMA
Epidural hematoma (EDH) is characterized by bleeding into the potential space between the skull and dura mater. The primary mechanism of EDH is trauma to the temporoparietal area with injury to the middle meningeal artery. In a small subset of pa­ tients, injury can occur in the posterior cranial fossa region re­ sulting in EDH from disruption of the dural sinuses.
Clinical Features\:
After trauma to the head, the patient may go into a coma, or there may be a momentary loss of consciousness followed by recovery of consciousness or the “lucid interval.” As the hema­ toma expands, the patient can deteriorate and may experience vomiting, drowsiness, confusion, headaches, seizures, aphasia, or hemiparesis. Without intervention, the hematoma will con­ tinue to expand resulting in elevated intracranial pressures (ie, Cushings reflex—HTN, bradycardia, respiratory depression) with possible transtentorial or uncal herniation that can result in an oculomotor nerve palsy (ie, ipsilateral dilated pupil; paralysis of adduction, elevation, and depression; eye rests in a “down and out” position). Following a comatose period, death will ensue.
On the CCS, as soon as you confirm the diagnosis of cancer, re­ member to “advise patient, cancer diagnosis,” which is available in the practice CCS. Try not to advise the patient at tine end ofthe CCS case because you are tested on the sequence ofyour actions.
Next Step\:
Step 1) The best initial test is with an unenhanced head CT scan. The classic finding on CT scan is a lens-shaped (ie, bicon­ vex or lenticular-shaped) mass ± midline shift (see Figure 11-2). On head CT scan, epidural hematomas do not cross suture lines because of the firm attachment of the dura to the sutures.
Step 2) Symptomatic patients require emergent surgical hematoma evacuation usually by burr hole evacuation (trephination) or open craniotomy. In addition, ligation of the bleeding vessel should be considered during the procedure. Only in select patients (ie, small EDH and asymptomatic) can surgical evacuation be deferred, but close monitoring should be emphasized with serial brain imaging.
Disposition\:
After initial management in the ED, patients should be trans­ ferred to the ICU or sent for surgical evacuation.
Pearls\:
• Epidural hematomas evolve more rapidly compared to sub­ dural hematomas.
• The lucid interval seen in EDH can be of shorter duration (several hours) if the EDH is due to a pumping arterial bleed, but if the culprit is a venous bleed the lucid interval can be several days to weeks.
FIGURE 11-2* Subdural and epidural hematoma. A. Subdural hematoma. Unenhanced CT scan demonstrating a large, hyperdense (white) crescent­ shaped lesion that spans over most of the right cerebral hemisphere. Also note the shift of the lateral ventricles across the midline. B. Epidural hematoma. Unenhanced CT scan demonstrating a hyperdense (white) lenticular-shaped lesion over the right parieto-occipital region. Fracture of the occipital bone was seen on bone windows. (Reproduced with permission from Greenberg DA, Aminoff MJ, Simon RP. Clinical Neurology. 8th ed. New York\: McGraw-Hill; 2012\:54.)

• Elevated intracranial pressures (ICP) can also be seen with obstruction of the confluence of sinuses located in the pos­ terior fossa.
• Not all patients will present with the classic lucid interval (ie, <20% of cases will demonstrate the lucid interval).
• Lumbar puncture is contraindicated in patients with sus­ pected EDH since there is a risk ofherniation.
• Spinal epidural hematomas may be related to trauma, coag­ ulopathies, neoplasms, or vascular malformations. Patients may complain of pain, paresthesias, sensory loss, weak­ ness, or bladder and bowel dysfunction. An MRI should be ordered in patients suspected of having a spinal epidural hematoma.
• On the CCS, ordering a complete physical exam would be considered suboptimal management since that would cost you extra time and delay treatment.
• On the CCS, “neuro checks” is available in the practice CCS, and it is an important monitoring parameter in patients with EDH since clinical deterioration can arise soon after the lu­ cid (clear) period.
1 SUBDURAL HEMATOMA
Subdural hematoma (SDH) is characterized by bleeding into the space between the dura and the arachnoid membranes. The primary mechanism of SDH is a sudden acceleration or deceleration of the brain in relation to fixed dural structures resulting in tearing of the bridging veins. In a small subset of patients, arterial rupture (eg, small cortical arteries) can also result in SDH.
Clinical Features\:
Subdural hematomas can be classified as acute, subacute, or chronic. The time from onset is arbitrarily defined as acute (1-2 days after injury), subacute (3-14 days after injury), and chronic (>14 days after injury).
Acute SDH—Patients with significant cerebral atrophy (ie, elderly and alcoholic patients) are at high risk for acute SDH, especially if they have any coagulopathies. After trauma to the head, the patient may go into a coma, or there may be a brief “lucid interval” followed by progressive neurologic de­ terioration and eventually coma if there is no intervention. Subdural hematomas can also form in the posterior fossa causing elevated intracranial pressures (ICP) and result­ ing in vomiting, headaches, dysphagia, anisocoria, cranial nerve palsies, stiff neck, or ataxia.
Chronic SDH—Chronic SDH is commonly seen in older adults (especially if they are taking anticoagulants), but the traumatic etiology may not be as apparent. Patients may have insignificant head trauma that they may not remember. The clinical presentation is often insidious and may include headaches, apathy, drowsiness, light­ headedness, cognitive dysfunction, unsteady gait, or occasionally seizures.
Next Step\:
Step 1) The best initial test is with an unenhanced head CT scan. The SDH can be unilateral or bilateral and is commonly located over the frontotemporal region. Findings on CT scan will demonstrate a crescent-shaped lesion ± midline shift (see Figure 11-2), and unlike epidural hematomas, SDH can cross suture lines. The density of the lesion on CT scan can give us a relative time frame of the injury in that an acute SDH the lesion is hyperdense (white), subacute SDH the lesion is isodense (in relation to the brain), and chronic SDH appears as hypodense (dark).
Step 2) Patients with acute or chronic SDH who continue to have progressive neurologic deterioration and signs of increas­ ing intracranial pressures (eg, Cushing’s reflex, dilated pupil(s), decorticate or decerebrate posturing) should undergo urgent surgical hematoma evacuation either by burr hole or craniotomy. In addition, ligation of the bleeding vessel should be considered during the procedure. Only in select patients (ie, small SDH and asymptomatic) can surgical evacuation be deferred, but close monitoring should be emphasized with serial brain imaging.
Disposition\:
After initial management in the ED, patients should be trans­ ferred to the ICU or sent for surgical evacuation.
Pearls\:
• The evolution of a subdural hematoma develops more slowly compared to an epidural hematoma because of its venous origin.
• Venous bleeding is usually stopped by the rising intracra­ nial pressures, which unlike arterial bleeds are steadily progressive.
• Lumbar puncture is contraindicated in patients with sus­ pected SDH since there is a risk of herniation.
• A hygroma (fluidlike sac) can form from liquefaction of a chronic SDH or from separation of the dura from the arach­ noid (eg, brain atrophy) resulting in an arachnoid tear al­ lowing CSF to escape into the subdural space. Hygromas can be indistinguishable from chronic SDH on imaging studies. Hygromas that fail to resolve spontaneously and continue to expand require surgical evacuation.
• CJ\: A 52-year-old alcoholic man complains of headaches in the emergency department. The patient vaguely states that he remembers hitting his head on the ground 9 days ago. The initial noncontrast head CT scan appears “normal” on preliminary results, but the index of suspicion for a subdu­ ral hematoma is high. What is your next best step? Answer\: Patients with subacute SDH or chronic SDH will present with an isodense or hypodense lesion on noncontrast CT, respectively. These lesions can appear as normal findings on noncontrast CT, and therefore, the next best step is to con­ sider an IV contrast CT or MRI. The contrast material will enhance the vascular capsule surrounding the hematoma.
• On the CCS, poor management would include failure to order any imaging study to identify the subdural hematoma.
CHAPTER 11 NEUROLOGY 153

154 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
CCS\: SUBARACHNOID HEMORRHAGE
CASE INTRODUCTION
Day 1 @ 22\:30 Emergency Room
A 55-year-old African American woman comes to the emergency department because of a headache.
Initial Vital Signs\:
Temperature\: 37.0°C (98.6°F) Pulse\: 80 beats/min Respiratory\: 16/min
Blood pressure\: 147/92 mm Hg Height\: 172.7 cm (68.0 inches) Weight\: 54.5 kg (120 lb)
BMI\: 18.2 kg/m2
Initial History\:
Reason(s) for visit\: Headache
HPI\:
A 55-year-old restaurant owner is brought into the emergency department by her husband because of a severe and sudden on­ set of a headache for the past 2 hours. She states that this is the “worst headache of my life” and rates her pain as 10/10 in se­ verity. The pain is mainly over her right temporal area without radiation. She also has visual changes, photophobia, stiff neck, and nausea without vomiting. She denies any fevers, chills, re­ cent trauma, or sick contacts. Over the past week, she has had two other episodes of sudden headaches without any relief from taking acetaminophen.
Review of Systems\:
General\:
Skin\:
HEENT\:
Musculoskeletal\:
Cardiorespiratory\:
Gastrointestinal\:
Genitourinary\: Negative
Past Medical History\: Past Surgical History\:
Medications\: Allergies\: Vaccinations\: Family History\:
Social History\:
Hypertension
Cesarean deliveries at ages 22 and 24.
HCTZ, amlodipine
None
Up to date
Father died oflung cancer at age
70. Mother diedof a subarachnoid hemorrhage at age 55. Older broth­ er, age 57, has hyperlipidemia. Smokes one pack per day X 30 years; drinks two martinis every day and more on the weekends; Hx of cocaine abuse; married with two children; restaurant owner; enjoys cooking
Neuropsychiatric\: Day 1 @ 22\:38
Physical Examination\: General appearance\:
HEENT/Neck\:
Chest/Lungs\:
Heart/Cardiovascular\: Abdomen\:
Extremities/Spine\:
Neuro/Psych\:
See HPI
Well nourished, well developed; in pain and uncomfortable. Normocephalic. Nontender to pal­ pation over the right temporal area. EOMI, PERRLA. Subhyaloid retinal hemorrhages seen on funduscopic examination. Hearing normal. Ear, nose, and mouth normal. Pharynx normal. Neck supple; trachea mid­ line; no masses or bruits; thyroid normal.
Chest wall normal. Diaphragm and chest moving equally and symmetri­ cally with respiration. Auscultation and percussion normal.
SI, S2 normal. No murmurs, rubs, gallops, or extra sounds. No JVD. Normal bowel sounds; no bruits. No tenderness. No masses. No hernias. No hepatosplenomegaly.
No joint deformity or warmth. No cyanosis or clubbing. No edema. Peripheral pulses normal. Spine exam normal.
GCS score of 13. Nuchal rigidity with positive Kernig’s and Brudz- inski’s sign. Cranial nerve exam normal. Sensory exam normal. Pronator drift absent or other motor deficit absent. Cerebellar function normal. Deep tendon reflexes normal.
See HPI Negative See HPI See HPI Negative See HPI

First Order Sheet\:
1) IV access
2) Ketorolac, IV, one time/bolus
Second Order Sheet\:
1) Head CT without contrast, stat
Third Order Sheet\:
1) Lumbarpuncture,stat
2) GSF cell count, stat
Fifth Order Sheet\:
1) NaCl tablets, oral, one time/bolus
2) Isotonic saline solution, IV continuous 3) BMP, routine, q6 hrs
Note\: Do not wait for the report time before transferring to the ICU.
Actions\:
1) ChangelocationtoICU
Note\: Vitals are automatically ordered as q4 hrs in the practice CCS.
Fourth Order Sheet\:
1) NPO
2) Urine output, routine, q8 hrs
3) Neuro checks, routine, ql hr
4) Pneumatic compression stocking
Seventh Order Sheet\:
1) Cerebralangiography,stat
5) Bedrest, complete
6) Omeprazole, oral, continuous
7) Docusate, oral, continuous
8) Pulse oximetry, stat
9) Continuous cardiac monitor, stat
10) Continuous blood pressure cuff, stat
11) 12-Lead EKG, stat
12) Neurosurgery consult, stat
13) Nimodipine, oral, continuous 14) PT/INR, stat
15) PTT, stat
16) CBC with differential, stat
17) BMP, stat
Result\: 97%
Result\: Regular sinus
Result\: 147/92 mm Hg
Result\: U waves present
Reason\: Suspected sub­ arachnoid hemorrhage.
Result\: PT-10 seconds (nl\: <12), INR-1.0 (nl\: 1.0-1.3)
Result\: 26 seconds (nl\: <28)
Result\: WBC-9,000, H/H-14/38%, Plt-200,000, Differential- normal
Result\: Glu-90, Urea-12, Na-134, K-3.9, Cl-103, HC03-26, Cr-1, Ca-9.3
Neurosurgery consult recommendations\: Based on a favor­ able clinical grade along with a multidisciplinary decision, the recommendation is neurosurgical clipping. After discussion with the patient regarding alternative treatments, risks and ben­ efits with surgery, the patient agrees with surgery. Thank you for the consult.
This case will end in the next few minutes of “real time.” You may add or delete orders at this time,
then enter a diagnosis on the following screen.
Eighth Order Sheet\:
1) Type and crossmatch, blood, stat
2) Chest x-ray, PA/lateral, stat
3) Counsel family/patient
4) Advise patient, no smoking
5) Advise patient, limit alcohol intake • 6) Advisepatient,noillegaldruguse
7) Advise patient, advance directive
Please enter your diagnosis\: Subarachnoid Hemorrhage
DISCUSSION\:
Subarachnoid hemorrhage (SAH) refers to bleeding into the subarachnoid space that is between the arachnoid membranes and pia mater. Most causes of SAH are due to a rupture of a saccular aneurysm. Other causes of SAH can be from nona- neurysmal mechanisms such as arteriovenous malformations or intracranial arterial dissection. Approximately 20% of strokes are hemorrhagic, with 10% accounting for SAH and 10% accounting for intracerebral hemorrhage. Unfortunately, about 10% of patients with SAH will die prior to reaching the hospital.
Result\: No blood seen in the ventricles or inter-
hemispheric fissures. No hydrocephalus. No mass effect Normal findings. .
Result\: Opening pressure 210 mm H20 (nl\: 70-
180 mm H20); gross blood obtained.
Result\: RBCs seen with a cellcountof7x 106/mm3
BMP result is now available
Vitals are now available Neuro signs available
Sixth Order Sheet\:
Glu-90, Urea-12,
1) 2)
Check cardiac monitor Pulse oximetry
,
Result\:
Na-138, K-3.9, Cl-103, HC03-26, Cr-1, Ca- 9.3
Result\: Temp-37°C, HR- 80, RR-16, BP-147/92
Result\: . Alert, PERRLA, moves all 4 extremities.
Result\: Regular sinus Result\: 97%
Result\:Rightmiddle cerebral artery (MCA) aneurysm detected.
CHAPTER 11
NEUROLOGY 155

156 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Risk Factors\:
Hypertension, smoking, heavy alcohol intake, sympathomimetic drugs (eg, cocaine), verylow BMI, familyhistory ofaneurysmal SAH (especially first-degree relatives), autosomal dominant polycystic kidney disease, Ehlers-Danlos syndrome type IV, glucocorticoid-remediable aldosteronism (GRA)
Clinical Features\:
Aneurysmal SAH is more likely to be seen in patients between 40 and 60 years of age, with a higher incidence seen in women compared to men. All ethnic groups are at risk of SAH, but blacks have a higher risk compared to whites. The classic pre­ sentation is a sudden onset of severe headaches (ie, thunderclap headache) that patients often describe as the “worst headache of my life.” Approximately 30% of these sudden headaches oc­ cur at night, and 30% of headaches will lateralize to the side of the aneurysm (eg, right-sided headaches with a right-sided MCA). A second presentation to be aware of in patients with SAH is prodromal signs and symptoms prior to the rupture of the aneurysm or the major SAH. Prodromal events can be due to sentinel leaks, emboli, or a mass effect. Sentinel leaks are “warning leaks” where patients lose a small amount of blood from the aneurysm resulting in sentinel headaches. Emboliza­ tion from a thrombus within an aneurysm can result in TIAs. A mass effect from an expanding aneurysm can result in neuro­ logic dysfunction that is based on the location of the aneurysm. For example, anterior communicating artery (hemiparesis, abu­ lia), middle cerebral artery (face and upper extremity paresis, aphasia, retro-orbital pain), internal carotid artery or large an­ eurysms (cavernous sinus compression affecting CN III, IV, Vv V2, and VI), PICA or AICA (occipital pain), and at the junction of the posterior communicating artery and internal carotid ar­ tery (CN 3- oculomotor nerve palsy). Finally, the last presenta­ tion to be aware of in patients with SAH is immediate loss of consciousness (LOC) soon after the rupture. Keep in mind that other associated features of SAH that may or may not be present are nausea, vomiting, seizures, subhyaloid retinal hemorrhages, or meningismus (ie, signs and symptoms of meningeal irrita­ tion but without actual infection).
Next Step Summary\:
Step 1) SAH is a medical emergency, and as you approach this case you want to consider your differential diagnosis, which in­ cludes meningitis, ischemic stroke, intracerebral hemorrhage, TIA, encephalitis, migraine, and cluster headache.
Step 2) Perform a targeted physical exam.
Step 3) Address any pain issues, and in this case, the patient was complaining of a 10/10 pain.
Step 4) The best initial diagnostic test is with a noncontrast head CT. The sensitivity of the CT is highest if performed within 12 hours of symptom onset. The sensitivity of the CT remains fairly high in the first 3 days, and then progressively declines until af­ ter the fifth to seventh day the CT shows an increase in nega­ tive CT scans for SAH. By the 10th day, most of the blood in the subarachnoid is resorbed. If the head CT is normal (ie, no
blood on CT) then the next best step is to perform a lumbar puncture (LP). The classic finding on LP for SAH is an elevat­ ed opening pressure and an elevated RBC count that can reach >1 million/mm3. The next question you have to consider is whether an elevated RBC count is due a traumatic LP or SAH. There are 3 ways you can differentiate between a traumatic LP and SAH. First, you can collect the CSF in 4 tubes, and ifthe RBC count is consistently elevated in all 4 tubes, it would suggest an SAH, but ifthe last tube has alower RBC count, it would suggest a traumatic LP. However, counting RBCs in the tubes is not always reliable since there are cases where there is a lower RBC count in the later tubes of SAH. The second way of differentiating between a traumatic LP and SAH is to quickly take your CSF samples and spin them down (centrifugation) to look for xanthochromia. If the supernatant appears pink or yellow, xanthochromia is present because the color reflects the breakdown of RBCs. Keep in mind that if xanthochromia is present, it means that blood has been in the CSF for at least 2 hours. On the other side, if you don’t have

xanthochromia it would imply that there is no blood in the CSF or there was not enough time for RBCs to break down (which suggests a traumatic LP). Therefore, it is important to centrifuge your samples quickly. Finally, the last way of differentiating be­ tween a traumatic LP and SAH is to look at the opening pressure. A traumatic LP will generally have a normal opening pressure since the puncture was probably a local vessel, but bleeding into the CSF from a SAH would elevate the opening pressure.
Step 5) All antiplatelet and anticoagulant therapy should be discontinued in patients with SAH until definitive treatment ofthe aneurysm. Remember to look at the patients medication(s) to deter­ mine ifyou want to discontinue them in all ofyour CCS cases.
Step 6) Admit suspected patients with SAH to the ICU for con­ tinuous monitoring and basic ICU care (eg, GI prophylaxis, stool softeners, bedrest, I/Os, pneumatic compression stocking, neuro checks). At this point, you can order your basic labs and a baseline EKG, but you do not want to wait for the report time on the CCS before ordering the treatment. Also be aware that EKG abnormalities are common in SAH, which is thought to repre­ sent myocardial injury from autonomic stimulation or release of catecholamines. Possible EKG abnormalities include ST depres­ sions, T wave inversions, prominent U waves, QT prolongation, tachycardia, or bradycardia.
Step 7) Consider the following treatment management of SAH\:
Blood pressure control—Hypertension should be controlled from the time of SAH symptom onset until the time of aneu­ rysm obliteration. It is thought that lowering the blood pres­ sure will reduce the risk of rebleeding, but it can also lead to cerebral ischemia. The target blood pressure is yet to be de­ fined, but the AHA/ASA guidelines recommend a decrease in systolic BP <160 mm Hg to be reasonable. For the boards, you can use IV labetalol but avoid nitroglycerin and nitroprusside because they can increase the intracranial pressure (ICP).
Aneurysm Repair—The goal of aneurysm repair is to pre­ vent rerupture. Aneurysm obliteration can be accomplished by “clipping” the aneurysm (via neurosurgeon) or “coiling” embolization of the aneurysm (via endovascular specialist).

The choice of procedure depends on the location of die aneurysm, the grade of the patient, and availability of the resources to perform the procedure;
Vasospasms—Vasospasms are a complication of SAH that can lead to cerebral ischemia and infarction. Vasospasms are the leading cause of mortality and morbidity after aneurysm rupture. Vasospasms typicallypeak 7 to 10 days after a rupture and spontaneously resolve after 21 days. Transcranial Doppler (TCD) can monitor for the development of a vasospasm. The calcium channel blocker nimodipine was initially used to pre­ vent vasospasms, but there is no substantial evidence that the drug affects the incidence of the vasospasms. However, since nimodipine has been shown to improve the neurological out­ comes, the use ofthe drug is still recommended and should be instituted within 96 hours (4 days) ofthe SAH.
Hyponatremia—Hyponatremia is fairly common follow­ ing SAH. Hyponatremia is typically due to SIADH and less commonly from cerebral salt-wasting. Cerebral salt- wasting results in volume depletion that eventually leads to the release of ADH. Treatment of cerebral salt-wasting can be accomplished by infusing isotonic saline, which will re­ store the volume status to euvolemia, eventually inhibiting the release of ADH. Treatment of SIADH is usually with fluid restriction, but in patients with SAH, you do not want to restrict fluid because hypovolemia can result in cerebral ischemia. Salt tablets coupled with isotonic saline can ini­ tially be attempted, but eventually 3% hypertonic saline so­ lution may be required if hyponatremia persists. Remember not to correct the sodium too quickly as it could result in central pontine myelinolysis.
Hydrocephalus—Acute symptomatic patients can be man­ aged by either lumbar CSF drainage or with a ventriculos­ tomy, which has an infectious risk but does have the benefit of direct measurement of the ICR
Seizures—Management of seizures that are related to SAH is an area of controversy. Avoid prophylaxis or treatment of seizures on the boards.
Step 8) Once the patient is medically stabilized, then cerebral angiography (ie, digital subtraction angiography [DSA] with 3-dimensional rotational angiography) should be performed in patients with SAH to determine the location(s) of the aneurysm, assess the anatomy, and to help guide treatment (ie, coiling vs. clipping). The timing of the cerebral angiography will usually de­ pend on the surgical considerations, but the timing of the surgery is still under debate. For board purposes, do not delay life-saving treatment for the sake of a cerebral angiography (eg, obtaining cerebral angiography before treating an acute hydrocephalus).
Disposition\:
Patients should be managed in the ICU, and those who undergo clipping or coiling should have a follow-up vascular imaging.
Pearls\:
• SAH is frequently misdiagnosed, and if it’s in your differen­ tial diagnosis for headache, be sure to work it up because it is a medical emergency.
• Pregnancy-does not appear to be a risk factor for the devel­ opment of aneurysmal SAH.
• Screening patients for an intracranial aneurysm is not rec­ ommended for the general population. In addition, routinely screening individual family members of an affected person with an intracranial aneurysm is not well established, but may be considered on an individual basis.
• Subhyaloid retinal hemorrhages can be seen in approximate­ ly 20% of SAH cases.
• In the majority of cases, if xanthochromia is truly present in the CSF it will show by 12 hours after the SAH event
• Xanthochromia can last in the CSF for >2 weeks.
• Xanthochromia can be detected either by the naked eye (com­ mon method) or by spectrophotometry (more sensitive).
• Spectrophotometry can detect breakdown products of blood with bilirubin as the end product of heme degradation. Bili­ rubin levelspeak at 48 hours after an SAH event and can last for. 4 weeks in the CSF.
• Digital subtraction angiography (DSA) is a fluoroscopy tech­ nique that involves taking images before and after contrast dye that results in subtracting bone and soft tissue from the images permitting clearer visualization of the blood vessels.
• Patients with SAH can have elevated troponin levels, espe­ cially if there are EKG abnormalities or LV dysfunction.
• Patients with SAH can also have elevated BNP levels, al­ though the cause is still unclear.
• Perimesencephalic nonaneurysmal SAH is a type of nonaneu- rysmal SAH where blood is isolated to the cisterns that are an­ terior to the brainstem. In the majority of cases, the underlying cause is unknown, but the clinical course is milder, fewer com­ plications, and overall better outcome compared to aneurysmal SAH. On imaging, CT may show blood in the interpeduncular cistern that is anterior to the midbrain, and patients will have a normal cerebral angiography. However, you should be aware that perimesencephalic aneurysmal SAH can also occur in a small subset of patients, and the aneurysm typically arises in the posterior circulation. Therefore, any patient with perimes­ encephalic SAH should undergo angiographic evaluation.
• Glucocorticoid therapy is not routinely used in SAH because there is little evidence that demonstrates a beneficial or adverse effect from therapy.
• Rebleeding is a complication ofSAH, and the risk ofrebleeding is greatest in the first 2 to 12 hours. Early rebleeding typically has a worse outcome compared to later rebleeding.
• In most cases, CSF taken from the LP should give you a normal WBC-to-RBC ratio of approximately 1\:700 to 1000. But be aware that in some cases there may be a brisk CSF leukocytosis that occurs within 48 hours secondary to chemical meningitis which is caused by the breakdown products of subarachnoid blood, thereby altering the WBC-to-RBC ratio. There may also be lowered CSF glucose and slightly elevated CSF protein levels.
• Meningismus seen in SAH is typically caused by the break­ down products of blood with signs and symptoms appearing after several hours of the event.
CHAPTER 11 NEUROLOGY 157

158 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Treatment for symptomatic vasospasms (ie, not prevention) has been attempted with the triple-H therapy, which indudes hypervolemia, induced hypertension, and hemodilution. Triple-H therapy is typically pursued after aneurysm oblit­ eration to prevent the risk of rebleeding. However, triple-H therapy is not routinely recommended because there are no randomized clinical trials on this type of intervention.
• On the CCS, “CSF xanthochromia” is not available on the practice CCS.
• On the CCS, “spectrophotometry” is not available on the practice CCS.
• On the CCS, “transcranial Doppler” is not available on the practice CCS.
• On the CCS, “DSA, cerebral” is not available on the practice CCS, but “cerebral angiography” is available.
• On the CCS, “coiling” or “clipping” are not available on the practice CCS, but “aneurysm repair, intracranial” is available.
• On the CCS, “ventriculostomy” is not available on the prac­ tice CCS, but “ventriculbdsternostomy” is available, which is the same thing (don’t be thrown off, just piece the words together).
• On the CCS, do not assume that any orders will be written for you (eg, vitals) during the CCS cases.
• On the CCS, “nimodipine” is available in the practice CCS. The medication should be given orally of by NG tube. Do not give as IV since it has been assodated with serious adverse events (eg, death, significant hypotension). Also, you want to order it as a continuous mode of frequency because it is given as q4 hrs for 21 days.
• On the CCS, suboptimal management would indude delay­ ing treatment (eg, waiting for the report time of labs before ordering a neurosurgery consult or nimodipine).
• On the CCS, poor management would include failure to or­ der a noncontrast head CT or to follow that up with an LP if the CT was negative.

Obstetrics
CHAPTER OUTLINE
Keywords Review...............................................1..5.9....
I ANTEPARTUM..............................................1.6.0.... Antepartum Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1.6.0. . . Congenital Abnormalities......................................1.6.0.... Pregnancy Concerns...........................................1..7.0....
I INTRAPARTUM.............................................1.8..0.... StagesofLabor.................................................1.8.0..... Intrapartum Surveillance......................................1.8.0.... Fetal Heart Rate and Activity...................................1.8.1...
KEYWORDS REVIEW.
Aneuploidy—Abnormal number of chromosomes most commonly from an extra chromosome (eg, trisomy) or from a loss of chromosome (eg, monosomy).
Argyll-Robertson pupil—Pupil that does not constrict to light but can constrict to accommodation. This is pathogno­ monic for tertiary or late syphilis.
Braxton-Hicks contractions—Sporadic uterine contractions usually felt in the third trimester, most commonly described as nonrhythmic or irregular contractions.
Chadwick's sign—Bluish discoloration of the vulva, vagina, and cervix secondary from venous congestion that occurs between the 8th and 12th weeks of gestation.
I
Indications for Cesarean Section..................................1.8.1.. Preterm Premature Rupture of Membranes.......................1.8.1
POSTPARTUM. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1.8. .5. . . . Breastfeeding Concerns..........................................1..8.5... Mental Health Concerns..........................................1.8.5.... Postpartum Fevers...............................................1..8.5..... Pubic Diastasis....................................................1.8.6.....
I CCS.............................................................1.8..8....... Ectopic Pregnancy................................................1.8.8.....
Colostrum—The first milk produced after delivery, which is a yellowish milky substance that contains more proteins and minerals with less fat and carbohydrates compared to mature breast milk. It also contains IgA, which offers the newborn immune protection.
Fetal hydrops—Accumulation of fluid in fetal tissue.
Goodell sign—Softening of the cervix occurring in the 6th week of gestation.
GPtpai—Gravid, Para, Term, Preterm, Abortions, Living Gravid—Total number of pregnancies.
Gumma—Central "gummy" necrotic lesion seen in tertiary or late syphilis.
159

160 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Hegar sign—Softening of the uterus occurring in the sixth week of gestation.
Holoprosencephaly—Failure of the forebrain to develop into two hemispheres.
Latent syphilis—The stage of syphilis after untreated secondary syphilis. Latent syphilis is characterized by no clinical manifesta­ tions but positive serology for the infection. It is further divided into early latent (<1 year after secondary syphilis) or late latent (>1 year after secondary syphilis or time of infection is unknown).
Linea nigra—Hyperpigmented vertical line that runs from the pubis to the umbilicus.
Melasma—Also referred to as chloasma and known as the "mask of pregnancy" or hyperpigmentation of the face. The exact cause is still unknown.
ANTEPARTUM
I ANTEPARTUMMANAGEMENT
Antepartum is a period of many developmental and physiologi­ cal changes in the mother and growing fetus (see Table 12-1). The health of the unborn child and pregnant woman is one of the greatest concerns and therefore, it is imperative to identify any problems through prenatal testing and fetal surveillance to achieve the best possible outcome (see Tables 12-1 and 12-2).
Table 12-1 • Antepartum Logistics Maternal Physiologic Changes
Para—Number of pregnancies that led to viability.
Post-term—Delivery after 42 weeks, also referred to as post dates.
Preterm—Delivery of a baby of less than 37 weeks gestational age.
Tabes dorsalis—Degeneration of the posterior columns, characterized by weakness, shooting pains, ataxia, or impaired vibratory and position sense. This condition is seen in tertiary or late syphilis.
Term—Delivery from 37 to 42 weeks.
I CONGENITALABNORMALITIES
Congenital abnormalities are a common cause of neonatal mor­ bidity and mortality and can occur in 2% to 4% of live births. Genetics, environment, and multifactorial factors contribute to birth defects.
Genetic Disorders
Common causes of genetic disorders can be broken down into single gene disorders (see Table 12-3) and chromosomal ab­ normalities (see Table 12-4). Genetic counseling is an integral
.............................. .
Dental—No increased incidence of dental caries. Occasionally, epulis gravidarum (ie, violaceous pedunculated lesions on gum line), which can bleed easily when brushing teeth.
Cardiovascular— T Cardiac output, T stroke volume, T heart rate, i systemic vascular resistance
Pulmonary—TTidal volume, T minute ventilation, T vital capacity, T inspiratory capacity, 1 expiratory reserve volume, -i residual volume,
i total lung capacity, respiratory rate is the same as prior to pregnancy
Renal— T Renin-angiotensin system, T GFR, i BUN, i Cr, (Note\: T GFR reduces Na level, but it is then compensated by renin-angiotensin system.) Gl—Nausea, vomiting, gastric reflux, i gastric motility, constipation, T alkaline phosphatase, gallbladder dilates
Hematology—T Plasma volume resulting in dilutional anemia, T RBC volume, T ESR, i hematocrit, i serum iron
Endocrine— T HPL, T progesterone, T estradiol, T cortisol, T aldosterone, T prolactin, T ACTH, TTBG, TTotal T3 andT4, no change inTSH Skin—Linea nigra, palmar erythema, spider angiomata, melasma (chloasma)
Important Timelines of Gestation
30 days gestation—Fetus develops red blood cell antigens.
4th-5th week—Gestational sac can be detected by transvaginal ultrasound.
5th-6th week—Fetal cardiac activity begins and cardiac motion can be visualized by transvaginal ultrasound.
10th-12th week—Fetal heart tone can be heard by Doppler ultrasound.
17th-20th week—Fetal activity felt by mother or "quickening" at 20 weeks, and fundus is approximately at the umbilicus in a normal size woman.
24th-25th week—Surfactant production begins.
Iron
Zinc
Calcium
Vitamin B6 (pyridoxine) Vitamin C
Vitamin D
Folate—Routine supplements contain 0.4mg/dy but should increase to 2-4mg/dy for patients with history of neural tube defects.
Standard Prenatal Vitamin Formulation

Table 12-1 ‘(Continued)
Routine Prenatal Testing and Procedures
Initial Visit and First Trimester
Second Trimester
"Triple screen" (15-20 weeks)3 "Quad screen" (15-20 weeks)3
Third Trimester
Glucose screen (24-28 weeks)13 RhoGAM (28-30 weeks)c Repeat CBC (35-37 weeks)
GBS rectovaginal culture (35-37 weeks) Repeat STD testing in high-risk groups (28-36 weeks)
Blood related
Urine related ID related
Procedures
CBC
Blood type
Rhesus type and antibody screenc Serum free (3-hCG (11-14 weeks)3 Serum PAPP-A (11-14 weeks)3
Urinalysis Urine culture
Chlamydia/Gonorrhea cervical culture Syphilis with RPR or VDRL
HIV screen with ELISA
Hepatitis B surface antigen
Rubella titer Varicella titer
Pap smear
US-Nuchal translucency (11-14 weeks)3 CVS (10-12 weeks)3
Hemoglobin electrophoresisd
US-Assess for fetal abnormalities (18-20 weeks) Amniocentesis (15-20 weeks)3
BUN—blood urea nitrogen; Cr—creatinine; CVS—chorionic villus sampling; ESR—erythrocyte sedimentation rate; GBS—group B streptococcus; GFR—glomerular filtration rate; HPL—human placental lactogen; ID—infectious disease; US—ultrasound. 0Referto"CongenitalAbnormalities"section;bReferto"GestationalDiabetes"section;cReferto"RhesusIncompatibility"section,dlndicatedinpatientswithahistoryofthalassemiasor ! hemoglobinopathies, generally cultures from Southeast Asia and Mediterranean regions
Table 12-2 • Antepartum Surveillance
Test
Amniocentesis
Chorionic villus sampling (CVS)
Percutaneous umbilical blood sampling (PUBS), also known as cordocentesis
Why?
• Commonly used to karyotype fetal cells to determine chromosomal abnormalities. AFP and acetylcholinesterase obtained to detect neural tube defects.
• Genetic analysis.
• Advantage to CVS
compared to amniocentesis is the ability to perform
the procedure earlier in pregnancy permitting earlier decision-making regarding pregnancy termination or relieving parental anxiety when results are normal.
Fetal blood can be used to assess fetal blood gases, karyotype, infections, meta­ bolic evaluation, and can serve to diagnosis and treat fetal anemia with an intrauterine transfusion.
When?
For genetic analysis between the 15th-20th week of gestation.
Between 10th-12th week of gestation.
Typically >20 weeks gestation but depending on the clinical situation such as suspicion for fetal anemia or metabolic concerns. If karyotyping results are needed earlier, results can be available within 1-2 days.
How? Comments
Inserting a needle trans- abdominally through ultrasound guidance and aspirating amniotic fluid for analysis.
Inserting a needle trans- abdominally or inserting a catheter transcervically under ultrasound guid­ ance and aspirating pla­ cental cells for analysis.
Transabdominal needle aspiration of fetal vein under ultrasound guidance.
• Complications can occur such as fetal loss or clubbed foot in the new­ born if the procedure is performed earlier such as the 11 th-13th week.
• Complications include fetal loss, limb defects,
or oromandibular malfor­ mations ifthe procedure is performed earlier than 10 weeks.
• CVS has a higher risk of fetal loss compared
to a second trimester amniocentesis.
• Complications include, cord hematoma, fetoma- ternal hemorrhage, or fetal bradycardia second­ ary to vasovagal response from puncturing the fetal artery instead of vein.
CHAPTER 12 OBSTETRICS 161
('Continued)

162 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Table 12-2 • Antepartum Surveillance (Continued)
Test
Nonstress test (NST)
Contraction stress test (CST)
Biophysical profile (BPP)
Why?
To test for fetal well-being by assessing fetal heart rate (FHR) to fetal movement.
To test for uteroplacental function.
To test for fetal well-being.The test can give us an indication of fetal acidemia in a noninvasive way based on five parameters, which are four ultrasound assessments and NST.
When?
Typically after 32 weeks gestation.
Typically in the second or third trimester when there is a nonreactive or nonreassuring NST.
Can be used as early as 26-28 weeks gestation.
How?
Mother is in left decubitus position, with external fetal monitor on abdomen that records FHR. Mother reports fetal movement, which is noted on monitor strip and then correlated with FHR.
Mother wears external monitor on abdomen and either spontaneous or induced contrac­ tions with oxyctocin are assessed along with the FHR.
Two points per param­ eter for total of 10 points. 1) Fetal breathing
2) Fetal body movements 3) Fetal tone
4) Amniotic fluid index
5) NST
Comments
AFP—Alpha-fetoprotein (Note\: AFP is obtained from amniotic fluid in the amniocentesis.)
part of prenatal care and should be offered to patients in the following cases\:
(Ashkenazi Jews) have a risk for cystic fibrosis, Tay-Sachs, and Gaucher disease. Non-Jewish Caucasians with a family history of cystic fibrosis (CF) are at risk for CF.
Single Gene Disorders
Single gene disorders are genetic conditions with a muta­ tion or alteration in a specific gene that can be passed down into the next family generation. Modes of inheritance can be described as autosomal dominant, autosomal recessive, X-linked recessive, X-linked dominant, and mitochondrial, to name a few.
Mitochondrial
Kearns-Sayre syndrome Leber-optic atrophy
• • • • • • •
Pregnant woman >35 years old
Consanguinity
Family history of known or suspected hereditary diseases
History of recurrent spontaneous abortions
Previous child born with birth defects or growth abnormalities
Abnormal screening results from first or second trimester
Ethnicity\: People of Mediterranean, Asian, and African de­ scent have a risk for hemoglobinopathies. Eastern Europeans
Table 12-3 • Single Gene Disorders
Autosomal Dominant
Achondroplasia
ADPKD
Ehlers-Danlos syndrome FAP
Huntington disease
HCM
Marfan syndrome
Neurofibromatosis type 1 and 2
von Willebrand disease
Autosomal Recessive
ARPKD
Cystic fibrosis Cystinuria
Gaucher disease Hemochromatosis Phenylketonuria (PKU) Sickle cell anemia Tay-Sachs disease Thalassemia syndromes Wilson disease
X-linked
X-linked recessive
• Androgen insensitivity syndrome • Duchene muscular dystrophy
. G6PD
• Hemophilia A and B
. XLA
X-linked dominant
• Fragile X syndrome (most common form of familial mental retardation)
ADPKD—autosomaldominantpolycystickidneydisease, ARPKD—autosomalrecessivepolycystickidneydisease, FAP—familialadenomatouspolyposis, HCM—hypertrophic cardiomyopathy
•
•
•
•
A normal reactive test is >2 accelerations of FHR each lasting 15 beats above baseline for at least
15 seconds in a 20-minute period.
A nonreactive test should be followed up with either a CST or BPP.
A negative test (normal) has no late decelerations on FHR.
A positive test (abnormal) has late decelerations following >50% of contractions.
Point scale\:
8-10 points—Reassuring
6 points—Concerning, needs further investigation.
0-4 points—Needs some intervention, most likely fetal acidemia.

Table 12-4 • Chromosomal Abnormalities
Genetic Disease
Trisomy 21 (Down syndrome)
Trisomy 18 (Edwards syndrome)
Trisomy 13 (Patau syndrome)
45,X0 (Turner's syndrome)
47,XXY (Klinefelter's syndrome)
Clinical Features
Mental retardation, epicanthal folds, slanted palpebral fissures, flat nasal bridge, transverse palmar crease, speckled iris (Brushfield spots), ASD, VSD, PDA, tetralogy of Fallot, duodenal atresia, celiac disease, Hirschsprung's disease, TEF, leukemia, sleep apnea, asthma, thyroid disease, atlantoaxial instability with possibility of C1-C2 dislocation, females are fertile, males typically infertile, hearing loss, t risk of Alzheimer's, life span is shorter than general population but can live up to 50 y, t maternal age increases risk of meiotic nondisjunction.
Clenched fist with overlapping fingers, mental retardation, omphalocele, VSD, ASD, PDA, rocker bottom feet; 50% die within first week.
Mental retardation, holoprosencephaly, deafness, cleft lip ± palate, extra fingers or toes, VSD, ASD, PDA, rocker bottom feet; 80% die within first month.
Webbed neck, broad chest with widely spaced nipples, short stature with squarelike appearance, horseshoe kidney, coarctation, bicuspid aortic valve, HTN, hypothyroidism, celiac disease, premature ovarian failure/"streaked gonads," most are infertile, scoliosis, sausagelike fingers and toes from lymph­ edema, absent Barr bodies, intelligence is typically normal, T maternal age does not increase risk ofTurner's syndrome.
Tall, gynecomastia, t risk of breast cancer and germ cell tumors, small testes, infertile, hypogonadism/ i testosterone levels, t FSH, T LH, intelligence is typically normal and is not in the disability range but still may have academic difficulties from other causes such as poor attention, T paternal age has been associated with increased risk of Klinefelter's syndrome.
Chromosomal Abnormality
Three copies of chromosome 21, Robertsonian transloca­ tion, or mosaicism
Three copies of chromosome 18
Three copies of chromosome 13
Loss of one of the sex chromosomes
Nondisjunction of the sex chromosome resulting in an extra X chromosome in each male cell
ASD—atrial septal defect; HTN— hypertension; PDA—patent ductus arteriosus; TEF—tracheoesophageal fistula; VSD—ventral septal defect
Autosomal Dominant
■t? ,
6 #5to
5m
• 50% chance of obtaining the affected condition. • Affected condition seen in every generation.
• Can affect men and women equally.
X-Linked Recessive
, 5tQ
<55oijo
56
• 50% chance of each son being affected and 50% chance of each daughter being a carrier from the mother carrier.
• There is no male-to-male transmission
Autosomal Recessive
6oS■
• 25% chance of obtaining the affected condition. • 75% chance of being asymptomatic.
• Consanguinity commonly found.
Mitochondrial Inheritance
• Transmission is only through females.
• Children of affected males will be unaffected. • Can affect both men and women.
o©o□m□
Female, Affected female, Carrier female, Male, Affected male, Carrier male, Consanguineous mating
CHAPTER 12 OBSTETRICS 163

164 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Table 12-5 • Prenatal Risk Assessment
First Trimester Second Trimester
Abnormality hCG PAPP-A
US CVS hCG MSAFP uE3 Inh A us Lookforan Womenwho t A A T Lookforan
Amniocentesis
Women who undergo 2nd trimester screen and test positive can have fetal karyotype determination
by amniocentesis (15-20 weeks gestation) for definitive diagnosis.
Can be performed if ultrasound is equivocal. Elevated amniotic AFP and AChE indicates an open NTD.
Trisomy
21 (Down syndrome)
Trisomy 18 (Edwards syndrome)
Trisomy 13 (Patau syndrome)
Neural tube defects (NTD)
t
A
A
1
A
A
increase in nuchal translucency
and absent nasal bone.
Structural anomalies can be detected in the 1st or 2nd trimester.
undergo 1st trimester screen and test posi­ tive can have fetal karyotype determination by CVS (10-12 weeks gesta­ tion) for defini­ tive diagnosis.
1
A
~
T
A
increase in nuchal fold.
Structural anomalies can be de­ tected in the 1st or 2nd trimester.
US along with MSAFP are good 2nd trimester screens.
AChE—acetylcholinesterase;AFP—alpha fetoprotein; Inh A—inhibin A; MSAFP—maternal serum alpha fetoprotein; US—ultrasound
Prenatal Risk Assessment
Prenatal risk assessment is performed during the first or second trimester to detect genetic or structural abnormalities ofthe fetus (see Table 12-5). Consider the following screening parameters\:
PAPP-A—Pregnancy associated plasma protein A can be measured between the 11th and 14th weeks of gestation. Often this specific marker is combined with the hCG, ultrasound (US), and maternal age to give a specific risk and is referred to as the “combined test” for the first trimester.
MSAFP—Maternal serum alpha-fetoprotein is measured in the second trimester and is part of the triple and quad screening. A common cause of abnormal MSAFP readings is an incorrect gestational age. On the boards, the next best step is to order an ultrasound to verify gestational age. Open neural tube defects (ie, skin is not covering the defect), ventral wall defects (eg, omphaloceles, gastroschisis), multifetal gestations, and fetal death have been associated with elevated MSAFP levels. Gestational trophoblastic disease and chromosomal trisomies have been associated with lower levels of MSAFP. MSAFP is expressed in multiple of the median (MoM). Essen­ tially the MoM normalizes the value allowing for differences in labs and the population. A value above 2.0 to 2.5 is consid­ ered elevated but is still within the upper limits of normal.
uE3—Unconjugated estriol is a marker for a viable fetus, functioning placenta, and mother well-being.
Inhibin A—Inhibin A is a protein produced by the placenta and corpus luteum that is a marker used in the “quad screen.”
Triple screen—Triple screen consists of the hCG, MSAFP, and uE3, which is performed between 15 and 20 weeks gestation.
Quad screen—Adding inhibin A to the triple screen com­ prises the quad screen and can also be performed between
15 and 20 weeks gestation.
Environmental Factors
Environmental factors such as drugs, physical agents, ma­ ternal medical conditions, and infections can potentially harm the developing fetus (see Table 12-6). The US Food and Drug Administration (FDA) has produced a drug safety pregnancy classification based on fetal risk from pharma­ ceuticals. The system was intended to help guide physicians with the appropriate use of medications during pregnancy (see Table 12-7).
Perinatal Infections
Neonatal Gonococcal Conjunctivitis
Transmission\:
The primary mode of transmission is during vaginal delivery from infected mothers, although in utero infection can occur after ruptured membranes.
Clinical Features\:
Gonococcal conjunctivitis usually presents 3 days after birth and should be differentiated from chemical conjunctivitis (ie, secondary from silver nitrate solution), which presents on the first day of life and resolves by the second or third day of birth. Babies will usually have bilateral purulent conjunctival discharge with swelling of the eyelids. Further progression can lead to corneal edema and ulceration.

Table 12-6 • Common Teratogens
Drugs Alcohol
ACE inhibitor Aminoglycosides Androgens Carbamazepine Cocaine Diethylstilbestrol (DES) Fluoroquinolones Iodide
Result
Fetal alcohol syndrome, growth restriction, microcephaly, congenital heart disease
Fetal hypotension, renal and skull defects
Hearing defects
Virilization of females
Neural tube defects, intrauterine growth restriction (IUGR), facial dysmorphology Cerebral infarctions, IUGR, risk for placental abruption
Clear cell adenocarcinoma of the vagina or cervix in adolescence Cartilage damage
Goiter
Ebstein anomaly
Lithium
Methotrexate Fetaldeath,CNSandcardiacdefects
Penicillamine Phenobarbital
Phenytoin Propylthiouracil Streptomycin Sulfonamides Tetracycline
Thalidomide
Valproic acid
Vitamin A and isotretinoin
Warfarin Physical Agents
Ionizing radiation
Lead
Organic mercury Tobacco smoke
Toluene
Maternal Conditions Diabetes—uncontrolled Drug addiction
Grave's disease Hypertension (HTN) Phenylketonuria (PKU) Lupus (SLE)
Cutis laxa (ie, loose redundant skin that hangs in folds)
Vitamin K deficiency/bleeding diathesis
IUGR, facial dysmorphology, mental retardation, ventral septal defect (VSD)
Goiter, hypothyroidism
Hearing defects
Kernicterus
Teeth discoloration, enamel hypoplasia
Phocomelia (limbs look like "flippers")
Neural tube defects
Cleft lip/palate, CNS and cardiac defects, facial dysmorphology. (Note\: Topical retinoids have no known risk, only systemic formulas. Also, high-dose vitamin A has been implicated in malformations.)
Nasal hypoplasia, stippled bone epiphyses, IUGR, mental retardation Result
Microcephaly, growth retardation Stillbirths in high exposures
Microcephaly, mental retardation, seizures IUGR, stillbirth
Mental retardation, facial dysmorphology
Result
Macrosomia, sacral anomalies, but most common are cardiac abnormalities IUGR, neonate withdrawal
Transient thyrotoxicosis
IUGR, fetal demise
Microcephaly, mental retardation, VSD
Congenital heart block, thrombocytopenia, neutropenia, anemia
Table 12-7-F 3od and Drug Administration (FDA) Pregnancy Categories
Category A Category B
Category C
Category D Category X
Adequate human studies show no risk to fetus in any of the trimesters.
Animal studies show no risk to fetus and there are no adequate human studies oranimal studies have shown harm but adequate human studies have failed to show risk to fetus. Benefit may outweigh risk.
Animal studies show harm to fetus and there are no adequate human studies or no animal studies conducted and there are no adequate human studies. Benefit may outweigh risk, but risk cannot be ruled out.
Positive evidence of human risk to fetus but benefit may outweigh risk in life-threatening situations. Contraindicated in pregnancy.
CHAPTER 12
OBSTETRICS 165

166 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Next Step\:
Step 1) Definitive diagnosis is by culturing the exudate on a Thayer-Martin medium, which will demonstrate a gram­ negative diplococci.
Step 2) Treat with 1 dose of intravenous (IV) or intramuscu­ lar (IM) ceftriaxone. However, IV or IM cefotaxime x 1 dose should be administered instead of ceftriaxone in the presence of hyperbilirubinemia. Topical antibiotics can be used on the eyes immediately after birth as prophylaxis but not for treatment.
Pearls\:
• If the neonate develops gonococcal arthritis or sepsis —> Treat with IV or IM ceftriaxone. IV or IM cefotaxime may be administered instead of ceftriaxone in the presence of hyper­ bilirubinemia. Duration oftreatment with either antibiotic is for 7 days, but extend therapy to 10 to 14 days if the neonate develops gonococcal meningitis.
• Evaluate the neonate for coinfection with chlamydia.
• Foundational point—Neisseria gonorrhoeae comes in pairs (diplococci) that look like two kidney beans facing each other. These bacteria contain pili that adhere to the host cell. They can evade the immune system by altering the antigens in the pili (ie, antigenic variation). Antigenic variation can also occur on the surface proteins called Opa (protein II or opacity related proteins). Since they are gram-negative bacteria, the endotoxin is within the LPS (ie, lipid A).
• Connecting point (pg. 2)—Know the definition of endo­ toxin and exotoxin.
Neonatal Chlamydial Conjunctivitis and Pneumonia
Transmission\:
The primary mode of transmission is during vaginal delivery
from mothers with Chlamydia trachomatis infection. Clinical Features\:
Conjunctivitis—Usually presents 5 to 14 days after birth. Babies may have watery eye discharge that can become purulent. Other symptoms include pseudomembrane formation, eyelid swelling, and red conjunctivae.
Pneumonia—Respiratory symptoms may not occur until after 2 to 3 weeks of birth. Babies will present with a staccato cough and may be in respiratory distress.
Next Step\:
Step 1) The gold standard for diagnosing neonatal Chlamydia tra­ chomatis is by culturing the conjunctiva and nasopharyngeal secre­ tions. Ancillary testing includes a chest x-ray, which will typically reveal hyperinflation ofthe lungs with bilateral interstitial infiltrates.
Step 2) Treatment is with oral erythromycin for 14 days for either conjunctivitis or pneumonia. Remember to initiate anti­ biotic treatment without delay for suspected pneumonia based on clinical evaluation and x-ray findings (ie, do not wait for the culture results to come back).
Pearls\:
• Chlamydia trachomatis is the most common sexually trans­ mitted genital infection.
• Do not be confused with the other types of Chlamydophila (formerly Chlamydia) species (eg, Chlamydophilapneumoniae and Chlamydophila psittaci) that can cause pneumonia (ie, atypical pneumonia).
• Conjunctivitis developed via infectious or noninfectious means in newborns is also referred to as ophthalmia neona­ torum (ie, neonatal conjunctivitis).
• There is a risk of pyloric stenosis with the use of oral eryth­ romycin.
• Do not forget to treat both the mother and her partner if they have a chlamydia infection.
• Foundational point—Chlamydia trachomatis (serotypes A, B, and C) can cause trachoma. Trachoma is a contagious eye infection that is the leading cause of blindness worldwide by infectious means. A key finding in active trachoma is follicles in the tarsal conjunctiva. With recurrent conjunctival inflam­ mation, patients can progress to cicatricial disease, which includes eyelid scarring, trichiasis (ingrown eyelashes), and blindness.
• Foundational point—Chlamydia trachomatis (serotypes D-K) primarily causes neonatal infections (eg, neonatal conjunctivitis, neonatal pneumonia) and genital disease in adults (eg, cervicitis, PID, urethritis).
• Foundational point—Chlamydia trachomatis (serotypes LI, L2, and L3) can cause lymphogranuloma venereum, which is a genital ulcer disease.
• Foundational point—Chlamydiae do not have a peptido- glycan layer and have no muramic acid. Muramic acid is a component in many bacterial cell walls.
• Foundational point—Chlamydiae are gram-negative, obli­ gate intracellular bacteria that rely on the host ATP since they cannot make their own.
• Foundational point—The life cycle of chlamydiae exists in two forms. First, they infect cells (affinity for columnar epi­ thelial cells) as elementary bodies. Once inside the cell, they transform into reticulate bodies (also called initial body). From there, some transform back into elementary bodies, and then they are released from the cell where they can infect more cells.
• Connecting point (pg. 255)—Know the features of Chla­ mydophila pneumoniae and Chlamydophila psittaci.
ToRCH Infections Related to Pregnancy
The acronym ToRCH (Toxoplasmosis, others [varicella, par­ vovirus B19, syphilis], Rubella, Cytomegalovirus, Herpes simplex) represents a group of pathogens that are respon­ sible, but not limited to, intrauterine and perinatal infec­ tions that can lead to significant neonatal morbidity and mortality.

Toxoplasmosis
Transmission\:
A pregnant woman can contract toxoplasmosis by ingesting the protozoan cysts from undercooked meats, raw meats, or cured meats. The other way of contraction is by fecal-oral transmission of the cysts from infected cat feces by cat litter, water, or soil. Once the mother is infected, the parasites can travel hematog- enously to the placenta transmitting the infection to the baby.
Clinical Features\:
Mother—Most infected mothers will be asymptomatic. How­ ever, symptoms will usually present with a mononucleosis-like syndrome that include fatigue, cervical lymphadenopathy, sore throat, and will be heterophile antibody negative.
Baby—Infected neonates will usually be asymptomatic at birth; however, the classic triad includes intracranial calcifications, chorioretinitis, and hydrocephalus. Late sequelae may include hearing loss, mental retardation, and seizures.
Next Step\:
Step 1) Diagnosis for maternal toxoplasmosis infection can be made with serology. Test the serum for Toxoplasma-specific IgG and IgM antibodies. An IgG positive, IgM positive result suggests that the mother has immunity and has been infected within the past year, respectively. In this case, the next best step is to test the serum for IgG avidity. A low IgG avidity suggests a recent infection. A prenatal diagnosis for fetal toxoplasmosis infection can be made by obtaining amniotic fluid (via amnio­ centesis) for Toxoplasma PCR. In addition, fetal ultrasound may be helpful for detecting fetal abnormalities (eg, intracranial cal­ cifications, ventricular dilatations).
Step 2) Initiate spiramycin in a pregnant woman if an acute infec­ tion is suspected as this medication can reduce the maternal-fetal transmission, but not actually treat established fetal infection.
Step 3) Administer pyrimethamine, sulfadiazine, and folinic acid once fetal infection has been established.
Pearl\:
• It is important during pregnancy to avoid eating uncooked meats, avoid feeding cats undercooked meats, wear gloves or delegate the duty to clean cat litter, wash fruits and veg­ etables, and to have good hand hygiene.
• Foundational point—Toxoplasma gondii is an obligate intra­ cellular protozoan that can exist in three forms (ie, oocysts, bradyzoites, tachyzoites). Humans can be infected by ingest­ ing the oocysts (shed only in cat feces) or by ingesting un­ cooked meats that contain the bradyzoites. Infection to the fetus occurs by a transformation into tachyzoites that can travel into the bloodstream and into the placenta.
Rubella (German Measles)
Transmission\:
The virus is spread by airborne droplets that can then replicate in the lymph tissue and spread hematogenously to the placenta
transmitting the infection to the baby. Adults are considered infectious 7 days before and 4 days after the appearance of the rash. Babies are considered contagious for several months to one year after delivery as they can shed the virus from the pharynx.
Clinical Features\:
Mother—Infected mothers will have prodromal symptoms pri­ or to the onset of the rash such as cough, coryza, conjunctivitis, low-grade fever, suboccipital and posterior auricular lymphade­ nopathy, or rose spots on the soft palate (Forchheimer spots). A maculopapular rash will then start on the face and spread toward the trunk and extremities.
Baby—Infected fetuses who acquire the infection during the first trimester are at risk of a spontaneous abortion or developing the congenital rubella syndrome. After 20 weeks gestation, congenital rubella syndrome is uncommon. Some ofthe features ofcongeni­ tal rubella syndrome include “blueberry muffin” rash, cataracts, patent ductus arteriosus, pulmonary artery stenosis, and radio- lucent bone lesions. Late sequelae include hearing loss, mental retardation, encephalitis, diabetes, and thyroid disease.
Next Step\:
Step 1) Diagnosis for maternal rubella infection can be made with a rubella culture or serology. A positive result for rubella- specific IgM or a significant rise in rubella-specific IgG between the acute and convalescent phase indicates an acute infection. Prenatal diagnosis for fetal rubella infection can be made by rubella PCR via CVS or amniocentesis.
Step 2) There is no specific treatment that targets the rubella
virus, only supportive care.
<■
CHAPTER 12 OBSTETRICS 167
Step 3) Remember that rubella serum evaluation is part of the prenatal care. If the patient is nonimmune, give her the MMR vaccination after delivery since it is a live attenuated virus. Con­ traception should be used for one month following postpartum immunization.
Pearls\:
• Immune globulin does not prevent or mitigate the infection.
• The mother can still have subclinical rubella “reinfection” despite previous rubella immunization.
• Foundational point—Rubella virus comes from the family Togaviridae of the genus Rubivirus and contains a positive- sense, single-stranded RNA.
Cytomegalovirus
Transmission\:
Cytomegalovirus (CMV) transmission can occur from infected saliva, nasopharyngeal secretions, cervical secretions, semen, blood, urine, or breast milk. The following are examples of transmission\:
• Transplacentally during pregnancy
• Hand-to-hand contact (eg, day care centers) • Vaginal delivery

168 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Sexual transmission
• Blood transfusions
• Organ transplantation
• Breastfeeding (Remember, it’s not a contraindication if infected.)
Clinical Features\:
Mother—Most infected mothers will be asymptomatic. How­ ever, symptoms will usually present with a mononucleosis-like syndrome that includes fatigue, cervical lymphadenopathy, and sore throat and will be heterophile antibody negative.
Baby—Most infected neonates will also be asymptomatic. How­ ever, features to look for include periventricular calcifications, chorioretinitis, microcephaly, “blueberry muffin rash,” IUGR, and hepatosplenomegaly. Late sequelae include sensorineural hearing loss, mental retardation, and seizures.
Next Step\:
Step 1) Diagnosis for maternal primary CMV infection can be made with serology. Seroconversion of CMV specific IgG in acute and convalescent sera is diagnostic for an acute infection. CMV specific IgM has a limited role in diagnosis since it may be present in recurrent infection, reactivation infection, and prima­ ry infection, may be positive for 1 year after infection, and is only found in 75% to 90% of women with acute infection. A prenatal diagnosis for fetal CMV infection can be made by obtaining am- niotic fluid (via amniocentesis) for CMV PCR. In addition, fetal ultrasound may be helpful for detecting fetal anomalies.
Step 2) There is no specific treatment for the pregnant mother, only supportive. Ganciclovir has been used in neonates when there are signs of end organ damage.
Pearls\:
• CMV is the most common congenital infection.
• Foundational point—The cells that CMV infect become enlarged, hence “cyto-megaly.” Within the cells, intra­ nuclear inclusions surrounded by a clear halo can be stained and an appearance of an “owl’s eye” can be seen on microscope.
• Foundational point—CMV belongs to the family of Her- pesviridae. Other members in this family include EBV (infectious mononucleosis), HSV-1 (“cold sores”), HSV-2 (genitalherpes),VZV(chickenpox,shingles),HHV-6(roseola infantum/sixth disease), HHV-7 (role in human disease is unknown), and HHV-8 (Kaposi’s sarcoma). The members of this family contain a double-stranded linear DNA and can form intranuclear inclusion bodies.
Herpes Simplex Virus
Transmission\:
Herpes simplex virus (HSV) transmission can occur from an ascending infection from the genital tract, transplacental trans­ mission, or by direct contact with the genital lesions during vaginal delivery.
Clinical Features\:
Mother—Infected mothers will present with the characteristic tender genital vesicles with ulceration. Mothers may also have fever, dysuria, and tender inguinal lymphadenopathy. Prodro­ mal symptoms such as pain, pruritus, or tingling may occur before the onset of genital lesions in mothers with recurrent disease.
Baby—Infected neonates can have the lesions on the skin, eyes, and mouth. The infection can also affect the nervous system (eg, seizures) and multiple organs (ie, disseminated disease).
Next Step\:
Step 1) Diagnosis for maternal HSV infection can be made by HSV culture of the vesicular fluid or HSV PCR.
Step 2) Treatment for first-episode genital herpes is with oral acyclovir for 7 to 10 days. Recurrent HSV infection during the first 35 weeks is not typically treated since the infection is short lived. However, suppressive antiviral therapy may be offered to patients with a history of genital HSV infection at 36 weeks gestation through delivery to reduce the risk of recurrence at term.
Step 3) Perform a cesarean section in mothers with active HSV lesions or mothers with prodromal symptoms at the time of delivery. Do not perform a prophylactic cesarean section in a woman with a history of recurrent genital HSV infection and without active genital HSV lesions.
Step 4) After delivery, neonates suspected of HSV infection should be given intravenous acyclovir until the infection is con­ firmed. In addition to acyclovir, add trifluridine eye drops if the neonate develops HSV keratitis.
Pearls\:
• Avoid fetal scalp electrode (FSE) monitoring during labor in women who have active genital herpes or history of HSV infection.
• HSV-2 has been the main causative agent for genital herpes in the past, but now HSV-1, which is the common agent for oropharyngeal herpes, has now increased in frequency for genital herpes.
• Asymptomatic viral shedding can occur up to 12 months after acquiring HSV-2.
• Foundational point—The Tzanck smear involves removing theblisterroofandscrapingthebaseofthevesicleandspread­ ing it onto a glass slide to look for multinucleate giant cells. The Tzanck smear aids in the diagnosis (ie, not a first-line test) of HSV-1, HSV-2, and VZV, which contain these cells.
Other Infections in Pregnancy Varicella
Transmission\:
The primary mode of transmission is by direct contact with the vesicular lesion and by airborne droplets. The mother is consid­ ered contagious 1 to 2 days before the onset of the rash until the

lesions crust over. It is thought that fetal infection is via trans­ placental transmission.
Clinical Features\:
Mother—Infected mothers will present with a flulike prodrome 1 to 4 days prior to the onset of a pruritic vesicular rash. The lesions can appear on the face, trunk, and extremities and will appear in groups or “crops.” The lesions will then take on differ­
ent stages of evolution and then crust over in 7 to 10 days.
Varicella pneumonia can occur and is considered an emer­ gency because of the relatively high mortality rate (40%) in un­ treated women. Symptoms will usually occur within one week of the rash and include fever, dry cough, and tachypnea.
Baby—Infected fetuses that acquire the infection before 20 weeks gestation can develop the congenital varicella syndrome, which includes chorioretinitis, microphthalmia, cortical atrophy, IUGR, cutaneous scarring, or limb hypoplasia. Con­ genital varicella syndrome after 20 weeks is uncommon, but perinatal infection just before or during delivery can result in neonatal varicella, which poses a serious threat. Manifestations can range from vesicular eruptions to the development of CNS disease (eg, meningoencephalitis) and disseminated visceral involvement (eg, varicella pneumonia).
Next Step\:
Step 1) Diagnosis for maternal varicella infection is made clini­ cally. Fetal varicella infection can be assessed by VZV PCR and fetal ultrasound to detect fetal anomalies.
Step 2) Consider the following management approach\:
Exposed to chickenpox—Pregnant women exposed to chickenpox should have their varicella IgG titers taken. If they are IgG positive, they are immune. If they are IgG negative, they should receive passive immunization with the varicella-zoster immune globulin (Trade name VariZIG) within 96 hours (4 days) of exposure to attenuate the infection.
Evidence of chickenpox—Neonates should be given varicella-zoster immune globulin (Trade name VariZIG) with a mother that has clinical evidence of chickenpox 5 days before or 2 days after delivery because of concern for neonatal varicella. If neonatal varicella develops, then treat with IV acyclovir.
Step 3) Remember that varicella serum evaluation is part of the prenatal care. Ifthe mother is nonimmune, give her the varicella vaccine (Trade name Varivax) after delivery since it is a live attenuated virus. The second vaccine dose should be given 4 to 8 weeks later. Contraception should be used for one month fol­ lowing each dose of the vaccine.
Pearls\:
• A nodular infiltrative pattern can be seen on chest x-ray in mothers with varicella pneumonia.
• A pregnant mother who develops varicella pneumonia should be hospitalized and treated with intravenous acyclovir.
• Varicella-zoster immune globulin (VariZIG) should be given to premature infants >28 weeks from mothers known to have no immunity to varicella and premature infants <28 weeks regardless of the mother’s immune status.
• Herpes zoster does not cause congenital malformations.
• Herpes zoster is considered contagious when the blisters are broken. Treat pregnant women with acyclovir if there is eye involvement (herpes zoster ophthalmicus) or ifthere is severe dermatomal pain.
• Foundational point—The varicella-zoster virus can estab­ lish latency in the sensory ganglia, and upon reactivation, there is intense inflammation of the dorsal root ganglion that can be accompanied by hemorrhagic necrosis of the nerve cells.
Parvovirus B19
Transmission\:
The primary mode of transmission is respiratory. Maternal viremia will result in fetal infection via transplacental transmis­ sion (vertical transmission). Infected blood products can also harbor parvovirus B19.
Clinical Features\:
Mother—Infected mothers will usually present with flulike symptoms prior to the onset of a red rash on the face giving a “slapped cheek” appearance (although not as common in adults compared to children). Subsequently, a symmetric rash will occur on the trunk or extremity with central clearing producing a “lacy-reticulated” rash. Adults will commonly present with symmetrical polyarthralgias that usually resolve within 2 weeks. Transient aplastic crisis can occur in adults with chronic anemia (eg, sickle cell, thalassemia).
Baby—Infection in fetuses can result in fetal loss or fetal ane­ mia leading to nonimmune hydrops fetalis (ie, accumulation of fluid in fetal tissues).
Next Step\:
Step 1) Diagnosis for maternal B19 infection can be made by serology. An IgG positive result indicates a prior infection with immunity. An IgM positive result is consistent with a recent infection, but be aware that IgM can be positive for several months or longer. However, to aid in the diagnosis, obtaining maternal serum for B19 PCR may be useful. A prenatal diag­ nosis for fetal B19 infection can be made by obtaining amniotic fluid (via amniocentesis) for B19 PCR.
Step 2) There is no specific vaccine or antiviral therapy for parvovirus B19 infection. The concern with infection is parvovirus-associated anemia in the fetus. If severe anemia is present, there will usually be an elevated middle cerebral ar­ tery (MCA) peak systolic velocity on MCA Doppler, and signs of hydrops will usually be present on fetal ultrasound. In such cases, fetal blood sampling and possible intrauterine blood transfusion may be warranted via percutaneous umbilical cord sampling (PUBS).
CHAPTER 12 OBSTETRICS 169

170 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Pearls\:
• Transient aplastic crisis will usually resolve on its own in pregnant women, but IVIG has been used for women that have chronic anemia with chronic parvovirus B19 infection.
• Foundational point—Parvovirus B19 belongs to the family of Parvoviridae and contains a linear single-stranded DNA. The virus is most contagious during the shedding phase, which usually occurs 5 to 10 days after exposure.
Syphilis
Transmission\:
The major mode of syphilis infection is by sexual transmission (horizontal transmission). Direct contact with abraded skin gives a portal entry for the pathogen. Transplacental transmission is the most common route for fetal infection, but direct contact with the lesion during delivery can also occur (vertical transmission). Transplacental transmission can occur at any time during preg­ nancy, but untreated mothers that are in the primary, secondary, or early latent stages of syphilis have a higher rate of transmission because of a higher spirochete load to transmit compared to the late latent stage and tertiary (late) stages of syphilis.
Clinical Features\:
Mother—Untreated mothers can present in any of the four stages of syphilis\:
Primary—Painless chancre, lymphadenopathy
Secondary—Maculopapular rash on palms and soles, con­ dyloma lata, mucous patches
Latent (early)—Asymptomatic, but positive serology; (late)—asymptomatic, but positive serology.
Tertiary (late)—Neurosyphilis (eg, Argyll-Robertson pu­ pils, tabes dorsalis), aortic aneurysm, aortic insufficiency, gumma formation
Baby—Untreated mothers can result in fetal loss, IUGR, pre­ term birth, or fetal infection. Infected infants can develop early or late congenital syphilis\:
Early (<2 years)—Rhinitis or “snuffles” (contagious), mac­ ulopapular or vesicular rash (contagious), condyloma lata (contagious), hepatosplenomegaly, hydrops fetalis, pseudo­ paralysis (ie, no extremity movement because of bone pain), periostitis, jaundice.
Late (>2 years)—Hutchinson triad (1) Hutchinson teeth, which are small, notched, widely spaced teeth; (2) sensorineu­ ral hearing loss; (3) interstitial keratitis, frontal bossing, perfo­ rated hard palate, saddle nose, Saber shins (ie, anterior bowing of the tibia), Clutton joints (ie, symmetrical joint swelling, pain­ less arthritis), Mulberry molars (ie, multiple cusps on the crown surface of the first molar giving it the appearance of a berry).
Next Step\:
Step 1) Syphilis screening is performed at the first prenatal care visit with a nontreponemal test such as VDRL or RPR. A reactive test is then confirmed with a specific treponemal test such as FTA-ABS, MHA-TP, or TP-PA.
Step 2) Treatment is based on the stage of infection of the preg­ nant mother\:
• Primary, secondary, or early latent —> Benzathine penicillin G intramuscularly (IM) x 1 dose.
• Late latent or tertiary (late) —» Benzathine penicillin G intramuscularly (IM) x 1 dose per week for a total of 3 doses.
• Neurosyphilis —> Aqueous crystalline penicillin G (IV) x 10 to 14 days or procaine penicillin G (IM) + probenecid (PO) x 10 to 14 days.
Step 3) VDRL or RPR titers are taken at 1, 3, 6, 12, and 24 months after therapy to see if there is an appropriate decline. A fourfold decline should be seen by the 6 month, and by 2 years the titers should be nonreactive. A fourfold rise or an inappro­ priate decline suggests treatment failure or reinfection, which may then warrant retreatment.
Pearls\:
• Treatment management for penicillin-allergic patients that are pregnant\: skin testing —» penicillin desensitization -4 penicillin treatment.
• Penicillin treatment is associated with the Jarisch-Herxheimer reaction, which may cause uterine contractions, preterm la­ bor, or fetal heart rate decelerations.
• Diagnosis can also be made by darkfield microscopy show­ ing the corkscrew motile spirochete or by direct fluorescent antibody test obtained from the lesion or exudate, but both require a fluorescent microscope.
• Specific treponemal tests (eg, FTA-ABS) do not reflect dis­ ease activity, and once they test positive, it remains positive for life, but it does not mean that the patient is immune.
• Women at high risk for syphilis should be retested with a non­ treponemal test (eg, RPR) in the third trimester and at delivery.
• Women with syphilis should have HIV testing because of the high risk for coinfection.
• Pregnancy does not alter the course of syphilis.
• Treponema pallidum is not secreted in breast milk.
• Upon vaginal delivery, a large edematous placenta and umbilical cord will be a clue that the mother was infected with syphilis.
• Foundational point—Tabes dorsalis (also known as loco­ motor ataxia) affects the posterior columns and dorsal roots.
• Foundational point—Syphilis is caused by the spirochete Treponema pallidum. The spirochete has a corkscrew-shaped appearance that cannot be cultured by ordinary media and is too small to see with light microscope.
i PREGNANCYCONCERNS
Spontaneous Abortion
Spontaneous abortion (ie, miscarriage), is the nonelective termination of a pregnancy before the fetus can reach viabil­ ity, or in other words <20 weeks gestation or <500 grams.

First trimester abortions are commonly caused by chromosomal abnormalities. Second trimester abortions are often due to maternal conditions such as infections, systemic diseases (eg, lupus, diabetes), anatomic abnormalities (eg, bicornuate uter­ us), or environmental factors (eg, smoking, radiation).
Clinical Features\:
There are different categories of abortion. See Table 12-8 for the classification.
Next Step\:
Step 1) Evaluate a first trimester bleed with a speculum exami­ nation, with attention to the cervical os (see Table 12-8).
Table 12-8 • Classification of Spontaneous Abortion
Step 2) An ultrasound should be performed to assess for prod­ ucts of conception and the presence of fetal cardiac activity, which should be visualized by the 6th week of gestation.
Step 3) If the uterus is empty on ultrasound, obtain a quantita­ tive P-HCG to determine if the discriminatory level has been reached (refer to page 190, CCS—Ectopic Pregnancy).
Step 4) Refer to Table 12-8 for specific treatment management.
Step 5) Administer anti-D immune globulin (RhoGAM) in an unsensitized Rh(D)-negative woman after a D&C, D&E, or upon diagnosis if medical or expectant management is planned.
Step 6) Offer grief counseling.
Categories
Threatened
Inevitable
Incomplete
Complete
Missed
Septic
Definitions
Think of this type as a "threat"; approximately 50% of these pregnan­ cies will abort.
Think of this type as an abortion that is unavoidable.
Think of this type as
the incomplete passage of POC. POC may be found at the level of
the cervical canal.
Think of this type as the complete passage of POC.
Fetal death <20 weeks gestation with retention of the fetal tissue for

4 weeks after fetal death.
Evidence of infection
Clinical Features
Vaginal bleeding? Yes, usually in the first half of pregnancy.
Abdominal/pelvic pain? Mild cramping. Cervical os? Closed.
Passage of POC? No, still retained.
Vaginal bleeding? Yes.
Abdominal/pelvic pain? Yes, crampy pelvic pain and even uterine contractions may be present.
Cervical os? Open.
Passage of POC? No, still retained.
Vaginal bleeding? Heavy.
Abdominal/pelvic pain? Yes, usually intense crampy pain.
Cervical os? Open.
Passage of POC? Partial expulsion.
Vaginal bleeding? Scant.
Abdominal/pelvic pain? Mild to absent.
Cervical os? Closed
Passage of POC? Complete expulsion.
Symptoms? After fetal death, women may or may not have any symptoms other than persistent amenorrhea.
Cervical os? Closed.
Passage of POC? No, still retained. Ultrasound? Gestational sac without fetal
cardiac activity.
Signs and symptoms? Fever, chills, vaginal bleeding, foul discharge, leukocytosis, tachycardia, tachypnea, abdominal pain/ tenderness, uterine tenderness, and malaise.
Next Step Treatment
There is no effective therapy. Bed rest is usually recommended, but it does not alter the course.
Evacuation with a D&C. Medical (ie, misoprostol) and expectant management are acceptable alternatives if the patient is stable, without infection, and there is no heavy bleeding.
Evacuation with a D&C, especially in the presence of profuse bleeding. If there is fever, administer antibiotics before curettage.
No specific treatment.
Treatment options include surgical (eg, D&C, D&E), medical (eg, misoprostol), or expectant management.
Step 1) Treat with broad-spectrum antibiotics to cover gram-positives, gram-negatives, and anaerobes.
Option 1\: IV ampicillin + IV gentamicin + IV clindamycin
Option 2\: IV ampicillin + IV gentamicin + IV metronidazole
Option 3\: IV levofloxacin + IV metronidazole Step 2) Uterine evacuation (eg, D&C)
D&C—dilatation and curettage;D&E—dilatation andevacuation; POC—products ofconception
CHAPTER 12 OBSTETRICS 171

172 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Follow-Up\:
Follow up in the office in 6 weeks, as menses should resume by this time. If no menses, obtain a serum P-HCG level and consider a new pregnancy, gestational trophoblastic disease, or intrauterine adhesions (ie, Asherman’s syndrome).
Pearls\:
• Differentials for first trimester bleeds include ectopic pregnancy, molar pregnancy, vaginal or cervical lacerations, polyps, infection, and postcoital bleed.
• When assessing for viability, a gestational sac should be visu­ alized by approximately 5 to 6 weeks of gestation. If no sac is visualized within the uterus but the patient has appropriate hCG levels for viability, consider an ectopic pregnancy.
• Only the words inevitable and incomplete abortions have the prefix in-, which can help you remember that the cervical os is open only in these two conditions because “you can only go in if it is open” (see Table 12-8).
• A dilatation and evacuation (D&E) is a procedure that is generally performed in the second trimester since the fetus is larger. A curette is used to scrape the walls of the uterus and forceps are used to remove parts of the fetus.
• On the CCS, both “D and C” and “D and E” are available in the practice CCS.
• On the CCS, “HCG, beta” is available in the practice CCS, but you have to pick either “qualitative” or “quantitative.” A qualitative will give you a negative or positive result, but a quantitative will give you a number to analyze.
Cervical Incompetence
Cervical incompetence is a condition in which the cervix begins to dilate and efface (ie, thin out) during pregnancy before reach­ ing term.
Risk Factors\:
History of gynecologic procedures (eg, LEEP, conization, curet­ tage), history of DES exposure, history of cervical lacerations during delivery, uterine anomalies
Clinical Features\:
Most women with an incompetent cervix will present with painless cervical dilatation in the second trimester (15-28 weeks) with absent to mild contractions. Also, some women may experience cramping, lower abdominal pressure, and vaginal discharge. Without intervention, the cervical dilata­ tion can lead to prolapse or bulging fetal membranes through the external cervical os with subsequent ruptured membranes and active uterine contractions leading to the expulsion of the fetus.
Next Step\:
Step 1) Diagnosis is based on history (ie, recurrent second trimester losses, preterm birth), physical exam (ie, advanced cervical dilatation or effacement), and transvaginal ultrasound.
Step 2) One course of treatment is with a transvaginal cervical cerclage, which is a surgical procedure that involves suturing in and around the cervix to reinforce and strengthen a weaken cervix. There are three different scenarios to consider when a cerclage is placed\:
Elective cerclage—Performed when there is a history of >3 unexplained second trimester losses or preterm births. Also, ultrasound evaluation should show a viable preg­ nancy without fetal anomalies. The procedure is performed between 13 and 16 weeks gestation.
Emergent cerclage—Emergent or rescue cerclage has been used in cases of advanced cervical dilatation or effacement with bulging membranes. The procedure has been per­ formed up to 26 weeks gestation.
Urgent cerclage—Urgent or therapeutic cerclage has been used with caution in cases of ultrasound changes consistent with a shorten cervix or funneling (ie, membranes filling the internal os but with a closed external os giving the cervix an appearance of a funnel). However, it is not recommended to perform a cerclage in the mother who has no history of recurrent pregnancy losses or early preterm births. In these cases, transvaginal ultrasound surveillance would be the more judicious approach.
Step 3) Cerclage removal is typically at 36 to 37 weeks gesta­ tion, if there is suspicion for infection, or in the event of preterm labor.
Follow-Up\:
After cerclage placement, patients are followed up with cervical exams and ultrasound evaluation as needed.
Pearls\:
• Women diagnosed with cervical incompetence usually have a shorten cervix, but having a shorten cervix is not diagnos­ tic of cervical incompetence.
• Transabdominal cerclage is a surgical procedure (via lapa­ rotomy) that involves placing a suture higher up at the cervicoisthmic junction (ie, at the level of the internal os). The procedure is usually reserved in cases when previous transvaginal cerclage has failed or when there are severe anatomical cervical defects.
• Transabdominal cerclage can be performed prior to preg­ nancy or at 11 to 14 weeks gestation.
• C-section is the mode of delivery after transabdominal cer­ clage placement.
• Contraindications to transabdominal or transvaginal cerclage include infections, bleeding, ruptured membranes, uterine contractions, or fetal anomalies.
Dermatoses of Pregnancy
Pregnant women may undergo normal physiological skin changes (eg, melasma) and sometimes specific dermatoses of pregnancy (see Table 12-9). Dermatoses of pregnancy repre­ sents a heterogeneous group of skin diseases that is exclusively associated with pregnancy and/or postpartum.

Table 12-9 • Dermatoses of Pregnancy
Disorder
Pruritus gravidarum (also known as intrahepatic cholestasis of pregnancy)
Pruritic urticarial papules and plaques of pregnancy (PUPPP)
Herpes gestationis (also known as pemphigoid gestationis)
Clinical Features
There are no primary skin changes except for excoriations from scratching. Patients will have severe generalized pruritus, characteristically on the palms and soles ofthe feet. Symptoms are worse at night. Other possible features include\: jaundice, steatorrhea, and signs of vitamin K deficiency. Symptoms and lab values normalize several days after delivery. Symptoms can recur in subsequent pregnancies.
When? Usually in the 2nd or 3rd trimester but sometimes 1st trimester.
Labs? Tserum bile acids, Talkaline phosphatase, TAST/ALT, T to normal levels of GGT, t total and direct bilirubin, Tcholic/chenodeoxycholic acid ratio.
Initially, erythematous papules and plaques start within the abdominal striae and then spread toward the extremities forming urticarial plaques while sparing the periumbilical area, face, soles, and palms. Small vesicles may
be seen but not large bullae. The lesions are pruritic. Symptoms generally resolve spontaneously postpartum.
When? Usually in the 3rd trimester and sometimes postpartum. Labs? No abnormalities.
Initially, erythematous urticarial plaques or papules begin on the trunk, usually periumbilical.The lesions progress to tense blisters and even bullae formation. The lesions can spread peripherally, affecting the palms and soles. Usually the face is spared, but mucosal lesions can be affected. The lesions are pruritic. Symptoms resolve within weeks to months after delivery. Symp­ toms can recur in subsequent pregnancies, after oral contraceptive use, or during menses.
When? Usually in the 2nd or 3rd trimester.
Labs? May see the presence of antithyroid antibodies.
Direct immunofluorescence? Should see the classic linear C3 band at the dermal-epidermal junction ± IgG.
Pearl\:This is an autoimmune disorder with an HLA association and not related to the herpes viral infection. This disorder can also occur with trophoblastic diseases.
Sterile pustules studded on the margins of an erythematous patch that then coalesce forming lakes of pus. The lesions begin at the flexures and spread peripherally. Mucous membranes are usually involved. Constitutional symptoms usually occur such as nausea, vomiting, or fatigue. The lesions
are typically nonpruritic. Symptoms resolve within weeks to months after delivery. Symptoms can recur in subsequent pregnancies, after oral contraceptive use, or with menses.
When? Usually in the 3rd trimester.
Labs? Hypocalcemia, hypoalbuminemia, leukocytosis.
Pearl\: Not related to herpes infection, and patients do not have a history
Next Step Management
1) Diagnosis is based on exclusion of other diseases along with a history of pruritus and elevated
lab values.
2) Treatment is with ursode­
oxycholic acid (Tbile flow), cholestyramine (4ileal absorption of bile salts), or hydroxyzine (antipruritic).
1) Diagnosis is made clinically. 2) Initial treatment is with
topical steroids. For severe pruritus, oral steroids
(eg, prednisone) may be needed.
1) Diagnosis is made clinically along with biopsy of
the lesion for direct immunofluorescence. Direct immunofluorescence helps differentiate between PUPPP and herpes gestationis.
2) Initial treatment is with topical steroids. In most cases, it is not effective and oral steroids
(eg, prednisone) are given.
1) Diagnosis is made clinically. 2) Treatment is with oral
steroids and sometimes antibiotics for secondary infections from ruptured pustules.
Impetigo herpetiformis (also known as pustular psoriasis of pregnancy)
of psoriasis.
GGT— Gamma glutamyl transpeptidase
Endocrine Disorder
Gestational Diabetes
Diabetes diagnosed during pregnancy is referred to as gesta­ tional diabetes. Pregnancy can be characterized as a state of insulin resistance and hyperinsulinemia. Gestational diabetes occurs in a subset of pregnant women who cannot compensate for the insulin resistance, which is predominately caused by cer­
tain hormones such as human placental lactogen (HPL), growth hormone, progesterone, and corticotropin releasing hormone.
Complications
Mother—Perineal injury from a macrosomic baby
Baby—Macrosomia and birth injury from the macrosomia (eg, brachial plexus injury)
CHAPTER 12 OBSTETRICS 173

174 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Antepartum Management\:
Screening
Oral glucose challenge test is performed between 24 and 28 weeks gestation.
Step 1) 50 gram oral glucose load given without regard to time of day or time of last meal.
Step 2) Plasma glucose level is measured in 1 hour.
Step 3) Plasma glucose level <130 mg/dL is normal and requires no further workup, but a glucose level >130 mg/dL is consid­ ered abnormal and is followed up by an oral glucose tolerance test (OGTT) for definitive diagnosis ofgestational diabetes.
Oral glucose tolerance test (OGTT)
Step 1) Fasting plasma glucose level is measured.
Step 2) 100 gram oral glucose load given to a fasting preg­ nant woman.
Step 3) Plasma glucose level is measured at 1,2, and 3 hours after ingestion.
Step 4) Two or more abnormal values indicate gestational diabetes\: fasting glucose >95 mg/dL; 1 hour glucose >180 mg/dL; 2 hour glucose >155 mg/dL; 3 hour glucose >140 mg/dL.
Treatment Management
Diet—First-line therapy for gestational diabetes is dietary mod­ ification.
Exercise—Moderate exercise may improve tissue sensitivity to insulin.
Glucose monitoring—Home glucose monitoring should be checked at least 4 times a day. Glucose goals for women with gestational diabetes are\:
Fasting glucose\: <95 mg/dL
1 hour postprandial glucose\: <130 to 140 mg/dL 2 hour postprandial glucose\: <120 mg/dL
Medications—Pharmacotherapy is indicated when euglycemia cannot be achieved by nutritional therapy and exercise. First- line agents are the insulins. Oral hypoglycemic agents are not approved by the FDA for gestational diabetes, although there is increasing support for glyburide.
Fetal Surveillance—Women with gestational diabetes who are on insulin are managed similarly to women with pregestational diabetes. Fetal surveillance is not required in gestational diabet­ ics who are well controlled on diet alone.
• Nonstress test (NST)—Twice weekly testing starting at 32 weeks gestation.
• Amniotic fluid index (AFI)—Twice weekly testing starting at 32 weeks gestation.
• Biophysical profile (BPP)—Can be used in place of NST or AFI since it includes both components.
• Obstetrical ultrasound—Assess fetal size, especially for the presence of macrosomia between 34 and 37 weeks gestation.
Intrapartum Management\:
Delivery Type and Timing Inductionoflabor—Performedinpatientswithwell-controlled gestational diabetes between 39 and 40 weeks gestation. Poorly controlled gestational diabetes or other maternal-fetal indications are offered earlier delivery between 37 and 38 weeks gestation after confirmation of fetal lung maturity via amniocentesis. A lecithin-sphingomyelin (L/S) ratio >2.0 or the presence of phosphatidylglycerol indicates fetal lung maturity.
C-section—A scheduled cesarean section is offered to patients when the estimated fetal weight (EFW) is >4500 g (ie, macrosomia) to avoid risk of shoulder dystocia and related birth injuries.
Glycemic Control
Glycemic goals—Achieve glucose levels between 70 and 110 mg/dL.
Glucose monitoring—Finger sticks every 1 to 2 hours to allow for adjustments in infusion rates.
Intravenous infusions—Five percent dextrose and short-acting insulins are administered and adjusted to maintain glycemic goals during the intrapartum period.
Postpartum Management\:
Early postpartum—Immediately after placenta delivery, the levels of HPL begin to diminish rapidly because of the short half-life, and the state of insulin resistance begins to decrease. As a result, the majority ofpatients with gestational diabetes do not require further insulin therapy. Routine finger-stick checks and insulin sliding scale are appropriate in this setting.
Late postpartum—An OGTT is performed between 6 and 12 weeks postpartum to detect any persistent diabetes in both diet-controlled and pharmacotherapy-controlled gestational diabetes.
Step 1) Fasting plasma glucose level is measured.
Step 2) 75 gram oral glucose load given to a fasting woman.
Step 3) Plasma glucose level is measured at 2 hours after ingestion.
Step 4) A fasting plasma glucose level >126 mg/dL or a 2-hour glucose level >200 mg/dL indicates overt diabetes. A fasting plasma glucose level between 100 and 125 mg/dL or a 2 hour glucose level between 140 and 199 mg/dL indicates glucose impairment or prediabetes.
Pearls\:
• Patients with gestational diabetes are at risk for developing type 2 diabetes within 5 to 10 years.
• A patient with gestational diabetes is at risk for developing gestational diabetes again in subsequent pregnancies.
• On the CCS, you can type in “ogtt” in the order sheet to obtain the OGTT. Both the 1 hour and 3 hour OGTT are available in the practice CCS, but the results do not give you the normal reference values.

• On the CCS, ifyou need to refer to prior test results during the CCS, click on the “Review Chart” tab and then look for the “Lab Reports” or “Other Tests” tabs to find what you’re looking for.
Pregestational Diabetes
Diabetes diagnosed prior to pregnancy is referred to as preges­ tational diabetes (ie, overt, type 1, or type 2 diabetes).
Complications
The incidence of complications is higher among patients with pregestational diabetes, especially those with poorly controlled diabetes, compared to gestational diabetes.
Mother—T risk of infections especially urinary tract infections (UTI), hypertension/preeclampsia, polyhydramnios, spontane­ ous abortion, preterm delivery, DKA, gastroparesis, worsening of diabetic retinopathy.
Baby—Congenital heart defects (eg, septal defects, tetralogy of Fallot), neural tube defects, caudal regression syndrome/caudal agenesis (ie, abnormal development in the caudal region), re­ spiratory distress syndrome (RDS), IUGR, renal agenesis, hy­ poglycemia, hypocalcemia, hyperbilirubinemia, polycythemia, stillbirth, macrosomia and related birth injuries.
Antepartum Management\:
Maternal Care—In addition to the routine prenatal testing, several additional tests and recommendations are advocated in pregestational diabetics. Consider the following tests in a relative head to toe fashion\:
Ophthalmology—Refer to ophthalmologist for a dilated eye examination to evaluate for retinopathy.
Cardiac—Obtain an EKG at the first prenatal visit. Patients that are hypertensive should be off ACE inhibitors and ARBs because they are teratogenic. Consider methyldopa, amlodipine, or nifedipine to treat hypertension.
Renal—Obtain a baseline renal function and assess protein levels with a 24-hour urine collection or a spot urine pro- tein-to-creatinine ratio (ie, more convenient for the patient).
Endocrine—Obtain a HbAlC at the first prenatal visit. A HbAlC >10% in the first trimester is associated with a higher risk of congenital malformations. Also, obtain a TSH with free T4 at the first prenatal visit.
Treatment Management
Diet—Caloric requirements are based on the patient s body weight and activity level. Carbohydrate composition should be approximately 55%, protein 20%, and fat 25%.
Exercise—Patients that were able to exercise prior to preg­ nancy and are not deconditioned during pregnancy may continue to exercise.
Glucose monitoring—Home glucose monitoring should be done 5 to 7 times a day. HbAlC should be obtained at every trimester. Glucose goals for women with pregesta­ tional diabetes are\:
HbAlC\: <6%
Fasting glucose\: <95 mg/dL
Preprandial glucose\: <100 mg/dL
1 hour postprandial glucose\: <140 mg/dL 2 hour postprandial glucose\: <120 mg/dL Bedtime\: Keep glucose levels >60 mg/dL
Medications—Type 1 diabetics should continue with their insulin, although it should be noted that the insulin require­ ments will increase by the second half of pregnancy. Type 2 diabetics who are not glycemic controlled by diet alone or are on oral hypoglycemic agents should be treated with insulin during pregnancy.
Fetal surveillance—The goal of fetal surveillance is to assess for fetal well-being, fetal growth, and to detect congenital anomalies, which occur more commonly in pregestational diabetics.
• Nonstress test (NST) or biophysical profile (BPP)— Twice weekly testing starting at 32 weeks gestation or 26 weeks gestation if there are complications with the preg­ nancy (eg, preeclampsia).
• Ultrasound and fetal echocardiogram at 18 weeks gesta­ tion to assess for congenital anomalies, especially con­ genital heart defects.
• Ultrasound and maternal serum alpha-fetoprotein (MSAFP) in the second trimester to screen for neural tube defects (NTDs) since the prevalence is higher with pregestational diabetes. Levels ofMSAFP in diabetics are naturally lower, and adjustments have to be made in or­ der to interpret the results.
• Ultrasound exam at 32 weeks to assess for fetal growth and again at 38 weeks for an estimated fetal weight (EFW) to determine the type of delivery.
Intrapartum Management\:
Management is the same as gestational diabetes (see “Intrapar­ tum Management”).
Postpartum Management\:
Type 1 diabetes—Insulin is reduced to approximately one- third to one-half of the prepartum dose once the patient is able to eat.
Type 2 diabetes—Oral hypoglycemic agents can be resumed 1 to 2 days after delivery, but in the interim treat with insulin if the patient is eating.
Pearls\:
• Diabetes does not increase the risk for fetal chromosomal abnormalities (ie, aneuploidy).
• Diabetes does lower the levels ofMSAFP, uE3, and inhibin A. Interpretation of the “triple” or “quad” screen should be adjusted accordingly.
• Postpartum depression is common among patients with pre­ gestational and gestational diabetes.
• Offspring of women with pregestational diabetes are at risk for developing diabetes and obesity later in their lives.
CHAPTER 12 OBSTETRICS 175

176 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
HematologicDisorder
Rhesus Incompatibility
There are many blood group systems, but the rhesus (Rh) sys­ tem is the most frequently involved. Within the Rh system, there are several different types of antigens—in particular, the big D antigen on the red blood cells, which is also referred to as Rh(D) positive. Keep in mind there is no little d in the nomenclature.
Clinical Progression\:
When an Rh(D) negative woman is exposed to Rh(D) positive blood cells (eg, fetomatemal hemorrhage, blood transfusions, transplantation), the woman will develop antibodies to the D antigen (ie, isoimmunization). Anti-D IgG antibodies in the maternal circulation can then cross the placenta into the fetal circulation. Antibodies can then bind to the D antigens on the fetal erythrocyte cells of an Rh(D) positive fetus leading to cell destruction. If the mother is in her first pregnancy, the fetal effect is less severe such as anemia and hyperbilirubinemia. However, in subsequent pregnancies there is an anamnestic response of the immune system that can result in erythroblastosis fetalis. Clini­ cal features of erythroblastosis fetalis may include anemia, jaun­ dice, heart failure, enlarged spleen and liver, or fetal hydrops.
Next Step\:
Step 1) Rh(D) typing and antibody screen via indirect Coombs test is performed at the first prenatal visit. The indirect Coombs test is a very accurate way to determine antibody titer levels.
Step 2) There are two clinical scenarios to consider in the man­ agement of an Rh (D) negative mother. Determine whether she has developed antibodies (ie, sensitized) or no antibodies (ie, unsensitized). Consider the following\:
Unsensitized—Determine if there are antibodies at the ini­ tial visit. If the there are no antibodies, the antibody screen is performed again at 28 weeks gestation and at delivery. If the mother is still unsensitized at 28 weeks gestation, anti- D immune globulin (RhoGAM) is given intramuscularly (IM). After delivery, fetal rhesus type is performed, and if the baby is Rh(D) negative, no further action is required. If the baby is Rh(D) positive, then anti-D immune globu­ lin (RhoGAM) is provided again to the mother preferably within 72 hours of delivery. Keep in mind that anti-D immune globulin (RhoGAM) can be given up to 28 days after delivery.
Sensitized—If the mother develops antibodies from her first pregnancy, the next best step is to check her antibody titer level. If a critical titer level is reached, which is a value >1\:16, then this indicates enough maternal antibodies to cause severe fetal anemia. Checking a titer level in later pregnancies from previously affected infants is not needed because fetal anemia will be certain and tracking the sever­ ity of anemia is not helpful. Keep in mind that providing anti-D immune globulin (RhoGAM) is not effective once the mother is sensitized. If a sensitized Rh (D) negative mother has reached her critical titer level, then the next best step is to determine the fetal rhesus type because if the fetus is Rh(D) negative, then there is no risk for fetal complications.
The least invasive way is by paternal Rh type and zygosity. Ifthe father s Rh type is Rh(D) negative, then there is no further workup since the fetus will be Rh(D) negative. If the father is Rh(D) positive, then determine the zygosity (ie, homozygous or heterozygous). Consider the following\:
Homozygous—If the father is homozygous, there is a 100% chance that the fetus will be Rh(D) positive, and therefore, there is no need to do fetal genotyping. At this point, you can manage the patient as a “sensitized pregnancy,” and it is important to institute fetal surveillance to detect fetal anemia. Amniotic fluid bilirubin level assessment (via am­ niocentesis), fetal middle cerebral artery Doppler (MCA) assessment, and fetal blood sampling are techniques used to check for fetal anemia. If there is severe fetal anemia, an intrauterine blood transfusion via PUBS may be indicated.
Heterozygous—If the father is heterozygous, the father is unavailable, or the identity of the father is in question, then there is a chance that the fetus may be Rh(D) posi­ tive. Therefore, the next best step is to do fetal genotyping, which can be performed by either obtaining fetal blood, amniocytes (via amniocentesis), or cell-free fetal DNA from maternal blood.
Follow-Up\:
In a woman who is in her first pregnancy that is Rh(D) nega­ tive and sensitized, but does not reach the critical titer level, the next best step is to repeat titer levels every month until 24 weeks gestation and then every 2 weeks until delivery.
Pearls\:
• Remember that an Rh(D) positive woman does not require anti-D immune globulin at any time.
• Fetal middle cerebral artery (MCA) Doppler is a noninva- sive way to detect fetal anemia. In an anemic fetus, blood will be shunted to the brain to maintain oxygenation and a peaked systolic velocity will be seen on Doppler because of an increased cardiac output and decreased blood viscosity.
• Foundational point—Rh(D) antigens are only present on red blood cells, and the D antigen is considered a potent alloantigen.
• Connecting point (pg. 3)—Know the principle actions of the other immunoglobulins.
• CJ\: A 25-year-old G1P0 at 17 weeks gestation who is Rh(D) neg­ ative and unsensitized is in the ED because of a blunt trauma to the abdomen from an automobile accident There is concern for fetomatemal hemorrhage. What is your next step? Answer\: The best initial step to determine fetomatemal hemorrhage is to screen with the Rosette test. If the result is negative, you still give the standard dose of anti-D immune globulin. If the result is positive, you need to determine the amount offetal red blood cells in maternal blood by the Kleihauer-Betke test. The Kleihauer-Betke test is valuable in determining if additional anti-D immune globulin is required from the standard dose. Other indications to give anti-D immune globulin (RhoGAM) in an Rh(D) negative woman who is not sensitized and has a fetus that is or possibly could be Rh(D) positive are\:

• Procedures (eg, amniocentesis, chorionic villus sampling, fetal blood sampling)
• Trauma (eg, blunt trauma to the abdomen)
• First trimester spontaneous or elective abortion
• Second or third trimester bleeding (eg, abruption, previa)
• Third trimester rescreen at 28 weeks gestation
• Ectopic pregnancy
• Molar pregnancy (ie, hydatidiform mole)
• Fetal demise
• External cephalic version (ie, from breech to vertex presentation)
Hypertensive Disorders
Mild Preeclampsia
Preeclampsia is a condition in which hypertension and protein­ uria arise after 20 weeks gestation in a previously normotensive woman. Preeclampsia can be further classified as mild or severe.
Risk Factors for Preeclampsia\:
Nulliparity, multiple gestation (eg, twins), age <20 or >40, previ­ ous history of preeclampsia, family history of preeclampsia, pre- gestational or gestational diabetes, antiphospholipid syndrome, chronic renal disease, chronic HTN, obesity.
Clinical Features\:
Most women with mild preeclampsia are asymptomatic. However, they can develop symptoms with progressive signs of end-organ damage (see Clinical Features under Severe Preeclampsia).
Next Step\:
Step 1) Diagnosis ofmild preeclampsia is confirmed when both HTN and proteinuria are present\:
HTN—Systolic pressure >140 or diastolic pressure >90 after 20 weeks measured on two occasions at least 6 hours but not more than 7 days apart.
Proteinuria—>0.3 g (300 mg) in a 24-hour urine collec­ tion. A random urine dipstick of 1+ or 30 mg/dL is not di­ agnostic but only suggestive of mild preeclampsia.
Step 2) Once the diagnosis is made, obtain a set oflaboratory tests that should include CBC, CMP, uric acid level, LDH, and a co­ agulation profile (PT, PTT, fibrinogen). Laboratory tests should be repeated weekly if there is no progression of preeclampsia but more frequently if there is suspicion for progression.
Step 3) Assess the fetus with an ultrasound, nonstress test, or biophysical profile on a weekly basis once the diagnosis of pre­ eclampsia is made.
Step4) Delweryis the definitive treatment for preedampsia. However, there are many factors to consider prior to delivery. Consider three different scenarios in the management of a patient with mild pre­ edampsia that may indude delivery, inpatient care, or outpatient care.
Indications for delivery—The following is adapted from the Working Group Report on High Blood Pressure in Pregnancy\:
• Gestational age >38 weeks
• Deteriorating hepatic or renal function
• Platelet <100,000/mm3
• Persistent headaches, visual changes, epigastric pain, nausea, or vomiting
• Suspected placental abruption
• Severe IUGR
• Oligohydramnios
• Nonreassuring fetal surveillance
Inpatient care—Admit to the hospital in these cases\: • Noncompliant patient
• Poor access to receive medical care
• Signs of progression (eg, SBP >150, DBP >100, protein­ uria >1 g/24 hours)
• Patient care may include\:
Anticonvulsants—Anticonvulsant therapy is con­ troversial for mild preeclampsia.
Antihypertensives—Do not treat unless BP >160/ 100 (see Severe Preeclampsia).
Fetal lung maturity—Administer steroids (ie, be­ tamethasone or dexamethasone) intramuscularly (IM) in women <34 weeks gestation.
Monitoring—Close monitoring with NST/BPP, ultrasound/AFI, lab testing, BP monitor, cervical exams, and laboratory testing as indicated in the in­ patient setting.
Outpatient care—Patients that are compliant, have good access to receive medical care, and show no signs of pro­ gression can be managed as an outpatient. Patients are rec­ ommended restricted physical activity.
Follow-Up\:
Patients managed as an outpatient should be evaluated for weekly blood pressure checks, physical exams, and NST/BPP. Ultrasound and AFI measurements are performed every 3 to 4 weeks.
Pearls\:
• Since women without preeclampsia naturally have edema during pregnancy, edema is no longer used as a criterion for the diagnosis of preeclampsia.
• Remember that indications for delivery do not mean im­ mediate C-section. Often, an induction of labor will be at­ tempted first.
• On the CCS, “NST” or “Nonstress test” is available in the practice CCS, and once the external monitor is attached, then type in “check fetal monitor” for future readings.
Severe Preedampsia
Severe preeclampsia can be differentiated from mild preeclamp­ sia by signs of end-organ damage.
CHAPTER 12 OBSTETRICS 177

178 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Clinical Features\:
Women may experience multiple end-organ signs or symptoms. It may be helpful to think from a relative head to toe fashion\:
Neurologic—Visual disturbances, persistent headaches, altered mental status
Cardiovascular—Hypertension (ie, BP >160/110)
Respiratory—Shortness ofbreath
Renal—Oliguria
GI—Epigastric pain, RUQ pain, nausea, vomiting
Pelvis—Signs of placental abruption (ie, vaginal bleeding, uterine pain), fetal movements
Heme—Bruising
Next Step\:
Step 1) A woman with severe preeclampsia should be hospital­ ized to confirm the diagnosis, assess the severity of the disease, monitor the progression ofthe disease, and intervene ifindicated.
Step 2) Diagnosis of severe preeclampsia is confirmed in the presence of mild preeclampsia plus any of the following\:
HTN—Systolic pressure >160 or diastolic pressure >110 after 20 weeks measured on two occasions at least 6 hours but not more than 7 days apart.
Proteinuria—>5 grams in a 24-hour urine collection. A random urine dipstick of 3+ is not diagnostic but only sug­ gestive of severe preeclampsia.
Neurologic—Visual disturbances, persistent headaches, or altered mental status
Respiratory—Pulmonary edema or cyanosis Renal—Oliguria (ie, <500 mL in 24 hours)
GI—Epigastric pain, RUQ pain, nausea, vomiting, or twice normal serum transaminases
Heme—Platelets <100,000/mm3 Fetus—IUGR
Step 3) Once the diagnosis is made, initial management should include\:
Anticonvulsants—Intravenous magnesium sulfate to pre­ vent a first seizure.
Antihypertensives—
Treat\: When BP >160/100
Goal\: SBP 140 to 150 and DBP 90 to 100
Acute therapy\: Intravenous labetalol or hydralazine
Long-term therapy\: Oral methyldopa, labetalol, or nife­ dipine
Contraindicated drugs\: ACE inhibitors and ARBs
Fetal lung maturity—Administer steroids (IM) in women between 24 and 34 weeks gestation.
Labs—CBC, CMP, uric acid level, LDH, coagulation profile (PT, PTT, fibrinogen).
Monitor—Close monitoring with NST/BPP, ultrasound/ AFI, BP monitoring every 1 to 2 hours, urine output, and physical exams.
Step 4) Delivery is the definitive treatment for preeclampsia. However, there are many factors to consider prior to delivery. Consider three different scenarios in the management of a pa­ tient with severe preeclampsia patient that may include delivery, expectant management, or termination\:
Indications for delivery
• Gestational age >34 weeks
• Signs of end organ damage\: Neurologic (headaches, visual disturbances, altered mental status), cardiovascu­ lar (uncontrolled BP), respiratory (pulmonary edema), renal (oliguria), GI (epigastric pain, RUQ pain), heme (severe thrombocytopenia).
• Eclampsia
• HELLP syndrome
• Fetal concerns\: nonreassuring fetal surveillance, oligo­ hydramnios.
• OB concerns\: placental abruption, PPROM, preterm labor.
Expectant management—Can be considered between 24 and 34 weeks gestation in select cases. Both mother and fe­ tus conditions should be reassuring.
Termination—Should be considered when <24 weeks gestation.
Follow-Up\:
Hypertension should resolve within 12 weeks postpartum in a patient with preeclampsia. Evaluate any women who continue to have hypertension beyond this time period.
Pearls\:
• There is a greater risk of recurrence of developing preeclamp­ sia in future pregnancies in women with severe preeclampsia who delivered prior to 30 weeks compared to patients with mild preeclampsia who delivered near term.
• Intravenous nitroprusside is sometimes used as a last ditch effort to control refractory hypertension, but caution is ad­ vised because it can cause fetal cyanide poisoning.
• CJ\: A women with severe preeclampsia is given intravenous magnesium sulfate. Over a period of time, the patients res­ piration has decreased to 8 per minute, the patient is brady- cardiac and shows loss of deep tendon reflexes. In addition, the fetal heart monitor shows decrease in FHR and baseline variability. What is your next step? Answer\: The patient is showing signs of magnesium toxicity. First, discontinue magnesium sulfate administration then provide supplemen­ tal oxygen, and start intravenous calcium gluconate.
• On the CCS, remember to transfer patients from the office setting to the inpatient setting to monitor the progression of severe preeclampsia.
Eclampsia
Eclampsia is characterized by new onset tonic-clonic seizure and/or coma in a patient with a history of preeclampsia and without any other attributable causes of the seizure. The etiology of eclamptic seizures is still unknown.

Clinical Features\:
Eclampsia can occur during the antepartum, intrapartum, or postpartum period. However, it typically occurs after 20 weeks gestation. Patients may have headaches, altered mental changes, visual disturbances, or epigastric pain prior to the onset of a sei­ zure. In a small subset of patients, there is no associated hyper­ tension or proteinuria. The seizure itself can occur more than once, with each seizure lasting between 60 and 75 seconds. After the tonic-clonic phase is the postictal phase, which can last for several minutes to hours. During the maternal seizure, the fetus will show signs of fetal bradycardia and then compensatory fetal tachycardia after resolution of the seizure.
Next Step\:
Step 1) Protect the airway! Roll the patient to the left decubitus position to prevent aspiration and improve uterine blood flow. Other steps to do in this life-threatening emergency include\: in­ sert a padded tongue depressor to prevent lacerations, elevate padded bedside rails, apply oxygen face mask, obtain pulse ox­ imetry readings, initiate cardiac monitoring, secure IV line, and suction oral secretions.
Step 2) Prevent another seizure with intravenous magnesium sulfate. In most cases, the initial seizure will have passed before therapy can even be given. Therefore, treatment is directed at preventing another seizure rather than “correcting” the seizure.
Step 3) Control the hypertension, if present, with intravenous labetalol or hydralazine (see step 3 under Severe Preeclampsia).
Step 4) Delivery is the definitive treatment for eclampsia in a woman at any gestational age and once the patient has been stabilized. Vaginal delivery can be considered in a patient >32 weeks gestation with a favorable cervix and in the absence of other complications (eg, fetal malpresentation). A cesarean section can be considered in women <32 weeks gestation with an unfavorable cervix.
Follow-Up\:
Follow up any patient within 1 to 2 weeks after delivery to reassess for residual effects ofthe seizure and to reassess the blood pressure.
Pearls\:
• The recurrence risk of eclampsia in future pregnancies is only 2%.
• On the CCS, once the patient is stabilized, you can perform a targeted physical exam and obtain your labs (eg, CBC, CMP, PT/PTT).
• On the CCS, essential monitoring parameters include a fetal monitor for the fetus and urine output for the mother.
• On the CCS, treatment of severe hypertension should in­ clude a "one time/bolus” of either intravenous hydralazine or labetalol. After each bolus, be sure to reassess the blood pressure by ordering vital signs. If the blood pressure does not drop after the first attempt, you may need to give another bolus every 10 to 15 minutes until you to see a response.
• On the CCS, magnesium sulfate is given to prevent another convulsion. It is typically given as an intravenous continuous in­ fusion, therefore, select “continuous” for the mode of frequency.
• On the CCS, once you suspect an eclamptic episode, be sure to order an “Ob/gyn consult” for immediate delivery. This is an ap­ propriate case to order a consult. Remember that you’re order­ ing a consult from the point ofview ofa primary care physician.
• On the CCS, as with any acute cases, your timing is essential in simulated time.
HELLP Syndrome
HELLP syndrome can be characterized by Hemolysis, Elevated Liver enzymes, and Low Platelets. Some experts believe that the HELLP syndrome is a variant of severe preeclampsia, while other experts believe that it is a separate entity since a subset of patients will not have hypertension or proteinuria.
Clinical Features\:
HELLP syndrome is commonly seen in the third trimester, although it can occasionally occur in the second trimester or postpartum. Women may experience multiple end-organ signs or symptoms, and it may be helpful to consider them in a rela­ tive head to toe fashion\:
Neurologic—Visual disturbances, headaches Respiratory—Shortness of breath Cardiovascular—Hypertension Renal—Proteinuria
GI—Epigastric pain, RUQ pain, nausea, vomiting, jaundice Heme—Bleeding
Systemic—Malaise
Next Step\:
Step 1) Diagnosis is made on findings based on the name HELLP\:
Hemolysis\: t LDH, i haptoglobin, T indirect bilirubin, presence of schistocytes/helmet cells
Elevated Liver enzymes\: T AST, T ALT Low Platelets\: <100,000/mm3
Step 2) A patient with HELLP syndrome should be hospitalized for further management, which should include\:
Anticonvulsants—Intravenous magnesium sulfate to pre­ vent seizures.
Antihypertensives—Do not treat unless BP >160/100 (see Severe Preeclampsia).
Fetal lung maturity—Administer steroids if<34 weeks ges­ tation if maternal and fetal conditions are reassuring, but do not delay immediate delivery in cases of rapid deterioration.
Platelet transfusions—Transfuse platelets when <20,000/ mm3 or when platelets are <50,000/mm3 if cesarean section is scheduled.
Step 3) Prompt delivery is the definitive treatment for HELLP syndrome.
Follow-Up\:
Follow up any abnormal lab values that persist. Typically, lab val­ ues should normalize by approximately the sixth day postpartum.
CHAPTER 12 OBSTETRICS 179

180 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Pearls\:
• Complications of the HELLP syndrome include DIC, pla­ cental abruption, hepatic hematoma with rupture, hepatic infarction, ascites, renal failure, and pulmonary edema.
INTRAPARTUM
I STAGES OF LABOR
Stage 1\: Cervical Dilatation
Latent phase—Cervical dilatation from 0 to 4 cm. Nullipa-
rous—<20 hours, multiparous—<14 hours.
Active phase—Cervical dilatation from 4 to 10 cm. Nul- liparous—cervix dilating at least 1.2 cm/hr. Multiparous- Cervix dilating at least 1.5 cm/hr.
Pearls\:
• ConsiderthetripleP’sifthereisanarrestintheactivephase (ie, >2 hours).
Power—Uterine contraction problems Pelvis—Size or shape of the pelvis Passenger—Size or presentation of the infant
• Greater than 200 Montevideo units within 10 minutes is con­ sidered adequate contractions.
Stage 2\: Delivery of the Baby Epidural—
Nulliparous—3 hours. Multiparous—2 hours.
No epidural—
Nulliparous—2 hours. Multiparous—1 hour.
Table 12-10 • Intrapartum Surveillance Test Comments
On the CCS, to cancel an order, click on the item that you want to cancel in the order sheet, and another screen will automatically appear to confirm your cancellation.
Pearl\:
• During this stage, the baby is undergoing the cardinal movements\: Engagement —» descent — > flexion —» internal rotation —> extension — > external rotation —> expulsion
Stage 3\: Delivery of the Placenta
This stage can take up to 30 minutes.
Pearl\:
• Signs of placental separation include a gush of blood, uterus feels firm and globular, uterine fundal rebound, and umbili­ cal cord lengthening.
Stage 4\: Maternal Physiologic Adjustments
• Immediately postpartum lasting up to 2 hours after delivery of the placenta.
Pearl\:
• Risk of uterine atony during this stage (ie, excessive vaginal bleeding, enlarged boggy fundus) —> First step in manage­ ment is bimanual massage of the uterus ± IV oxytocin.
I INTRAPARTUMSURVEILLANCE
The principal goal of intrapartum surveillance is to assess the fetal well-being and to prevent an adverse fetal outcome. Intrapartum fetal surveillance (see Table 12-10) includes both electronic meth­ ods and nonelectronic methods (eg, fetal scalp blood sampling).
Fetal scalp blood pH
Fetal scalp stimulation Electronic monitoring
• Fetal blood pH can help clarify fetal acid-base status. • Interpretation\: Normal value— pH >7.25
• Preacidotic— pH 7.20-7.24
• Fetal acidosis—pH <7.19 on two collections 5-10 minutes apart —> Immediate delivery
• Fetal scalp stimulation should elicit an FHR acceleration of 15 bpm lasting for 15 seconds, which corresponds to a scalp pH of >7.20.
External monitoring\:
Fetal heart rate—An external transducer similar to an ultrasound, strapped onto the woman's abdomen. Uterine contractions—An external transducer (tocodynamometer) is strapped onto the abdomen.
Internal monitoring\:
Fetal heart rate—A fetal scalp electrode (FSE) is directly applied to the fetal scalp through the cervix once
the membranes have ruptured. FSE is more invasive compared to the external monitor, but it is more accurate in determining the beat-to-beat variability.
Uterine contraction—An intrauterine pressure catheter (IUPC) is inserted into the chorioamniotic sac once
the membranes have ruptured. Similar to FSE, IUPC is used when external monitoring provides poor tracings or artifact. IUPC can provide accurate readings of the strength, duration, and amplitude of the contractions.

I FETALHEARTRATEANDACTIVITY
The FHR pattern is an important index of cardiac activity that is regulated through an interplay of the sympathetic and parasym­ pathetic nervous system.
Fetal Heart Rate
Normal\: 110 to 160 bpm.
Tachycardia\: >160 bpm. Causes\: Maternal infection, maternal thyrotoxicosis, fetal anemia, medications (eg, atropine).
Bradycardia\: <110 bpm. Causes\: fetal congenital heart block, fetal anoxia, medications (eg, (3-blockers).
Sinusoidal heart rate\: A smooth undulating sinusoidal pattern that has been associated with fetal anemia. It should be noted that the sinusoidal pattern is not part of the definition of FHR variability since it is described as having a regular fluctuation (see Figure 12-1).
Baseline Variability
Baseline variability describes an irregular fluctuation along the baseline of two cycles per minute or greater. The baseline vari­ ability gives us insight to the fetal cardiovascular function. See Figure 12-1 for the different patterns of FHR variability.
Absent—Undetectable, a flat appearance (ominous sign) Minimal—Amplitude <5 bpm
Moderate (Normal)—Amplitude 6 to 25 bpm Marked—Amplitude >25 bpm
Acceleration
An abrupt increase in FHR above baseline. Adequate accelera­ tions occur if\:
<32 weeks—Accelerations >10 bpm above baseline for >10 seconds

32 weeks—Accelerations >15 bpm above baseline for >15 seconds
Deceleration
A deceleration is visualized as a dip or decrease in the FHR. Consider four types of decelerations (see Figure 12-2)\:
Early Deceleration
Pattern\: The decelerations onset, nadir, and termination are co­ incident with the onset, peak, and termination of the maternal uterine contraction. Also, the FHR has a gradual decrease with return to baseline.
Cause\: Fetal head compression
Late Deceleration
Pattern\: The deceleration is delayed and occurs after the termi­ nation of a contraction. Also, the FHR has a gradual decrease with return to baseline.
Cause\: Uteroplacental insufficiency (ominous sign).
Variable Deceleration
Pattern\: The deceleration may start before, during, or after a uterine contraction. Also, the FHR has an abrupt decrease with a rapid return.
Cause\: Umbilical cord compression
Prolonged Deceleration
Pattern\: A deceleration below the baseline of >15 bpm and last­ ing for at least 2 minutes but <10 minutes from onset to return to baseline.
Cause\: Uterine hyperactivity, maternal hypotension, cord en­ tanglement
Summary of Nonreassuring Fetal Heart Patterns
• • • • •
1
Bradycardia
Absent variability
Sinusoidal pattern
Recurrent late decelerations Recurrent variable decelerations
INDICATIONS FOR CESAREAN SECTION
CHAPTER 12 OBSTETRICS 181
The optimal mode of delivery is based on many factors to en­ sure the best possible maternal-fetal outcome. The decision to undergo a cesarean delivery is based on concerns of the mother, fetus, or a combination of the two (see Table 12-11).
I PRETERM PREMATURE RUPTURE OF MEMBRANES
Premature rupture of membranes (PROM) refers to rupture of fetal membranes prior to the onset of labor. When fetal membranes rupture prior to term (<37 weeks), it is referred to as preterm premature rupture of membranes (PPROM).
Risk Factors\:
Smoking, intrauterine infection, history of PPROM, antepar­ tum bleeding.
Clinical Features\:
Some patients will experience a sudden gush of vaginal fluid, while others may notice a gradual leak of fluid. The vaginal fluid can appear as a clear color to a meconium-stained appearance.
Next Step\:
Step 1) Avoid a digital cervical examination unless delivery is imminent because it can increase the risk of infection and de­ crease the time from rupture to delivery (ie, latency period).
Step 2) A sterile speculum exam should reveal pooling of the vaginal vault.
Step 3) Confirm the diagnosis with the Fern test, which should reveal a “ferning” pattern under a microscope. Also, the Nitrazine test is used to assess the pH ofthe fluid, which should reveal an alkaline pH of 7.0 to 7.3, or visually the nitrazine paper will turn blue.

182 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
-j—__——-wm--240-r—]-■'r
i
■
-h~ ””=F
- mrni-240-r— --
1 rlZ—H
- -I-
1
-—-eh H- - ___ z_ ___F
—_ -A-z _ _ —i—
Z i
I
-- ——— 4-—
——r* z_HHh-z ztz
1
1
i
—
—i—— —
i
-30-1—
__-210-j—_ ____Z__z
_z_
j-210-j— _ _ _ tz
_ _ _
1 ~~~j~
\
—r210
——— Lisoi- — —
—
— zj—— —~| '— — — b33!— ———f— t — —=1=
—— —
— 3]sEattj V-1 4- \is[Z/1ZAlt i c~zj3 7 31|UA
i
i
i
_ 1
__ — S^-
I
-1804;; b-180- —-3 ——b —— —
P 541
azn1T1 1J\_MlrqItf zjla1tzZLELii
i
i
i
r -150^ri
jn TIT□
5i 1
ztL £
r 3- n QL rr~11L2 i\:
~~z t___
1
h—
1 n zjrr~ ~Zi rvz
_ _12o4—_ __ __ K ____Z__ ——3—___ 2
■
to —l—~F — —
i
———_
j
i
——— _ —=H—— _—z—_———— z^ i i _ _
1 —————
_ — z — 4- -j-
—
i
TM" ■ —r
!
— —j
“■ —■ 333 3— -P
1
i
-90-1—
i
31 3j 31 ~T~-j
—\--- E-30-
tH 333- 3 33
1 minute
!
_|
....dz mH _z
333_
a3 E aa
33
i
i
i
—
m p-
| ll
-120-z _ _ _ _ _ _
1
_ _ _
_ __
! ——————
—
1
1
“—— ““
F#
_
_-
_
—
i
—
j-60-j—
_
—3 3St 3
FIGURE 12-1 • Fetal heart rate variability (panels 1-4), sinusoidal pattern (panel 5). 1. Absent variability. 2. Minimal variability, <5 bpm. 3. Moderate (normal) variability, 6-25 bpm. 4. Marked variability, >25 bpm. 5. Sinusoidal pattern is excluded from the definition of fetal heart rate variability. Note the smooth, sinelike pattern with regular fluctuation. (Reproduced with permission from Cunningham FG,etal. Williams Obstetrics. 23rd ed. New York\: McGraw-Hill; 2010\:418.)
l
1 1
_
— 1
1
11
1 THm9?tJ_ -1~
—— 71 -1 i ~7*/ift 11 H
— --
Leo-j— zj
zyz I
lDj
_ m _l_ r* _ _ -120-J-
_ -bjz =1=

C 26257
143 PAGES LEFT
26258
MEDS MEDS DO. on OIL
EFF STA ROM
i ftp
AJy*'
&F
STA 1, ROM pH An PH
P&E TEMP.
fu£e
142 PAGES LEFT
jr BIP L-=o—
FIGURE 12*2 • Decelerations. A. Early deceleration—Note that the nadir of the
FHR (top panel) and the peak of the uterine contractions (lower panel) occur at
about the same time (see arrows). B. Late deceleration—Note that the nadir of the deceleration (top panel) occurs after the peak of the uterine contractions (lower panel). C. Variable deceleration—Note the abrupt decrease in FHR (top panel) compared
to the gradual decrease in FHR in A and B.The onset, duration, and depth of the decelerations vary with successive uterine contractions, hence the term variable. (Reproduced with permission from Callahan TL, Caughey AB. Blueprints Obstetrics and Gynecology. 6th ed. Philadelphia, LWW; 2013\:46.)
CHAPTER 12
OBSTETRICS 183

184 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Table 12-11 - Indications for Cesarean Section
Maternal Fetal Maternal-Fetal
• Abdominal cerclage
• Active herpes simplex virus infection
• HIV infection
• Previous C-section
• Previous uterine surgery including
myomectomy
• Cervical cancer
• Eclampsia with unfavorable cervix
<32 weeks gestation
• Birth canal obstruction\:
• Condylomata
• Ovarian tumors • Fibroids
• Fetal distress
• Fetal acidemia
• Bradycardia
• Absent variability
• Fetal malpresentation • Breech
• Transverse lie • Fetal anomalies
• Hydrocephalus
• Macrosomia
• Osteogenesis imperfecta
• Twins
• Nonvertex first twin • Conjoined twins
• Failed induction of labor
• Cephalopelvic disproportion • Placenta abruption
• Placenta accreta
• Placenta previa
• Vasa previa
Step 4) Obtain cultures for chlamydia, gonorrhea, and Group B streptococcus.
Step 5) Laboratory testing\: CBC, urinalysis with urine culture.
Step 6) Obtain amniotic fluid from the vaginal vault to assess for fetal lung maturity.
Step 7) Ultrasound to assess for AFI, fetal presentation, gesta­ tional age, and potential cord prolapse.
Step 8) Consider three scenarios for the management of PPROM, and in all three cases, admit to the hospital.
Immediate Delivery
• Infection
• Fetal distress
• Placental abruption
• Cord prolapse
24 to 33 Weeks Gestation
Delivery—Expectant management, but okay to deliver at 33
weeks if fetal lungs are mature.
Fetal lungs—Administer steroids.
GBS ppx—Yes, if GBS positive or status unknown.
Prolong latency—Yes, with antibiotics\: IV ampicillin + IV eryth­ romycin x 2 days, then PO amoxicillin + PO erythromycin x 5 days.

34 Weeks Gestation
Delivery—Proceed to deliver.
Fetal lungs—No steroids.
GBS ppx—Yes, if GBS positive or status unknown. Prolong latency—No need.
Follow-Up\:
• Cord prolapse
Close follow-up is warranted in patients being treated for infec­ tion (eg, chorioamnionitis) since intrauterine infections can be the source of a neonatal sepsis.
Pearls\:
• Approximately 90% of term patients and 50% of preterm patients who experience fetal membrane rupture will enter labor within 24 hours.
• A false positive result can occur with the nitrazine test if blood, semen, or alkaline soap is present in the vaginal fluid.
• Another test that can confirm ruptured membranes is a placental alpha microglobulin-1 protein assay (Market name\: AmniSure). AmniSure is a rapid, noninvasive test that does not require a speculum exam, but does require inserting a sterile swab into the vagina to obtain a sample of the fluid. The results are not affected by the presence of blood, semen, or soap.
• An amniotic fluid index (AFI) <5 cm is considered oligohydram­ nios, which would be suggestive of fetal membrane rupture.
• The use of antibiotics can prolong the time from rupture to delivery and reduce the chance of infection.
• Tocolytics (eg, terbutaline) can be used for the first 48 hours when administering steroids if the patient is having a con­ traction. However, in the setting of chorioamnionitis, tocoly- sis should not be used.
• Complications of PPROM include infections, prematurity, cord prolapse, oligohydramnios, and pulmonary hypoplasia.
• On the CCS, both “Nitrazine test” and “Fern test” are avail­ able in the practice CCS.
• On the CCS, pay attention to the initial vital signs as fever and tachycardia will point you toward an infectious etiol­ ogy and help you take the appropriate and timely actions of administering antibiotics.

POSTPARTUM
I BREASTFEEDINGCONCERNS
R f .. . u Breastfeeding problems is not uncommon in the postpartum
period. It is important to recognize some of these problems to prevent early termination of breastfeeding and to maintain the associated health benefits for the infant (see Table 12-12).
Table 12-12 • Breastfeeding Concerns Concerns Comments
1 MENTALHEAI-THCONCERNS See Table 12-13.
IPOSTPARTUMFEVER
Postpartum febrile morbidity is defined as a temperature of 38.0°C (100.4°F) or higher, on at least two occasions ofthe first 10 days postpartum, exclusive ofthe first 24 hours (see Table 12-14).
Breast engorgement
Cracked nipples
Plugged ducts
Mastitis
Breast abscess
Candidal infections
Breastfeeding jaundice
Breast milk jaundice
Bilateral breast engorgement can occur in a woman who does not breastfeed or those with ineffective breastfeeding techniques. Engorgement can be seen 3-5 days after delivery. Pain and "milk fever"are
common. However, the fever usually resolves within 24 hours.
Next step—Frequent breastfeeding, cold ice packs, acetaminophen or ibuprofen for pain control (safe to use). Breast pumps can be used but should be avoided if possible since they are inefficient and can actually stimulate milk letdown.
Poor breastfeeding technique is a common cause for cracked nipples. In most cases, the infant is sucking only on the nipple and sucking harder to extract more milk.
Next step—Reevaluate latch-on technique, allow the baby to suck on both the nipple and areola thereby com­ pressing the milk ducts and stimulating milk letdown. Allow the baby to nurse on the less sore breast first before transitioning to the breast with the cracked nipple as the baby will usually suck less vigorously on the second breast. A nipple shield may be used on the affected breast to protect the nipple as it heals.
Plugged ducts can cause milk stasis in the ducts, which would appear as a tender lump from the outside. If ducts do not become unplugged, a galactocele or retention cyst can form. From the outside, the galactocele may appear as a fluctuant mass mimicking an abscess. A cheesy substance can be extruded from the nipple. However, there are no fevers or systemic symptoms with either a plugged duct or galactocele.
Next step—Reevaluate latch-on, frequent feedings, and possibly needle aspiration if the galactocele does not resolve on its own.
Patients will experience a red, tender, hard breast with fever.
Next step—Antibiotics with dicloxacillin or cephalexin, acetaminophen or ibuprofen for pain control, and con­ tinue breastfeeding during medical therapy.
Patients will experience a tender, fluctuant mass, with fever.
Next step—Drainage, antibiotics (dicloxacillin or cephalexin pending culture results), analgesics, continue breast­ feeding during treatment.
Infants with thrush may be an indication that the mother has a candidal infection on her nipples.
Next step—Apply topical nystatin on the affected breast, then wash off the medication prior to breastfeeding. Oral fluconazole may be given to the mother if the condition is persistent despite topical nystatin.
Jaundice that occurs from inadequate milk intake that may result in dehydration, hypovolemia, slower elimination of bilirubin, and T enterohepatic circulation with elevated bilirubin levels. Symptoms occur within the first 2-3 days of life or at least by the first week of life. Remember that jaundice within the first 24 hours of life is always pathologic and other causes such as sepsis, hemolysis, or hemorrhage should be considered.
Next step—Reevaluate breastfeeding technique, increase breastfeeding frequency, or briefly provide formula sup­ plementation.
Jaundice that occurs beyond the physiologic jaundice period. Physiologic jaundice is due to T RBC cell mass, shortened RBC life span, i bilirubin clearance, and T enterohepatic circulation. In term infants, indirect bilirubin increases by the
3rd or 4th day of life to levels >5 mg/dL and then resolves within 1-2 weeks after birth. In contrast, preterm infants' bilirubin levels are greater and prolonged. Breast milk jaundice persists beyond the normal physiologic period in either term or preterm infants. However, it is still unknown what is in the breast milk that causes breast milkjaundice. A brief discontinuation of breastfeeding results in a decline in bilirubin levels.
Next step—Formula supplementation may be provided during the interim. Discontinuation of breastfeeding is not recommended unless bilirubin levels are >20 mg/dL, in which case phototherapy or possibly exchange transfusion may be indicated.
Pearl\: An easy way to differentiate breastfeeding jaundice from breast milk jaundice is that breastfeeding jaundice has something to do with the breastfeeding (ie, not feeding enough) while breast milk jaundice has something to do with the breast milk (ie, an unknown inhibitor or substance).
CHAPTER 12
OBSTETRICS 185
(Continued)

186 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Table 12-12 • Breastfeeding Concerns (Continued) Concerns Comments
Bloody nipple discharge
Lactational amenorrhea method Overactive letdown
Green frothy stools
Contraindications to breastfeeding
Acceptable conditions to breastfeeding
Weaning
A bloody nipple discharge can be seen a few days postpartum and it is related to the vascularization effects of the ducts. The condition should resolve within days, but if not, consider a cracked nipple with bleeding or an intra­ ductal papilloma, in which case, send the milk for cytology.
Lactational amenorrhea method is a form of contraception that is highly effective if the mother is exclusively breastfeeding, amenorrheic, and less than 6 months postpartum. Mean time ovulation in breastfeeding
mothers is 190 days, and 45 days for non-breastfeeding mothers.
Forceful milk ejection can occur from overactive letdown resulting in the infant gagging. In some cases, the infant will be very upset and go on a nursing strike.
Next step—Upon letdown, catch the milk on a piece of cloth, and then put the infant back onto the breast as the flow will lessen. The goal is to reduce or control the flow of milk.
Infants who produce green frothy stools can be seen with mothers who produce large amounts of milk and have
a habit of switching from one breast to the other without full completion of one breast before moving on to the next. The residual milk or the milk that's left behind has a higher fat content that retards gut motility allowing for normal digestion at the small intestine level. Without the higher fat content, lactose will be digested at the level of the large bowel where green frothy stools are produced.
Next step—Full completion of one breast before moving on to the next breast.
• Mother has alcohol or street drug abuse.
• Mother has HIV infection in the United States, although in developing countries the benefits may outweigh the risk. • Mother has T-cell lymphotropic virus infection (HTLV-1 or 2).
• Mother has active and untreated tuberculosis.
• Mother has active herpes lesions on the breast.
• Mother is on antiretroviral medications.
• Mother is on chemotherapy or antimetabolite agents.
• Mother is undergoing radioactive therapy.
• Infant has galactosemia.
• Mother has silicone breast implants.
• Mother smokes cigarettes.
• Mother had postpartum varicella vaccination.
• Mother had postpartum MMR vaccination.
• Mother contracted toxoplasmosis during pregnancy.
• Mother contracted CMV infection during pregnancy.
• Mother contracted measles (rubeola) during pregnancy.
• Mother has hepatitis C infection.
• Mother has hepatitis B infection—Provide the passive immunization with the hepatitis B immune globulin (HBIG) and first dose of the active immunization with the hepatitis B vaccine to the newborn. The second and third doses of the vaccine should be given at the appropriate times, but there is no need to delay breastfeeding until the baby is fully immunized.
Exclusive breastfeeding can occur until 6 months of age. After that time, breast milk won't meet the energy or nutritional demands of the growing infant. In addition, the baby's iron stores are good for 4-6 months after deliv­ ery. Iron-fortified supplementation and solids can be introduced at that time. Remember not to give whole cow's milk prior to 12 months of age, as it is low in iron content and can cause intestinal irritation leading to microscopic bleeding, which can lead to iron-deficiency anemia.
I PUBIC DIASTASIS
Pubic diastasis is the separation of the pubic bones. In nonpregnant women, the normal pubic symphysis gap is between 4 and 5 mm. During pregnancy, the connecting pel­ vic ligaments loosen and can cause the gap to increase up to
10 mm.
Clinical Features\:
Symptoms of pubic diastasis may include any of the following\:
• Suprapubic pain at rest or with palpation
• Waddling gait
• Swelling around the suprapubic area
• Pain exacerbated with weight-bearing
• Radiating pain into the legs or back
• Palpable displacement
Next Step\:
Step 1) Pubic diastasis is a clinical diagnosis. Obtaining pelvic x-ray or other imaging is unnecessary. However, a pubic sym­ physis gap >10 mm seen on x-ray, confirms the diagnosis.
Step 2) Treatment is conservative and includes bed rest in the lateral decubitus position and pelvic support with an appropri­ ately fitted pelvic binder.

Table 12-13 • Mental Health Concerns Postpartum Depression
Postpartum Blues
Within 3-5 days after delivery
Days to weeks, but usually within 2 weeks postpartum
No
• Less debilitating than post­ partum depression.
• Mood swings, sadness, crying spells, anxiety, mild depressed mood, sometimes sleep disturbance, no suicidal thoughts.
No
Supportive care, the condition is self-limiting.
Postpartum Psychosis
Within several days to weeks after delivery and almost always within 8 weeks
Variable Yes
• Mood swings, depressed mood, elated mood, delusions, hallucinations, suspiciousness, irrational statements, insomnia, suicidal thoughts, negative feelings toward infant.
• High rate of recurrence with subse­ quent pregnancies.
Yes
• This is considered a psychiatric emergency.
• Antidepressants, antipsychotics, mood stabilizers (eg, lithium).
• Discontinue breast-feeding.
• Possible psychiatric unit transfer. • Consider ECTfor rapid effective
treatment.
Onset Duration
History of mood disorder
Clinical features
Thoughts of harming infant?
Next step management
Within 3-6 months after delivery
Months to years if untreated
Yes
• Indistinguishable from major depression.
• Anxiety, depressed mood, inadequacy, insomnia, anhe- donia, appetite disturbance, suicidal thoughts, ambiva­ lent feelings toward infant, decreased bonding with infant.
• High risk for future episodes. Yes
• Psychosocial therapy in mild to moderate cases.
• Antidepressants + psychoso­ cial therapy in moderate to severe cases.
• Consider electroconvulsive therapy (ECT) for rapid treatment when mother has active suicidal ideation.
------------------------------------------------------------------------------------------------------------------------------------------------------------ ! Table 12-14 • Postpartum Fever
Postpartum Day 0-1
1-2 2-3
4-5 5-6 7-21 Anytime
7Ws
Wind—Atelectasis, pneumonia
Water—UTI Womb—Endometritis
Wound—Episiotomy infection, wound site infection
Walk—DVT, PE, septic pelvic thrombophlebitis
Weaning—Breast engorge­ ment, breast abscess, mastitis
Wonder drugs—Drug fever
Comments
Atelectasis and aspiration pneumonia are more common when general anesthesia is used. Encourage incentive spirometry and coughing.
Frequent bladder catheterizations secondary to epidural anesthesia or C-section deliveries can introduce bacteria into the lower urinary tract.
Endometritis is a common cause of postpartum fever secondary to prolonged labor, prolonged rupture of membranes, C-section, or manual placental removal. Diagnosis is mainly clinical and should be suspected when the mother has fever, foul lochia, uterine tenderness, and tachycardia. Endometrial cultures are not helpful. Leukocytosis may be seen but may be skewed by normal physiologic leukocytosis from pregnancy. Treatment is with IV clindamycin and gentamicin. If no response by 72 hours, add IV ampicillin and consider further workup with imaging (eg, pelvic ultrasound, CT abdomen, or chest x-ray).
Consider in patients with a C-section. Look for signs of wound erythema or drainage.
Consider in patients with calf or thigh pain, dyspnea, cough, pleuritic pain, or pelvic tenderness.
Fever in breast engorgement is usually self-limiting, especially if the mother is breast-feeding. Breast abscess and mastitis may require antibiotics and drainage.
Common offending agents include aminoglycosides, anesthetics, anticholinergics, carbamazepine, cephalosporins, corticosteroids, heparin, macrolides, neuroleptics, penicillins, and vancomycin.
CHAPTER 12 OBSTETRICS 187

188 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Step 3) Surgery is sometimes performed with symphyseal sepa­ rations >4 cm (ie, 40 mm).
Follow-Up\:
Patients should been seen within 1 month postpartum as the pain typically subsides.
CCS\: ECTOPIC PREGNANCY CASE INTRODUCTION
Day 1 @ 10\:00 Office
A 25-year-old African American woman presents to the office because ofvaginal bleeding and abdominal pain. She also men- tions that she missed her last two menstrual periods.
Initial Vital Signs\:
Temperature\: 37.0°C (98.6°F)
Pulse\: 70 beats/min, regular rhythm Respiratory\: 15/min
Blood pressure\: 120/70 mm Hg Height\: 160 cm (62.9 inches) Weight\: 59 kg (130 lb)
BMI\: 23.0 kg/m2
Initial History\:
Reason(s) for visit\: Vaginal bleeding, abdominal pain, missed periods.
HPI\:
A 25-year-old G,P2002 sales associate has been having scant vagi­ nal bleeding for the past 2 days. She describes the vaginal bleeding as a dark brownish-red color that occurs intermittently through­ out the day. She also has lower abdominal pain for the past 4 weeks, which she describes as “on and off?’ The abdominal pain is described as a dull aching pain without radiation. When she experiences the pain she rates it 5/10 in severity with relief with acetaminophen. The patient states that her last menstrual period was 8 weeks ago with her previous menstrual cycles as “regular.”
Pearls\:
• It is thought that the hormones progesterone and relaxin loosen tlie pelvic ligaments during pregnancy along with the fetal head exerting pressure on the pelvic ligaments contribute to the sepa­ ration of the pubic symphysis during vaginal delivery.
• Pubic diastasis can recur with subsequent pregnancies.
Past Medical History\: Past Surgical History\:
Medications\: Allergies\:
History of PID
Vaginal deliveries without complication at ages 21 and 24.
None None
Vaccinations\: Family History\:
Social History\:
Review of Systems\:
General\:
HEENT\: Musculoskeletal\: Cardiorespiratory\: Gastrointestinal\: Genitourinary\: Neuropsychiatric\:
Day 1 @ 10\:10
Physical Examination\: General appearance\:
HEENT/Neck\:
Chest/Lungs\:
Heart/Cardiovascular\:
Up to date
Father, age 55, has hypertension. Mother, age 53, is healthy. No siblings.
Smokes 1 ppd x 7 years; drinks
1 to 2 glasses ofwine on the weekends; married; two children; sales associate; high school graduate; enjoys watching movies and reading.
See HPI Negative Negative Negative See HPI See HPI Negative
Well nourished, well developed, appears to be in mild discomfort. Normocephalic. EOMI, PERRLA. Hearing normal. Ears, nose, mouth normal. Pharynx normal. Neck supple; trachea midline; no masses or bruits; thyroid normal. Chest wall normal. Diaphragm moving equally and symmetrically with respiration. Auscultation and percussion normal.
SI, S2 normal. No murmurs, rubs, gallops, or extra sounds. No JVD.

Abdomen\:
Genitalia\:
Rectal\:
First Order Sheet\:
1) HCG, beta, urine,
qualitative, stat
Second Order Sheet\: I) Transvaginal pelvic
ultrasound, stat
Third Order Sheet\:
1) HCG, beta, serum,
quantitative, stat
2) CBC with differential, stat
3) Blood type and screen, stat
4) CMP, stat
5) Gonococcal culture, cervix, routine
6) Chlamydia culture, cervix, routine
Actions\:
1) Change location to home
2) Schedule appointment\: In 2 days
Day 3
The patient has arrived for the appointment.
Recorded Vital Signs\: Temperature\: 37.0°C (98.6°F)
Pulse\: 70 beats/min, regular rhythm Respiratory\: 15/min
Blood pressure\: 120/70 mm Hg
2) Schedule appointment\: In 4 days
This case will end in the next few minutes of “real time.” You may add or delete orders at this time,
then enter a diagnosis on the following screen.
Normal bowel sounds; no. bruit. Right lower quadrant tenderness. No masses. No hernias. Nohepa- tosplenomegaly.
Labia normal. Scant dark brown­ ish-red blood coming out from the cervical os. Cervix closed. Cervical motion tenderness. Mild uterine enlargement. No adnexal tenderness or mass appreciated. Sphincter tone normal. No mass or lesions. No occult blood.
Result\: Positive
Result\: Real time ultrasound shows no
abnormal mass. Normal uterus, fallopian tubes, and ovaries.
Result\: 1200 mlU/ mL (nl\: 0-3)
Result\: WBC-8,000, H/H-12/40%, Plt-250,000, Differential-normal
Result\: Blood type O, Rh(D) negative, no antibodies detected
Result\: Ca-9.2, Glu-110, Urea-14, Cr-1, Prot-7, Alb-4, TBil-0.8, AlkP-60, AST-25, ALT-30, Na-140, K-4, Cl-102, HC03-25
Result\: No Neisseria gonorrhoeae recovered
Result\: No Chlamydia trachomatis isolated
Physical Examination\: Chest/Lung\:
Heart/Cardiovascular\: Abdominal\:
Genitalia\:
Fourth Order Sheet\: 1) HCG, beta, serum,
quantitative, stat
2) Transvaginal pelvic trasound, stat
Fifth Order Sheet\:
1) Methotrexate, IM, one time
2) RhoGAM, IM, one time
Actions\:
1) Change location to home
Chest wall normal. Diaphragm moving equally and symmetrically with respiration. Auscul­ tation and percussion normaL
SI, S2 normal. No murmurs, rubs, gallops, or extra sounds. No JVD.
Normal bowel sounds; no bruit. Right lower quadrant tenderness. No masses. No hernias. No hepatosplenomegaly.
Labia normal. Scant
dark brownish-red blood coming from cervical os. Cervix closed. Cervical motion tenderness. Mild uterine enlargement. No adnexal tenderness or mass appreciated.
Result\: 1800 mlU /mL (nl\: 0-3)
Result\: Normal uterus
and ovaries. Fallopian tube is normal on left. Right side demonstrates a tubal ring with a yolk sac but no cardiac activity. Tubal size is 2.0 cm on the right.
Sixth Order Sheet\:
1) HCG, beta, serum,
quantitative, routine Future date\: In 4 days
Result\: 1440 mlU/
mL (nl\: 0-3)
Note\: (3-HCG level has decreased more than 15%
CHAPTER 12 OBSTETRICS 189

190 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
2) Advise patient, no smoking
3) Advise patient, no intercourse
4) Advise patient, no aspirin
5) Advise patient, side effects of medication
Please enter your diagnosis\:
Ectopic pregnancy
DISCUSSION\:
Approximately 95% of ectopic pregnancies implant within the various parts of the fallopian tube. The remaining 5% can implant in the ovary, cervix, peritoneal cavity, and at cesarean scar locations.
Risk Factors\:
Previous ectopic pregnancy, tubal/pelvic surgery, IUD, PID, in utero DES exposure, infertility, multiple sex partners, and smoking. In this particular case, the patient had a history of PID and currently smokes.
Clinical Features\:
The classic presentation is abdominal pain, amenorrhea, and vaginal bleeding. Other features that may be present include cervical motion tenderness, adnexal tenderness, peritoneal signs, uterine enlargement, and early pregnancy symptoms (eg, breast fullness, nausea). Patients can also present with referred shoulder pain from diaphragmatic irritation secondary to blood leakage from a fallopian tube. Remember, a ruptured ectopic pregnancy will usually present with a clinically unstable person.
Next Step Summary\:
Step 1) Look at the vital signs because if the patient is he- modynamically unstable, you need start ordering IV access, continuous cardiac monitoring, continuous blood pressure cuff, pulse oximetry, type and crossmatch, CBC with differential, CMP, PTT, PT/INR, and an ob-gyn consult for presumed rup­ tured ectopic pregnancy. The ob-gyn will determine whether to do a laparotomy or a laparoscopic approach in addition to re­ moving the entire fallopian tube (ie, salpingectomy) or creating a new opening (ie, salpingostomy).
Step 2) In this particular case, ectopic pregnancy may not be clearly apparent in the HPI. The best initial test is to rule out a pregnancy with a qualitative P-HCG. At this point, if you’re still unsure of the diagnosis, keep the differentials broad\: appen­ dicitis, ovarian torsion, ovarian cyst, PID, UTI, fibroids, endo­ metriosis, molar pregnancy, spontaneous abortion, and kidney stones.
Step 3) A positive p-HCG test should prompt you to look for an intrauterine pregnancy with a transvaginal ultrasound.
Step 4) If an intrauterine pregnancy cannot be visualized with an ultrasound, as in this case, a quantitative p-HCG is
ordered to see if it exceeds the discriminatory level. The dis­ criminatory level is the p-HCG level, at which a gestational sac should be visualized by an ultrasound by approximately 5 weeks gestation. If you’re using a transvaginal ultrasound, the discriminatory level is >1500 mlU/mL, but if you’re using a transabdominal ultrasound, the discriminatory level is >6500 mlU/mL. In this particular case, the initial p-HCG level was 1200 mlU/mL using a transvaginal ultrasound, which is be­ low the discriminatory level and may indicate an ectopic preg­ nancy or an early intrauterine pregnancy. If the P-HCG level is above the discriminatory level without a pregnancy seen on ultrasound, then you still consider an ectopic pregnancy or multifetal gestation.
Step 5) When the discriminatory level is below 1500 mlU/mL and no pregnancy is seen on ultrasound, then repeat both ultra­ sound and quantitative p-HCG in 48 hours (2 days). A viable intrauterine pregnancy should have a p-HCG level doubling ev­ ery 2 days until 6 to 7 weeks gestation. In our case, the patient was sent home and came back in 2 days with a repeat p-HCG of 1800 mlU/mL. We would expect a P-HCG level of 2400 mlU/ mL from the initial 1200 mlU/mL in a viable intrauterine preg­ nancy. Since our case shows a suboptimal rise or possibly an HCG plateau, an ectopic pregnancy is most likely. In addition, a repeat transvaginal ultrasound in this case showed a right-sided tubal pregnancy. Keep in mind that an ultrasound is operator dependent and you may not always pick up an abnormality on the first evaluation as in this case.
Step 6) In a hemodynamically stable patient, the patient can undergo medical, surgical, or expectant management.
Medical—The patient can be treated with methotrexate with the following indications\:
• Ectopic size <3.5 cm
• No fetal cardiac activity
• P-HCG level <5000 mlU/mL
• Absence of blood, kidney, and liver dysfunction. • Patient is not breastfeeding.
Surgical—Patients can also be treated surgically if they have contraindications to methotrexate, failed medical therapy, or had a previous ectopic in the same fallopian tube. Remember to order an ob-gyn consult on the CCS with a reason for the consultation in 10 words or less.
Expectant—In select cases, patients can be offered expect­ ant management if they are asymptomatic, unruptured ectopic pregnancy, and a P-HCG level <200 mlU/mL that is declining.
Follow-Up\:
Patients being treated with methotrexate should have a decrease in their p-HCG level between days 4 and 7. If P-HCG levels fall more than 15%, no further treatment is required and the patient can be followed weekly until P-HCG levels are undetectable. If the P-HCG level does not fall more than 15%, the patient may require an additional dose of methotrexate.

Pearls\:
• In this particular CCS case, if the repeat P-HCG is doubling, an intrauterine pregnancy is still possible. The patient should be followed up with a transvaginal ultrasound to locate the pregnancy.
• Unsensitized Rh(D) negative patients should receive Rho- GAM.
• Be able to understand the concept of type and screen. The typing refers to the recipient’s ABO and Rh status while screening for antibodies in the recipient’s plasma that may react to the donor’s blood. If the screen is positive for anti­ bodies then further investigation with an antibody panel of the recipient’s plasma may be warranted or the blood bank may proceed to identify compatible blood units. If the screen is negative for antibodies in the recipient’s plasma, then the ABO and Rh status of the donor’s blood is determined.
• The standard technique in the antibody screen is with the indirect Coombs test.
• Be able to understand the concept of type and crossmatch. Once the ABO and Rh type is determined in the recipient and donor, then a crossmatch is performed to detect ABO incompatibility as well as other significant antibodies by in­ cubating the recipient’s plasma with the donor’s RBCs. Es­ sentially, the crossmatch ensures optimal safety compared to the screen.
• In the event of a surgical procedure that is unlikely to require blood —> order a type and screen.
• In the event of a surgical procedure that is highly likely to require blood —> order a type and crossmatch.
• In the event that the patient is exsanguinating and there is an urgent need to transfuse blood but the patients ABO and Rh status is unknown and there is no time to complete compat­ ibility testing —» administer type O, Rh-negative blood.
Obtaining serum progesterone levels is considered ancillary testing. However, a serum progesterone level >25 ng/mL most likely excludes ectopic pregnancy but a value <5 ng/mL suggests an ectopic pregnancy.
On the CCS, “Type and screen,” “Type and crossmatch” and “Type and Rh factor” are available in the practice CCS.
On the CCS, “advise patient, no smoking” since it is a risk factor for ectopic pregnancy.
On the CCS, “advise patient, no intercourse” until after p-HCG levels are undetectable while on methotrexate therapy.
On the CCS, “advise patient, no NSAIDs” while on metho­ trexate because it can potentially increase the serum concen­ trations of methotrexate.
On the CCS, “advise patient, side effects ofmedication” since methotrexate can cause nausea, vomiting, stomatitis, and pharyngitis.
On the CCS, remember when you relocate patients from office to home or office to ED, the patients should always be stable or stabilized, respectively.
On the CCS, the quantitative p-HCG measurements was managed as an outpatient basis in this particular case be­ cause the patient appeared stable and was judged to have low risk for an ectopic rupture. If you feel the patient is clinically unstable such as hypotension, tachycardia, fever, or apparent tubal mass >3.5 cm then admit and manage the patient in the hospital.
On the CCS, always be aware of the “Report Time” when you order labs. If a report time for a lab result is 6 hours, you do not want your patient to be in your office for that long. In emergent cases, you will generally want to order your labs stat, but in routine office-based cases it is acceptable to send your patients home and then have them come back for a scheduled appointment.
CHAPTER 12 OBSTETRICS 191

Ophthalmology
CHAPTER OUTLINE
Keywords Review............................................1.9.3........ I GLAUCOMA...............................................1.9..7......... I CORNEA.................................................1.9..4......... Open-angleGlaucoma........................................1.9.7.......
I I
Angle-closure Glaucoma......................................1.9.9.......
Corneal Abrasion...........................................1.9.4.........
I NEURO-OPHTHALMOLOGY. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2.0.0. . . .
LENS....................................................1..9.5.......... Amblyopia...................................................2.0.0...........
Cataract....................................................1.9.5..........
I INFLAMMATORY CONDITIONS...........................2.0..0...
RETINA..................................................1.9.5.......... Chalazion....................................................2.0.0.......... RetinalDetachment........................................1.9.5........ Hordeolum...................................................2.0.1..........
Macular Degeneration......................................1..9.6......
Conjunctivitis................................................2.0.1..........
good depth perception (stereopsis) since you are viewing the image with binocular vision.
Keratitis—Inflammation of the cornea.
Metamorphopsia—Visual distortion of shapes or images.
Miosis—Pupil contraction.
Mydriasis—Pupil dilatation.
Myopia—Nearsightedness
Optotype—Letters (Snellen) or figures (Allen) used in testing visual acuity.
Palpebral or tarsal conjunctiva—Membrane lining the inner eyelid.
Photopsia—Flashes or sparks seen due to retinal irritation. 193
KEYWORDS REVIEW
Blepharitis—Inflammation of the eyelids.
Bulbar conjunctiva—Membrane lining the sclera of the eye.
Direct ophthalmoscope—Commonly used during a routine physical exam; provides an upright image.
Drusen—Extracellular material that develops beneath the retinal pigment epithelium and can appear as yellow deposits on ophthalmoscopy.
Hyperopia—Farsightedness.
Indirect ophthalmoscope—Provides a larger view of the fundus compared to direct ophthalmoscope. The components include a light attached to a headband plus a handheld lens to view the fundus.The image is inverted, but it allows for

194 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
CORNEA
1 CORNEAL ABRASION
Corneal abrasions occur when the integrity of the corneal epi­ thelium has been disrupted. Abrasions may result from trauma, foreign body, contact lens, or spontaneous defects.
Clinical Features\:
Corneal abrasions can cause eye pain, tearing, blurring vision, photophobia, or an inability to open the eye. The type of injury can help delineate the etiology. Consider the following\:
Trauma—Patients may have an abrasion from a finger­ nail, animal paw, paper, leaves, makeup applicator, or hand tool.
Foreign body—A foreign body sensation may be felt when material such as glass, plastic, rust, or vegetable material is embedded in the cornea.
Contact lens—Patients may a history of using contact lens. On eye exam, patients may have corneal white spots that reflect an ulcer or infiltrates.
Spontaneous defects—Patients typically do not have an immediate disruption of the cornea, but rather a history of a corneal abrasion that healed (also known as recurrent corneal erosion syndrome). Eye pain is usually felt in the middle of the night or upon awakening in the morning when they try to open their eyes.
Next Step\:
Step 1) Perform an eye examination. Most patients with a cor­ neal abrasion will have a reactive miosis of the affected eye. If a patient has severe eye pain, a topical anesthetic (eg, propara- caine) may be given to facilitate visual acuity testing and the rest of the eye exam. Relief of the eye pain from the anesthetic is indicative of a corneal abrasion.
Step 2) Instill a drop offluorescein into the eye and then visualize the eye with a cobalt blue filter or Wood’s lamp. Any corneal defects will appear yellow-green. If a slit lamp with a cobalt blue light is available, look for leaking of the aqueous humor (Seidel sign), which is indicative of a penetrating ocular trauma.
Step 3) The treatment of corneal abrasions is based on the type of injury. Consider the following\:
Trauma—Topical antibiotics (eg, erythromycin ointment or drops of ofloxacin, ciprofloxacin, polymyxin/trimeth­ oprim, or sulfacetamide) may be given. Pain relief with topical cycloplegics (eg, cyclopentolate or homatropine) can also be given. Cycloplegics work by relaxing the ciliary body (ie, inhibit pupil constriction to light).
Foreign body—An attempt should be made to remove the foreign body with irrigation. If the foreign body cannot be removed, the patient should have a referral to an ophthal­ mologist. In the meantime, patients may be given topical
antibiotics and cycloplegics (same as trauma) until they see the ophthalmologist.
Contact lens—Patients who wear contact lens are suscep­ tible to infectious keratitis. If corneal white spots are seen on examination, the patient should have an urgent refer­ ral to an ophthalmologist. If there are no corneal white spots, but there are corneal defects via fluorescein stain, the next best step is to give topical antibiotics that are effective against Pseudomonas (eg, tobramycin, ofloxacin, or ciprofloxacin).
Spontaneous defects—The goal of recurrent corneal ero­ sion syndrome is to restore the corneal epithelium. Small erosions may spontaneously heal on their own. For persis­ tent cases, the management may include lubricant therapy (given at night), antibiotics, and cycloplegics. Further man­ agement with an ophthalmologist may include debride­ ment, wearing soft contact lenses that act as a "bandage,” or anterior stromal micropuncture.
Follow-Up\:
Most corneal abrasions heal on their own. Minor abrasions usually heal within 48 hours and do not require a follow-up if asymptomatic. For patients with larger abrasions, contact lens abrasion, or persistent symptoms (eg, recurrent cor­ neal erosion syndrome) may require a follow-up within 48 to 72 hours.
Pearls\:
• Avoid treating patients with a topical anesthetic since it can potentially delay corneal healing.
• Avoid treating patients with topical atropine or scopol­ amine (ie, cycloplegic effects) since these agents can last for weeks.
• Do not treat corneal abrasions with topical steroids.
• Patching was a major treatment modality in the past for corneal abrasions. Studies are now showing the lack of benefit from patching and possibly harm (eg, infectious keratitis secondary to a nice and warm environment under the patch).
• Definitely do not patch an eye in a patient who wears contact lenses or is at high risk of infection (eg, vegetable matter, fin­ gernails) because of the risk of infectious keratitis.
• Foundational point—The cornea is a very sensitive tissue that is richly innervated by the sensory nerve fibers of the ophthalmic division of the trigeminal nerve (CN Vj), so you can imagine the pain the patient feels with injury to the cornea.
• On the CCS, “corneal foreign body removal” is available in the practice CCS.
• On the CCS, poor management would include the failure to prescribe the appropriate antibiotics in patients with corneal abrasions secondary to contact lenses since infec­ tious pseudomonas keratitis can result in vision loss.

LENS
I CATARACT
A cataract is an opacity of the lens of the eye that is a common cause of visual impairment in children and is a leading cause of blindness in the world. Children and adults have different conditions and risk factors in the development of a cataract.
Children—Turnersyndrome,Downsyndrome(trisomy21), Patau syndrome (trisomy 13), Edwards syndrome (trisomy 18), Alport syndrome, neurofibromatosis type 2, TORCH infections, galactosemia, type 1 diabetes, glucocorticoid use, ionizing radiation, trauma
Adults—Age, smoking, alcohol use, diabetes mellitus, glu­ cocorticoid use, UV light, trauma
Clinical Features\:
Cataracts can present as a painless, gradual loss of vision-. Common complaints include an increased glare and near­ sightedness (“myopic shift”). In a preverbal child, there may be delays in the developmental milestones. On direct ophthal­ moscope, the red reflex is usually diminished in the dilated or undilated eye. Patients may also have problems with visual acuity in the affected eye, which can be assessed by optotype (Snellen) testing.
Next Step\:
Step 1) An ophthalmologic examination usually makes the diagnosis. Further testing with a slit lamp examination may be indicated to rule out other pathology. The slit lamp exam can
RETINA
1 RETINAL DETACHMENT
Retinal detachment is the separation of the neurosensory retina from the underlying retinal pigment epithelium (RPE) and choroid. The most common type of retinal detachment is the rhegmatogenous type (rhegma means “break” in Greek). In the rhegmatogenous retinal detachment, a retinal tear gives a por­ tal entry for vitreous fluid to enter and separate the retina from the RPE. Other mechanisms of detachment include exudative (serous) retinal detachment (accumulation of subretinal fluid causing detachment but without a retinal break) and tractional retinal detachment (pulling of the retina from the RPE without a retinal break).
Clinical Features\:
Patients will often complain of floaters that may be described as “cobwebs.” The sudden onset of floaters suggests a posterior vitreous detachment (PVD) with a retinal tear. Patients will also
assess other ocular structures in the anterior segment ofthe eye (eg, conjunctiva, iris, cornea, anterior chamber, lens).
Step 2) Treatment involves cataract extraction with surgery and replacement with an intraocular lens (IOL) in adults and older children. Aphakic contact lenses may be given to children <9 months of age.
Follow-Up\:
As a primary care physician, it is important to do a good eye exam (ie, find the red reflex) since a delay in the diagnosis of a cataract can lead to amblyopia in children and possibly irre­ versible vision loss.
Pearls\:
• Adults may continue their aspirin or warfarin if cataract ex­ traction is planned.
• If a white pupillary reflex (leukocoria) is seen in a child, the next best step is to promptly refer to an ophthalmologist to exclude the diagnosis of a retinoblastoma.
• Retinoblastoma is the most common ocular malignancy that results from a mutation in the retinoblastoma (RBI) gene mapped to chromosome 13ql4. Other dues to a retinoblastoma indude a family history, strabismus, and ocular inflammation.
• Leukocoria can be seen in a whole host of other conditions such as retinal detachment, cataracts, ocular trauma, Coats disease, and endophthalmitis.
• Galactosemia may present with cataracts, jaundice, hepato­ megaly, failure to thrive, lethargy, and bruising.
• On the CCS, “slit lamp examination” is available in the prac­ tice CCS.
frequently complain of photopsia that is usually of short dura­ tion. The photopsia is often due to the tugging of the vitreous onto the corresponding retina (mechanical stimulation) which results in depolarization of the retina. If the patient complains of seeing many black dots, it is indicative of a vitreous hemor­ rhage. If the retinal detachment involves the macula or fovea centralis, visual acuity will be affected.
Next Step\:
Step 1) Retinal detachment is considered an ophthalmologic emergency, and patients should be seen by an ophthalmologist as soon as possible (<24 hours). An ophthalmologist will usu­ ally perform a dilated indirect ophthalmoscopic evaluation to assess the fundus of the eye. The fundal exam will typically reveal tentlike elevations of the retina (see Figure 13-1 and Color Plate 11). An ophthalmologist will also perform a slit- lamp biomicroscopy to assess the anterior segment of the eye. If retinal pigment epithelial cells (“tobacco dust”) are seen behind the lens, it suggests that these cells have broken from the RPE layer and are floating in the vitreous.
CHAPTER 13 OPHTHALMOLOGY 195

196 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
FIGURE 13-1 • Retinal detachment. Depicted is a superior retinal detachment with billowing or elevation of the retina with folds that can produce an inferior scotoma. Also, note that the fovea was spared, which led to normal visual acuity in this patient. (Reproduced with permission from Hauser SL, Josephson SA, et al. Harrison's Neurology in Clinical Medicine. 2nd ed. New York\: McGraw-Hill; 2010\:183.)
Step 2) Retinal detachments are treated by reattaching the retina through various techniques (eg, scleral buckling, pneu­ matic retinopexy, vitrectomy). In cases of a symptomatic reti­ nal tear without a retinal detachment, most patients are treated with a barrier procedure such as laser photocoagulation or cryoretinopexy (ie, use of a cold probe to cause focal adhesion) to prevent a retinal detachment. In cases of only a posterior vitreous detachment (PVD) without a retinal tear, no specific therapy is indicated.
Disposition\:
An immediate ophthalmologic referral is warranted in patients suspected of having a retinal detachment.
Pearls\:
• Patients at risk of developing a retinal detachment include those with ocular trauma, myopia, or a history of cataract surgery.
• Common causes of tractional retinal detachment include proliferative diabetic retinopathy, sickle cell disease, pen­ etrating trauma, and retinopathy of prematurity.
• Common causes of exudative retinal detachment include inflammatory conditions, neoplasms, and malignant hyper­ tension.
• On the CCS, suboptimal management would include de­ laying the diagnosis of retinal detachment and getting the appropriate ophthalmology consult, stat.
• On the CCS, poor management would include the failure to order an eye exam and going straight to the ophthalmology consult.
I MACULAR DEGENERATION
Age-related macular degeneration (ARMD) is a degenerative disease of the macula that results in central visual loss. Two
types of macular degeneration are wet (exudative) ARMD and dry (nonexudative) ARMD. The pathophysiology of dry ARMD is unknown, but it is associated with drusen formation under­ neath the retinal pigment epithelium (RPE). Wet ARMD is due to choroidal neovascularization that can result in leakage of fluid and blood into the subretinal space causing serous detachment of the fovea leading to vision loss.
Risk Factors\:
Smoking (major modifiable risk factor), increasing age, family history.
Clinical Features\:
Patients with ARMD will often complain of painless central visual impairment (central scotomas). Metamorphopsia may or may not be present in either type of ARMD. Dry ARMD usually has an insidious onset that can affect one or both eyes. Wet ARMD can have an insidious or acute onset that usually affects one eye, but both eyes can be affected. The cause for an acute onset in wet ARMD is usually the development of a subretinal hemorrhage.
Next Step\:
Step 1) An ophthalmologist will usually perform a dilated fun- doscopic examination with slit lamp biomicroscopy that will reveal characteristic findings of ARMD (see Figure 13-2 and Color Plate 12). In addition, the following adjunctive tests may be performed to assess ARMD.
Amsler grid evaluation—Amsler grid is a grid with horizontal and vertical lines with a dot in the middle. In normal vision, the lines will appear normal (straight) when focusing on the central dot. In ARMD, the lines will appear distorted (eg, wavy, bent) or absent when focusing on the central dot.
Retinal angiography—-Following a bolus of dye (fluores­ cein or indocyanine green) into a peripheral vein, an an­ giogram is taken of the eye. Consistent with wet ARMD is leakage of the dye (hyperfluorescence) secondary from the choroidal neovascular vessels.
Optical coherence tomography (OCT)—OCT produces cross-sectional images of the retina that are useful in de­ tecting subretinal fluid in wet ARMD.
Step 2) Smokers should be counseled to stop smoking.
Step 3) The clinical management depends on the type ofARMD.
Consider the following\:
Dry ARMD—There is no effective therapy for dry ARMD. Oral supplements with vitamin C, vitamin E, beta-carotene, zinc, and copper are recommended in pa­ tients with moderate ARMD since it has been shown to lower the risk of progression to advanced ARMD. How­ ever, patients with mild ARMD do not seem to benefit from the supplements.

FIGURE 13-2 • Macular degeneration. A. Dry ARMD—Depicted are soft yellow drusen that are beginning to coalesce. B. Wet ARMD—A clearly
evident subretinal hemorrhage over the macula may not always be present as in this case. However, further investigation with a fluorescein angiogram revealed leakage of fluorescein dye (hyperfluorescence) into the subretinal space of the macula in this patient. (Reproduced with permission from Gerstenblith AT, Rabinowitz MP, et al. The Wills Eye Manual\: Office and Emergency Room Diagnosis and Treatment ofEye Disease. 6th ed. Philadelphia, LWW; 2012\:323-324.)
Wet ARMD—Effective therapies for wet ARMD include VGEF inhibitors, photodynamic therapy, and thermal laser photocoagulation. Consider the following treatments\:
Vascular endothelial growth factor (VGEF) inhibitors\:
VGEF plays an important role in ocular angiogenesis. Intravitreous injection of VGEF inhibitors (eg, ranibi- zumab, bevacizumab, pegaptanib, aflibercept) suppress­ es neovascularization.
Photodynamic therapy\: Following an intravenous injection of verteporfin (photosensitive dye), a light of a certain wavelength is applied to the eye. The dye becomes activated by the light and induces occlusion via thrombosis of the abnormal vessels that usually retain most of the dye.
Thermal laser photocoagulation\: Photocoagulation can destroy abnormal choroidal vessels, but it is not routinely used since it can cause a permanent blind spot in patients. It is generally reserved for patients who have abnormal vessels outside of the fovea.
Supplements\: Similar to dry ARMD, patients are rec ommended vitamin C, vitamin E, beta-carotene, zinc, and copper to decrease the progression to advanced ARMD.
GLAUCOMA
I OPEN-ANGLEGLAUCOMA
Glaucoma is the second leading cause of blindness in the world following cataracts. Primary open-angle glaucoma (POAG) is a progressive optic neuropathy that may or may not be accom­ panied by an elevated intraocular pressure (IOP). Open-angle
Follow-Up\:
Patients are given an Amsler grid to take home to assess their vision on a regular basis. Patients should follow up with their ophthalmologist in the event ofvisual changes in daily activities or new changes with the Amsler grid.
Pearls\:
• Dry (sometimes called atrophic) ARMD is more common than wet ARMD.
• Wet ARMD accounts for approximately 80% of legal blindness.
• Dry ARMD can sometimes progress to wet ARMD.
• Patients with a unilateral wet ARMD are at risk of developing neovascularization in the contralateral eye.
• Beta-carotene has been associated with an increased risk of lung cancer, therefore, advise patients who smoke to exclude beta-carotene from the recommended supplements.
• Foundational point—In wet ARMD, new vessels usually grow from the choroid through Bruchs membrane and into the subretinal or sub-RPE space.
• On the CCS, “advise patient, no smoking” if the patient smokes.
glaucoma results in optic nerve damage involving loss of retinal ganglion cells. The mechanism of optic nerve injury second­ ary to elevated IOP is unknown, nor do we know the cause of elevated IOP.
Risk Factors\:
Increasing age (especially >40 years of age), blacks > whites, elevated IOP, family history.
CHAPTER 13 OPHTHALMOLOGY 197

198 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Clinical Features\:
Open-angle glaucoma has an insidious onset, and patients may be asymptomatic until late in the disease when they will have visual complaints. Patients typically do not complain of any eye pain, unlike angle-closure glaucoma. The characteristic pattern of open-angle glaucoma involves peripheral visual loss followed by central field loss in which patients may have “tunnel vision.” Once visual field loss occurs, it is irreversible. Open-angle glau­ coma is usually bilateral, but frequently asymmetric. As the neural rim of the optic disc is destroyed, the cup within the optic disc becomes larger. This is referred to as “cupping,” which appears as an excavation of the optic nerve. Over time, the cup-to-disc ratio may increase in glaucoma.
Next Step\:
Step 1) The diagnosis of open-angle glaucoma is based on the fundoscopic examination that demonstrates optic nerve damage (eg, cupping) and the presence ofvisual field defects. Consider the following adjunctive tests that are used to support the diagnosis.
Automated perimetry—This test evaluates the peripheral vision by having patients focus their eyes on a central point while light of varying intensities is displayed in their visual field.
Tonometry—Tonometry measures IOP. Normal IOPs are approximately 10 to 20 mm Hg.
Pachymetry—Pachymetry measures the corneal thickness. Patients with thin corneas are at risk in developing open- angle glaucoma.
Gonioscopy—Gonioscopy is performed to rule out angle- closure glaucoma.
Slit-lamp exam—Slit lamp may be used to examine the ante­ rior segment (eg, cornea, iris, lens, anterior chamber) and posterior segment ofthe eye (eg, fundus, optic disc, vitreous).
Step 2) Treating patients with open-angle glaucoma is based on the clinical judgment of the ophthalmologist. There are no set criteria or IOPs that all ophthalmologist use to treat patients. For example, a patient with open-angle glaucoma with a normal IOP (also referred to as normal-tension or low- tension glaucoma) but with optic nerve changes (eg, thin­ ning of the optic disc rim) and visual field defects are usually treated. On the flip side, patients with a onetime elevation in the IOP with a healthy optic nerve and normal visual field may not be treated unless the IOP is persistently elevated. If the deci­ sion is to treat, pharmacologic therapy with the goal of lowering the IOP is the initial choice before more invasive procedures are pursued. Consider the following therapies\:
Pharmacologic Therapy
Beta-blockers—Beta-blocker eye drops decrease aqueous humor production by the ciliary body. Agents that can be used include timolol, betaxolol, levobunolol, carteolol, or metipranolol. Beta-blocker drops should not be used in patients with heart blocks (unless they have a pacemaker), bronchospastic disease, bradycardia, or uncompensated heart failure.
Alpha-2 adrenergic agonists—Alpha agonist eye drops such as brimonidine can decrease aqueous humor production and increase uveoscleral outflow. Apraclonidine is another agent that can be used, but it functions to only decrease aqueous humor formation. Side effects include ocular pruritus, allergic conjunctivitis, contact dermatitis, and hyperemia.
Prostaglandin analogs—Prostaglandin eye drops increase uveoscleral outflow. Agents that can be used include latano- prost, travoprost, brimatoprost, or tafluprost. Side effects include discoloration of the iris, burning, stinging, blurring, and hyperemia.
Cholinergic agonists—Cholinergic eye drops increase aqueous outflow secondary to contraction of the cili­ ary muscle. Agents include pilocarpine or carbachol. Side effects include miosis, myopia, headaches, salivation, lacri- mation, and hypertension.
Carbonic anhydrase (CA) inhibitors—CA inhibitors de­ crease aqueous humor production. This class ofdrug is con­ sidered second-line treatment. Topical agents that can be used include brinzolamide or dorzolamide. Oral (systemic) agents that can be used include acetazolamide or meth- azolamide. Topical side effects include bitter taste, burning, stinging, blurring, and superficial punctate keratitis. Oral side effects include myopia, taste alteration, decreased ap­ petite, diarrhea, and agranulocytosis.
Invasive Procedures
Laser therapy—A trabeculoplasty can be accomplished by laser therapy, which increase aqueous outflow.
Surgery—A trabeculectomy may be performed or place­ ment of a shunt or “valve” may be attempted to release the aqueous fluid from the eye.
Follow-Up\:
The vast majority of patients will require long-term follow-up with their ophthalmologist because of the insidious and pro­ gressive nature of the disease. Most patients may also be noncompliant simply because they are asymptomatic or the side effects of the medications are troublesome.
Pearls\:
• Although not every patient with open-angle glaucoma will have an elevated IOP, those patients with an elevated IOP without characteristic findings of open-angle glaucoma (ie, cupping or visual field defects) should still be watched and evaluated carefully because they are still at risk in devel­ oping and progressing into open-angle glaucoma.
• Screening patients for open-angle glaucoma remains an area of controversy.
• Secondary glaucoma refers to glaucoma with an identifi­ able cause that can elevate the IOP resulting in optic nerve damage. Such causes include eye injury, inflammation (eg, uveitis), drug therapy (eg, glucocorticoid), tumors, advanced cataracts, or congenital conditions.
• Foundational point—Aqueous humor is produced by the ciliary process in the posterior chamber and passes through

the pupil and into the anterior chamber. The fluid then passes through the trabecular meshwork (fenestrated structure) and then through the iridocorneal angle and into Schlemm’s canal, where it drains into the episcleral vein.
• On the CCS, “tonometry” is available in the practice CCS and will give you the result with the normal values.
• On the CCS, remember to “advise patient, side effects of medication” if you prescribe any medications.
B ANGLE-CLOSURE GLAUCOMA
Angle-closure glaucoma is characterized by the narrowing ofthe anterior chamber angle. When there is greater contact between the lens and the iris, aqueous humor cannot flow through the pupil (pupillary block). Increasing IOPs will then close the anterior chamber angle and obstruct drainage of the aqueous fluid. Without treatment, elevated IOPs can damage the optic nerve and cause vision loss.
Risk Factors\:
Asians, Eskimos, females, increasing age (>40 years of age), family history, hyperopia, thick iris, dim lighting, medica­ tions (eg, anticholinergics, antidepressants, antipsychotics, anti­ convulsants, sympathomimetics, decongestants, antihistamines, mydriatics).
Clinical Features\:
Angle-closure glaucoma has an abrupt onset, and patients typi­ cally complain of eye pain. Patients may see halos or blurry vi­ sion secondary to corneal edema. On examination, the cornea may be hazy or cloudy with a mid-dilated nonreactive pupil. The ocular globe may be hard. Conjunctival injection can also be present. Nonocular symptoms include headaches, nausea, and vomiting.
Next Step\:
Step 1) Angle-closure glaucoma is an ophthalmologic emer­ gency. Provide analgesics for pain control and antiemetics (eg, ondansetron) for nausea and vomiting (ie, you do not want to have the patient to vomit on you while you’re examining them). It should be noted that the pain and vomiting can potentially increase the already elevated IOP.
Step 2) The patient should be in the supine position because theoretically the lens will fall away from the iris and alleviate the pupillary block. Also, do not dim the lights or put a patch over the eye because mydriasis (pupillary dilatation) may exacerbate the condition. Perform an eye examination (eg, visual acuity, visual fields, ocular motility, fundus), but again, avoid dilating the eye for the fundus exam.
Step 3) Two important test to perform are gonioscopy (consid­ ered the gold standard) and tonometry. Gonioscopy will assess the angle of the anterior chamber while tonometry will typically reveal an IOP > 30 mm Hg in acute-angle glaucoma. Adjunctive testing with a slit lamp may also be useful in evaluating for corneal edema or abnormalities in the lens, iris, or pupil shape.
Step 4) Initiate treatment to lower the IOPs. Consider the following cocktail\:
• IV or PO acetazolamide, stat, plus ...
• Eye drop of timolol (if no contraindications exist), then
• Eye drop of apraclonidine (decreases aqueous production), then
• Eye drop of prednisolone (reduces ocular inflammation), then
• Reassess the IOP.
Now consider two scenarios. First, if the IOP is reduced then you can instill pilocarpine (pulls iris tissue away from the angle). However, instilling pilocarpine when the IOP is elevated is ineffective because the elevated pressures cause a pressure- induced ischemic paralysis of the iris. Second, if the IOP is persistently elevated despite the above cocktail, then the next best step is to consider an osmotic agent such as IV mannitol (reduces vitreous volume). Alternative osmotic agents include oral glycerol and isosorbide.
Step 5) Once the IOP is controlled, definitive treatment is with laser peripheral iridotomy. In this procedure, a tiny hole is made in the peripheral iris that allows the aqueous humor to flow through the hole, thereby creating a detour from the pupillary block. Prophylactic laser peripheral iridotomy may be offered to the patient in the other eye if a narrow angle is found on exam.
Disposition/Follow-Up\:
An ophthalmic consultation should be obtained as soon as possible in the ED since damage to the optic nerve is irrevers­ ible and can occur within hours. Ideally, systemic medications (eg, IV mannitol) should be given in conjunction with an ophthalmologist, but certainly an ED physician should initi­ ate treatment without delay. Upon discharge, patients who received laser peripheral iridotomy may be seen in the office for reevaluation of the anterior chamber angle via gonios­ copy.
Pearls\:
• Patients with angle-closure glaucoma can develop IOPs >60 mm Hg.
• Secondary angle closure refers to an underlying identifiable cause for narrowing ofthe anterior chamber angle (eg, tumor, trauma, surgery, displaced lens). If angle closure results in an elevated IOP that causes optic nerve damage, it is referred to as secondary angle-closure glaucoma.
• Patients with angle-closure glaucoma in one eye are at risk of developing an attack in the other eye. Therefore, it is im­ portant to exam both eyes and decide if the patient needs prophylactic laser peripheral iridotomy.
• On the CCS, this case is an emergency; move the simulated time judiciously.
• On the CCS, do not do a neurologic or GI workup in this type of case since that would delay treatment and would be considered suboptimal management.
CHAPTER 13 OPHTHALMOLOGY 199

200 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
NEURO-OPHTHALMOLOGY
B AMBLYOPIA
Amblyopia (“dimness of vision” in Greek) is characterized by impaired visual acuity in the affected eye. It is thought that im­ ages are not properly projected onto the fovea and thereby fail to transmit information through the optic nerve and into the brain during a critical period of visual development. Therefore, the brain favors the visual input from the normal eye.
Clinical Features\:
Amblyopia is a common visual impairment in children. Con­ sider the following causes and clinical findings of amblyopia.
Strabismus—Strabismus is ocular misalignment. The brain may favor visual input in one eye and suppress the other eye. One eye may move normally, while the other eye may point inward (esotropia), outward (exotropia), upward (hypertropia), or downward (hypotropia). Since patients are unable to use both eyes properly, depth per­ ception (stereopsis) may be affected. It should be noted that strabismus does not always cause amblyopia, but it is a common cause.
Anisometropia—Anisometropia results in unequal refrac­ tive error between the eyes. The image that is clearer will usually become the dominant eye. Anisometropia can be a little tricky and easily missed because there are no obvious physical manifestations (ie, just by examining the eyes you cannot tell if there is a refractive error). However, an un­ equal red reflex (ie, one eye appears to be brighter than the other) may suggest unequal refraction.
Visual deprivation—The brain does not receive visual in­ put from the affected eye. Common causes include cata­ racts, ptosis, or corneal opacities. Clinical exam may reveal a diminished red reflex or drooping of the eyelid.
Next Step\:
Step 1) Vision screening should be performed in children <5 years old beginning in the newborn period and at all well-child visits. Children >5 years old should also be periodically assessed at all health maintenance visits. Consider the following\:
INFLAMMATORY CONDITIONS
1 CHALAZION
Chalazion is a benign nodular lesion that develops from an obstruction ofthe meibomian gland or Zeis gland that are within the eyelid.
Clinical Features\:
Chalazia are usually rubbery, cystic, and painless. Patients may have a history of chalazia since they can recur.
Preverbal child—Visual inspection of the ocular globe may re­ veal misalignment as seen in strabismus. The cover test can also evaluate for strabismus by having the child fixate on a distant object, then covering one of the eyes. If the uncovered eye is the strabismic eye, the eye will move and refixate on the object. However, if the uncovered eye is the normal straight eye, there will be no eye movement because the eye is already fixated on the object Finally, another test can be performed to assess for amblyopia. Covering one ofthe eyes will cause a response. Ifthe amblyopic eye is covered, the child may not be upset. However, covering the normal eye will cause the child to be agitated.
Verbal child—In older children, the diagnosis ofamblyopia can be made when there is a >2 line difference in visual acuity between the eyes using a Snellen (letter) chart. However, the letters should be presented in rows (ie, crowding of letters will cause the amblyopic eye to do worse on visual acuity) because visual acuity is better when optotypes are presented in isolation (crowding phenomenon).
Step 2) Treatment of amblyopia begins with correcting any visual disturbances (eg, cataracts, ptosis) and refractive errors via glasses or contact lenses.
Step 3) The next step in management is to encourage the use ofthe amblyopic eye by occlusion therapy (ie, patching the good eye) or penalization therapy of the good eye. Penalization can be accom­ plished by spectacles or by cycloplegic eye drops (eg, atropine).
Follow-Up\:
The earlier amblyopia is detected during vision screening, the better the prognosis.
Pearls\:
• From the newborn period to 6 months of age, infants have the capacity to fix and follow an object. By 2 months of age and definitely by 6 months of age, infants should be able to shift their fixation across midline.
• On the CCS, long delays in the diagnosis of amblyopia would be considered suboptimal management because the patient is at risk of losing vision in the amblyopic eye. In general, with all your CCS cases, think about the conse­ quence of delaying your diagnosis and not providing the appropriate treatment in a timely fashion. Remember, your goal is to use good sound judgment without delays.
Next Step\:
Step 1) A chalazion is a clinical diagnosis.
Step 2) Small chalazia often resolve on its own. For larger chalazia, warm compresses may be attempted. For persistent lesions (>4 weeks), a referral to an ophthalmologist may be indicated for an incision and curettage or glucocorticoid injection into the lesion.
Follow-Up\:
For persistent or recurring chalazia, a biopsy should be obtained for histologic evaluation since it may represent a carcinoma of the sebaceous cell, meibomian gland, or basal cell.

Pearls\:
• Chalazia can be associated with rosacea and blepharitis.
• Both meibomian gland and Zeis gland are a type of seba­ ceous gland located within the palpebral conjunctiva, but the Zeis glands are near the margin of the eyelid since they keep the eyelashes clean.
• Foundational point—A chalazion is characterized by a chronic granulomatous inflammation. On histopathological examination, lipid-laden macrophages and lymphocytes can be observed.
• On the CCS, if you ever get “lost” during a CCS case, get yourselfgrounded again by quickly reviewing the case history and figure out what important steps to take in managing the patient. In this approach, you’re hitting the “refresh” button in your mind.
1 HORDEOLUM
Hordeolum is an acute focal infection (usually Staphylococcus aureus) that can affect the meibomian glands (internal hordeo­ lum) or the Zeis glands (external hordeolum or stye).
Clinical Features\:
Patients with a hordeolum will generally have a swollen, painful, red eyelid. A stye will be near the lid-margin, but an internal hordeolum will be in the inner surface of the tarsal plate.
Next Step\:
Step 1) A hordeolum is a clinical diagnosis.
Step 2) Patients may benefit from warm compresses and eryth­ romycin ophthalmic ointment. Systemic antibiotics are gener­ ally not indicated unless the hordeolum is associated with a preseptal cellulitis.
Follow-Up\:
If resolution does not occur within 2 weeks, the patient should be referred to an ophthalmologist.
Pearls\:
• A hordeolum can harden into a chalazion.
• On the CCS, “warm compresses” is available in the practice CCS.
1 CONJUNCTIVITIS
Conjunctivitis is a common cause of “red eye” secondary to an inflammation of the conjunctiva from bacteria, virus, allergies, fungus, or irritants. When the cornea is also involved, it is re­ ferred to as keratoconjunctivitis.
Clinical Features\:
The clinical presentation of conjunctivitis can vary based on the etiology. Consider the following\:
Bacterial—Bacterial conjunctivitis typically presents as a painless mucopurulent discharge that can be unilateral or
bilateral. Often, the eyelids are stuck together upon awaken­ ing. Chemosis (conjunctiva edema) maybe present. Common organisms in this category include Staphylococcus aureus (commonly seen in adults), Streptococcus pneumoniae, Mo- raxella catarrhalis, and Haemophilus influenzae. Patients are very contagious, and they can spread the infection from their secretions and from contaminated objects.
Viral—Viral conjunctivitis typically presents as a painless watery discharge. Often, one eye is infected and then the other eye becomes infected a couple of days later. Patients may report a gritty sensation in the eye. Patients will fre­ quently have a prodrome (eg, upper respiratory infection, fever, pharyngitis, adenopathy) before viral conjunctivi­ tis appears. On examination, there may be conjunctival injection, follicles (“bumps”) on the tarsal conjunctiva, and a tender preauricular lymphadenopathy. Viral conjuncti­ vitis is typically caused by adenovirus. Similar to bacterial conjunctivitis, adenovirus is very contagious. Adenovirus can also cause a unique condition called epidemic keratoconjunctivitis (EKC). As the name states, it occurs in epidemics. Patients with this condition will often have a foreign body sensation in the eye, photophobia, excessive tearing, and preauricular lymphadenopathy.
Allergies—Allergic conjunctivitis typically presents as pain­ less watery discharge that is usually bilateral. The cardinal fea­ ture of allergic conjunctivitis is itchy eyes. Patients often have a history of atopy or allergies. On examination, the eyelids and conjunctivae may be edematous and erythematous. Simi­ lar to viral conjunctivitis, a bumpy appearance (cobblestone papillae) may be present on the tarsal conjunctiva.
Next Step\:
Step 1) Conjunctivitis is a clinical diagnosis. Cultures and sensitivities are generally not needed in bacterial conjuncti­ vitis unless it is severe, recurrent, or resistant.
Step2) Treatment is based on the type of conjunctivitis. Consider the following\:
Bacterial conjunctivitis
Option 1\: Erythromycin ophthalmic ointment x 5 to 7 days
Option 2\: Polymyxin-trimethoprim eye drops x 5 to 7 days
Option 3\: Patients who wear contact lenses and do not have corneal white spots can be treated with tobramycin, ofloxacin, or ciprofloxacin to cover Pseudomonas. In the presence of corneal white spots, an urgent referral to an ophthalmologist is warranted since an ocular perforation can occur.
Viral conjunctivitis—Viral conjunctivitis is a self­ limited condition.
Allergic conjunctivitis—Allergic conjunctivitis is a self­ limited condition. Avoid the allergen if possible. Patients may benefit from a topical antihistamine/vasoconstric­ tor (eg, naphazoline/pheniramine). The vasoconstrictor component alleviates chemosis (conjunctival edema).
CHAPTER 13 OPHTHALMOLOGY 201

202 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Severe symptoms may require topical steroids, but ad­ ministration should be under the guidance of an oph­ thalmologist since topical steroids can cause cataracts and glaucoma.
Follow-Up\:
Patients with bacterial conjunctivitis should respond to therapy within 5 days of administering antibiotics. Viral and allergic conjunctivitis may take 1 to 3 weeks. Patients should follow up with an ophthalmologist if symptoms persist beyond the expected time.
Pearls\:
• Emphasize hand washing to patients with bacterial and viral conjunctivitis since both conditions are very contagious.
Treating physicians should also wash their hands since they are at risk of spreading the infection.
• Ideally, patients with bacterial or viral conjunctivitis should stay at home to prevent the spread of infection.
• Foundational point—Allergic conjunctivitis is a type I, IgE- mediated hypersensitivity.
• Connecting point (pgs. 164, 166)—Know how to manage neonatal gonococcal and chlamydial conjunctivitis.
• On the CCS, if you prescribe a medication for the patient to take home, remember to use the “continuous” mode of frequency because it takes into account the periodic admin­ istration. Keep in mind that there is no PRN.

Orthopedics
KEYWORDS REVIEW
Chondrolysis—Loss or lysis of articular cartilage.
Closed reduction—Manipulation of bone fragments without surgical exposure.
Comminution—Broken bone fragments. Malunion—Union in a faulty position after a fracture. Nonunion—An unhealed fracture.
Open reduction—Anatomic restoration of bone fragments with surgical exposure.
Paresthesia—An abnormal sensation such as tingling, prickling, or burning.
Shortening—Overriding of bone fragments.
203

204 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
SPINE
I IDIOPATHICSCOLIOSIS
Idiopathic scoliosis is the most common type of scoliosis, which is defined as an unknown cause for a lateral curvature of the spine usually with rotation. Idiopathic scoliosis can be further classified as infant (0-3 years), juvenile (4-9 years), and adolescent (>10 years). Adolescent idiopathic scoliosis (AIS) is the most common of the three idiopathic types, and further discussion will be based on AIS.
Clinical Features\:
Idiopathic scoliosis is typically a painless disorder with a gradu­ al curve progression. Patients usually do not complain of neuro­ logical symptoms such as bowel or bladder changes, numbness, or weakness. Patients may notice an unleveling of the shoulder or scapulae, forward rotation of a shoulder, or an asymmetric waistline. On exam, an Adams forward bend test is usually performed in which the patient bends forward allowing the arms to hang freely and the clinician observes from behind. The test assesses the rotational component of the scoliosis, and typi­ cally, a rib hump or lumbar prominence can be seen.
Next Step\:
Step 1) Diagnosis of AIS is made on clinical and radiographic evaluation. A scoliometer (inclinometer) is a screening device used in the office to assess trunk rotation. While the patient is in the Adams forward bending position, a scoliometer is placed on the back to measure the highest point of the curve providing measurements of the angle of rotation.
Step 2) Obtain a PA and lateral x-ray of the spine in the stand­ ing position if the angle of rotation from a scoliometer is >7° or obvious scoliosis noted on exam. Once the x-ray films are obtained, two pieces of information can be extracted, the degree of curvature, Cobb’s angle, and the degree of skeletal maturity, the Risser sign. A Cobb’s angle >10°, age >10, and exclusion of other causes for scoliosis confirms the diagnosis. The Risser sign has a grading system (0-5), with a grade 0 showing no ossifica­ tion and grade 5 as skeletally matured.
SHOULDER
I CLAVICLE FRACTURES
Most clavicle fractures occur from a direct blow to the shoulder such as a fall to the ground. Less common causes are indirect forces such as a fall onto an outstretched hand.
Clinical Features\:
There are three different types of clavicle fractures to consider\:
Proximal third—Medial fractures are the least common types of clavicle fractures. However, it can be the most
Step 3) Refer to orthopedic surgeon with a Cobbs angle >20° or signs of progression of the Cobb’s angle >5°. Treatment options for scoliosis can be broken down to the triple O’s.
Observe—Skeletally immature patients (Risser 0-2) with a Cobb’s angle <30° can be observed and followed up every 6 months for evaluation ± PA x-rays. There is no need to repeat lateral views if the initial films demonstrated normal configuration.
Orthosis—The basis of the bracing is to prevent curve pro­ gression and not necessarily correct the curvature. There­ fore, bracing would not be appropriate for a skeletally matured patient (Risser 4-5). Skeletally immature patients (Risser 0-2) with a Cobb’s angle between 30° and 40° or those with curve progression >5° at the 6-month visit from the observation phase can be braced.
Operate—A spinal fusion can be considered in skeletally immature patients with a Cobb’s angle between 40° and 50°. Surgery should definitely be considered with a Cobb’s angle >50° regardless of the skeletal maturity.
Follow-Up\:
Patients with scoliometer angle <7° can be followed up every 6 months without repeating x-rays.
Pearls\:
• Family history of scoliosis occurs frequently.
• Girls may be affected at a slightly higher rate than boys, but the risk of curvature progression is certainly higher in girls.
• Less common types ofacquired or congenital scoliosis include neuromuscular scoliosis, which is associated with neuro­ logical conditions (eg, cerebral palsy, vertebral tumors), or congenital scoliosis, which can be due to vertebral mal­ formations (eg, hemivertebrae). Unlike idiopathic scoliosis, findings of neurological symptoms, pain, or rapid progression can be seen with the less common types of scoliosis.
• On the CCS, an “X-ray, spine” is available in the practice CCS. However, you need to specify which part of the spine you want to evaluate (ie, cervical, thoracic, lumbosacral, or sacrum/coccyx).
serious type of fracture because it is close to the sternum, which may result in intrathoracic injuries. Therefore, it is important to do a good neurovascular (eg, brachial plexus injury) and lung examination (eg, pneumothorax).
Middle third—Midshaft fractures are the most common types of clavicle fractures. Patients may have pain, tender­ ness, swelling, ecchymosis, or limited range of motion of the arm. Most often, patients will hear a “crack” at the time of injury.
Distal third—Distal third fractures have three subtypes, and they can sometimes be confused with acromioclavicu­ lar joint injuries. Type I are nondisplaced fractures with

FIGURE 14-1 • Anatomy of the shoulder. The site for distal clavicle fractures. (Reproduced with permission from Tintinalli JE, Stapczynski JS, Ma OJ, et al. Emergency Medicine\: A Comprehensive Study Guide. 7th ed. New York\: McGraw-Hill; 2011\:1832.)
lization and healing usually occurs within 6 to 8 weeks. An urgent orthopedic referral should be obtained for neurovascular injuries, open fractures, or fracture displace­ ment (for reduction).
Middle third—For nondisplaced midshaft fractures, patients can be managed with a sling or a figure of eight bandage until union occurs. An urgent orthopedic referral should be ob­ tained for open fractures, displacement, or a “floating shoul­ der” (ie, glenoid neck fracture along with the clavicle).
Distal third—For types I and III, there is no displacement or minimal displacement. Therefore, patients can be man­ aged with a sling for immobilization. An orthopedic referral should be obtained for type II fractures (displaced) since they may be prone to nonunion.
Disposition\:
Most nondisplaced or minimally displaced fractures will heal within 6 to 12 weeks with conservative management.
• Open reduction internal fixation (ORIF) refers to open sur­ gery and fixation with plates, screws, rods, or pins. ORIF may be required in displaced fractures with comminution that would not heal correctly with splinting alone.
• Patients with open fractures may require a tetanus shot and prophylactic antibiotics.
intact ligaments holding the fragment in place. Type II are
displaced fractures, which can occur by two mechanisms
(Type IIA are displaced fractures with intact coracoclavicular Pearls\: ligaments and Type IIB are displaced fractures with a torn coracoclavicular ligament). It should be noted that the coracoclavicular ligament consists of two ligaments, die
trapezoid and conoid. Type III involves articular surface
injury at the acromioclavicular joint without displacement
or ligament disruption (see Figure 14-1). In essence, type II
fractures are displaced fractures and only type IIB fractures
involve a torn ligament.
Next Step\:
Step 1) Along with your clinical assessment, an AP x-ray view of the clavicle will confirm the diagnosis. Sometimes when nothing is found on standard AP x-ray views, a 45° cephalic tilt view (ie, x-ray tube pointed at 45°) may provide a better assessment of the clavicle.
Step 2) The initial management steps is to provide pain relief (analgesics), ice, and upper extremity support. Consider the following management approach\:
Proximal third—For nondisplaced medial fractures, pa­ tients can be managed with a sling to maintain immobi­
ELBOW
I NURSEMAID'S ELBOW
Nursemaid’s elbow (radial head subluxation) is a common el­ bow injury in children and typically occurs between the ages of 1 and 4 years old. The mechanism of injury is a sudden longi­ tudinal traction on the arm with the forearm in pronation and the elbow in extension, which usually occurs while the child falls and is lifted up forcefully by the hand of another person.
• When examining an x-ray of the clavicle, a general guideline for displacement is a clavicle that is displaced greater than one bone width from its original position.
• Complications of clavicle fractures include malunion, non­ union, arthritis (especially with proximal third fractures), and neurovascular injuries.
• Risk factors for malunion or nonunion include comminution, shortening, improper immobilization, and elderly patients.
• On the CCS, “sling, arm” is available in the practice CCS, but there is no “figure of eight bandage.”
• On the CCS, an “X-ray, clavicle” is available in the practice CCS, but there is no option for a 45° cephalic tilt.
During this event, a circular ligament (annular ligament) “slips” over the radial head.
Clinical Features\:
Children will usually be protective of the affected arm, hold­ ing the arm close to the body with a slightly flexed or extended elbow and the forearm in the pronated position. Patients will usually complain of pain with any attempt to supinate the fore­ arm. Tenderness over the radial head (ie, elbow end) is typically present. Patients should be able to move their wrist or digits but reluctant to do so because of fear of reproducing the pain.
CHAPTER 14 ORTHOPEDICS 205

206 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Next Step\:
Step 1) Nursemaid’s elbow is a clinical diagnosis. X-ray is usual­ ly not required unless there is a suspicion for a fracture or failed attempts at reduction.
Step 2) Treatment is by reduction, which can be painful but does not require anesthesia. Two types of reduction procedures include\:
Supination-flexion technique—Pressure is applied to the radial head with one finger with gentle traction of the fore­ arm. The forearm is then supinated and the elbow is then fully flexed. A click is usually felt over the radial head dur­ ing the reduction.
Hyperpronation technique—Pressure is applied to the ra­ dial head with one finger while holding the distal forearm
HAND
1 SCAPHOID FRACTURES
Scaphoid fractures are common injuries involving the carpus and are typically due to a high-energy axial load on the wrist such as falling on an outstretched hand. Most scaphoid fractures go unnoticed, resulting in nonunion, delayed union, or avascu­ lar necrosis (AVN).
Clinical Features\:
Patients will often complain of pain and swelling along the radi­ al side of the wrist. The scaphoid (navicular) bone is situated on the thumb side of the wrist and articulates with the radius. The scaphoid bone can be broken down to the distal third (ie, closest to the nail end), central third (ie, referred to as the waist), and proximal third (ie, closest to the radius). Palpating and elicit­ ing point tenderness in the three different areas of the scaphoid bone can help determine the area of fracture. The scaphoid bone has a bony prominence (tubercle) at the distal end, and palpating in that specific area would indicate a distal fracture. Tenderness along the anatomic snuffbox would indicate a frac­ ture at the waist of the scaphoid, while tenderness toward the radius would be a clue to a proximal fracture.
Next Step\:
Step 1) When a scaphoid fracture is suggested in the clinical assessment, obtain an x-ray in the PA, lateral, oblique, and scaphoid view (ie, wrist in ulnar deviation) of the wrist. Approx­ imately 10% of initial x-rays will not detect a fracture, therefore if the initial x-ray films are negative, place the patient in a thumb spica splint and reimage in 7 to 10 days. For a rapid diagnosis and to avoid prolonged immobilization, a CT or MRI (MRI can
and then subsequently hyperpronating the forearm. A click is usually felt over the radial head during the reduction.
Disposition\:
Patients will usually have immediate pain relief after a successful reduction and can go home and resume normal activity.
Pearls\:
• Nursemaids elbow commonly affects more girls than boys.
• Nursemaid’s elbow can recur but usually not after 4 years old because the radial head becomes more bulbous and the annular ligament becomes stronger.
also provide information on soft tissue injuries) are acceptable alternatives.
Step 2) Treatment for a nondisplaced distal scaphoid frac­ ture is immobilization in a short-arm thumb spica cast for 4 to 6 weeks. Treatment for a nondisplaced central or proxi­ mal scaphoid fracture is immobilization in a long-arm thumb spica cast for 6 weeks then converted to a short-arm thumb spica cast for another 6 to 14 weeks. Referral to an orthopedic surgeon is indicated when there is an open frac­ ture, associated neurovascular injuries, displacement more than 1 mm, AVN, nonunion, or carpal instability (eg, scaph- olunate dissociation).
Disposition\:
Patients seen in the ED with negative x-ray imaging for a scaphoid fracture should have close follow-up with their primary care physician to repeat the x-ray because delayed diagnosis and treatment results in an increased risk of nonunion.
Pearls\:
• Proximal scaphoid fractures have a greater risk of nonunion, delayed union, and avascularnecrosis (leading to degenerative joint disease) because the blood supply starts at the distal end of the scaphoid from the palmar carpal branch of the radial artery and finishes off at the proximal end of the scaphoid. A fracture can easily disrupt blood flow to the proximal segment.
• On the CCS, an “X-ray, wrist” will automatically give you radiographic readings of the AP, lateral, and oblique views, but not a scaphoid view in the practice CCS.
• On the CCS, both “splint extremity” and “cast extremity” are available in the practice CCS.

HIP______
I HIP DISORDERS See Table 14-1.
Table 14-1 *Hip Disorders
Age Definition
Etiology
Clinical features
Next step
Developmental Dysplasia of the Hip (DDH)
Infants
Acetabular dysplasia with hip joint instability.
Multifactorial
• Asymmetric skinfolds of the upper thigh.
• Unequal leg length.
• Older children may have limping,
toe-walking, or out-toeing.
Step 1) Perform the Barlow test, which attempts to dislocate the hip, and with the Ortolani test a "clunk"should be heard when you reduce the hip back.
Step 2) Ultrasound the hip for patients <6 months, or an AP and frog lateral x-rays for patients >6 months.
Step 3) Treat patients <6 months of age wth Pavlik harness (ie,
puts patient in a flexed and ab­ ducted position). Treat patients 6-18 months with closed reduction under anesthesia and hip spica casting. Treat patients

18 months with open reduction.
Transient Synovitis (TS) 3-8 years old
Transient inflammation of the synovium of the hip.
Unknown
• Appears nontoxic.
• Fever usually absent but
can occur.
• URI usually present and
precedes hip symptoms. • Acute hip pain.
• May have referred knee
or thigh pain.
Step 1) Obtain CBC, ESR, and CRP. If labs are normal, patient is afebrile, and nontoxic then patient can be followed clinically. If patient is febrile, ESR >20, tWBC, or T CRP —»obtain hip ultrasound to look for joint effusion and consider arthrocentesis to rule out septic arthritis.
Step 2) Treatment of TS is conservative with limited activities and NSAIDs. Full recovery is expected in
1 -4 weeks.
• TS can be bilateral in 5% of patients.
• Any hip pathology can cause referred pain to the thigh or knee.
• A small number of patients with TS can develop Legg-Calve- Perthes disease.
Legg-Calve-Perthes (LCP) Disease
3-12 years old
Avascular necrosis of the proximal femoral head.
Unknown
• "Painless" limp.
• Decreased internal
rotation and abduction
of the hip.
• May have referred knee
or thigh pain.
Step 1) Obtain AP and frog lateral x-rays of the pelvis, which will show fragmentation, flattening, and sclerosis of the proximal femur.
Step 2) Treatment involves minimal weight bearing and containing the femoral head within the acetabulum by bracing or surgery.
• LCP can be bilateral in 10%-20% of patients.
• Older children >10 years who develop the
disease are at risk of developing osteoarthritis of the hip as an adult.
Slipped Capital Femoral Epiphysis (SCFE)
8-15 years old
Epiphysis appears to "slip" posteriorly and interiorly.
Unknown
• Obese adolescents. • Hip pain.
• Limp.
• Decreased internal
rotation of hip, seen mainly in external rotation.
• May have referred knee or thigh pain.
Step 1) Obtain AP and frog lateral x-rays of pelvis with early signs of SCFE showing widening of the physis.
Step 2) Refer to ortho­ pedic surgeon for in situ fixation of the hip.
• SCFE can be bilat­ eral in 20%-40% of patients.
• Complications of SCFE are AVN and chondrolysis.
• SCFE is associated with panhypopituita­ rism, hypothyroidism, GH supplementation, and hypogonadism.
Pearls • •
• •
DDH can be bilateral in 20% of patients.
Risk factors include breech position, female, family history, firstborn.
DDH commonly occurs in healthy infants and is usually referred to as typical DDH. DDH can occur with underlying neuromuscular disorders
that occur in utero and is referred to as teratologic DDH.
AP—Anteroposterior;AVN—Avascularnecrosis;GH—Growth hormone;URI—Upperrespiratoryinfection
CHAPTER 14 ORTHOPEDICS 207

208 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
KNEE
1 ANTERIORCRUCIATELIGAMENTINJURY
Anterior cruciate ligament (ACL) injuries can occur from con­ tact injuries (eg, a blow to the lateral knee) or more commonly from noncontact mechanisms such as sudden deceleration, cut­ ting, or pivoting of the lower extremity.
Clinical Features\:
Patients with noncontact injuries will often complain of a “pop” at the time of injury, followed by pain and swelling of the knee. Most patients with acute injuries will develop a knee effusion secondary to hemarthrosis. Patients usually do not return to play because of the instability or giving-way of the knee. Patients with contact injuries will typically have associated injuries or the “unhappy triad,” which includes ACL, medial collateral ligament (MCL), and meniscus tears (lateral > medial).
Next Step\:
Step 1) Evaluate the patient soon after the injury. The evalua­ tion should include inspection, palpation, range of motion, gait, strength, and neurovascular examination. There are three knee maneuvers to help with the assessment of ACL injuries\:
Anterior drawer test—The knee is flexed at 90° with anterior pulling of the proximal tibia to check for anterior translation, which would indicate a positive test for an ACL tear.
Lachman test—The knee is flexed at 30° with anterior pull­ ing of the proximal tibia and assessing for the quality of the endpoint of anterior translation. An intact ACL will have a distinct endpoint in contrast to a torn ACL, which will have a vague or soft endpoint.
Pivot shift test—The knee is in extension while internally rotating the tibia, followed by placing a valgus (abduction) force on the knee. While maintaining the forces described, the examiner flexes the knee which causes a reduction in the subluxed tibia. If a "clunk” is sensed by the examiner, it constitutes a positive test for an ACL-deficient knee.
Step 2) Most ACL injuries are a clinical diagnosis, but MRI is the primary modality to confirm a torn ACL.
Step 3) Acute management for patients without obvious defor­ mities can be initially treated with RICE (Rest, Ice, Compression, Elevation) and NSAIDs.
NEOPLASM
1 OSTEOSARCOMA
Osteosarcoma (osteogenic sarcoma) is the most common pediatric bone tumor. Osteosarcoma is a primary malignant bone tumor that can be characterized by the production of
Step 4) Treatment options include nonsurgical or surgical.
Nonsurgical treatment—Patients with low activity level, low demand on the knee, or small partial tears may be treated nonoperatively. Bracing is sometimes used to protect the knee from instability.
Surgical treatment—Patients that place high demand on the knee, young athletes, or patients with associated torn liga­ ments (eg, “unhappy triad”) generally undergo arthroscopic repair.
Step 5) A rehabilitation program is part of the management, regardless of surgical or nonsurgical treatment.
Disposition\:
It may take 6 to 12 months to return to full activity following surgical repair with a rehabilitation program.
Pearls\:
• Patients with an ACL rupture are at risk of developing osteo­ arthritis in the future even after a successful surgery.
• Surgical intervention is usually delayed soon after an ACL injury to prevent scar tissue (arthrofibrosis) from developing.
• Placing a valgus stress at the lateral knee while holding the medial ankle will cause the lower leg to move out laterally, as if a “knocked knee.” (A good way to remember this is to associate the letter L in valgus with the letter L in laterally.) Excessive medial laxity would suggest a medial collateral ligament (MCL) tear.
• Placing a varus stress at the medial knee while holding the lateral ankle will cause the lower leg to be adducted, as if a “bowlegged” person. Excessive lateral laxity would suggest a lateral collateral ligament (LCL) tear.
• On the CCS, an “arthroscopy” is available in the practice CCS, but you will be redirected to a “Prerequisite Order” screen to order a consult with “orthopedic surgery.”
• On the CCS, you are evaluated in knowing when to order an appropriate consult. Do not assume that the CCS will always redirect you to the appropriate consultant when a procedure is ordered.
osteoid (unmineralized bone) by the malignant cells. The etiol­ ogy of osteosarcoma is unknown.
Risk Factors\:
Prior irradiation or chemotherapy, Paget’s disease, hereditary retinoblastoma (RBI gene mutation), Li-Fraumeni syndrome (p53 mutation), Rothmund-Thomson syndrome, bone dyspla­ sias, bone infarcts.

Clinical Features\: Pearls\:
Osteosarcoma can occur in all age groups but usually has a bimodal age distribution with peaks in adolescence and in adults older than 65 years. In the pediatric population, osteosarcoma usually arises in a sporadic fashion and is considered a primary cancer. In adults, osteosarcoma is thought to arise as a secondary neoplasm (eg, Paget’s disease, bone dysplasias). Osteosarcoma can affect any bone, but it has a predilection for the metaphysis of long bones and common sites include the distal femur, proximal tibia, and proximal humerus. Other possible sites include the pelvis, proximal femur, and jaw (seen in elderly patients). The most com­ mon symptom is localized pain that be present for months. In children, the pain may be dismissed as “growing pains.” Signs and symptoms of fever, night sweats, weight loss, or regional lymphadenopathy is usually absent. On examina­ tion, a soft tender mass may be present. Distant metastases usually involve the lungs, and patients can develop respira­ tory symptoms.
Next Step\:
Step 1) The best initial test is to obtain a plain x-ray of the involved bone. The x-ray may reveal a lytic lesion (radiolucent) mixed with a sclerotic appearance (radiodense). However, there is no single feature that is diagnostic for osteosarcoma. Other ancillary testing may include a CBC, LDH, and CMP. Within the CMP, you want to look closely at the renal func­ tion, LFTs, electrolytes, and alkaline phosphatase. Be aware that the alkaline phosphatase and LDH are usually elevated in osteosarcoma. In addition, an elevated LDH usually indicates a poor outcome.
Step 2) Confirm the diagnosis with a biopsy (ie, “tissue is the issue”).
Step 3) Once the diagnosis is confirmed, the patient should have a staging workup, which should include an MRI with gadolinium, CT chest to detect lung metastases, and a radio­ nuclide bone scan with technetium to detect metastases to the bony skeleton.
Step 4) Treatment of osteosarcoma involves surgery and adju­ vant chemotherapy. There is no standard chemotherapy regi­ men, but most include cisplatin and doxorubicin.
Follow-Up\:
Patients should have surveillance after initial treatment. Fol­ low-ups usually include physical exams, blood work, and im­ aging. Survival has improved significantly to >70% (5-year survival rate) with the addition of adjuvant chemotherapy. Prognosis is lower (<50%) in patients with pulmonary metas­ tases and an even poorer prognosis when metastases affect the bone.
• Males are affected more than females.
• Osteosarcoma tends to metastasize to bone as well as lung. • The most common site for disease relapse is the lung.
• Survival benefit appears to be similar when using neoadju­ vant (preoperative) chemotherapy compared to adjuvant (postoperative) chemotherapy.
• Radiation therapy is not part of the routine management of osteosarcoma because they are radioresistant.
• Ewing sarcoma is radiosensitive, and radiation therapy is part of the management.
•
• • •
• •
•
• •
• •
• •
Ewing sarcoma can produce the “Codman’s triangle” on x- ray and multiple layers of the periosteal reaction can produce an “onion peel” appearance. Other descriptive terms used to describe Ewing sarcoma is a “moth-eaten” or “permeative” appearance that reflects the destructive nature of the lesion.
Doxorubicin is cardiotoxic. Cisplatin is neurotoxic.
Osteosarcoma has a predilection for areas with high activity for bone cell mitosis.
Foundational point—The neoplastic bone appears to have a lacelike architecture on histology.
Foundational point—There are different histologic types of osteosarcoma. The most common type is the conven­ tional (intramedullary) osteosarcoma. Another type is the telangiectatic (vascular) osteosarcoma, which is mainly a lytic lesion without sclerosis and appears cystic (ie, sometimes confused with an aneurysmal bone cyst).
Foundational point—The tumor in osteosarcoma can elevate the periosteum resulting in the “Codman’s triangle” on x-ray. With further extension of the tumor through the periosteum, the mass may be ossified resulting in the “sun­ burst” appearance on x-ray.
On the CCS, a “bone scan” is available in the practice CCS, but there is no option for “radionuclide bone scan.”
On the CCS, if you type in “biopsy” in the order sheet, the CCS practice software will provide you with a full list ofbody sites to take the biopsy.
On the CCS, remember to “advise patient, cancer diagnosis” once the diagnosis is established.
On the CCS, do not give chemotherapy by yourself. Remem­ ber you are the primary care physician. You need to have an oncology consult.
On the CCS, remember you should be doing most of the workup before ordering an oncology consult.
On the CCS, remember to “advise patient, side effects ofmed­ ication” if it’s decided to give chemotherapy to the patient.
CHAPTER 14 ORTHOPEDICS 209

210 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
CCS\: CARPALTUNNEL SYNDROME CASE INTRODUCTION
Day 1 @ 14\:00 Office
A 50-year-old white female comes to the office because of pain and tingling in her right hand.
Initial Vital Signs\:
Temperature\: 37.0CC (98.6°F) Pulse\: 75 beats/min, regular rhythm Respiratory\: 17/min
Blood pressure\: 125/75 mm Hg Height\: 154.9 cm (61.0 inches) Weight\: 59 kg (130 lb)
BMI\: 24.6 kg/m2
Initial History\:
Reason(s) for visit\: Pain and tingling in her hand.
HPI\:
A 50-year-old computer assistant comes to your office because of pain and tingling in her right hand. The patient states that her symptoms had been intermittent for the last 6 months but has become more persistent over the last 2 weeks. She has a dull aching pain over the ventral aspect of her right wrist with radiation into her forearm. Tingling is felt predominately over her right index finger, middle finger, ring finger, and thumb but sparing the thenar eminence. The patient states that her symp­ toms are exacerbated when she drives, types on the computer, and reads the newspaper. Her symptoms are worse at night and often wakes her up as she has to “flick” her wrist to alleviate her pain. She states that NSAIDs provides no relief. Over the last 2 weeks, she feels more “clumsy” since she has been dropping objects on the ground and has difficulty opening doors.
Review of Systems\:
General\:
HEENT\: Musculoskeletal\: Cardiorespiratory\: Gastrointestinal\: Genitourinary\: Neuropsychiatric\:
Day 1 @ 14\: 04 Physical Examination\:
General appearance\: Skin\: Extremities/Spine\:
Neuro/Psych\:
See HPI Negative See HPI Negative Negative Negative See HPI
Well nourished, well developed; in no apparent distress.
Normal turgor. No lesions. Hair and nails normal.
Tenderness over the ventral
aspect of the right wrist. No joint deformity or warmth. No cyanosis or clubbing. No edema. Peripheral pulses normal. Spine exam
normal.
Mental status normal. Cranial nerve normal. Cerebellar
function normal. Deep tendon reflexes normal. Sensory deficits noted over the palmar and dorsal aspects of the right thumb, index, middle, and ring finger. Normal sensation over the thenar eminence and hypothenar eminence. Motor exam demonstrates weakness in right thumb abduction and opposition. Moderate flattening over the right thenar eminence. Tinel sign-Positive, Phalen test- Positive, Carpal compression test-Positive, Hand elevation test-Positive.
Result\: Patient fitted for wrist splint
Past Medical History\: Past Surgical History\:
Medications\: Allergies\: Vaccinations\: Family History\:
Social History\:
None
Cesarean deliveries at ages 27 and 30.
None
None
Up to date
Father died of a heart attack at age 67. Mother died of COPD complications at age 62. One sister, age 53, has diabetes. One brother, age 48, has hypertension. Does not smoke; drinks one glass of wine with dinner; married; two chil­ dren; computer assistant for 25 years; high school graduate; enjoys reading and karaoke.
First Order Sheet\:
1) Wrist splint, routine
Actions\:
1) Reevaluate case\: In 30 days
Day 31
The patient has arrived for the appointment.

Recorded Vital Signs\: Temperature\: 37.0°C (98.6°F) Pulse\: 75 beats/miri, regular rhythm Respiratory\: 17/min
Blood pressure\: 125/75 mm Hg
Follow-Up History\:
The patient’s wrist feels “better” since the last visit.
Physical Examination\: Extremities/Spine\:
Neuro/Psych\:
Very tender over the ventral aspect of the right wrist. No joint deformity or warmth. No
; cyanosis or clubbing. No edema. Peripheral pulses normal. Spine exam normal.
Mental status normal Cranial
nerve normaL Cerebellar
function normal. Deep tendon re­ flexes normaL Sensory deficits noted over the palmar and dorsal aspects of the right thumb, index, middle, and ring finger. Normal sensation over the thenar eminence and hypothenar eminence. Motor exam demonstrates weakness hi right thumb abduction and opposition. Moderate flattening over the right thenar eminence flattening is observed. Tinel sign- Positive, Phalen test-Positive,
Carpal compression test-Positive, Hand elevation test-Positive.
Result\: Delayed latencies
and slowed conduction velocities across the carpal tunnel.
Result\: Mild to moderate denervation.
Note\: Methylprednisolone injected into the carpal tunnel.
Physical Examination\: Extremities/Spine\:
Neuro/Psych\:
Decrease tenderness over the ventral aspect of the right wrist since the last visit. No joint deformity or warmth. No cyanosis or clubbing. No edema. Peripheral pulses normal. Spine exam normal.
Mental status normal. Cranial nerve normal. Cerebellar
function normal. Deep tendon reflexes normal. Sensory deficits noted over the palmar and dorsal aspects of the right thumb, index, middle, and ring finger. Normal sensation over the thenar eminence and hypothenar eminence. Motor exam demonstrates weakness in right thumb abduction and opposition. Moderate flattening over the right thenar eminence. Tinel sign-Positive, Phalen test-Positive, Carpal compression test-Positive, Hand elevation test- Positive.
Actions\:
1) Reevaluate case\: In 30 days
Day 55
Patient’s Condition—The patient’s condition is not improving, the pain and tingling is getting worse.
Actions\:
1) Stop clock now.
2) Change location from home to office.
Day 55
The patient has arrived for the appointment.
Recorded Vital Signs\: Temperature\: 37.0°C (98.6°F) Pulse\: 75 beats/min, regular rhythm Respiratory\: 17/min.
Blood pressure\: 125/75 mm Hg
This case will end in the next few minutes of “real time.” You may add or delete orders at this time,
then enter a diagnosis on the following screen.
Fourth Order Sheet\:
1) Advise patient, no aspirin
2) Refer patient, occupational therapy Please enter your diagnosis\:
Carpal tunnel syndrome
DISCUSSION\:
Carpal tunnel syndrome (CTS) is a very common entrapment neuropathy involving compression of the median nerve with an unknown etiology.
Risk Factors\:
Hypothyroidism, rheumatoid arthritis, diabetes, amyloidosis, sarcoidosis, obesity, female, pregnancy, trauma, mass lesions.
Second Order Sheet\:
1) Nerve conduction
study, routine
2) Electromyography, routine
Third Order Sheet\:
1) Methylprednisolone,
one time
CHAPTER 14 ORTHOPEDICS 211

212 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Clinical Features\:
The classic presentation is pain and paresthesia along the me­ dian nerve distribution. The sensory branch of the median nerve innervates the palmar side of the thumb, index, middle, and half the ring finger, as well as the dorsal side of the index, middle, and half the ring finger. Even though the median nerve innervates selected areas, patients will complain of pain and paresthesia in all fingers (ie, including the pinky finger). How­ ever, patients should not complain of sensory changes in the thenar eminence because a sensory branch (ie, palmar cutane­ ous branch) of the median nerve branches off proximally and superficially to the flexor retinaculum, thereby passing over the carpal tunnel to directly innervate the thenar eminence. Night­ time symptoms that awaken patients are usually specific for CTS. Flexing or extending the wrist can elicit CTS symptoms such as driving a car, typing, or reading the newspaper. Patients flicking their wrist to alleviate their pain is referred to as the “flick sign.” Patients may also have radiation of their sensory symptoms to the forearm and shoulder. In the later stages of CTS, patients may have weakness and clumsiness in their hands with atrophy seen in the thenar eminence. The motor branch of the median nerve supplies the thenar muscles, and there­ fore, patients will usually have weakness in thumb abduction and opposition. Several hand maneuvers have been described to help with the assessment, but fair short of their reliability. A positive Tinel test involves pain or paresthesia when the me­ dian nerve is percussed. A positive Phalen test involves pain or paresthesia when the dorsums of the hands are placed against each other causing hyperflexion. A positive carpal compres­ sion test involves reproducing the symptoms after firm pressure over the carpal tunnel. A positive hand elevation test involves reproducing the symptoms when the hands are raised over the head for at least 1 minute.
Next Step Summary\:
Step 1) CTS is a clinical diagnosis. Nerve conduction studies (NCS) and electromyography (EMG) are used to confirm the diagnosis. In this particular case, the patient was doing well with wrist splints, but then apparently started to have problems in her second month wearing the splints. If the diagnosis becomes unclear as in this case, testing with NCS and EMG would be the next best step. Suboptimal management would be to order an MRI, unless you suspect a mass lesion.
Step 2) First line treatment begins with wrist splinting, particularly at night. Patients should continue nocturnal splinting for at least 1 to 2 months. If patients continue to be symptomatic during that time, another modality of treatment should be added. In this particular case, methylprednisolone was injected into the carpal tunnel. An alternative to steroid injection is to administer oral steroids (eg, prednisone) for 10 to 14 days. Patients that continue to have sensory symp­
toms, motor dysfunction, and are refractory to conservative treatment should consider surgical carpal tunnel release as the next best step.
Follow-Up\:
Patients should be seen in 4 to 6 weeks after treatment to reas­ sess the patient’s condition as in this case.
Pearls\:
• Bilateral CTS is common.
• Differential diagnosis for CTS may include cervical radicu­ lopathy, flexor carpi radialis tenosynovitis, Raynaud phe­ nomenon, or median nerve compression at the elbow.
• CTS may not always present in the classic median nerve dis­ tribution.
• Anomalous innervations do exist within the hand.
• Patients experiencing sensory changes over the ring and pinky finger should think about ulnar nerve entrapments.
• Obtain a TSH, rheumatoid factor (RF), or HbAlC in patients who you suspect as having hypothyroidism, rheumatoid ar­ thritis, or diabetes, respectively.
• Repetitive hand maneuvers, especially in the workplace en­ vironment have been implicated as a cause for CTS, but the evidence is still inconclusive.
• NSAIDs (including aspirin), diuretics, and vitamin B6 (pyri- doxine) have shown to have no significant benefits when compared to placebo.
• Foundational point—The median nerve originates from roots C6 and C7 (lateral cord) plus roots C8 and T1 (medial cord).
• On the CCS, you cannot order “corticosteroid” but rather the generic or trade names.
• On the CCS, there is no option in the practice CCS to inject the steroid into the carpal tunnel or beneath the flexor reti­ naculum.
• On the CCS, in nonacute, routine office-based CCS cases, you are expected to advance the clock in weeks or months to change the patient’s condition.
• On the CCS, the “Interval Hx” tab has an “Interval/follow up” option that is basically asking how the patient is doing.
• On the CCS, sometimes a “PATIENT UPDATE” may pop up on the screen as you advance the clock. You have to decide if these messages will affect your management plans. In this case, the patient was asked to come back to the office for a reevaluation before the appointment day. Remember, you cannot assess a patient at home; you have to relocate the patient back to a medical setting. If the patient is at home, the practice CCS software will not allow you to do a physical examination.

Otolaryngology Head and Neck
CHAPTER OUTLINE
KeywordsReview............................................2.1.3........ MOUTHANDTHROATDISORDERS......................2.2.0..
I
I
EAR DISORDERS........................................2..1.4....... Acoustic Neuroma..........................................2..1.4........ Meniere's Disease..........................................2..1.5........ Acute Otitis Media..........................................2.1.6........ TympanicMembrane Perforation............................2.1.7....
NOSEAND PARANASALSINUSES......................2.1..8..
Acute Sinusitis..............................................2.1.8......... Chronic Sinusitis............................................2.1.9........
Croup......................................................2.2..0.......... PeritonsillarAbscess........................................2.2.2........ Streptococcal Pharyngitis...................................2.2..2.....
KEYWORDS REVIEW
Chemosis—Swelling of the ocular (bulbar) conjunctiva.
Coryza—Acute rhinitis usually associated with a runny nose.
Endolymph—Fluid within the membranous labyrinth of the ear.
Hyposmia—Decreased sense of smell. Odynophagia—Painful swallowing.
Otalgia—Ear pain.
Perilymph—Fluid that resides in the bony labyrinth.The bony labyrinth surrounds the membranous labyrinth and within the membranous labyrinth is the endolymph. The endolymph is completely separate from the perilymph.
Trismus—Inability to fully open the mouth (lockjaw).
213

214 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
EAR DISORDERS
1 ACOUSTIC NEUROMA
Acoustic neuroma (vestibular schwannoma) is a slow-growing intracranial tumor that is derived from the Schwann cell sheath that invests the vestibulocochlear nerve (cranial nerve VIII). In the majority of cases, the tumor arises from the vestibular division (superior and inferior branches) and rarely from the cochlear division of CN VIII. The tumor resides within the internal auditory canal, and as it grows, it can extend into the posterior fossa to occupy the cerebellopontine angle (CPA).
Clinical Features\:
Acoustic neuromas typically present in patients that are in their fifth or sixth decade of life. Patients will present with a chronic unilateral sensorineural hearing loss, although sud­ den hearing loss can sometimes occur. Other findings include tinnitus and equilibrium disturbances that are not like true spinning vertigo. As the tumor progresses, other cranial nerves can be affected. Impingement of the trigeminal nerve (V) can lead to facial pain, numbness, hypesthesia, or a decrease in ipsilateral corneal reflex (afferent limb). Impingement of the facial nerve (VII) can result in taste disturbances, facial weak­ ness, or a decrease in ipsilateral corneal reflex (efferent limb). Larger tumors can cause cerebellum or brainstem compression resulting in ataxia and secondary hydrocephalus, respectively. On exam, a unilateral sensorineural hearing loss will demon­ strate sound lateralization to the good ear in the Weber test. In the Rinne test, a sensorineural hearing loss will demonstrate air conduction (AC) > bone conduction (BC) in both the good and bad ear.
Next Step\:
Step 1) The best initial test is with a hearing test or audiom­ etry. The most common abnormality is an asymmetrical (left versus right) high-frequency sensorineural hearing loss. In addition, the audiogram will typically demonstrate poor speech discrimination scores that are out ofproportion to the pure tone average.
Step 2) An MRI with gadolinium is the next best step in patients suspected of having an acoustic neuroma with an abnormal hearing test. An MRI can help establish a diagnosis by detecting tumors as small as 1 to 2 mm in diameter. A CT with contrast is an acceptable alternative in patients that have a contraindication to an MRI, but may not be reliable in detecting tumors that are <15 mm.
Step 3) Treatment approach includes surgical removal, stereo­ tactic radiation therapy, or observation with serial imaging and audiometry.
Follow-Up\:
Since acoustic neuromas are slow-growing tumors, patients that elect interventional treatment or observation require regular follow-ups with MRI imaging and audiometry (ie, if hearing preservation is a concern).
Pearls\:
• Approximately 80% to 90% of tumors found within the CPA are acoustic neuromas.
• Other lesions that occupy the CPA include meningiomas and dermoid cysts.
• Although most acoustic neuromas are slow-growing tu­ mors (1-2 mm/yr on imaging), a rapidly growing tumor (>2.5 mm/yr on imaging) is an indication for therapeutic in­ tervention.
• Normal hearing threshold levels should be between 0 and 25 decibels (dB) on the audiogram. Threshold levels greater than 25 dB are considered abnormal.
• Symmetrical hearing impairment is an uncommon finding on the audiogram in patients with acoustic neuroma; however, it does not exclude the diagnosis (ie, infrequently, patients may present with a symmetrical sensorineural hearing loss).
• Bilateral acoustic neuromas can be seen in patients with neu­ rofibromatosis type 2 (NF2). This can be easily remembered by “2 and 2” (ie, NF2 gives you 2 acoustic neuromas).
• Ancillary testing would include an auditory brainstem- evoked response (ABR/AER) that would demonstrate nerve conduction delays (ie, abnormal latencies) on the side of the tumor.
• A unilateral conductive hearing loss will demonstrate sound lateralization to the bad ear in the Weber test. In the Rinne test, a conductive hearing loss will demonstrate bone con­ duction > air conduction in the bad ear and air conduction > bone conduction in the good ear.
• Presbycusis (age-related hearing loss) is a progressive and symmetrical sensorineural hearing loss in elderly people that typically affects the high frequencies (eg, 4000-8000 Hertz), but with relative preservation of the speech discrimination scores.
• Connecting point (pg. 162)—Know that neurofibromatosis type 1 and type 2 are autosomal dominant disorders.
. CJ\: A 77-year-old man with an acoustic neuroma is follow­ ing up with annual MRIs for tumor surveillance. The last 2 years revealed a tumor growth rate of 1.9 mm/yr followed by 2.0 mm/yr. Last week his most recent MRI demonstrated a tumor growth rate of 2.8 mm/yr. The patient is concerned about the tumor progression and is worried about losing his hearing. He is willing to undergo surgery to preserve his hearing. He currently volunteers at the local library, drives his car, walks his dogs to the park, and has an active social life. What do you recommend? Answer\: Age is not a contra­ indication to undergo surgery especially in this man with an active lifestyle. There is evidence of tumor progression, and the patient should undergo surgery with an attempt to pre­ serve his hearing on the affected side.
• On the CCS, “audiometry” is available in the practice CCS.
• On the CCS, remember to counsel your patients once the diagnosis of cancer is made or “advise patient, cancer diag­ nosis,” which is available in the practice CCS.

0 MENIERE'S DISEASE
Meniere’s disease is a disorder ofthe inner ear that is associated with an increase in endolymph resulting in distention of the endolym­ phatic system (endolymphatic hydrops). All patients with Meniere’s disease will demonstrate endolymphatic hydrops on postmortem examination, but not all patients with endolymphatic hydrops will have signs or symptoms of Meniere’s disease. The exact etiology of excessive endolymph in the endolymphatic system is still unknown.
Clinical Features\:
Meniere’s disease can occur at any age but is frequently seen in the fifth decade oflife. Patients will present with true spinning vertigo (rotational vertigo) that is episodic. The onset of vertigo is usually sudden, and it can last from several minutes to several hours and may vary in frequency (ie, sporadic or clusters). The vertiginous attacks can also vary in severity. In some cases, patients may experience a violent drop attack in which the patient falls, but does not lose consciousness. During acute attacks, a horizontal nystag­ mus with a rotary component can be observed. After the attack subsides, patients feel exhausted and may experience nausea and vomiting. A low-frequency fluctuating sensorineural hearing loss is typically seen early in the disease. With each successive vertiginous attack, there appears to be a progressive deterioration in hearing. Later in the course, all frequencies are usually affected and hearing loss is often permanent. A low-tone tinnitus that is described as a “roaring” or “blowing” sound and aural fullness maybecontinuousorintermittentduringthecourseofthedisease.
Next Step\:
Step 1) Meniere’s disease is a clinical diagnosis, although fur­ ther testing is often performed to rule out other conditions that may have symptoms that overlap with Meniere’s disease. Con­ sider the following ancillary testing\:
Labs—BMP (assess electrolytes), TSH (rule out hyperthy­ roidism or hypothyroidism), hemoglobin A1C (rule out diabetes), RPR or VDRL (rule out neurosyphilis), or ANA (rule out autoimmune disease).
Audiometry—Hearing loss may be seen in the low frequen­ cies (early in the disease) or with a mixed presentation (low and high frequencies). Later in the disease, the audiogram appears to flatten out affecting all frequencies.
Electronystagmography (ENG)—ENG, particularly the caloric testing (warm and cool water ear irrigation) may demonstrate a peripheral vestibular dysfunction (ie, ther­ mally induced nystagmus is impaired on the affected side).
MRI—MRI can help rule out CNS abnormalities (eg, tumors, multiple sclerosis).
Step 2) Provide counseling and educate patients about the disease and treatment options.
Step 3) Short-term management\: During an acute vertiginous attack, the patient should rest in bed since most patients will find a position that will minimize the vertigo. In the ED setting, you can provide the patient with an antihistamine (eg, IV/IM diphenhydramine) and an antiemetic (eg, IV/IM promethazine,
prochlorperazine, ondansetron, or metoclopramide) for nausea and vomiting. At home, a patient can be given an anticholiner­ gic agent such as a scopolamine transdermal patch that can be easily applied to the skin behind the ear. Treatment in the short­ term management can be easily remembered by the triple A’s (Antihistamines, Antiemetics, Anticholinergic).
Step 4) Long-term management\: Long-term management is focused on controlling the vertigo since there is no effective therapy for the hearing loss, tinnitus, or aural fullness. Conser­ vative therapy should be attempted first, and then patients can go onto more aggressive approaches for disabling and intrac­ table vertigo. Consider the following approaches\:
Conservative Approaches
Lifestyle modification—Avoid possible triggers such as limiting high salt intake, caffeine, alcohol, nicotine, mono­ sodium glutamate (MSG), or stress.
Medical therapy—When lifestyle changes are not effective, a diuretic (eg, HCTZ) along with pm (as-needed) vestibular suppressants (eg, meclizine, diphenhydramine, diazepam, clonazepam) and antiemetics (eg, ondansetron) can be used.
Vestibular rehabilitation (VRT)—VRT is an exercised- based program to promote central nervous system compen­ sation for inner ear deficits.
Invasive Approaches
• Intratympanicgentamicin
• Labyrinthectomy
• Vestibular nerve section
• Endolymphatic sac decompression • Air pressure pulse generator
Follow-Up\:
Patients may need ongoing care since there is no cure for Meniere’s disease and the disease pattern follows a period of remission that is speckled with periods of exacerbation.
Pearls\:
• Meniere’s disease is usually unilateral, but it can be bilateral in approximately 15% to 20% of cases.
• Loop diuretics (eg, furosemide) should be avoided since it can be ototoxic to the ear.
• In a person with a normal vestibular system, an induced hori­ zontal nystagmus can be obtained by caloric reflex testing. When cold water (or air) is irrigated into the ear, a fast-beating nystag­ mus should move away from the stimulated ear, while warm water (or air) will cause a fast-beating nystagmus to move to­ ward the stimulated ear. The mnemonic COWS (cold-opposite, warm-same) is used to describe this effect, and another way to remember one ofits effects is “cold-contralateral.”
• Vertigo can be seen in other conditions such as benign paroxysmal positional vertigo (vertigo is provoked by head position and lasts <1 minute) and vestibular neuronitis (vertigo is spontaneous and lasts 24-48 hours).
CHAPTER 15 OTOLARYNGOLOGY—HEAD AND NECK 215

216 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• On the CCS, sometimes the diagnosis is clearly evident in the initial history. In other cases, the diagnosis may be ambigu­ ous. In these types of situations, be sure to do appropriate physicals exams and order tests based on the initial history. Remember that an efficient approach will probably give you a higher score, but a thorough approach using your clinical judgment may not necessarily deduct from your score.
• On the CCS, remember to “bridge” your therapy by treating the acute issues (eg, vertiginous attack) along with the long­ term care of the vertigo.
H ACUTEOTITISMEDIA
Acute otitis media (AOM) is an acute bacterial infection of the middle ear. In the majority of cases, a viral upper respiratory tract infection is the triggering event that causes inflammation resulting in obstruction of the eustachian tube, thereby disrupt­ ing the aeration of the middle ear. Fluid accumulates in the middle ear and can become secondarily infected by bacteria. The most common bacteria in descending order are Streptococcus pneumoniae > nontypeable Haemophilus influenzae > Moraxella catarrhalis.
Risk Factors\:
Young age (strong risk factor), family history, pacifier use, absence of breastfeeding, altered immunity, day care, crowded conditions, tobacco smoke exposure, craniofacial abnormalities, fall or winter seasons, and race (Native Americans, Eskimos, Australian aborigine).
Clinical Features\:
AOM can occur at any age, but the peak incidence is between 6 and 18 months of age with a slightly higher incidence in boys than girls1. Clinical manifestations may include fever, otalgia, otorrhea, rubbing of the ear, diminished hearing, or coexistent upper respiratory tract infection. In the young infant, feeding difficulties or irritability may be the presenting feature. Otoscopic examination may reveal several key elements. Consider the following\:
Color—Marked redness of the tympanic membrane (TM) can be seen in AOM, which suggests acute inflammation.
Translucency—The tympanic membrane should normally be translucent, but ifit appears opaque, it indicates fluid in the middle ear. In addition, an air-fluid level may be appreciated on exam. Consider AOM or otitis media with effusion (OME) (ie, noninfected) in patients with an opaque TM.
Position—A bulging tympanic membrane is a key find­ ing in AOM and represents an important marker for acute inflammation.
Mobility—Pneumatic insufflation will demonstrate poor tympanic mobility with a fluid-filled middle ear.
Next Step\:
Step 1) AOM is a clinical diagnosis that is based on signs and symptoms of middle ear inflammation (eg, bulging TM, red
TM not due to crying, otalgia, or fever) plus evidence of middle ear effusion (MME). MME can be observed on otoscopic exam
(eg, air-fluid level, bubbles, or opaque TM), pneumatic otoscopy (>l TM mobility), or tympanometry (no peak or poor compli­
ance at all frequencies).
Step 2) Treat the patient’s pain with analgesics (eg, acetamino­ phen, ibuprofen).
Step 3) The initial management in AOM is to immediately treat with antibiotics or to observe for a period of 48 to 72 hours followed by antibiotics if there is no clinical improvement during that time. Based on the American Academy of Pediatrics (AAP)/American Academy of Family Physicians (AAFP) guidelines, the observation strategy can be offered to children 6 to 23 months of age with nonsevere unilateral AOM (ie, temperature <39°C [102.2°F] and mild ear pain for <48 hours) or in children >24 months of age with nonsevere unilateral or bilateral AOM. If the decision is to pursue antibiot­ ics, there are several choices to consider. The typical duration of antibiotics can vary from 7 to 10 days.
Option 1\: Oral amoxicillin is a first-line agent that is rec­ ommended for most patients.
Option 2\: Amoxicillin-clavulanate for patients with a recent history of amoxicillin use (<30 days), unresponsive to amoxicillin in a patient with recurrent AOM, or patients with coexisting purulent conjunctivitis.
Option 3\: Cefuroxime, ceftriaxone, cefdinir, or cefpodox- ime in patients with a penicillin allergy but without a type 1 hypersensitivity (ie, anaphylaxis, angioedema, broncho- spasm, or urticaria).
Option 4\: Azithromycin, erythromycin, clarithromycin, or clindamycin with a type 1 hypersensitivity to a beta-lactam antibiotic.
Step 4) Administer a pneumococcal conjugate vaccine (PCV13) according to the recommended schedule of 2, 4, 6, and 12-15 months of age. Also, provide an inactivated influenza vaccine for children 6 to 23 months of age or either inactivated or live attenuated influenza vaccine for children >24 months of age. However, do not give a live attenuated influenza vaccine in patients who have asthma, are immunosuppressed, are in close contact with a severely immunocompromised patient, are in concomitant use with aspirin therapy, or have an anaphylactic reaction to chicken, egg, gelatin, gentamicin, or arginine.
Follow-Up\:
There are three important elements in the follow-up care. First, patients that are being observed and that fail to improve or worsen within 48 to 72 hours should begin antibiotics. Second, patients that were given antibiotics from the beginning but fail to improve after 48 to 72 hours should be reevaluated and pos­ sibly consider changing antibiotics to provide broader coverage (eg, amoxicillin-clavulanate or ceftriaxone). If ceftriaxone is given, it is given as IM or IV and up to 3 doses. If the patient responds to the first dose, then the second and third dose is not necessary. Finally, the AAP/AAFP guidelines recommend that patients may be offered tympanostomy tubes for recurrent

AOM, which is defined as >3 episodes within 6 months or >4 episodes within 12 months.
Pearls\:
• It is important to differentiate between AOM and OME (sometimes referred to as serous otitis media), since you do not want to unnecessarily give antibiotics to OME.
• OME and AOM may be part of a disease continuum in which OME precedes and predispose to AOM, or OME may be the result of AOM.
• Although both OME and AOM may demonstrate decreased tympanic mobility on pneumatic otoscopy, the tympanic membrane is usually retracted in OME but is bulging in AOM.
• Do not prescribe prophylactic antibiotics to reduce the fre­ quency of AOM.
• Tympanocentesis (aspiration of the middle ear fluid) for culture is not routinely performed since treatment is with empiric antibiotics. Tympanocentesis may be considered in patients that have failed previous antibiotics.
• Otalgia in a nonverbal child may present as rubbing, tugging, or holding the ear.
• MME can last from several days up to several weeks, despite appropriate antibiotics for a resolved AOM (ie, sterilized effusion). The presence of an effusion does not indicate treatment failure.
• MME can cause hearing loss, but should resolve as the fluid is resorbed. If hearing loss is persistent, consider further evaluation with hearing and language testing.
• Tympanic membrane perforation (secondary to an increase in middle ear pressure) with associated otorrhea can be a complication of AOM. The preferred treatment in a patient with an acute perforation and AOM is with oral amoxicillin (rather than quinolone otic drops) since it covers the most likely pathogen in AOM (S pneumoniae), but it also has coverage against group A streptococci (GAS), which have been associated with a higher rate of TM perfora­ tion in AOM. Ironically, the perforation actually helps to alleviate the middle ear pressure by draining the fluid. The TM perforation will often heal on its own, but if it doesn’t, it may lead to chronic otitis media (COM), which is defined as TM perforation in the setting of recurrent ear infections. COM with otorrhea through the perforation is referred to as chronic suppurative otitis media (CSOM) and it is treated with ciprofloxacin or ofloxacin otic drops.
• On the CCS, along with your clinical exams, remember to use the “Interval/Follow up” to see how the patient is doing in the follow-up visits.
• On the CCS, if the mother is the caretaker for a young infant with AOM, it is important to “counsel family/patient” which is in the practice CCS. This option will essentially educate the mother to care for her child since the child may not be able to understand any type of counseling.
I TYMPANIC MEMBRANE PERFORATION
Tympanic membrane (TM) perforation can be the result of middle ear infections (eg, otitis media), blunt trauma (eg, blow to the ear), penetrating trauma (eg, Q-tips), barotrauma (eg, scuba diving), slag burns (eg, welding), or lightening.
Clinical Features\:
Clinical manifestations typically include an acute onset of ear pain and a conductive hearing loss. In serious cases that include disruption of the inner ear, patients can experience vertigo, nystagmus, tinnitus, and a sensorineural hearing loss.
Next Step\:
Step 1) Tympanic membrane perforation is a clinical diagnosis. On otoscopic examination, a tympanic membrane perforation will be apparent with or without bloody otorrhea (see Figure 15-1 and Color Plate 13).
Step 2) An audiometry should be performed within 24 hours since a conductive hearing loss >35 dB may be associated with ossicular injury. Prompt otolaryngology consultation should be considered in patients with a hearing loss >35 dB, facial nerve paresis/paralysis, significant bleeding, or signs and symptoms of inner ear injury (ie, vertigo, nausea, vomiting, nystagmus, tinnitus, clear otorrhea).
Step 3) Most TM perforations will spontaneously heal. Larger perforations that do not heal completely may be repaired by an otolaryngologist. Otologic care includes educating the patient to avoid water entering the ears and forceful blowing of the nose, analgesics for pain, and antibiotic ear drops (eg, ciprofloxacin otic drops) for patients with contaminated injuries (eg, foreign material in the ear).
Follow-Up\:
Patients should have a follow-up audiometry in 4 weeks along with an evaluation of the tympanic membrane. Patients that
CHAPTER 15 OTOLARYNGOLOGY—HEAD AND NECK 217
FIGURE 15-1 • Acute tympanic membrane perforation. Note the clean- cut margins of the perforation, which is commonly seen in traumatic cases. Also examine the hyperemic tympanic membrane, which suggests an acute process. (Photo Contributor\: Richard A. Chole, MD, PhD. Reproduced with permission from Knoop KJ, et al. TheAtlas ofEmergency Medicine. 3rd ed. McGraw-Hill, www.accessmedicine.com.)

218 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
have persistent hearing loss or an unhealed tympanic mem­ brane should be referred to an otolaryngologist.
Pearls\:
• Patients that have a history of vertigo, nystagmus, tinnitus, and a sensorineural hearing loss are suggestive of an injury to the stapes footplate (footplate subluxation), which repre­ sents an otologic emergency.
• Do not perform ear irrigation in patients with a TM perfora­ tion since you may force more debris into the middle ear.
NOSE AND PARANASAL SINUSES
I ACUTESINUSITIS
Acute sinusitis (or rhinosinusitis) is characterized by inflam­ mation of the mucosal lining of the paranasal sinuses and nasal cavity. Noninfectious causes (eg, allergic rhinitis, polyp obstruction, Wegener s granulomatosis, cystic fibrosis) can result in impaired mucus clearance and obstruction of the sinus ostia. Infectious causes (eg, viruses, bacteria, fungi) can also result in acute sinusitis with viruses as the most common etiology. Bacte­ rial sinusitis can be the result of a secondary infection following a viral infection. Most acute cases of fungal sinusitis occur in immunocompromised patients, patients with poorly controlled diabetes, transplant recipients, and patients receiving chronic steroids.
Clinical Features\:
Differentiating between viral and bacterial sinusitis is difficult based on clinical assessment. Viral sinusitis may present in close proximity to the time of a viral upper respiratory tract infec­ tion and usually symptoms of the sinusitis resolves within 7 to 10 days. Common clinical manifestations of sinusitis include nasal congestion, facial pain or pressure (worse when bending forward), fever, maxillary tooth pain, hyposmia, headache, hali­ tosis, or ear pressure. On examination, there maybe tenderness over the sinuses. Nasal speculum may demonstrate mucosal edema, discolored rhinorrhea, purulent discharge, or polyps. Symptom duration can be classified as acute (<4 weeks), sub­ acute (4 to 12 weeks), or chronic (>12 weeks).
Next Step\:
Step 1) The diagnosis of uncomplicated acute sinusitis is made on clinical assessment. Imaging and cultures are not routinely performed in the initial evaluation of an uncomplicated case of acute sinusitis unless there is a reason to believe that there are complications (ie, orbital or intracranial extension of the infection).
Step 2) The best initial treatment approach in patients with mild symptoms is to recommend supportive care such as analgesics,
• Injury to the facial nerve will typically present with facial weakness and may include injury to the chorda tympani, a branch of the facial nerve that runs through the middle ear and is responsible for carrying sensory afferent fibers that provide taste sensation from the ipsilateral anterior two- thirds of the tongue.
• On the CCS, if a consult is needed, remember you are asking a consult from the point of view of a primary care physician.
nasal saline (sterile) irrigation, proper fluid intake, and intra­ nasal glucocorticoids (eg, mometasone) for patients with a history of allergic rhinitis. As mentioned before, uncompli­ cated viral sinusitis will resolve within 7 to 10 days and does not require antibiotics. Empiric antibiotics are indicated in patients with bacterial sinusitis. The key features to consider for a bacterial etiology include severe symptoms (eg, fever >39°C or >102.2°F, purulent discharge), persistent symptoms >10 days, or the patient was clinically improving following a viral upper respiratory tract infection and then turns the corner into an apparent worsening. Consider the following antibiotics for bacterial sinusitis\:
Option 1\: Oral amoxicillin for 10 to 14 days is recommended as the initial therapy for most patients.
Option 2\: Doxycycline or a fluoroquinolone (levofloxacin or moxifloxacin) can be given to penicillin allergic patients.
Option 3\: High-dose amoxicillin-clavulanate or a fluoro­ quinolone (levofloxacin or moxifloxacin) can be given to patients with a recent history of antibiotic therapy within the past 4 weeks.
Follow-Up\:
Patients receiving antibiotic therapy for a bacterial sinus­ itis should respond to treatment after 3 to 5 days of initiating therapy. If there is no response to the initial treatment, consider changing to a different class of empiric antibiotics that will provide broader coverage (eg, amoxicillin-clavulanate, levoflox­ acin, or moxifloxacin). If patients respond from the change in antibiotics, then complete a 7- to 10-day course. If there is no improvement, consider obtaining cultures to redirect antibiotic therapy or order a CT scan.
Pearls\:
• The most common causes of community-acquired bacte­ rial sinusitis are Streptococcus pneumoniae, nontypable Hae­ mophilus influenzae, and Moraxella catarrhalis.
• The most common causes of viral sinusitis are rhinovirus, influenza virus, and parainfluenza virus.
• Mucormycosis (zygomycosis) is a fungal infection in the order of Mucorales that can infect the rhino-orbital-cerebral areas leading to a life-threatening condition.

Thick purulent nasal discharge is suggestive of a bacterial infection, but it is not completely specific to a bacterial infec­ tion since it can sometimes occur in early viral infections.
Cultures can be obtained by endoscopy-guided middle meatal cultures or by direct antral puncture (sinus aspirate culture).
Obtaining cultures of purulent nasal secretions or nasal swabs of the nasal cavity is of limited value because of con­ tamination by the normal bacterial flora.
Although endoscopy-directed cultures can be contaminated by nasal flora, it is more commonly performed than direct sinus puncture because of the pain and discomfort associ­ ated with the sinus tap.
Obtaining cultures is the most accurate test to determine the underlying bacterial pathogen, which can help guide antimicrobial therapy.
Obtaining viral cultures is unnecessary.
Transillumination of the sinuses is of limited value.
A sinus CT scan or plain sinus x-ray is not routinely recom­ mended in the initial evaluation of an uncomplicated case of acute sinusitis.
A noncontrast sinus CT scan is the preferred imaging modal­ ity over plain sinus radiographs in cases of treatment failure.
Typical findings seen in acute sinusitis are air-fluid levels and mucosal edema on sinus CT scan.
A contrast head CT scan is indicated when complications are suspected such as cavernous sinus thrombosis, orbital cel­ lulitis, osteomyelitis of the frontal bone (Pott puffy tumor), or brain abscess.
Use sterile water for nasal irrigation since there have been reports of an amoeba infection from using tap water resulting in amebic encephalitis.
Mucolytics (eg, guaifenesin) and antihistamines are not rou­ tinely recommended for acute sinusitis.
Topical decongestants can be used for nasal congestion, but should not be used for more than 3 days since they can cause rebound congestion.
CJ\: A 35-year-old man with a history of sinusitis presents to the office with nasal congestion, runny nose, and a headache for the past 6 days. You recommend supportive therapy and ask that he come back in 1 week for a reassessment. The patient comes back in 4 days and complains of worsening headache, fever, diplopia, and right-sided eye swelling that was not there 4 days ago. On exam, the patient appears more distracted from the last visit. You note chemosis, ptosis, and lateral gaze palsy (ie, CN VI dysfunction). You suspect cavernous sinus thrombosis, so you decide to order an urgent head CT with contrast. The CT findings demonstrate a filling defect in the cavernous sinus with thickening of the vessel wall. What is your next best initial step? Answer\: Prompt administration of broad-spectrum antibiotics should be given to patients with cavernous sinus thrombosis. Ideally, cultures should be obtained prior to antibiotics, but treatment should not be delayed. Empiric antibiotics should
include coverage against gram-positives with IV nafcillin (or IV oxacillin). If patients fail to respond to penicillin or MRSA is suspected, replace with IV vancomycin. Empiric antibiotics should also include broad gram-negative cover­ age with IV ceftriaxone (or IV cefepime). IV metronidazole should also be added to cover anaerobes if a sinus or dental infection is suspected. IV antibiotics are recommended for a minimum of 3 weeks.
• Connecting point (pg. 156)—An expanding intracranial aneurysm can result in compression of the cavernous sinus resulting in prodromal signs and symptoms prior to a subarachnoid hemorrhage.
• On the CCS, “Nasal C&S” is available in the practice CCS.
• On the CCS, remember to order “Advise patient, no smoking” if the patient smokes.
• On the CCS, ifyou’re treating bacterial sinusitis with antibiot­ ics, remember to set the antibiotic therapy in the continuous mode of frequency rather than a one-time/bolus. The “con­ tinuous” option takes into account periodic administration (eg, q6 hours).
B CHRONICSINUSITIS
Chronic sinusitis (or rhinosinusitis) is an inflammatory condition of the paranasal sinuses and nasal cavity resulting in symp­ toms lasting >12 weeks. Most patients have undergone multiple treatments and unfortunately have suffered significant morbidity.
Clinical Features\:
The clinical manifestations of chronic sinusitis can vary. How­ ever, fever is usually absent in most patients. The following features are suggestive of chronic sinusitis\:
1) Mucopurulentdrainage
2) Nasalobstruction/congestion 3) Facialpain/fullness
4) Hyposmia
Next Step\:
Step 1) The diagnosis of chronic sinusitis is based on TWO of the FOUR suggestive features in the preceding list plus objective evidenceofmucosalinflammation.whichcanbeobtainedbynasal endoscopy or CT imaging.
Nasal endoscopy—Findings may reveal mucosal edema, purulent discharge, or polyps.
Noncontrast sinus CT—Findings may reveal sinus opacification or mucoperiosteal thickening. Air-fluid levels are an uncommon finding in chronic sinusitis. Anatomic detail may also reveal sinus ostial obstruc­ tion, which may help guide future sinus surgery, if warranted.
Step 2) The goal oftherapy is to control the inflammation, facili­ tate sinus drainage, and appropriately treat infections that may
CHAPTER 15 OTOLARYNGOLOGY—HEAD AND NECK 219

220 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
be present. In essence, this requires a multi-interventional approach that may require\:
• Nasal saline (sterile) irrigation
• Intranasal glucocorticoids (eg, fluticasone, triamcinolone)
• Oral glucocorticoids (eg, prednisone)
• Oral antibiotics of 2 to 4 weeks duration (preferably culture- directed)
Step 3) When symptoms continue to persist despite maximal medical therapy, the patient should be referred to an otolaryn­ gologist for functional endoscopic sinus surgery (FESS). FESS attempts to restore sinus health by improving drainage and facilitating normal mucociliary flow. FESS does not control the underlying inflammation; therefore, medical management needs to be maintained following surgery.
Step 4) Counsel patients with chronic sinusitis since their quality of life can be reduced if the condition is left untreated. Also, advise patients not to smoke since it can increase their risk of sinusitis.
Follow-Up\:
Patients often require regular follow-ups to reassess the patient’s condition with the goal of improving quality of life since most cases of chronic sinusitis cannot be cured.
Pearls\:
• Allergic fungal rhinosinusitis can cause chronic fungal si­ nusitis, which is typically seen in immunocompetent pa­ tients that have an IgE-mediated allergy to a fungus. Patients can have nasal polyps, and they tend to have a very thick inspissated mucus (allergic mucin), which is usually identi­ fied at the time of surgery. Diagnosis is made by culturing the
MOUTH ANDTHROAT DISORDERS
0 CROUP
Croup, also referred to as laryngotracheitis or laryngotra- cheobronchitis (ie, if the illness extends to the bronchi) is a respiratory illness that is typically caused by viruses. The most common type of virus is the parainfluenza virus type 1, which is responsible for most of the fall and winter epidemics. Other viruses that can cause croup include parainfluenza type 2 and type 3, RSV, influenza, rhinovi- rus, adenovirus, human bocavirus, and measles. Once the virus infects the nasal or pharyngeal mucosa, the infection progresses to the larynx and trachea. Inflammation can cause subglottic narrowing of the airway producing the classic “steeple sign” on x-ray.
allergic mucin, which demonstrates fungal hyphae. Treatment involves surgical removal of the impacted mucus followed by oral and topical glucocorticoids.
• A 10- to 14-day course of antibiotics is typically given to patients with chronic sinusitis if a bacterial infection is sus­ pected of causing an acute exacerbation.
• Patients are considered to have recurrent acute rhinosinusitis when there are >4 episodes per year of acute bacterial sinus­ itis without clinical manifestations of rhinosinusitis between the episodes.
• Allergy skin testing can be considered in patients with chronic sinusitis or recurrent acute rhinosinusitis.
• Nasal polyps can recur after surgical removal.
• Oral glucocorticoids can not only reduce inflammation, but also reduce the size of nasal polyps.
• Patients that have a combination of asthma, chronic rhino­ sinusitis with nasal polyposis, and sensitivity to aspirin or other COX-1 inhibiting NSAID (eg, ibuprofen, naproxen) have a condition referred to as aspirin exacerbated re­ spiratory disease (AERD) or Samter’s triad. Following ingestion of aspirin or COX-1 inhibiting NSAID, patients can develop ocular symptoms (eg, watery eyes), nasal symptoms (eg, nasal congestion), flushing, chest tightness, wheezing, cough, or headaches. Patients should avoid COX-1 inhibiting NSAIDS or undergo aspirin desensi­ tization followed by aspirin therapy. Once desensitized, patients can ingest other COX-1 inhibiting NSAIDS, but patients must continue to take a daily aspirin or NSAID to maintain desensitization.
• On the CCS, ifyou decide to consult an otorhinolaryngolo- gist, remember to implement a course of action before the consultant is able to see your patient.
Clinical Features\:
Croup is typically seen in children that are between 6 months and 3 years old. The clinical onset of croup is usually gradual. Patients may initially present with a prodrome of a low-grade fever, cough, sore throat, nasal congestion, or rhinorrhea. Within 1 to 2 days, patients will typically progress to the clas­ sic manifestations of croup, which include a “barking (brassy) cough,” hoarseness, and inspiratory stridor. On exam, two important features to be concerned about are chest wall re­ tractions and stridor at rest, which indicates significant upper airway obstruction. Keep in mind that children have smaller airways compared to adults, and therefore children can rapidly deteriorate from an airway obstruction.
Next Step\:
Step 1) The best initial step is to approach the patient carefully since any anxiety can worsen the airway obstruction. Keep the child calm and comfortable by having him or her sit on the caretaker’s lap.

Step 2) The diagnosis of croup is made on clinical assessment. Laboratory tests and imaging is usually unnecessary in the initial evaluation.
Step 3) Treatment of croup depends on the severity of the con­ dition and the clinical setting (ie, ED, home, office). Consider the following management approach\:
Mild Disease
• Patients with mild disease may have a brassy cough and hoarseness, but without stridor at rest.
• Patients managed at home may only require supportive care such as humidified air (mist therapy), antipyretics, and proper fluid intake.
• Patients seen in the ED or office may recommend supportive care as well as providing a single dose of oral dexamethasone.
Moderate—Severe Disease
• Patients with moderate to severe disease may appear more anxious, exhibit stridor at rest, or have chest wall retractions.
• Monitor patients with a pulse oximetry, and if hypoxemic (02 saturation <92% on room air), then provide humidified oxygen. If nonhypoxemic, then provided humidified air.
• Provide nebulized epinephrine to improve airway edema.
• Provide glucocorticoids in oral, intravenous, or intramuscu­ lar routes of administration.
• Dexamethasone is commonly used for croup and is available in the PO, IV, and IM forms. Inhaled steroids given as neb­ ulized budesonide can be used as an alternative in patients who are vomiting.
Disposition/Follow-Up\:
Patients should be observed in the ED for at least 3 hours after the last nebulized epinephrine since the effects of the epinephrine last less than 2 hours and patients can experience a “rebound phenomenon” where the patient appears to be worsening. Patients that fail to improve despite medical therapy (eg, more than 2 treatments of epinephrine) should be admitted to the hos­ pital. Soon after discharge from the hospital, all patients should be seen by their primary care physician for a follow-up visit.
Pearls\:
• Croup is usually a self-limited condition that resolves within 3 to 7 days.
• A biphasic inspiratory and expiratory stridor can be heard if there is a critically fixed airway obstruction.
• Leukocytosis can sometimes be seen in patients with croup. On the differentials, a lymphocytosis is suggestive of a viral cause, while elevated band neutrophils may indicate a bacte­ rial etiology for the croup.
• All routes of administration (ie, PO, IV, IM) of dexametha­ sone to treat croup are equally effective. Inhaled budesonide has also been shown to be as effective as oral or parenteral dexamethasone.
• Patients with mild, moderate, or severe symptoms of croup all benefit from the use of steroids.
• The clinical efficacy of mist therapy (humidified air) is still unproven; however, the humidified air may provide a sense of comfort and may prevent the airway secretions from drying out.
• Mist tents (croup tents) should be avoided since they can in­ crease the anxiety of the child.
• Nebulized epinephrine can be given as either racemic epineph­ rine (which has both D- and L-isomers) or as L-epinephrine. Either type is acceptable since there is no significant difference in the response to treatment between the two formulas.
• Decongestants and antitussives are not recommended because of their unproven benefit in the management of croup.
• Patients in the hospital that require ongoing epinephrine treatments should have cardiac monitoring.
• Spasmodic croup (recurrent croup) is characterized by crou­ plike symptoms but without fever, occurs at night, has an abrupt onset, abrupt cessation, short duration, and recurrent episodes, and patients usually feel okay between the attacks. The etiology is still unclear, but it is thought that a virus may still trigger the event or there may be an allergic mechanism in patients with atopic diseases. Treatment is usually focused on comforting the child with humidified air. Nebulized epi­ nephrine and corticosteroids are generally not indicated.
• Impending respiratory failure can be a complication of croup. The child may appear cyanotic, with decreased con­ sciousness, decreased chest wall retractions, and stridor at rest. Patients should be prepared for an emergent intubation.
• Patients with croup may demonstrate a distended hypophar- ynx during inspiration on a lateral neck x-ray. On posterior- anterior chest x-ray, the subglottic narrowing (steeple sign) may not always be seen and is not pathognomonic for croup since it can also be seen in bacterial tracheitis.
• CJ\: A 3-year-old boy presents to the ED with stridor, fever, brassy cough, and hoarseness. On exam, the patient ap­ pears toxic, with no drooling, and the patient prefers to lie flat during the evaluation. You decide to administer nebu­ lized epinephrine and a single dose of dexamethasone. The patient does not respond to the second treatment of nebu­ lized epinephrine. You decide to order a lateral neck and AP x-ray that demonstrates subglottic narrowing and irregular tracheal margins. Your working diagnosis has changed to bacterial tracheitis, and you decide to consult an otolaryn­ gologist. An otolaryngologist sees your patient and decides to go to the operating room with the patient for sedation, intubation, and bronchoscopy. Endoscopy reveals purulent secretions. Specimens for Gram’s stain and cultures (aerobic and anaerobic) are obtained from suctioning of the tracheal membranes. Your next step is to treat with antibiotics, and the patient does not have any known drug allergies. What is the initial choice of antibiotics pending the results of the cul­ tures? Answer\: Bacterial tracheitis (bacterial croup) can be a primaryorsecondaryinfection(usuallyafteraviralinfection).
CHAPTER 15 OTOLARYNGOLOGY—HEAD AND NECK 221

222 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
The most common cause of bacterial tracheitis is from Staphylococcus aureus. Clindamycin plus a third-generation cephalosporin (eg, ceftriaxone, cefotaxime) or clindamy­ cin plus ampicillin-sulbactam are acceptable choices. In areas of increasing MRSA, vancomycin can be substituted for clindamycin.
• Foundational point—Epinephrine works by causing vaso­ constriction of the precapillary arterioles, which leads to a decrease in capillary hydrostatic pressure causing fluid re­ sorption with improvement of the mucosal edema.
• On the CCS, be cognizant about transferring the patient to the appropriate setting (ie, if the patient becomes intubated, be sure to transfer to the ICU for continued monitoring).
• On the CCS, “comfort patient” is available in the practice CCS.
• On the CCS, suboptimal management include delaying treatment in patients with croup that are in respiratory dis­ tress since neither laboratory tests nor imaging are necessary to make the diagnosis.
• On the CCS, keep in mind that if the patient has poor oral intake, consider other routes of administration of a medica­ tion other than the oral form.
I PERITONSILLARABSCESS
Peritonsillar abscess (PTA), also referred to as quinsy, is a poly­ microbial accumulation of pus in the peritonsillar space. It is thought that the development of a PTA begins with an infection (ie, tonsillitis or pharyngitis) that progresses into a peritonsillar cellulitis and then into an abscess. In the absence of a preceding infection, obstruction of the Weber glands (ie, salivary glands that clear the tonsillar area ofdebris) resulting in a local cellulitis have been implicated in the formation of a PTA.
Clinical Features\:
Peritonsillar abscess commonly occurs in older children and adolescent, although it can occur at any age. Patients may pres­ ent with a fever, unilateral sore throat for several days, trismus, muffled voice (“hot potato”), odynophagia, drooling (ie, diffi­ culty swallowing their saliva), or ipsilateral referred otalgia (ie, secondary from neck swelling). On exam, findings may reveal a medial and inferior displacement of the tonsil, deviated uvula away from the involved side, and an edematous soft palate.
Next Step\:
Step 1) The diagnosis of peritonsillar abscess is usually made on clinical assessment. Laboratory tests and imaging are usu­ ally unnecessary in patients that have displacement of the tonsil with a deviated uvula.
Step 2) Treatment of a PTA involves supportive care (eg, an­ tipyretics, analgesics, adequate hydration), antibiotics, and drainage of the abscess via needle aspiration, incision and drainage, or tonsillectomy. Cultures and gram staining of the abscess fluid should be obtained at the time of drainage fol­ lowed by empiric antibiotics that can be altered pending the
results of the cultures and sensitivities. Acceptable choices of empiric antibiotics include either IV clindamycin or IV ampi­ cillin-sulbactam. If the patient is able to tolerate oral intake, either oral clindamycin or oral amoxicillin-clavulanate can be given for a 14-day course.
Disposition\:
If the patient is discharged from the ED, arrange follow-up care within 24 hours of an aspiration to reassess any reaccumula­ tion of pus and to assess the patient’s well-being since further testing (ie, CT with contrast) or drainage procedures might be necessary.
Pearls\:
• Bilateral peritonsillar abscess is uncommon.
• Drooling or pooling of saliva is also seen in epiglottitis.
• CT with IV contrast will reveal a hypodense fluid collection with ring enhancement in patients with a PTA. CT may also reveal spread of infection into other deep neck spaces.
• A CT with IV contrast is a reasonable option in children that lack cooperation or who present with trismus that prevents an adequate intraoral examination.
• When comparing needle aspiration to I&D, there is no dif­ ference in outcome.
• Tonsillectomy is typically performed in patients with recur­ rent infections (eg, tonsillitis, pharyngitis, PTA) or upper airway obstructions (eg, sleep apnea).
• Although most PTAs are polymicrobial, the most common bacteria isolated is Group A Streptococcus (GAS). Other bacteria that are present include anaerobes, Staphylococcus aureus, and Haemophilus species.
• CJ\: A 10-year-old boy presents to the ED with fever, right­ sided sore throat for 7 days, drooling, and right-sided ear pain. On intraoral exam, there is marked erythema of the soft palate, but without uvula deviation or displacement of the tonsils. What is your next step? Answer\: It is often diffi­ cult to differentiate a peritonsillar cellulitis from a peritonsil­ lar abscess. A peritonsillar cellulitis will not form a discrete collection ofpus, and you won’t be able to palpate a fluctuant mass. The patient can be admitted to the hospital for a 24- hour treatment of IV antibiotics. Patients with a peritonsillar cellulitis will usually respond to antibiotics, but antibiotics alone are generally not sufficient to treat a true abscess.
• On the CCS, “ampicillin-sulbactam,” “amoxicillin-clavulanate,” and “clindamycin” are available in the practice CCS.
• On the CCS, the initial vital signs in every CCS case will give you a clue whether a case might be acute or non-life threatening.
1 STREPTOCOCCAL PHARYNGITIS
Streptococcus pyogenes (Group A P-hemolytic Streptococcus, GAS) is the most common cause of bacterial pharyngitis, however, viruses are still the more common cause of acute pharyngitis.

Clinical Features\:
GAS is primarily seen in the age group of 5 to 15 years old and uncommonly seen in children <3 years old. The peak incidence of GAS typically occurs during the winter and early spring seasons. It should be noted that there is no single sign or symptom that can reliably predict the etiologic agent (ie, virus vs bacteria). However, the following features of GAS may in­ clude an abrupt clinical onset, fever, sore throat, lack of cough, nausea, vomiting, abdominal pain, or headache. On exam, there may be tonsillar exudates, tender anterior cervical lymphadenopathy, or palatal petechiae (petechiae can also be seen in viral infections).
Next Step\:
Step 1) The diagnostic approach for GAS pharyngitis is not definitively established. However, the diagnostic tests used to identify GAS are a rapid antigen detection test (RADT) or a throat culture. Both tests require specimens by swabbing the back of the throat. The throat culture is considered the gold standard, but results can take 24 to 48 hours, which would be more problematic for a culture follow-up in the ED setting. RADT can provide results in a shorter time and permit earlier administration of antibiotics if warranted. If the RADT result is positive for GAS, then proceed with antibiotic therapy. If the RADT result is negative for GAS, then proceed with a throat culture for children and adolescents (adults do not need a follow-up culture given the lower prevalence of GAS in this age bracket).
Step 2) Treatment of GAS pharyngitis is with antibiotics. Antibiotics can reduce the symptom duration, transmission, and complications (ie, acute rheumatic fever). Consider the following antibiotics\:
Option 1\: Oral penicillin V X 10 days Option 2\: Oral amoxicillin x 10 days
Option 3\: Single IM dose of penicillin G benzathine for potentially noncompliant patients.
Option 4\: Macrolides can be given to patients with allergies to beta-lactam antibiotics (ie, penicillin, cephalosporins). Consider oral erythromycin or clarithromycin for 10 days or azithromycin for 5 days.
Follow-Up\:
Clinical improvement should be seen within 3 days after initiat­ ing antibiotics. Patients that fail to respond to antibiotics should have a follow-up visit for further investigation.
Pearls\:
• Suppurative complications of GAS pharyngitis include mas­ toiditis, peritonsillar abscess, sinusitis, and otitis media.
• Nonsuppurative complications of GAS pharyngitis include post streptococcal glomerulonephritis and acute rheumatic fever.
• GAS pharyngitis is a self-limiting condition even without the use of antibiotic therapy. Symptoms typically resolve within 5 days, but antibiotics will hasten the recovery.
• Initiating antibiotic therapy for GAS pharyngitis can prevent acute rheumatic fever, but there is lack of evidence that it can prevent poststreptococcal glomerulonephritis.
• Group C and group G streptococci can also cause pharyngitis, but it does not cause acute rheumatic fever.
• Do not initiate empiric antibiotics prior to collecting your specimens since giving antibiotics before your collection may give you a false negative result.
• Clinical features that may indicate a viral pharyngitis include coryzal symptoms (rhinovirus, coronavirus), conjunctivitis (adenovirus), splenomegaly (EBV), ulcerations and vesicula- tions (HSV, Coxsackie A virus which can cause herpangina), stomatitis (HSV), or cough and myalgias (influenza).
• Continuous antimicrobial prophylaxis (penicillin V, penicillin G benzathine, or sulfadiazine) should be given to patients with a history of rheumatic fever or evidence of rheumatic heart disease (eg, rheumatic mitral stenosis) to prevent recurrent rheumatic fever (ie, secondary prevention).
• RADT has a high specificity (>95%) but variable sensitivities (70%-90%).
• Antistreptolysin O (ASO) streptococcal antibodies typically peak between the fourth and fifth weeks following a strepto­ coccal pharyngitis. The ASO titers then begin to decline over the next several months.
• Serologic testing with the ASO titers may be useful when considering streptococcal sequelae (ie, rheumatic fever) but not in the evaluation of acute pharyngitis.
• Foundational point—Streptococcus pyogenes is a group A, beta-hemolytic, catalase-negative, bacitracin sensitive, fac­ ultative, gram-positive coccus that grows in chains. This organism is involved in skin infections (eg, necrotizing fasciitis, cellulitis, erysipelas, impetigo), streptococcal phar­ yngitis, scarlet fever, streptococcal toxic shock syndrome, rheumatic fever (type II hypersensitivity), and poststrepto­ coccal glomerulonephritis (type III hypersensitivity).
• Foundational point—Microbiologic features of Streptococcus pyogenes include streptokinase (converts plasminogen to plasmin, which then degrades fibrin into fragments), hyaluronidase (hydrolyzes hyaluronic acid), DNAase
(hydrolyzes DNA), NADase (hydrolyzes NAD), streptoly­ sin S (lyses RBCs, nonantigenic, 02 stable), streptolysin O (lyses RBCs, antigenic, 02 labile), M-protein (helps evade phagocytosis, but antibodies can bind to M-protein and aid in opsonization), lipoteichoic acid (component of cell wall), protein F (adherence factor), and pyrogenic exotoxins (also called erythrogenic toxins).
• Foundational point—Similar to staphylococcal toxins (ie, TSST-1), pyrogenic exotoxins can act as superantigens by binding to both T cell receptors and MHC class II molecules on the antigen presenting cell and causing T cell proliferation and secretion of cytokines (IL-1, IL-6, IFN-gamma, TNF- alpha, and TNF-beta).
• Foundational point—Streptococcus pyogenes (pus-produc­ ing) and group C and G streptococci can produce strepto­ lysin O, which is a membrane-damaging extracellular toxin.
CHAPTER 15 OTOLARYNGOLOGY—HEAD AND NECK 223

224 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
The O stands for oxygen-labile,which is inactivated by oxygen butreactivatedbythiolcompounds.StreptolysinOcandestroy red blood cells, hence {3-hemolytic. On blood agar, a clear zone can be seen when Streptococcus pyogenes is cultured on the plate. Since streptolysin O is antigenic, antibodies will develop, hence, ASO antibodies.
• Connecting point (pg. 258)—Know the other types of streptococci.
• Connecting point (pgs. 8, 9)—Know the other types of hy­ persensitivity reactions.
• Connecting point (pg. 12)—Remember that if a test has a high specificity, it is most likely going to test negative for a disease with fewer false positive results. Therefore, if a test with high specificity comes back positive for a condition, it helps to establish a diagnosis. However, a negative test result does not rule out the condition.
• Connecting point (pg. 30)—Patients that have rheumatic mitral stenosis should receive prophylactic antibiotics to prevent rheumatic fever.
• CJ\: An 18-year-old male comes to your office, and you strongly suspect streptococcal pharyngitis. You decide to do a throat culture and initiate empiric amoxicillin while the results of the culture are pending. After 2 days of antibiotic treatment, the patient notices a maculopapular rash over the trunk of his body. What does your clinical suspicion tell you? Answer\: Patients with infectious mononucleosis can develop a rash following administration of amoxicillin or ampicillin. Obtaining a “Monospot” test would show reactive hetero- phile antibodies, which would be consistent with an EBV infection.
• On the CCS, keep a targeted physical exam in this type of case. An example in this case would be to do general appear­ ance, lymph nodes, HEENT, chest, heart, and abdomen.
• On the CCS, “rapid strep screen” and “throat culture, Streptococcus” are both available in the practice CCS.

Psychiatry
CHAPTER OUTLINE
Keywords Review............................................2.2.5........ Conversion Disorder... 233
I
I
I
I I
ANXIETY DISORDERS....................................2.2.6..... Somatization Disorder. 233 PanicDisorder..............................................2.2..6........ Hypochondriasis....... .234
General Anxiety Disorder...................•................2..2.7.
TRAUMA-ANDSTRESSOR-RELATEDDISORDERS.....2.28 PosttraumaticStress Disorder................................2.2.8..... Acute Stress Disorder.......................................2..2.9.......
OBSESSIVE-COMPULSIVE AND RELATED DISORDERS..............................................2.2.9......... Obsessive-compulsive Disorder..............................2.2.9.... Body Dysmorphic Disorder..................................2.3.0......
DISSOCIATIVE DISORDERS.............................2..3.1....
SOMATIC SYMPTOMS AND RELATEDDISORDERS. . . . . .232 Factitious Disorder Imposed on Self.........................2..3.2... Factitious Disorder Imposed on Another......................2.3.2..
Pain Disorder........... .234 PERSONALITY DISORDERS. .235
NEURODEVELOPMENTAL DISORDERS.... ,237 Autism................................................ .237 Tourette's Disorder............................. 239 Persistent (Chronic) Motor or Vocal Tic Disorder. .239 Provisional Tic Disorder............................. .240
CLINICAL ATTENTION.......................... 240 Malingering.......................................... .240
KEYWORDS REVIEW
Circumstantial speech—A roundabout discussion, but eventually gets back to the original point.
Coprolalia—Obscene words. Copropraxia—Obscene gestures.
Countertransference—A clinician's counter emotional reac­ tion (usually unaware) to a patient's response when the
patient unconsciously transfers his or her feelings onto the clinician, usually based on unresolved childhood conflicts (eg, resentment toward parents).
Echolalia—Repeating a word or phrase just spoken by an­ other person.
Echopraxia—Mimicking movements of another person.
225

226 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Fugue—In Latin, it refers to "flight." As seen in dissociative fugue, a person takes flight to another location (similar to a "fugitive").
Global Assessment of Functioning (GAF)—GAF is part of the Axis V in the evaluation of patients and is given a score from 1 to 100. For a general guideline, a score of 1 represents danger to themselves or others, a score of 50 represents severe impairment in functioning, and a score of 100 rep­ resents superior functioning. (DSM-5 Alert\: The multiaxial system is removed from the DSM-5 and has transitioned into a nonaxial documentation of diagnosis [formerly Axes I, II, and III] with separate notations for psychological and contextual factors [formerly Axis IV] and disability [formerly Axis V]. The GAF is removed from DSM-5 and is replaced with WHODAS for disability assessment. For board purposes, GAF is retained in this section because the transition to the DSM-5 might not have been implemented on the large pool of exam questions).
ANXIETY DISORDERS
Anxiety disorders are serious mental illnesses that can be char­ acterized by emotions of fear and anxiety.
DSM-5 Alert\: Obsessive-compulsive disorder (OCD), posttrau- matic stress disorder (PTSD), and acute stress disorder are no longer part of anxiety disorders.
I PANICDISORDER
Panic disorder is an anxiety disorder than can be characterized by recurrent, spontaneous panic attacks.
DSM-5 Alert\: Agoraphobia is now a separate codable diagnosis (ie, agoraphobia has diagnostic criteria and can occur irre­ spective of panic disorder). According to the DSM-5 criteria, diagnosis of agoraphobia can be made if (1) there is marked fear or anxiety about >2 of the 5 situations (public trans­ portation, open spaces [eg, farmers’ market], closed spaces [eg, theater], being in a crowd, being outside of the home alone), (2) fears or avoids situations because of thoughts that escape would be difficult or help would not be available in the event of developing symptoms, (3) fear or anxiety is always provoked from agoraphobic situations, (4) agoraphobic situations are avoided, tolerated with intense fear or anxiety, or require a companion, (5) fear or anxiety is out of propor­ tion to the actual danger, (6) emotions (eg, fear, anxiety) or behavior (eg, avoidance) is >6 months, (7) the disturbance impairs functioning in important areas (eg, work, school, relationships), (8) emotions (eg, fear, anxiety) or behavior
Hyperlexia—The precocious ability to read well without prior training. As seen in autism, individuals may read well, but with little comprehension.
Ideas of reference—The perception that the world is "refer­ encing" the patient through special messages. Delusions of reference are similar in content, but the false beliefs are held with greater conviction.
Neologisms—Creating new words.
Palilalia—Repeating their own word or phrase.
Peregrinate—Travel
Stereotypy—Repetition of a meaningless act.
Tangential speech—The discussion is off-course and never gets back to the original point.
Trichotillomania—A compulsive urge to pull out one's own hair. Word salad—Words thrown together that make no sense.
(eg, avoidance) is clearly excessive even in the presence of co- morbid conditions, and (9) the disturbance cannot be explained by another mental disorder.
Clinical Features\:
Panic disorder can occur at any age but typically peaks in late adolescence or later in the third to fifth decade of life. The first panic attack is usually unexpected, with anticipatory anxiety for the following attacks. The panic attacks typically last 20 to 30 minutes, but rarely more than 1 hour. Panic dis­ order can be accompanied by agoraphobia, but they would be considered two separate diagnoses according to the DSM-5. A panic attack is characterized as having an intense fear for a discrete period of time with >4 of the following symp­ toms that develop abruptly and peak within minutes. It may be helpful to remember these symptoms in a head to toe fashion\:
Neuro—Dizziness, trembling, paresthesias, chills or heat sensations, light-headedness
Psych—Fear of dying, fear of going crazy, sense of choking, sense of shortness of breath, derealization, depersonalization
Cardiac—Palpitations, chest pain, sweating, t HR GI—Nausea, GI upset
Next Step\:
Step 1) A thorough history and physical is important to rule out any organic causes. Limited diagnostic testing may be ap­ propriate and may include a TSH, CBC, BMP, EKG, CXR, urine toxicology screen, and pulse oximetry.

Step 2) The diagnosis of panic disorder is established when all of the following occur\:
• Patient has recurrent, unexpected panic attacks
• Following the attacks, >1 month of having a maladaptive change in behavior, worried about the consequences, or per­ sistent fear of having more attacks.
Step 3) Provide reassurance and educate patients that they are not “going to go crazy”
Step 4) Short-term management\: Patients that are having a panic attack can be given benzodiazepines (eg, alprazol­ am, clonazepam). Benzodiazepines can be given for a short period of time and may serve as a bridge before a clinical response to SSRIs (can take 4-8 weeks). Caution is advised for patients who are elderly, are substance abusers, or have respiratory disorders.
Step 5) Long-term management\: Cognitive behavioral therapy (CBT) and/or SSRIs. Alternatives to SSRIs include TCAs (eg, clomipramine, imipramine) and MAO inhibitors (eg, phenelzine). Patients that respond to pharmacotherapy should continue for at least 1 year after the symptoms are controlled.
Follow-Up\:
Panic disorder is a chronic illness with a variable course. Ongo­ ing support and care is important as well as awareness of other comorbid conditions.
Pearls\:
• Panic disorder is associated with major depressive disorder, social phobia, specific phobia, generalized anxiety disorder, PTSD, OCD, substance abuse, personality disorders, and hypochondriasis.
• On the CCS, remember to “bridge” your therapy by address­ ing any acute issues along with the long-term care of the patient.
• Clinical snapshot\: A 52-year-old woman develops recurrent chest pain, palpitations, tingling sensations in her fingers, and feeling extremely warm within several minutes every time she sits in her comfortable reclining chair. For the past 2 months, she now worries about having a heart attack if she sits in the reclining chair.
I GENERALANXIETYDISORDER
General anxiety disorder (GAD) is characterized by excessive worrying about many things without a focus on specific items, which causes significant distress and impairment in important areas of functioning.
Clinical Features\:
The anxiety and worry that patients have with GAD are associated -with symptoms that can be easily remembered into motor or cognitive domains. Consider the following symptoms\:
Motor—Muscular tension, resdessness, fatigability Cognitive—Poor concentration, irritability, sleep disturbances
Next Step\:
Step 1) A thorough history and physical are important with emphasis on ruling out caffeine intoxication, stimulant abuse, alcohol, and anxiolytic withdrawal. Limited diagnostic testing may be appropriate and may include a TSH, CBC, BMP, EKG, and urine toxicology screen.
Step 2) The diagnosis of GAD is established when all of the following occur\:
• Excessive anxiety and worry about a number of events or activities for at least 6 months
• Difficulty controlling the worry
• 2\:3 symptoms (see Clinical Features)
Step 3) Management of GAD may include behavioral therapy and/or medications.
CBT—Components of CBT for GAD may include relaxation techniques, biofeedback, and education.
SSRIs—Onset of action is within 1 week, but a full response may not be evident for up to 4 to 8 weeks.
Buspirone—Buspirone can take up to 2 to 4 weeks for a clinical response.
Benzodiazepines—Benzodiazepines can be used as a short­ term therapy and concomitandy with either SSRIs or bus- pirone to serve as bridge until the other meds take effect. Caution is advised for patients that are elderly, are substance abusers, or have respiratory disorders.
Follow-Up\:
GAD is a chronic illness that may be lifelong. Be aware that patients may seek many specialists for their complaints.
Pearls\:
• GAD = Excessive worry + £3 symptoms + 6 months
• Generalized anxiety disorder is associated with major de­ pressive disorder, dysthymic disorder, social phobia, specific phobia, panic disorder, and substance abuse.
• Clinical snapshot\: A 24-year-old premedical student has had difficulty concentrating in his premedical classes for the past year because he is worried about his academic per­ formance. He is constantly tapping his legs on the ground during lectures, and he has difficulty falling asleep at night. He does not have any other medical condition and does not use caffeine or substances to keep him up. He lives 1 hour away from his family and is constantly worried about their well-being. He is also worried about his own health because of the demands of getting into medical school. He has tried exercising as an outlet to control his symptoms and to improve his health, but without success. He has seen his primary care physician and a neurologist for his sleep disturbances.
CHAPTER 16 PSYCHIATRY 227

228 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
TRAUMA-AND STRESSOR- RELATED DISORDERS
DSM-5 Alert\: Trauma- and stressor-related disorders is a new category of mental disorders that include PTSD, acute stress disorder, reactive attachment disorder, disinhibited social en­ gagement disorder, and adjustment disorders.
0 POSTTRAUMATICSTRESSDISORDER
PTSD is a mental disorder that develops from a traumatic stressor that results in psychological trauma.
DSM-5 Alert\: The diagnostic criteria have changed signifi­ cantly from the DSM-IV. Please refer to Step 1 to compare these changes. The following changes include (1) the diagnostic crite­ ria can now be applied to children older than 6 years old with a different diagnostic criteria for children <6 years old, (2) the traumatic event is now explicit if the patient experienced direcdy, witnessed, or experienced indirectly (eg, learning of an event that occurred to somebody close to him or her), (3) the trau­ matic event no longer involves a response of intense fear, help­ lessness, or horror, (4) the traumatic event can now specifically include sexual violence, (5) the traumatic event can now include a recurring exposure that can be applied to first responders or police officers, (6) the numbing of general responsiveness is removed, (7) a new cluster is added that retains most of the numbing symptoms and is referred to as negative alterations in cognitions and mood (eg, feeling detached, loss of interest, inability to remember important information regarding the event, persistent negative emotions, persistent and exaggerated nega­ tive beliefs, inability to experience positive emotions, distorted cognitions about the cause), and (8) reckless or self-destructive behavior is added to heightened arousal. For board purposes, the DSM-IV criteria are retained in this section because the changes might not have been implemented on any given test.
Clinical Features\:
The onset of PTSD can occur shordy after the traumatic event or can be delayed as long as 30 years. Traumatic events may in­ clude war, physical abuse, sexual abuse, terrorist events, natural disasters, car accidents, plane crashes, severe physical injury, or medical complications.
Next Step\:
Step 1) The diagnosis of PTSD is established when all of the following occur\:
• Experiencing a traumatic event that causes intense fear, helplessness, or horror. In addition, the individual experiences or witnesses an event that involves actual or threatened death or serious injury.
• Constantiy reexperiencing the event (eg, images, dissocia­ tive flashbacks, symbolic cues, dreams).
• Avoiding anything associated with the event and numbing of general responsiveness (eg, feeling detached, loss of interest,
restricted range of affect, inability to remember important information regarding the event, avoiding feelings, thoughts, or places related to the event).
• Hyperarousal (eg, startled, irritability, angry outbursts, hy­ pervigilance, sleep disturbances, poor concentration).
• Duration of symptoms >1 month.
• Impaired functioning in important areas (eg, work, school, relationships).
Step 2) Following the traumatic event, support and education are important especially to destigmatize the idea that PTSD is an unworthy condition.
Step 3) Short-term management\: Patients that have acute, severe symptoms of hyperarousal or anxiety immediately following the traumatic event can be temporarily treated with benzodiazepines (eg, lorazepam). Benzodiazepines should not be continued once the acute episode has resolved.
Step 4) Long-term management\: Patients may require both pharmacologic therapy and psychotherapy when either modal­ ity is ineffective as a monotherapy. First-line pharmacologic therapies are the SSRIs (eg, sertraline, paroxetine). Remember that the clinical response to SSRIs can take up to 4 to 8 weeks. If medication is effective, the medication can be continued for at least 6 months to a year to prevent relapse. Psychotherapies may include CBT, psychodynamic psychotherapy, or eye movement desensitization and reprocessing (EMDR). In addition to the individual psychotherapies, family therapy and group therapy may be beneficial.
Follow-Up\:
PTSD is usually a chronic condition requiring ongoing support. Approximately one-third of patients with PTSD will never fully recover.
Pearls\:
• A good prognosis usually occurs in the setting of a good social support system, rapid engagement of treatment, short onset and duration of symptoms, good premorbid function­ ing, and absence of substance abuse and other psychiatric conditions.
• Foundational point—Benzodiazepines facilitate the inhibi­ tory actions of GABA, which triggers the opening of chloride channels leading to an increase in chloride conductance.
• On the CCS, remember to “bridge” your therapy by treat­ ing the acute stages of PTSD with the long-term care of PTSD.
• Clinical snapshot\: A 32-year-old Chicago firefighter sus­ tained second and third degree burns over 80% of his body. He has been recovering over the past 3 months at a burn medical center. As he looks out his hospital room window, he sees hospital employees lighting up a cigarette with smoke over their heads. The patient becomes startled and quickly looks away. The patient knows exactly what time of day to avoid looking outside. He’s had these symptoms for more than one month.

0 ACUTESTRESSDISORDER
Acute stress disorder (ASD) is an anxiety disorder that develops within the initial month of a traumatic stressor and can poten­ tially progress to PTSD after one month.
DSM-5 Alert\: The diagnostic criteria have been updated. Please refer to Step 1 to compare these changes. The following changes include (1) the traumatic event is now explicit if the patient experienced directly, witnessed, or experienced indirectly (eg, learning of an event that occurred to somebody close to him or her), (2) the traumatic event no longer involves a response of intense fear, helplessness, or horror, (3) the traumatic event can now specifically include sexual violence, (4) the traumatic event can now include a recurring exposure that can be applied to first responders or police officers, (5) >9 symptoms from any of the five categories that include intrusion symptoms (eg, intrusive dis­ tressing memories, recurrent distressing dreams, flashbacks, reac­ tions to internal or external cues), negative mood (eg, inability to experience positive emotions), dissociative symptoms (eg, dazed, inability to recall information from the event, having a dif­ ferent perspective from the environment or oneself), avoidance symptoms (eg, avoiding feelings, thoughts, or places related to the event), and arousal symptoms (eg, startled, irritability, angry out­ bursts, hypervigilance, sleep disturbances, poor concentration), and (6) duration of symptoms is 3 days to 1 month after the event. Keep in mind that acute stress disorder cannot be diagnosed until 3 days after the stressor. For board purposes, the DSM-IV criterias are left in place because the transition to the DSM-5 criteria might not have been implemented on the large pool of exam questions.
Clinical Features\:
TheonsetofASDsymptomstypicallyoccurswithinthefirstfewdays or weeks after the traumatic event. Similar to PTSD, the traumatic event can be a horrible experience for the patient. The two main differences between PTSD and ASD are the duration of symptoms (see step 1) and the presence of at least three dissociative symptoms.
Next Step\:
Step 1) The diagnosis of ASD is established when all of the fol­ lowing occur\:
• Experiencing a traumatic event that causes intense fear, helplessness, or horror
• Reexperiencing the event
OBSESSIVE-COMPULSIVE
AND RELATED DISORDERS
DSM-5 Alert\: Obsessive-compulsive and related disorders is a new category of mental disorders that include OCD, body dysmor­ phic disorder, hoarding disorder, trichotillomania (hair-pulling disorder), excoriation (skin-picking) disorder, substance/med­ ication-induced obsessive-compulsive and related disorder, and
• Avoidance of stimuli
• Hyperarousal
• Onset of symptoms must occur within 4 weeks of the trau­ matic stressor, and the duration of symptoms occurs for at least 2 days, but no longer than 4 weeks.
• Impaired functioning in important areas (eg, work, school, relationships).
• Experience at least 3 dissociative symptoms from the fol­ lowing “5 D’s”\:
1) Detached (ie, feeling numb)
2) Dazed(ie,feeling“outofit,”)
3) Derealization (ie, feeling separated from the external environment)
4) Depersonalization (ie, feeling separated from one’s body)
5) Dissociativeamnesia(ie,inabilitytorecallinformation)
Step 2) Following the traumatic event, provide support and education.
Step 3) First-line treatment is early intervention with trauma- focused CBT to reduce the likelihood of developing PTSD. Ben­ zodiazepines can be given following the traumatic event to help with anxiety or sleep disturbances.
Follow-Up\:
Patients experiencing ASD should be seen closely for the first month to ensure that they are provided with therapeutic treat­ ment.
Pearls\:
• It is not clear why some patients with ASD develop PTSD and others do not.
• Connecting point (pg. 231)—Know the different dissocia­ tive disorders and symptoms.
• Clinical snapshot\: A 27-year-old woman was carjacked one week ago. Over the past week, she has had difficulty with reading newspapers, avoids driving, dreams of the event in her sleep, cannot recall the sequence of events while awake, feeling dazed, has flashbacks, easily startled, and avoids talking to friends or family about the event. She states to her therapist, “I feel a sense of cloudiness ev­ ery day where I’m on top of the clouds.”
obsessive-compulsive and related disorder due to another medi­ cal condition.
1 OBSESSIVE-COMPULSIVE DISORDER
It may be helpful to think of OCD as a “mental-behavior” dis-\: order. The mental component is intrusive thoughts, and the be­ havior component is compulsive acts or repetitive behaviors to alleviate the distress associated with the thoughts.
CHAPTER 16 PSYCHIATRY 229

230 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
DSM-5 Alert\: OCD is no longer part of anxiety disorders. Changes to the OCD criteria include (1) the presence of ob­ sessions, compulsions, or both to make the diagnosis of OCD, (2) the removal of “obsessions are not simply excessive worries about real-life problems” and the “individual recognizes that the obsession are a product of his or her mind” (see step 1), (3) different degrees on the spectrum of insight with specifiers described as poor insight (retained from DSM-IV), good or fair insight, or absent insight/delusional beliefs, and (4) addition of a tic-related specifier for OCD since patients may have a comorbid tic disorder.
Clinical Features\:
The onset of obsessions or compulsions can occur together or separately. If the compulsions occur with the obsessions, the compulsion may not always alleviate the distress associated with obsession. Examples of concurrent obsessions-compulsions include fear of contamination—constantly washing, doubts— constantly checking, need for symmetry—constantly arranging, and unwanted sexual or aggressive thoughts—always praying.
Next Step\:
Step 1) The diagnosis of OCD is established when all of the following occur\:
• Presence of obsessions or compulsions.
• The obsessions are recurrent, the individual tries to suppress the obsessions, the obsessions are not simply excessive wor­ ries about real-life problems, and the individual recognizes that the obsessions are a product of his or her mind.
• The compulsions are acts of repetitive behaviors and the acts are aimed at reducing the distress.
• Patients recognize that the obsessions or compulsions are irrational.
• Impairment in normal life functioning (eg, work, school, rela­ tionships), the disturbance is time-consuming (>1 hour a day), and the disturbance causes marked distress to the individual.
Step 2) Management of OCD may include behavioral therapy and/or medications.
CBT—Components of CBT for OCD include exposure and prevention, cognitive therapy, and education.
SSRIs—SSRIs (eg, fluoxetine, fluvoxamine) are typically better tolerated than clomipramine.
TCA—Clomipramine can cause dry mouth, sedation, con­ stipation, and orthostatic hypotension.
Follow-Up\:
OCD is a chronic illness that requires ongoing care. Although symptoms may improve with treatment, patients may experience a waxing and waning of their symptoms during their lifetime.
Pearls\:
• Side effects of SSRIs include sexual dysfunction, weight gain, agitation, insomnia, orthostatic hypotension, nausea, GI discomfort, and QTc prolongation.
• Clinical snapshot\: A 32-year-old man is always late to work because he takes at least 2 hours to shave his face because he strives for extreme precision. He is preoccupied about the symmetry of how he shaves one side of his face compared to the other side.
1 BODYDYSMORPHICDISORDER
Body dysmorphic disorder can be characterized as having a pre­ occupation with a nonexistent bodily defect. However, if there is actually a slight defect, the concerns are overly excessive.
DSM-5 Alert\: Body dysmorphic disorder is no longer catego­ rized as a somatoform disorder. Changes to body dysmorphic disorder include (1) additional criterion that describes repeti­ tive behaviors (eg, mirror checking, skin picking) and mental acts (eg, comparing appearance with others), (2) addition of degrees of insight specifiers (poor, good or fair, or absent insight/ delusional beliefs), and (3) addition of a muscle dysmorphia specifier (preoccupied that his or her body build is too small or insufficiently muscular).
Clinical Features\:
Patients with body dysmorphic disorder will feel some type of “ugliness” with some body part, even though they look completely normal. They may feel that other people are noticing their assumed flaw. The preoccupation usually involves the face (eg, ears, nose, chin, hair) or sexual parts (eg, breast, genitals). The body part may change during the course of the disorder. The preoccupations can be time consuming and can lead to social and occupational impairments.
Next Step Treatment\:
Step 1) Physicians should know that reassurance or compli­ ments will not alleviate the patients’ concerns. Even dermato­ logic or plastic surgical procedures will typically be unsuccessful.
Step 2) Primary treatment usually consists of SSRIs (eg, fluox­ etine) and CBT.
Follow-Up\:
Patients on SSRIs should have monitoring of any side effects such as sexual dysfunction, sleep disturbances, nausea, diar­ rhea, agitation, or weight gain.
Pearls\:
• Common age of onset is between 15 and 30 years old.
• Women are typically more affected than men.
• Patients are unlikely to get married.
• Body dysmorphic disorder is a chronic disease that typically waxes and wanes over time.
• Clinical snapshot\: A 28-year-old woman who recently underwent a rhinoplasty still feels that there is a defect with her nose. She is homebound most of the time because she is worried about being ridiculed about her nose.

DISSOCIATIVE DISORDERS
Dissociative disorders are a group of mental disorders that affect the patients’ consciousness, memory, identity, or awareness of their environment (see Table 16-1). An easy way to remember dissociative disorders is that patients are dissociated from a sense of self or environment.
DSM-5 Alert\: Changes to dissociative disorders include (1) dissociative fugue is no longer a separate diagnosis but
rather a specifier to the diagnosis of dissociative amnesia, (2) derealization (feeling detached from the environment) is added to depersonalization disorder and the condition is now named depersonalization/derealization disorder, and (3) dis­ sociative identity disorder may be reported or observed, gaps in the recall of events may occur for everyday events (not just traumatic events), and the disruption of identity may include descriptions in some cultures as an experience of possession. For board purposes, dissociative fugue is retained in Table 16-1 in the event that the exam continues to reflect DSM-IV.
Table 16-1 • Dissociative Disorders Dissociative Amnesia
Dissociative Fugue
Sudden, unexpected travel from home or one's workplace. When they arrive at the new lo­ cation, patients assume a new identity or are confused about their personal identity. They forget everything in the past and are usually unaware of their forgetfulness. When they return to their former selves, they don't remember the fugue, but they can remember the time of onset of the fugue.
Similar to dissociative amnesia, psychotherapy with hypnosis or drug-facilitated interviews.
• Patients that have mood disorders, histrionic personalities, borderline personalities, and schizoid personalities are predis­ posed to the development of dissociative fugue.
• Travel is usually purposeful. • Patients usually live quiet,
modest lives.
• Patients often have
experienced a traumatic event in their lives.
A 45-year-old video store clerk from Chicago suddenly left, leaving behind his wife and children. After several months, an anonymous tip found him in L.A. working in a bookstore.
Dissociative Identity Disorder
The presence of two or more identities within one person. There can be five
to ten personalities, but at least two are taking control of the behaviors. Personali­ ties can be of different ages, races, or sexes. Personalities can be aware of each other, and sometimes they can
be friends or adversaries. Patients are unable to recall personal information.
Treatment involves insight- oriented psychotherapy. Antidepressants and antianxiety meds may serve as an adjunct to psycho­ therapy. Antipsychotics are rarely indicated.
Depersonalization Disorder
Recurrent feelings of detachment from one's body or thought process, even in the presence of intact reality testing. Patients frequently encounter detachment from the external environment (derealiza­ tion) such as normal­ appearing objects that are changing shape.
There is no effective treatment. Antianxiety agents are sometimes used in these patients since anxiety usually accompanies this condition.
• Usually occurs between the ages of 15 and 30 years.
• Comorbid conditions include anxiety disor­ ders, OCD, depression, avoidant personality and borderline personality.
The patient replies to the therapist,"1 feel like I'm in a dream. I'm here, but I'm really not here. My right hand feels ten times bigger than my left hand."
Clinical features
The inability to recall impor­ tant personal information that is usually of a stressful
or traumatic nature. Patients are usually aware that they have lost their memories. The memory loss can be short term (hours to days) or a lifetime experience.
Treatment of choice is with psychotherapy augmented with either hypnosis or drug-assisted interviews (eg, thiopental).
• Occurs more often in women than in men.
• More common in young adults than older adults.
• Confabulation is an adaptive strategy to cover up their memory loss.
A 22-year-old teacher was found on a park bench. She could not remember her home address. As a young girl, she would run to the park whenever there was domestic violence at home.
Next step treatment
Pearls
• •
•
This disorder is also known as multiple personality disorder. Women are affected more than men, but
in children, boys are more likely to be affected than girls. Patients often have experienced a previous traumatic event, especially physical or sexual abuse.
Clinical snapshots
During therapy, the therapist engages all seven personalities in a 37-year-old woman who was sexually abused by her uncle.The therapist can now reinte­ grate the different personali­ ties to control her behaviors.
CHAPTER 16 PSYCHIATRY 231

232 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
SOMATIC SYMPTOM
AND RELATED DISORDERS
DSM-5 Alert\: Somatic symptom and related disorders is a new category that includes factitious disorder, somatic symptom dis­ order, illness anxiety disorder, conversion disorder (functional neurological symptom disorder), and psychological factors affecting other medical conditions. The diagnosis of somatiza­ tion disorder, hypochondriasis, and pain disorder have been removed in DSM-5, but for board purposes these topics will remain in this section in the event that the exam continues to reflect DSM-IV.
1 FACTITIOUSDISORDERIMPOSEDONSELF
Factitious disorder imposed on self can be characterized by the perpetrator’s deliberate act of causing deception by creating or exaggerating an illness.
DSM-5 Alert\: Factious disorder imposed on self is a new term but it is still coded and diagnosed as a factitious disorder. In ad­ dition, the motivation for the behavior to assume the sick role that was seen in DSM-IV is now removed from DSM-5. For board purposes, the new terms seen in DSM-5 will be applied to this chapter to reflect the transition to include both DSM-IV and DSM-5 terminology on the exam.
Clinical Features\:
The deceptive behavior is usually apparent even when the external rewards are not clearly evident (eg, money, shelter, avoiding legal responsibility). One of the motivations for the deceptive behavior is to assume the sick role. Perpetrators will intentionally produce medical or mental disorders, or they will pretend to have the disorders. The signs and symptoms ofthe intended dis­ order can be predominantly psychological or physical. If both types are present but neither predominates, then it is considered a mixed presentation. Examples of physical signs may include hematoma, hypoglycemia, hemoptysis, hematuria, rigid abdo­ men, intentional dehiscence, seizures, or self-trauma. Examples of psychological symptoms may include depression, conver­ sion symptoms, suicide, homicide, or hallucinations. It should be noted that drug-seeking behavior may be part of the profile such as seeking psychoactive drugs or analgesics.
Next Step\:
Step 1) Know that with every negative test that is returned to you, the patient may become more hostile.
Step 2) Request to interview the patients reliable sources such as family or friends to uncover the nature of the patient’s condition. If consent is not given, this may be a clue to the diagnosis.
Step 3) There is no specific therapy for factitious disorder. However, you should treat the self-induced injury and protect patients from self-harm or harm to others if they presented with suicidal or homicidal tendency.
Follow-Up\:
Perpetrators will usually have familiarity with the medical jargon and will present the problem cleverly. However, an astute physician may have a sense that the patient is not truthful based on a careful history and prior diagnostic results (ie, clinical judgment).
Pearls\:
• Munchausen syndrome is a chronic and dramatic variant of factitious disorder with predominantly physical signs and symptoms. These patients are characterized by having dangerous manipulations of the body (eg, surgery, excessive warfarin), move from place to place (peregrinate), and make false claims about their accomplishments or relationships with famous people (pseudologia fantastica).
• Clinical snapshot\: A 25-year-old woman has punched her­ self in the face causing a black eye. She was seen in the emer­ gency department and stated that a friend accidentally hit her with her elbow.
9 FACTITIOUSDISORDERIMPOSED
ON ANOTHER
Factitious disorder imposed on another can be characterized by the perpetrator’s deliberate act of causing deception by creating or exaggerating an illness onto another person.
DSM-5 Alert\: Factitious disorder imposed on another replaced the previous term, factitious disorder by proxy. Factitious disorder by proxy was coded and diagnosed as factitious disorder not otherwise specified in DSM-IV, but it is now coded and diagnosed as a factious disorder in DSM-5.
Clinical Features\:
The deceptive behavior is usually apparent even when the exter­ nal rewards are not clearly evident. The victim is under the care of the perpetrator and is usually a child but may be an adult. The perpetrator will intentionally produce medical or mental disorders or will pretend or fabricate a disorder through the victim. The perpetrator usually appears concerned about the victim in the hospital, is well liked by the medical staff, and has familiarity with the medical terminology. Examples of induced conditions include bleeding, vomiting, diarrhea, seizures, apnea, fever, or rashes.
Next Step\:
Step 1) Know that it can be difficult to prove that the perpetra­ tor is causing the condition.
Step 2) Suspicion should arise when there is a discrepancy between the history and physical exam, the patient is not responding to treatment as expected, or additional problems occur after the perpetrator is told that the victim is improving.
Step 3) When factitious disorder imposed on another is sus­ pected, the goal is to ensure the safety of the victim. Children may be admitted to the hospital to ensure their safety and to be

treated for their induced condition. In addition, child protective services, social services, or law enforcement may be required to facilitate the safety of the victim.
Follow-Up\:
Measures must be in place to prevent the perpetrator from fleeing with the victim once it has been revealed that factitious disorder imposed on another is present.
Pearls\:
• When the perpetrator is separated from the victim, the prob­ lem usually resolves.
• The perpetrator is usually more concerned about his or her own welfare than about the actual victim.
• Clinical snapshot\: A 37-year-old nurse who has diabetes has been crushing her metformin tablets into the food of her 10-year-old son. Her son has been having diarrhea, nausea, vomiting, and gas. After a negative medical workup, the pri­ mary care physician is still perplexed.
1 CONVERSION DISORDER
Conversion disorder can be characterized as “converting” into a condition that is not “real” and causes considerable dysfunction in the patient.
DSM-5 Alert\: Conversion disorder can now synonymously be called functional neurological symptom disorder. Modification to the conversion disorder criteria include (1) the incompat­ ibility between the symptom and recognized neurological or medical conditions based on clinical findings, (2) the diagnosis can be specified with or without a psychological stressor, which demonstrates the importance that psychological factors may or may not be present at the time of diagnosis, (3) the diagnosis can be specified by the duration of symptoms (ie, <6 months is considered an acute episode and >6 months is considered per­ sistent), and (4) the DSM-5 no longer requires that the symp­ tom is not intentionally produced or feigned.
Clinical Features\:
The symptoms or deficits typically affect voluntary motor or sensory function, which suggests a neurological component, but cannot be explained by a known neurological or medical disorder. A psychological component is usually associated with the symptoms or deficits. Common examples of conversion dis­ order include mutism, paralysis, blindness, pseudoseizures, an­ esthesia, paresthesia, deafness, tunnel vision, gait disturbances, tics, and tremors. The DSM-IV required that symptom is not intentionally produced or feigned.
Next Step Treatment\:
Step 1) Know that the symptoms of conversion disorder usually resolve spontaneously.
Step 2) Maintain a therapeutic alliance with the patient and acknowledge the reality of the symptoms. Telling patients that their symptoms are imaginary often worsens their condition.
Step 3) Psychotherapy may be helpful.
Follow-Up\:
In the majority of cases, the symptoms will resolve within a few days or in less than a month. However, the longer the symptoms persist, the worse the prognosis.
Pearls\:
• The lack of concern about the impairment (la belle indif­ ference) has been associated with conversion disorder, but it is an inaccurate way to determine if the patient has conver­ sion disorder because it is nonspecific for the condition.
• Approximately 25% of patients will have another episode in a setting of another stressor.
• Conversion disorder can sometimes be confused with soma­ tization disorder because conversion conditions can be seen in somatization disorder.
• Clinical snapshot\: A 17-year-old girl who was recently dumped by her boyfriend states that she feels a lump in her throat. After a negative examination, the physician acknowl­ edges her symptoms and asks her to come back in a week for a follow-up visit.
1 SOMATIZATION DISORDER
Somatization disorder is characterized by many somatic symp­ toms that are not medically explainable.
DSM-5 Alert\: Somatization disorder is removed from DSM-5. A new disorder in DSM-5 is called somatic symptom disorder. Patients previously diagnosed with somatization disorder may meet the diagnosis for somatic symptom disorder if they also have maladaptive thoughts, feelings, and behaviors. The diagnostic criteria for somatic symptom disorder include (1) >1 somatic symptom causes significant disruption in his or her daily life, (2) the excessive thoughts, feelings, and behaviors of the somatic symptom cause a persistent high level of anxiety, take excessive time and energy devoted to the symptoms, or include persistent thoughts of the symptoms, and (3) persistent symptoms (ie, not all symptoms may be neces­ sarily continuous) that usually last >6 months. In addition, the diagnosis can be specified with pain (previously pain disorder). For board purposes, somatization disorder is retained in this chapter because the changes might not have been implemented on any given test.
Clinical Features\:
The onset of the physical complaints is before the age of 30. The following conditions can occur at any time and must meet the “4-2-l-lM (easily remembered by pager number 4-2-1-1)\:
4 pain symptoms—Examples include pain related to the head, chest, abdomen, back, joints, extremities, dysmenor­ rhea, dyspareunia, dysuria, dyschezia.
2 gastrointestinal symptoms—Examples include nausea, vomiting, diarrhea, gas, bloating (note that there is no pain- related symptom).
CHAPTER 16 PSYCHIATRY 233

234
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
1 sexual symptom—Examples include erectile or ejaculatory dysfunction, irregular menses, excessive menstrual bleeding (note that there is no pain-related symptom).
1 pseudoneurological symptom—Conversion type condi­ tions such as blindness, deafness, double vision, aphonia, hoarseness, seizures, amnesia, hallucinations, imbalance, paralysis, muscle weakness, fainting, lump in the throat.
Next Step Treatment\:
Step 1) Establish a single physician as the primary caretaker.
Step 2) Acknowledge any new complaint and reassure that the most serious disease is ruled out.
Step 3) Limit diagnostic or therapeutic interventions unless they are clinically warranted.
Step 4) Educate patients on how to cope with their physical symptoms.
Step 5) Consider psychotherapy, especially CBT. Step 6) Schedule relatively brief monthly visits.
Follow-Up\:
Follow up with other physicians since most patients will go “doctor shopping” and unnecessary, costly tests will be ordered.
Pearls\:
• There is no pretending or intention in somatization disorder.
• Clinical snapshot\: A 20-year-old woman who has a history of back pain, menometrorrhagia, constipation, diarrhea, left leg pain, and pain during sexual intercourse is in your office fol­ lowing a negative workup for her chest pain. She was speaking to your office staff prior to going into the examination room. As you ask her questions, she is now completely mute.
1 HYPOCHONDRIASIS
Hypochondriasis can be characterized as having a preoccupa­ tion with having a serious medical illness despite appropriate medical reassurance.
DSM-5 Alert\: Hypochondriasis is removed from DSM-5. Patients previously diagnosed with hypochondriasis who have high anxiety about their health, but without moderate to severe somatic symptoms can now be diagnosed with illness anxiety disorder, which is a new DSM-5 disorder. For board purposes, hypochondriasis is retained in this chapter because changes might not have been implemented on the large pool of exam questions.
Clinical Features\:
The fear ofhaving a serious medical condition usually arises from a misinterpretation of bodily symptoms or functions. For exam­ ple, normal abdominal pressure may be perceived as abdominal pain. Despite a negative medical workup, patients believe that they have a particular disease that will continue to persist. Over time, the belief may actually be transferred to another disease. The belief must last at least 6 months for a diagnosis.
Next Step Treatment\:
Step 1) Know that most patients may be resistant to psychiatric
treatment.
Step 2) Establish a single physician as the primary caretaker.
Step 3) Acknowledge the patient’s symptoms, provide consis­ tent reassurance, and have a nonjudgmental stance.
Step 4) Psychotherapy is considered first-line treatment.
Step 5) Schedule regular visits to reassure patients that they are not being abandoned.
Follow-Up\:
Follow up with other physicians since most patients will go “doctor shopping” and unnecessary, costly tests will be ordered.
Pearls\:
• Patients will be convinced that they have a specific disorder, but their beliefs are not so rigidly fixed as to be a delusional disorder.
• Clinical snapshot\: After a negative workup for colon cancer, a 55-year-old man is still convinced that he has colon cancer after 8 months. He states that he has “thin caliber stools” and he read somewhere on the Internet that people with colon cancer can have these kinds of stools.
1 PAIN DISORDER
Pain disorder is characterized by having pain as the primary complaint in one or more body part that cannot be fully attrib­ uted to a known medical disorder. The pain is sufficient to cause social and occupational impairments.
DSM-5 Alert\: Pain disorder is removed as a separate diagnosis and now used as a specifier for the diagnosis of somatic symp­ tom disorder in DSM-5. For board purposes, pain disorder is re­ tained in this chapter because the changes might not have been implemented on any given test.
Clinical Features\:
Pain disorder can be divided into two main subtypes\:
1) Paindisorderwithapsychologicalcomponent—Thepsy­ chological component plays a major role in the onset, sever­ ity, exacerbation, or maintenance of the pain. The duration can be acute (<6 months) or chronic (>6 months).
2) Pain disorder with a psychological component + general medical condition—Both the psychological component and the general medical condition play important roles in the onset, severity, exacerbation, or maintenance of the pain. The duration can be acute (<6 months) or chronic (>6 months).
Next Step Treatment\:
Step 1) Know that the patients’ experience of their pain is real.
Step 2) Empathize with the patients’ suffering, and do not con­ front them (ie, do not say, “Your pain is not real”).

Step 3) Educate patients that there is a link between psychologi­ cal factors causing psychogenic pain.
Step 4) Psychotherapy may be helpful.
Step 5) Treat comorbid conditions (eg, SSRIs for depression).
Follow-Up\:
Maintain regular follow-ups since the pain disorder can be chronic and disabling. Ensure that patients have the coping skills to deal with their symptoms since the overall goal is bring them back to a functioning level by reducing their social and occupational impairments.
Pearls\:
• There is no pretending or intention in pain disorder.
• Judicious use of analgesics should be maintained because long-term analgesic treatment can lead to substance abuse.
• Be vigilant in patients that might have a substance abuse problem since patients will use alcohol and other substances to reduce their pain.
• Associated conditions include anxiety disorders and depres­ sive disorders (eg, major depression, dysthymia).
PERSONALITY DISORDERS
Personality disorders are grouped into three clusters, and these mental disorders reflect a deeply ingrained way of thinking
Table 16-2 • Personality Disorders
Type Clinical Features | Cluster A—"Eerie"
•
•
•
•
Pain disorder can sometimes be confused with somatization disorder since pain is part of the “4-2-1-1.” However, in pain disorder, the psychological component must be significantly involved in the pain symptoms.
Pain disorder without a psychological component, but with an associated general medical condition is not considered a mental disorder.
Examples of a psychological component may include trau­ ma, abuse, stressors in the family, finance, occupation, or academics.
Clinical snapshot\: A 52-year-old restaurant manager has been seen in the office for low back pain for the past 10 months. He is becoming socially withdrawn and start­ ing to skip work. He has a negative medical workup for any serious medical condition, and he has tried physical therapy, heating pads, massage therapy, and ibuprofen with minimal success. Upon questioning his family his­ tory, he reveals that his brother to whom he had been very close died 1 year ago. With every family gathering since his brother’s passing, his back pain seems to worsen the
following day.
Paranoid—"Distrust" • • • •
Schizoid—"Detached" • • •
Schizotypal—"Odd" • • • •
•
j Cluster B—"Emotional"
Antisocial—"Trouble" • • • • •
Suspicious
Reluctant to confide in others Misinterprets benign remarks Bears grudges
No interest in relationships Appears cold and aloof Lacks friends and sex
Magical thinking
Eccentric behavior
Odd speech
Ideas of reference, but the false beliefs are not firmly fixed Paranoid ideation
Disregard for others
Deceitful
Irresponsible, impulsive Conduct disorder before age 15 Must be at least age 18
Next Step Behavioral Approach
Clinical interaction should be honest, straightforward, and apologetic if appropriate.
The clinician should have a calm and reassuring stance.
Maintain a nonjudgmental stance.
Set firm behavioral limits.
Clinical Snapshots
A 70-year-old woman is constantly accusing her husband of infidelity with another woman.
A 32-year-old man lives in a rural area and has no friends in his town.
A 45-year-old man wears a hat and sunglasses while watching TV because he believes that the messages are directed
at him.
A 22-year-old man who has been in and out ofjail states that he has no remorse for stealing a woman's purse.
CHAPTER 16 PSYCHIATRY 235
and behaving that is very different from the patients cultures expectations and that can lead to impaired functioning in work, school, or relationships (see Table 16-2).
( Continued)

236 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Table 16-2 • Personality Disorders (Continued)
[
Type Borderline—"Splitting"
Clinical Features
• Splits (ie, sees people as all good or all bad)
• Intense and unstable relationships
• Inappropriate anger
• Impulsive (eg, sex, drugs,
spending)
• Suicidal and self-mutilating
behavior
• Feeling empty all the time
• Seductive
• Attention-seeking • Speech lacks detail • Emotionally labile
• Grandiosity
• Fantasies of success or ideal
love
• Exploitative
• Envious
• Excessive admiration • Empathy is lacking
Next Step
Behavioral Approach
1) Politely confront the patient that no one is all good or all bad.
2) Have good communication with all the medical staff.
3) Be aware of countertrans­ ference, which can impair clinical judgment.
4) Be able to establish clear boundaries with respect to treatment and behavior toward others.
Be professional and avoid any close relationships.
Be professional, avoid being defensive, and be able to tol­ erate the patient's character.
1) Allow patients to be actively involved and take ownership of their healthcare.
2) Avoid being authoritative.
3) Be aware of countertrans­ ference.
Maintain a trusting doctor- patient relationship. Be accepting of the patient's fears of criticism.
Be alert that patients may withhold information.
Clinical Snapshots
A 35-year-old woman treats the nursing staff with disrespect but acknowledges the treating physician as a "superb doctor."
A 25-year-old woman wearing a provocative dress is seen by a young male ED resident for knee pain. She is quick to draw up her dress to show her knee and begins to flirt with him.
A 59-year-old judge is request­ ing to be transferred to another inpatient room. He states that because he is a judge and has
a "special" role in society, he demands a cleaner and better room.
A45-year-old man is unable
to discard his old socks that
he has had for 3 years even though there is no sentimental value.
A 38-year-old unmarried woman says she begins to tense up while interviewing for a job.
She is afraid of being ridiculed for saying something wrong.
A 25-year-old woman is in an abusive relationship with her husband. The husband is the sole provider of the family and makes all the decisions in the household. The patient be­ comes tense when the clinician discusses her husband.
Histrionic—"Dramatic"
Narcissistic—"Entitlement"
Cluster C—"Edgy and Embarrassed"
Obsessive-compulsive personality disorder (OCPD)—"Perfectionist"
• Preoccupied with orders and rules
• Organized
• Overconscientious
• Stingy and stubborn
• Devoted to work
• Reluctant to delegate tasks
• Unlike other personality disorders,
OCPD patients are aware of their
suffering.
• Unlike OCD, there are no
obsessive thoughts or compulsive behaviors in patients with OCPD.
• Fear of disapproval or rejection • Feeling inadequate
• Unlike schizoid, patients desire
relationships but fear criticism.
• Difficulty making decisions • Difficulty expressing
disagreement
• Fear of being alone
• Nonproactive because of low
self-confidence
• Needs support from others
• Seeks new relationships when
one ends
• Submissive
Avoidant—"Shy"
Dependent—"Clingy"

NEURODEVELOPMENTAL
DISORDERS
DSM-5 Alert\: Neurodevelopmental disorders is a new cat­ egory of mental disorders that include intellectual disabilities, communication disorders, autism spectrum disorder, ADHD, specific learning disorder, and motor disorders (eg, Tourette’s disorder, persistent motor or vocal tic disorder, provisional tic disorder). In addition, the term mental retardation used in
DSM-IV is now replaced with intellectual disability (intellectual development disorder).
I AUTISM
Autism is characterized by impairments ofthree major develop­ mental domains\: communication, behavior, and socialization. Autism is categorized as a pervasive developmental disorder, a classification that also includes Rett’s disorder, childhood disin­ tegrative disorder, and Asperger’s disorder (see Table 16-3). The etiology of autism is still unknown.
Table 16-3 • Pervasive Developmental Disorders (DSM-IVTerminology)
Clinical features
Rett's Disorder
• Occurs exclusively in females. • Initially develops normally,
then deteriorates.
• Head circumference is normal
at birth, then over time there is deceleration of head growth that can then result in microcephaly.
• Height and weight eventually decline.
• Loss of purposeful hand movements, replaced by ste­ reotypic hand movements.
• Loss of acquired speech.
• Deterioration in milestones. • Psychomotor retardation.
• Poor coordination and gait
abnormalities.
• Associated conditions include
respiratory irregularities, seizures, dementia, scoliosis, cardiac abnormalities, sleep disturbances, and fractures.
No specific therapy for Rett's disorder, but the goal is symptomatic intervention. Antiepileptics for seizures, physiotherapy for muscular dysfunction, medication and behavior therapy for behavioral problems.
After the first 6 months of ap­ parently normal development, an 18-month-old toddler can
no longer say "mama." Her head growth has declined, and she now has frequent hand-wringing.
Childhood Disintegrative Disorder (CDD) • Initially develops normally for at
least the first 2 years of life, then
"disintegrates."
• Boys > girls.
• Minimum age of onset is 2 years old,
with the vast majority occurring be­
tween 3 and 4 years old.
• Before the age of 10, there is loss of
previously acquired skills in any of the following\:
• Bowel or bladder control • Language
• Social skills
• Motor skills
• Play
• Similar to autism, CDD can affect Com­ munication, Behavior, and Socialization ("CBS").
• Unlike autism, patients previously ac­ quired normal development in CDD.
• Unlike Rett's, there are no hand stereo­ typies, and onset is usually a little later in CDD.
• The main associated condition is seizure disorder.
Treatment of CDD is similar to autism. There is no known medication that specifi­ cally addresses CDD. A multidisciplinary approach is optimal.
A 5-year-old boy who previously spoke in sentences can now only speak in frag­ ments. He can no longer draw stick figures, is no longer toilet trained, and no longer accepts hugs from his parents.
Asperger's Disorder
• Boys > girls.
• Asperger's is similar to autism, but
the main distinction is the lack of language delay. In addition, there is no delay in cognitive develop­ ment, adaptive behavior, or age- appropriate learning skills.
• Individuals can use single words by age 2 and communicative phrases by age 3. However, they have difficulty with a give-and-take conversation (ie, usually one-sided conversation).
• Functional use of language may be odd such as using sarcasm inappropriately.
• The tone and rhythm of language may be odd such as speaking in a theatrical manner.
• Individuals with a normal IQ and high-level social skills are likely to have the best prognosis.
• Associated conditions include ADHD, depression, mood disor­ ders, tic disorders, anxiety, and oppositional defiant disorder.
Similar to autism, a multidisciplinary approach is required. Patients do better in a structured and organized environment. Initially address depression by nonpharmacologic methods (eg, counseling), if unsuccessful, consider medication. Consider risperidone for disruptive behavior when nonpharmacologic methods are unsuccessful.
A 9-year-old boy with a history of ADHD has repetitive hand flap­
ping and has difficulty with normal reciprocal social interactions.There are no issues with language, but he sometimes speaks to his teachers in a professorlike tone.
Next step treatment
Clinical snapshots
CHAPTER 16 PSYCHIATRY 237

238 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
DSM-5 Alert\: Autistic disorder, Asperger’s disorder, Rett’s disorder, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified are no longer separate disorders, but rather compose a new DSM-5 disor­ der called autism spectrum disorder. Patients previously diag­ nosed with autistic disorder, Asperger’s disorder, or pervasive developmental disorder not otherwise specified can be given the diagnosis of autism spectrum disorder, but those disorders that do not meet the criteria for autism spectrum disorder (eg, Rett’s disorder, childhood disintegrative disorder) may need to be evaluated for social (pragmatic) communication disorder, which is a new DSM-5 disorder. Diagnostic criteria for autism
spectrum disorder include (1) deficits in social communica­ tion and social interactions, (2) restricted repetitive behaviors, interests, and activities, (3) symptoms are present in early de­ velopment, (4) significant functional impairment (eg, social, work, school), and (5) the disturbance is not better explained by intellectual disability or global developmental delay. In addi­ tion, autism spectrum disorder can specified with or without an accompanying intellectual impairment or language impairment. For board purposes, autistic disorder, Rett’s disorder, childhood disintegrative disorder, and Asperger’s disorder are retained in this chapter because changes might not have been implemented on the large pool of exam questions.
Clinical Features\:
The onset of symptoms of autism occurs by the age of 3. Boys are 4 times more affected than girls. In the majority of cases, autistic individuals will have mental retardation with an IQ <70. However, in a subset of individuals, they can be “high function­ ing” with an IQ >70. Regardless of the level of intelligence, some individuals have very special skills (ie, “savant skills”) such as an extraordinary ability in mathematics, calendar calculation, puzzles, hyperlexia, singing, playing music, or memorizing and reciting. The three major impairments in autism are com­ munication, behavior, and socialization, which can be best remembered by the mnemonic “CBS.” CBS is a major television network, which is a form of communication. In autism, com­ munication is impaired, behavior is broadcasted in a stereotype pattern, and patients live in a socially isolated system.
Communication
• Inability to use language to communicate
• Both expressive and receptive language are usually affected
• Inability to have a conversation
• Inability to make a sentence even if they have an expansive vocabulary
• Repetitive use of language such as echolalia
• Inability to engage in spontaneous imaginative play
Behavior
• Preoccupation with a stereotype behavior
• Preoccupation with parts of an object
• Adherence to routines or rituals and resistant to changes or transition
• Stereotyped motor mannerisms such as rocking, hand flap­ ping, or head banging
Socialization
• Failure to develop peer relationships
• Failure to have normal reciprocal social interactions
• Failure to seek shared enjoyment or achievements with others
• Failure to show social relatedness with nonverbal behaviors such as normal eye-to-eye gaze, facial expressions, or body gestures
Next Step\:
Step 1) The diagnosis of autism is a clinical diagnosis that is based on impairments in three key areas\: communication, be­ havior, and socialization, with the onset prior to age 3 years. Step 2) In addition to a comprehensive evaluation, additional assessments may be indicated to identify comorbid conditions. The following conditions are associated with autism\:
• Seizures
• Macrocephaly
• Phenylketonuria (PKU)
• Tuberous sclerosis complex (hypopigmented macules)
• Fragile X syndrome (large ears, long face, large testes)
• Angelman syndrome (happy appearance, ataxic gait, lan­ guage delay)
Step 3) There is no cure for autism. Family education and coun­ seling is essential since families are often distraught. Manage­ ment of autistic individuals is with behavioral and educational interventions with the goal of improving overall function. Phar­ macologic agents are only used if behavioral and educational interventions are ineffective, and the agents are used to target a specific type ofcondition (eg, irritability, aggression, self-injury). Only aripiprazole and risperidone are FDA approved for use in children with autistic disorders.
Follow-Up\:
Autistic individuals need ongoing care and require the same routine preventive and screening healthcare as other people.
Pearls\:
• Individuals with a higher IQ and those who can use language by 5 to 7 years of age are likely to have the best prognosis.
• High-functioning individuals can find employment and live independently, while low-functioning individuals usually require dependence and home or residential care.
• To date, there is no evidence to support the association be­ tween autism and vaccines, especially the measles, mumps, and rubella (MMR) vaccine.
• To date, there is no evidence to support the association be­ tween autism and the mercury-based preservative, thimerosal, which is found in some vaccines.
• Connecting point (pg. 162)—Autism can be associated with fragile X syndrome.

• Clinical snapshot\: A 6-year-old boy with autistic disorder frequently looks from the corner of his eyes. He does not make eye-to-eye contact with anybody. He is preoccupied with shiny surfaces and the edges of a ruler. His parents were concerned about his language development when he was 18 months old because he could only say “mama.” At home, he would repeat words that he heard during the school day. He also has a tendency to pinch himself and twist his torso and is resistant to being touched. Now, his parents have to lock the bathroom door because he would flush the toilet all day. At school, he played by himselfin the corner ofthe room. He played with the same toy day after day, and if another child picked up the toy, he would have a tantrum. His parents are receiving family counseling, mostly because they don’t feel the same reciprocal family love from him.
a TOURETTE'S DISORDER
Tourette’s disorder is characterized by both involuntary motor and vocal tics with the onset usually in childhood.
DSM-5 Alert\: The DSM-5 criteria no longer require a tic-free period of more than 3 consecutive months (see step 1).
Clinical Features\:
Tourette’s disorder is 3 times more common in boys than in girls. The motor tic usually emerges by the age of 7, and vocal tics typically appear by the age of 11 years. Examples of the motor component may include body gyrations, eye blinking, head shaking, kicking, grimacing, abdomen tensing, nasal exhalations, nasal flaring, echopraxia, or copropraxia. Examples of the vocal component may include coprolalia, pali­ lalia, echolalia, grunting, sniffing, throat clearing, humming, or clucking.
Next Step\:
Step 1) Tourette’s disorder is a clinical diagnosis based on the following features\:
• Onset before the age of 18 years.
• Both multiple motor and £1 vocal tics are present during the course of the disorder, but they don’t have to be present at the same time.
• Tics occur multiple times per day and almost every day for >1 year without a tic-free period greater than 3 consecutive months.
Step 2) An early part of management is to provide education to the patient, family, and those who interact with the patient.
Step 3) Patients that are doing well academically and socially may not require any treatment. On the other end of the spec­ trum, patients that are having a difficult time academically, pro­ fessionally, or socially may require some type of intervention. The following therapies are available\:
Nonpharmacologic Therapy
Behavioral therapy—Habit reversal training (HRT) may be effective in some patients.
Pharmacologic Therapy
Antipsychotics—Haloperidol, pimozide, and fluphenazine
can reduce the effects of the tics.
SSRIs—SSRIs (eg, fluoxetine) are effective in treating co- morbid OCD.
Stimulants—Stimulants (eg, methylphenidate, dextroam­ phetamine) are used in patients with comorbid ADHD.
Follow-Up\:
Patients that are on antipsychotics should be closely monitored for extrapyramidal symptoms (EPS).
Pearls\:
• Up to 30% to 40% of patients with Tourette’s disorder will have OCD.
• Up to 50% to 60% of patients with Tourette’s disorder will have ADHD.
• Patients with comorbid ADHD are treated with CNS stim­ ulants, but caution is advised because the stimulants can potentially exacerbate preexisting tics.
• Tourette’sdisorderisalifelongdiseasethatcanwaxandwane throughout the course of the disorder.
• Clinical snapshot\: A 12-year-old boy with a history of ADHD has rapid, recurrent shoulder shrugging and eye blinking that started by age 6. By age 10, he feels compelled to chirp in the classroom. After school, most of his peers tease him, calling him “birdman.”
0 PERSISTENT(CHRONIC)MOTOR
OR VOCAL TIC DISORDER
Chronic motor or vocal tic disorder is characterized by the pres­ ence of a tic for a longer period of time compared to provisional tic disorder.
DSM-5 Alert\: Chronic motor tic disorder can now synony­ mously be called persistent motor tic disorder. In addition, the DSM-5 criteria no longer require a tic-free period of more than 3 consecutive months (see step 1).
Clinical Features\:
Unlike Tourette’s disorder, patients can only have a motor or vocal tic. In addition, patients cannot have a history of Tourette’s disorder.
Next Step\:
Step 1) The diagnosis of chronic motor or vocal tic disorder is
based on the following features\:
• Onset before the age of 18 years.
• Single or multiple motor or vocal tics are present, not both.
• Tics occur multiple times per day and almost every day for >1 year without a tic-free period greater than 3 consecutive months.
Step 2) Depending on the severity of the tic and how debilitat­ ing it is socially or academically, psychotherapy may be helpful.
CHAPTER 16 PSYCHIATRY 239

240 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Follow-Up\:
Patients that develop the disorder between 6 and 8 years of age usually do well. Symptoms may last 4 to 6 years and then resolve in early adolescence.
Pearls\:
• Chronic motor or vocal tic disorder is more common than Tourette’s disorder.
• Clinical snapshot\: A 10-year-old boy has chronic throat clear­ ing for the past 2 years. He does not have any comorbid condi­ tions and he has never been diagnosed with Tourette’s disorder.
I PROVISIONALTICDISORDER
Provisional tic disorder is characterized by the presence of tics for relatively short periods.
DSM-5 Alert\: Transient tic order has been replaced with the name provisional tic disorder. In addition, the DSM-5 criteria no longer require a minimum of 4 weeks, but still require that tics are no longer than 1 year since tic onset (see step 1).
Clinical Features\:
Similar to Tourette’s disorder, patients can have both motor and vocal tics. However, patients cannot have a history of Tourette’s disorder or chronic motor or vocal tic disorder.
CLINICAL ATTENTION
The content in this section represents issues that can be seen in clinical practice, but do not represent true mental disorders.
1 MALINGERING
Malingering can be characterized by the perpetrator’s objective in achieving a recognizable goal through fabricating signs and symptoms of a medical condition.
Clinical Features\:
The goal ofthe perpetrator is to reach external incentives through means of intentionally producing a false medical or mental dis­ order. External incentives may include avoiding responsibili­ ties (eg, military duty), punishment (eg, criminal prosecution), danger (eg, gang/mobs), difficult times (eg, unemployment), or obtaining rewards (eg, workers’ compensation, drugs, free room and board). Once the perpetrators have achieved their goals or realize that it is too dangerous to continue, they can usually stop producing their signs and symptoms.
Next Step\:
Step 1) Suspicion should arise when there is a discrepancy between the history and physical examination, the patient is
Next Step\:
Step 1) The diagnosis of transient tic disorder is based on the following features\:
• Onset before the age of 18 years.
• Single or multiple motor and/or vocal tics.
• The time frame is for at least 4 weeks, but no longer than 12 consecutive months.
Step 2) The initial step in management is to encourage the fam­ ily to disregard the tic because focusing attention on the tic may exacerbate the problem. Psychopharmacology is not necessary unless it is causing severe impairment.
Follow-Up\:
Patients may have complete resolution of their tics, or they may recur during periods of stress.
Pearls\:
• A small subset of patients can progress to Tourette’s disorder or chronic motor or vocal tic disorder.
• Clinical snapshot\: An 8-year-old boy had echolalia for the past 6 weeks that seemed to abate.
presented in a medicolegal context, or the patient is uncoopera­ tive with care.
Step 2) Avoid confronting or accusing the patient of malin­ gering. By not discrediting the perpetrator, the doctor-patient relationship can be preserved and further positive intervention is still possible.
Follow-Up\:
Care must be taken to avoid hostile behavior from the perpetra­ tor if the malingerer’s claims are continually challenged.
Pearls\:
• Malingering and factitious disorders are voluntarily pro­ duced, but not somatoform disorders.
• The objective in malingering is to reach an external incentive through means of a medical problem, but external incentives are absent in factitious disorder.
• Antisocial personality disorder is associated with malingering.
• Clinical snapshot\: A 32-year-old homeless person is in the emergency department complaining of upper back pain. He is requesting to have pain medication (ie, drug seeking) to alleviate his pain and hoping to stay in the hospital (ie, to get room and board).

Pulmonary
CHAPTER OUTLINE
Keywords Review............................................2.4.2........ I
I
I
I
NEOPLASM................................................2..5.9......... Lung Cancer..................................................2.5..9.........
OBSTRUCTIVE DISEASES...............................2..4.3....
Nonacute Asthma..........................................2..4.3........I
NonacuteCOPD.............................................2.4.5......... Pneumothorax...............................................2.6.1.........
TRAUMA...................................................2.6.1..........
Tension Pneumothorax........................................2.6.3....... Asbestosis..................................................2.4.7........I.. CCS.........................................................2.6.4............
RESTRICTIVE DISEASE..................................2.4..7.....
VASCULAR DISEASE.....................................2.4.8...... Pulmonary Embolism.......................................2.4.8.......
COPDExacerbation...........................................2.6..4........
I INFECTIONS.............................................2..5.1........
Tuberculosis.............................................. 251 Community-acquired Pneumonia—Adults..................2.5.5..
241

242 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
KEYWORDS REVIEW
Time-------------►
itk
\/ ERV;i.5L)
V/ i r FRC \:3.0L)
ik
RV (1.5L)
^ r ' r
\ IRV (2.5L) k
1C (! i.OL)
AAA/ /\/V\"!r rr
VC(4.5L)
, r
Volumes\: IRV—inspiratory reserve volume; TV—tidal volume; ERV—expiratory reserve volume; RV—residual volume. Capacities\: TLC—total lung capacity; 1C—inspiratory capacity; FRC—functional residual capacity; VC—vital capacity. Note\: Values are approximates for a 70-kg person.
Bilevel positive airway pressure (BPAP)—Also incorrectly referred to as BiPAP, since BiPAP Is the name of a portable ventilator device. BPAP is a mode used to deliver a preset inspiratory positive airway pressure (IPAP) and an expiratory positive airway pressure (EPAP).
Continuous positive airway pressure (CPAP)—The continuous delivery of airflow throughout the respiratory cycle with no dif­ ference in the pressures delivered from inspiration to expiration.
Expiratory reserve volume (ERV)—The maximum volume of air that can be expired starting at the end of a normal tidal expiration.
measured by spirometry because it includes the residual volume.
Inspiratory capacity (1C)—The volume of air inhaled during a maximal inspiratory effort starting at the end of a normal tidal expiration.
Inspiratory reserve volume (IRV)—The maximum volume of air that can be inspired starting at the end of a normal tidal inspiration.
Peak expiratory flow rate (PEFR)—The PEFR can be obtained by a handheld device that measures the greatest flow velocity during a forced exhalation starting from a maximal
FEF2s%_75%—Forcedexpiratoryflowbetween25%and75% inhalation.PEFRisnotsufficienttodiagnosisasthma,butit
of the FVC, or in other words, the airflow halfway through
a forced exhale after a maximal inspiration. The FEF25%_75% generally indicates the status of medium to small sized airways. Decreased flow rates are usually seen in the early stages of obstructive diseases. However, in restrictive diseases the FEF25%_75%values are usually normal. Although abnormal findings may suggest small airway changes, the FEF25%.75%should not be used to diagnosis small airway disease because of poor reproducibility.
FEV,—Forced expiratory volume in one second after a maximal inspiration.
FEV6—Forced expiratory volume in 6 seconds, which is sometimes used as a surrogate for FVC.
Forced vital capacity (FVC)—The amount of air that can be forcibly expired after a maximal inspiration.
Functional residual capacity (FRC)—The volume of air remaining after the tidal volume is expired. FRC cannot be
is useful for Hbme monitoring in asthma patients because
it can detect gross changes in airway function. PEFR is also useful for making bedside assessments in response to bron- chodilators, given that there is a baseline PEFR.
Positive end-expiratory pressure (PEEP)—The positive airway pressure (alveolar pressure > atmospheric pressure) in the lungs at the end of expiration to help prevent atelectasis. PEEP can be applied by a mechanical ventilator (extrinsic PEEP) or caused by an incomplete exhalation (intrinsic PEEP). Extrinsic PEEP (applied PEEP) can range from 0 to 20 cm H20 and is usually adjusted in 2.5 to 5.0 cm H20 increments.
Residual volume (RV)—The volume of air that remains in the lungs after a maximal expiration. RV cannot be measured by spirometry.
Tidal volume (TV)—The volume of air that is inspired or expired with each normal breath.
Volumes Capacities
kikikik
3.5L) TLC 6.0L)

Total lung capacity (TLC)—The sum of all 4 lung volumes. TLC cannot be measured by spirometry because it includes the residual volume.
OBSTRUCTIVE DISEASES
I NONACUTE ASTHMA
Asthma is a chronic disorder of the airways that can be characterized by reversible airway obstruction, bronchial hyperresponsiveness, and an underlying inflammation. The cumulative effect of secretions in the airway, mucosal edema, and contraction of the smooth muscle within the bronchial walls result in a decrease in airway diameter with increased airway resistance.
Asthma Triggers\:
Allergens—Animal dander, house-dust mites, cockroaches, pollens, mold
Climate changes—Cool dry air, hot humid air, barometric pressure changes
Inhaled irritants—Smoke, odors, fumes, dust, pollutants, aerosol sprays
Medical conditions—Stress, depression, rhinitis, sinusitis, GERD
Medications—Nonselective beta-blockers, aspirin, NSAIDS
Physical activity—Exercise
Respiratory infections—Primarily viral infections
Sulfite-containing foods—Dried fruit, processed potatoes, shrimp, wine, beer, pickles, vinegar
Vital capacity (VC)—The volume of air expired after a maximal inspiration. VC usually decreases with diseases that decrease pulmonary compliance.
Clinical Features\:
The presentation of asthma can vary among individuals from progression of the disease to signs and symptoms. The following are key elements to consider\:
Onset
• Asthma can occur at any age.
• In the majority of cases, asthma is diagnosed in childhood or by adolescence.
• Asthma can occur in older people, but they will less fre­ quently develop new-onset asthma.
Pattern
• Episodic—Patients can be asymptomatic between periods of recurrent symptoms.
• Continual—Patient can have chronic symptoms with inter­ mittent worsening of their symptoms.
History
• Previous hospitalizations for asthma.
• Childhood diagnosis of “wheezy bronchitis” or “recurrent bronchitis.”
• Inquire about a history ofatopic diseases since there is an asso­ ciation between asthma and atopic diseases (eg, atopic derma­ titis, allergic rhinitis, food allergy, allergic conjunctivitis).
Severity
• The severity of asthma can be classified as intermittent, mild persistent, moderate persistent, and severe persistent (see Table 17-1).
Table 17-1 - Asthma Severity and Treatment for Youths > 12 Years Old and Adults
Normal FEV/FVC Reference Values
8-19 yrs\: 85% 20-39 yrs\: 80% 40-59 yrs\: 75% 60-80 yrs\: 70%
Severity
Lung Function
Symptoms <2 dys/wk

2 dys/wk, but not daily
Daily
Throughout the day
Nighttime Awakenings
<2x/mo
3-4x/mo
1 x/wk, but not nightly
Often 7x/wk
Treatment Initiation PRN\:SABA
Option 1\: Low-dose ICS PRN\: SABA
Option 1\: Low-dose ICS + LABA
Option 2\: Medium-dose ICS
PRN\: SABA
Note\: Consider short course of oral corticosteroids
Option 1\: Medium-dose ICS + LABA
Option 2\: High-dose ICS + LABA
PRN\: SABA
Note\: Consider short course of oral corticoste­ roids, and for patients with allergies consider omalizumab.
Intermittent • FEV/FVC normal
• FEV, >80% predicted
Mild • FEV/FVC normal persistent • FEV1 >80% predicted
Moderate • FEV/FVC persistent reduced 5%
• FEV160%-80% predicted
Severe • FEV/FVC persistent reduced >5%
• FEV, <60% predicted
ICS—inhaledcorticosteroid; LABA—inhaledlong-acting beta3-agonist; SABA—inhaledshort-acting beta3-agonist; wk—week. Note\:Assign theseverityoftheasthma to themostseverecategoryforwhich anyofthe threefeaturesarepresent.
CHAPTER 17 PULMONARY 243

244 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Symptoms
• Patients may report some or all of the following symptoms\:
Cough—Nocturnal cough, recurrent cough during spe­ cific seasons, cough in the presence of triggers, or persis­ tent cough (several weeks).
Wheeze—A high-pitched whistling sound may be heard on expiration.
Difficulty breathing—Patients may complain of chronic or acute episodes of shortness of breath (SOB).
Chest tightness—A bandlike constriction will com­ monly be reported as opposed to a sharp pain.
Physical Exam
• Physical exam findings may be unremarkable when the patient is asymptomatic, but the presence of abnormal find­ ings becomes more prominent with increasing severity of asthma or during acute exacerbations.
Inspection—An increase in anterior-posterior diameter of the chest due to air trapping; hunched shoulders; use of accessory muscles.
Percussion—Hyperresonant.
Auscultation—Prolong expiratory phase; wheezes typi­
cally heard on expiration; wheezes can be heard on both inspiration and expiration as the severity of the obstruc­ tion increases and then becomes potentially inaudible with no airflow.
Extrapulmonary findings—Conjunctival congestion (allergic conjunctivitis), eczematous lesions (atopic der­ matitis), or pale bluish nasal mucosa with turbinate ede­ ma (allergic rhinitis).
Next Step\:
Step 1) Establishing a diagnosis ofasthma involves a careful clin­ ical assessment that should determine (1) episodic symptoms of airflow obstruction are present, (2) airflow obstruction is reversible, and (3) exclusion of alternative diagnoses. Pulmo­ nary function testing (PFT) such as a spirometry is an objective tool that can establish airflow obstruction, severity, and revers­ ibility. Spirometry can be performed in children >5 years of age, and spirometry measurements should be taken before and after administration of a short-acting bronchodilator to assess revers­ ibility. Spirometry results may show the following\:
Airflow Limitation
• FEV, and FEV,/FVC (or FEV1/FEV6) values are typically reduced relative to the predicted or reference values that indicate an airflow obstruction (see Table 17-1).
• Reversibility is indicated by an increase in FEV, of >12% and >200 mL from baseline after inhalation of a short-acting bronchodilator.
No Airflow Limitation
• Patients may have a normal spirometry test at the time of an evaluation.
• The next step in these patients is to either repeat the spi­ rometry when they are symptomatic or challenge them with a bronchoprovocation test with methacholine, mannitol, or exercise to demonstrate reversible airflow obstruction.
Step 2) Once the diagnosis has been established, it is impor­ tant to characterize the severity of the asthma, which will help guide decisions for initiating treatment (see Tables 17-1 and 17-2).
Step 3) Educate patients on asthma self-management, which can take the form of a written “asthma action plan” that will
Table 17-2 • Asthma Medications
1 --------!-------- Net Effect
Bronchodilates '
Bronchodilates
Medications
Inhaled Short-acting (32-agonists (SABA)
• Albuterol
• Levalbuterol
• Pirbuterol
Inhaled Long-acting (32-agonists (LABA)
• Salmeterol • Formoterol
Inhaled Corticosteroids (ICS)
• Beclomethasone • Budesonide
• Flunisolide
• Fluticasone
• Mometasone • Triamcinolone
acetonide
Systemic Corticosteroids
Drug Category
Beta2 agonist
Beta2 agonist
Corticosteroid Anti-inflammatory
• Methylprednisolone Corticosteroid Anti-inflammatory j • Prednisolone
• Prednisone
| Immunomodulator
•
Omalizumab
Monoclonal antibody (Binds to IgE)
LTRA
LTRA 5-Lipoxygenase inhibitor
Mitigates an allergic response to an allergen
4- bronchoconstriction +
i vascular permeability
| Leukotriene Modifiers • Montelukast
• Zafirlukast • Zileuton
j Methylxanthines • Theophylline
Mast Cell Stabilizers
• Cromolyn
• Nedocromil
Theophylline Bronchodilates derivative
LTRA—Leukotriene ReceptorAntagonist
Mast cell stabilizer
Modulates mast cell ! mediator release

help guide patients to recognize and handle worsening asthma and daily management.
Follow-Up\:
Patients should be periodically evaluated for their asthma control. Well-controlled patients may be seen every 1 to 6 months, but uncontrolled asthma patients should be seen more ffequendy (eg, 2-6 weeks). In addition, patients that are on chronic high-dose inhaled glucocorticoids should be monitored for potential side effects such as thrush, dysphonia, cataracts, or growth velocity deceleration (in children).
Pearls\:
• Not every asthmatic patient will wheeze.
• Bronchoprovocation challenge testing is contraindicated in patients with known aortic aneurysm, myocardial infarction, or stroke in the last 3 months, uncontrolled hypertension, and severe airflow limitation (ie, FEVj <50% predicted).
• Children are more likely to have complete remission com­ pared to adults; however, children with severe asthma are more likely to continue to have asthma as adults.
• Peak expiratory flow rate (PEFR) can be measured by a peak flow meter, which is a relatively inexpensive, portable device in which the patients draws in a maximal inhalation and then exhales forcefully into the device. PEFR is not partic­ ularly useful in detecting airflow limitation, and thus not a primary tool for the diagnosis of asthma, but rather it is used to monitor trends in the patient’s lung function.
• The forced expiratory volume in 6 seconds (FEV6) is some­ times used as an approximation for the FVC.
• The diffusing capacity for carbon monoxide (DCLO) is normal to elevated in patients with asthma, but decreased in patients with emphysema.
• The chest x-ray is usually normal or may demonstrate hyper­ inflation in patients with asthma, but ordering a chest x-ray may be useful for excluding other diagnoses.
• Allergy testing is not useful for the diagnosis of asthma but as a useful adjunct in determining contributing factors to asthma. Allergy testing may be useful in patients with a history of allergies, persistent asthma, and in patients with moderate-to-severe symptoms.
• A spacer or valved holding chamber is attached to the me­ tered dose inhaler (MDI), which is typically recommended for children or any patient that has difficulty with the coordi­ nation between actuation and inhalation ofthe MDI or when inhaled glucocorticoid is being administered.
• By adding a spacer or holding chamber to the MDI, there is some evaporative loss of the propellant (chlorofluorocarbon [CFC] or hydrofluoroalkane [HFA]) that decreases the size of the medication droplets and thereby leads to an increase in smaller particles being inhaled and reduces the amount of medication being deposited in the back of the throat.
• Asthma patients should avoid nonselective beta-blockers (including eye preparations).
• Patients with asthma plus chronic rhinosinusitis with nasal polyposis may experience asthmatic symptoms, conjunctival congestion, nasal congestion, rhinorrhea, and facial flushing upon ingesting a cox-1 inhibitor (eg, aspirin, NSAIDs). This condition is referred to as aspirin exacerbated respiratory disease (AERD).
• Leukotriene modifiers, theophylline, and the mast cell sta­ bilizers are not the preferred agents to treat asthma, but are considered alternative agents.
• Theophylline requires regular drug level monitoring to avoid toxicity, and zileuton requires liver function testing to moni­ tor hepatotoxicity.
• Cromolyn and nedocromil can be used as preventive treat­ ment for either exercise-induced bronchoconstriction or unavoidable exposure to known allergens.
• An inhaled short-acting (32-agonist (SABA) is the preferred prophylactic agent for exercise-induced bronchoconstriction and should be taken 10 minutes before exercise.
• Foundational point—Bronchi and bronchioles can be plugged up by mucous plugs. On microscopic findings of the plugs, Curschmann’s spirals can be seen. Curschmann’s spirals are coiled shed epithelium that can be seen in asthma, bronchitis, and other lung diseases.
• Foundational point—Charcot-Leyden crystals can also be found in sputum from patients with asthma or para­ sitic infections (eg, ascariasis). On microscopic findings of the sputum, Charcot-Leyden crystals appear as needlelike structures with pointed ends. These crystals consist of lyso- phospholipase, which is an eosinophil-derived enzyme, and their presence indicates an eosinophil response.
• Foundational point—Typical lung volume and capacities seen in asthma are normal or T total lung capacity (TLC), T func­ tional residual capacity (FRC), and T residual volume (RV).
• On the CCS, it is important to order “advise patient, asthma care” because education is a component of asthma management.
• On the CCS, “advise patient, side effects of medication.”
• On the CCS, if you order “spirometry” to evaluate a patient for asthma, be careful not to order “incentive spirometry,” which is used for a breathing exercise, especially after surgery.
• On the CCS, it is acceptable to order either “PFT” or “spi­ rometry, flow” to evaluate for asthma, but be aware that the PFTs will provide a more inclusive set of lung function tests compared to the spirometry in the practice CCS.
1 NONACUTECOPD
Chronic obstructive pulmonary disease (COPD) is charac­ terized by a progressive airflow limitation that is not fully reversible. It is thought that the parenchymal tissue destruction that results in emphysema (4 elastic recoil) and the structural changes of the small airways that result in obstructive bron­ chiolitis (T increased airway resistance) are due to a chronic inflammatory response to noxious particles or gases.
CHAPTER 17 PULMONARY 245

246 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Clinical Features\:
Symptoms
• The three most common symptoms in COPD are cough, sputum production, and exertional dyspnea.
Cough—Chronic cough is usually the first symptom to develop in COPD, which may start as an intermittent cough that then becomes more noticeable throughout the day.
Sputum production—Patients may have a pattern of chronic sputum production that is usually mucoid in ap­ pearance but can become purulent during exacerbations.
Dyspnea—Patients may describe their dyspnea as “air hunger” or “heaviness.” As COPD advances, the principal feature is dyspnea on exertion, which can then become noticeable even at rest.
Physical Exam
• Physical exam findings may be unremarkable in the early stages of COPD but becomes more prominent in the pres­ ence of significant impairment of lung function.
Inspection—An increase in anterior-posterior diam­ eter due to hyperinflation (“barrel chest”); sitting in the characteristic "tripod” position to facilitate the accessory muscles.
Percussion—Hyperresonant.
Auscultation—Prolong expiratory phase; expiratory wheezes; diffusely decreased breath sounds; coarse crackles on inspiration.
Next Step\:
Step 1) A diagnosis of COPD should be considered in any patient who reports any combination of chronic cough, chronic sputum production, dyspnea, and a history ofexposure to smoke, dust, or chemicals. Patients who have any of these indicators for COPD should have a PFT such as a spirometry. The diagnosis ofCOPD is confirmed when there is airflow limitation based on the spi­ rometry (FEV1/FVC <0.70), symptoms compatible with COPD, and exclusion of other diagnoses.
Step 2) Managing patients with stable COPD involves multiple medical therapies, which include\:
Bronchodilators
• Inhaled short-acting bronchodilators—A short-acting (52- agonists (see Table 17-2) or a short-acting anticholinergic (eg, ipratropium) can be used for symptomatic relief when needed. Combination therapy with both beta agonist and anticholinergic (eg, albuterol/ipratropium) can provide a greater bronchodilator response compared to using a single agent, but monotherapy is still acceptable.
• Inhaled long-acting bronchodilators—Either a long- acting (52-agonists (see Table 17-2) or a long-acting anti­ cholinergic (eg, tiotropium) should be regularly scheduled when the short-acting bronchodilators cannot control the symptoms.
Pulmonary Rehabilitation
• Pulmonary rehabilitation should be considered in patients that have persistent pulmonary symptoms or have decreased functional status despite optimal medical therapy.
Smoking Cessation
• Smoking cessation is important because it can reduce the rate of FEVj decline in smokers with COPD.
• A guideline to help patients quit smoking is\: Ask -4 Advice -4 Assess —> Assist -4 Arrange.
Supplemental Oxygen
• Long-term oxygen therapy should be given to patients with a resting arterial oxygen tension (Pa02) <55 mm Hg or a pulse arterial oxygen saturation (Sa02) <88%.
• In the presence of cor pulmonale, long-term oxygen thera­ py should be given to patients with a Pa02 <59 mm Hg or Sa02 <89%.
• Long-term oxygen therapy reduces mortality rates in patients with severe resting hypoxemia.
Vaccinations
• An annual influenza vaccine should be given to all COPD patients.
• A pneumococcal vaccine should be offered to all patients >65 years old or <65 years old with a FEV1 <40%.
Step 3) Patient education is an important part of COPD management because it can help improve the patients health status.
Follow-Up\:
Routine follow-up care is important in patients with COPD. Monitoring airflow (ie, spirometry), symptoms, and functional status can determine when to modify therapy or identify any complications.
Pearls\:
• DCLO is decreased in proportion to the severity ofemphysema.
• The chest x-ray is not required to make the diagnosis of COPD, but is still commonly performed. Radiographic features of COPD may reveal hyperinflation of the lungs, increase in retrosternal airspace, and flattening of the diaphragm.
• Pulse oximetry can be used as a simple test to assess for hypox­ emia by measuring the arterial oxygen saturation (Sa02).
• An ABG can also assess for hypoxemia by measuring the arterial oxygen tension (Pa02), but also the severity of the hypercapnia. For reference, a patient with mild COPD may only have mild to moderate hypoxemia with no hypercapnia.
• Chronic respiratory acidosis leads to compensatory meta­ bolic alkalosis (ie, T serum bicarbonate).
• Chronic hypoxemia can lead to polycythemia (ie, T hema­ tocrit level).
• When patients continue to have significant symptoms or repeated exacerbations even with the optimal use of a

• •
• •
• •
•
•
•
long-acting bronchodilator, the next best step is to add an inhaled corticosteroid (see Table 17-2) as part of a combination therapy.
Theophylline (oral or IV) is considered a second-line agent compared to the other bronchodilators.
Roflumilast is an oral medication (phosphodiesterase-4 enzyme inhibitor) that is used to reduce the frequency of COPD exacerbations.
Guaifenesin is an oral expectorant that offers little value to patients with COPD.
Mucolytic agents (eg, acetylcysteine, dornase alfa) should not be used as routine care for patients with stable COPD because long-term studies have been controversial.
Prophylactic antibiotics are not recommended in patients with stable COPD.
The short-acting anticholinergic ipratropium can be remem­ bered because of its “immediate” effect, and the long-acting anticholinergic, tiotropium can be remembered because it is “totally longer.”
Surgery may be considered when patients continue to have significant symptoms despite optimal medical therapy and pulmonary rehabilitation. Lung transplantation or a lung volume reduction surgery (for patients with emphysema) may be helpful.
The definition of chronic bronchitis as a chronic productive cough for 3 months in each of 2 consecutive years with other causes of cough excluded is still used clinically, but is not included in the Global Initiative for Chronic Lung Disease (GOLD) reports.
Since most COPD patients have a mixture of emphysema and small airway disease, the terms “pink puffer” and “blue bloater” are incorrectly applied because both terms represent pure forms of emphysema and bronchitis, respectively.
• Type A pathophysiology\: “Pink puffer,” predominantly emphysema, dyspnea, thin, wasted, not cyanotic, 4 P02, normal or -1 PC02, 4 elastic recoil, -1DCLO, normal hema­
tocrit, cor pulmonale is infrequent.
• Type B pathophysiology\: “Blue bloater,” predominantly bron­ chitis, cough and sputum, obese, cyanotic, >14 P02, normal or T PC02, normal elastic recoil, normal DCLO, hematocrit
is often elevated, cor pulmonale is common.
• Foundational point—PFT measurements that are indicative of hyperinflation include a T TLC, T FRC, f RV, 4 inspira­ tory capacity, and 4 vital capacity.
• Foundational point—In restrictive lung disease, the lung volumes typically show a pattern of4 TLC, 4 FRC, and 4 RV.
• Foundational point—In restrictive lung disease, the FEVt and FVC are both typically reduced in proportion to de­ creased lung volumes, resulting in a FEV1/FVC ratio that is normal or increased. In obstructive lung disease, the FEVL is reduced more than FVC, therefore if the numerator is re­ duced more than the denominator, the resulting FEVj/FVC ratio is reduced.
• Foundational point—Three morphologic forms of emphy­ sema are centriacinar (associated with smoking), panacinar (associated with alpha 1-antitrypsin deficiency), and para- septal/distal acinar (least common, associated with bullae formation which can lead to spontaneous pneumothorax).
• Foundational point—Ipratropium is a quaternary derivative of atropine and when inhaled, it competitively blocks mus­ carinic receptors in the airway and thereby, prevents vagally mediated bronchoconstriction.
• On the CCS, remember to “counsel family/patient” since education is a component of COPD management.
• On the CCS, remember to “advise patient, no smoking.” • On the CCS, “advise patient, side effects of medication.”
Risk Factors\:
Individuals at risk of developing asbestosis are workers in asbestos mining and milling, textiles, shipyard workers, cement workers, plumbers, electricians, carpenters, insulators, welders, sheet metal workers, pipefitters, steamfitters, boilermakers, power plant work­ ers, workers in brake linings and clutch pads, and individuals ex­ posed to the soiled clothes brought home by an asbestos worker.
Clinical Features\:
Patients are typically asymptomatic for 20 to 30 years from the time of the initial asbestos exposure. However, it is thought that the duration and intensity influences the latency period. Typically, short-term, high-intensity asbestos exposure is associated with a shorter latency compared to prolonged, lower intensity exposure. Patients may develop any of the following clinical manifestations\:
• Dyspnea on exertion is a common symptom.
• End-inspiratory crackles can be fine or coarse, usually at the bases of the lungs.
RESTRICTIVE DISEASE
i ASBESTOSIS
Asbestosis is a pneumoconiosis caused by inhaling asbestos fibers (ie, fibrous silicate). The asbestos fibers can be long and curly, which are referred to as serpentine fibers (eg, chrysotile), or fibers can be long and straight and are referred to as amphi- bole fibers (eg, crocidolite, amosite). Asbestos exposure has been associated with the following\:
• Parenchymal interstitial fibrosis
• Pleural plaques
• Pleural thickening
• Pleural effusions
• Small-cell and non-small cell carcinoma of the lungs
• Mesothelioma
CHAPTER 17 PULMONARY 247

248 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Dry, nonproductive cough.
• Clubbing.
• Cor pulmonale is usually seen in advanced disease and can present as jugular venous distention, hepatojugular reflux, and peripheral edema, and a loud P2 heart sound may be heard if there is pulmonary hypertension.
Next Step\:
Step 1) Diagnosis of asbestosis is based on evidence of expo­ sure, evidence of pathology consistent with asbestos-related disease, and exclusion of other causes. Diagnostic modalities include the following\:
PFT—The classic finding is a restrictive pattern, although a mixed restrictive and obstructive pattern can sometimes be seen. Characteristic findings include 4 vital capacity,
4 TLC, 4 DLCO, normal ratio of FEV/FVC.
Chest X-ray—Initially, irregular parenchymal opacities begin in the lower lobes bilaterally, and over time, the opaci­ ties can be seen in the middle and upper zones of the lung. Abnormal pleural findings on chest x-ray are good indica­ tors of asbestos exposure since pleural findings in other interstitial lung diseases are uncommon. .
High resolution computed tomography (HRCT)—HRCT is the next best step when PFTs or chest x-ray findings are indeterminate because HRCT is better at delineating pleu­ ral plaques, thickening, “rounded atelectasis” due to pleural adhesions, and parenchymal lesions.
Bronchoalveolar lavage (BAL)—BAL can detect asbestos fibers and asbestos bodies (ie, fibers coated with protein and iron, which appear as beaded rods with knobbed ends). When inorganic particulates become coated with protein and iron complexes, the generic term ferruginous bodies is used.
Transbronchial biopsy—Rarely performed to establish a diagnosis since BAL recovers more material and therefore offers a better indicator of tissue burden.
Step 2) There is no specific therapy for asbestosis. Managing patients with asbestosis includes the following\:
• Withdraw from further asbestos exposure, and report to state or federal agencies
• Smoking cessation
VASCULAR DISEASE
1 PULMONARYEMBOLISM
• Prompt attention and treatment of respiratory infections
• Pneumococcal and influenza vaccinations
• Assess the degree of functional impairment because it will determine how closely they need to be monitored (ie, PFT’s, chest films, office visits)
Follow-Up\:
Screening patients for lung cancer or mesothelioma with chest x-ray or CT is not recommended because it has not been shown to prevent mortality.
Pearls\:
• There is a higher risk of lung cancer in people who were exposed to asbestos and are smokers since there is a multi­ plicative effect.
• Asbestos exposure increases the risk of developing malig­ nant mesothelioma.
• It appears that long, straight asbestos fibers (ie, amphibole fibers) are more toxic than long, curly asbestos fibers (ie, ser­ pentine fibers) because they are deposited further into the dis­ tal lung tissue and therefore, the rate of clearance is reduced.
• It appears that exposure to amphibole fibers has a higher risk of lung cancer compared to the serpentine fibers.
• Asbestos bodies are not pathognomonic for asbestos since as­ bestos bodies can be seen in people without known exposure.
• Honeycombing is typically seen in advanced disease.
• When there is a good history of asbestos exposure and chest x-ray findings clearly demonstrate asbestos-related disease, no further imaging is necessary for diagnosis.
• The clinical exam findings in patients with interstitial lung disease are typically nonspecific.
• Foundational point—Asbestos bodies can be found inside macrophages in the process of phagocytosis. The iron com­ ponent of the asbestos body is thought to arise from phago­ cyte ferritin.
• On the CCS, “pulmonary function tests” or “PFT” is avail­ able in the practice CCS.
• On the CCS, basic chest x-ray films should include both the PA and lateral views.
• On the CCS, “bronchoalveolar lavage” or “BAL” is not recog­ nized in the practice CCS.
Risk Factors\:
Risk factors for pulmonary emboli can be remembered by Virchow’s triad\:
Stasis
Immobility, postoperative state, prolong inactivity during travel, obesity, stroke, paralysis, CHF
Endothelial Injury
Surgery, trauma, central venous instrumentation
Pulmonary embolism (PE) refers to an obstruction of the pulmonary artery or one of its branches by any substance that can travel within the bloodstream such as air, fat, tumor cells, foreign bodies, amniotic fluid, septic emboli, or thrombus. For the remainder of the review, this topic will focus on pulmonary embolism secondary from a thrombus.

Hypercoagulable States
Acquired conditions—Medications (eg, OCP, HRT, tamox­ ifen), pregnancy, smokers, medical illness (eg, malignancy, multiple myeloma, polycythemia, nephrotic syndrome, antiphospholipid syndrome, history ofvenous thromboem­ bolism, bums)
Inherited conditions—Factor V Leiden mutation, prothrom­ bin gene mutation, protein C deficiency, protein S deficiency, antithrombin III deficiency, hyperhomocystinemia
Clinical Features\:
There is no single symptom or sign that is specific to pulmonary embolism. However, commonly reported signs and symptoms include acute onset of dyspnea, pleuritic chest pain, cough, hemoptysis, tachypnea, tachycardia, and rales. Keep in mind that patients can be completely asymptomatic to having clinical features suggestive of a massive PE, which may include any of the following\:
• Hypotension
• Syncope
• Cyanosis
• JVD
• Right-sided S3
• Parasternal lift
Next Step\:
Step 1) The initial steps to a patient suspected of having a PE is to stabilize the patient. Provide supplemental oxygen to patients with hypoxemia, and consider intubation if the patient is in respira­ tory failure. Intravenous fluids (eg, normal saline) can be carefully given to patients who present with hypotension and appropriate monitoring are important initial steps in caring for the patient
Step 2) Administer empiric anticoagulation in patients for whom clinical suspicion of PE is high. Do not delay treatment in these patients while awaiting diagnostic confirmation for a PE. Patients that have low or moderate clinical suspicion for a PE may proceed with prompt diagnostic investigations for a PE.
Step 3) There are several different diagnostic modalities to evaluate a patient with suspected PE. Not every test should be ordered, but for board purposes, it is important to know the different features of each test.
ABG—ABG results are nonspecific for PE, but possible findings include hypoxemia, hypocapnia with respiratory alkalosis (due to hyperventilation), or hypercapnia with respiratory acidosis (due to a massive PE causing respira­ tory collapse). The alveolar-to-arterial 02 partial pressure gradient (A-a gradient) is typically elevated in patients with PE, but a small subset of patients will have a normal A-a gradient.
Chest x-ray—Possible findings include a normal chest x-ray, atelectasis, pleural effusions, localized area of decreased vascular markings corresponding to vessel occlusion (Westermark’s sign), or a wedge-shaped opacity near the pleural base which represents a pulmonary infarction
(Hampton’s hump). Chest x-ray is an appropriate study to rule out other diseases, but it also allows interpretation ofthe V/Q scan if the scan is going to be ordered in the near future.
EKG—Possible abnormalities include sinus tachycardia, nonspecific ST-segment and T-wave changes, SjQ3T3 pattern, new incomplete right bundle branch block, RVH, or right axis deviation.
D-dimer—D-dimer is a protein that represents a degrada­ tion product of cross-linked fibrin, which can be detected in the serum by using different assays (eg, ELISA). D-dimer is a good “rule-out” test because a PE can be excluded in patients with low or moderate clinical pretest probability for a PE with a normal D-dimer level. However, a D-dimer has rather poor specificity since an elevated D-dimer level is considered nonspecific. Elevated D-dimer can also be seen in patients with an MI, atrial fibrillation, stroke, DIC, sepsis, surgery, trauma, malignancy, severe liver disease, renal dis­ ease, and pregnancy. Therefore, ordering a D-dimer level in the hospital setting has a limited role.
Duplex ultrasound—Since DVT and PE are closely related, ultrasound of the lower extremities is sometimes performed in the evaluation of a PE. When a positive ultrasound con­ firms a DVT, no further testing is required and treatment can be initiated. However, a normal ultrasound of the lower extremities does not rule out a PE since a clot could be in the pelvic veins, iliac veins, or has already embolized to the lungs. Further diagnostic testing is often required in pa­ tients with a normal ultrasound but with suspicion for a PE.
CT pulmonary angiography (CTPA)—CTPA is rapidly becoming the initial diagnostic evaluation for suspected PE. CTPA involves the use of intravenous contrast to detect a clot as a filling defect in the pulmonary vasculature from a CT scan. Advantages of CTPA is the availability, relative quickness of the procedure, noninvasive, less costly than conventional pulmonary angiography, and the ability to diagnosis other diseases (especially if there is an underlying cardiac or lung disease). Disadvantages of CTPA is that it re­ quires an experienced reader, is contraindicated in patients with renal insufficiency and contrast allergy, and finally, is not as sensitive at detecting thromboemboli in smaller ves­ sels compared to conventional pulmonary angiography.
V/Q scan—The diagnostic evaluation for a PE is in a state of transition as CPTA is emerging as the imaging modality of choice. However, V/Q scans are still used, especially if there is a contraindication to CPTA such as contrast allergy or renal disease. The V/Q scan involves two parts that include injecting an isotope into the patient and ob­ serving for a perfusion defect, and secondly, having the patient inhale an isotope to observe for ventilation defects. Patients with a PE will typically have a perfusion defect, but a normal ventilation scan. Patients with airway disease will typically have both a perfusion and ventilation defects in the same corresponding areas. The probability of having a PE from the V/Q scan can be categorized as high, interme­ diate, low, and normal. V/Q scans that are high probability or normal are most helpful because there is sufficient evi­ dence to initiate treatment for high probability scans and to
CHAPTER 17 PULMONARY 249

250
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
exclude the diagnosis of PE in normal scans. Unfortunately, up to 75% ofV/Q scans are nondiagnostic (ie, low or inter­ mediate) and further testing is usually required.
Pulmonary angiography—Conventional pulmonary angi­ ography is considered the “gold standard” in the diagnosis of PE. Pulmonary angiography is a safe, but invasive proce­ dure that involves threading a catheter through the jugular or femoral vein into the pulmonary arteries and injecting contrast to detect a clot as a filling defect.
Step 4) The primary treatment for a PE is anticoagulation, but other therapies include thrombolysis, IVC filter, and embolectomy.
Anticoagulation
Unfractionated heparin (UFH)
• UFH has a short half-life, which would be a good choice to treat a patient if they were to undergo an invasive procedure (eg, embolectomy), the patient has a risk of bleeding because it can be reversed with protamine sulfate, or allows for a smoother transition from UFH to thrombolytic therapy when thrombolysis is still considered during the evaluation process.
• When severe renal insufficiency exists (ie, CrCl <30 mL/min), UFH is the preferred agent over LMWH or subcutaneous fondaparinux.
• Disadvantages of UFH are monitoring the aPTT to achieve a target level, heparin dose adjustments, and risk of developing heparin-induced thrombocytopenia (HIT).
• The importance of achieving a therapeutic aPTT within 24 hours cannot be overstated because failure to do so has been associated with a higher risk of PE recurrence.
Low molecular weight heparin (LMWH)
• LMWH such as enoxaparin, dalteparin, tinzaparin exhibit a longer half-life, more predictable dose-response, requires no monitoring, less likely to cause a HIT, and ideal for home- based therapy.
Factor Xa inhibitor
• Fondaparinux can be given subcutaneously, requires no monitoring, but is contraindicated in patients with severe renal insufficiency.
• Consider fondaparinux in patients with a history of HIT because it has little to no antiplatelet effects.
Warfarin
• The effects of warfarin are monitored by the INR with a target of 2.5 for an acute PE.
• Warfarin can be initiated on the same day as UFH, LMWH, or fondaparinux.
• Overlap UFH, LMWH, or fondaparinux with warfarin for at least 5 days until the INR is in the therapeutic range of 2.0 to 3.0 for at least 24 hours.
• Duration of anticoagulation should be individualized to the patient’s circumstances, but typically 3 months of treatment and then reassessed. Patients that have reversible risk factors (eg, surgery, trauma, immobilization) may only require a total
of3 months, but patients that have recurrent disease or irrevers­ ible risk factors (eg, cancer, factor V Leiden mutation, protein C and S deficiency) usually require long-term anticoagulation.
Thrombolytic Therapy
• Thrombolytic agents such as alteplase (rtPA), streptokinase, and urokinase increase plasmin levels, which cause lysis of the clot.
• The main indication for thrombolysis is in a patient with confirmed diagnosis of PE who is hemodynamically unsta­ ble (ie, hypotension) in which thrombolytic therapy may be lifesaving.
• Contraindications to thrombolytic therapy include\: bleed­ ing diathesis, internal bleeding within the past 6 months, recent surgery or trauma, intracranial disease (eg, neoplasm, aneurysm), stroke within past 2 months, and uncontrolled hypertension.
IVC Filter
• The two main indications for an IVC filter placement is a con­ traindication to anticoagulation or failure of anticoagulation.
Embolectomy
• Embolectomy can be performed surgically or using a cath­ eter and is considered a last resort effort in patients who have failed thrombolytic therapy or a contraindication exists for thrombolytic therapy.
Disposition\:
Patients diagnosed with acute PE are typically admitted to the hospital and patients with severe PE may require admission to the ICU.
Pearls\:
• It can be easily remembered that warfarin is in “war” with the vitamin K-dependent clotting factors (II, VII, IX, and IX), which results in impaired production of the factors. Factor VII (extrinsic pathway) can be considered the first victim because any preexisting factor VII in the circulation will be cleared fairly quickly because it has a short half-life (4-6 hours) which will eventually result in a prolong PT in the first few days of therapy. However, it takes approximately 5 days for the full effect of anticoagulation with warfarin because the intrinsic and common pathways are still intact (ie, longer half-lives of the other clotting factors).
• UFH and LMWH are the preferred agents to use during preg­ nancy since warfarin is a category X drug and is generally contraindicated in pregnancy, but it is okay to give warfarin postpartum since it does not cross into breast milk.
• Serum troponins can be elevated in 50% of patients with moderate to large pulmonary embolism, which is thought to be due to an acute right ventricular myocardial stretch.
• Care should be taken when administering IV fluids to patients with hypotension because an increase in right

ventricular stress, especially in patients with right ventricu­ lar dysfunction, can result in worsening of their heart.
• Foundational point—Of the several different fibrin degra­ dation products (FDP), one is called a D-dimer. The D stands for domains, hence, two identical domains that have been crosslinked by factor XIII.
• Foundational point—If there is complete airway obstruc­ tion, but perfusion is normal, then the V/Q is equal to zero and thus, referred to as intrapulmonary shunt. In contrast, if perfusion is completely obstructed (eg, pulmonary embolus), but ventilation is normal, then the V/Q approaches infinity and is referred to as alveolar dead space.
• Foundational point—Ventilation and perfusion are both greater in the bases (gravity-dependent regions) compared to the apices. Since the gradient between the apical and basilar perfusion is greater than the gradient between the apical and basilar ventilation, the V/Q ratio is higher in the apices com­ pared to the bases. In an upright lung, the V/Q ratio in the apices is >1.0 resulting in T P02 and 4 PC02, but the V/Q ratio in the bases is <1.0 resulting in 4 P02 and t PC02.
• CJ\: A 32-year-old businesswoman presents with an acute onset of dyspnea, cough, right-sided chest pain, but no reports of leg pain. She is a heavy smoker, on OCPs, with no previous history of DVT/PE, no history of malignancy, no recent surger­ ies or trauma, no contraindications to anticoagulation, but has an anaphylactic reaction (type I hypersensitivity) to contrast media. Her vitals are 37.0°, 95/62, HR-115, RR-32. What are your initial steps?
Physical Examination\:
General appearance\: In apparent respiratory distress
Chest/Lungs\: Tachypnea. Clear breath sounds over left lung; rales over right lower lobe.
Heart/Cardiovascular\: Tachycardia. No extra heart sounds. NoJVD.
Abdomen\: Normal bowel sounds. No bruits. No mass or tenderness.
Extremities/Spine\: No edema. No clubbing or cyanosis. Second Order Sheet\:
First Order Sheet\:
1) IV access
2) NSS,0.9%NaCl,IV, continuous
3) Pulse oximetry, stat
4) Supplementaloxygen
5) Continuouscardiac monitor, stat
6) Continuous blood pressure cuff, stat
INFECTIONS
I TUBERCULOSIS
Third Order Sheet\:
1) Heparin, IV, continuous 2) PTT, routine, q4 hours
Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is transmitted from person to person through direct inhalation of aerosolized droplets of the organism. Upon establishing a focus infection in the lung, the infection can progress to clinically active disease (progressive primary disease), remain dormant with reactivation at a later time, or immediate clearance of the organism.
• On the CCS, “V/Q scan” and “CTA, chest, with contrast” are both available in the practice CCS.
Risk Factors\:
Close contact to a person with active TB, recent immigrant (<5 years) where TB incidence is high, history of a positive test for M tuberculosis, health-care workers, homeless people, prisoners, nursing home residents, alcoholics, drug users, and patients with medical conditions that put them at risk for TB (eg, AIDS, HIV, transplant recipients, silicosis, renal failure requiring dialysis, head and neck'cancer, lung cancer, lymphoma, leukemia, intestinal bypass surgery (eg, jejunoileal bypass), gas­ trectomy, diabetes, chronic glucocorticoid users, >10% below ideal body weight).
Result\: 87%
Fourth Order Sheet\: 1) V/Qscan,stat
2) D-Dimer, stat
Pearl\:
Result\:Perfusionscan—Diminished perfusion in right lower lobe, Venti­ lation scan—Normal findings
Result\: 500 mcg/L (nl\: <250)
1) ABG, stat
2) CXR, portable, AP, stat
3) EKG, 12 lead, stat
4) CBC with diff, stat 5) BMP, stat
6) CK-MB, stat
7) Troponin I, stat
8) PT/INR, stat
9) PTT.stat
Result\: pH-7.5, pCO2-30, pO2-60, HCOj-22
Result\: Normal findings
Result\: Sinus tachycardia, T-wave inversion in aVR
Result\: Leukocytosis
Result\: WNL
Result\: WNL
Result\: WNL
Result\: PT-13.0 seconds (nl\: <12), INR-0.9
Result\: 30.0 seconds (nl\: <28)
CHAPTER 17 PULMONARY 251

252 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Clinical Features\:
Latent TB—Patients are asymptomatic.
Active TB—Patients may present with any of the systemic and pulmonary features\:
Systemic—Fever, night sweats, malaise, weight loss.
Pulmonary—Productive cough, hemoptysis, pleuritic chest pain, rales, or bronchial breath sounds over involved lung (ie, indication of consolidation).
Extrapulmonary TB—Up to 20% of TB cases will be extrapul- monary. Extrapulmonary manifestations can occur at the same time as the primary infection or at the time of reactivation. The following are extrapulmonary sites with its manifestations listed from a relative head to toe fashion\:
Neurologic—Tuberculous meningitis, tuberculoma (round mass lesion).
Cardiac—Pericarditis.
Pleura—Pleural effusions.
GI—Peritonitis, enteritis, liver disease.
Genitourinary—Renal granulomas, ureteral strictures, genital TB.
Adrenals—Adrenal insufficiency.
Bone—Spinal TB (Pott’s disease).
Lymphatics—Painless cervical and supraclavicular lymph- adenopathy. Mediastinal, hilar, and retroperitoneal lymph nodes are other sites.
Dermatologic—Ulcers, abscesses, lupus vulgaris.
Disseminated—Also referred to as miliary TB; results from hematogenous dissemination of M tuberculosis that can affect multiple organs. Clinical manifestations are usually nonspecific and can occur at the time of a primary infection or at the time of reactivation. The lesions within the organs typically resemble “millet seeds.”
Next Step\:
Step 1) Patients suspected of having TB should be placed into a separate waiting room wearing a surgical mask, and health-care workers caring for the patient should also be masked.
Step 2) Evaluation for latent, active, and extrapulmonary TB is the following\:
Latent TB
• Evaluate for latent TB in individuals with contact to pa­ tients with active TB or individuals with an increased risk of reactivation (eg, silicosis, diabetes, renal failure requiring dialysis, head and neck cancer, lung cancer, lymphoma, leu­ kemia, >10% below ideal body weight, transplant recipients, TNF-alpha inhibitors, chemotherapy, glucocorticoid users, CXR with fibrotic changes consistent with prior TB, HIV infection).
• Treatment for latent TB (see step 3) should only commence once active TB has been ruled out.
Table 17-3 • Interpretation of the PPD PPD Size Groups
1
•
CXR—chestx-ray; IV—intravenous; RF—renal failure; TB—tuberculosis
The tuberculin skin test (TST) and the interferon gamma release assay (IGRA) are tests used to evaluate latent TB by assessing the cell-mediated immunity of the patient. Consider the two tests\:
TST—The Mantoux test involves the intradermal injec­ tion of purified protein derivative (PPD) to assess previous exposure to mycobacterial antigens by stimulating the type IV-delayed type hypersensitivity response. Only skin induration is assessed 48 to 72 hours after injection, and a positive test is interpreted as indicated in Table 17-3.
PPD positive—Proceed to evaluate for active TB, but keep in mind that false positive tests can occur in pa­ tients that received the Bacille Calmette-Guerin (BCG) vaccination or have been exposed to nontuberculous mycobacteria (eg, M avium complex, M kansasii).
PPD negative—Repeat the PPD in 8 weeks for patients exposed to someone with active TB because it take as long as 8 weeks for the sensitization and development of the delayed hypersensitivity response in someone never exposed to the mycobacterial antigen. Keep in mind that false negative tests can result from improper administration, waning immunity, or someone who is immunosuppressed.
IGRA
• IGRA is an in vitro blood test that can detect the pro­
duction of IFN-gamma from T lymphocytes follow­ ing stimulation with M. tuberculosis antigens.
• IGRA testing does not give false positive results because it is not affected by prior BCG vaccination or prior sen­ sitization from nontuberculous mycobacteria.
• Routine testing with both IGRA and PPD is not recommended.

5mm • • • •
10mm • •
• • •
15mm •
HIV-infected
Close contact with someone with active TB
CXR with fibrotic changes consistent with prior TB Immunosuppressed (transplant recipients, TNF-alpha inhibitors, chemotherapy, glucocorticoid users)
Children <4 years
Recent immigrants (<5 years) where TB incidence is high
Health care workers
Prisoners, homeless, IV drug users
Risk of reactivation (silicosis, diabetes, RF requiring dialysis, head and neck cancer, lung cancer, lymphoma, leukemia, >10% below
ideal body weight)
No known risk factors for TB

• The CDC recommends that IGRA testing is preferred in individuals with a history of a BCG vaccination and individuals from groups that have historically have poor rates of returning to have their PPD read (eg, homeless people, drug users).
Active TB
• Evaluate for active TB in individuals where there is a suspi­ cion for tuberculosis, which can be based on the presence of risk factors, history of prior TB infection (ie, positive PPD or IGRA), possible exposure to active TB, signs and symptoms of TB, or an incidental finding on CXR suggestive of TB.
• It may not always be possible to establish a definitive diag­ nosis ofTB prior to the start oftreatment, therefore, empiric therapy to treat active TB (refer to step 3) can be initiated when there is a high clinical suspicion for TB based on the patients history including epidemiologic factors (ie, expo­ sure to TB), physical findings, radiographic findings, and a preliminary AFB smear-positive result.
Chest X-ray—The CXR is the initial diagnostic step in evaluating a patient with active TB. In primary active TB, nonspecific infiltrates may be found in any area of the lung. In reactivation TB, cavitation can sometimes be present, and infiltrates are typically found in the upper lobes (apical-posterior segments) or lower lobes (apical segment) of the lungs. Other features that maybe present in active TB are hilar or mediastinal adenopathy, pleural effusions (ie, exudate), tuberculoma (mass lesion), and re- ticulonodular infiltrates (ie, miliary pattern).
Sputum samples—Sputum samples should be collected in patients whose chest x-ray demonstrate infiltrates ± cavitation. Three samples should be collected for add-fast bacilli (AFB) smear and culture, and at least one specimen should be reserved for nudeic acid amplification (NAA) testing in individuals with signs and symptoms ofpulmo­ nary TB for which a diagnosis of TB is still considered.
AFB smear—AFB smear is rapid and inexpen­ sive, but has relatively low sensitivity (40%-80%). The smears can be stained with the traditional Ziehl-Neelsen dye or with a more sensitive dye, auramine-O.
Culture—Culture is important for identification of M. tuberculosis and drug susceptibility. Unfortu­ nately, results can take a long time (3-8 weeks).
Nudeic acid amplification—NAA testing is a useful adjunct in the early stages of patient evaluation because results can be obtained fairly quickly (24-48 hours) while the cultures are still pending. NAA testing provides a greater positive predictive value in AFB smear-positive results where nontuber- culous mycobacteria is common, and NAA testing can rapidly confirm the presence of M. tuberculosis in 50%-80% of AFB smear-negative results, but cul­ ture-positive specimens.
Extrapulmonary TB
• To establish a diagnosis of extrapulmonary TB, obtain fluid or tissue specimens for AFB smear, culture, and drug suscep­ tibility testing (eg, synovial, pericardial, peritoneal, pleural fluid, CSF, bone, or lymph tissue).
Step 3) Treatment for tuberculosis typically consists of a com­ bination of first-line antituberculosis agents which are isonia- zid (INH), pyrazinamide (PZA), ethambutol (EMB), rifampin (RIF), and the newer rifamycins, rifabutin and rifapentine.
Latent TB
• Treatment for latent TB includes INH therapy for 9 months in HIV-negative or HIV-infected patients.
• Regardless of the test result for latent TB infection, HIV-infected patients should still be treated in cases of recent contact with someone with active TB or in a HIV-infected patient with a history of untreated TB.
Active TB
• For the first 2 months (initial phase) treat with RIPE (Rifampin + Isoniazid + Pyrazinamide + Ethambutol), then obtain sputum cultures at the completion of the initial phase, followed by INH + RIF for the next 4 months (continuation phase) for a total of 6 months of treatment.
• Extend treatment in the continuation phase to 7 months (total of 9 months of treatment) in patients who did not receive PZA in the initial phase or patients that initially had a cavitation in the initial chest films + positive sputum cultures at the completion of the initial phase.
Extrapulmonary TB
• The basic principles for the treatment of pulmonary TB applies to extrapulmonary TB with a standard 6-month course of treatment, except for TB meningitis (total of 9-12 months) and bone and joint TB (total of 6-9 months of at least including RIF).
• Adjunctive glucocorticoid therapy is recommended in patients with TB meningitis and TB pericarditis.
Special Populations Pregnancy
• The same basic principles are used to treat latent TB and ac­ tive TB with the exception of excluding PZA from the initial phase because of the uncertainty of causing adverse effects in pregnancy (Category C drug rating).
• Do not use streptomycin because it is a known teratogen that can cause congenital deafness (Category D drug rating).
• Breastfeeding is not a contraindication in mothers being treated only with first-line agents for active or latent TB.
• Mothers that are breastfeeding and receiving INH should be given supplemental pyridoxine (vitamin Bg) to both infants and mothers.
CHAPTER 17 PULMONARY 253

254 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Children
• Drug regimens for adults are generally the same regimens for children.
• Treatment should be started as soon as the diagnosis is suspected in children <4 years because of a high risk of TB to disseminate.
• Visual acuity monitoring is usually performed in patients receiving ethambutol (EMB) since the drug can cause optic neuritis.
HIV-infected
• The general approach to TB treatment is the same as HIV-negative patients. However, HIV-infected patients should be treated with rifabutin instead of rifampin because there are drug interactions, particularly with protease inhibitors.
Step 4) TB is a reportable disease, and any suspected or con­ firmed cases ofTB should be reported to the health department.
Disposition\:
In the majority of cases, patients with TB can be initially treated as an outpatient, but it is important for the ER physicians to contact public health services or physicians for the long-term management of the patient.
Pearls\:
• Individuals with latent TB are not considered contagious.
• Individuals with active, untreated pulmonary TB (especially in the presence of cavitary lesions) are considered contagious.
• Individuals with only extrapulmonary TB without pulmo­ nary disease are not contagious.
• TB is not transmitted by fomites.
• IGRA or PPD should not be used to diagnosis active TB.
• Patients receiving INH can have neurologic side effects such as peripheral neuropathy, ataxia, or paresthesia, there­ fore, add vitamin Bfi (pyridoxine) in patients who are at risk for INH-induced neurotoxicity, which includes pregnant women, breastfeeding women, infants, children, elderly, HIV-infected, diabetics, alcoholics, chronic liver disease, renal failure, and nutritional deficiency.
• A two-step skin testing involves a second PPD testing 1 to 2 weeks after a negative PPD result. The idea behind a second testing is for individuals who were previously exposed to TB may have a waning response to the PPD over time that may give a false-negative result if only one PPD test is given. Performing the first PPD in the two-step testing may actu­ ally “boost” the immune system, which will allow a better reflection of the patient’s status when given a second PPD. If the second test is negative, then the patient is truly negative. Two-step testing is useful for individuals that are tested pe­ riodically (eg, health-care workers, nursing home residents).
• Patients with continued positive cultures after 4 months of treatment are considered a failing course of treatment, and another single agent should never be added to a failing regi­ men because of concerns for resistance to the drug.
• Direct observation oftherapy (DOT) is to assure that patients are ingesting anti-TB agents by having a health-care provider watch the patient swallow the medications. DOT should be instituted in children, individuals with memory impairment, psychiatric illness, drug users, homeless, HIV infection, pul­ monary TB with positive sputum cultures, prior treatment with active or latent TB, drug resistance, relapse, and patients with treatment failure.
• Ghon focus refers to a granulomatous structure (tubercle) which represents the initial primary lesion in the lung from a TB infection.
• Ghon complex refers to the Ghon focus accompanied by perihilar lymph node involvement (ie, remember it’s a com­ plex of things together).
• Ranke complex refers to the evolution of the Ghon complex as a healed, calcified lesion.
• Formation of a cavity can occur when a caseous lesion erodes into a bronchiole allowing drainage of the necrotic material.
• Since M tuberculosis is an obligate aerobe, it has a predilec­ tion to settle in areas of high oxygen content after hematog­ enous spread. Therefore, upon reactivation, characteristic locations typically involve the apical segment of the upper lobe since there is a higher oxygen partial pressure.
• Foundational point—Mycobacterium tuberculosis is an obli­ gate aerobic, acid-fast, non-spore-forming, rod-shaped bacte­ rium. Although M tuberculosis is neutral on Gram’s staining, it is still considered a gram-positive bacterium since it lacks a true outer membrane. However, the cell envelope distinguishes this organism. The constituents ofthe cell envelope include mycolic acids, peptidoglycan, arabinogalactan, lipopolysaccharide (but without a lipid A), and lipoarabinomannan (LAM).
• Foundational point—Two notable organisms that are acid- fast are Mycobacteria species and Nocardia. What makes acid-fast unique is the ability of the mycolic acids (large fatty acid) to resist destaining by acid alcohol after being stained and holding “fast” to the initial stain.
• Foundational point—Although M tuberculosis does not have exotoxins or endotoxins, what makes M tuberculosis virulent is the sulfatides, catalase-peroxidase, LAM, mycolic acid gly- colipids, and trehalose dimycolate (also known as cord factor).
• Foundational point—One of the defense mechanisms to contain the bacteria is the presence of a caseous necrotic (“soft cheese”) granuloma that has a low pH and low oxygen tension that inhibit the growth of the bacteria but keep them viable for dormancy.
• Foundational point—Within the caseating granulomas are Langhans giant cells, which have a characteristic “horseshoe” pattern of nuclei.
• CJ\: A 45-year-old HIV-infected man started anti-TB medi­ cations 5 days ago and presents with fever, presence of new lymph nodes, inflamed and increased size ofpreexisting lymph nodes, and worsening ofhis respiratory symptoms along with worsening of his CXR. What is your next step? Answer\: The patient is experiencing a paradoxical reaction or immune reconstitution syndrome, which is a temporary exacerbation

of the infection after starting anti-TB medications. Although this reaction can occur in anybody, HIV-infected patients are commonly affected. The first step is to rule out other causes (eg, treatment failure, resistance), but the treatment for a para­ doxical reaction is supportive as it is a self-limited condition.
• CJ\: A 35-year-old woman is on RIF, INH, PZA, and EMB. Her AST is 5 times the upper limit of normal but she is as­ ymptomatic. Do you want continue treatment? Answer\: No. Hepatotoxicity can occur in RIF, INH, PZA, or EMB. Dis­ continue anti-TB agents if a patients aminotransferase is 5 times the upper limits of normal ± symptoms or 3 times the upper limit of normal in the presence of symptoms.
• Connecting point (pg. 290)—Patients that are taking TNF- alpha inhibitors (eg, adalimumab, etanercept, infliximab) for their rheumatoid arthritis are at risk of reactivation of TB.
• Connecting point (pgs. 8, 9)—Know the other types of hy­ persensitivity reactions.
• On the CCS, “PPD” or “Tuberculin skin test” are available in the practice CCS.
• On the CCS, ordering “sputum” will allow you to select the AFB smear and C&S in the practice CCS.
• On the CCS, “NAA” is not recognized, but “Nucleic acid am­ plification, mycobacteria RNA” is available in the practice CCS.
• On the CCS, remember to order “Notify public health de­ partment” during the case.
• On the CCS, “Advise patient, side effects of medication” since anti-TB agents can cause the following\:
Rifampin—Red-orange discoloration of body fluids, flulike syndrome, hepatitis
Isoniazid—CNS effects, lupus-like syndrome, hepatitis
Pyrazinamide—Hyperuricemia, GI upset, hepatitis Ethambutol—Optic neuritis, decrease in red-green
color discrimination, hepatitis
I COMMUNITY-ACQUIREDPNEUMONIA—ADULTS
Community-acquired pneumonia (CAP) refers to a pneumonia that is acquired in the community as opposed to the hospital (ie, hospital-acquired pneumonia).
Clinical Features\:
The clinical presentation of CAP is usually nonspecific and no single sign or symptom is pathognomonic for CAP. However, classic findings for “typical” bacterial pneumonias include fever, dyspnea, pleuritic chest pain, and a productive cough. Although the patient’s history and clinical features cannot always identify the etiologic pathogen, the clinical clues are listed in Table 17-4 for background knowledge.
Next Step\:
Step 1) The initial approach to a patient with CAP is the clinical assessment followed by a chest x-ray. Unfortunately, the radio- graphic findings cannot reliably distinguish bacterial from non- bacterial causes of pneumonia. However, it is still good to keep in the back of your mind that lobar consolidation, cavitation, and pleural effusions are suggestive of a bacterial etiology, while interstitial infiltrates are associated with viral causes.
Step 2) Once CAP is diagnosed or suspected, the decision has to be made to care for the patient either as an outpatient, inpa­ tient, or in the ICU. There are several different prediction scores (eg, CURB-65, PSI) that can assess the severity of the illness;
Table 17-4 • Clinical Clues to Pathogens in Community-acquired Pneumonia
Pathogen
Anaerobes
(eg, Bacteroides spp, Fusobacterium)
Chlamydophila pneumoniae
Chlamydophila psittaci
Coxiella burnetti
(Q fever)
Haemophilus influenzae (nontypeable)
Klebsiella pneumoniae
Associations
• Aspiration • Anesthesia • Alcoholics
• Atypical bug
• Young adults • Elderly people
• Atypical bug
• Exposure to infected birds
• Atypical bug
• Tick bite or inhalation of contaminated aerosols
from birth products of infected animals (eg, goats, cattle, sheep, cats, dogs, rabbits)
• COPD
• Cystic fibrosis • Elderly
• Alcoholics • Diabetics
• Nosocomial
Clinical Features
Gradual onset, "foul-smelling"sputum, poor dental hygiene, chills are uncommon
Gradual onset, hoarseness, sore throat (pharyngitis), occasional sinusitis
Abrupt onset of fever; dry cough, headache; other manifestations that may be present include chest pain, splenomegaly, maculopapular rash (Horder spots)
Acute\: Self-limited flulike illness, pneumonia, hepatitis
Chronic (>6 months)\: Endocarditis, vascular aneurysm
Gradual onset, fever, dyspnea, productive cough
Acute onset, fever, dyspnea, cough, "currant jelly" sputum
CHAPTER 17 PULMONARY 255
(Continued)

256 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Table 17-4 • Clinical Clues to Pathogens in Community-acquired Pneumonia (Continued)
Pathogen
Legionella spp
Moraxella catarrhalis
Mycoplasma pneumoniae
Pseudomonas aeruginosa
Staphylococcus aureus
Associations
• Atypical bug
• Exposure to aerosolized water with the bug
(eg, AC, whirlpool, showers) • Causes legionellosis
• COPD
• Atypical bug • Young adults
• COPD
• Cystic fibrosis
• Immunocompromised • Recently hospitalized
• Postinfluenza • IV drug users • Nosocomial
Clinical Features
Legionellosis is associated with two clinically distinct syndromes\:
1) Legionnaire's disease—Fever, pneumonia, and any of the following may be present\: nausea, vomiting, diarrhea, lethargy, confusion, chest pain, hyponatremia, hematuria
2) Pontiac fever—Fever, flulike illness, but self-limited condition
Less commonly, M catarrhalis causes pneumonia, which presents similarly to H influenzae (gradual onset, fever, dyspnea, productive cough).
More commonly, M catarrhalis causes COPD exacerbation (dyspnea increases, cough frequency increases, sputum production volume increases).
Gradual onset, fever, chills (rarely rigors),
dry cough, headache, and sometimes extrapulmonary causes (eg, bullous myringitis, hemolytic anemia, skin rashes, CNS, cardiac, and Gl involvement)
Fever, chills, dyspnea, productive cough, confusion
Fever, dyspnea, productive cough
Classic presentation includes acute onset, fever, chills, dyspnea, productive cough,"rust-colored" sputum, pleuritic chest pain
Sudden onset of fever, chills, nonproductive cough, rhinorrhea, sore throat, myalgias, headache
Streptococcus • pneumoniae
Viruses • (eg, influenza, RSV, adenovirus)
Most common cause of CAP
Influenza is a common viral cause of CAP seen in adults
A/C—airconditioner; RSV—respiratorysyncytial virus; spp—species
however, in clinical practice the prediction scores serves as an adjunct to the physician’s overall clinical judgment. For board purposes, the following will serve as a general guideline for managing a patient with CAP\:
Reasons to manage as an outpatient—Relatively young (<50 years), healthy, active, compliant, no comorbidities, unremarkable physical exam
Reasons to admit to the inpatient—Any combination of the following using your clinical judgment\: elderly, presence ofcomorbid conditions, altered mental status, T respiratory rate, T heart rate, T temperature, i blood pressure, hypox­ emia based on the pulse oximetry, inability to maintain oral intake, possible complications of the pneumonia itself (eg, development of pleural effusions, abscess, or respiratory failure)
Reasons to admit to the ICU—Patient in septic shock re­ quiring vasopressors, or patient requiring intubation and mechanical ventilation
Step 3) Initial treatment for adults with CAP is empiric antibi­ otics, which depends on the clinical setting. The following list is based on the guidelines from the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS)\:
Outpatient treatment for the uncomplicated patient
If the patient is previously healthy and no antibiotics within the previous 3 months, then\:
Option 1\: Macrolide (eg, azithromycin, clarithromycin, or erythromycin)
Option 2\: Tetracycline (eg, doxycycline)

Outpatient treatment for the more complicated patient
If the patient has comorbidities, use of immunosuppressive drugs, or use of antibiotics within the previous 3 months, then\:
Option 1\: Respiratory fluoroquinolone (eg, moxifloxacin, gemifloxacin, or levofloxacin)
Option 2\: Beta-lactam (eg, amoxicillin) + macrolide
Inpatient treatment
Option 1\: Respiratory fluoroquinolone
Option 2\: Antipneumococcal beta-lactam (eg, ceftriaxone, cefotaxime, or ampicillin-sulbactam) + macrolide
ICU treatment
Option 1\: Antipneumococcal beta-lactam + azithromycin
Option 2\: Antipneumococcal beta-lactam + respiratory fluoroquinolone
Option 3\: For penicillin-allergic patients use respiratory fluoroquinolone + aztreonam
Treatment with Special Concerns
Community-acquired MRSA
Option 1\: Add vancomycin or linezolid to the inpatient or ICU regimens.
Pseudomonas infection
Option 1\: Antipseudomonal beta-lactam (eg, piperacillin- tazobactam, cefepime, imipenem, or meropenem) + cipro­ floxacin or levofloxacin
Option 2\: Antipseudomonal beta-lactam + aminoglycoside + azithromycin
Option 3\: Antipseudomonal beta-lactam + aminoglycoside + respiratory fluoroquinolone
Option 4\: For penicillin-allergic patients, substitute aztreo­ nam for above beta-lactam
Step 4) Vaccinate for the influenza infection during the influ­ enza season. Pneumococcal vaccination should also be given to\:
• Persons >65 years old
• Younger people that are at risk ofpneumococcal disease\: im­ munocompromised, asplenia, alcoholics, smokers, nursing home residents, CSF leaks, DM, and chronic cardiac, pulmo­ nary, renal, or liver disease
Follow-Up\:
Patients managed in the outpatient setting or discharged from the hospital should follow up in 1 week with their physician for a reassessment, but a repeat chest x-ray is unnecessary if the patient is clinically improving.
Pearls\:
• Routine diagnostic testing to establish an etiologic diagnosis in outpatients with CAP is usually unnecessary since empiric treatment is usually successful.
• Patients admitted to the inpatient ward usually require more diagnostic testing such as blood and sputum cultures.
• Patients in the ICU usually require extensive diagnostic testing such as blood cultures, sputum specimen for culture and Gram stain, urinary antigen testing (UAT) for Legionella and Streptococcus pneumoniae, and endotracheal aspirate if intubated.
• “Atypical” bugs are atypical because they cannot be detected on Grams stain or cultivated on standard bacteria media.
• In approximately 50% of patients with CAP, no specific pathogen can be identified, and if identified, it is usually Streptococcus pneumoniae.
• The most common cause ofpneumonias in children <5 years old are viral pathogens (RSV most common), but in older children >5 years old the most common causes of CAP are Streptococcus pneumoniae, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.
• Both Chlamydophila pneumoniae and Chlamydophila psittaci are transmitted by respiratory route.
• Duration of antibiotic treatment for patients with CAP is a minimum of 5 days.
• Patients that are on intravenous antibiotics can be switched to oral therapy when they are hemodynamically stable, able to ingest orals, and are clinically improving.
• Foundational point—Bacteroides melaninogenicus and Fu- sobacterium are both anaerobic, gram-negative rods that can cause a necrotizing aspiration pneumonia. A key difference between the organisms is that Bacteroides melaninogenicus does not contain lipid A (ie, no endotoxin), but Fusobacte- rium does contain an endotoxic LPS.
• Foundational point—Coxiella burnetii is morphologically similar to Rickettsia. They are both obligate intracellular (use host ATP), gram-negative bacteria. What is unique to Coxi­ ella is that it can exist in an endospore form, which can make it resistant to heat and drying conditions. In addition, it does not require an arthropod vector, unlike Rickettsia.
• Foundational point—Haemophilus influenzae is a gram­ negative coccobacillus. H influenzae can be encapsulated (“typeable”) or unencapsulated (“nontypeable”). The encap­ sulated has six serotypes (a, b, c, d, e, f), and type b is known for causing meningitis, epiglottitis, sepsis, and septic arthri­ tis. The nontypeable H influenzae species are involved in up­ per and lower respiratory tract infections such as sinusitis, otitis media, pneumonia, and bronchitis. As with most gram­ negative bacteria, the outer membrane has an endotoxic LPS. H influenzae can also produce IgA proteases, which makes sense since they are under attack from the humoral immunity. H influenzae can be grown on chocolate agar, but require factor V (NAD) and factor X (hemin), which are both found in blood, hence the term Haemophilus (“blood loving”).
• Foundational point—Klebsiella pneumoniae is a gram­ negative, nonmotile, lactose-fermenting, rod. K pneumoniae is encapsulated, and some strains can produce a mucovis- cous capsule.
CHAPTER 17 PULMONARY 257

258 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Foundational point—Legionella pneumophila is a gram- negative, motile rod that is a facultative intracellular parasite to macrophages. What is unique about this organism is that it poorly stains with a Gram’s stain, but can be stained using a silver stain. In addition, L pneumophila grows on specialized media of buffered charcoal yeast extract with L-cysteine, iron, antibiotics, and dyes. L pneumophila is not transmitted from person to person.
• Foundational point—Moraxella catarrhalis (also known as Neisseria catarrhalis and Branhamella catarrhalis) is a gram-negative, aerobic diplococcus. M catarrhalis resembles Neisseria species on gram stain, but what is unique to this organism is that when grown on agar (chocolate or blood); the colonies can be pushed across the surface like a hockey puck (“hockey puck sign”).
• Foundational point—Mycoplasma pneumoniae is one of the smallest free-living bacteria. It lacks a cell wall (ie, no pepti- doglycan layer) and therefore, you cannot gram stain it and certain antibiotics (eg, penicillins, cephalosporins) are inef­ fective. However, M pneumoniae does have a cell membrane that is composed of cholesterol, which allows for the various shapes ofthe organism. Antibodies (IgM) to M. pneumoniae can develop and cross react with RBC antigens (ie, I antigen) at cold temperature, hence cold agglutinins (ie, RBCs clump­ ing together secondary to antibodies binding to antigen). Other causes of cold agglutinin include infectious mononu­ cleosis, influenza, and Rickettsia infection. Warm agglutinins (IgG instead) can be caused by CLL, SLE, viral infections, blood transfusions, and drugs (eg, methyldopa, penicillin). Autoimmune hemolytic anemia can be due to the presence of warm or cold agglutinins.
• Foundational point—Pseudomonas aeruginosa is a gram­ negative, obligate aerobe, non-lactose-fermenting, oxidase positive rod that can produce pyocyanin (blue pigment) and pyoverdin (fluorescent pigment) giving it a blue-green ap­ pearance. It also has a distinctive fruity, grapelike smell. Some of the key distinctive features include the presence of an en­ dotoxin, produces exotoxin A, produces alginate (biofilm for­ mation to protect against antibiotics), secretes phospholipase C (lyses RBCs), and secretes elastase (degrades IgG).
• Foundational point—Staphylococcus aureus is a gram-posi­ tive coccus that appears in grapelike clusters on Gram’s stain and has a golden pigment, hence the word aureus (Latin for gold). S aureus is also catalase positive (converts H202 to H20 and 02) and coagulase positive (fibrin formation for protection). Distinctive features of S aureus include protease A (binds Fc region of IgG thereby preventing opsonization and phagocytosis), leukocidins (kills leukocytes), hemolysins (lysis of RBCs), beta-lactamase (hydrolysis of the (3-lactam ring), lipase (digests lipids), hyaluronidase (breaks down con­ nective tissue), staphylokinase (dissolves fibrin), transpepti­ dase (cross-links peptidoglycan chains to form a cell wall), and releases exotoxins (eg, TSST-1, exfoliatin, enterotoxin).
• Foundational point—Staphylococcus epidermidis and Staph­ ylococcus saprophyticus are both catalase positive but coagu­ lase negative.
• Foundational point—Methicillin-resistant Staphylococcus aureus (MRSA) is defined by the presence of the mec gene, which encodes for penicillin binding protein 2a (PBP2a). Penicillin binding protein is a normal constituent of most bacteria and naturally binds to penicillins, hence the name. The function of these proteins is the biogenesis of the cell wall; however, PBP2a has a low affinity for the beta-lactam antibiotics, making these bugs resistant.
•
Foundational point—Streptococci are gram-positive cocci that can exist in pairs or chains. They are also catalase negative. There are five major types of streptococci to consider based on their surface (Lancefield) antigens and simply by their species\: Lancefield group A, Lancefield group B, Lancefield group D, Streptococcus viridians (no Lancefield), and Streptococcus pneu­ moniae (no Lancefield). The organisms can also be classified by their ability to lyse RBCs on blood agar. Beta-hemolytic organ­ isms can completely lyse RBCs, alpha-hemolytic can partially lyse RBCs leaving a green color on culture, and gamma- hemolytic (ie, nonhemolytic) cannot lyse RBCs on blood agar. Examples of the streptococci include Streptococcus pyogenes (group A, beta-hemolytic, bacitracin sensitive), Streptococcus agalactiae (group B, beta-hemolytic, bacitracin resistant), and Streptococcus bovis (group D, nonhemolytic). It should be noted that Enterococci are gram-positive cocci that were for­ merly classified as group D streptococci.
Foundational point—Streptococcus pneumoniae and Strep­ tococcus viridians are both alpha-hemolytic. However, Strep­ tococcus pneumoniae is optochin sensitive, bile soluble, and has a positive Quellung reaction (ie, indicates the presence of a capsule since it swells when antisera against the capsule is added). On the contrary, Streptococcus viridians is optochin resistant, bile insoluble, and lacks a capsule.
Foundational point—Influenza virus is an orthomyxovirus that has a negative, segmented, single-stranded RNA that can replicate within the nucleus. There are three types of influenza (A, B, and C). Influenza A and B can cause sea­ sonal epidemics in the United States, but influenza C does not appear to cause epidemics. Influenza A and B both have important antigenic glycoproteins studded along the surface membrane. First, hemagglutinin (H) is a protein that binds to host sialic acid receptors. Second, neuraminidase (N) is an enzyme that cleaves sialic acid allowing the virus to be released from the host cell. The hemagglutinin and neur­ aminidase is often used to describe the strain of the virus (eg, H1N1 influenza).
Foundational point—Antigenic drift occurs when there is a relatively minor change in the antigenicity of the virus (eg, point mutation in the H or N) that can result in a localized outbreak with mild disease. Antigenic shifts can also occur in the influenza virus because it has a segmented genome that can result in high rates of reassortment leading to com­ plete different antigenicity. The result can be more serious leading to epidemics and pandemics.
•
•
•
• Foundational point—RSV is a paramyxovirus that has a negative, unsegmented, single-stranded RNA that repli­ cates in the cytoplasm. It does not have hemagglutinin or

neuraminidase. As with most paramyxovirus (eg, mumps, measles, parainfluenza), it has an F protein on the surface of the virus that allows them to fuse with other cells resulting in multinucleated cells (ie, syncytial cells).
• Foundational point—Adenovirus is a lytic, nonenveloped virus that contains a double-stranded linear DNA. Host de­ fense against adenovirus is through cell-mediated immunity
• Connecting point (pg. 166)—Know the different serotypes of Chlamydia trachomatis. Also, know the microbiologic features and life cycle of Chlamydophila (formerly Chlamydia) pneu­ moniae and Chlamydophila (formerly Chlamydia) psittaci, which are both similar to Chlamydia trachomatis.
• On the CCS, “advise patient, no smoking.”
NEOPLASM
0 LUNGCANCER
Lung cancer is the leading cause of cancer-related death in both men and women not only in the United States, but also world­ wide. There are several different histologic types of lung cancer (see Table 17-5).
Clinical Features\:
The clinical presentation of lung cancer can be best understood by the "on-site” or “off-site” effects of the lung cancer.
On-site Effects (Direct Invasion)
Lung parenchyma invasion—Cough, hemoptysis, dyspnea Tumor obstruction—Pneumonia
Esophageal invasion—Dysphagia
Chest wall invasion—Chest pain
Recurrent laryngeal nerve invasion—Hoarseness
Phrenic nerve invasion—Diaphragm paralysis (ie, elevated hemidiaphragm, dyspnea)
Pleural invasion—Pleural effusion (ie, exudates) Pericardial invasion—Pericarditis, tamponade
Superior vena cava (SVC) obstruction—SVC syndrome (ie, facial and arm swelling, dyspnea, cough)
Sympathetic ganglia invasion—Horners syndrome (ie, miosis, ptosis, anhidrosis/no sweating)
Superior sulcus tumors with invasion into adjacent tis­ sues—A constellation ofsymptoms referred to as Pancoast’s syndrome\: SVC syndrome, Horner’s syndrome, brachial plexus invasion (shoulder pain, atrophy of hand and arm muscles), recurrent laryngeal nerve invasion (hoarseness), phrenic nerve invasion (diaphragm paralysis), supracla­ vicular lymph node enlargement, spinal cord compression
Off-site Effects (Distant Effects)
Metastasis—Frequent sites are LABB (Liver, Adrenal, Bone, Brain)
• On the CCS, ifyou order “vaccine” you will be able to select influenza and pneumococcal vaccine in the practice CCS.
• On the CCS, "urinary antigen test” is not recognized in the order menu, but type in “antigen” and you will be able to locate “Antigen, bacterial, pneumococcus, urine” and “An­ tigen, Legionella, urine” in the practice CCS. If you cannot find your order in the CCS, there are three approaches to take. First, type the order in the most specific format (eg, urinary antigen test). Second, type in a very broad term (eg, antigen). Finally, if you cannot find your order then you can click on the “Broaden Search” tab under the “Order Verifica­ tion” screen. The "Broaden Search” tab will provide you with a larger list of items from your original order input.
Paraneoplastic syndromes
Cushing’s syndrome—“Moon facies,” hirsutism, HTN, muscle weakness, glucose intolerance
Dermatomyositis/Polymyositis—Symmetrical proximal muscle weakness ± skin manifestations
Hypercalcemia—Nausea, vomiting, constipation, polyuria, polydipsia, lethargy
Hypertrophic osteoarthropathy—Clubbing, symmetrical painful arthropathy of the elbows, wrist, knees, and ankles
Lambert-Eaton myasthenic syndrome—Symmetrical prox­ imal muscle weakness, extraocular muscles usually spared (unlike myasthenia gravis), muscle strength improves after brief muscle stimulation (myasthenia gravis), dry mouth, erectile dysfunction, -i DTR
SIADH—Symptoms related to hyponatremia that may in­ clude nausea, vomiting, irritability, malaise, anorexia, mus­ cle cramps, or neurologic dysfunction
Trousseau’s syndrome—Migratory or recurrent superficial thrombophlebitis
Next Step\:
Step 1) The initial approach to a patient with suspected lung cancer is a thorough clinical assessment followed by a chest x-ray (CXR). If a mass is identified on CXR, the location of the lesion may provide an indirect clue to the histology of the cancer (see Table 17-5).
Step 2) Further testing is usually performed if a mass is identi­ fied on CXR\:
CBC—To check for anemia
CMP—To check for electrolytes, calcium level, alkaline phosphatase, and aminotransferases
CT Chest with contrast—Characterizes the primary tumor with possible pleural and mediastinal extension
Step 3) To establish a diagnosis and to differentiate small-cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC), tissue sampling is required from any of the following modalities\:
CHAPTER 17 PULMONARY 259

260 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Table 17-5 • Histologic Types of Lung Cancer
Type
Small Cell (Oat Cell)
Location Central
High Yield Features
• Strongly related to smoking
• Highly malignant
• Commonly presents as a large hilar mass with mediastinal adenopathy • Usually metastatic at the time of diagnosis
• Rarely amenable to surgery
• Median survival is 6-18 weeks if untreated
• Frequently associated with the paraneoplastic syndromes\:
1) SIADH
2) Cushing'ssyndrome(TACTH)
3) Hypercalcemia
4) Lambert-Eatonmyasthenicsyndrome 5) Dermatomyositis/polymyositis
Foundational point—Histologically, small "blue" malignant cells that can contain neurosecretory granules.
• Related to smoking
• Cancer spread may be associated with hilar adenopathy and mediastinal widening on CXR • Lesion can cavitate
• Frequently associated with the paraneoplastic syndrome\:
1) HypercalcemiaduetoTPTHrP
Foundational point—Histologically, the presence of keratin and/or desmosomes ("intracellular bridges").
• Overall, most common type of lung cancer
• Commonly seen in women and nonsmokers
• Frequently associated with the paraneoplastic syndrome\:
1) Hypertrophicosteoarthropathy 2) Trousseau's syndrome
3) Dermatomyositis/polymyositis
Foundational point—Histologically, the presence of mucin or neoplastic gland formation.
• Least common compared to the other types • Undifferentiated tumor
• Typically, presents as a large peripheral mass • Lesion can cavitate
Foundational point—Histologically, large pleomorphic cells with vesicular nuclei, prominent nucleoli, and abundant cytoplasm.
Non-Small Cell Squamous cell
Adenocarcinoma
Large cell
Central
Peripheral
Peripheral
ACTH—adrenocorticotropichormone;CXR—chestx-ray;PTHrP—parathyroidhormone-relatedprotein; SIADH—syndrome ofinappropriate antidiuretic hormone secretion
• Transbronchial needle aspiration or biopsy
• Transthoracic needle aspiration or biopsy
• Thoracoscopic lung biopsy or pleural biopsy
• Thoracentesis of the pleural effusion
• Bronchoscopy with direct biopsy
• Mediastinoscopy with tissue sampling
• Fine-needle aspiration (FNA) of the lymph node
• Needle biopsy
• Sputum cytology
Step 4) Once the diagnosis of lung cancer is established, staging the disease will provide information on the extent of the cancer and management of the disease. Additional testing is usually required and may include a CT abdomen with contrast (to detect liver or adrenal metastasis), CT or MRI of the brain (to detect brain metastasis), bone scan, PET scan primarily for patients with NSCLC, or bone marrow biopsies primarily for patients with SCLC who have an abnormal CBC or peripheral blood smear. The staging system for SCLC and NSCLC differ in the following way\:

SCLC Staging Schema
Limited disease—Disease confined to one hemithorax and regional lymph nodes
Extensive disease—Disease outside of the hemithorax to distant sites
NSCLC Simplified Staging Schema
Stage I—Cancer confined to lung with no lymph node in­ volvement
Stage II—Cancer spread to adjacent structures or lymph nodes within the lung
Stage IIIA—Cancer spread to adjacent structures with mediastinal lymph node involvement
Stage IIIB—Cancer spread to adjacent structures with lymph node involvement of the mediastinum, supraclavicu­ lar, or scalene regions
Stage IV—Metastatic
Step 5) Treatment oflung cancer depends on the cell type, stage of the disease, and the functional capacity of the patient.
SCLC Treatment
Limited disease—Chemotherapy (eg, cisplatin) + radiation Extensive disease—Chemotherapy (eg, cisplatin)
NSCLC Treatment
Stage I—Consider surgical resection
Stage II—Consider surgical resection
Stage IIIA—Chemotherapy (eg, cisplatin) + radiation, but surgical resection in select patients
Stage IIIB—Chemotherapy (eg, cisplatin) + radiation
Stage IV—Palliative systemic therapy that may include chemotherapy, radiation therapy, or molecular-targeted therapy
Follow-Up\:
Patients treated with a curative intent approach should have regular surveillance with a clinical assessment and imaging study (CXR or CT) every 6 months for 2 years, then annually.
TRAUMA
1 PNEUMOTHORAX
Pneumothorax (PTX) refers to an accumulation of air into the pleural space. The pressure in the intrapleural space is subatmo- spheric resulting in the tendency for air to readily flow into the pleural space if there is any communication with atmospheric pressure. There are several descriptions of pneumothorax that include the following\:
Pearls\:
• Patients with NSCLC in stages I-III are managed with a cura­ tive intent approach.
• Patients should have a PFT prior to having a surgical resection.
• Any of the histologic types of lung cancer can result in a paraneoplastic syndrome.
• It is not recommended to routinely screen for lung cancer with a CT, CXR, or sputum cytology.
• Hypercalcemia of malignancy can be due to an ectopic production of PTH, secretion of PTHrP, osteolysis from the tumor cells, or an increased production of 1,25- dihydroxyvitamin D.
• 5-year survival rate for SCLC-limited disease is 10% to 13% and for SCLC-extensive disease 1% to 2%.
• 5-year survival rate for NSCLC is Stage I >60%, Stage II40% to 50%, Stage IIIA 10% to 35%, and Stage IIIB and IV <5%.
• Bronchoscopy is well suited for suspected central lesions since it allows for direct visualization of the tumor with bi­ opsy, cytology brushing or lavage, or transbronchial biopsies.
• The sensitivity of sputum cytology varies by location of the lung cancer with the highest yield from large central tumors. Further diagnostic testing is recommended in patients with a negative or equivocal sputum cytology, but with clinical sus­ picion for lung cancer.
• The treatment approach to patients with small-cell lung cancer and SIADH should be focused on treating the ma­ lignancy since the hyponatremia will usually resolve once chemotherapy is started. However, patients with severe symptomatic hyponatremia should be treated with hyper­ tonic (3%) saline infusion.
• On the CCS, "advise patient, no smoking.”
• On the CCS, a “transthoracic needle biopsy” is equivalent to
a “percutaneous biopsy, lung” in the practice CCS.
• On the CCS, a “transbronchial biopsy” will automatically be converted to a “bronchoscopy” in the practice CCS.
• On the CCS, remember that a thoracoscopic lung biopsy or lung resection will require a surgical consult. This would be the appropriate time and consultant for this type ofprocedure.
• On the CCS, remember to order an oncology consult if you’re going to use chemotherapy.
Primary spontaneous pneumothorax (PSP)—A pneumo­ thorax that occurs in the absence of a precipitating event and without an underlying history of lung disease. PSP is usually the result of a pleural bleb rupture and typically seen in tall, thin, young adults who are smokers.
Secondary spontaneous pneumothorax (SSP)—A pneu­ mothorax that occurs as a complication from an underlying lung disease (eg, COPD, cystic fibrosis).
Traumatic pneumothorax—Blunt or penetrating trauma that disrupts the parietal or visceral pleura.
CHAPTER 17 PULMONARY 261

262
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Iatrogenic pneumothorax—A pneumothorax that results from any diagnostic or therapeutic interventions.
Tension pneumothorax—A buildup of air in the pleural space without means of escape because of a check-valve mechanism.
Open pneumothorax—A chest wall defect that appears as a “sucking chest wound” upon inspiration and resulting in equilibration of atmospheric pressure within the intra­ pleural space.
Hemopneumothorax—An accumulation of blood and air in the pleural cavity.
Catamenial pneumothorax—A pneumothorax believed to be caused by endometriosis of the pleura. Onset of symp­ toms usually occurs within 24 to 48 hours of menstruation, and typically the pneumothorax is on the right side.
Clinical Features\:
Patients may be completely asymptomatic, especially if the pneumothorax is small. If the pneumothorax is large, then any of the following features may be present\:
• Sudden onset of dyspnea
• Subcutaneous emphysema may be present
• Decreased tactile fremitus
• Decreased chest movement on the affected side
• Absent or decreased breath sounds on the affected side
• Hyperresonance to percussion on the affected side
• Acute pleuritic chest pain
• Hypoxemia
Next Step\:
Step 1) The patient’s clinical condition determines the initial management in patients with a pneumothorax. Patients that are clinically unstable (eg, tension pneumothorax), require imme­ diate intervention. Patients that are clinically stable based on the respiratory rate, pulse, blood pressure, and oxygen satura­ tion can undergo a chest x-ray to establish the diagnosis of a pneumothorax. The expected finding on chest x-ray is a white visceral pleural line separated by a radiolucent area devoid of vascular markings. For board purposes, it may be helpful to estimate the size of a pneumothorax if the exam presents a radiograph. Based on the American College of Chest Physi­ cians, a small pneumothorax is a measurement of <3 cm from the thoracic apex to the lung cupola and a large pneumothorax has a size >3 cm apex-to-cupola distance (see Figure 17-1).
Step 2) Patients should be provided supplemental oxygen while in the emergency room or in the inpatient unit. A summary of the different treatments for pneumothorax is as follows\:
Clinically unstable with any size PTX—Chest tube + admit to hospital
Clinically stable with large PTX—Chest tube + admit to hospital
Clinically stable with first small PSP—Observe —> repeat CXR —» PTX does not progress —> Discharge
FIGURE 17-1 • Large pneumothorax. Depicted is a large right pneumo­ thorax. Note the white visceral pleural line (arrows) that has a convex shape toward the chest wall. Beyond the visceral pleura is an increased lucency (air density) with avascular lung markings. (Reproduced with permission from Loscalzo, J. Harrison's Pulmonary and Critical Care Medicine. New York\: McGraw-Hill; 2010\:53.)
Clinically stable with recurrent PSP—Chest tube followed by thoracoscopy + admit to hospital
Hemopneumothorax—Chest tube followed by thoracos­ copy + admit to hospital
Clinically stable with small SSP—Admit to hospital and either observe or simple aspiration
Disposition\:
Upon discharge from the hospital, patients should have close follow-up with their physician to assess the patients condition.
Pearls\:
• Instilling a sclerosing agent through a chest tube (ie, chemi­ cal pleurodesis) to prevent a recurrent pneumothorax is an acceptable alternative if thoracoscopic pleurodesis (ie, surgi­ cally creating adhesions) is not available.
• Chest x-ray is the most common diagnostic tool for detect­ ing a pneumothorax, but CT scanning is more accurate and is usually used in more complex or equivocal cases.
• A pneumothorax may be detected by CXR in the supine, lateral decubitus, or upright position. The lateral decubitus position is the most sensitive, while the supine position is the least sensitive.
• Providing supplemental oxygen is an important part of man­ agement because it can increase the rate of pleural air resorp­ tion three- to fourfold compared to room air.
• Patients with catamenial pneumothorax are acutely managed as other patients with a pneumothorax, but the underlying cause is eventually treated with either hormonal therapy (eg, oral contraceptives, progestins) or surgery.

•
•
Caution is advised in patients with SSP because they have an underlying lung disease that compromises their pulmonary reserve volume.
CJ\: A 30-year-old man presents to the ED with an apparent chest wound. As the patient breathes, air can be seen bubbling through the blood surrounding the wound. What are your next steps? Answer\: The diagnosis is an open pneumotho­ rax, and the initial steps is to provide oxygen to the patient and then cover the wound with an impermeable dressing taped on three sides. Once the size of the hole is two-thirds the diameter of the trachea, air will preferentially enter the hole rather than the trachea because of lower airflow resis­ tance. Tire dressing creates a one-way flap valve that prevents air into the chest on inspiration, but allows air to escape on the untaped side on expiration. Taping on all four sides of the dressing can create a tension pneumothorax. Definitive treat­ ment is to close the wound and place a chest tube.
• On the CCS, “advise patient, no smoking” since smoking cessation will reduce the risk of a recurrent pneumothorax.
• On the CCS, both “chemical pleurodesis” and “thoracoscopic pleurodesis” are available in the practice CCS, but a surgical consult with a reason for the consult is required for the tho­ racoscopic pleurodesis.
• On the CCS, “video-assisted thoracoscopic surgery (VATS)” is not recognized in the practice CCS, but a “thoracoscopy” requiring a surgical consult is available.
• On the CCS, if a procedure is not warranted, the patient will let you know on a “Patient Update” screen that the “proce­ dure is declined at this time.”
• On the CCS, be aware that consultants are rarely helpful. Remember that the CCS is designed to assess your reasoning process and not to rely on the consultants. However, you are still evaluated on ordering the appropriate consultant at the appropriate time.
I TENSION PNEUMOTHORAX
A tension pneumothorax is a life-threatening condition that occurs when air is trapped in the pleural space. A one-way valve mechanism allows air to enter the pleural space on inspiration but prohibits outflow of air on expiration. Accumulation of gas within the pleural space can result in collapse of the ipsilateral lung and tracheal and mediastinal shift toward the contralateral side, which can compress the contralateral lung as well as impair venous return to the right atrium (see Figure 17-2).
Clinical Features\:
Patients with tension pneumothorax may present with any of the following features\:
• Respiratory distress • Hypotension
• Marked tachycardia
• Tracheal and mediastinal deviation away from the injured side
• Jugular venous distension (T central venous pressure)
FIGURE 17-2 • Tension pneumothorax. Depicted is a left-sided tension pneumothorax. Note the "tense" pressure that results in tracheal deviation, mediastinal shift to the right, contralateral compressed lung, ipsilateral collapsed lung, and a marked depression of the left hemidiaphragm. Also, examine the striking left-sided "deep sulcus sign"that is seen in the supine position. In this position, air is able to collect anteriorly and basally, which accentuates the deepening of the left costophrenic angle. (Reproduced with permission from Knoop KJ, Stack LB, et al. TheAtlas ofEmergency Medicine. 3rd ed. New York\: McGraw-Hill; 2010\:161.)
• Absent or decreased breath sounds on injured side
• Hyperresonance to percussion on injured side
• Acute pleuritic chest pain • Hypoxemia
Next Step\:
Step 1) Tension pneumothorax is a clinical diagnosis and a medical emergency that requires immediate decompression. Rapidly decompress with a needle thoracostomy performed on the injured side through the second or third intercostal space at the anterior, midclavicular line. A rush of air should be heard upon insertion of the needle and diagnosis of a tension pneu­ mothorax is then confirmed. The tension pneumothorax has now been converted to a simple pneumothorax.
Step 2) Arrange for a chest tube thoracostomy, which is con­ sidered definitive treatment. Chest tube placement is typically placed through the fifth intercostal space at the midaxillary line.
Step 3) Connect the chest tube to a water seal device ± suction (ie, some physicians will only apply suction if the lungs fail to re-expand).
Step 4) Order a portable chest x-ray to confirm chest tube place­ ment and assess lung re-expansion.
CHAPTER 17
PULMONARY 263

264 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Disposition\:
Remember to treat and stabilize the patient in the emergency room before admitting the patient into the hospital for further observation.
Pearls\:
• Do not order a chest x-ray and wait for confirmation of the results before treating the patient because it may lead to the patient’s death.
• Upon placing a needle into the intercostal space, remember to avoid the lower margin of the involved rib to prevent injury to the neurovascular bundle.
• Tension pneumothorax is commonly caused by trauma (blunt or penetrating) and iatrogenic (eg, medical procedures, baro­ trauma secondary to positive pressure ventilation), but 1% to 2% of PSP may develop a tension pneumothorax.
• A chest tube thoracostomy is preferable over a needle thora­ costomy because of controlled placement of the chest tube compared to blindly inserting a needle. However, if the chest tube is not readily available or your clinical judgment (ie, respiratory distress, hemodynamically unstable) tells you
CCS\: COPD EXACERBATION CASE INTRODUCTION
Day 1 @ 17\:00 Emergency Room
A 67-year-old white male comes to the emergency department because of worsening dyspnea, increased frequency of cough, increased volume of sputum production, and change in color of sputum from white to yellow.
Initial Vital Signs\:
Temperature\: 38.6°C (101.5°F) Pulse\: 110 beats/min, bounding Respiratory\: 28/min
Blood pressure\: 140/90 mm Hg Height\: 177.8 cm (70.0 inches) Weight\: 68.2 kg (150 lb)
BMI\: 21.6 kg/m2
Initial History\:
Reason(s) for visit\: Dyspnea, productive cough, sputum changes
HPI\:
The patient, a 67-year-old retired physician, has been experiencing increased dyspnea, increased frequency of cough, and increased sputum volume with purulence over the past 4 days, which has been beyond his normal day-to-day variation. He states that he
that the patient would not be able to withstand the few extra minutes to perform a tube thoracostomy, the best next step would be the needle thoracostomy, which would serve as a bridge until a chest tube can be placed.
• On the CCS, remember not to do a complete physical exam in acute cases, but rather a focused physical exam.
• On the CCS, remember to monitor patients closely dur­ ing emergent cases. In this case, you want to measure the oxygen saturation with a pulse oximetry. Also, try typing in “continuous” in the order menu, and a list of monitoring devices will be available. In this particular case, you will want to order “continuous blood pressure cuff” and “continuous cardiac monitoring.” For future blood pressure and cardiac readings, you will have to order “check blood pressure” and “check cardiac monitor,” respectively.
• On the CCS, timing is critical in this type of case. Remember not to order anything that would delay treatment.
• On the CCS, you will be evaluated on your sequence of actions. Therefore, do not order a chest x-ray before treat­ ment, but rather after treatment to assess lung re-expansion.
feels better when he is sitting up and in the forward position to alleviate his dyspnea. He admits to being a long time smoker and states “back in my day, we use to smoke inside the hospital.” He has been admitted to the hospital 4 times over the past year for COPD exacerbation with his most recent admission 2.5 months ago.
Past Medical History\:
Past Surgical History\: Medications\:
Allergies\: Vaccinations\: Family History\:
Social History\:
Four hospitalizations for COPD exacerbations that each required anti­ biotic therapy. Hypercholesterolemia. None
Atorvastatin, tiotropium once daily, albuterol prn, supplemental home oxygen
None
Up to date
Father died of lung cancer. Mother died of breast cancer. No siblings. Quit smoking 7 years ago, but previously smoked 1 ppd x 42 years; no longer drinks alcoholic beverages; denies use of illegal drugs; married; four children; retired physician; enjoys playing golf and going to operas.

Review of Systems\: General\:
Skin\:
HEENT\: Musculoskeletal\: Cardiorespiratory\: Gastrointestinal\: Genitourinary\: Neuropsychiatric\:
Dayf@ 17\:07
Physical Examination\: General appearance\:
HEENT/Neck;
Chest/Lungs\:
Heart/Cardiovascular\: Abdomen\:
Extremities/Spine\:
First Order Sheet\: 1) Sit upright
2) Suction upper airway, stat
3) Pulse oximetry, stat
4) Supplemental oxygen, continuous
5) PEFR, stat
6) IVaccess
7) Continuous cardiac monitoring, stat
8) Continuous blood pressure cuff, stat
See HPI Negative Negative Negative See HPI Negative Negative Negative
Thin, undernourished; in respira­ tory distress, sitting in the tripod position.
Normocephalic. EOMI, PERRLA. Copious oral secretions. No cyanosis of the lips. Full use of the accessory muscles of the neck. Trachea midline. Thyroid normal. Increase AP diameter ofthe chest. Hyperresonant to percussion. Expiration through pursed lips. Generalized expiratory wheezes, bilateral crackles at the lung bases. Inward retraction of the lower rib cage
on inspiration.
Tachycardia. No murmurs, rubs, gallops, or extra sounds. No JVD. Normal bowel sounds; no bruits. No tenderness. No masses. No hernias. No hepatosplenomegaly. Extremities symmetric. No cyanosis or clubbing. No edema. Periph­
eral pulses bounding. Full range of motion of the extremities. Spine examination normal.
Result\: Difficult to clear all secretions
Result\: 87% (nl\: 94-100)
Result\: The patient is unable to cooperate.
Result\: Sinus tachycardia Result\: 140/90 mm Hg
Second Order Sheet\:
1) Albuterol, inhalation, continuous
2) Ipratropium, inhalation, continuous
3) Methylprednisolone, IV, one time/bolus 4) Levofloxacin, IV, continuous
Third Order Sheet\:
1)
2)
3)
4)
ABG, stat
EKG, 12-lead, stat
Chest x-ray, PA/lateral, stat
CBCwith differential, stat
Result\: pH-7.35, pCO2-50 mm Hg, p02-52 mm Hg, HCO3-30 mEq/L, 0 2 saturation-87%
Result\: Rhythm- sinus tachycardia, Axis- +30 degrees, P waves-wnl, QRS complexes-wnl, ST-T waves-wnl, Other findings-none, Interpretation-sinus tachycardia
Result\: Increased radiolucency in both lung fields, flattened diaphragm, nodular infiltrate with tree-in-bud opacities in left lower lobe.
Result\:WBC-14,000,H/H-16/55%, Plt-300,000, Differential\: Neutrophils-65% (nl\: 54%-62%) Band neutrophils-10% (nl\: 3%-5%), Lymphs-25% (nl\: 25%-33%)
Result\: Glu-100, Urea-16, Na-143, K-4.0, Cl-103, HCO3-30, Cr-0.8, Ca-9.5
Result\: WNL
5) BMP, stat
6) Urinalysis, stat
Follow-Up History\:
The patient is feeling better.
Physical Examination\: HEENT/Neck\:
Chest/Lungs\: Heart/Cardiovascular\:
Fourth Order Sheet\:
1) Pulse oximetry, stat
2) Check cardiac monitor, stat
3) Vital signs, stat 4) ABG, stat
No straining ofthe accessory muscles of the neck.
Improved breath sounds. Minimal wheezing.
SI and S2 normal. No murmurs, rubs, gallops, or extra sounds. No JVD.
Result\: 90% (nl\: 94-100) Result\: Regular sinus
Result\: 37.8°C (100.2°F), HR-96, RR-20, BP-138/88 mm Hg
Result\: pH-7.37, pC02-48 mm Hg, p02-58 mm Hg, HC03-29 mEq/L, 0 2 saturation-90%
Actions\:
1) Change location to inpatient unit
CHAPTER 17
PULMONARY 265

266 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Fifth Order Sheet\: 1) Ambulate at will
2) Urine output, routine 3) Low fat diet
This case will end in the next few minutes of “real time.” You may add or delete orders at this time,
then enter a diagnosis on the following screen.
Sixth Order Sheet\:
1) Counselfamily/patient
2) Advise patierit, no smoking
3) Advise patient, side effects of medication 4) Vaccine, influenza, IM, one time
5) Vaccine, pneumococcal, IM, one time
Please enter your primary diagnosis only\: COPD Exacerbation
DISCUSSION\:
COPD exacerbation is typically triggered by a respiratory in­ fection, but other precipitants that have been implicated are environmental pollutants, medications, and medical condi­ tions (eg, pneumonia, pulmonary embolism, CHF). Common viral causes include influenza, rhinoviruses, adenoviruses, and coronaviruses. Common bacterial causes include nontypeable Haemophilus influenzae. Streptococcus pneumoniae, Moraxella catarrhalis, and Pseudomonas aeruginosa (particularly in pa­ tients with severe COPD).
Clinical Features\:
Patients with a COPD exacerbation will usually have acute changes from their baseline symptoms, which can include any of the following\: t dyspnea, T cough, T sputum production, and/ or changes in the quality of sputum. Patients with worsening dyspnea will try to alleviate their symptom by leaning forward with outstretched arms, exhaling through pursed lips, and using their accessory muscles (scalene, sternocleidomastoid, and intercostalmuscles).Patientswithworseninghypoxemia(ie,Sa02 <90%) will start to have changes in mental status, tachycardia, tachypnea, hypertension, and cyanosis.
Next Step Summary\:
Step 1) Perform a targeted physical exam as with most acute cases.
Step 2) Address the oxygen status and cardiovascular status with the appropriate monitoring equipment.
Step 3) Diagnosis ofa COPD exacerbation is based on the clini­ cal presentation (ie, acute changes from their baseline symp­ toms); therefore, no single test will confirm the diagnosis. Do not delay treatment in a patient that is in respiratory distress. Once treatment is given to the patient (see Step 4), initial evalu­ ation should include\:
ABG—To access the add-base status.
BMP—To access the electrolytes and to have a baseline potassium since (32-agonists can lower potassium levels.
CBC—In this case, elevated white count with increase in bands suggest an infection. Also, the hematocrit is elevated, which suggest chronic hypoxemia.
CXR—To exclude other causes and to identify coexisting diseases.
EKG—To access for other coexisting cardiac disease since cardiac ischemia can also cause hypoxia.
UA—To identify potential sources of infection.
Step 4) Treatment for COPD exacerbation should strive for adequate oxygenation, “open up the airways,” and treat the un­ derlying cause. Consider the following interventions\:
Supplemental oxygen—The target for adequate oxygen­ ation is an arterial oxygen saturation (Sa02) of 90% to 94% or an arterial oxygen tension (Pa02) of60 to 70 mm Hg.
Bronchodilators—The combination therapy of an inhaled short-acting (32-agonist (eg, albuterol) with an inhaled short acting anticholinergic (eg, ipratropium) is thought to have an additive effect than either agent alone.
Systemic corticosteroids—Adding systemic corticosteroids can improve symptoms, lung function, shorten the length of hospital stays, and decrease the rate of return of ED visits. Route of administration can be given orally (eg, po prednisone) or intravenously (eg, IV methylprednisolone). In this CCS case, if there is any concern for the patient to swallow, the intravenous route would be safer, and once the patient is able to tolerate orals, then you can switch to oral medication. Typical duration of corticosteroid therapy is 10 to 14 days.
Antibiotics—Antibiotic therapy is usually given to patients when there is evidence of infection. In this particular CCS case, the patient had an increase in sputum production, increase in sputum purulence, increase in dyspnea, and the CBC showed an elevated white count with bands, which cu­ mulatively suggests a bacterial infection. In addition, this patient had risk factors for a pseudomonas infection because he was recently hospitalized within the past 90 days and he had multiple antibiotics over the past year (>4 courses of antibiotics). In this particular CCS case, the choice of anti­ biotics was tailored towards a pseudomonas infection with levofloxacin, but other antipseudomonals can also be used such as ciprofloxacin, piperacillin-tazobactam, cefepime, or ceftazidime. Ideally, initial antibiotics should target the most likely bacteria (ie, H influenzae, M catarrhalis, S pneu­ moniae), and good empiric treatment can be started with trimethoprim-sulfamethoxazole (TMP-SMZ), doxycycline, or amoxicillin-clavulanate. Typical duration of antibiotic therapy is 3 to 7 days.
Noninvasive positive pressure ventilation (NPPV)—NPPV refers to positive pressure ventilation delivered by nasal mask, facemask, or mouthpiece. Positive pressure ventilation

can be delivered by either one of two modes\: continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BPAP). Indications for NPPV include severe dyspnea with use of accessory muscles or pH <7.35 and/ or PaC02 >45 mm Hg. Contraindications to NPPV include copious secretions, inability to clear secretions, high risk of aspiration, uncooperative patient, obtunded patient, hemo­ dynamic instability, unstable cardiac arrhythmia, respira­ tory arrest, recent facial or gastroesophageal surgery, burns, extreme obesity, or craniofacial abnormalities.
Step 4) Reassess the patient by using the interval/follow-up, performing a focus physical exam, monitoring the vitals and oxygen saturation.
Disposition\:
Patients should be considered for admission when they fail to improve adequately despite treatment, significant comor­ bidities, change in mental status, older age, inability to care for themselves, or inadequate home support.
Pearls\:
• Oral or intravenous glucocorticoids are both equally effec­ tive in treating COPD exacerbations.
• The route of delivery of an inhaled short-acting broncho- dilator can be given by a nebulizer or metered-dose inhaler (MDI) with proper technique since studies have shown no difference in FEVj when either device is given.
• The PEFR, which is also known as “peak flow,” can be ob­ tained by spirometry or a peak flow meter (inexpensive
• •
•
• • • •
•
portable device). If the patient is able to cooperate during a COPD exacerbation, a value of<100 L/min usually indicates a severe exacerbation.
Patients that are taking theophylline should have their the­ ophylline levels checked because of concerns for toxicity.
Sputum cultures and gram stain is usually not useful in patients with COPD exacerbations, however, the sputum cultures and antibiotic sensitivities should be considered when the patient is not responding to the initial antibiotic treatment.
Patients with severe airway obstruction will have the characteristic hyperinflation of the lungs with a flattened diaphragm that can result in inward contraction of the diaphragm instead of downward, which will appear as a paradoxical retraction of the lower intercostal spaces on inspiration (Hoover’s sign).
On the CCS, both “CPAP” and "Continuous positive airway pressure” are available in the practice CCS.
On the CCS, either “BiPAP” or “Bilevel positive airway pres­ sure” is available in the practice CCS, but not “BPAP.”
On the CCS, delaying treatment would be considered sub- optimal management.
On the CCS, failure to monitor or follow up on the patients oxygen status, vital signs, cardiac status, and physical condi­ tion would be considered suboptimal management.
On the CCS, be cognizant about the simulated time because you want to complete your diagnostic and therapeutic inter­ ventions in a timely fashion in acute cases.
CHAPTER 17 PULMONARY 267

Renal and Genitourinary
CHAPTER OUTLINE
Key Findings Review.........................................2.6..9.......I I HEREDITARY DISORDERS..............................2..7.2....
URINARYTRACTDISORDER..............................2.7.5..... Nephrolithiasis...............................................2.7.5.........
NEOPLASM................................................2.7..9........ Wilms'Tumor................................................2.7..9.........
Autosomal DominantPolycysticKidneyDisease..............2..7.2 Autosomal RecessivePolycysticKidneyDisease...............2.7.4.
KEY FINDINGS REVIEW
URINE INSPECTION
Color
White-cloudy—Due to chyle, pus, or phosphate crystals.
Red-brown—Due to hematuria, hemoglobinuria, myoglo­ binuria, bile pigments, fava beans, or beets.
Black-brown—Due to methemoglobin, melanin, methyldopa, or levodopa.
Green-blue—Due to biliverdin, Pseudomonas infection, or propofol.
Odor
Sweet or fruity—Due to ketones.
Fecal—Due to Gl-bladder fistula.
Maple—Due to maple syrup urine disease Mousy or musty—Due to phenylketonuria (PKU). Pungent—Think UTIs.
I
Ammoniac—Think urease-producing organisms or struvite stones.
URINE DIPSTICK
Urine pH—Urine pH ranges from 4.5 to 8.0. Urine pH >7.0 suggests calcium phosphate or struvite stones. Urine
pH <5.5 suggests uric acid stones. Urine pH <5.3 suggests type 4 RTA, urine pH >5.3 suggests type 1 (distal) RTA, and a variable urine pH suggests type 2 (proximal) RTA.
Specific gravity (SG)—SG can range from 1.003 to 1.030.
SG can give you an idea of the kidney's ability to concentrate, patient's hydration status, or an estimate of the urine osmolality. A rough SG guideline includes SG <1.003 indicates a very dilute urine, SG <1.010 indicates hydration, SG >1.020 indicates dehydration, and SG = 1.009 correlates with a urine osmolality of approximately 280 mOsmol/kg.
Ketones—Can be found in DKA, fasting, carb-free diets, strenuous exercise, or pregnancy. A positive dipstick
269

270 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
indicates the presence of acetoacetate or acetone (ie, only nitroprusside reacts with those 2 ketones), but not |3-hydroxybutyrate.
Glucose—Glycosuria occurs if the kidneys cannot reabsorb filtered glucose (eg, Fanconi's syndrome) or urinary spillage of glucose because of high plasma glucose levels which is not seen until plasma glucose is >180 mg/dL.
Nitrites—Indicates bacteriuria because the bacteria (primarily Enterobacteriaceae species, which are gram-negatives) can convert nitrates to nitrites from the enzyme nitrate reductase. However, false negatives can occur if there is an infection with enterococcus (gram-positive), which expresses low levels of nitrate reductase.
Leukocyte esterase (LE)—Indicates the presence of white blood cells (ie, produces LE). A positive result is suggestive of a bacterial infection, but not diagnostic.
Bilirubin—No bilirubin should be detected on dipstick. A positive dipstick suggests an elevated conjugated bilirubin because it is water soluble, which allows it to pass through the glomerulus, but unconjugated bilirubin is water insoluble, which does not pass through the glomerulus.
Urobilinogen—Urobilinogen is an end product of conjugated bilirubin, and only small amounts are normally present in the urine. If elevated levels are seen, it may be due to hemolysis or liver disease, while a decreased level may be due to bile duct obstruction or antibiotics.
Blood—A positive dipstick can be the result of erythrocytes, hemoglobin, myoglobin, menstrual bleed, or semen (ie,
false positive). If you centrifuge your sample and a red color is seen in the supernatant, then it suggests hemoglobin or myoglobin, but if the sediment appears red, then it suggests hematuria. Further microscopic studies are needed by taking the sediment and examining for red blood cells as the cause of hematuria.
Protein—Dipstick is sensitive for albumin, but not for other types of proteins (eg, globulins, Bence-Jones proteins). However, performing a follow-up test with sulfosalicylic acid (SSA) can detect all proteins in the urine. The dipstick
is not sensitive enough to detect moderately increased albuminuria (formerly called microalbuminuria).The level of proteins (ie, trace, 1+, 2+, 3+) in the urine is not completely reliable because it depends on the urine concentration. If proteinuria is found, break it down to primary glomerular causes (eg, nephrotic syndrome), secondary glomerular causes (eg, SLE, DM), tubular causes (eg, tubulointerstitial nephritis, drugs), overflow causes (eg, multiple myeloma), or transient causes (eg, dehydration, exercise, orthostatic postural proteinuria).
URINE SEDIMENT (MICROSCOPIC EXAM)
After centrifugation of the urine sample, the supernatant is poured off and the remaining pellet is agitated so
that the sediment can be placed on a slide for evaluation.
Cells
Transitional epithelial cells—Normal finding, but if found in clumps or large numbers then it suggests neoplasm.
Squamous epithelial cells—Suggests contamination.
Renal tubular cells—Larger than WBCs; their presence suggests tubular damage or inflammation.
Erythrocytes—Findings >2 RBCs on high-power field (HPF) is considered abnormal.
Leukocytes—Men generally have <2 WBCs on HPF, and women typically have <5 WBCs on HPF. Eosinophils detected with either Hansel's or Wright's stain suggests allergic interstitial nephritis.
Bugs—Bacteria can be further characterized by gram staining, yeast will show hyphae or budding forms, and Trichomonas will be swimming around with their motile flagellum.
Casts
Casts have a cylindrical structure that are formed in the distal tubules and collecting ducts as result of the precipitation of a protein (ie,Tamm-Horsfall mucoprotein).
RBC casts—Suggests glomerulonephritis or vasculitis.
WBC casts—Suggests pyelonephritis, interstitial nephritis, or glomerulonephritis.
Fatty casts—Suggests heavy proteinuria or nephrotic syndrome. Under polarized light, a "Maltese cross" can be seen in the fat droplets.
Broad casts—Suggests advanced chronic kidney disease.
Waxy casts—Nonspecific finding, but can be seen in renal failure patients and in rapidly progressive glomerulonephritis.
Hyaline casts—Nonspecific finding, but can be seen in concentrated normal urine or in renal disease.
Granular casts—Nonspecific finding, but may suggest renal disease (ie, ATN, tubulointerstitial disease, glomerulonephritis) or the result of degeneration from other casts. Granular casts can be coarse ("muddy brown") or fine.
Epithelial casts—Renal tubular epithelial cell casts suggests acute tubular necrosis (ATN), acute interstitial nephritis, proliferative glomerulonephritis, or nephrotic syndrome.

Crystals
See Nephrolithiasis section (seeTable 18-1, Figure 18-1, and Color Plate 14).
Table 18-1 • Nephrolithiasis Profile
Stones
Calcium oxalate (CaOx)
Causes
Hypercalciuria\: Idiopathic hypercalciuria, primary hyperparathyroidism Hyperoxaluria\: Diet high in oxalate (eg, spinach, rhubarb, kale, beets, berries, bean, nuts, wheat, chocolate), enteric causes (eg, fat malabsorption, bowel diversion
or resection, IBD), or conversion to oxalate (eg, vitamin C) Hypocitraturia\: Distal (type 1) RTA, chronic diarrhea, carbonic anhydrase inhibitors
Same as calcium oxalate except
for hyperoxaluria. Distal RTA usually causes an alkaline pH, which favors calcium phosphate crystals.
Infection with urease-producing organisms such as\:
• Klebsiella species
• Proteus species
• Pseudomonas aerugionsa
• Providencia species
• Haemophilus influenzae
• Staphylococcus aureus
• Ureaplasma urealyticum
T Uric acid production
• Gout
• Alcohol
• High purine diet
• Lesch-Nyhan syndrome
Diabetes mellitus
Obesity
Metabolic syndrome
Chronic diarrhea (ie, 4 HC03_)
Cystinuria, which is an inherited disorder that results in a defective transport channel in the proximal convoluted tubule leading to excess cystine in the urine.
Diagnostic Clues Imaging\: Radiopaque
Urine pH\: Crystal formation is independent on the urine pH Crystal shape\: Dumbbell-shaped or envelope-shaped (Note\: Looks like squares with lines intersecting in the center. If the lines do not intersect in the middle, it may be mistaken for a triple phosphate crystal.)
Color\: Colorless
Imaging\: Radiopaque
Urine pH\: Alkaline (>7.0)
Crystal shape\: Pleomorphic (needle, star, rosette, prism, flat plates)
Color\: Colorless
Clinically\: Look for a UTI (more com­ mon in women)
Imaging\: Radiopaque, staghorn (branched) calculus
Urine pH\: Alkaline (>7.0)
Crystal shape\: Rectangular prisms or "coffin lids"
Color\: Colorless
Imaging\: Radiolucent
Urine pH\: Acidic (<5.5)
Crystal shape\: Pleomorphic (rosette, rhomboid prism, diamond, amorphous, needle)
Color\: Colorless to yellow or red-brown
Imaging\: Radiopaque
Urine pH\: Presents primarily in acidic urine, but as the pH rises so does the solubility of cystine. Crystal shape\: Hexagonal
Color\: Colorless
Next Step Treatment Approach
Step 1) Initial treatment should begin with dietary changes (ie,
T fluid intake, T phytate, T K+, T diet Ca2+, 4 sucrose, 4 fructose, 4 animal protein, 4 oxalate foods, 4 Na+, reduce excessive Ca2+ and vitamin C supplements) for at least
3-6 months.
Step 2) If resistant to step 1, then consider meds\:
Hypercalciuria\: Thiazides Hyperoxaluria\: Cholestyramine Hypocitraturia\: Alkalinization (eg, K+ citrate, K+ bicarbonate)
Step 1) Same as CaOx, except
for limiting oxalate foods or vitamin C.
Step 2) Meds can be attempted with thiazides to 4 urine calcium, and alkalinization should be used with caution.
Step 1) Treat the acute infection (eg, UTI) with antibiotics.
Step 2) Definitive therapy is to remove the stone with PNL as the preferred surgical approach in
most patients. Patients that
cannot tolerate surgical intervention may be given a urease inhibitor (acetohydroxamic acid) instead.
Step 1) Initial treatment may begin with t fluid intake, 4 alcohol intake, 4 protein intake, and alkalinizing the urine with either potassium bicarbonate or potassium citrate. Step 2) Allopurinol may be given in patients resistant to step 1.
Step 1) Initial treatment may begin with T fluid intake and alkalinizing the urine with either potassium bicarbonate or potassium citrate. Step2) A thio-containing drug (peni­ cillamine or tiopronin) can increase the solubility of cystine and may be given to patients resistant to step 1.
Calcium phosphate
Struvite (MgNH4P04)
Uric acid
Cystine
PNL—percutaneous nephrolithotomy
CHAPTER 18
RENAL AND GENITOURINARY 271

272
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
E
FIGURE 18-1 • Urinary crystals. A. Calcium oxalate—Envelope-shaped crystals with a prominent "X"crossing at the center. B. Calcium phosphate—Needle-shaped crystals. C. Triple phosphate—"Coffin lid"appearance. D. Uric acid—Rosette formation. E. Cystine—Hexagonal plates. (Reproduced with permission from Mundt LA, Shanahan K. Graff. TextbookofUrinalysis and BodyFluids. 2nd ed. Philadelphia, LWW; 2011\: 66, 67, 76, 123, 133.)
HEREDITARY DISORDERS
I AUTOSOMAL DOMINANT POLYCYSTIC
KIDNEY DISEASE
Autosomal dominant polycystic kidney disease (ADPKD), formerly called adult polycystic kidney disease, is the most common inherited kidney disease. The two genes that account for ADPKD include mutations in the PKD-1 (encodes poly- cystin-1) and PKD-2 (encodes polycystin-2) genes. PKD-1
mutations are more common, present earlier, and cause more severe disease compared to PKD-2 mutations. PKD-2 muta­ tions have a later onset and slower progression.
Clinical Features\:
Symptoms of ADPKD often do not appear until ages 30 to 40, but they can begin in childhood. The most common symptom is pain in the abdomen, flank, or back. The development of cysts is universally bilateral, and palpable bilateral flank masses felt on exam may suggest advanced ADPKD. Consider the following renal manifestations\:

Hypertension—Hypertension is an early manifestation with a mean age of onset of 30 years. HTN occurs in approxi­ mately 60% ofpatients with normal kidney function before a reduction in GFR. Once kidney function is impaired, a pro­ gressive decline ensues with an average decline in the GFR of 4.0 to 5.0 mL/min/yr.
Hematuria—Hematuria is frequently a presenting manifes­ tation and can be due to a cystic rupture into the collecting system, nephrolithiasis, or UTI.
Stones—Nephrolithiasis can occur in up to 20% to 25% of patients with 50% composed of uric acid stones and the remainder as calcium oxalate stones.
Concentrating defect—A decrease in the concentrating ability is usually an early manifestation that is initially mild, but worsens with increasing age and declining kidney func­ tion. Patients will often complain of polydipsia, polyuria, and nocturia. Plasma vasopressin is usually elevated with normal serum osmolarity.
Proteinuria—Patients may have mild proteinuria (ie, not a prominent feature in ADPKD).
Pain—An acute sharp pain may be due to a cystic rupture, hemorrhage into a cyst with expansion, cyst infection, pa­ renchymal infection, or passage of a stone. A chronic, dull, nagging pain may be the result of an enlarged kidney with a mass effect. If the kidney enlarges such that there is an in­ crease in abdominal girth, patients may complain of lower back pain secondary to lumbar lordosis.
ADPKD can also have extrarenal manifestations that include the following from a relative head to toe fashion\:
Cerebral aneurysms—Approximately 5% to 20% of pa­ tients will have an aneurysm, which most often occurs in the anterior circulation. A ruptured aneurysm can result in either a subarachnoid or an intracerebral hemorrhage.
Cardiac valve disease—Valve disease include mitral valve prolapse, aortic regurgitation, or mitral regurgitation.
Hepatic cysts—Hepatic cysts are a common extrarenal manifestation with most patients that are asymptomatic with preserved hepatic function. However, hepatic enlarge­ ment secondary to hepatic cyst formation can result in pain, early satiety, or shortness of breath.
Abdominal wall and inguinal hernias—These hernias occur with a higher frequency than the general population.
Colonic diverticula—Colonic diverticula are common and can potentially result in colonic perforation.
Cysts—Other possible cysts seen in ADPKD include subarach­ noid, thyroid, pancreatic, splenic, and seminal vesicle cysts.
Next Step\:
Step 1) Diagnosis of ADPKD is most often made by a positive family history (ie, every generation will be affected with an au­ tosomal dominant inheritance) and imaging studies. The best initial imaging modality is with an ultrasound, which will typi­ cally show multiple bilateral kidney cysts with possible evidence of liver, splenic, or pancreatic cysts. In cases when ultrasound
findings are equivocal and disease status must be determined with greater certainty (eg, potential kidney donor), then the next best step is to consider genetic testing ± MRI or CT.
Step 2) Counseling should be offered once the diagnosis is established, and patients should be advised to avoid competi­ tive contact sports.
Step 3) There is no specific treatment that will delay or prevent ADPKD. Treatment is mainly supportive. However, there may be concerns during the management of ADPKD. Consider the following\:
ESRD—Approximately 60% of patients with ADPKD will have end-stage renal disease (ESRD) by the age of 70, and ei­ ther dialysis or renal transplantation is required. Nephrectomy is typically avoided, but may be warranted prior to a transplant in cases of recurrent infection or very large kidneys.
Hypertension—Target blood pressure should be <130/ 80 mm Hg. Choice of agent can be with either an ACE inhibitor (eg, lisinopril) or an ARB (eg, losartan) for those intolerant of an ACE inhibitor (eg, cough, angioedema).
Hematuria—Hematuria secondary to a cystic rupture into the collecting system will typically resolve within 7 days, and supportive therapy is generally recommended.
Infected cyst—Most cysts are infected with gram-negative organisms. Antibiotics that have good lipid-soluble penetra­ tion into the cysts are with fluoroquinolones (eg, ciprofloxa­ cin), trimethoprim sulfamethoxazole, or chloramphenicol. Unfortunately, cephalosporins and aminoglycosides do not adequately penetrate infected cysts.
Cerebral aneurysms—Routine screening for cerebral aneu­ rysms is not recommended unless there is a family history of cerebral aneurysms, personal history of a rupture, high- risk occupation, or prior to surgery (eg, renal transplant).
Follow-Up\:
The most common cause ofdeath from ADPKD is from cardio­ vascular-related problems. Therefore, periodic follow-ups for blood pressure management and lipid assessment are essential. If plasma creatinine or potassium levels are elevated second­ ary to an ACE inhibitor or ARB, consider another agent (eg, calcium channel blocker, beta-blocker).
Pearls\:
• ADPKD accounts for approximately 5% of ESRD in the United Sates and Europe.
• Risk factors for progressive kidney disease include PKD-1 mu­ tation, early onset, HTN, male, black race, and large kidneys.
• There is an inverse relationship between the kidney size and GFR.
• ADPKD does not appear to increase the risk of renal cell carcinoma (RCC) compared to the general population.
• Perinephric abscess should be considered in patients who continue to have persistent symptoms (eg, fever, flank pain, dysuria) despite antibiotic therapy, and therefore drainage of the abscess may be indicated.
CHAPTER 18 RENAL AND GENITOURINARY 273

274 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Caveat 1—Avoid using gadolinium-containing contrast ClinicalFeatures\:
(eg, MRI) since it can cause nephrogenic systemic fibrosis in patients with kidney failure.
• Caveat 2—Avoid ACE inhibitors and ARBs during pregnancy (Category D) and consider alternative agents (eg, methyl- dopa, hydralazine, labetalol).
• Caveat 3—Infected cysts may not always communicate with the collecting system, and therefore your urinalysis and urine culture will be negative. Blood cultures may in fact identify the organism more often than the urine culture.
• An elevated hematocrit and hemoglobin concentration can sometimes be seen in ADPKD because of an increase in erythropoietin secretion from the cysts.
• GERD-like symptoms and early satiety can result from a mass effect of the enlarged kidneys onto the GI tract.
• ADPKD is predominantly seen in adults, although it can occur in childhood. Children may be asymptomatic un­ til adulthood or they may present during childhood with renal manifestations similar to adults, but hepatic, splenic, and pancreatic cysts are uncommon manifestations. How­ ever, children may have a higher frequency in an increased left ventricular mass.
• Routine screening for ADPKD in patients <18 years of age is controversial.
• Foundational point—The PKD-1 gene is located on chromo­ some 16, and the PKD-2 gene is located on chromosome 4.
• Connecting point (pg. 156)—Know the management of subarachnoid hemorrhage.
• Connecting point (pgs. 30, 32, 35)—Be able to differentiate the murmur sounds ofmitral regurgitation, mitral valve pro­ lapse, and aortic regurgitation.
• Connecting point (pg. 271)—Know the management of calcium oxalate and uric acid stones.
• Connecting point (pg. 163)—Recognize the genetic pedigree chart of autosomal dominant genes and know that children have a 50% chance of acquiring ADPKD.
• On the CCS, “genetic counseling” is available in the practice CCS.
• On the CCS, if you’re not sure which ultrasound to choose for ADPKD (abdomen vs transabdominal/pelvis), there is an op­ tion for “kidney ultrasound” on the practice CCS. The kidney ultrasound is essentially the same as the abdomen ultrasound and will provide you with the essential information for ADPKD (ie, findings of the kidney, liver, spleen, and pancreas).
1 AUTOSOMAL RECESSIVE POLYCYSTIC
KIDNEY DISEASE
Autosomal recessive polycystic kidney disease (ARPKD), for­ merly called infantile polycystic kidney disease, is less common than ADPKD. The gene that accounts for ARPKD is a mutation in the PKHD1 gene that codes for a protein called polyductin or fibrocystin. ARPKD is primarily a disease of infants and chil­ dren with the kidney and liver as the primary affected organs.
The clinical presentation of ARPKD can vary. There may be promi­ nent features in different age settings. Consider the following\:
Neonates—Enlarged echogenic kidneys is usually present in the neonatal period, and in fact, enlarged kidneys may be seen after 24 weeks gestation by ultrasound. Hypertension, oligu­ ria, and acute renal failure may be seen in the neonatal period. Pregnancies may be complicated by oligohydramnios, which could result in Potter syndrome (ie, pulmonary hypoplasia, clubfeet, Potters facies [flat nose, low-set ears, micrognathia, pseudoepicanthus]). Feeding difficulties may also may be present secondary to fatigue (eg, pulmonary insufficiency) or compression of the stomach by the enlarged kidneys. Death can occur in approximately 30% to 50% of neonates due to pulmonary insufficiency secondary to pulmonary hypoplasia.
Infants—Bilateral palpable flank masses may be appreci­ ated on physical exam and may even be felt soon after birth. Renal dysfunction may become more noticeable during this time period and beyond such as hyponatremia, reduced concentrating ability, proteinuria, or metabolic acidosis. Hypertension continues to occur during the first few years of life and if inadequately controlled, then CHF or cardiac hypertrophy may develop. Infants may also present with pneumomediastinum or pulmonary related-complications (eg, pneumothorax secondary to poor lung development).
Childhood and young adulthood—Hepatic abnormalities are the prominent presenting features in this age group. Bili­ ary ductal plate abnormalities can result in congenital hepatic fibrosis, and the fibrosis can lead to portal hypertension and its complication (eg, esophageal varices). In addition, patients have a higher risk of developing bacterial cholangitis. On exam, hepatosplenomegaly may be appreciated secondary to portal hypertension. Again, hypertension may be present and typically occurs in more than 60% of children. Interest­ ingly, the kidney size does not continue to grow significantly anymore, but eventually there is a progressive decline in kidney function in most patients.
Next Step\:
Step 1) Diagnosis of ARPKD is most often made by the clinical evaluation, labs, and imaging. The best initial imaging modality is with an ultrasound, which will typically show bilateral enlarged echogenic kidneys with poor cortico-medullary differentiation. The ultrasound of the liver may reveal dilatation of the intrahe- patic biliary ducts (ie, duct ectasia) and occasionally hepatic cysts. In cases when ultrasound findings are equivocal, an MRI or CT may be considered as adjunctive testing, but remember to limit the radiation exposure in children (ie, CT). Genetic testing is not routinely performed to make the diagnosis, but in cases of uncer­ tainty, genetic testing can be used to confirm the diagnosis. The following labs may also support the diagnosis\:
CBC—Low platelet levels may be seen secondary to splenic sequestration.
CMP—Hyponatremia may be seen; creatinine levels may be normal or elevated; low HC03- may be seen secondary

to metabolic acidosis; LFTs are usually normal; check albu­ min level to assess hepatic synthetic function.
Coags—PT and PTT will also give you an idea of the he­ patic synthetic function.
Urine osmolality—Assess for impaired urinary concentra­ tion (ie, 1 urine osmolality)
Step 2) Counseling should be offered to families and individuals once the diagnosis is established.
Step 3) There is no specific treatment that will delay or prevent ARPKD. Treatment is mainly supportive. However, there may be concerns during the management of ARPKD. Consider the following\:
ESRD—Dialysis or renal transplantation are options for ESRD.
Hypertension—Multiple agents maybe required to control the hypertension, but ACE inhibitors may be initially attempted.
Respiratory distress—Neonates may require mechanical ventilation secondary to pulmonary hypoplasia.
Feeding difficulties—Patients may need a higher caloric formula or supplemental feedings with an NG or gastros­ tomy tube.
Progressive portal hypertension—A portacaval shunt may be necessary or liver transplantation is another viable option.
Esophageal varices—Nonselective beta-blocker, sclerother­ apy, or endoscopic banding may be necessary.
Immunizations—Patients with severe portal hyperten­ sion and splenic dysfunction should be immunized against encapsulated bugs (eg, meningococcus, pneumococcus, H influenza type B).
Nephrotoxic agent avoidance—Patients should avoid ami­ noglycosides and NSAIDs.
Follow-Up\:
Patients need frequent monitoring for their blood pressure, re­ nal function, liver assessment, weight gain, and linear growth.
Pearls\:
• Neonates that survive the neonatal period (ie, first month of life) have approximately an 80% chance of living >10 years of age.
• ARPKD patients that have findings of congenital hepatic fibrosis with bile duct dilatation have a syndrome referred to as Caroli syndrome.
URINARYTRACT DISORDER
1 NEPHROLITHIASIS
Nephrolithiasis involves the interplay between supersaturation of urinary solutes and the lack of inhibitors (eg, citrate) in the urine that prevent crystal formation. The majority of stones are
• Patients that develop acute cholangitis may have the classic Charcot triad (ie, fever, RUQ pain, and jaundice).
• The absence of renal cysts in either parent on ultrasound helps to differentiate ARPKD from ADPKD (ie, ADPKD parents will typically demonstrate cysts, but if they are young parents without cysts then you might have to look at the grandparents for the cysts).
• Foundational point—The PKHD1 gene is located on chro­ mosome 6.
• Foundational point—Macrocysts are more typical ofADPKD.
• Foundational point—Microcysts (ie, less than 3-4 mm) are seen in ARPKD and typically radiate from the medulla to the cortex, but macrocysts can be seen in older children with ARPKD, which could make it difficult to differentiate between ADPKD.
• Foundational point—Cystic dilatations can be seen in all parts of the nephron in ADPKD, but cystic dilatations in ARPKD are typically in the collecting tubules.
• Connecting point (pg. 184)—Oligohydramnios (ie, amniotic fluid index <5 cm) can also be the result of ruptured fetal membranes.
• Connecting point (pg. 161)—Prenatal genetic testing can be offered to patients affected with the mutation. Know what week of gestation to do either an amniocentesis or chorionic villus sampling (CVS).
• Connecting point (pg. 163)—Recognize the genetic pedi­ gree chart of autosomal recessive genes. If the parents are heterozygotes (ie, carriers of one disease allele), then their child has a 25% chance (1 out of 4) of inheriting both disease alleles and developing the disease, 50% chance of inheriting one disease allele and being a carrier (1 out of 2), 25% chance of not inheriting any disease allele, and 75% chance (3 out of 4) of becoming asymptomatic (remember heterozygotes can be asymptomatic). Also, know that consanguinity is sugges­ tive of autosomal recessive inheritance.
• On the CCS, both “peritoneal dialysis” and “hemodialysis” are available in the practice CCS.
• On the CCS, “renal transplant” is available in the practice CCS, but remember to get a pediatric nephrology consult.
• On the CCS, if you require mechanical ventilation during any CCS cases, the prerequisites are either an intubation or tracheostomy. You are not required to know the mechanical ventilator settings (eg, PEEP, tidal volume, respiratory rate, Fi02,1\:E ratio).
calcium stones (75%), which are primarily composed of calcium oxalate and less often of calcium phosphate. Other stones include struvite stones (10%-15%), uric acid stones (5%-10%), and cystine stones (l%-2%).
Clinical Features\:
Patients with nephrolithiasis can sometimes be asymptom­ atic with stones that are discovered incidentally on radiologic
CHAPTER 18 RENAL AND GENITOURINARY 275

276 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
imaging for an unrelated reason. However, the classic symp­ tom is an acute onset of intermittent pain. The pain in acute renal colic can vary from mild to excruciating and typically waxes and wanes. The location of the stone usually correlates with the location ofthe pain in that an obstruction in the upper ureter will refer pain to the flank, mid-ureter will refer pain to the lower anterior quadrant, and lower ureter obstruction will refer pain to the ipsilateral testicle or labium. If the stone is lodged in the ureterovesical junction, patients will often com­ plain of urinary urgency, frequency, and dysuria. Associated signs and symptoms that may or may not be present include nausea, vomiting, and hematuria. On physical examination, most patients will be unable to find a comfortable position or they may appear to wiggle on the stretcher or writhe in pain, which is unlike an acute abdomen where patients tend to be still. Ipsilateral costovertebral angle tenderness is also a com­ mon finding on exam.
Next Step\:
Step 1) Patients in severe pain should be given analgesics. NSAIDs provide pain relief and have a direct effect on the ureter by the inhibition of prostaglandin synthesis. Opiates do not have a direct effect on the ureter but are still used for pain relief. However, the combination of NSAIDs (eg, ketorolac) and opioids (eg, morphine) is effective in pain control and may be superior to either agent alone based on randomized trials. The route of administration can be IV for faster pain relief, but the oral form can be given if the patient is able to tolerate oral intake.
Step 2) Antiemetics (eg, metodopramide) should be given to patients with nausea and vomiting, as these symptoms are often associated with acute renal colic. In addition to providing relief from nausea, metodopramide has also been shown to provide pain relief that is equivalent to narcotic analgesics in 2 double- blinded studies.
Step 3) The initial workup in patients with nephrolithiasis should include labs and imaging. First, consider the following labs and use your clinical judgment on what tests are appropri­ ate for that given patient.
|$-HCG—A qualitative (J-HCG should be obtained in females of childbearing age due to a risk of radiation exposure if imaging is pursued and to differentiate from other possible diagnoses.
Urinalysis—UA will determine the pH of the urine where a pH <5.5 would suggest a uric acid stone but more alka­ line urine with a pH >7 would suggest a struvite or calcium phosphate stone. UA can also detect hematuria and possible infection. A positive leukocyte esterase (LE) plus a positive nitrite should prompt you to order a urine culture with sen­ sitivities. Microscopic examination of the urine sediment can detect crystals that would provide information on the type of stone (see Figure 18-1 and Color Plate 14).
Urine culture—Obtain a urine culture if an infection is found. In addition, a urine culture should be obtained in all pediatric patients suspected of having nephrolithiasis because a UTI may also be present.
BMP—Assess for the BUN and creatinine since some stone formers will have a reduced creatinine clearance.
CBC—Check to see if there is leukocytosis if the patient is febrile or you speculate a systemic infection. However, be aware that mild leukocytosis can accompany acute renal colic secondary to an adrenergic response.
Second, the initial evaluation should also include imaging studies. Consider the following imaging modalities and again using your clinical judgment on what tests are appropriate for that given patient.
Noncontrast CT—The preferred imaging modality is with a noncontrast abdomen/pelvis CT because it has a very high sensitivity and specificity. However, a CT should be avoided in pregnant women to avoid radiation exposure. CT has the advantage of detecting radiolucent uric acid stones that are often missed on KUB. Unfortu­ nately, nonopaque stones due to HIV protease inhibitors (eg, indinavir, atazanavir) are often missed with non­ contrast CT scan, and in these patients, a contrast CT should be considered.
Ultrasound—Ultrasound is the preferred imaging modal­ ity in pregnant women and in patients where you want to minimize radiation exposure (eg, children). Ultrasound has the advantage of detecting hydronephrosis and can detect radiolucent stones that are missed on KUB. The disadvan­ tage of ultrasound is that it may miss small stones (<5 mm) and stones located in the mid-ureter region.
Abdominal plain film—A flat plate or kidney-ureter-blad­ der film (KUB) can detect large radiopaque stones (eg, cal­ cium, cystine, and struvite) but will often miss radiolucent stones (eg, uric acid). The KUB is not the best initial test because it has a fairly low sensitivity and specificity.
Intravenous pyelogram (IVP)—IVP or urography was once considered the gold standard but has been largely replaced by noncontrast CT. IVP has the advantage of outlining the urinary system where a mild hydronephro­ sis could easily be detected or nonopaque stones could be identified as a filling defect. The disadvantage of IVP is that contrast material is required and patients are exposed to radiation.
Step 4) Most stones that are <4 mm (0.4 cm) will spontaneously pass, but as the stone becomes larger in diameter (>5 mm), the passage rates decline and stones >10 mm (1.0 cm) are unlikely to pass. Patients who have well-controlled symptoms, adequate renal function, and stones <10 mm can initially be observed and offered medical expulsive therapy (MET) during the observa­ tion period. However, patients that have unrelenting symptoms or persistent obstruction should be seen by a urologist with possible intervention. Consider the following management approach\:
Acute Management
• Hydration—Patients should be encouraged to increase their fluid intake. However, forced IV hydration does not neces­ sarily increase the rate of stone passage.

• Pain control—Provide adequate analgesics but be aware of the potential for drug abuse with opioids and avoid NSAIDs in patients with a history of GI bleeds or preexisting renal disease.
• Stone passage facilitators—MET with alpha-blockers (eg, tamsulosin, doxazosin) or calcium channel blockers (eg, nifedipine) can increase the rate of ureteral stone passage.
• Straining—Patients should be advised to strain their urine for the next several days to retrieve any stone for analysis, which will elucidate the type of stone and will help target preventative therapy.
• Empiric antibiotics—Patients can be given empiric antibi­ otics on an outpatient basis if there is an associated UTI, but without systemic infection or significant obstruction. The choice of antibiotics should cover gram-negative rods and reasonable options include ciprofloxacin for 10 to 14 days, levofloxacin for 10 to 14 days, or other antibiotics based on local sensitivities.
• Urology consult—An urgent urologic consult should be obtained in patients with intractable pain or vomiting, anuria, acute renal failure, obstruction (hydronephrosis), or uro­ sepsis. An outpatient urologic referral should be obtained in patients with stones >10 mm (1.0 cm), stones that have not passed in more than 4 to 6 weeks despite fluid intake or with MET, or if significant discomfort develops.
• Urologic procedures—Shock wave lithotripsy and ureteros- copy are two common techniques used to remove ureteral stones, and both are considered first-line procedures.
Extracorporeal shock wave lithotripsy (ESWL)\: ESWL is the procedure of choice for small proximal ureteral stones (<10 mm). However, ESWL is not the ideal modality for large stones, stones of harder com­ position (eg, calcium oxalate, cystine), or patients with complex renal anatomy.
Ureteroscopy (URS)\: URS is the procedure of choice for middle and distal ureteral stones, although the pro­ cedure can still be performed for proximal ureteral stones. URS involves the passage of a small endoscope into the bladder and up the ureter with retrieval of the stone using a grasping forceps or stone basket.
Percutaneous nephrolithotomy (PNL)\: PNL involves percutaneous access to the kidney that requires general anesthesia. The stones can be visualized with a nephro- scope and the calculi can be fragmented using a device attached to the scope that delivers localized energy (eg, laser, ultrasonic, pneumatic) to a specific area (intracor- poreal lithotripsy). The urologist can then retrieve the stones using grasping forceps. PNL is typically reserved for large stones (>20 mm or 2.0 cm) or complex renal stones.
Chronic Management
• 24-hour urine collection—A 24-hour urine collection may be advisable in recurrent stone formers with an unknown stone composition or in patients with their first stone but
with high risk features for a stone (eg, family history, obesity, diabetes, bowel surgery, malabsorption). The patient’s interest to perform a urine study and willingness to make lifestyle changes after the study are important factors to proceed with a metabolic evaluation. The urine study has the benefit oftargeting preventive therapy and detecting possible metabolic disorders. The test is usually performed twice on an outpatient basis and usually 1 to 2 months after the acute episode or after any intervention. The idea is to evaluate the urine composition while the patient is on his or her normal day-to-day diet. The variables that are usually measured include the urine volume, pH, calcium, oxalate, citrate, uric acid, sodium, potassium, phosphorus, and creatinine.
• Preventative therapy—Once the stone is analyzed and/or the urine collections are evaluated, then management can be tailored to the underlying stone (see Table 18-1).
Disposition\:
Patients should be admitted to the hospital if they have urosep­ sis, acute renal failure, intractable pain or vomiting, medical comorbidities, or significant obstruction with infection.
Pearls\:
• Approximately 25% to 40% of patients will have recurrence of another stone within 5 years.
• Open stone surgery has a limited role since the advent of other procedures (eg, ESWL, URS).
• A phlebolith (ie, a calculus in a vein) can be confused with a ureteral stone. On KUB, a lucent center can be seen in a phlebolith but not with a ureteral stone. On CT, a “rim” sign, which is a halo surrounding the stones (secondary to circumferential edema of the soft tissue), can be seen.
• Two common stones seen in ADPKD are calcium oxalate and uric acid stones.
• The predominant type of stones in pregnancy is calcium phosphate because of an increase in calcium excretion and a rise in pH during pregnancy.
• Transvaginal ultrasound can detect distal ureteral stones bet­ ter than a transabdominal ultrasound.
• Caveat 1—Alkali therapy is the treatment for distal (type 1) RTA, but caution is advised in patients with calcium phos­ phate stones since alkalinization of the urine promotes this type of stone.
• Caveat 2—Acetohydroxamic acid (AHA) should be used with caution because it has many side effects such as nausea, vomiting, tremors, palpitations, and headaches. AHA is con­ traindicated in pregnancy (Category X).
• Caveat 3—ESWL is contraindicated in pregnancy.
• Caveat 4—Cholestyramine is an oxalate and bile acid resin that may cause unwanted side effects (eg, abdominal pain, bloating, nausea, constipation).
• Caveat 5—Sodium salts used in alkalinization (eg, sodium bicarbonate, sodium citrate) can actually increase urinary calcium excretion.
CHAPTER 18 RENAL AND GENITOURINARY 277

278 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Caveat 6—An expanding or ruptured AAA is often misdiag­ nosed as an acute renal colic.
• There is controversy in the role of hyperuricosuria in the for­ mation of calcium oxalate stones.
• Low dietary calcium may actually increase the risk of calcium stone formation because calcium normally binds to oxalate in the gut forming an insoluble salt, thereby preventing free oxalate from absorption and eventual excretion into the urine.
• Patients with fat malabsorption will cause calcium to bind with fatty acids instead of oxalate in the gut resulting in free oxalate absorption and eventual excretion into the urine (referred to as enteric hyperoxaluria).
• The dietary risk factors that increase the risk of calcium stone formation include 4 fluid intake, 4 phytate (eg, seeds, grains, nuts), 4 potassium (eg, fruits and vegetables), 4 diet calcium, T sucrose, T fructose, T animal protein, T oxalate foods, t sodium intake, T vitamin C.
• Citrate is a principal inhibitor in the urine to prevent calcium stone formation. Excretion of citrate is enhanced by alkalin- izing the plasma because it will decrease the uptake of citrate from the proximal tubular cells.
• Although there are many foods that contain oxalate, there is no need to have complete restriction of oxalate-containing foods because of the potential health and nutritional benefits from the foods.
• Thiazides cause reabsorption of calcium in the distal tubules resulting in a decrease in urinary calcium, unlike loop diuretics (eg, furosemide) which causes the calcium to “loop” through the tubules resulting in an increase in urinary calcium.
• The formation of calcium oxalate crystals does not depend on urine pH since the crystals can form in acidic, neutral, or alkaline urine.
• In the event of ethylene glycol (antifreeze) poisoning, an increased number of calcium oxalate crystals can be seen in the urine since ethylene glycol is an oxalate precursor that becomes oxidized by alcohol dehydrogenase and aldehyde dehydrogenase. Fomepizole or ethanol is used to treat ethyl­ ene glycol poisoning since both competitively inhibit alcohol dehydrogenase.
• Struvite stones are usually composed of magnesium-ammo­ nium-phosphate crystals admixed with calcium carbonate apatite.
• Urease-producing organisms produce urease, which results in an increase in ammonium (NH+) in the urine and causes the urine to become alkaline, which in turn favors the pre­ cipitation of struvite and apatite.
• Patients treated with medical management alone for struvite stones are rarely successful.
• Uric acid crystals are seen primarily in acidic urine (pH <5.5), but when the urine pH is >5.5 the uric acid is in its ionized form as urate salts (eg, amorphous urate's).
• Alkalinizing the urine in patients with cystine stones increases the solubility of cystine.
• Cystine can be detected by the cyanide-nitroprusside test. A positive reaction turns the urine into a red-purple color and indicates a urine cystine concentration of at least >75 mg/L. A quantitative urinary cystine excretion test can be performed and most individuals with cystinuria will excrete >400 mg/dy.
• The defective cystine transporter is not only involved in cys­ tine, but also other dibasic amino acids such as lysine, argi­ nine, and ornithine. Although these dibasic amino acids are also lost in the urine, they are relatively soluble and thereby do not lead into stones.
• Indinavir crystals can appear as a starburst shape, fan­ shaped, or platelike shape.
• Foundational point—Cystine is made up of two cysteine molecules linked by a disulfide bond.
• Connecting point (pg. 24)—Know the drug profile for bile acid sequestrants.
• Connecting point (pg. 73)—If the clinical picture presents as “bones, stone, abdominal and psychic moans” think pri­ mary hyperparathyroidism and order a serum calcium level along with an intact PTH.
• Connecting point (pg. 162)—Know the other types of auto­ somal recessive disorders.
• CJ\: A 52-year-old man was found to have urosepsis with an obstructing stone in the ED. What is your next step? Answer\: The patient needs an emergent decompression with either percutaneous drainage (ie, nephrostomy tube) or a ureteral stent in combination with appropriate antibiotics. An emergency decompression is also warranted in patients with a solitary kidney with complete obstruction and in patients with bilateral obstruction with acute kidney injury.
• On the CCS, “percutaneous nephrostomy” and “ureteral stent” are available in the practice CCS.
• On the CCS, “lithotripsy” is available in the practice CCS, but remember to order a consult for the procedure.
• On the CCS, “strain urine for stone” is available in the prac­ tice CCS.
• On the CCS, if a stone is retrieved during the CCS, there is an option for “ureteral calculi analysis” in the practice CCS.
• On the CCS, a “24-hour urine collection” is not available in the practice CCS. Instead, you are required to order the specific components of the urine collection and only urine calcium, oxalate, uric acid, phosphorus, and creatinine will give you the results based on a 24-hour time period in the practice CCS.
• On the CCS, remember to use the “Interval/follow up” to see how the patient is doing, especially after giving analgesics.
• On the CCS, remember to “bridge” your therapy by address­ ing the acute stages ofyour therapy (eg, analgesics) with the chronic stages of therapy (eg, prevention).
• On the CCS, this a type of case that will require you to become comfortable in moving patients to different locations and advancing the time. Therefore, start practicing with each chapter review!

NEOPLASM
1 WILMS'TUMOR
Wilms’ tumor is the most common renal malignancy in chil­ dren younger than 15 years of age. Wilms’ tumor is associated with a number ofgene alterations (eg, deletions, mutations), but the exact pathogenesis to the development of Wilms’ tumor is still unknown. Interestingly, the genetic abnormalities in Wilms’ tumor are mapped to the same general vicinity (chromosome 11) as 3 recognizable malformation syndromes\: WAGR, Denys- Drash, and Beckwith-Wiedemann.
Clinical Features\:
Wilms’ tumor is more common in blacks compared to whites with even a lower risk in the Asian population. In the majority of cases, children will present with an asymptomatic abdomi­ nal mass that is usually discovered incidentally by the parents. Wilms’ tumor can be bilateral or unilateral with usually an earlier diagnosis or later diagnosis, respectively. The mass is usually smooth and nontender and typically does not cross the midline unless the mass is very large. Other possible signs and symptoms to be aware of include abdominal pain, vomit­ ing, hematuria, hypertension, fever, anemia, anorexia, weight loss, intestinal obstruction, or venous obstruction (eg, edema, varicocele, engorged veins). In advanced disease, children may have respiratory problems secondary to metastases to the lungs. Consider the associated syndromes of Wilms’ tumor\:
WAGR—Wilms’ tumor, Aniridia, Genitourinary anoma­ lies, Retardation (intellectual disability)
Deny-Drash syndrome—Wilms’ tumor, male pseudoher­ maphroditism, early onset nephrotic syndrome that pro­ gresses to renal failure
Beckwith-Wiedemann syndrome—Wilms’ tumor (5%-20% of cases), macrosomia, macroglossia, gigantism, omphalocele/ exomphalos, enlarged organs (visceromegaly), earlobe creases, hyperinsulinemia, hypoglycemia
Next Step\:
Step 1) The best initial test in patients suspected of having Wilms’ tumor is an abdominal ultrasound because it is rela­ tively inexpensive and it does not give off harmful radiation. Doppler ultrasound can detect the patency of blood flow in the event that the tumor has infiltrated the IVC. Further evalua­ tion with a contrast abdominal CT is recommended to assess if there is bilateral renal involvement, lymph node involvement, or metastases to the liver. Imaging should also be performed on the chest to evaluate for lung metastases, but the preferred modality (chest x-ray vs chest CT) is still under debate.
Step 2) Laboratory testing should include the following\:
CBC—Look for signs of anemia (ie, -i Hb).
CMP—Assess LFTs to check for possible liver metastases; calcium levels for hypercalcemia; and serum creatinine levels to detect a decrease in GFR.
Coags—PT and PTT should be checked since approximately 5%-10% ofpatients will have acquired von Willebrand’s dis­ ease at the time of diagnosis.
Urinalysis—Assess for hematuria; check proteinuria which would suggest Deny-Drash syndrome.
Step 3) Definitive diagnosis of Wilms’ tumor requires a tissue sample usually at the time of surgical excision. At the time of surgical excision, staging is performed based on the anatomic extent of the malignancy. In the United States, attempts are made to obtain a unilateral nephrectomy prior to the initiation of chemotherapy unless there is bilateral renal involvement (in which case preoperative chemotherapy followed by surgery is considered). In Europe, attempts are made to give preoperative chemotherapy (ie, shrink the tumor) prior to resection. Therefore, there are two different staging systems and the major system used in the United States is the National Wilms’ Tumor Study (NWTS). For board purposes, the following is a simplified staging schema for Wilms’ tumor\:
Stage I—Tumor limited to the kidney.
Stage II—Tumor extends beyond the kidney, but is com­ pletely resected without evidence of tumor at or beyond the margins of resection.
Stage III—Residual tumor confined to the abdomen after surgery.
Stage IV—Hematogenous metastases or metastases to dis­ tant lymph nodes (beyond abdomen/pelvis).
Stage V—Bilateral renal involvement.
Step 4) Treatment is typically based on staging and tumor histology. In patients with stage I-IV and a favorable histology, the common approach is first with a unilateral nephrectomy followed by chemotherapy with radiation reserved for stages III and IV. Treatment in stage V is more challenging, and treat­ ment approach is usually individualized with the oncologist (eg, preoperative chemo followed by surgery or initial surgical resection).
Follow-Up\:
Follow-up care is important for treatment-related complica­ tions and ongoing surveillance with the lungs as the most com­ mon site for recurrence.
Pearls\:
• The 5-year overall survival rate is approximately 90% with either the US or European treatment approach.
• The mean age at diagnosis is approximately 3.5 years of age.
• Caveat 1—Avoid vigorous abdominal palpation on exam because the tumor can rupture and result in spillage into the peritoneal cavity leading to a higher tumor stage.
• Caveat 2—Avoid transcutaneous biopsy because tumor spillage can occur in the peritoneal cavity.
• Caveat 3—Patients treated for Wilms’ tumor can develop secondary malignancies (eg, leukemias, solid tumors).
CHAPTER 18 RENAL AND GENITOURINARY 279

280 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Caveat 4—Common chemotherapeutic agents used to treat Wilms’ tumor can cause cardiotoxicity (ie, doxorubicin), or hepatotoxicity (ie, vincristine and dactinomycin).
• Aniridia is the congenital absence of the iris seen in WAGR syndrome.
• Wilms’ tumor is a nephroblastoma not a neuroblastoma. A neuroblastoma is a tumor that arises from primitive sympa­ thetic ganglion cells.
• Foundational point—Patients with the WAGR syndrome have a chromosomal deletion of the WT1 gene located on chromosome 11.
• Foundational point—Patients with the Denys-Drash syndrome have a mutation in the WT1 gene located on chromosome 11.
• Foundational point—Patients with the Beckwith-Wiedemann syndrome have a mutation in the WT2 gene located on chromosome 11.
• Foundational point—Favorable histology seen in Wilms’ tumor includes epithelial cells, stromal cells, and blastemal cells. An unfavorable histology includes anaplastic features (eg, enlarged hyperchromatic nuclei, abnormal mitoses), which have a poorer outcome.
• Foundational point—On pathological exam of a Wilms’ tumor, the mass is typically a well-circumscribed mass with a tan to gray color appearance on cut section.
• Connecting point (pg. 132)—Know the other types of acquired von Willebrand disease (vWD).
• On the CCS, if you decide to order a pediatric nephrology consult, remember to implement a course of action before the consultant is able to see your patient (eg, preordering ultrasound, CT, and labs).

Rheumatology
CHAPTER OUTLINE
Keywords Review............................................2.8.1........ INFLAMMATORY MYOPATHIES.........................2.8..6..
I I
METABOLIC DISORDER.................................2.8..2..... Dermatomyositisand Polymyositis...........................2.8.6....
Osteoporosis...............................................2.8.2.......... InclusionBodyMyositis.....................................2..8.8...... CRYSTAL-INDUCED ARTHROPATHIES..................2.8..3 I INFLAMMATORY DISORDERS...........................2.8.8...
Gout.......................................................2.8.3...........RheumatoidArthritis.......................................2.8..8....... Pseudogout................................................2.8.6........I.. CCS......................................................2..9.1...........
Polymyalgia Rheumatica....................................2.9.1......
infections, vasculitis, tumor involvement, autoimmune- mediated diseases, or diabetes.
Pannus—An inflammatory exudate that overlies the synovial membrane in rheumatoid arthritis. In Latin, pannus means "a piece of cloth."
Peak bone mass—The maximum amount of bone mass accumulated during early adult life.
Podagra—A painful condition at the base of the great toe usually caused by gout.
Swan-neck deformity—Hyperextension at the PIP joint with flexion at the DIP joint, which is characteristic of rheumatoid arthritis.
Tophus—Deposits of monosodium urate crystals into soft tissue with a surrounding inflammatory response. Tophi (plural) are pathognomonic for gout.
KEYWORDS REVIEW
Bouchard's nodes—Hard, bony enlargements at the PIP joints, which are characteristic of OA.
Boutonniere deformity—Flexion at the PIP joint with hyperextension of the DIP joint, which is characteristic of rheumatoid arthritis.
Chondrocalcinosis—Calcification of cartilage. In pseudo­ gout, the calcification is due to CPPD crystals depositing into fibrocartilage (eg, menisci of the knee) or articular cartilage that will appear as punctate or linear densities on x-ray. Chondrocalcinosis is not pathognomonic for pseudogout.
Heberden's nodes—Prominent osteophytes in the DIP joints, which are characteristically seen in OA (women > men).
Mononeuritis multiplex—Nerve damage that occurs in two or more separate areas of the body and can be due to

282 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
METABOLIC DISORDER
9 OSTEOPOROSIS
Osteoporosis is the most common metabolic bone disease in the United States. Osteoporosis (“porous bone”) can be charac­ terized by low bone mass and microarchitectural deterioration, which can lead to fractures.
Risk Factors\:
Advanced age, white or Asian race, female gender, postmeno­ pause, low body weight (<127 lbs [58 kg]), personal history of fracture,familyhistoryofosteoporoticfracture,excessivealcohol intake (>3 drinks/dy), tobacco use, low calcium or vitamin D intake, excess vitamin A intake, medications (glucocorticoids >5 mg/dy for >3 months, phenytoin, phenobarbital, heparin, lithium, proton pump inhibitors, cyclosporine), endocrine disorders (Cushing’s syndrome, adrenal insufficiency, diabetes mellitus, hyperparathyroidism, thyrotoxicosis, hypogonadism, estrogen deficiency, androgen deficiency), genetic disorders (osteogenesis imperfecta, Marfan’s syndrome), GI disorders (celiac disease, chronic liver disease, gastric bypass), heme disorders (leukemia, lymphoma, multiple myeloma), renal disorders (renal failure, dialysis patients), respiratory disorder (COPD), rheumatoid disorders (rheumatoid arthritis, anky­ losing spondylitis, SLE), organ transplantation.
Clinical Features\:
Osteoporosis is usually an asymptomatic condition. Patients can have fragility fractures, which are fractures that would normally not occur due to minimal force or low trauma. Common sites for fractures include the hip, humerus, distal radius (Colies fracture), and vertebrae. Patients with vertebral fractures will typically show progressive kyphosis ("dowager’s hump”) or a loss of height. Approximately two-thirds of patients with vertebral fractures will be asymptomatic. Patients that are symptomatic from a vertebral fracture will usually complain of acute back pain after bending, lifting, or coughing.
Next Step\:
Step 1) Based on the National Osteoporosis Foundation (NOF) guidelines, perform a dual-energy x-ray absorptiometry (DEXA) of the hip and spine in all women >65 years old and all men >70 years old, regardless of risk factors. Also, perform a DEXA in younger postmenopausal women and men 50 to 69 years of age who have risk factors for a fracture.
Step 2) The World Health Organization (WHO) has established diagnostic categories based on the bone mineral density (BMD)\:
Normal\: T-score >-1.0
Osteopenia\: T-score between -1.0 and -2.5
Osteoporosis\: T-score <-2.5
Severe osteoporosis\: T-score <-2.5 and in the presence of one or more fragility fractures
Step 3) Any postmenopausal women or men with a T-score <-2.5 or has a fragility fracture should have baseline labs to help
exclude secondary causes of osteoporosis (see list of medica­ tions and medical conditions in “Risk Factors” section). The labs should include a CBC, CMP (to look at calcium, alkaline phos­ phatase, LFTs, electrolytes, creatinine, albumin, protein), serum phosphorus, 24-hour urinary calcium level, 25-hydroxyvitamin D, and serum testosterone (only men).
Step 4) Encourage nonpharmacologic treatment to postmeno­ pausal women and all men >50 years of age that includes\:
Lifestyle modification—Reduce alcohol consumption to <3 drinks/dy, smoking cessation, weight-bearing and muscle-strengthening exercise.
Calcium and vitamin D intake—Calcium intake of at least 1200 mg/dy and vitamin D intake of 800IU.
Fall prevention—Identify risk factors for falls, check hearing and vision, review medications.
Step 5) In general, patients that are at risk of developing fractures should be treated with pharmacologic therapy. The NOF recommends treatment in patients with hip or verte­ bral fractures, T-score <-2.5 at the femoral neck or spine by DEXA, or those with osteopenia (T-score between -1.0 and -2.5) who have a 10-year hip fracture probability of >3% or a 10-year major osteoporosis-related fracture probability >20% based on the US-adapted WHO absolute fracture risk model. The following are the approved FDA pharmacologic modali­ ties for the prevention and/or treatment of osteoporosis\:
Bisphosphonates
• Bisphosphonates are considered first-line agents.
• Bisphosphonates inhibit osteoclastic activity.
• Alendronate, risedronate, and zoledronic acid reduce verte­ bral and hip fractures. Only zoledronic acid is available in the IV route of administration.
• Ibandronate is only effective at reducing vertebral fractures.
• Oral bisphosphonates can cause GI problems such as diffi­ culty swallowing, esophagitis, gastric ulcers, or GERD.
• IV zoledronic acid can cause an acute phase reaction (eg, flu­ like symptoms, fever, myalgia) and rare reports of osteone­ crosis of the jaw.
Selective Estrogen Receptor Modulator (SERMs)
• Raloxifene can increase BMD.
• Raloxifene is only effective at reducing vertebral fractures.
• Raloxifene has estrogen agonist activity on the bones and lipids, but has estrogen antagonistic activity on the breast and uterus.
• Raloxifene can increase vasomotor symptoms (hot flashes), increase the risk ofvenous thromboembolism, and although it can decrease total cholesterol and LDL, it does not reduce the risk of coronary heart disease.
• Raloxifene can decrease the risk of invasive breast cancer in postmenopausal women with osteoporosis.
• Ideally, raloxifene would be best suited for a patient who does not have hot flashes, and has no risk of thromboembo­ lism but a high risk of breast cancer.

• Tamoxifen is another SERM, but it is not prescribed for the treatment of osteoporosis.
• Tamoxifen has estrogen agonist activity on the bones (preserves bone density) and on the endometrium (t risk ofendometrial cancers), but it has estrogen antagonistic activity on the breast.
Estrogen-Progestin Therapy
• Estrogen-progestin therapy is not considered a first-line agent becausethebenefitsdonotoutweightheriskofastroke,venous thromboembolism, coronary heart disease, and breast cancer.
• Consider other medical treatment if estrogen-progestin therapy is used only for the treatment of osteoporosis.
• If estrogen-progestin therapy is used, it should be in the low­ est effective dose and for the shortest period of time that attains treatment goals.
Calcitonin
• Salmon calcitonin is not considered first-line treatment.
• Salmon calcitonin can be used in women who are at least 5 years postmenopausal.
• Salmon calcitonin is only effective at reducing vertebral fractures.
Parathyroid Hormone
• Teriparatide is a recombinant human parathyroid hormone that is typically reserved for patients with severe osteoporosis, high risk for fractures, or failed other treatments.
• Teriparatide reduces vertebral and hip fractures.
Follow-Up\:
Monitor the response to osteoporosis therapy every 2 years with DEXA testing and then less frequently thereafter if the BMD assessments show signs of improvement or are stable.
Pearls\:
• Be vigilant about patients that have a history of an osteopo­ rotic fracture because they are prone to have another fracture in the future.
CRYSTAL-INDUCED ARTHROPATHIES
I GOUT
Gout is a disease that is associated with hyperuricemia due to an overproduction or underexcretion of uric acid (see Table 19-1). When uric acid levels reach the point of supersaturation or exceed the solubility limits, urate salts can precipitate out into monosodium urate (MSU) crystals and deposit into joints, soft tissues, and kidneys. The resulting clinical manifestations include gouty arthritis, tophi, uric acid nephrolithiasis, and urate nephropathy.
• Although men have a lower lifetime risk of a hip fracture compared to women, men have twice the mortality from hip fractures compared to women.
• Peak bone mass most likely occurs by the third decade of life, and age-related bone loss occurs soon thereafter with most of the bone loss occurring at >65 years of age.
• A T-score is a comparison of the BMD (BMD) of a patient to that of a young healthy adult of the same sex and is ex­ pressed in terms of standard deviations (SD) above or below the mean.
• A Z-score is a comparison of the BMD of a patient to that of the patient’s age and sex (age-matched population). A Z-score <-2.0 is considered a low BMD for that chronologi­ cal age, but a Z-score >-2.0 would be considered within the expected range for that age.
• Osteoporosis will typically have a reduction in both bone matrix and mineralization, but osteomalacia will have an in­ tact bone matrix but reduced bone mineralization.
• Common lab findings for nutritional osteomalacia include i calcium, J- phosphorus, i 25-hydroxyvitamin D level, T PTH, t alkaline phosphatase.
• Although patients can be asymptomatic with osteomalacia, bone pain is a common symptom.
• Bisphosphonates that are not FDA approved for osteoporosis include pamidronate, etidronate, and tiludronate.
• On the CCS, “DEXA scan” or “bone densitometry” are avail­ able in the practice CCS.
• On the CCS, the practice CCS does not recognize “zoledronic acid.”
• On the CCS, if you order a medication during the case, remember to “advise patient, side effects of medication.”
• On the CCS, be sure to also order “advise patient, limit alco­ hol intake,” “advise patient, no smoking,” and “advise patient, exercise program.”
Clinical Features\:
Gout commonly affects adult men and postmenopausal women. Gout occurs in three progressive stages\: acute gouty arthritis, intercritical (interval) gout, and chronic (tophaceous) gout.
Acute gouty arthritis—The majority of initial gout attacks are monoarticular, especially the first metatarsophalange­ al joint (podagra). In addition to the great toe, other sites include the insteps, heels, ankles, knees, wrists, fingers, or bursae. Patients will often present with signs ofinflammation, which include a sudden onset of pain, erythema, edema, and warmth, and sometimes with fever. In some cases, the inflammation can extend beyond the joint mimicking a cellu­ litis or tenosynovitis. In elderly people who have concomitant osteoarthritis, inflamed Heberden’s or Bouchard’s node may
CHAPTER 19 RHEUMATOLOGY 283

284 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
—Table 19-1 • Causes of Hyperuricemia
Chronic gout—'This stage can be characterized by the pres­ ence of tophi and is typically seen 10 years after the initial at­ tack. Tophi are usually nontender, but the tophi are surrounded by an intense inflammatory response that can cause symptoms similar to an acute gouty attack. Tophi can deposit into the helix of die ear, olecranon bursae, prepatellar bursae, Achilles tendon, toes, and over the Heberden’s or Bouchards node. Of­ ten the presence of subcutaneous nodules is mistaken for the diagnosis of rheumatoid arthritis. Over time, tophi can lead to nerve compression, joint destruction, or soft tissue damage.
Next Step\:
Step 1) Definitive diagnosis should be made with a needle aspi­ ration of the joint fluid or tophi, which will reveal the needle- shaped, negatively birefringent urate crystals when examined under a compensated polarized light microscope. See Table 19-2 for synovial fluid analysis.
Step 2) Gout is managed with anti-inflammatory therapy, antihyperuricemic therapy, and lifestyle modifications. Treat­ ment of gout is as follows\:
Acute Gout Therapy
• NSAIDs (eg, indomethacin, naproxen) are considered first- line therapy at the first sign of an attack, but it should be avoided in patients with renal insufficiency or those intoler­ ant to the GI side effects.
• COX-2 inhibitors (eg, celecoxib) is an alternative for patients that have GI side effects associated with NSAIDs and do not have known cardiovascular disease.
Overproducers
• Conditions
• Lymphoproliferative
disorders
• Myeloproliferative
disorders
• Malignancies
• Hemolytic disorders
• Polycythemia vera
• Psoriasis
• Obesity
• Purine-rich diet
• Vitamin B]2 deficiency
• Agents
• Alcohol
• Fructose
• Nicotinic add
• Warfarin
Underexcretors
• Conditions
• Renal insufficiency
• Volume depletion
• DKA
• Lactic acidosis
• Sarcoidosis
• Berylliosis
• Obesity
• Hypothyroidism
• Hyperparathyroidism
• Agents
• Alcohal
• Loop and thiazide diuretics
• Low-dose aspirin • Levodopa
• Pyrazinamide
• Ethambutol
be the sole or initial manifestation of a gout attack. Untreated gout attacks typically resolve within 7 to 10 days.
Intercritical gout—After an acute gout attack resolves, the patient enters an asymptomatic period. Most untreated patients will have another gout attack within 2 years of the initial attack, and over time the asymptomatic intervals will shorten between the attacks.
Table 19-2 • Synovial Fluid Analysis
Parameters
Volume (mL) at the knee
Color
Clarity
Viscosity Glucose (mg/dL)
WBC per mm3 PMN cells (%) Culture
Other features
Normal <3.5 mL
Clear
Transparent
High/thick
Close to serum glucose
<200 <25% Negative
Noninflammatory Inflammatory
Septic
Usually >3.5 mL
Yellow-green Cloudy
Variable
Very low, <25 mg/dL
15,000-200,000 >75%
Usually positive
Usually presents with a single swollen, painful joint.
Hemorrhagic Usually >3.5 mL
Red Bloody
Variable
Close to serum glucose
200-2000 50%-75% Negative
Look for a history of trauma or bleeding disorders.
CPPD—calcium pyrophosphate dihydrate; MSU—monosodium urate;PMN—polymorphonuclear
Usually >3.5 mL
Yellow
Transparent
High/thick
Close to serum glucose
200-2000
<25%
Negative
Osteoarthritis and trauma are examples.
Usually >3.5 mL
Yellow
Cloudy
Low/thin
Low, but >25 mg/dL
2000-100,000

50%
Negative
Gout—MSU crystals; needle shaped, nega­ tively birefringent. Pseudogout— CPPD crystals; rhomboid shaped, weakly positively birefringent.

• Colchicine is an alternative agent that would be an appropri­ ate therapy for patients who cannot take NSAIDs or steroid therapy. Low-dose oral colchicine is most effective if it is given within the first 24 hours of an attack. Oral colchicine does have GI side effects (ie, nausea, vomiting, diarrhea, abdominal cramping), and intravenous colchicine is no longer produced or shipped to the United States because of the risk of bone marrow suppression, hepatic necrosis, and death.
• Intra-articular glucocorticoid (eg, triamcinolone) injection can be used in patients who cannot take NSAIDs or colchi­ cine (eg, both NSAIDs and colchicine have GI side effects) and present with only one or two inflamed joints.
• Systemic glucocorticoid (eg, prednisone) therapy would be appropriate in patients who cannot take NSAIDs or colchi­ cine but present with polyarticular joint involvement.
Prophylactic Gout Therapy
• The goal of prophylactic gout therapy is to prevent another gout attack.
• Low-dose colchicine can be given for a period of time (eg, 3-6 months) to help serve as a bridge from an acute attack to preventive therapy (ie, lowering uric acid levels) since col­ chicine only decreases the frequency of gout flares without lowering uric acid levels.
Preventive Gout Therapy
• The goal of preventive gout therapy is to lower uric acid levels by dietary changes, adjusting medications (see Table 19-1), and antihyperuricemic medications.
• Weight reduction—Patients that are obese can reduce their risk of gout by reducing their weight.
• Dietary changes—Reduce red meat, seafood, alcohol (par­ ticularly beer and hard alcohol), high-fructose corn syrup based drinks, but encourage low-fat dairy products.
• Medication changes—Consider alternatives to medica­ tions when appropriate. For example, both thiazide and loop diuretics can elevate urate levels, but the antihypertensive medication losartan, might be a preferable choice because it can actually lower the urate levels.
Antihyperuricemic Medications
• Antihyperuricemic medication should be encouraged in patients with frequent painful gout, recurrent kidney stones, presence of tophi, joint damage seen on x-ray, or those with disabling gout.
• Underexcretors as determined by excreting <800 mg of uric acid in a 24-hour urine sample on a standard diet can be treated with the uricosuric agent probenecid. Probenecid is contraindicated in patients with uric acid kidney stones or those taking aspirin concomitantly.
• Overexcretors (ie, >800 mg of uric acid in 24-hour urine sample on a standard diet) can be treated with allopurinol.
• Both probenecid and allopurinol should not commence until after the acute gout attack resolves because it can precipitate another attack.
• Patients that have a gout attack while on antihyperuricemic medications should continue to take their antihyperuricemics, but also treat the acute gout with NSAIDs, colchicine, or steroids.
Follow-Up\:
Patients should initially be seen every 1 to 2 months when start­ ing antihyperuricemic medication to achieve a target serum uric acid level of <6 mg/dL, because this is below the level of its saturation point (ie, 6.7 mg/dL).
Pearls\:
• Although hyperuricemia is a risk factor for the development of gout, not all people with hyperuricemia will develop gout and therefore they should not be treated ifthere are no symptoms.
• Although serum uric acid levels can be elevated during an acute gout attack, some people may have normal or even low serum uric acid levels at the time of an attack.
• An elevated serum uric acid level does not confirm the diag­ nosis of acute gout, and a normal serum uric acid level does not rule out the diagnosis of acute gout.
• Less than 20% of initial gout attacks will be polyarticular, but over time, the gout attacks will be polyarticular later in the course of untreated gout.
• Although aspirin is considered an NSAID, it is not recom­ mended to treat an acute gout attack because it can alter the uric acid levels either (high or low) depending on the dose.
• Foundational point—Colchicine is an inhibitor of micro­ tubule assembly by binding to tubulin. The end result is re­ duced leukocyte migration, chemotaxis, and phagocytosis.
• Foundational point—Probenecid competes with uric acid for reabsorption at the proximal convoluted tubule, thereby promoting net renal excretion of uric acid.
• Foundational point—The sequential steps to uric acid synthesisincludesnucleicacids—>hypoxanthine—»xanthine —> uric acid. Xanthine oxidase is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and again cata­ lyzes the oxidation of xanthine to uric acid. Allopurinol is an inhibitor of xanthine oxidase, thereby reducing the produc­ tion of uric acid, but without disrupting the biosynthesis of vital purines.
• On the CCS, “arthrocentesis” and “joint fluid tap” are the same procedure and are both available in the practice CCS. The results will provide you with the amount (mL) of fluid withdrawn from the joint and the color of the fluid.
• OntheCCS,eitherarthrocentesisorjointfluidtapareprerequi­ sites to obtaining specific joint fluid tests (eg, joint fluid culture).
• On the CCS, when you type in “joint fluid” in the order menu, a list ofjoint fluid items can be selected.
• On the CCS, manage gout by selecting “join fluid analysis” which will give you the glucose, cell count, crystals, mucin, and viscosity. However, you will have to order the “joint fluid culture” and the “joint fluid Gram stain” individually.
• On the CCS, in addition to ordering a CBC, BMP, PT, PTT, and UA, other ancillary testing would include an ESR, serum
CHAPTER 19 RHEUMATOLOGY 285

286 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
uric acid level, 24-hour urine uric acid, and an x-ray of the involved joint (radiographic findings may reveal either soft tissue swelling [early phase], punched-out lesion [intermedi­ ate phase], or tophi [late phase]).
• On the CCS, by the end of the case, be sure to order “advise patient, medication compliance,” “advise patient, no alcohol,” “advise patient, no aspirin,” “advise patient, side effects of medication,” and “diet, low protein.”
• On the CCS, remember to “bridge” your therapy by treating the acute stages of the disease (eg, gout attack) with the long­ term care (eg, prevention).
BPSEUDOGOUT
Pseudogout is a calcium pyrophosphate dihydrate (CPPD) crys­ tal deposition disease that can be characterized by acute gout­ like attacks. The attacks are elicited from CPPD crystals that can deposit into articular cartilage, synovium, tendons, ligaments, and soft tissues.
Risk Factors\:
Although the cause of CPPD crystal deposition is unknown, the following conditions increase the risk of accumu­ lating CPPD crystals\: old age, joint trauma, join surgery, famil­ ial chondrocalcinosis, hemochromatosis, hyperparathyroidism, hypothyroidism, hypophosphatasia, hypomagnesemia, Gitleman’s syndrome (inherited renal tubular disorder).
Clinical Features\:
Pseudogout attacks usually affect one or a few joints at a time (ie, monoarticular > oligoarticular). The knees and wrists are common affected sites, but other places include the shoulders, elbows, hands, and ankles. Similarly to gout, signs of inflamma­ tion can occur that include pain, erythema, edema, and warmth. The attacks are usually self-limiting, lasting days to weeks. Inter­ estingly, attacks commonly occur following a parathyroidectomy.
Next Step\:
Step 1) Definitive diagnosis should be made with a needle aspiration of the joint fluid or articular tissue, which will reveal the rhomboid-shaped, weakly positively birefringent crystals when examined under a compensated polarized light micro­ scope. See Table 19-2 for synovial fluid analysis.
Step 2) Pseudogout is primarily managed with anti-inflammatory therapy since there is no effective treatment for preventing the
INFLAMMATORY MYOPATHIES
1 DERMATOMYOSITISANDPOLYMYOSITIS
Dermatomyositis (DM) and polymyositis (PM) are both idio­ pathic inflammatory myopathies that are thought to be medi­ ated by an immunologic mechanism.
deposition of CPPD crystals or removing CPPD crystals that are already deposited. Treatment of pseudogout is as follows\:
Acute Pseudogout Therapy
• Joint aspiration can serve as both diagnosis and treatment.
• Joint immobilization should be temporarily advised until the pain and swelling reduce.
• NSAIDs (eg, indomethacin, naproxen) can be used if there is no contraindication.
• Colchicine is an alternative agent that can be used to treat acute inflammation.
• Steroids can be used ifthere is a contraindication to NSAIDs or colchicine. Either intra-articular glucocorticoid (eg, tri­ amcinolone) injection for 1 or 2 involved joints, or systemic (oral) glucocorticoids for multiple joints may be attempted.
Prophylactic Pseudogout Therapy
• Low-dose colchicine can be given to patients that have recur­ rent attacks (ie, >3 attacks/yr).
Follow-Up\:
Patients treated for an acute attack may return to baseline in less than 10 days. If patients continue to have symptoms, consider the worst-case scenario (ie, septic arthritis) that may require prompt reassessment.
Pearls\:
• Pseudogout is associated with normal serum urate levels.
• CPPD crystal deposition disease can present similarly to rheumatoid arthritis and is notably termed pseudorheu- matoid arthritis. Patients can present with multiple joint involvement with symmetric distribution, morning stiff­ ness, fatigue, synovial thickening, elevated ESR, and 10% of patients will have a positive rheumatoid factor (RF).
• CPPD crystal deposition disease can present similarly to osteoarthritis and is notably termed pseudo-osteoarthritis. Patients can have progressive joint degeneration involving the shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, hips, knees, and spine.
• On the CCS, other testing that might be helpful (refer to the risk factor section) include serum calcium, phosphorus, magnesium, iron, ferritin, transferrin, TSH, and an x-ray ofthe involved joint (radiographic findings may reveal chondrocalcinosis).
Clinical Features\:
Females are twice as likely as males to have both DM and PM. Peak age of onset for DM is 5 to 10 years old and 40 to 50 years old. Peak age of onset for PM is also 40 to 50 years old, but children are rarely affected with juvenile PM. Both DM and PM are multisystem disorders whose principal clinical feature is proximal muscle weakness. The following

are other affected organ systems in a relative head to toe fashion\:
Esophagus—Involvement of the oropharyngeal muscles or upper esophagus can result in dysphagia, nasal regurgita­ tion, or aspiration.
Cardiac—Arrhythmias, conduction disturbances, myocar­ ditis, pericarditis, or CHE
Respiratory—Interstitial lung disease (ILD) or thoracic muscle weakness that can lead to pulmonary dysfunction.
Musculoskeletal—A symmetric, proximal weakness that progresses over a period of weeks to months. Patients will have difficulty combing their hair, climbing steps, or getting up from a chair. Both facial and ocular muscles are spared (unlike myasthenia gravis), but neck muscles can be affected resulting in a head drop. Fine-motor movements are usually affected late in the disease. Myalgias and muscle tenderness can occur in a subset of patients.
Systemic—Fever, weight loss, malaise, nondestructive ar­ thritis, or Raynaud’s phenomenon.
Skin—Cutaneous manifestations are usually associated only widi DM. However, PM has been associated with me­ chanics hands. The following are rashes that can precede or accompany the muscle weakness\:
Heliotrope rash\: A violaceous erythematous rash over the upper eyelids ± periorbital edema (see Figure 19-1 and Color Plate 15).
Gottron papules\: Violaceous erythematous papules over the dorsal aspects of the MCP and interphalangeal (IP) joints (see Figure 19-2 and Color Plate 16). Note that Gottron “sign” may be referred to as erythematous lesions at sites other than the hands (eg, elbows, knees, or ankles).
Shawl sign\: An erythematous rash over the chest, shoul­ ders, and upper back.
V sign\: An erythematous rash over the anterior neck and chest.
FIGURE 19-2 • Gottron papules. A raised, erythematous, scaly eruption can be seen over the dorsa of the hands and fingers, especially over the metacarpophalangeal and interphalangeal joints. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick's ColorAtlas ofSynopsis of Clinical Dermatology. 6th ed. New York\: McGraw-Hill; 2009\:372.)
Mechanic’s hands\: Rough, scaly, cracked, fissured hands seen in both DM and PM.
Erythema\: Erythema can be seen over the forehead and malar region (resembles SLE). Violaceous linear streaks on the trunk can also be observed (flagellate erythema).
Periungual changes\: Periungual erythema and telangi- ectasias can be observed.
Calcinosis cutis\: Deposition of calcium in the skin that commonly occurs in juvenile DM.
Next Step\:
Step 1) Initial diagnostic testing may include the following with the expected results\:
Muscle enzymes—T creatine kinase, T aldolase, T LDH, T ALT, T AST
Autoantibodies—ANA elevated 80% of the time, anti- Jo-1 elevated 20% to 30% of the time
RF—Elevated only 20% to 30% of the time ESR—Elevated only 50% of the time EMG—Myopathic pattern
Step 2) Definitive diagnosis is made by muscle biopsy. In PM, there is direct injury to the myofibers, but without vacuoles. Inflammatory cells (CD8+ T cells) are found primarily within the muscle fiber and the fibrous sheath that surrounds an individual muscle fiber (endomysium). In DM, the inflammatory cells (CD4+ T cells) are located around capillaries (perivascular), around a bundle of muscle fibers (perifascicular), fibrous sheath that surrounds the muscle fascicles (perimysium), and will demonstrate atrophy around the fascicle (perifascicular atrophy). Often the presence of perifascicular atrophy is sufficient to diagnosis DM, even in the absence of inflammation.
Step 3) Initial treatment for both DM and PM involves systemic steroids (eg, prednisone) for 4 to 6 weeks, followed by tapering doses until the lowest effective dose is reached. Unfortunately, about 75% of patients will ultimately require other adjuvant immunosuppressive therapy (eg, azathioprine, methotrexate).
FIGURE 19-1 • Heliotrope rash. Note the reddish-purple rash over the upper eyelid with edema over the lower lids. The purplish hue is likened to the flower Heliotropium peruvianum. This patient developed severe muscle weakness of the shoulder girdle and presented with a lump in the breast that proved to be carcinoma. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick'sColorAtlasofSynopsisofClinicalDermatology.6th ed. New York\: McGraw-Hill; 2009\:371.)
CHAPTER 19
RHEUMATOLOGY 287

288 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Step 4) Initiate gender and age-appropriate cancer screening. Although both DM and PM are at risk of cancer, it appears that there is a higher risk of cancer with DM. The most common tumors include breast cancer, ovarian cancer, cervical cancer, lung cancer, gastric cancer, colon cancer, melanoma, and non- Hodgkin’s lymphoma.
Follow-Up\:
Once therapy has started, patients should be seen every few weeks to objectively assess their muscle strength. Obtaining serum cre­ atine kinase (CK) does not reliably assess the response to treatment.
Pearls\:
• Patients with SLE will also have an erythematous rash over the dorsal aspect of the hand, but will spare the skin over the IP joints, which is opposite to the Gottron sign.
• It is not uncommon to have an elevated CK-MB, but order a troponin I if there is suspicion for cardiac damage.
• The anti-Jo-1 antibody is associated with the antisynthetase syndrome, which includes mechanic’s hand, ILD, arthritis, and Raynaud’s phenomenon.
• On the CCS, remember to order “sun block” and “advise patient, avoid sun” in patients with DM because the rash is often related to photosensitivity.
i INCLUSIONBODYMYOSITIS
Inclusion body myositis (IBM) is considered the most common acquired idiopathic inflammatory myopathy after the age of 50.
Clinical Features\:
Men are more likely to be affected than women, with the mean age of onset of 60 years old. IBM follows an insidious course, occurring over a period of years rather than weeks or months. Muscular weakness can affect both proximal and distal muscles groups. An index of suspicion should occur when there is involvement of the quadriceps, foot extensors, and wrist/finger flexors. Patients may have a history of falls (ie, quadriceps weakness), difficulty with ankle dorsiflexion, or difficulty with grip strength (eg, holding objects). The muscular
INFLAMMATORY DISORDERS
I RHEUMATOIDARTHRITIS
Rheumatoid arthritis (RA) is a chronic systemic inflamma­ tory condition that can affect many tissues and organs, but principally affects the synovial membranes of multiple joints. Over time, there is proliferation and hyperplasia of the syno­ vial linings that can lead to the development of pannus. The pannus contains proteinases that can ultimately lead to cartilage destruction and bony erosions. The etiology of rheumatoid ar­ thritis is unknown.
weakness can sometimes be accompanied with muscular atrophy or myalgias. The distribution of the symptoms can be symmetric or asymmetric. IBM can also affect facial muscles, but the ocular muscles are usually spared. The cricopharyngeal muscles can be affected resulting in dysphagia, which occurs in approximately 60% of patients with IBM. On exam, sensory evaluation is usually normal, but deep tendon reflexes can be normal or decreased.
Next Step\:
Step 1) Initial diagnostic testing may include the following with the expected results\:
Muscle enzyme—Serum CK may be normal or moderately elevated.
Autoantibodies—ANA is usually not elevated. ESR—ESR is usually not elevated.
EMG—Myopathic pattern or mixed pattern showing both myopathic and neurogenic changes.
Nerve conduction studies—Normal.
Step 2) Definitive diagnosis is made by muscle biopsy. Similar to PM, inflammatory cells (CD8+ T cells) are found within the endomysium. Characteristic findings include rimmed vacuoles within the muscle fiber, beta-amyloid deposits, and tubular filamentous inclusions seen on electron microscopy.
Step 3) IBM is resistant to immunosuppressive therapies. Often, prednisone is combined with azathioprine or methotrexate for several months, but then ultimately discontinued because of minimal benefit from the therapy.
Follow-Up\:
An evaluation for an assistive device (eg, walker) may be neces­ sary for patients with an older age of onset (>60 years old), since there is a rapid decline compared to an earlier age of onset.
Pearls\:
• IBM has the least favorable prognosis compared to DM and PM.
• On the CCS, remember that medications cannot be ordered as PRN.
Clinical Features\:
Rheumatoid arthritis affects women 3 times more than men. The peak age of onset is 30 to 50 years of age. The onset of RA is usually insidious, but approximately 10% ofpatients can have an acute onset of polyarthritis along with constitutional symptoms. Prodromal symptoms of weight loss, fever, malaise, weakness, and vague arthralgias can occur before joint pain or articular in­ flammation is apparent. Patients will typically present with joint pain, swelling, and stiffness. Stiffness is frequently seen after a period of prolonged inactivity or morning stiffness >1 hour that eventually subsides during the day. The pattern ofjoint in­ volvement is usually symmetric, but a subset of patients can

have asymmetry. Patients may initially have polyarthritis or they may have monoarthritis for a period oftime before polyarthritis develops. In other cases, patients may only have monoarthritis usually of the large joints (eg, shoulder, hip, knee). Patients can have episodic attacks of one or more joints before abating to a symptom-free period that is referred to as palindromic rheumatism. There are a number of joints involved in RA, which include, from head to toe\:
1) Temporomandibularjointcanresultinjawpain.
2) Cricoarytenoid joint can result in hoarseness or stridor.
3) Cervical spine can result in cervical subluxation.
4) Shoulders are usually involved late in the disease.
5) Elbows are very common sites for subcutaneous rheumatoid nodules.
6) Wrists are common sites that can result in carpal tunnel syndrome.
7) Hands—MCP and PIP joints are commonly affected (DIP joints are rarely affected, instead think of OA or psoriatic arthritis), swan-neck deformities, Boutonniere deformi­ ties, ulnar deviation of the digits with radial deviation at the wrist, and tenosynovitis can be seen.
8) Hipsareusuallyinvolvedlateinthedisease.
9) Knees—Baker’s cyst can develop behind the knees second­ ary to an extended inflamed synovium.
10) Anklescandeveloparthritis.
11) Feet—Especially the MTP joints are involved early in the disease.
Rheumatoid arthritis can also have extra-articular involvement, which includes the following in a relative head to toe fashion\:
Neurologic—Nerve entrapments, mononeuritis multiplex (eg, foot-drop and wrist-drop), CNS rheumatoid nodules
Eye—Episcleritis, scleritis
Cardiac—Atherosclerotic coronary artery disease, pericar­
ditis, cardiac rheumatoid nodules
Respiratory—Pleural effusions, interstitial fibrosis, BOOP, pulmonary rheumatoid nodules
Hematologic—Anemia (ie, normochromic-normocytic), Felty’s syndrome (ie, RA, neutropenia, splenomegaly), lym­ phoma
Dermatologic—Subcutaneous rheumatoid nodules, skin ulcers, digital necrosis
Autoimmune—Sjogren’s syndrome (dry eyes, dry mouth) has been associated with RA
Next Step\:
Step 1) There is no single clinical feature or test used to make the diagnosis of RA. Instead, the diagnosis is based on a com­ bination of clinical features, laboratory studies, and imaging features. Based on the American College of Rheumatology (ACR) 1987 revised classification criteria for RA, the presence of 4 or more criteria must be present in order for the patient to
be classified as having RA. The classification criteria were in­ tended for investigational purposes, but they have been useful as a guideline for making a diagnosis of RA.
1) Morning stiffness lasting 1 hour for >6 weeks
2) ArthritisinvolvingS3jointareasfor>6weeks
3) Arthritis of hand joints (wrist, MCP, or PIP joint) for >6 weeks
4) Symmetricarthritisfor>6weeks
5) Presenceofsubcutaneousrheumatoidnodules 6) PositiveRF
7) Bonyerosionsonx-ray
Step 2) Pharmacotherapy is the primary treatment for pa­ tients with rheumatoid arthritis. No single medication can cure rheumatoid arthritis, but the goal is to provide pain relief, con­ trol inflammation, and maintain structure and function. Five classes of drugs to consider are nonbiologic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, steroids, NSAIDs, and analgesics.
Nonbiologic DMARDs
• Improvement in symptoms can take weeks to months with nonbiologic DMARDs.
• Nonbiologic DMARDs can be given alone or in combination with other medication.
Methotrexate—Considered first-line, but contraindicatecj in pregnancy, chronic liver disease, and blood dyscrasias.
Leflunomide—Commonly used in RA patients who do not respond to methotrexate. Contraindicated in pregnancy and patients with preexisting liver disease.
Sulfasalazine—Considered a second-line agent; can cause hemolysis in G6PD-deficient patients.
Hydroxychloroquine—An antimalarial drug that necessi­ tates periodic eye exams because of the feared adverse effect of ophthalmologic toxicity.
Biologic DMARDs
• The basis of biologic DMARDs therapy is to target cytokines or molecules on the cell surface.
• Biologic DMARDs tend to work rapidly compared to nonbiologic DMARDs.
• Biologic DMARDs are typically started after an unsuccessful attempt with a nonbiologic DMARD.
• Patients taking biologic DMARDs are at risk of opportunistic infections.
• TB screening with a PPD should be given to RA patients being considered for biologic DMARDs.
• Biologic DMARDs are not recommended in patients with untreated chronic hepatitis B, or treated chronic hepatitis B with Child-Pugh class B and higher.
• Biologic DMARDs can be given alone or in combination with other medication.
CHAPTER 19 RHEUMATOLOGY 289

290 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Anti-TNF Agents
• Anti-TNF agents include adalimumab, infliximab, and etan- ercept.
• Anti-TNF agents are not recommended in patients with CHF (NYHA class III/IV with EF <50%).
Non-TNF Agents
• Non-TNF agents include anakinra (IL-1 receptor antagonist), tocilizumab (IL-6 receptor antagonist), abatacept (T-cell co-stimulator blocker), and rituximab (B-cell depleting monoclonal antibody).
Steroids
• Glucocorticoids are commonly used to treat flares or to bridge the time until DMARDs become effective.
• Glucocorticoids (eg, prednisolone) can be given by oral, in­ travenous, or intra-articular routes.
NSAIDs
• NSAIDs have both analgesic and anti-inflammatory proper­ ties and are ideally used for short-term management.
Analgesics
• Analgesics such as acetaminophen, tramadol, or topicals (eg, capsaicin) can be used for pain control.
Follow-Up\:
Regular follow-ups are necessary to monitor side effects from the medications and to assess disease activity, most often by clinical evaluation, imaging, and laboratory studies. It should be noted that RF titers are not useful for following disease activity.
Pearls\:
• Anti-cyclic citrullinated peptides (CCP) are often used to evaluate patients with RA since they have similar sensitivity to RF, but much better specificity.
• ESR and CRP are often elevated in patients with active RA. Both ESR and CRP are used to follow disease activity and to assess the response to medications.
• RF is not specific for rheumatoid arthritis as it is found in 5% of healthy people and it is also associated with other diseases including SLE, sarcoidosis, Sjogren’s, scleroderma, syphilis, schistosomiasis, subacute bacterial endocarditis, TB, hepatitis B, chronic liver disease, DM, and PM.
• Subcutaneous rheumatoid nodules are firm or rubbery lesions that are typically seen over pressure points (eg, olecranon process), but also on tendon sheaths (eg, Achilles tendon, palmar tendon). The lesions are usually not painful, but in a subset of patients they can be painful, especially if the overlying skin breaks down.
• Morning stiffness is not pathognomonic for RA as it is seen in other inflammatory disorders.
• When you think ofOA, think ofHeberden’s nodes, Bouchard’s nodes, involvement at the carpometacarpal joint ofthe thumb, affected joints are hard and bony, “evening stiffness,” stiff­ ness after effort, normal ESR and CRP, negative RF and CCP, noninflammatory synovial fluid (WBC <2000 cells/mm3, see Table 19-2).
• Prior and current cigarette smoking increases the risk of RA.
• The life expectancy of patients with RA is shortened by ap­ proximately 3 to 7 years.
• Pregnant women with RA often have improvement during pregnancy, but approximately 90% of patients will have post­ partum flares.
• Thrombocytosis is associated with very active disease.
• RA patients that have not started anti-TNF or non-TNF agents can receive live attenuated vaccines (eg, herpes zos­ ter), killed vaccines (eg, influenza, pneumococcal, hepatitis B), and recombinant vaccines (eg, HPV vaccine for cervi­ cal cancer). However, once the patient starts an anti-TNF or non-TNF agent, the patient should not receive any live vac­ cines, but it is acceptable to receive killed and recombinant vaccines.
• Patients with RA have an increase in mortality due to accel­ erated cardiovascular disease.
• Foundational point—Adalimumab and infliximab can bind to TNF-alpha molecules and thereby block their action to the cell surface TNF receptors. Etanercept can bind both TNF- alpha and TNF-beta molecules and thereby block their action to the cell surface TNF receptors. The end result of anti-TNF agents is neutralizing the biological activity of TNF-alpha, which is normally involved in induction of proinflammatory cytokines (ie, interleukins), leukocyte migration, leuko­ cyte activation, induction of tissue degrading enzymes, and induction of acute phase reactants.
• Foundational point—TNF-alpha and interleukin-1 (IL-1) are two important cytokines that are involved in inducing an inflammatory response. Once these cytokines bind to their cell surface receptors, they activate NF-kB proteins, which are normally sequestered in the cytosol in the inactive form. Once activated, they can translocate into the nucleus and turn on the transcription of genes that are involved in the inflammatory response. Unfortunately, when the actions of NF-kB proteins are excessive, the overdrive ofthe inflamma­ tory response can damage healthy tissue and cause pain as seen in rheumatoid arthritis.
• CJ\: An RA patient is about to start a biologic agent, but the PPD is positive. What is your next step? Answer\: The patient should be followed up with a chest x-ray, and if suggestive of TB (ie, infiltrates ± cavitation), then obtain sputum cul­ tures for acid-fast bacilli (AFB). Patients that have active TB should be treated completely for the active TB before start­ ing a biologic agent. Patients that have latent TB should be treated for at least 1 month for the latent TB before starting a biologic agent.
• On the CCS, patients with RA have an increased risk of cor­ onary atherosclerosis, and it is important to “advise patient,

no smoking,” “diet, low cholesterol,” and “advise patient, ex­ ercise program.”
• On the CCS, remember to “refer patient, physical therapy” and “refer patient, occupational therapy.”
• On the CCS, consider an arthrocentesis to rule out other causes (see Table 19-2).
CCS\: POLYMYALGIA RHEUMATICA CASE INTRODUCTION
Day 1 @ 15\:00 Office
A 70-year-old white female comes to the office because of pain and stiffness in the shoulders and hips.
Initial Vital Signs\:
Temperature\: 37.3°C (99.14°F) Pulse\: 70 beats/min, regular rhythm Respiratory\: 16/min
Blood pressure\: 130/86 mm Hg Height\: 152.4 cm (60.0 inches) Weight\: 57.6 kg (127 lb)
BMI\: 24.8 kg/m2
Initial History\:
Reason(s) for visit\: Shoulder and hip pain; stiffness
HPI\:
A 70-year-old white female has experienced “achiness” and stiffness in the shoulders and hips for the past 5 weeks. Initially, the pain and stiffness started in her left shoulder, but now it has progressed to the right shoulder and both hips. Her pain is worse with movement, which has caused many sleepless nights. Acetaminophen provides minimal pain relief. She also reports having stiffness after periods of prolonged inactivity and morn­ ing stiffness lasting at least 30 to 60 minutes, but eventually “loosens up” by the midafternoon. She has difficulty combing her hair, brushing her teeth, putting on a coat or jacket, get­ ting up from a chair or bed, and turning over in bed. There is also diffuse swelling and pitting edema over her hands and feet. She reports having fatigue, low-grade fever, and weight loss accompanying her musculoskeletal symptoms.
• On the CCS, remember to bridge the early stage oftreatment (ie, pain relief) with NSAIDs or glucocorticoids with the later stag­ es of treatment (ie, slowing joint damage) with the DMARDs.
• On the CCS, in office-based cases, you will need to advance the clock (sometimes in weeks) to see if there is a response to the medications you ordered.
Past Medical History\:
Past Surgical History\:
Hypercholesterolemia, hypertension, history of breast cancer, osteopenia (T-score\: —1.5)
Left-sided mastectomy 15 years ago; childbirth at ages 25 and 27
Medications\: Allergies\: Vaccinations\: Family History\:
Social History\:
Review of Systems\:
General\:
Skin\:
HEENT\: Musculoskeletal\: Cardiorespiratory\: Gastrointestinal\: Genitourinary\: Neuropsychiatric\:
Day 1 @ 15\:11
Physical Examination\: General appearance\:
Skin\:
Breasts\:
Lymph nodes\: HEENT/Neck\:
Atorvastatin, amlodipine, alendronate None
Up to date
Mother died ofmyocardial infarction, age 60. Father died of prostate can­ cer, age 70. One younger sister is still alive, age 65, and has hypertension. Never smoked; no longer drinks alcoholic beverages; denies use of illegal drugs; widowed; two children; retired; college education; enjoys reading and playing bridge.
See HPI See HPI Negative See HPI Negative Negative Negative Negative
Well nourished, well developed; in no apparent distress.
Normal turgor. No nodules. Scar noted over left breast area. Hair and nails normal.
Left breast removed without any abnormal mass. Right breast exam normal.
No lymphadenopathy. Normocephalic. EOMI, PERRLA. Hearing normal. Ears, nose, mouth normal. Pharynx normal. Neck supple; trachea midline; no masses or bruits; thyroid normal.
CHAPTER 19 RHEUMATOLOGY 291

292 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Chest/Lungs\:
Heart/Cardiovascular\: Abdomen\:
Extremities/Spine\:
Neuro/Psych\:
Chest wall normal. Diaphragm moving equally and symmetrically with respiration. Auscultation and percussion normal.
SI, S2 normal. No murmurs, rubs, gallops, or extra sounds. No JVD. Normal bowel sounds; no bruits. No tenderness. No masses. No hernias. No hepatosplenomegaly.
Bilateral swelling and pitting edema over the hands, wrists, ankles, and feet. Decrease range of motion, most notably over the shoulders, neck, and hips. Muscle tenderness to palpation, but no pain along the tender point areas. No muscle atrophy. Mild kyphosis on spine exam
Mental status normal. Cranial nerve and sensory exam normal. Motor strength 5/5 throughout. Cerebellar function normal. Deep tendon reflexes normal. Gait normal.
Second Order Sheet\:
1) Prednisone, oral, continuous
2) Calcium-enriched diet
3) Calcium carbonate, oral, continuous
4) Vitamin D3 (cholecalciferol), oral, continuous
Actions\:
1) Changelocationtohome
2) Schedule appointment\: In 3 days
Day 3
The patient has arrived for the appointment.
Recorded Vital Signs\: Temperature\: 37.0°C (98.6°F) Pulse\: 70 beats/min, regular rhythm Respiratory\: 16/min
Blood pressure\: 130/86 mm Hg
Follow-Up History\:
The patient’s pain and stiffness has improved significantly.
Physical Examination\:
Extremities/Spine\: Reduced swelling of the hands, wrists, ankles, and feet. Improved range of motion over the shoulders, neck, and hips. Decrease muscle tenderness. Normal peripheral pulses. Mild kyphosis on spine exam.
Neuro/Psych\: Mental status normal. Normal motor, sensory, and cranial nerve exam. Cerebellar function normal. Deep tendon reflexes normal. Gait normal.
Actions\:
1) Reevaluate case\: In 14 days
This case will end in the next few minutes of “real time.” You may add or delete orders at this time,
then enter a diagnosis on the following screen.
First Order Sheet\:
1) CBC with differential, routine
2) Peripheral smear, routine
3) CMP, routine
4) ESR, routine
5) Creatinekinase, serum, routine
6) Aldolase, serum, routine 7) TSH, serum, routine
8) ANA, serum, routine
9) Rheumatoid factor, routine 10) Anti-CCP, routine
11) Urinalysis, routine
Result\: WBC-7000, H/H-11/37%, Plt-450,000, Differential- WNL, MCV-85, MCHC-33% (nl\: 31%-36%), RDW-12% (nl\: 11.5-13.6).
Result\: Normochromic normocytic erythrocytes; leukocytes normal in number and morphology; platelets elevated in number.
Result\: Ca-9.5, Glu-100, Urea-15, Cr-1, Prot.-7.2, Alb.-4.5, T.Bil.-0.7, AlkP-130, AST-30, ALT-30, Na-141, K-4.2, Cl-103, HC03-24
Result\: 87 mm/hr (nl\: 0-20) Result\: 50 U/L (nl\: 10-70)
Result\: 8.3 U/L (nl\: 1.5-12.0)
Result\: 4.0 mU/L (nl\: 0.5-5.0)
Result\: Negative
Result\: 1\:20 (normal <1\:40) Result\: Negative
Result\: WNL
Third Order Sheet\: 1) ESR, routine
Future date\: In 60 days
2) CBC with differential, routine Future date\: In 60 days
3) Peripheral smear, routine Future date\: In 60 days
Result\: 15 mm/hr (nl\: 0-20)
Result\: WBC-7000, H/H-14/37%, Plt-300,000, Differential- WNL, MCV-85, MCHC-33% (nl\: 31%-36%), RDW-12% (nl\: 11.5-13.6).
Result\: Normochromic normocytic erythrocytes; leukocytes and platelets normal in number and morphology.

4) Advise patient, side effects of medication 5) Advise patient, medication compliance 6) Advise patient, exercise program
Please enter your diagnosis\: Polymyalgia Rheiimatica
DISCUSSION\:
Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology. PMR is closely associated with giant cell ar­ teritis (GCA), which is also known as temporal arteritis. It is still not clear if PMR and GCA represent two separate diseases or part ofa spectrum from a single disease process. Approximately 30% of patients with PMR will develop GCA, while 50% ofpatients with GCA will develop PMR. It should be noted that the clinical course of PMR and GCA may not be synchro­ nous (ie, one condition may be completely inactive while the other condition starts to flare, and vice-versa).
Clinical Features\:
The average age at diagnosis for PMR is 70 years, and symptoms are generally present for more than 1 month before patients seek help. Symptoms ofPMR may develop abruptly or insidiously. The classic presentation is pain and stiffness in the shoulders, hips, neck, and upper body. Pain is usually worse with movement Early in the course of the disease, shoulder pain may be the initial presentation while sparing the lower extremities. However, in a subset of patients the neck and hip are involved at onset Symp­ toms may initially begin unilaterally, but eventually they become bilateral after a few weeks. Morning stiffness lasting 30 minutes and stiffness after periods of rest (gel phenomenon) are charac­ teristic of PMR. Synovitis, tenosynovitis, and bursitis can occur around the joints. As a result, the local inflammation is thought to contribute to the swelling and pitting edema seen over the hands, wrists, ankles, and feet In some cases, patients can develop carpal tunnel syndrome from the tenosynovitis. Despite the term poly­ myalgia (“pain in many muscles”), patients may exhibit muscle tenderness, but the tenderness is most likely due to the synovial and bursal inflammation. On examination, patients will have nor­ mal muscle strength and decrease range ofmotion ofthe involved areas secondary from the pain. Constitutional symptoms such as fever, fatigue, and weight loss may be associated with the PMR symptoms as they are thought to represent the systemic effects of the cytokines that are released from the inflammatory process.
Next Step Summary\:
Step 1) PMR is a clinical diagnosis. Although there are no vali­ dated diagnostic criteria, the presence of the following can help with the diagnosis of PMR\:
• Age of onset >50 years
• ESR >40 mm/hr
• Morning stiffness lasting >30 minutes
• Pain persisting for >1 month involving at least two areas including the neck, shoulders, or pelvic girdle
• A response to low-dose steroids
Step 2) As you approach this case, think about the labs or tests that you would order. The characteristic laboratory finding for PMR is an elevated ESR that can exceed 100 mm/hr. Nonspecific laboratory findings that may be present in patients with PMR include thrombocytosis (reflects an inflammatory, response), normocytic anemia, and elevated liver enzymes, particularly the alkaline phosphatase. Also, as you go through the case, consider tiie differential diagnosis and the tests that you would order. The following are the differentials to consider\:
Polymyositis (PM)—Patients with PM will have proximal muscle weakness and will have elevated muscle enzymes (ie, creatine kinase (CK), aldolase).
Fibromyalgia—Thepatientinthiscasehadnoabnormalities on tender point examination, and the ESR is usually normal in patients with fibromyalgia.
Malignancy—Patients can have a paraneoplastic syndrome that can result in myalgias or joint pain. In this case, the patient did have a history of breast cancer and presented with weight loss, but the breast and lymph node exam appeared normal, calcium levels were within normal limits, and she responded well to low-dose steroids.
Drug-induced myalgia—The patient in this case was on a statin, but the CK was within normal limits.
Pseudogout—Patients with pseudogout can present with pain and edema of the shoulders and lower extremities, but they will have the characteristic rhomboid-shaped, weakly positively birefringent crystals on synovial fluid analysis and chondrocalcinosis may be present on x-ray.
Hypothyroidism—Patients with hypothyroidism can pres­ ent with stiffness and arthralgias. However, the thyroid exam appeared normal and the TSH was within normal limits in this case.
Rheumatoid arthritis—Patients with rheumatoid arthritis can also present with joint pain, swelling, stiffness, and constitutional symptoms. However, in this case the patient did have a rheumatoid factor (RF) level within normal limits, a negative anti-cyclic citrullinated peptide (CCP), which has a better specificity than RF at detecting rheumatoid ar­ thritis, and the patient responded well to low-dose steroids.
Step 3) Patients with PMR typically respond well to low-dose oral steroids (eg, prednisone), typically within 3 days of starting the medication. Although there are no evidence-based guidelines for the dosing and duration oftreatment, most patients are maintained on steroids until they are asymptomatic and then eventually ta­ pered off. Ifpatients do not respond to low-dose steroids, then you can try to incrementally increase the dose of the steroids to see if there is a response. However, there is no option to increase the dose on the CCS, and therefore, you have to reconsider the differential diagnosis and pursue further workup (eg, imaging, muscle biopsy, EMG, joint fluid analysis). In this particular case, the patient re­ sponded well to low-dose steroids, and thereby, we did not have to subject the patient to unnecessary radiation or painful procedures.
Step 4) Most patients with PMR will be on steroids for several months and it is important to prevent glucocorticoid-induced
CHAPTER 19 RHEUMATOLOGY 293

294 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
osteoporosis. In this case, the patient is already on a bisphos- phonate (alendronate) for her osteopenia, but we also added calcium and vitamin D supplementation.
Follow-Up\:
Patients on steroid treatment should have monthly follow­ ups to monitor the response to therapy and to assess the side effects of steroids including hypertension, glucose intolerance, and osteoporosis. Lab testing for ESR is often obtained every 2 to 3 months while on steroid therapy as normalization of the acute-phase reactant is expected with remission of the symptoms.
Pearls\:
• PMR can affect not only the shoulder and hip girdle, but also the proximal aspects of the upper arms and thighs, respectively.
• Muscle atrophy is not typically seen early in the course of the disease, but can be seen later if there is disuse of the proximal muscles.
• EMG and muscle biopsy findings are normal in patients with PMR.
• Inflammation is not at the level of the muscle, but rather the synovium and bursae.
• One of the side effects of amlodipine is peripheral swelling, which might have thrown you off in this case.
• Most patients with GGA will typically respond to high-dose steroids rather than low-dose steroids.
• PMR is a self-limited disorder with a duration of approxi­ mately 2 to 3 years.
• Patients can relapse from the steroid therapy, especially if the steroid dose is tapered too quickly.
• CJ\: A 75-year-old woman has pain and stiffness in the shoul­ der and also complains ofjaw pain, headaches, visual distur­ bances, arid tenderness over the right temporal area. What is your next step? Answer\: When GCA is suspected, initiate high-dose steroids (eg, prednisone). Do not delay treatment because the patient can potentially lose her vision.
• Connecting point (pg. 296)—Know the clinical features of GCA.
• On the CCS, it is acceptable to pick either “vitamin D3” (ie, cholecalciferol) or “vitamin D, therapy” (ie, ergocalciferol) for prevention of glucocorticoid-induced osteoporosis, but some studies have suggested that cholecalciferol increases 25-hydroxyvitamin D (ie, 250HD) more efficiently than
\: ergocalciferol (ie, vitamin D2).
• On the CCS, once you advance the clock forward, you can­ not go backward in simulated time.
• On the CCS, after you treat a patient, be sure to monitor the patient’s condition. As in this case, a follow-up office visit with the appropriate physical exam was performed with labs ordered for a future date.

Vascular
CHAPTER OUTLINE
Keywords Review............................................2..9.5........
I ARTERIAL...............................................2..9.6........ Giant Cell Arteritis..........................................2.9.6........I Kawasaki Disease...........................................2.9.7........
KEYWORDS REVIEW
Desquamation—Shedding or peeling of the epidermis.
Livedo reticularis—A mottled reticulated or lacelike (netlike) vascular pattern that appears purplish or bluish (livedo) in
color that typically does not blanch upon active pressure. Livedo reticularis can be seen during a cold response in patients with Raynaud's phenomenon and can be reversible upon rewarming. Livedo reticularis can also be seen in other vasculitis disease (eg, PAN), vascular occlusive disease (eg, PAD), or autoimmune disease (eg, antiphospholipid syndrome).
Phlegmasia alba dolens—A clinical manifestation as a result of a massive venous thrombosis obstruction of the venous vasculature. It is commonly the result from precipitants
of thrombosis (eg, DVT, malignancy, hypercoagulability). The thrombosis typically obstructs the major deep venous channels of the extremity, but sparing the collateral
veins and thereby preserving some venous flow. Clinical features include edema, pain, and blanching or white (alba)
Peripheral Arterial Disease....................................2.9..8..... Polyarteritis Nodosa..........................................3.0..0.......
VENOUS...................................................3..0.1.......... VaricoseVeins................................................3.0.1..........
appearance of the affected extremity, but without ischemia. Phlegmasia alba dolens can potentially progress to phleg­ masia cerulea dolens.
Phlegmasia cerulea dolens—Phlegmasia cerulea dolens occurs by the same mechanism as phlegmasia alba dolens, but both major deep venous channels and collateral
veins are affected resulting in complete venous outflow obstruction. The result is significant edema (ie, t venous congestion), pain, cyanosis (ie, cerulea means blue), and with ischemia. In addition, gangrene can develop as a sequela of the disease. Approximately 50% to 60% of cases of phlegma­ sia cerulea dolens is preceded by phlegmasia alba dolens.
Sclerotherapy—A type of medical procedure that involves injecting a sclerosing agent into a target vein with the goal of shrinking the vessel over a period of time. Sclerotherapy is primarily used to treat telangiectasias, reticular veins, or small varicose veins.
295

296 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
ARTERIAL
1 GIANTCELLARTERITIS
Giant cell arteritis (GCA), also referred to as temporal arteritis, is a chronic vasculitis that affects medium and large-sized arteries. GCA has a predilection for the extracranial branches of the carotid artery, most notably the temporal artery. The etiol­ ogy of GCA is unknown.
Clinical Features\:
GCA is typically seen in patients >50 years of age, female > male, and in individuals of European descent. Onset of symptoms is usually gradual, but abrupt presentations can occur. Clinical manifestations can vary, and it may be helpful to consider the features from a relative head to toe fashion\:
Neurologic—New onset headache in any location (frontal, temporal, parietal, occipital)
Eyes—Diplopia or visual loss in one or both eyes that can be due to amaurosis fugax, anterior ischemic optic neuropathy (AION), posterior ischemic optic neuropathy (PION), cen­ tral retinal artery occlusion, branch retinal artery occlusion, or homonymous hemianopsia
Lower face—Jaw claudication, tongue pain
Neck—Throat pain
Respiratory—Nonproductive cough
Aorta—Aortic aneurysms (ascending > descending), arm claudication, aortic dissection
Musculoskeletal—Polymyalgia rheumatic (PMR) Systemic—Fever, fatigue, or anorexia
On physical exam, several key elements should be inspected. The temporal artery may be tender, thickened, or cordlike. Early in the disease, the temporal artery may be pulsatile, but it may diminish over time. Individuals may also have scalp pain upon palpation. On funduscopic exam, a pale swollen optic disc may be seen if AION has developed. In addition, if the optic nerve circulation is compromised, patients can develop a relative afferent pupillary defect (ie, Marcus-Gunn pupil). Finally, bruits may be heard over the carotids, axillary, bra­ chial, abdomen, or femorals, which may be an indication of a partial occlusion.
Next Step\:
Step 1) Clinical suspicion for GCA (eg, age >50, new onset headache, temporal artery tenderness, jaw claudication, Hx or symptoms of PMR, visual disturbances, constitutional symp­ toms) should prompt you to initiate treatment with glucocorti­ coids before the diagnosis is confirmed! Either oral prednisone or IV methylprednisolone is an acceptable choice. Patients will typically report clinical improvement within 48 hours of initiat­ ing steroids, which would also support the diagnosis of GCA. In addition to giving steroids, low-dose aspirin should be given to reduce ischemic complications.
Step 2) Schedule the patient for a temporal artery biopsy to confirm the diagnosis. Other adjunctive testing to support the diagnosis includes\:
ESR—Elevated ESR can reach >100 mm/hr.
C-reactive protein (CRP)—CRP levels may also be elevat­ ed. In some patients, the CRP shows a better reflection of disease activity compared to the ESR. In other cases, the CRP may be a better indicator of disease activity, therefore, order both CRP and ESR.
CBC—Normocytic normochromic anemia and thrombo­ cytosis can sometimes be present.
CMP—Alkaline phosphatase and aminotransferases can sometimes be elevated; albumin levels can sometimes be decreased.
Step 3) Counsel patients about the anticipated side effects of steroids (eg, emotional instability, insomnia, impaired wound healing, osteoporosis) since the duration of glucocorticoid treatment is typically for one month followed by a gradual taper. Supplemental calcium and vitamin D may be recommended, and if there is concern for osteoporosis, your next best step is to order a DEXA scan and possibly treat with bisphosphonates if the T-score is <-2.5.
Disposition\:
GCA usually runs a self-limited course that can take several months to years. The ESR or CRP are useful indicators of dis­ ease activity and may be used as adjuncts to the clinical decision making for a steroid tapering schedule.
Pearls\:
• Takayasu arteritis is also a chronic vasculitis with an unknown etiology that can affect medium and large-sized arteries, primarily the aortic arch and its primary branches. The presentation to look for includes Asian descent, age ^40 years, female > male, constitutional symptoms, claudica­ tion of the extremities, skin lesions, marked weakening of the arterial pulses in the upper and lower extremity that may be asymmetric (pulseless disease), >10 mm Hg systolic BP difference between the arms, bruits (ie, carotids, subclavian, brachial, or abdomen), renovascular hypertension, T ESR, T CRP. Unlike GCA, do not take a biopsy (ie, Do you really want take a biopsy of the aorta or its primary branches?); rather, imaging is usually used to confirm the diagnosis (eg, arteriography, MRI/MRA). Like GCA, treatment is with glucocorticoids.
• Foundational point—Histopathologically, GCA has pre­ dilection for the internal elastic lamina, which is usually fragmented. In addition, granulomatous inflammation is seen with variable numbers of multinucleated giant cells in close proximity to the fragmented elastic lamina. It should be noted that the morphologic changes seen in Takayasu ar­ teritis may be indistinguishable from GCA (ie, presence of a granulomatous inflammation with giant cells).
• Connecting point (pg. 19)—Know the clinical clues of reno­ vascular hypertension that can be seen in Takayasu arteritis.

• Connecting point (pg. 140)—Know the meaning of hom­ onymous hemianopsia.
• Connecting point (pg. 142)—Know the meaning of a Marcus Gunn pupil. ^
• Connecting point (pg. 144)—Recognize the clinical features of amaurosis fugax.
• Connecting point (pg. 293)—Recognize the clinical features of polymyalgia rheumatica.
• Connecting point (pg. 282)—Know the management of osteoporosiss.
• On the CCS, timing is important in the management of GCA, and poor management would include delaying treat­ ment (eg, waiting for the results of the ESR or temporal ar­ tery biopsy) since withholding glucocorticoid treatment can potentially result in irreversible vision loss.
• On the CCS, remember to order oral prednisone in the con­ tinuous mode of frequency. Once you decide to taper the prednisone, then you can discontinue the medication since it will be understood by the CCS and the examiner.
• On the CCS, “temporal artery biopsy” is available in the practice CCS.
• On the CCS, when the case is about to end, you will receive a 2-minute warning. Ifyou feel that you managed GCA appro­ priately, you can order an ESR and/or CRP to follow disease activity at a later date.
• On the CCS, remember to “advise patient, side effects of medication.”
I KAWASAKI DISEASE
Kawasaki disease (KD), also referred to as mucocutaneous lymph node syndrome, is a vasculitis that affects small, medium, and large-sized arteries. KD has a predilection for medium­ sized arteries, especially the coronary arteries, which can lead to its most notable complication of a coronary artery aneurysm (CAA). Therefore, early diagnosis is essential to achieve the best possible treatment result. The etiology of KD is unknown.
Clinical Features\:
KD is a common vasculitis seen in children. Boys are affected more than girls, and in the majority of cases, KD is seen in chil­ dren <5 years old and uncommonly seen in children <6 months. A higher incidence of KD is seen in children of Asian descent. The clinical features of KD will be reviewed in step 1 (see Next Step) since the diagnostic criteria are based on the clinical man­ ifestations of KD. For the remainder of this section, the disease stages will be discussed with important highlights in each stage.
Acute stage—The acute phase is approximately the first 2 weeks. The hallmark of this stage is fever. Clinical mani­ festations of KD are likely to be present in this stage such as a rash or edema and induration of the hands or feet. Inflam­ mation during this phase can also affect the myocardium, pericardium, AV node, and coronary artery, which can lead
to myocarditis, pericarditis, arrhythmias, and coronary arte­ ritis (without aneurysms), respectively. Do not be surprised if you observe tachycardia, a gallop, hyperdynamic precordi- um, or an innocent flow murmur in this stage of the disease.
Subacute stage—The subacute phase is approximately the next 2 to 4 weeks. The hallmark of this stage is a decrease or abatement of the fever, thrombocytosis (usually peaks in the third week), periungual desquamation (usually of the hands or feet) within 2 to 3 weeks after fever onset, and the development of coronary artery aneurysms.
Convalescent stage—The convalescent phase is approxi­ mately the next 4 to 6 weeks. CAA may still be apparent in this stage.
Next Step\:
Step 1) Early recognition of KD is important because you want to provide timely and appropriate treatment, which could potentially mitigate the morbidity and mortality associated with KD. Diagnosis of KD includes the presence of unex­ plained FEVER FOR > FIVE DAYS and at least FOUR of the FIVE physical findings. Think of the physical findings in a rela­ tive head to toe fashion\:
1) Eyes—Bilateralbulbarnonexudativeconjunctivitis
2) Oral—Lips and oral mucous membrane changes that can include a strawberry tongue, injected oral or pharyngeal mucosae, or injected, cracked, or fissured lips
3) Neck—Cervicallymphadenopathy(atleastonelymphnode >1.5 cm in diameter)
4) Extremities—Peripheralextremitychangesthatcaninclude erythema of the palms or soles, edema of the hands or feet, or periungual desquamation
5) Dermatologic—Polymorphous (ie, many forms or stages) rash
Step 2) Treatment should be initiated if patients fulfill the diagnostic criteria seen in step 1. IVIG should be admin­ istered as an infusion over 8 to 12 hours and is typically effective in reducing the prevalence of CAA if given within the first 7 to 10 days of the illness. Oral administration of high-dose aspirin should also be given to achieve an anti­ inflammatory effect.
Step 3) Echocardiography should also be performed expedi­ tiously and definitely within the acute phase to establish a baseline study (ie, keep in mind that you may not find a CAA in the acute stage but rather after the acute phase subsides).
Step 4) Once the patient is afebrile for at least 48 to 72 hours, you can switch high-dose aspirin to low-dose aspirin for its an­ tiplatelet effect.
Step 5) Counsel patients and families about discontinuing aspi­ rin therapy upon signs and symptoms of a varicella or influenza infection since aspirin is a risk factor for the development of Reyes syndrome. However, patients deemed to be on long-term aspirin therapy after being discharged from the hospital should
CHAPTER 20 VASCULAR 297

298 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
receive an inactivated influenza (>6 months of age) and varicella (>12 months of age) vaccination to prevent the possibility of de­ veloping Reyes syndrome.
Disposition/Follow-Up\:
Patients seen in the ED and who fulfill the diagnostic criteria for KD should be admitted to the hospital for IVIG infusion and an echo. After hospital discharge, patients should have a repeat echo in the subacute stage, convalescent stage, and beyond.
Pearls\:
• KD is usually a self-limited condition.
• The use of glucocorticoids is controversial in the initial therapy of KD.
• Aspirin does not appear to affect the formation of CAA.
• Low-dose aspirin can usually be discontinued once the patient has a total of 6 to 8 weeks of aspirin therapy and there is no evidence of coronary artery abnormalities via echocardiography. Patients with coronary artery abnormali­ ties should continue with low-dose aspirin until it resolves or indefinitely.
• CAA can lead to myocardial ischemia, MI, or sudden death.
• Not every child will develop a CAA, and in fact, approxi­ mately 25% of untreated children will develop CAA.
• Valvular dysfunction (eg, mitral regurgitation) can occur if inflammation affects the heart valves.
• Other possible features to be aware of in KD include ante­ rior uveitis, sensorineural hearing loss, arthritis, Raynaud’s’ phenomenon, gallbladder hydrops, or an induration of a BCG inoculation site.
• Reyes syndrome typically develops several days after recov­ ery from a viral illness (usually varicella or influenza, but other viruses can also precipitate the disease), and salicylates (particularly aspirin) have been implicated as a risk factor. Reyes syndrome can also develop after vaccination with live viral vaccines. Features to look for in Reyes syndrome include vomiting, altered consciousness, seizures, coma, hepatomegaly, i DTRs, t AST, t ALT, T PT and PTT time, t ammonia levels, hypoglycemia, or metabolic acidosis.
• CJ\: A 3-year-old Asian boy presents with fever for the last 5 days, diffuse maculopapular eruption, dry red lips, and edematous feet. What is your next step? Answer\: The patient does not fulfill the criteria for classic KD but rather incomplete KD. Incomplete KD is considered in patients with fever >5 days but associated with only 2 or 3 of the classic features of KD. In our patient, the patient had fever for 5 days and only had 3 of the diagnostic criteria, and therefore, the next best step is to order an ESR and CRP. Based on the recommendation of the American Heart As­ sociation (AHA)/American Academy of Pediatrics (AAP), an ESR and CRP should be obtained in patients suspected of having incomplete KD. Treatment with IVIG plus high-dose aspirin should be initiated (echo can be obtained afterward) if the ESR is >40 mm/hr and/or CRP is >3 mg/dL plus the presence of >3 supplemental labs that include either an al­
bumin <3 g/dL, anemia for age, T ALT, platelets >450,000/ mm3 (after 7 days of fever onset), WBC >15,000/mm3, or the presence of pyuria (urine >10 WBCs/high power field). However, if the ESR is >40 mm/hr and/or CRP is >3 mg/dL, but the laboratory criteria is not met (ie, <3 supplemental labs), then the next best step is to order an echo, and if the echo is abnormal then treat.
• On the CCS, “IVIG” is available in the practice CCS.
• On the CCS, “counsel family/patient” since the develop­ ment of a CAA puts a patient at risk for early atherosclerotic disease.
• On the CCS, a pediatric cardiologist should be consulted be­ cause patients should have regular follow-ups with the car­ diologist if they developed any cardiovascular complications during the course of the disease.
• On the CCS, if the patient fulfills the diagnostic criteria for classic KD, it should prompt you to initiate treatment with­ out delay. Suboptimal management includes ordering un­ necessary tests that would waste time because you have to keep in mind that there is no single definitive diagnostic test for classic KD.
• On the CCS, poor management includes failure to order an echo to possibly detect a CAA (remember not every­ body will develop a CAA but the presence of a CAA is still a major complication that you need to potentially identify).
1 PERIPHERALARTERIALDISEASE
Peripheral arterial disease (PAD) is characterized by stenosis of the aorta and its branch arteries. The most common disease process affecting the arterial vasculature is atherosclerosis. The lower extremity vessels are affected more commonly than the upper extremity vessels, and therefore the remainder of the dis­ cussion will be based on the lower extremities.
Risk Factors\:
Risk factors for PAD are similar to those of coronary artery dis­ ease, which include smoking, diabetes, hypertension, hyperlip­ idemia, homocysteinemia, and metabolic syndrome. It should be noted that smoking (current and past) or diabetes are both very strong risk factors that have a two- to fourfold increase in the development of lower extremity PAD.
Clinical Features\:
Approximately 20% to 50% of patients with PAD are asymp­ tomatic. The classic symptom that is seen in approximately 10% to 35% of patients with PAD is intermittent claudica­ tion. Claudication literally means “to limp” in Latin, however patients will often describe the symptom as cramping, aching, painful, numbness, weakness, or fatigue in the muscles (not joints) upon sustained exercise, but relieved by rest. The symp­ toms can be reproducible, and unlike neurogenic claudication (pseudoclaudication), there is no effect (ie, relief, exacerba­ tion) with body positions seen in PAD (eg, relief with flexion

or extension). Symptoms of claudication are typically distal to the site of the occlusion. For example, claudication in the lower calf may be the result of arterial disease in the popliteal artery, and discomfort in the butt or hips is usually the result of aor- toiliac disease. In men, aortoiliac occlusive disease can give rise to Leriche syndrome, which is a triad of erectile dysfunction (impotence), claudication, and absent or decreased femoral pulses. On physical exam, possible findings in PAD include diminished pulses, bruits, hair loss, smooth and shiny skin, pallor, livedo reticularis, reduced skin temperature, or muscle atrophy. Approximately 1% to 2% of patients will have severe compromise of blood flow to an affected extremity, which is referred to as critical limb ischemia. Critical limb ischemia is characterized by rest pain and the development of ulcers or gangrene.
Next Step\:
Step 1) The best initial test to establish lower extremity PAD in patients with the classic symptoms of claudication is a cal­ culation of the ankle-brachial index (ABI) (ie, compares the systolic BP in the arm to the ankle). The following is an inter­ pretation of the ABI\:
ABI >1.3 (suggests calcified vessels) ABI between 0.91-1.3 (normal) ABI <0.90 (PAD)
ABI <0.40 (severe PAD)
Step 2) Several different therapeutic strategies are recommend­ ed in the initial treatment approach with patients that have lifestyle-limiting claudication and an ABI <0.90. Consider the following\:
Risk Factor Reduction
1) Smokingcessationcannotbeoverstated.Helppatientswith either behavior modification or pharmacologic therapy (eg, nicotine patch, bupropion).
2) Appropriatelytreatdiabetesmellitus. 3) Appropriatelytreathypertension.
4) Appropriatelytreathyperlipidemia.
Lifestyle Changes
1) Implement a supervised exercise program in patients with a lifestyle-limiting claudication for at least a 3-month period.
2) Pharmacologic therapy with cilostazol may be used in conjunction with a supervised exercise program since it is effective in increasing walking distance. Once the drug is discontinued, the effect of increased distance is lost.
Vascular Complication Prevention
1) Aspirin (75-325 mg) is given to reduce the risk of strokes or MI. Clopidogrel can be given as an alternative if aspirin cannot be given.
2) Donotgivewarfarinsinceithasnotbeenshowntoimprove outcomes in patients with PAD.
Follow-Up\:
Patients should be seen regularly to assess the efficacy of treat­ ment, and physicians should be aware that it may take up to 4 to 12 weeks for the benefits of cilostazol to be apparent. In ad­ dition, patients may need to be seen more frequently if being treated for coexistent diabetes, hypertension, or hyperlipidemia.
Pearls\:
• Cilostazol is a phosphodiesterase type 3 inhibitor that increas­ es cAMP, which eventually results in arterial vasodilation and platelet aggregation suppression. Cilostazol is contraindicat­ ed in patients with heart failure.
• Pentoxifylline reduces blood viscosity and is considered a second-line agent compared to cilostazol. The efficacyofpent­ oxifylline in improving walking distances is still questionable.
• Beta-blockers are not contraindicated in patients with PAD who have coexistent hypertension or coronary artery disease.
• Conventional contrast angiography is considered the gold standard in assessing vascular anatomy, but neither conventional contrast angiography, MRA, nor CTA is rou­ tinely performed in the initial assessment of PAD unless revascularization intervention is considered.
• The diagnosis of PAD should serve as a marker for coexistent cardiovascular disease (eg, coronary artery disease).
• Buerger’s disease (thromboangiitis obliterans) is a segmental, thrombosing vasculitis that affects small and medium-sized arteries and veins. There is minimal to absent atherosclerosis in the vessels. Patients are typically young (<45 years) and there is a strong association with smoking or using tobacco products. Patients can present with claudication, Raynaud phenomenon, pain at rest, ulcers, or gangrene.
• CJ\: A 62-year-old man with a history of smoking and coro­ nary artery disease presents to the ED with an acute onset of the following signs and symptoms of his right leg\: 1. Pain 2. Pallor 3. Pulselessness 4. Paralysis 5. Paresthesias 6. Polar (ie, cold). What is your next step? Answer\: The patient has the hallmark signs and symptoms of an acute limb ischemia, which requires an emergent evaluation (eg, ABI or duplex ultrasound) and possibly immediate revascularization in consultation with a vascular specialist. The signs and symp­ toms of an acute limb ischemia can be easily remembered by the “Triple P’s x 2.” Be aware that an acute limb ischemia is not the same as critical limb ischemia (ie, chronic rest pain). However, critical limb ischemia needs to be evaluated and treated expeditiously as well.
• Connecting point (pgs. 142, 143)—Know the difference between neurogenic and vascular claudication.
• Connecting point (pgs. 79, 82)—Know the management of diabetes mellitus.
• Connecting point (pg. 19)—Know the management of hypertension.
• Connecting point (pg. 23)—Know the management of hyperlipidemia.
• On the CCS, “ABI” is available in the practice CCS.
CHAPTER 20 VASCULAR 299

300 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• On the CCS, “cilostazol” is available in the practice CCS.
• On the CCS, remember to “advise patient, no smoking.”
• On the CCS, remember to “advise patient, exercise program.”
1 POLYARTERITIS NODOSA
Polyarteritis nodosa (PAN) is a transmural necrotizing vasculi­ tis that affects small and medium-sized muscular arteries and has multiorgan involvement. The etiology of PAN is unknown, but it has been associated with hepatitis B, hepatitis C, and hairy cell leukemia. Two unique features of PAN are that it is not as­ sociated with antineutrophil cytoplasmic antibodies (ANCA) and the lungs are usually spared (although the bronchial arter­ ies have been involved on occasion).
Clinical Features\:
PAN is predominantly seen between the fourth and sixth decades oflife, although it can still be seen in children. PAN is a “PAN-systemic” or multisystem disease that commonly affects the CNS (ie, neuropathy), renal, GI, derm, and musculoskeletal systems. However, it is good to see the whole clinical picture, and therefore, consider the following possible clinical manifes­ tations from a relative head to toe fashion\:
Psychiatric—Depression, psychosis
Neurologic—Strokes, AMS, seizure, confusion, or mono­ neuritis multiplex (ie, isolated damage in >2 separate nerves in different parts of the body, which can affect both sen­ sory and motor function). Examples include a “wrist drop” (ie, radial nerve), “foot drop” (ie, sciatic or peroneal nerve), or an abnormal sensation along the little finger (ie, ulnar nerve). Mononeuropathy is usually asymmetric in the be­ ginning, but over time, it can lead to distal symmetric poly­ neuropathy.
Eyes—Visual disturbances (eg, ischemic optic neuropathy)
Cardiovascular—CHF, myocardial infarction, or pericarditis
Renal—HTN, new onset diastolic BP >90 mm Hg, renal insufficiency/failure, or hematuria
GI—Abdominal pain (ie, mesenteric arteritis), GI bleed, nausea, or vomiting
Genitourinary—Testicular pain (ie, orchitis)
Dermatologic—Tender nodules, livedo reticularis, gangrene, ulcers, or purpura
Musculoskeletal—Arthralgias, myalgias, or muscle weakness Systemic—Fever, fatigue, or weight loss
Next Step\:
Step 1) The clinical manifestation of PAN is nonspecific, and the initial diagnosis may not be readily apparent. In addition, there is no single diagnostic lab test to confirm the diagnosis of PAN. The following adjunctive tests maybe used in the initial approach, and you should use your clinical judgment on what test would be appropriate for that given patient (ie, What symp­ toms is the patient complaining about?). Consider the possible findings of each test\:
CBC—Normochromic anemia, leukocytosis, or thrombo­ cytosis.
CMP-T BUN, t Cr, or T LFTs.
ESR or CRP—May be elevated.
ANCA—Usually negative, but ifpositive p-ANCA > c-ANCA. Also, the presence of antibodies against proteinase-3 and my­ eloperoxidase suggests a different vascular (ANCA) disease.
Cryoglobulins and complements—The presence of cryo­ globulins and a fall in complements (-1 C3, 4 C4) suggests mixed cryoglobulinemia, which is associated with hepatitis C and less often with hepatitis B and HIV.
Hepatitis B and hepatitis C serologies—May be positive.
Rheumatoid factor—If elevated levels are observed, you have to consider either rheumatoid vasculitis or mixed cryoglobulinemia (now you also have to consider hepatitis B and C).
Creatinine kinase—May be elevated.
EMG—In patients with mononeuritis multiplex, an EMG may help characterize the disease as myopathic or neurogenic.
CXR—Used to exclude other diseases since PAN usually spares the lungs.
Occult blood, stool—If positive, may suggest mesenteric arteritis.
Urinalysis—May show hematuria, may show mild protein­ uria, but usually no red blood cell casts (ie, no glomerulo­ nephritis).
Step 2) Diagnosis is confirmed with a biopsy of the affected organ (eg, skin, GI, renal) and preferably the most accessible site. It should be noted that a punch biopsy of the affected skin may not do the job since it may only reach the superficial der­ mis. Instead, you may need a deeper biopsy (eg, elliptical surgi­ cal biopsy) to reach a medium muscular artery. In the absence of an accessible tissue site, the alternative to a biopsy is an ar­ teriography of the renal, hepatic, or mesenteric vasculature. Findings may reveal aneurysms of the vessels, but this is not a pathognomonic feature.
Step 3) Treatment in patients with PAN is with glucocorticoids (eg, prednisone). Oral prednisone is typically given for one month followed by a gradual taper. Patients that present with serious manifestations (eg, mesenteric ischemia, renal insuffi­ ciency) or are refractory to initial steroids should be given pred­ nisone in conjunction with oral cyclophosphamide.
Follow-Up\:
Patients given cyclophosphamide should be monitored for hemorrhagic cystitis, and their blood counts should be checked regularly while on therapy.
Pearls\:
• When PAN is left untreated, the 5-year survival rate is approxi­ mately 13%. Major causes of mortality include strokes, MI, renal failure, and GI complications (eg, infarction, perforation).

Keep in mind that IV drug users are predisposed to contract­ ing hepatitis B or C, which would also predispose them to developing PAN.
Patients with PAN-associated hepatitis B should also be treated with antivirals (eg, interferon alfa).
High levels of eosinophilia suggest the diagnosis of Churg- Strauss syndrome.
PAN is not associated with veins.
PAN is not associated with granulomatous inflammation on histopathology.
Foundational point—Histologically, PAN is characterized by a transmural inflammation of the muscular arterial wall with infiltration of neutrophils, eosinophils, and mononuclear cells. Necrosis of the arterial wall may be observed and is often referred to as fibrinoid necrosis.
Connecting point (pg. 98)—Where else did we see ANCA? Crohn’s disease is usually p-ANCA negative, and ulcerative colitis is usually p-ANCA positive.
VENOUS
I VARICOSEVEINS
Varicose veins are characterized as dilated, tortuous subcuta­ neous veins. Most primary varicosities are due to hereditary causes, while secondary varicosities are due to the sequelae of trauma, prior DVT, pregnancy, prolonged standing, congenital lesions, perforator vein incompetence, or AV fistulas. However, the common feature of both primary and secondary varicosities is venous reflux caused by valvular incompetence. The venous anatomy of the lower extremity involves the deep and super­ ficial veins. The two major superficial veins are the great and small (lesser) saphenous veins. The superficial venous system is interconnected to the deep venous system through perfora­ tor veins (which also have valves), the saphenofemoral junction, and the saphenopopliteal junction.
Clinical Features\:
Patients may complain for purely aesthetic reasons of the un­ sightly appearance of the veins. Others may complain of an “aching,” “burning,” “throbbing,” “heaviness,” or “soreness” in their legs. Symptoms may worsen with pregnancy, menstrual cycle, or from prolonged standing. Leg elevation usually relieves the symptoms, but if it worsens, then it is unlikely a varicosity. Keep in mind that the severity of the patients symptoms does not necessarily correlate with the appearance of the visible vari­ cosities or with the volume of the reflux. On exam, varicose veins may be visibly apparent, but if they are not visibly apparent then palpation of the lower extremity may reveal a dilated vein.
Next Step\:
Step 1) The diagnosis of varicose veins may be apparent on clinical evaluation. A duplex ultrasound is a useful adjunct in
• On the CCS, if you decide to treat with cyclophosphamide, you can give it orally (typically given everyday for one year) or it can be given intravenously (typically on a monthly basis for one year).
• On the CCS, remember to “advise patient, side effects of medication.”
• On the CCS, remember to always use your clinical judg­ ment when admitting a patient to the hospital. For example, if a PAN patient has a life-threatening GI bleed or you sus­ pect a mesenteric arterial thrombosis (eg, sudden severe abdominal pain, abdominal tenderness, nausea, vomit­ ing, guarding) and your clinical assessment coincides with your clinical diagnosis, be sure to work up your patient and treat the patient appropriately in the hospital. Do not send the patient home, or most likely the CCS case will end early.
identifying varicose veins that are not visibly apparent, identify­ ing a DVT, and useful in treatment planning.
Step 2) The initial treatment approach in patients with symp­ tomatic complaints is with conservative management, which includes avoiding prolonged standing, elevating legs periodi­ cally, walking, exercise (eg, flexion and extension of the feet), and wearing elastic compression stockings for external support.
Step 3) Patients that are refractory to conservative management or who have cosmetic reasons may require a more invasive management approach to remove the varicose veins. Consider the following approaches\:
• Sclerotherapy
• Endovenous laser ablation
• Endovenous radiofrequency ablation • Ambulatory phlebectomy
• Surgical ligation and stripping
Follow-Up\:
When patients continue to have persistent symptoms despite conservative management, be sure to always rule out a DVT.
Pearls\:
• Varicosities should not be ablated or removed ifthere is a deep venous outflow obstruction because the enlarged superficial veins are serving as collaterals that bypass the obstruction.
• The Perthes maneuver involves placing a tourniquet over the proximal part of the leg to compress the superficial vari­ cose veins, but without affecting the deep venous system. The patient is asked to walk or pump the calf muscle, which would normally empty or drain the varicose vein. If the vari­ cose vein becomes paradoxically congested, that suggests a deep venous obstruction.
CHAPTER 20 VASCULAR 301

302 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• When considering a DVT, think about the risk factors for DVT (eg, immobilization, travel, malignancy) and the signs and symptoms of DVT (eg, leg tenderness along the venous system, pitting edema, warmth, palpable cord, swelling, ery­ thema, pain).
• Chronic venous insufficiency is usually associated with chronic venous reflux. Chronic venous insufficiency can typically be identified by the presence of skin changes (eg, discoloration of the skin), skin ulcer, or edema.
• Telangiectasias (also referred to as spider veins, thread veins, or hyphen webs) are a confluence ofdilated intradermal venules.
• Reticular veins are dilated bluish subdermal veins that are larger than telangiectasias in diameter, but smaller than varicose veins.
• Both telangiectasias and reticular veins may also indicate the presence of chronic venous insufficiency.
• Superficial thrombophlebitis (STP) is the result of a throm­ bosis in the superficial vein that leads to inflammation, hence “thrombophlebitis.” There may be tenderness, induration,
erythema, and pain along the course of the superficial vein. Upon palpation, the vein may feel “cordlike.” STP is often associated with varicose veins, IV injections, or indwelling catheters. Diagnosis of STP is mainly clinical, but if a DVT is suspected, then a duplex ultrasound should be ordered. STP is typically a self-limited condition, but treatment may include supportive measures such as NSAIDs, warm or cold compress, compression stockings, extremity elevation, and continuation of daily activities. Antibiotics are not routinely ordered unless there are signs of an infection (eg, purulent discharge, fever).
• On the CCS, in nonemergent CCS cases, you may be required to advance the clock in weeks to months. Prior to your Step 3 exam, select your own system of advancing the clock so that on exam day, you become more comfortable throughout your cases. Be aware that as you advance the clock, the patient’s condition may change and a “Patient Update” will appear. At that point, you have to decide to either change the course of management or stay the course.

Pattern Recognition
The basis of pattern recognition is for you to “feel” or “recognize” the pattern of the disorder with both typical and atypical presenta­ tions. Pattern recognition is not meant for you to memorize ev­ ery feature of the disorder, but rather to develop your gut instinct about a disease. Once you review this section several times, you should be able to quickly draw a clinical impression of the disor­ der on longer-type questions and answer the questions with more confidence. As you read through the pattern recognition, keep in mind that not every patient will present the same way, and some patients may only present with a partial list of the disease.
Acute myelogenous leukemia (AML)—Fatigue, anemia, thrombocytopenia, varied WBC count (low, normal, or high), hepatosplenomegaly, petechiae, ecchymoses, gingival bleeding, sternal tenderness, arthralgias, myeloid sarcoma (ie, extramedullary disease), fever secondary to infection, lymphadenopathy is uncommon, men > women, implicated risk factors (eg, radiation, chemotherapy, chemical exposures, familial syndromes, myelodysplastic syndrome), leukemic blasts in the peripheral blood and bone marrow, Auer rods (ie, indicates myeloid origin), myeloperoxidase positive, DIC, proliferation of myeloid precursors, maturational arrest of myeloid precursors, >20% ofblasts in bone marrow as defined by the World Health Organization, most common in adults, infrequently seen in children (<10% of cases), pallor, cardiac flow murmur, hypokalemia, lactic acidosis, Sudan black B positive, leukemia cutis, T LDH, T uric acid, poor prognosis associated with advancing age.
Acute promyelocytic leukemia (APL)—Previously called AML-M3, is a distinct variant of AML, APL defined by the translocation of chromosome 15 and 17, which can be writ­ ten as t(15;17) or defined by the product of the translocation PML/RARa, APL associated with bleeding secondary to DIC,
medical emergency, atypical promyelocytes in peripheral blood and bone marrow, dumbbell-shaped or kidney-shaped nuclei, granular cytoplasm obscuring the nucleus, common in adults, pancytopenia, menorrhagia, epistaxis, Auer rods in the cyto­ plasm, early mortality if untreated.
Acute lymphoblastic leukemia (ALL)—Bleeding, fever, bone pain, headache, lymphadenopathy, painless testicular enlargement, mediastinal mass, anemia, thrombocytope­ nia, varied WBC count (low, normal, or high), neutropenia, t LDH, >25% lymphoblasts on bone marrow, most common in children, increased risk in Down syndrome, increased risk in neurofibromatosis type 1, negative myeloperoxidase, positive TdT, precursor B cell or precursor T cell ALL exists, precursor B cell ALL associated with poorer prognosis, Phil­ adelphia chromosome in a minority of patients, T uric acid secondary to high tumor burden, splenomegaly, petechiae, ecchymoses, pallor, cardiac flow murmur, infection, fatigue, dyspnea, infrequently DIC.
Chronic myeloid leukemia (CML)—Fatigue, weight loss, bleeding, abdominal fullness, hepatosplenomegaly, lower sternal tenderness, T uric acid, asymptomatic, normochro­ mic normocytic anemia, leukocytosis, normal or elevated platelets, i leukocyte alkaline phosphatase (LAP) which is also called neutrophil alkaline phosphatase (NAP), elevated neutrophils, basophilia, eosinophilia, early satiety secondary to splenomegaly, triphasic course (accelerated phase, chron­ ic phase, blast crisis), majority of patients have the Philadel­ phia chromosome that results from t(9;22) giving rise to a fusion protein product Bcr-Abl, constitutive kinase activity of Bcr-Abl, bone pain in blast crisis, peripheral smear dem­ onstrates immature and mature granulocytes, most common in adults.
303

304 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Chronic lymphocytic leukemia (CLL)—Lymphocytosis, ab­ solute B-lymphocytes >5000/microL in the peripheral blood, painless lymphadenopathy (usually in the cervical area but can occur in the supraclavicular or axillary regions), hepatospleno- megaly, leukemia cutis, fevers, fatigue, weight loss, night sweats, common in the elderly, smudge cells on peripheral smear (ie, represents the fragility of the lymphocyte during slide prepara­ tion), expression of B cell antigens (CD 19, CD20, and CD23), expression of T cell antigen (CD5), predominance of mature- appearing small lymphocytes, Richter s transformation (ie, CLL transformation to an aggressive diffuse large B cell lymphoma).
Sickle cell disease (SCD)—Recurrent painful episodes (previ­ ously called sickle cell crisis), bone pain, anemia, aplastic crisis due to parvovirus B19, growth retardation, avascular necro­ sis, stroke, ptosis, mutation in the (3-globin gene that leads to a change in the sixth amino acid position from glutamic acid to valine (Glu —> Val), cholelithiasis secondary to pigmented gall­ stones, leg ulcers, splenic sequestration, infection due to encap­ sulated bugs (ie, Streptococcus pneumoniae and Haemophilus influenzae), dactylitis/hand-foot syndrome (painful swelling of the hands and/or feet secondary to bone infarction of those small bones), delayed puberty, rapidly enlarging spleen, bone infarction, osteomyelitis secondary to Salmonella or Staphy­ lococcus aureus, sensory hearing loss, vestibular dysfunction, cardiac involvement (chamber enlargement), priapism, pulmo­ nary hypertension, acute chest syndrome, unconjugated hyper­ bilirubinemia, renal failure, retinopathy, reticulocytosis, T LDH, 1 haptoglobin, Howell-Jolly bodies, reduced splenic function (functional asplenia or hyposplenism), pneumonia, target cells and sickle cells on peripheral smear, HbSS or homozygous sickle cellanemiaelectrophoresis(zeropercentageofHbA,ttHbS, T HbF), structure of HbS (2 normal alpha chains/2 sickle beta chains).
Systemic lupus erythematosus (SLE)—Malar rash, fever, fa­ tigue, weight loss, arthralgia, weight gain, discoid rash, Raynaud phenomenon, minimal mesangial lupus nephritis, mesangial proliferative lupus nephritis, alopecia, photosensitivity, pur­ pura, urticaria, joint effusions, subcutaneous nodules, avascu­ lar necrosis, muscle weakness, fibromyalgia, annular plaques, erythematous papules, periungual erythema, telangiectasias, livedo reticularis, hypoalbuminemia, leukopenia, hemolytic anemia with reticulocytosis, thrombocytopenia, lymphade­ nopathy, splenomegaly, T ESR, false-positive VDRL, focal lu­ pus nephritis, diffuse lupus nephritis, membranous lupus ne­ phritis, advanced sclerosing lupus nephritis, abnormal levels of IgG or IgM anticardiolipin antibodies, hepatomegaly, liver enzyme abnormalities, mesenteric vasculitis, pancreatitis, dys­ phagia, dyspepsia, pleural effusion, pulmonary hypertension, pericarditis, Libman-Sacks verrucous endocarditis, myocar­ ditis, congenital heart block, delirium, psychosis, seizures, peripheral neuropathies, keratoconjunctivitis sicca, thrombo­ embolic events, oral ulcers, ± HTN, creatinine levels (normal or elevated), ± hematuria, nasal ulcers, pleurisy, erythematous rash over dorsa of the hands sparing the interphalangeal joints, interstitial lung disease, ± subendothelial deposits on im­ munofluorescence, increased risk of coronary artery disease,
persistent proteinuria >0.5 g/dy, headaches, arthritis, lympho­ penia, anti-double stranded DNA (dsDNA), anti-Smith (SM) antibodies, cellular casts (granular, RBC, hemoglobin, tubular, mixed), pneumonitis, valvular disease, low C3, low C4, sero- sitis, abdominal pain, nausea, vomiting, bullous skin lesions, >3+ proteinuria, thrombophilia, recurrent miscarriage, ne­ phrotic syndrome, neonatal lupus (cardiac and cutaneous man­ ifestations) from mothers that are positive for anti-Ro/SSA and/ or anti-La/SSB antibodies, peritonitis, positive ANA, positive for lupus anticoagulant, anti-Ul RNP antibodies, early mortal­ ity due to disease activity (eg, CNS, cardiac, renal involvement, infection secondary to immunosuppression), late mortality due to strokes, MI, cancer, and treatment complications.
Neurofibromatosis type 1 (NF1)—Cafe au lait macules, freck­ ling in the axillary or inguinal regions, learning disabilities, Lisch nodules (iris hamartomas), neurofibromas (cutaneous, subcutaneous, nodular plexiform, diffuse plexiform), long bone dysplasia, optic glioma, von Recklinghausen disease, familial disorder, autosomal dominant, hypertension, cognitive deficits, sporadic mutations, NF1 gene mutation on chromosome 17, decreased production of the protein product neurofibromin, in­ creased risk for brainstem gliomas, astrocytomas, and soft tissue sarcomas, bony lesion, short stature, scoliosis, 1 bone density, macrocephaly, pseudoarthrosis, seizures, speech delay, short­ ened life span compared to the general population.
Neurofibromatosis type 2 (NF2)—Bilateral vestibular schwan­ nomas (ie, fairly common), meningiomas, dumbbell-shaped spinal cord schwannomas, neuropathies, cataracts, retinal ham­ artomas, absence of Lisch nodules, optic nerve meningiomas, skin plaques, unilateral vestibular schwannomas can occur, ab­ sence of cognitive impairment, posterior subcapsular lenticular opacities, autosomal dominant, sporadic mutations, NF2 gene mutation on chromosome 22, decreased production of the pro­ tein product merlin (also known as schwannomin) that acts as a tumor suppressor, ependymomas, epiretinal membranes, schwannomas rarely undergo malignant transformation, short­ ened survival.
Parkinson’s disease—Resting tremor (“pill-rolling”), cog­ wheel rigidity (oscillating pattern of resistance and relax­ ation), bradykinesia, postural instability, positive “pull” test (ie, patient takes multiple steps backwards when pulled from behind), blurred vision, hallucinations, masked facial expres­ sion, decreased eye blinking, impaired upward gaze and con­ vergence, positive glabellar tap sign (ie, persistent blinking with repetitive tapping over the glabella area), speech impair­ ment, lead-pipe rigidity (smooth resistance), dysphagia, dys­ tonia, stooped posture, rapid repetition of a word or phrase, Lewy bodies, excessive saliva, REM sleep behavior disorder, scoliosis, lid apraxia, impaired vestibulo-ocular reflex, my­ oclonus, shuffling gait, short strides, flexed posture, sensory abnormalities and pain, dementia, hyposmia, abulia, consti­ pation, forgetfulness, urinary urgency, kyphosis, reduced pul­ monary capacity secondary to kyphosis, depigmented cells in the substantia nigra and locus ceruleus, sleep disturbances, autonomic dysfunction, sexual dysfunction, seborrheic der­ matitis, decreased arm swing, depression, slow thinking,

weakness, excessive daytime somnolence, micrographia (small handwriting), soft speech, cognitive dysfunction, psychosis, fatigue, difficulty turning in bed, apathy, freezing (transient inability to walk), poor articulation, festination (acceleration of gait), orthostasis.
Cystic fibrosis (CF)—Thick secretions, meconium ileus, bron­ chiectasis, pancreatic insufficiency, chronic productive cough, PFTs consistent with obstructive disease (1 FEVp i FEV,/FVC ratio, t RV/TLC ratio, i FEF25% 75%), male infertility second­
ary to absent vas deferens, normal spermatogenesis, obstruc­ tive azoospermia, females can become pregnant, 4 fertility in
females secondary to thick cervical mucus, osteoporosis, digi­ tal clubbing, sinusitis, wheezing, recurrent pancreatitis, rectal prolapse, amenorrhea, autosomal recessive, high prevalence in whites, sweat chloride >60 mmol/L (ie, abnormally high result), normal or intermediate sweat chloride result, mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene located on chromosome 7, delta 508 mutation (most com­ mon mutation in the CFTR gene), nephrolithiasis, hypochlore­ mic hyponatremic alkalosis, bronchiolitis, vomiting, jaundice, failure to thrive, diabetes mellitus, dermatitis, hyperinflated lungs on CXR (ie, T TLC, T residual volume), susceptible to col­ onization in the respiratory tract (ie, Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Aspergillus), allergic bronchopulmonary aspergillosis (ABPA), undescended testicles, fat malabsorption, GERD, intussusception, constipa­ tion, T frequency of stools, vitamin deficiencies (A, D, E, K), nasal polyps, affected sibling, biliary cirrhosis, periportal fibro­ sis, portal hypertension, hypertrophic osteoarthropathy, cho­ lelithiasis, foul-smelling stools, nephrocalcinosis, weight loss, abdominal distension, hyperresonant chest percussions, small intestine bacterial overgrowth, hydrocele, volvulus, abnormal nasal potential difference, airway hyperreactivity, peribronchial cuffing and “tram tracks” on CXR, steatorrhea, poor appetite, distal intestinal obstructive syndrome (DIOS), cause of death is typically due to respiratory failure and cor pulmonale, short­ ened survival.
HIV—Fever, sore throat, rash, myalgia, headache, nontender lymphadenopathy (occipital, cervical, axillary), arthralgia, fatigue, night sweats, diarrhea, hepatosplenomegaly, muco­ cutaneous ulcerations, rash, nausea, weight loss, anorexia, aseptic meningitis, asymptomatic (clinical latent period), STDs, contaminated blood products, high viral load >100,000 copies/mL, increased risk for opportunistic infections (Pneu­ mocystisjirovecii, toxoplasma, Mycobacterium avium complex, histoplasma, Candida, coccidioides, cryptococcus, Cryptospo­ ridium, CMV), positive p24 antigen (viral core protein), toxo­ plasmosis (fever, headache, seizure, focal neurologic deficits, aphasia, IgG anti-toxoplasma, hemiparesis, pneumonitis, al­ tered mental status, single or multiple ring enhancing lesions with surrounding edema, posterior uveitis), X CD4 T cell count after seroconversion (usually 1-6 months after exposure), CD4 count <200 mm3 is considered AIDS, shared IV drug users, pri­ mary CNS lymphoma (aphasia, hemiparesis, seizures, confu­ sion, lethargy, fever, memory loss, night sweats, focal neurologic deficits, headaches, ring enhancement lesions on MRI, multiple
solitary enhancing lesions on MRI, ring and solitary lesions can occur concomitantly, systemic lymphoma), sexual intercourse transmission, mother-to-child transmission, progressive mul­ tifocal leukoencephalopathy (white matter demyelination sec­ ondary to JC virus, ataxia, hemiparesis, no mass effect, hemi- anopia, aphasia, cognitive impairment, visual field defects, no contrast enhancement on MRI), retroviruses, HIV-1 is respon­ sible for the majority of infections, HIV encephalopathy (de­ mentia, forgetfulness, depression, apathy, abnormal gait, poor balance, changes in the Mini-Mental Status Examination score, cerebral atrophy on MRI), HIV-2 infection is seen in endemic areas (eg, West Africa), HIV-2 is a slower progressing disease and does not transmit the infection as efficiently as HIV-1, CMV (polyradiculopathy, urinary retention, areflexia, hyperac­ tive reflexes, difficulty walking, delirium, confusion, lower ex­ tremity weakness, peripheral neuropathy, altered mental status, encephalitis, periventricular enhancement on MRI, myelitis, CMV retinitis, painless progressive vision loss).
Sarcoidosis—Noncaseating granulomas (lung, heart, brain, kidneys, eyes, GI tract, lymph nodes, joints, skin), common in blacks, T ESR, T ACE, frequently affects the lungs, PFTs may or may not demonstrate a restrictive pattern (i FVC, i FEVj, normal or T FEVj/FVC ratio, i TLC, 1 FRC, normal FEF25% 75%), cough, chest pain, dyspnea, bilateral hilar adenopathy and re­ ticular opacities on CXR, uveitis, fatigue, wheezing, weight loss, crackles, peripheral neuropathies, valvular dysfunction, keratoconjunctivitis, xerostomia, proximal muscle weakness, normal or elevated creatine kinase, nephrolithiasis, maculo- papular eruptions, systemic inflammation, anemia of chron­ ic disease, violaceous plaque (lupus pernio), unexplained hoarseness, splenomegaly, Bells palsy, positive RF, hypercal­ cemia, T alkaline phosphatase, T GGT, tachyarrhythmias, sud­ den death, glomerulonephritis, cystic bone lesions, Lofgren syndrome (fever, polyarthralgias, hilar adenopathy, erythema nodosum), anorexia, hypercalciuria, nephrocalcinosis, heart block, sudden death, pulmonary hypertension, heart failure, hepatomegaly, presence of histiocytes in the granulomas on histology, interstitial nephritis, optic neuritis, cor pulmonale, carpal tunnel syndrome, central diabetes insipidus, pituitary or hypothalamic involvement disrupting the endocrine axis, cranial nerve palsies, hydrocephalus, lymphocytic meningi­ tis, hypergammaglobulinemia, parotid gland enlargement, rhinosinusitis, goiter, leukopenia, eosinophilia, vl diffusing capacity for carbon monoxide (DLCO), nasal polyps, lacrimal gland swelling, t CD4/CD8 ratio on bronchoalveolar lavage.
Hepatitis B serologies—The components include hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti- HBs), hepatitis B core antibody (IgM or IgG), hepatitis B e antigen (HBeAg) ,which reflects HBV replication and infec- tivity, hepatitis B e antibody (anti-HBe), HBV DNA, and ALT. Acute infection (early phase)\: HBsAg (+), anti-HBs (-), IgM anti-HBc (+), HBeAg (+), anti-HBe (-), t HBV DNA, t ALT. Acute infection (window phase)\: Only IgM anti-HBc (+). Acute infection (recovery phase)\: IgG anti-HBc (+), anti-HBs (+), anti-HBe (+), ALT normalization. Chronic infection (rep­ licative phase)\: HBsAg (+) for >6 months, anti-HBs (-), IgG
APPENDIX A PATTERN RECOGNITION 305

306 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
anti-HBc (+), HBeAg (+), anti-HBe (-), t HBV DNA. Chronic infection (nonreplicative phase/inactive carrier state)\: HB-
sAg (+) for >6 months, anti-HBs (-), IgG anti-HBc (+), HBeAg (-), anti-HBe (+). Prior HBV infection\: IgG anti-HBc (+), anti- HBs (+), anti-HBe (+). Vaccination\: Only anti-HBs (+).
Celiac disease—Also known as celiac (nontropical) sprue or gluten-sensitive enteropathy, malabsorption, flatulence, diar­ rhea, steatorrhea, weight loss, water- and fat-soluble vitamin deficiencies, bleeding diathesis secondary to vitamin K defi­ ciency, fatigue, headaches, cheilosis, Down syndrome, Turner syndrome, histology on small bowel biopsy (crypt hyperpla­ sia, villous atrophy, T intraepithelial lymphocytes), minor GI complaints, recurrent abdominal pain, stunted growth/ short stature, delayed puberty, learning disorders, first degree relatives, female infertility, common in whites, hypocalcemia, selective IgA deficiency, T-cell response, osteoporosis, osteo­ penia, hypothyroidism > hyperthyroidism, abdominal bloat­ ing, anemia, arthritis, GERD, anxiety, genetic predisposition (HLA-DQ2, HLA-DQ8), enamel defects, male infertility, mo­ tor weakness, T aminotransferases, autoimmune thyroiditis, silent disease (asymptomatic but positive for serologies and intestinal mucosa consistent with celiac disease), latent disease (asymptomatic with normal intestinal mucosa), seizures, atro­ phic glossitis, type 1 diabetes, depression, delayed menarche, secondary amenorrhea, osteomalacia, tympanic abdomen, ataxia, peripheral neuropathy, iron deficiency, folate deficien­ cy, dermatitis herpetiformis, IBD, triggering gluten-containing grains (wheat, barley, rye), resolution of symptoms and mu­ cosal lesions upon withdrawal of gluten-containing foods, in­ creased risk for lymphoma and GI cancers, positive antibodies (IgA or IgG) to the following\: gliadin, endomysium, and tissue transglutaminase.
Hemochromatosis—Skin bronzing, hepatomegaly, hyperpig­ mentation, hypogonadism, cirrhosis, iron deposition (pituitary,
heart, liver, pancreas), dilated cardiomyopathy, restrictive car­ diomyopathy, T plasma iron, T plasma ferritin (in the absence of inflammation), T transferrin saturation (ie, ratio of iron to TIBC with normal ranges expressed between 20% and 50%), weakness, heart failure, hypothyroidism, conduction defects, hepatocyte iron accumulation on Peris Prussian blue stain, amenorrhea, diabetes mellitus, asymptomatic, arthralgia, T LFTs, impotence, supraventricular arrhythmias, homozygous C282Y mutation of the HFE gene (common), mutation in the transferrin receptor 2 gene (uncommon), increased risk of hepatocellular carcinoma (HCC), 1 libido, hooklike osteo­ phytes on x-ray, autosomal recessive, sick sinus syndrome, hair loss, chondrocalcinosis secondary to calcium pyrophosphate dihydrate (CPPD), -l bone density, koilonychia, ventricular ar­ rhythmias, juvenile hemochromatosis (earlier onset, cardiomy­ opathy, hypogonadism, autosomal recessive, hemojuvelin gene mutation, liver disease not as prominent), absence or presence of cirrhosis is a major prognostic factor.
Hypokalemia—Muscle weakness, cardiac arrhythmias, muscle cramps, palpitations, fatigue, t blood pressure, rhabdomyolysis, T ammonia production, myoglobinuria, ileus, paroxysmal atrial
tachycardia, sinus bradycardia, abdominal distension, asymp­ tomatic, causes (t GI loss, T urinary loss, hypothermia, 1 po­
tassium intake, T sweat loss, T insulin, dialysis), diaphragmatic weakness, AV blocks, premature atrial beat, ventricular fibrilla­
tion, constipation, premature ventricular beats, impaired renal concentrating ability, T U wave amplitude, 1 T wave amplitude, prolonged QT, ST segment depression, 1 insulin secretion, worsening diabetes control.
Hyperkalemia—Muscle weakness, cardiac arrhythmias, palpi­ tations, flaccid paralysis, 1 deep tendon reflexes (DTRs), i renal
ammoniagenesis, LBBB, RBBB, AV blocks, sinus bradycardia, peaked T waves, widen QRS, shortened QT, prolonged PR, ab­ sent P wave, asymptomatic, causes (1 insulin, 1 urinary K+ loss, i aldosterone secretion, renal failure, nonselective beta-block­ ers, succinylcholine, metabolic acidosis, acute digitalis toxicity, hyperosmolality), ventricular tachycardia, ventricular fibrilla­ tion, paresthesias, asystole.
Hyponatremia—Nausea, malaise, headache, lethargy, obtun­ dation, dizziness, gait disturbances, seizures, coma, confusion, ileus, respiratory arrest, central pontine myelinolysis second­ ary to rapid sodium correction, hypotonic (<275 mOsmol/ kg H20), normotonic (275-295 mOsmol/kg H20), hypertonic (>295 mOsmol/kg H20), hypertonic hyponatremia (eg, man­ nitol, maltose, hyperglycemia), normotonic hyponatremia (eg, hyperlipidemia, hyperproteinemia, bladder irrigation), hypovo­ lemic hypotonic hyponatremia plus urine sodium <10 mmol/L (eg, extrarenal sodium losses), hypovolemic hypotonic hypona­ tremia plus urine sodium >20 mmol/L (eg, renal sodium loss, hypoaldosteronism, vomiting, diuretics), euvolemic hypotonic hyponatremia plus urine osmolality >100 mOsmol/kg H20 (eg, SIADH), hypotonic hyponatremia plus urine osmolality <100 mOsmol/kg H20 (eg, primary polydipsia), hypervolemic hypotonic hyponatremia (eg, CHF, cirrhosis, nephrotic syn­ drome, renal insufficiency).
Hypernatremia—Irritability, lethargy, weakness, subarachnoid hemorrhages, cognitive dysfunction, twitching, coma, seizures, confusion, intracerebral hemorrhage, focal neurologic deficits, causes (diuretics, central diabetes insipidus, nephrogenic diabe­ tes insipidus, osmotic diuresis, mannitol, hyperglycemia, vom­ iting, diarrhea, NG suction, sweating, burns, impaired thirst/ primary hypodipsia, sodium overload).
Hypomagnesemia—Neuromuscular hyperexcitability, hyper- reflexia, hypocalcemia, hypokalemia, weakness, muscle cramps, ileus, apathy, cardiac arrhythmias, delirium, paresthesias, muscular fibrillation, coma, tremor, ventricular tachycar­ dia, tetany, seizures, T DTRs, muscle spasms, causes (vomit­ ing, diarrhea, NG suction, malabsorption, laxatives, surgical bowel resection, diuretics, alcohol, hypercalcemia, amino­ glycosides, amphotericin B, pentamidine, cisplatin, cyclospo­ rine, acute pancreatitis, chronic metabolic acidosis, inherited disorders, hungry bone syndrome, proton pump inhibitors), ventricular premature contractions, positive Chvostek and Trousseau signs, vertical nystagmus, widen QRS, prolonged PR, prolonged QT, peaked T waves, depressed T waves, Na- K-ATPase inhibition, potentiates digitalis toxicity, X PTH

secretion, skeletal resistance to PTH, 4 1,25-dihydroxyvitamin D (calcitriol), common in ICU patients, respiratory muscle failure, torsades de pointes.
Hypermagnesemia—Lethargy, X DTRs, hypocalcemia, hypo­ tension, headache, nausea, vomiting, flushing, muscle weakness, drowsiness, bradycardia, somnolence, respiratory paralysis, cardiac arrest, muscle paralysis, prolonged PR, t QT interval, T QRS duration, complete heart block, respiratory failure, X PTH secretion, causes (renal insufficiency, magnesium infusion, Epsom salts, lithium therapy, milk-alkali syndrome, tumor lysis syndrome, hypothyroidism, adrenal insufficiency, primary hyperparathyroidism, familial hypocalciuric hypercalcemia, magnesium-containing laxatives, enemas and antacids).
Hypophosphatemia—Muscle weakness, irritability, confu­ sion, delirium, paresthesias, coma, seizures, dysphagia, il­ eus, asymptomatic, hemolysis, thrombocytopenia, impaired WBC function, ATP depletion, rhabdomyolysis, bone pain, Xmyocardial contraction, heart failure, causes (i intestinal absorption, chronic diarrhea, vitamin D deficiency, mal­ absorption, inadequate intake, aluminum or magnesium- containing antacids, alcoholism, T urinary loss, inherited disorders, Fanconi syndrome, primary and secondary hyper­ parathyroidism, acetazolamide, intracellular shift of phos­ phate, T insulin, hungry bone syndrome, acute respiratory alkalosis), respiratory failure secondary to diaphragmatic weakness, t CPK, impaired platelet function, X 2,3-DPG shifting hemoglobin-02 dissociation curve to the left, T af­ finity of hemoglobin for Or
Hyperphosphatemia—Asymptomatic, signs and symptoms of hypocalcemia, signs and symptoms related to the underly­ ing cause, causes (extracellular shift of phosphate, tumor lysis syndrome, rhabdomyolysis, hemolysis, DKA, lactic acidosis, ■i renal excretion, renal failure, T absorption, vitamin D tox­ icity, bisphosphonates, leukemia, acromegaly, thyrotoxicosis, hypoparathyroidism, pseudohypoparathyroidism, phosphate- containing laxatives).
Acute rheumatic fever—Sydenham chorea, erythema mar­ ginatum, carditis, valvulitis, migratory arthritis (common sites
include elbows, wrists, knees, and ankles), subcutaneous nod­ ules, fever, t ESR, T CRP, arthralgia, prolonged PR, sequela of group A streptococcus pharyngitis, positive rapid antigen test or throat culture for Group A beta-hemolytic streptococci, in­ voluntary movements, common in children 5 to 15 years of age, transient joint pain, muscle weakness, mitral valve pro­ lapse, “milkmaid’s grip” (unable to maintain a grip when asked to squeeze examiner’s hand), hypotonia, crying outbursts, personality changes, T antistreptolysin O (ASO) titers, syno­ vial fluid analysis revealing sterile inflammatory fluid, mitral regurgitation, heart block, annular skin lesions with pale cen­ ters, heart failure, jerking of the face and feet, facial grimacing, ballismus, loss of fine-motor skills, pericarditis, cardiomegaly on CXR, pericardial effusion, motor symptoms improvement during sleep, emotional lability, tongue fasciculations, speech dysarthria, evanescent nonpruritic rash, pericardial friction
rub, erythematous serpiginous skin lesions, pancarditis (peri­ cardium, epicardium, myocardium, endocardium), painless nodules (bony surfaces, prominences, tendon sheaths), short­ lived (1-2 weeks) subcutaneous nodules, rheumatic heart dis­ ease (mitral valve > aortic valve), erythema marginatum typi­ cally spares the face, cardiovascular disease is leading cause of death.
Tetralogy of Fallot—PROVe (pulmonary stenosis, right ventricular hypertrophy, overriding aorta, VSD, extracar­ diac anomalies\: patent foramen ovale, atrioventricular septal defects, PDA, ASD, multiple ventricular defects, persistent left-sided superior vena cava, aortic valve regurgitation, right­ sided aortic arch, LAD arising from the right coronary artery instead of the left coronary artery, collateral vessels arising from the aorta to the lungs, absent ductus arteriosus, bilateral ductus arteriosus, scoliosis), Down syndrome, Di George syn­ drome, left-to-right shunt (acyanotic), single S2 (ie, inaudible P2), right-to-left shunt (cyanosis), hypercyanotic (“tet”) spells, right axis deviation, prominent R waves in lead Vt, small size for ex­ pected age, right ventricular predominance on palpation, fail­ ure to thrive, systolic thrill on palpation along the left sternal border, feeding difficulty, clubbing of the fingers and toes, early systolic click along the left sternal border, exertional dyspnea, asymptomatic/acyanotic (“pink tetralogy”), “boot-shaped” heart on CXR, absent murmur during tet spells, pulmonary valve (bicuspid or unicuspid), harsh systolic ejection murmur along the left sternal border and pulmonic area, decrease in pul­ monary vascularity on CXR, continuous murmurs in patients with aorticopulmonary collateral vessels or PDA, anterior and cephalad displacement of the infundibular septum, right atrial enlargement, T P wave amplitude in lead Vj, pulmonary valve atresia (uncommon), murmurs not related to VSD but rather right ventricular outflow obstruction (common cause), squat­ ting improve symptoms (T peripheral vascular resistance and thereby Xright-to-left shunt).
Henoch-Schonlein purpura—Also known as IgA vascu­ litis, rash (face, upper extremities, trunk, buttocks, lower extremities), arthralgia, abdominal pain, nonthrombocytope­ nic palpable purpura, renal disease, arthritis (lower extrem­ ity > upper extremity), pruritic petechiae, fever, ecchymoses, common in children, intussusception, subcutaneous edema, hematuria, nausea, orchitis, vomiting, proteinuria, normal or T platelet count, nonambulatory, diarrhea, normal coagulation studies, constipation, IgA deposition (arterioles, capillaries, and venules), nephritis, 50% of cases preceded by upper respiratory infection (usually streptococcus), T ESR and leukocytosis sec­ ondary to infection, joint swelling without effusion, GI bleed, anemia secondary to GI bleed, urticarial wheals, normal he­ moglobin levels, acute pancreatitis (uncommon), scrotal pain and swelling, absence of purpura as the initial presentation, unknown etiology, ± red cell casts, ± guaiac-positive stool, trig­ gering event (infection, food, drugs, insect bites, vaccinations), mesangium deposits (IgA, C3, IgG, fibrin, IgM), transient ar­ thritis, bowel perforation, ambulating with a limp, scalp edema, skin lesion biopsy revealing leukocytoclastic vasculitis, can still occur in adults but less common, male > female, self-limited
APPENDIX A PATTERN RECOGNITION 307

308 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
condition, nephrotic syndrome uncommon, immune-mediated vasculitis, recurrence.
Cor pulmonale—Altered structure and/or function of the right ventricle secondary to disease of the lung parenchyma and/or pulmonary vasculature, right-sided heart failure not due to left-sided heart failure or congenital heart disease, shortness of breath, lethargy, dyspnea on exertion, dizziness, lower extremity edema, accentuated P2 upon inspiration, chronic cor pulmonale (slow progressive course with de­ velopment of RVH —» RV dilatation —> right-sided heart failure), pulmonary arterial hypertension, fatigue, palpita­ tions, chest pain, acute cor pulmonale secondary to massive PE (RV dilatation —> heart failure without RVH seen during the entire process), RBBB in PE, cardiomegaly on CXR, mean pulmonary artery pressure >25 mmHg at rest, exertional syn­ cope, systolic pulmonary ejection click over the pulmonic area, RVH, prominent “a wave” on jugular venous pulsations secondary to RVH, right-sided S4, left parasternal heave, RVH on EKG (prominent R wave in lead Vp right axis deviation), signs and symptoms of the underlying lung disease (eg, COPD, CF, sarcoidosis), prominent pulmonary arteries on CXR, T BNP, pulmonary capillary wedge pressure <15 mmHg, right atrial enlargement on EKG (T P wave amplitude in lead Vt and/or lead II), tricuspid regurgitation secondary to right ven­ tricular dilatation, holosystolic murmur along the left sternal border (tricuspid regurgitation), prominent “v wave” on jugu­ lar venous pulsations secondary to right ventricular dilatation, loss of retrosternal space on lateral view CXR, signs of RV fail­ ure (T JVP, hepatomegaly, hepatojugular reflux, pulsatile liver, right-sided S3, peripheral edema, ± ascites), end-stage cor pul­ monale (cyanosis, low cardiac output, cool extremities, hypo­ tension, cool extremities, pulmonary edema).
Stevens-Johnson syndrome (SJS)—Prodromal symptoms (fe­ ver, arthralgias, photophobia, skin tenderness, conjunctival itching or burning, malaise), milder form of toxic epidermal necrolysis (TEN), risk factors for SJS and TEN (HIV infection, genetics, SLE), drug exposure followed by 1 to 3 weeks before symptoms appear, diffuse erythema, targetlike erythematous macules, rash may initially start on the face and upper torso, vesicles and bullae form which then slough off, denuded skin, secondary infection, 80% of cases of TEN are triggered by medications, positive Nikolsky sign (ie, elicitation of a blister upon lateral pressure on the skin), 50% of cases of SJS are trig­ gered by medications, mucosal involvement (conjunctiva, lips, buccal mucosa, esophagus, trachea, urethra, vagina, anus), SJS (skin sloughing <10%), TEN (skin sloughing >30%), SJS/TEN overlap syndrome (skin sloughing >10% but <30%), keratitis, triggering drugs for SJS and TEN (allopurinol, lamotrigine, sulfamethoxazole, sulfasalazine, sulfadiazine, sulfapyridine, ampicillin, amoxicillin, carbamazepine, phenobarbital, phe- nytoin, piroxicam, cephalosporins, NSAIDs), corneal erosions, urethritis, hyperemia, tracheobronchitis, mucous membranes (erosions, crusts, ulcerations, necrosis, blistering), 15% of cases of SJS are triggered by infections (eg, Mycoplasma pneumonia, herpes virus), full-thickness epidermal necrosis and detach­ ment on histology.
Alport syndrome—Bilateral sensorineural hearing loss (high frequency initially), ocular abnormalities, renal abnormali­ ties, X-linked (80% of cases), autosomal recessive (10%-15% of cases), autosomal dominant (5% of cases), early childhood hematuria, hereditary nephritis, multiple leiomyomas (found in the respiratory, GI, and female reproductive tracts), micro­ scopic hematuria, anterior lenticonus (ie, conical protrusion of the anterior surface of the lens), gross hematuria, abnormali­ ties in the alpha chains of type IV collagen (seen in the cochlea, eye, and kidney), progressive hearing loss to low frequencies, family history, glomerulosclerosis, primary dysfunction is type IV collagen, not an autoimmune disease, post-renal transplant anti-glomerular basement membrane antibody disease (3%-5% of transplanted males), hypertension, predominantly males in X-linked Alport syndrome (no male-to-male transmission), thinning of the glomerular basement membrane (early stage), X-linked female carriers (varied presentation secondary to ly- onization), thickening of the glomerular basement membrane (over time), proteinuria, gene mutation (COL4A3, COL4A4, or COL4A5), corneal changes (posterior polymorphous dystro­ phy), end-stage renal disease, laminated GBM (ie, splitting of the lamina densa of the GBM over time), retinal changes (peri- macular dot-and-fleck retinopathy).
Hydrocele—Painless scrotal mass, fluid between the parietal and visceral layers of the tunica vaginalis, communicating hy­ drocele (patent processus vaginalis, T peritoneal fluid during Valsalva, reducible, associated indirect inguinal hernia), non­ communicating hydrocele (closed processus vaginalis, no affect during Valsalva, nonreducible, fluid arises from the mesothelial lining of the tunica vaginalis), positive scrotum transillumina­ tion, superior and anterior to the testis, unilateral or bilateral.
Varicocele—Painless scrotal mass, “bag ofworms” texture upon standing or Valsalva, scrotal pain, dilated pampiniform plexus of the spermatic cord veins, left > right, diminished varico­ cele upon supine position, scrotal heaviness, negative scrotum transillumination, 4 fertility, unilateral or bilateral, postpuber- tal males, rule out obstruction or thrombosis of the IVC (for right-sided varicocele, acute onset, or nonreducible varicocele in the supine position), “nutcracker effect” (ie, increased pres­ sure in left testicular vein secondary to compression of the left renal vein by the superior mesenteric artery and aorta), testicu­ lar atrophy.
Spermatocele—Painless scrotal mass, arises at the head (caput) of the epididymis, positive scrotum transillumination, epididy- mal cyst, benign, no affect during Valsalva, fluid may contain sperm, located superior and/or posterior to the testicle, no ef­ fect on fertility, unknown etiology, incidental finding.
Primary sclerosing cholangitis (PSC)—Pruritus, jaundice, hepatomegaly, fatigue, excoriations, progressive disease, sple­ nomegaly, right upper quadrant pain, asymptomatic, TT al­ kaline phosphatase, unknown etiology, normal albumin levels (early stage), T serum aminotransferases (usually <300 IU/L), chronic cholestasis, men > women, inflammation and fibrosis of medium to large intrahepatic and/or extrahepatic biliary ducts, t GGT, intrahepatic and extrahepatic biliary duct strictures and

dilatations on cholangiography, ± T direct (conjugated) bilirubin (ie, bilirubin levels can fluctuate but an increase suggests biliary obstruction), mean age of diagnosis is 40 years old, steatorrhea, stricturing and beading on cholangiography, increased risk for cholangiocarcinoma, fat-soluble vitamin deficiencies (A, D, E, K), recurrent febrile bacterial cholangitis secondary to biliary obstruction (Charcot’s triad—fever, RUQ pain, jaundice), posi­ tive P-ANCA, hypergammaglobulinemia, patients with PSC have a fairly high likelihood (75%-90% of cases) of IBD (ulcer­ ative colitis > Crohn’s disease), increased risk for colon cancer (in the presence of PSC + UC), patients with IBD have a fairly low likelihood of PSC (l%-5% of cases), hypoalbuminemia (seen with concomitant active IBD), concentric periductal fibrosis on histology (“onion skin” pattern), cholelithiasis, increased risk for gallbladder cancer, secondary biliary cirrhosis, portal hyperten­ sion, end-stage liver disease, small duct PSC or “pericholangi­ tis” (ie, variant of PSC with histology consistent with PSC but normal cholangiography), increased risk for hepatocellular car­ cinoma in patients with cirrhosis, metabolic bone disease (ie, osteoporosis), histology may be similar to PBC (eg, bridging fibrosis), t serum IgM, PSC-autoimmune hepatitis overlap syn­ drome (ie, cholangiographic abnormalities characteristic of PSC but serologic features of autoimmune hepatitis such as T ANA or T smooth muscle antibodies), median survival without liver transplantation from time of diagnosis is 9 to 12 years.
Pelvic inflammatory disease (PID)—Lower abdominal pain (dull, crampy, or constant), cervical motion tenderness, fever, uterine tenderness, infection of the upper genital tract (uterus, oviducts, ovaries) and nearby pelvic organs, adnexal tenderness, sexually active young women, abdominal pain <7 days (unlikely if >3 weeks), multiple partners, cervical or vaginal mucopuru­ lent discharge, pelvic pain developing a few days after the onset of a menstrual period or at the end of menses, diffuse bilateral lower abdominal pain exacerbated by sexual activity or move­ ment, palpable adnexal mass, tubo-ovarian abscess, history of STDs, bacterial vaginosis, nonbarrier contraception, Fitz-Hugh- Curtis syndrome (perihepatitis, pleuritic RUQ pain ± radiation to shoulder, “violin string” adhesions on the surface of the liv­ er, ± t aminotransferases, jaundice), salpingitis, periappendi­ citis secondary to salpingitis, ectopic pregnancy, tubal edema and erythema, controversial role or lack of a clear consensus of OCPs on PID risk, decreased bowel sounds, Gram’s stain positive for gram-negative intracellular diplococci, abnormal uterine bleeding. Neisseria gonorrhoeae infection, menorrhagia, urethritis, Chlamydia trachomatis infection, unknown etiology, polymicrobial, plasma cell endometritis, T ESR, T CRP, nausea, vomiting, leukocytosis, oophoritis, abnormal fimbriae, T WBCs on saline microscopy of vaginal secretions, chills, T CA-125, new vaginal discharge, postcoital bleeding, urinary symptoms, malaise, peritonitis, rebound tenderness, cul-de-sac fluid, invol­ untary guarding, previous history of PID, parametritis, young age at first intercourse, vaginal douching, fluid-filled oviduct (hydrosalpinx), myometritis, infertility, vaginal spotting, IUD increases risk only in the first 3 weeks after insertion, uncom­ mon during pregnancy (except the first 12 weeks of gestation before mucus plug seals oflf the uterus), chronic pelvic pain (ie, sequela of PID).
Irritable bowel syndrome (IBS)—Chronic abdominal pain, absence of organic pathology, altered bowel habits, abdominal distention, diarrhea and/or constipation, absence of weight loss, flatulence, women > men, GERD, absence of anemia, dyspa- reunia, abdominal pain with variable locations (upper, lower, right-sided, left-sided), improvement with defecation, nausea, vomiting, unclear pathophysiology, absence of fever, abdomi­ nal discomfort (ie, not pain), pellet-shaped stools, postpran­ dial stool urgency, dysmenorrhea, absence of rectal bleeding, subjective feeling of incomplete evacuation, abdominal pain without radiation, belching, hard narrow-caliber stools, con­ stant abdominal pain, episodic abdominal pain superimposed on constant ache, stool straining, recurrent abdominal pain in the last 3 months, dysphagia, normal labs (CBC, BMP, ESR), absence of painless diarrhea, altered stool appearance and/or frequency at onset of symptoms, urinary frequency, abdomi­ nal pain precipitated by meals or stress, onset in young patients (<45 years old), absence of steatorrhea, comorbid fibromyalgia, crampy pain, dyspepsia, sexual dysfunction, absence of progres­ sive abdominal pain, stool accompanied by mucus, small vol­ umes of loose stools, stool urgency prior to defecation, work absenteeism, noncardiac chest pain, absence of nocturnal ab­ dominal pain.
Psoriasis—Skin lesions, pruritus, asymptomatic, uveitis, con­ junctivitis, genetic predisposition (HLA-Cw6), blepharitis, T T cell activity, triggering factors (trauma, infection, stress,
cold, alcohol, lithium, beta blockers, antimalarial drugs), cor­ neal lesions, dry eye, plaque psoriasis (silvery scales, common type, affects the scalp, trunk, and extensor surfaces of the el­ bows and knees), inverse psoriasis (smooth red lesions without scales, inverse of extensor surfaces such as the flexural areas of the armpit, under the breast, groin, creases of the butt), guttate psoriasis (“droplike” lesions, small erythematous papules or plaques, preceded by streptococcal infection, primarily affects the trunk, spontaneously remits or progresses to chronic plaque psoriasis), pustular psoriasis (pustules affecting the palms, soles, distal digit, or anywhere on the body), nail psoriasis (nail pit­ ting, nail bed hyperkeratosis, splinter hemorrhages, onycholy­ sis, visually indistinguishable from onychomycosis, brown “oil spot” sign, occurs as a solo condition or commonly with psori­ atic arthritis), psoriatic arthritis (DIP joint arthritis, symmetric polyarthritis, asymmetric oligoarthritis, sacroiliitis, spondylitis, arthritis mutilans/deforming arthritis, nail involvement, teno­ synovitis, ± rheumatoid factor, enthesitis/inflammation at the ligament insertion into bone, dactylitis (“sausage digit”), psori­ atic skin lesions, family history ofpsoriasis, ocular involvement, “pencil-in-cup” appearance on hand x-ray), erythrodermic psoriasis (uncommon type, generalized erythema and scaling of the entire body, constitutional symptoms, high risk for com­ plications), worsening psoriasis in HIV patients, improvement in warm sunny weather.
Hodgkin’s lymphoma—B symptoms (fever, night sweats, weight loss), mediastinal mass, painless lymphadenopathy (oc­ cipital, preauricular, cervical, Waldeyer’s tonsillar ring, supracla­ vicular, infraclavicular, mediastinal, hilar, axillary, epitrochlear/ upper inner elbow, spleen, liver, paraaortic, mesenteric, iliac,
APPENDIX A PATTERN RECOGNITION 309

310 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
inguinal, femoral, popliteal), pruritus, hepatomegaly, supradia­ phragmatic lymphadenopathy > subdiaphragmatic lymphade- nopathy, contiguous spread via lymphatic system (early stage), splenomegaly, noncontiguous spread via lymphatic system (later in the course of disease), bimodal age distribution (15-30 years old and >50 years old), intermittent fever (ie, Pel-Ebstein fever), fatigue, hematogenous dissemination (later in the course of disease), mediastinal related problems (retrosternal chest pain, dysphagia, shortness of breath, cough, superior vena cava syndrome), rubbery consistency of the lymph node, anemia, ± EBV infection, extranodal involvement (eg, bone marrow, pul­ monary, skeletal), hypercalcemia, pain over involved bone or nodal sites upon drinking alcohol, neoplastic Reed-Sternberg cells (“owl’s eyes” appearance) in the setting of mixed inflam­ matory cells seen in classical Hodgkins lymphoma, neoplastic cells derived from germinal center B cells, Reed-Sternberg cell positive for CD 15 and CD30, 5 types of Hodgkins lymphoma (4 subtypes of the classical Hodgkin’s lymphoma and 1 type re­ ferred to as nodular lymphocyte predominant Hodgkin’s lym­ phoma), 4 subtypes of classical Hodgkin’s lymphoma\: nodular sclerosis (70%-80% of cases) > mixed cellularity (20%-25% of cases) > lymphocyte rich (5% of cases) > lymphocyte depleted
(<1% of cases), paraneoplastic syndrome (eg, CNS abnormali­ ties, hypertrophic osteoarthropathy, nephrotic syndrome, cu­ taneous manifestations), nodular lymphocyte predominant Hodgkin’s lymphoma (“nonclassical,” 5% of cases of Hodgkin’s lymphoma, L&H cell that is a variant of a Reed-Sternberg cell, L&H cell negative for CD 15 and CD30), eosinophilia, neutrope­ nia, leukocytosis, lymphopenia, thrombocytosis, thrombocyto­ penia, autoimmune hemolytic anemia, early stage large medias­ tinal mass (greater than one-third of the intrathoracic diameter of the chest wall) is an unfavorable prognostic factor.
Amyotrophic lateral sclerosis (ALS)—Also known as Lou Gehrig’s disease or motor neuron disease, mixed upper and lower motor neuron deficit, anterior horn cell degeneration, corticospinal tract degeneration, loss of Betz cells in the motor cortex, asymmetric limb weakness, upper motor neuron find­ ings (spasticity, stiffness, hyperreflexia, T DTRs, poor dexter­ ity, Babinski/extensor plantar response, Hoffman’s sign), lower motor neuron findings (fasciculations, fibrillations on EMG, twitching, cramping, muscle weakness, reduced reflexes, amy­ otrophy/muscular atrophy, respiratory difficulties, tripping sec­ ondary to a foot drop), progressive neurodegenerative disorder, sporadic (90% of cases) > familial (5%-10% of cases), autosomal dominant pattern (superoxide dismutase 1 mutation) in famil­ ial cases, unknown etiology in sporadic cases, normal sensory exam, motor nuclei degeneration in the brainstem (trigeminal motor nucleus, hypoglossal nucleus, nucleus ambiguus), bulbar findings (dysarthria, dysphagia, drooling, aspiration, choking, tongue weakness, slurred speech, hoarseness, vocal cord weak­ ness, trismus, chewing difficulty, laryngospasm, incomplete eye closure, reduced volume of speech, jaw stiffhess/clenching, poor lip seal, pseudobulbar affect/involuntary crying or laughing), cervical findings (head drop, intrinsic hand muscle weakness, shoulder girdle muscle weakness, wrist drop, difficulty eating, grooming, bathing, or writing secondary to upper extremity weakness), thoracic findings (abdominal protuberance, truncal
weakness, difficulty maintaining an erect posture, hand walking on their thighs to support their trunk, diaphragmatic weakness, dyspnea, respiratory muscle weakness, weak cough, orthopnea, tachypnea, sleep disordered breathing), lumbosacral findings (lower extremity weakness, imbalance, foot drop secondary to foot/ankle weakness, gait dysfunction, difficulty rising from chairs or climbing stairs, lumbar lordosis), fibrillations and fas­ ciculations on EMG, extraocular motility is typically spared but dysfunction can present in late stages, incontinence is uncom­ mon, gliosis of the corticospinal tract, sphincter control of the bowel and bladder is typically spared, urinary and fecal urgency without incontinence (ie, preserved sphincter function) can oc­ cur in late stages, thinning of the ventral roots, sensory func­ tion is typically preserved, frontotemporal dementia (personal­ ity changes, ritualized behaviors, impaired judgment, unusual eating patterns), evidence of muscle denervation and reinner­ vation, normal sensory nerve conduction study, sometimes abnormal sensory nerve conduction study, sometimes abnor­ mal sensory evoked potentials, signs of parkinsonism, reduced amplitudes of the compound motor action potential on nerve conduction studies, most common cause of death is respiratory failure, median survival from time ofdiagnosis is 3 to 5 years.
Granulomatosis with polyangiitis (Wegener’s)—Also known as GPA, systemic vasculitis, systemic features (eg, fever, weight loss, malaise, migratory arthralgias, night sweats), necrotiz­ ing granulomatous inflammation, renal and respiratory tract manifestations predominate, whites > blacks, unknown etiol­ ogy, multiorgan involvement (CNS, parotids, thyroid, lungs, heart, breast, GI, fiver, prostate, ureters, skin), nasal crusting, epistaxis, sinusitis, tracheal stenosis, stridor, wheezing, pro­ teinase 3-ANCA > myeloperoxidase-ANCA (Note\: P-ANCA correlates with myeloperoxidase and C-ANCA correlates with proteinase 3), conjunctivitis, negative ANCA (<10% of cases), T ESR, T CRP, episcleritis, otitis media, ± T creatinine levels, purulent nasal discharge, uveitis, corneal ulceration, few or absent immune deposits in the glomeruli (ie, pauci-immune glomerulonephritis), leukocytosis, thrombocytosis, ear pain, hemoptysis, DVT, acute kidney injury, urticaria, ± rheumatoid factor, dyspnea, nasal ulcers, chest discomfort, coronary vas­ culitis, normochromic-normocytic anemia, pericarditis, T or X DLCO, subglottic stenosis, strawberry gingival hyperplasia, pulmonary effusion, pulmonary consolidation, CNS granulo­ matous mass, visual loss, abnormal findings on CXR (cavitary pulmonary nodules, noncavitating pulmonary nodules, opaci­ ties, or hilar adenopathy), atelectasis, proteinuria, eye pain, oral ulcers, persistent rhinorrhea, dacryocystitis, hematuria, livida reticularis, hearing loss (conductive and sensorineural), absence of nasal polyps, diffuse alveolar hemorrhage (DAH) secondary to pulmonary capillaritis, cough, vesicles, papules, petechiae, mastoiditis, optic neuropathy, cranial nerve palsies, otorrhea, proptosis, focal and segmental glomerulonephritis that can evolve into a necrotizing crescentic glomerulonephri­ tis, hyperthyroidism, bronchial stenosis, retinal vasculitis, re­ nal failure, abdominal pain secondary to splanchnic vasculitis, myalgias, cardiac conduction defects, saddle nose deformity secondary to nasal septal perforation (ie, loss of nasal support), purpura ± ulceration, peripheral neuropathy, myocarditis,

± hypergammaglobulinemia (IgA), hoarseness, pleuritic pain, airflow obstruction, subcutaneous nodules, bronchial ulcer­ ation, leukocytoclastic vasculitis on skin biopsy, mononeuritis multiplex, ± red cell casts, limited GPA (ie, isolated respiratory tract manifestations with the possibility of renal manifestations later in the course of disease), biopsy of the involved organ may show some or all of the findings\: granulomatous inflammation, necrosis, vasculitis.
Anti-GBM antibody (Goodpasture’s) disease—Autoimmune disorder, rapidly progressive glomerulonephritis (RPGN), he­
maturia, hemoptysis, proteinuria, acute renal failure, red cell casts, granular casts, cough, shortness of breath, T DLCO sec­
ondary to hemoglobin in the alveoli, pulmonary hemorrhage, hemoptysis precipitated by lung injury (eg, cocaine, smoking, inhaled hydrocarbons), hypertension, renal plus lung disease (most common presentation), bimodal age distribution (30s and 60s), isolated renal disease (20%-40% of cases), tachypnea, crackles, isolated lung disease (<10% of cases), ± T creatinine, systemic features are usually absent (eg, fever, weight loss, mal­ aise), myeloperoxidase-ANCA > proteinase 3-ANCA, absence of vasculitis, up to 30% of patients are double positive (ie, posi­ tive anti-GBM antibodies + positive myeloperoxidase ANCA), immunofluorescence demonstrating linear deposition of IgG (sometimes IgA or IgM) along the basement membranes (glo­ merular basement membrane > alveolar basement membrane), light microscopy from a renal biopsy demonstrating crescentic glomerulonephritis, cyanosis, nonspecific pulmonary infiltrates on CXR, edema, anti-GBM antibodies (mainly IgG but some­ times IgA or IgM) against the alpha chains of type IV collagen, oliguria, iron deficiency anemia secondary to prolonged pulmo­ nary hemorrhage, genetic predisposition (HLA-DR15 previous­ ly known as HLA-DR2), pulmonary fibrosis secondary to recur­ rent episodes ofpulmonary bleeding, type II hypersensitivity.
Vitamin A (retinol)—Deficiency\: Night blindness, xerophthal­ mia (dry eye), poor bone development, Bitot’s spots (abnormal squamous proliferation and keratinization of the conjunctiva), follicular hyperkeratosis, keratomalacia (ulceration of the cor­ nea), dry skin, hyperkeratosis of the skin, impaired immune system. Acute toxicity\: Nausea, vomiting, vertigo, blurry vi­ sion, drowsiness, irritability, teratogenic. Chronic toxicity\: Dry skin, pruritus, yellow-orange skin discoloration (ie, excess P-carotene), alopecia, anorexia, T CSF pressure, pseudotumor cerebri, papilledema, visual impairments, headache, hepato- toxicity, hepatomegaly, hyperostosis, bone pain, bone fractures, ataxia, teratogenic.
Vitamin D (ergocaldferol/D2, cholecaldferol/D3)—Deficiency\: Rickets (children), osteomalacia (adults), hypocalcemia, sec­ ondary hyperparathyroidism, severe deficiency (4 serum Ca, •1 serum P04, -l 25 (OHD), T PTH, T alkaline phosphatase). Toxicity\: Hypercalcemia, bone pain, backache, nausea, vomit­ ing, polydipsia, polyuria, anorexia, abdominal pain, constipa­ tion, confusion, muscle weakness, shortened QT.
Vitamin E (a-tocopherol)—Deficiency\: Hemolytic anemia, neurologic abnormalities (ataxia, hyporeflexia, X proprio­ ception, i vibratory sensation, retinopathy, skeletal muscle
atrophy. Toxicity\: Nausea, fatigue, blurred vision, muscle weakness.
Vitamin K (phylloquinone/Kj, menaquinone/K2, menadi- one/K3)—Deficiency\: Bleeding, easy bruisability, hematuria, melena, prolonged PT. Toxicity\: Menadione formulation (vita­ min K3) can cause hyperbilirubinemia, hemolytic anemia, jaun­ dice, kernicterus, and blocks the effects of oral anticoagulants.
Vitamin C (ascorbic acid)—Deficiency\: Scurvy (poor wound healing, petechiae, ecchymosis, bleeding gums, coiled hairs, joint swelling, perifollicular hyperkeratotic papules, fatigue). Toxicity\: Diarrhea, abdominal cramps, false-negative stool guaiac results.
Vitamin B1 (thiamine)—Deficiency\: Wernicke-Korsakoffsyn­ drome (ataxia, confusion, nystagmus, ophthalmoplegia, mem­ ory impairment, confabulation), infantile beriberi (cyanosis, dyspnea, vomiting, tachycardia, cardiomegaly, heart failure), adult wet beriberi (high-output CHF, cardiomegaly, tachycar­ dia, peripheral edema, peripheral neuritis), adult dry beriberi (i reflexes, motor and sensory peripheral neuropathy primarily affecting the legs).
Vitamin B2 (riboflavin)—Deficiency\: Angular stomatitis (in­ flammation at the corner of the mouth), smooth tongue sec­ ondary to glossitis (ie, loss of papillae), seborrheic dermatitis, corneal vascularization, anemia.
Vitamin B3 (niacin)—Deficiency\: Pellagra (dermatitis, diar­ rhea, dementia, death). Acute toxicity\: Flushing can be seen with nicotinic acid but not with nicotinamide. Chronic toxic­ ity\: Nicotinic acid can cause elevated aminotransferases, elevat­ ed uric acid, and peptic ulcers.
Vitamin Bs (pantothenic acid)—Deficiency\: GI disturbances, paresthesias, dysesthesias ("burning feet” syndrome).
Vitamin Bg (pyridoxine)—Deficiency\: Stomatitis, glossitis, seborrheic dermatitis, peripheral neuropathy, depression, con­ fusion, irritability, seizures, anemia, elevated homocysteine lev­ els. Toxicity\: Photosensitivity, dermatitis, unstable gait second­ ary to sensory neuropathy.
Vitamin B12 (cobalamin)—Deficiency\: Megaloblastic anemia (pernicious anemia), subacute combined degeneration of the dorsal and lateral columns, loss of vibration and position sense, positive Romberg test, ataxia, paresthesias, urinary and fecal incontinence, dementia, glossitis, optic neuropathy, elevated homocysteine levels, elevated methylmalonic acid, hyperseg- mented neutrophils.
Folate—Deficiency\: Megaloblastic anemia, absence of neu­ rologic disturbances, elevated homocysteine levels, hyperseg- mented neutrophils, neural tube defects, earlier disease onset compared to vitamin B12 deficiency secondary to a smaller stor­ age capacity for folate.
Biotin—Deficiency\: Anorexia, nausea, paresthesia, psychologi­ cal disturbances (depression, hallucinations, apathy), myalgia, rash, fine hair, alopecia, seborrheic dermatitis. (Note\: Eating large amounts of raw egg whites can lead to biotin deficiency secondary to the protein avidin in egg whites that binds strongly to biotin.)
APPENDIX A PATTERN RECOGNITION 311

Rapid-fire Clinical Judgments
The rapid-fire clinical judgment section focuses on patient management with the intention to “keep you on your toes” during your preparation. Initially, try to answer the questions without looking at the answer. By your final review, you should be able to confidently answer all the questions without hesitation.
1) 45 y.o. man presents to the ED with cyanosis, dyspnea, headache, and weakness. Pulse oximetry reading dem­ onstrates 86% on room air. The patient was given 100% oxygen with no improvement. Blood was drawn for fur­ ther evaluation, and it was noted that his blood appeared “chocolate brown.” He later tells the resident physician that earlier in the day he was given a topical mucosal anesthetic for an in-office biopsy procedure. The resident orders a co-oximeter, which reveals an elevated level of methemo- globin (>25%). What is the primary medical treatment?
The treatment of choice for methemoglobinemia is an IV infusion of methylene blue given over 5 to 10 minutes. Methemoglobinemia can be due to congenital or acquired causes. Acquired causes include topical anesthetic agents (benzocaine, lidocaine, prilocaine), dapsone, nitrites/nitrates, nitroglycerin, metoclopramide, menadione, sulfonamides, primaquine, naphthalene, phenazopyridine, benzene derivatives, and aniline dyes. Pulse oximetry readings are unreliable because they only measure two wavelengths of light and the partial pressure of oxygen (PO.,) on ABG will be typically be normal. Co-oximetry can measure al least four wavelengths of light and is capable of detecting
methemoglobinemia. Methylene blue should not be given to patients with G6PD deficiency because it is ineffective and it can potentially trigger an acute hemolytic anemia.
2) 62 y.o. woman presents to the office with a nonproduc­ tive cough, nasal congestion, facial edema, dyspnea on exertion, dilated right jugular vein, and a prominent venous pattern on her chest. A CXR reveals a widened mediastinum and a right-sided mass in her chest. A chest CT with contrast demonstrates a narrowed supe­ rior vena cava (SVC), presence of collateral vessels, and the absence of thrombosis. Sputum cytology results are pending, and a bronchoscopy is scheduled. The pa­ tient expresses significant discomfort and feels that she cannot wait until the scheduled bronchoscopy. What is the best treatment option in this patient?
In this patient that presents with SVC syndrome, a percutaneous endovascular stent can be performed for rapid relief while the histologic diagnosis is being pursued. Upon histologic diagnosis of the malignancy, initiation of chemotherapy or radiotherapy can be per­ formed for chemosensitive or radiosensitive tumors, respectively. Endovascular stenting is also a viable op­ tion in patients with SVC syndrome that have failed chemotherapy or radiotherapy.
3) 65 y.o. man presents with blood oozing from his IV lines in the inpatient ward. Lab workup demonstrates a low platelet count, prolonged PT/PTT, decreased plasma fi­ brinogen, increased fibrin degradation products, and an
313

314
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
4)
elevated D-dimer level. Peripheral smear demonstrates Auer rods in the cytoplasm and bilobed nuclei of abnor­ mal promyelocytes. Your clinical suspicion suggests DIC with an underlying acute promyelocytic leukemia (pre­ viously called AML-M3). What is the primary medical treatment?
Treat the underlying disorder in DIC, which is the acute promyelocytic leukemia (APL). APL is considered a medi­ cal emergency, and when APL is suspected, treatment should be initiated with induction therapy of all-trans reti­ noic acid (ATRA) and chemotherapy.
65 y.o. woman presents to the ED with clinical suspicion for diverticulitis. What is the imaging of choice to con­ firm the diagnosis of acute diverticulitis?
A CT scan of the abdomen is the best imaging method. In­ stitutions will vary on the use of oral plus IV contrast in the evaluation of acute diverticulitis, but typically, the oral contrast does not reach the sigmoid colon. However, the use of oral and IV contrast can reach sensitivities of 97% and specificities of 100%. Barium enema and colonoscopy are contraindicated in the acute stages due to a risk of peri­ tonitis and perforation.
(for unstable patients) or IV infusion. Atropine can be given as a temporizing measure prior to giving digoxin- specific antibody (Fab) fragments. Activated charcoal may be given as an adjunctive therapy and is effective if given within 1 to 2 hours of ingestion, but in this case, the patient is beyond that time period and is experiencing symptom­ atic bradycardia. Drugs that can increase digoxin serum levels include amiodarone, clarithromycin, cyclosporine, diltiazem, erythromycin, itraconazole, ketoconazole, quin- idine, and verapamil. Digoxin toxicity can result in neu­ rologic, cardiac, and GI manifestations. Digoxin toxicity can cause almost any arrhythmias (eg, sinus bradycardia, AV blocks, PVCs, ventricular tachycardia, ventricular fi­ brillation, junctional rhythms, ventricular bigeminy, su­ praventricular tachyarrhythmias). Remember that once you obtain the potassium level, toxicity will correlate with hyperkalemia rather than the serum digoxin level. The hy­ perkalemia will correct itself once digoxin-specific anti­ body (Fab) fragments are given, and therefore, caution is advised of aggressive correction of the hyperkalemia prior to digoxin-specific antibody (Fab) fragments since it can lead to hypokalemia.
7) 34 y.o. woman has been in the inpatient ward for the past 7 days. On day 1, she received a double lumen central catheter that is being flushed with heparin to maintain patency. Her platelet count has dropped to 75,000/mm3, which has been more than a 50% drop from her baseline platelet count on day 1. Skin necro­ sis can be observed near the heparin flush site. What is your next best step?
The patient is presenting with heparin-induced thrombo­ cytopenia (HIT). The next best step is to discontinue hepa­ rin flushes and stop any further heparin products including unfractionated and low molecular weight heparin. The pa­ tient needs anticoagulation because the risk for thrombosis is highest in the first 1 to 2 weeks. Acceptable nonheparin anticoagulation includes SubQ fondaparinux, IV argatro- ban, or IV bivalirudin. It should be noted that lepirudin and danaparoid are not available in the United States. The transition to warfarin should not occur until the platelet count is above 150,000/mm3 and the patient has been sta­ bly anticoagulated with the nonheparin agent. There are two types of HIT, type 1 (nonimmune) and type 2 (im- mune-mediated). In HIT 1, which occurs in approximately 10% of patients, a transient thrombocytopenia is usually observed 1 to 2 days after heparin administration and the platelet count returns to normal levels even in the presence of continued heparin therapy. In this case, HIT 2, which occurs in less than 5% of patients, the thrombocytopenia is usually seen 5 to 10 days after heparin administration, but it can occur earlier (ie, hours to <1 day) if previously exposed to heparin. The risk ofthrombosis (arterial and ve­ nous) is seen with HIT 2, but not with HIT 1, which is more of a benign self-limited condition. When HIT is suspected, always remember the “4 T’s”\: thrombocytopenia, timing of the platelet drop, thrombosis, and thrombocytopenia due
5) Whatarethetreatmentoptionsforacutediverticulitis?
Uncomplicated diverticulitis can be treated with outpatient antibiotics that cover gram-negative rods and anaerobes. Oral metronidazole plus ciprofloxacin can be given 10 to 14 days. An alternative is oral amoxicillin-clavulanate mono­ therapy for 10 to 14 days. Patients with poor oral intake and patients who are elderly, have comorbidities, or are im- munosuppressed usually require inpatient management, which include NPO, IV fluids, and IV antibiotics. Several options for IV antibiotics include IV ampicillin-sulbactam, IV piperacillin-tazobactam, or IV metronidazole plus IV ceftriaxone. Patients with a bowel perforation, obstruction, fistula, ruptured abscess, failed percutaneous drainage of the abscess, peritonitis, recurrent attacks, or failed medical response typically require surgical intervention, IV antibi­ otics, IV fluids, and NPO status.
6) 60y.o.manondigoxintherapyforhisheartfailurepres­ ents to the ED with nausea, vomiting, weakness, abdomi­ nal pain, dizziness, and visualizing yellow-green halos for the past 10 hours. Vitals are HR- 55, BP-105/70, RR-16. Recently, the patient started taking clarithromycin for his community-acquired pneumonia. The treating resident physician orders IV access, pulse oximetry (result = 95%), continuous blood pressure monitoring, continu­ ous cardiac monitor, EKG (result = sinus bradycardia), finger-stick glucose (result =115 mg/dL), labs (potassi­ um result = 6.0 mEq/L), and digoxin level (result = wnl). The resident orders IV atropine x 1 dose and the patient responds from the symptomatic bradycardia. What is the primary medical treatment in this patient?
The treatment of choice for digoxin toxicity is digoxin- specific antibody (Fab) fragments given as a slow IV push

to other causes. There are several different assays to diagno­ sis HIT 2, but the 14C-serotonin release assay is considered the gold standard.
8) 52 y.o. man presents to the ED with crampy abdomi­ nal pain and at least 10 episodes of watery diarrhea per day for the past 2 days. The patient is afebrile, and physical exam reveals decreased skin turgor and lower abdominal tenderness without guarding or rebound tenderness. Recently, the patient finished a course of levofloxacin for an upper respiratory infection. A workup of the patient revealed a WBC of 12,000/mm3, positive enzyme immunoassay (EIA) detection for C difficile glutamate dehydrogenase (GDH), and positive EIA detection for C difficile toxin A and B. What is the clinical management in patients with Clostridium diffi­ cile infection (CDI)?
The general management is to discontinue the offending antibiotic, IV fluids for dehydration, avoid antimotility agents (eg, loperamide, opiates), place the patient on con­ tact precautions, and good hand hygiene. Symptoms of CDI can occur during or after the antibiotic is discontinued. Al­ most any antibiotic can cause CDI, but common culprits include fluoroquinolones, cephalosporins, clindamycin, and ampicillin/amoxicillin. Patients that are asymptom­ atic but test positive for CDI do not require antibiotics. However, in this case, the patient has mild to moderate CDI and can be treated with oral metronidazole for 10 to 14 days. IV metronidazole is an alternative to oral therapy if the patient cannot tolerate oral intake. Patients with se­ vere CDI (eg, marked leukocytosis, fever, ill appearance) are usually given oral vancomycin for 10 to 14 days in the inpatient unit. Unlike IV metronidazole, IV vancomycin is ineffective at the colonic level, and it is not recommended for CDI. The management in patients with their first re­ currence depends on the severity as it did for the initial episode. Unfortunately, there is no standard treatment for patients that continue to have multiple recurrences.
9) 21 y.o. man presents to the ED after sustaining a bite to the hand from a raccoon. The patient states that he was opening the lid of his garbage can and saw a raccoon scavenging through his garbage. At that time, the rac­ coon bit the patient's hand and ran off. The patient is as­ ymptomatic, and the physical exam revealed a deep bite wound on the dorsum of his right hand. The patient’s his­ tory reveals that he is an avid spelunker, and 6 months ago he was bitten by a bat during one of his expeditions. At the time of the bat bite, the treating resident physi­ cian gave the patient a rabies postexposure prophylaxis (PEP) that included rabies immunoglobulin plus a ra­ bies vaccine. (1) What is the treatment management in this patient? (2) The patient tells you that he completed the tetanus immunization series as a child and received his last booster Tdap at age 12. Would you still give him a tetanus prophylaxis? If yes, what would you give him? (Please see the discussion in question 10 for the answer in part 2.)
The patient’s wound should be cleansed with a virucidal agent (eg, povidone-iodine solution). At the time of his earlier bat bite, the patient was not previously immunized to rabies, and so it was acceptable to administer both im­ munoglobulin ("passive immunization”) and vaccine (“ac­ tive immunization”) as a PEP. Recall that passive immu­ nization refers to an immediate antibody neutralization from an already pooled source (eg, immunized humans), but active immunization requires time (7-10 days) for the human body to actively produce antibodies against a tar­ get antigen. In this case, the PEP should only include the rabies vaccine and not the rabies immunoglobulin because the patient is technically immunized and there should be an anamnestic immune response from the previous vac­ cine. When considering PEP, the type of animal is taken into account. Bats, raccoons, skunks, foxes, coyote, bobcats, and other carnivores are generally regarded as rabid unless proven negative. If these types of animals are not caught and unavailable to be euthanized for further testing, PEP should begin immediately. Keep in mind that capture and observation for signs of rabies is not recommended for these types of animals. Patients bitten by a dog, cat, or fer­ ret may be given PEP if the bite was on the head or neck, the animal appeared rabid, the animal was available for ob­ servation for at least 10 days and showed signs of rabies, or the animal is unavailable for observation and there is uncertainty. In this area of medicine where there can be a great deal of uncertainty it is best to err on the side of safety because you can always discontinue PEP if testing is nega­ tive, but if treatment is delayed and clinical signs of rabies develop it is too late since it usually leads to a fatality. It should be noted that in most unprovoked attacks, the ani­ mal is most likely rabid. In this case, we are not sure if the raccoon was rabid or simply startled from the opening of the garbage can lid. As mentioned, symptomatic rabies vir­ tually always leads to death, and unfortunately, there is no proven medical treatment. The goal of rabies management is prevention. Once rabies is confirmed in the patient, the rabies immunoglobulin and rabies vaccine no longer pro­ vide a pivotal role in management and should be avoided at this point.
10) 28y.o.womanpresentstotheEDaftersustainingacutto her finger while slicing vegetables with a knife. The lac­ eration is not deep, and it measures less than 1 cm long. There are no motor or sensory deficits of the finger, and there is no foreign body in the wound. The patient’s teta­ nus immunization status is unknown. How do you man­ age tetanus prophylaxis in this patient?
Recall that tetanus prophylaxis consists of a tetanus toxoid vaccine (“active immunization”) ± tetanus immune globu­ lin (“passive immunization”). In this case, the patient does not need the tetanus immune globulin (TIG) because it is a clean and minor wound. However, she does need the vaccine because we do not know her tetanus immuniza­ tion history. The woman should receive her first dose of Td today in a 3-dose primary tetanus vaccination series.
APPENDIX B RAPID-FIRE CLINICAL JUDGMENTS 315

CLINICAL JUDGMENT USMLE STEP 3 REVIEW
The 3-dose primary series in adults consists of 3 doses of Td with the first 2 doses separated by 4 weeks and the third dose separated 6 to 12 months from the second dose. Tdap should be substituted for Td at least one time in the 3-dose primary series. If this patient had <3 doses of the tetanus toxoid vaccine, then she can continue to finish her vaccine series. If this patient had >3 doses of the tetanus toxoid vac­ cine and it has been >10 years since her last dose, then she can be given a single dose of Td or Tdap (if she never re­ ceived Tdap before).
The 21-year-old patient in question 9 sustained a wound that would be considered risky because he was exposed to the saliva of a raccoon when he was bitten. Examples of risk­ ier wounds would include puncture wounds, dirty wounds (eg, soil, saliva, or stool, which can be remembered by the “Triple S”), avulsions, burns, frostbite, crushing wounds, and shrapnel wounds. Since the patient completed his teta­ nus series as a child, which normally consists of a 5-dose primary series and a onetime booster, he does not require the tetanus immune globulin (TIG) because he received >3 doses of the tetanus toxoid vaccine. If his tetanus status was unknown or he received <3 doses of the tetanus toxoid vac­ cine, then the patient would require the tetanus immune globulin (TIG). The next part we have to consider in the tetanus prophylaxis is the tetanus toxoid vaccine for this young man. If a patient received >3 doses of the tetanus toxoid vaccine and his last dose of the tetanus toxoid vac­ cine was >5 years ago, the patient would require a dose of the tetanus toxoid vaccine. In this case, the 21-year-old man had >3 doses of the tetanus toxoid vaccine and his last vaccine dose was at age 12, which is >5 years ago, and so he should re­ ceive the Td vaccine. Note that he is due for his 10-year booster Td vaccine until age 22, but it is acceptable to give the Td now. If his tetanus immunization status were unknown or he had <3 doses ofthe tetanus toxoid vaccine, then you would admin­ ister the 3-dose primary tetanus vaccination series or contin­ ue to finish the vaccine series, respectively. To refresh your memory of the tetanus immunization schedule for chil­ dren, the DTaP vaccine is given as a 5-dose series at ages 2,4, 6, and 15 to 18 months and 4 to 6 years old. Then, the child receives a booster vaccine called the Tdap vaccine at age 11 or 12. Subsequentiy, at ages >19 years old the patient receives a booster called the Td vaccine every 10 years with a onetime substitution of Tdap for Td in those who have never had Tdap before or whose tetanus immunization status is unknown. It should be noted that Tdap vaccine is recommended to pregnant women with each pregnancy regardless of their last Td/Tdap vaccination. The major players in tetanus prophylaxis include tetanus immune globulin (TIG), which binds to unbound toxin for neutral­ ization; diphtheria-tetanus-acellular pertussis (DTaP) vac­ cine, which is part of the routine immunization schedule in children; diphtheria-tetanus (DT) vaccine if pertussis antigen is contraindicated; and tetanus toxoid (TT) vaccine if pertussis and diphtheria antigens are contraindicated. Tetanus-reduced diphtheria-acellular pertussis (Tdap) and tetanus-reduced diphtheria (Td) vaccines are typically used
as booster vaccines, but they can also serve as primary im­ munization as seen in the 28-year-old woman above.
11) 32 y.o. man was started on fluphenazine for his schizo­ phrenia. Three days later the patient presents to the ED with lead pipe rigidity, agitation, profuse sweating, and a temperature of 38.3°C (100.94°F). Workup of the patient demonstrates a negative head CT scan, leukocytosis, el­ evated creatine kinase, elevated LDH, elevated alkaline phosphatase, elevated ALT and AST, hyperkalemia, hy­ ponatremia, hypocalcemia, hypomagnesemia, and a de­ creased serum iron concentration. What is the diagnosis, management, and disposition for this patient?
The patient is presenting with neuroleptic malignant syn­ drome (NMS). Triggering factors include typical antipsy- chotics, atypical antipsychotics, and antiemetics. NMS is characterized by a tetrad of hyperthermia, muscular rigid­ ity (eg, cogwheel, tremor, dystonia, dyskinesia), altered mental status (eg, agitation, mutism, confusion, delirium), and autonomic dysfunction (eg, labile blood pressure, dia­ phoresis, tachycardia, tachypnea, urinary incontinence). Laboratory abnormalities can occur (eg, hyponatremia, hypernatremia, myoglobinuria, metabolic acidosis), but no single test is specific for NMS. In this case, the inciting agent is fluphenazine, and this medication should be dis­ continued along with any other psychotropic medications (eg, lithium, anticholinergics). The patient should be trans­ ferred to the ICU for further monitoring and supportive care. Supportive care may include mechanical ventilation, IV fluids for insensible fluid loss, IV fluids with urine alka- linization to prevent acute renal failure secondary to rhab- domyolysis, cooling blankets for fever, or IV lorazepam for agitation. Dantrolene, bromocriptine, amantadine, and electroconvulsive therapy have been used to treat NMS, but there are no controlled studies to support their efficacy. Re­ ported mortality rates can be as high as 20%.
12) 20 y.o. man is in the operating room for an elective sur­ gical procedure. This is the patient’s first surgery, and no family perioperative problems could be obtained since he was adopted as a young boy. The anesthesiology resident premedicates the patient with IV midazolam. Subsequently, an induction sequence of propofol and a onetime dose of succinylcholine (to facilitate tracheal intubation) is administered. The patient is intubated, and inhalational sevoflurane is administered for main­ tenance anesthesia. Fifteen minutes into the case the patient develops sinus tachycardia, masseter muscle rigidity, and hypercarbia. Pulse oximetry demonstrates 98% oxygen saturation, capnography shows an end-tidal carbon dioxide (ETC02) of 70 mmHg, and the patient has a core temperature of 37°C (98.6°C). The concerned resident decides to increase the patient’s minute ventila­ tion to control the hypercarbia, but the ET0O2 remains at 70 mmHg. The soda lime carbon dioxide absorbent can­ ister is warm to touch (exothermic reaction), and there is a change in color from white to purple (indication of C02 exhaustion). The anesthesiology resident makes

a presumptive diagnosis, tells the surgeon to abort the case, and calls for anesthesiology backup. Inhalational sevoflurane and succinylcholine are discontinued, IV propofol is administered to complete the case, and high- flow 100% oxygen is administered to hasten the removal of residual sevoflurane. What is the diagnosis and the next most important step?
The patient is presenting with malignant hyperthermia (MH). The next best step is to administer IV dantrolene, which will interfere with calcium release from the sarco­ plasmic reticulum. Cooling measures should be instituted if there is hyperthermia, but be aware that hyperthermia is usually a late finding. Labs and venous blood gas should be sent out. Acidosis can be treated with bicarbonate. Hy­ perkalemia can be treated with insulin (drives K+ into the cell), D50 (prevents hypoglycemia from the insulin), and bicarbonate. Dysrhythmias usually respond by correcting the hyperkalemia and acidosis. It is important not to ad­ minister a calcium channel blocker when using dantrolene because it can potentially exacerbate the hyperkalemia and enhance the negative inotropic effect on the heart. MH is caused by mutations in the RYR1 receptor gene that are inherited as an autosomal dominant trait. The receptor is involved in the regulation of calcium into the intracellular space. It should be noted that an elevated ETC02 level that is resistant to increasing the patients minute ventilation is one of the most sensitive and early signs of MH. Trig­ gering agents include anesthetic agents (eg, sevoflurane, desflurane, enflurane, isoflurane, halothane) and a depolar­ izing neuromuscular blocker (succinylcholine). Abnormal findings include elevated creatine kinase, myoglobinuria, elevated serum myoglobin, hyperkalemia, peaked T waves on EKG, and a mixed respiratory acidosis and metabolic acidosis (i pH, t pC02, i HCO“).
13) 12 y.o. boy presents to the ED with nausea, vomiting, and acute scrotal pain. The exact duration of pain is un­ known, but the patient believes that is has been for at least 3 hours. The patient denies fever, chills, dysuria, or trauma. On exam, the right testicle is tender to touch and there is no scrotal edema. There is a high-riding right testicle in the horizontal position. Scrotal elevation does not alleviate the pain, and stroking the upper right thigh does not elicit the cremasteric reflex. What is the best treatment option in this patient?
The patient is presenting with testicular torsion. The best treatment option in this patient is immediate surgical ex­ ploration with detorsion and fixation (orchipexy) because you want to preserve the viability of the affected testicle. It should be noted that testicular salvage rates are usually very good if detorsion occurs in less than 6 hours of symp­ toms, but salvage rates decline precipitously thereafter. In this case, we are not sure about the exact duration of symp­ toms, and therefore, time is of the essence. This patient is presenting with classic signs and symptoms of testicular torsion, so there is no need to do imaging. Color Doppler ultrasound (which would show decreased or absent testicu­
lar blood flow) or radionuclide scintigraphy (which would show decreased blood flow) can be used for equivocal pre­ sentations, but they should not delay treatment. If there is a delay in surgical intervention, manual detorsion is an op­ tion, but the procedure should not be performed if there is significant scrotal swelling. In the technique, with appro­ priate analgesia, the testicle is detorsed by rotating it in a medial to lateral motion since most testicular torsions twist in a lateral to medial rotation. An easy way to remember this is to rotate the “nut out” (take the testicle and laterally rotate the nut out toward the thigh). However, it should be noted that upon successful manual detorsion, the patient should still undergo surgical fixation (orchipexy) to pre­ vent a recurrence. Testicular torsion is usually the result of abnormal fixation of the testicle within the tunica vagina­ lis. The tunica vaginalis is a closed peritoneal sac that cov­ ers the anterior portion of the testis and epididymis. If the tunica vaginalis is inappropriately high (covers the distal spermatic cord), the testis can lie horizontally (“bell clapper deformity”) and the spermatic cord can twist. The absence of the cremasteric reflex can help differentiate other causes ofscrotal pain, but the Prehn sign (reliefwith scrotal eleva­ tion) is unreliable for a clinical diagnosis. Scrotal swelling can occur early or late (>12 hours) in the course of disease.
14) 10y.o.boywithapastmedicalhistoryof21-hydroxylase deficiency has recovered from a cough, sore throat, and runny nose 2 weeks ago. Subsequently, the patient develops palpable purpura over the buttocks and lower extremities and develops periarticular swelling and tenderness over the knees and ankles. One week after the skin and joint manifestations, the patient develops colicky abdominal pain and now presents to the office accompanied by his mother, who happens to be a nurse. The medical resident makes the diagnosis of Henoch- Schonlein purpura (HSP) and decides to order a urinalysis, stool guaiac, platelet count, and coagulation studies, which all turn out to be normal. The resident recommends supportive care, which included hydration and NSAIDs for abdominal and joint pain. The mother inquires if there is an increased risk of developing renal disease even though the patient is taking long-term glucocorticoid for his congenital adrenal hyperplasia. The resident finds a retrospective study that examined the relationship of developing renal disease in patients with HSP and the use of long-term glucocorticoids for other comorbid conditions (p = 0.004, odds ratio 0.65, 95% Cl 0.63-0.67). What do you tell the mother, and what would be your next best step?
Based on the article, it is less likely that the patient will de­ velop renal disease when using long-term glucocorticoid. Since the odds ratio is less than one, the estimated risk of developing renal disease is decreased. The confidence in­ tervals (Cl) are narrow, which indicates a large sample size that will give a larger number of observations and more precise estimates. In addition, the Cl may serve as a proxy for the presence of statistical significance if it does not
APPENDIX B RAPID-FIRE CLINICAL JUDGMENTS 317

318
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
overlap the null value (in this case it would be OR =1), but we already see that the p-value is less than 0.05, which indicates statistical significance. In this case, the patient has not developed any signs of renal abnormalities such as hematuria or proteinuria. The next best step is to monitor the patient’s blood pressure and urinalysis. In the event of elevated blood pressures, hematuria, or proteinuria, the patient should have his renal function assessed with a se­ rum creatinine level. The classic tetrad of HSP includes a rash (95%-100%), arthralgias (60%-80%), abdominal pain (60%-80%), and renal disease (20%-60%) that can be pre­ ceded by an upper respiratory infection in approximately 50% of cases. In the majority of cases, HSP is a self-limited condition and treatment is aimed at supportive care and pain management. The use of glucocorticoids is contro­ versial, but it has been used for severe GI, joint, or scro­ tal disease. There is no definitive evidence to support the use of glucocorticoids to prevent renal disease, and it is not recommended. However, in this case, the patient is using glucocorticoids for another purpose, and it is important to learn how to apply biostatistical concepts into patient man­ agement. In the majority ofpatients with mild nephropathy secondary to HSP, a renal biopsy is usually unnecessary un­ less there is severe renal disease or the diagnosis is in ques­ tion. However, a skin biopsy, which is less invasive than a renal biopsy, is an alternative in confirming the diagnosis of HSP. Patients with mild nephropathy should be monitored closely for impaired renal function and elevated blood pressures (keep in mind that patients with 21-hydroxylase deficiency are usually hypotensive).
15) 65 y.o. man presents to the office with headache, am­ aurosis fitgax, and vertigo. The patient states that he has intense itching after taking a shower, particularly with warm water. On exam, there is a ruddy complex­ ion of the face, hepatomegaly, splenomegaly, and the patient is hypertensive. The medical resident performs a workup of the patient and significant findings include WBC (15,000/mm3), Hb (20 g/dL), Hct (60%), plate­ lets (550,000/mm3), Sa02 (98%), red cell distribution width (RDW) of 18% (normal\: 11.5-13.5), red cell mass of 50 mL/kg (normal in males\: 20-36 mL/kg), normal RBC morphology, and erythropoietin (EPO) level of 1 mU/mL (normal\: 0-20). What is (1) the most likely diagnosis (2) the cornerstone of therapy, and (3) what would you recommend for his pruritus-related shower concerns?
The diagnosis is polycythemia vera (PV). The cornerstone oftherapy is serial phlebotomy to reduce the blood viscosity and maintaining a hematocrit below 45% in men and 42% in women. Although phlebotomy induces a relative state of iron deficiency, it is not recommended to give patients iron supplements because it can accelerate red cell mass produc­ tion (ie, “adding fuel to the fire”). Adjunctive therapies may include hydroxyurea (for myelosuppression), anagrelide (to reduce platelet counts), and allopurinol (for gout). In addition, low-dose aspirin (ifno contraindications exist)
is typically given to all patients to reduce the risk of blood clots, and aspirin is particularly helpful in patients with erythromelalgia. The intense itching after showering or bathing without visible skin changes is referred to as aqua- genic pruritus. Initially, treatment of aquagenic pruritus may consist of reducing the temperature of the water and afterward gently patting the skin dry with a towel rather than rubbing the skin. In addition, patients may attempt to use an antihistamine to relieve their symptoms. PV involves the clonal proliferation of myeloid cells, which can affect the red blood cells, granulocytes, and platelets. Because there can be such a high turnover of hematopoietic cells, there may be an increase in uric acid, which can cause secondary gout or uric acid stones. One of the hallmark features of PV is the hyperviscosity of the blood, which can be deleterious to the body, and it makes sense that the EPO levels would be low to avoid further erythropoiesis. Clinical manifestations may relate to the involved vessels of the body (eg, neuro­ logic, cardiac, mesenteric), and other findings that may be seen include systolic hypertension, thrombosis, bleeding, acquired von Willebrand disease, and erythromelalgia (ie, burning pain, erythema, and warmth in the hands or feet). Abnormal lab findings (other than described above) in­ clude an elevated leukocyte alkaline phosphatase, elevated serum B12, elevated uric acid, iron deficiency secondary to bleeding, and the presence of JAK2 mutations. In this case, it should be mentioned that the elevated RDW is due to iron deficiency secondary to an occult bleeding and that the Sa02 demonstrates the absence of hypoxia that could have been a possible cause of erythrocytosis.
16) 65 y.o. white woman presents to the office for a routine checkup. The patient is asymptomatic, and the physi­ cal examination is completely normal. The patient is a smoker and is trying to quit with the help of the resident physician. The patient relays her concerns about a fam­ ily history of abdominal aortic aneurysms (AAA). The patient turned 65 years old last week and is now covered under the Medicare program, which allows a onetime ul­ trasound for patients with a family history of AAA. The ultrasound reveals a 3.2 cm abdominal aneurysm. What is the next best step, and what is the single most impor­ tant modifiable risk factor for AAA?
The next best step is for the patient to come back in 6 months for another ultrasound to assess for aortic expan­ sion. The most important modifiable risk factor for AAA is smoking cessation, which the patient is already doing with her treating physician. In most adults, the abdomi­ nal aorta is approximately 2.0 cm, and AAA is diagnosed when the aorta is >3.0 cm. Risk factors for AAA include smoking, advancing age, atherosclerosis, white race, fam­ ily history, presence of peripheral aneurysms, hyperten­ sion, and male gender. It should be noted that AAA is more prevalent in men, but the risk of rupture is higher in women compared to men of the same aortic diameter. The USPSTF recommends a one-time screening for AAA by ul­ trasound in men aged 65 to 75 who have ever smoked and

actually recommends against routine screening for AAA in women. However, other organizations include women that are at risk (eg, smoker, family history, >65 years old) and, in fact, Medicare Part B actually covers a onetime ultrasound for women and men who have a family history of AAA. Clinical features of AAA may include any of the follow­ ing\: asymptomatic, pain (back, flank, abdominal, pelvic, or groin), nausea, vomiting, pulsatile abdominal mass, flank ecchymosis (Grey Turner sign), periumbilical ecchymosis (Cullen sign), limb ischemia, AMS, hypotension, tachycar­ dia, cyanosis, mottling. Asymptomatic patients with AAA diameter <5.5 cm can be managed with risk modification, periodic clinical exams, and AAA surveillance. It should be noted that there is no standardized AAA surveillance schedule, but patients typically have annual imaging for aneurysms <4.5 cm or at more frequent intervals (eg, ev­ ery 6 months) for those at higher risk (eg, rapid expansion, women, aneurysms >4.5 cm). In this case, the patient is a woman, which places her at a higher risk for rupture, and because it is her first ultrasound, we want to assess the ex­ pansion rate in 6 months or even in 3 months rather than a year. The decision to pursue elective AAA repair for as­ ymptomatic AAA is based on the risk of the aneurysm to rupture, which is typically an AAA diameter of >5.5 cm and a rapidly expanding AAA. However, elective repair is also based on advanced comorbidities, advanced age, pres­ ence of PAD, and gender. An immediate surgical repair (emergent AAA repair) is performed on patients with a ruptured AAA. Features to look for are any combination of hemodynamically unstable (eg, hypotensive, tachycardic), back/flank pain, pulsatile mass, AMS, skin mottling, Cullen sign, or Grey Turner sign. The decision to pursue an urgent repair (within 24 hours) in a patient that is symptomatic (attributable to the AAA), hemodynamically stable, has an unruptured AAA, and irrespective of the aneurysm size presents more of a challenge. There is no clear-cut answer, and the clinical management is usually individualized. In one circumstance, the patient may benefit from an urgent AAA repair, but in another circumstance, the patient may benefit from preoperative optimization (eg, beta-blockers in the setting of hypertension). Notable figures who have died from AAA include Albert Einstein, Lucille Ball, and George C. Scott.
17) 35 y.o. woman presents to the office with nausea, vom­ iting, visual disturbances, and headaches. The headache is located over the right parietal region and is described as “throbbing” throughout the day. The headaches are aggravated by bending forward, and there is minimal re­ lief with NSAlDs. The headaches do not seem to bother her at night, and there are no early morning awaken­ ings secondary to the headache. The patient states that she hears a “rush of water” in her right ear intermit­ tently during the daytime and says that she is not sure if it is associated with her headaches. The visual changes include double vision, sees “flashes of light,” bilateral dimness in vision for approximately 20 seconds after standing up, and has pain behind the right eye. Initial
vital signs include a temperature of 37°C (98.6°F), pulse 78 bpm, respiration 16/min, blood pressure 138/88, height 152.4 cm (60.0 inches), weight 79.4 kg (175 lb), and BMI 34.2 kg/m2. On exam, the right eye is turned medi­ ally (esotropia) and the left eye is in the normal position on forward gaze. Upon horizontal gaze to the patient’s right side, there is limited abduction of the right eye and normal adduction ofthe left eye. Visual field loss is noted in both eyes, and the visual acuity testing demonstrates 20/70 OD (right eye) and 20/50 OS (left eye). On fiindu- scopic exam, bilateral papilledema is seen. The medical resident orders labs (eg, CBC, BMP, ESR, ANA, anti- dsDNA, PT/INR, PTT, Lyme disease serology, and serum iron) and a head MRI with gadolinium. No significant findings are seen on imaging or lab workup. The resident decides to order a lumbar puncture (LP) with CSF stud­ ies, and the findings demonstrate a glucose of 50 mg/dL (nl\: 40-70), protein of 20 mg/dL (nl\: < 40), chloride of 120 mEq/L (nl\: 118-132), opening pressure of 285 mm H20 (nl\: 70-180), zero cell count (nl\: 0-5/mm3), no atypical cells on cytology, negative VDRL, and no growth on bac­ terial culture. What is the most likely diagnosis, and what is the best initial treatment management for this patient?
The diagnosis is idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri or benign intracranial hypertension. The initial treatment management should in­ clude weight reduction and the carbonic anhydrase inhibi­ tor acetazolamide to lower the CSF pressure. In this case, the patient is obese (BMI 34.2 kg/m2), and weight loss would serve 3 purposes\: (1) it may alleviate the symptoms of IIH; (2) the patient has prehypertension; and (3) the health ben­ efits of losing weight. Patients that continue to have persis­ tent headaches or progressive visual loss despite maximum medical treatment may consider surgical intervention. Optic nerve sheath fenestration and CSF shunting (eg, ven­ triculoperitoneal or lumboperitoneal shunt) are the main surgical procedures for IIH. Although IIH is idiopathic in nature, the strongest associations with this disease are the use of retinoids, tetracycline derivatives, growth hormone, and being an obese woman of childbearing age. The clinical features of IIH include visual abnormalities (eg, photopsia, papilledema, sixth cranial nerve palsy secondary to T ICP on the abducens nerve, diplopia secondary to sixth cranial nerve palsy, transient visual obscurations, visual field loss, reduced visual acuity secondary to papilledema, retrobulbar pain), pulsatile tinnitus (“rush of water” sound), and head­ aches. The headaches in IIH are usually nonspecific and can vary from patient to patient. However, increasing intratho- racic pressure such as bending forward, Valsalva maneuver, coughing, or sneezing can sometimes worsen the headache by increasing the intracranial pressure (ICP). In this case, the patient has a unilateral abducens nerve palsy of the right eye. The inward deviation of the right eye is due to the loss of normal resting tone in the right lateral rectus muscle, and this condition might have contributed to the worsen­ ing of her visual acuity on the right eye compared to her left eye. Also, there is limited abduction of the right eye on
APPENDIX B RAPID-FIRE CLINICAL JUDGMENTS 319

320
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
horizontal gaze secondary to paresis of the right lateral rec­ tus muscle. IIH is a diagnosis of exclusion, and in this case, all labs and neuroimaging were normal. To avoid a cerebral herniation, an intracranial mass was ruled out on neuro­ imaging prior to an LP. IIH will typically present with an elevated opening pressure on LP with normal CSF composi­ tion. Keep in mind that the opening pressure should be read with the patient in the lateral decubitus position to prevent a falsely elevated pressure reading that can occur if the patient is in the sitting position.
18) 20 y.o. man presents to the office complaining of a sore throat, rash, fatigue, fever, and nausea for the past 5 days. The medical resident performs a good physical examination and reveals bilateral upper eyelid edema, pharyngeal inflammation with tonsillar exudates, pala­ tal petechiae, bilateral posterior cervical lymphadenopa- thy, generalized maculopapular rash, and splenomegaly. The resident orders labs, and significant findings reveal a WBC of 15,000/mm3 (nl\: 4500-11,000), platelets of 145,000/mm3 (nl\: 150,000-400,000), lymphocytes of 75% (nl\: 25%-33%), ALT of 60 U/L (nl\: 10-40), AST of 70 U/L (nl\: 15-40), presence of atypical lymphocytes on periph­ eral blood smear, and a negative result on the heterophile antibody screen (“Monospot” test). The resident makes a diagnosis of infectious mononucleosis (IM) and recom­ mends supportive care that includes rest and analgesia (eg, NSAIDs, acetaminophen). A follow-up appointment is scheduled in 2 weeks to reassess the patient and repeat the Monospot test. The patient is concerned because he is a college wrestler and he is competing in the Division 1 Collegiate Wrestling Championships next week. The medical resident strongly recommends against compet­ ing in the tournament and any other contact sports for 4 weeks. The patient ignores the resident’s advice and competes the following week. During the tournament, the patient is injured. He is rushed to a nearby university hospital and is complaining of severe left shoulder pain that is worse upon inspiration in the ambulance. Vital signs include blood pressure 98/63, pulse 106, and res­ piration 14/min. No external hemorrhage is observed, and the patient continues to be tachycardic despite a fluid challenge. The bedside ultrasound or Focused Assessment with Sonography for Trauma (FAST exam) demonstrates intraperitoneal fluid in the splenorenal and splenodiaphragmatic recess. What is the most likely diagnosis, and what is the primary treatment option in this patient?
The diagnosis is a splenic rupture as a complication from IM. Since the patient is hemodynamically unstable and in­ traperitoneal fluid is seen on the FAST exam, the patient needs an emergent exploratory laparotomy. If findings on the FAST exam were equivocal, a diagnostic peritoneal as­ piration/lavage (DPA/DPL) could be performed to detect intraperitoneal blood. If the patient were hemodynamically stable, then there would be time for an abdominal CT scan with contrast. The CT scan can aid in the grading of the
splenic injury, and it may identify extravasation of the con­ trast. Once the splenic injury is graded, the patient may be observed, undergo splenic angiographic embolization, or go straight to surgery. Note that in this case the patients left shoulder pain is a referred pain (Kehr’s signs) second­ ary to the irritation of the phrenic nerve from blood that is located under the left hemidiaphragm. The patients IM is due to the Epstein-Barr virus (EBV), which is part of the herpes virus family. The primary mode of transmission of EBV is through saliva (“kissing disease”). Clinical features of IM (other than described above) include hepatomegaly, hepatitis, myocarditis, cranial nerve palsies, enlarged ton­ sils (“kissing tonsils”), pharyngitis (exudative or nonexu­ dative), Guillain-Barre syndrome, meningoencephalitis, aplastic anemia, hemolytic anemia, tender lymphadenopa- thy (posterior cervical chains > anterior cervical chains), transverse myelitis, optic neuritis, peripheral neuritis, and aseptic meningitis. Note that the viral rash of EBV in this case is not the same as the drug-induced rash (ie, from ad­ ministration of ampicillin or amoxicillin) during an IM infection. However, both types of rashes are clues to an EBV infection, and it should be mentioned that the drug- induced rash of IM does not represent a true drug allergy. If this patient had waited until at least the third week of ill­ ness, the splenic rupture probably would not have occurred since the spleen usually returns to near normal size within 3 weeks of the illness. Expected abnormal lab findings in­ clude leukocytosis, lymphocytosis, >10% atypical lympho­ cytes on peripheral smear, mild thrombocytopenia, mild elevation of transaminases, and positive for heterophile antibodies. Keep in mind that the false negative rates for heterophile antibody test (Monospot test) is highest early in the course of the disease, and it may take until the second or third week of the illness for the heterophile antibody re­ sponse to become positive or reactive to the Monospot test. In this case, a repeat Monospot test was recommended for the patient in 2 weeks, and it is very acceptable to repeat the test in a patient who has the clinical manifestations of IM but a negative Monospot test. Treatment of IM is mainly supportive, and it is recommended to avoid contact sports for 4 weeks, which is when the spleen should have receded. The routine use of corticosteroids is not recommended but can be given to patients with impending airway obstruction secondary to enlarged tonsils, persistent severe disease, se­ vere thrombocytopenia, autoimmune hemolytic anemia, and aplastic anemia.
19) 22y.o.womanpresentstotheofficewithlowerabdomi­ nal pain and fishy vaginal odor, particularly after sexu­ al intercourse, for the past week. The patient rates her abdominal pain as 6/10 in severity. The patient denies fevers, chills, nausea, vomiting, or diarrhea. On pelvic examination, there is cervical motion tenderness and adnexal tenderness on the right side without a palpa­ ble mass. On speculum exam, there is gray-white dis­ charge on the vaginal walls. The ob-gyn resident orders labs that include a qualitative urine (5-HCG (negative result), WBC of 9,000/mm3 (nl\: 4500-11,000), ESR of

82 mm/h (nl\: 0-20), urinalysis (within normal limits), vaginal pH of 6.2 (nl\: 3.8-4.5), wet mount of vaginal se­ cretions (presence of clue cells detected and >10 WBC/ high-power field), positive whiff test (aminelike odor upon KOH), VDRL (nonreactive), HIV rapid antibody test (none detected). Gram stain of the cervix (no gram­ negative intracellular diplococci detected), Chlamydia culture of the cervix (pending), and Gonococcal culture of the cervix (pending). The ob-gyn resident prescribes IM ceftriaxone (single dose) + PO doxycyciine (14-day course) + PO metronidazole (14-day course) and a follow-up visit to the office in 3 days. The patient returns to the office with minimal improvement, rating her abdominal pain as 5/10 in severity. The ob-gyn resident performs a transvaginal ultrasound that demonstrates a fluid-filled tube along with a complex adnexal mass on the right side. Further delineation of the mass reveals a thickened wall, fluid-containing mass, multiple inter­ nal echoes, and a size of 2.6 cm in diameter. What is the (1) diagnosis, (2) disposition of the patient, and (3) treatment management?
The diagnosis is a tubo-ovarian abscess (TOA) as a com­ plication from pelvic inflammatory disease (PID). The dis­ position of the patient is to admit her to the hospital for further treatment. The majority of small TOAs (<9 cm in diameter) will resolve with antibiotics alone, but the initial antibiotic regimen should have broad coverage since TOAs are typically polymicrobial. There are 3 first-line inpatient antibiotic options that could be used to treat PID with TOAs and PID alone. The following options are based on the CDC recommendations, which include (1) IV cefoxi­ tin + IV doxycyciine; (2) IV cefotetan + IV doxycyciine; or (3) IV clindamycin + IV gentamicin. Direct inpatient observation is recommended to see if the patient is clini­ cally improving or worsening and to assess if the mass is enlarging (via imaging) or there are signs of a rupture TOA (eg, sepsis, acute abdomen). Patients with TOAs that do not respond to parenteral antibiotics after 48 to 72 hours require percutaneous drainage or surgery (laparoscopic or open). However, patients with TOAs that do respond to parenteral antibiotics can transition to oral therapy after 24 hours of sustained clinical improvement. Oral therapy should include PO clindamycin or PO metronidazole for anaerobic coverage plus PO doxycyciine for a total of 14 days of antibiotic therapy. In addition to treating the patient, male sexual partners of women with PID should be evaluated and treated if they had sexual contact with the patient during the 60 days prior to the patients onset of symptoms. In this case, there were several deviations from the classic presentation. First, the patient presented with bacterial vaginosis, which can be associated with PID. Second, the patient did not present with fever, which may only be seen in approximately 50% of patients with PID. Third, most patients with TOA will have leukocytosis, but not all patients. Finally, the patient did not present with an acute onset (eg, 2-day history of symptoms) that is typi­ cally seen in acute PID alone, but it may not be an unusual
presentation in PID with a complicating TOA. Also, note that the ob-gyn resident was unable to palpate an adnexal mass on the right side, which is not uncommon if the TOA is small. When you work up a patient with suspected PID, always remember to obtain a pregnancy test. Keep in mind that there is no single test that is highly sensitive or specific for PID. However, abnormal findings of PID may include T ESR, T CRP, T WBCs on wet mount (vaginal secretions), ± leukocytosis, T CA-125, leukocytes on urinalysis (sec­ ondary to pelvic inflammation). The decision to treat PID is based on the principle of having a high index of suspicion for PID with a low threshold to initiate treatment in order to minimize the long-term sequelae of untreated or delayed treatment. The CDC recommends that empiric therapy of PID should begin in sexually active women and those at risk of STDs in the presence of lower abdominal or pelvic pain plus >1 of the following\: cervical motion tenderness, adnexal tenderness, or uterine tenderness. There are 3 first- line outpatient antibiotic options for PID. The following options are based on the CDC recommendations, which include (1) IM ceftriaxone (single dose) + PO doxycyciine (14 days) ± PO metronidazole (14 days); (2) IM cefoxitin (single dose) + PO probenecid (single dose; probenecid prolongs cephalosporin serum levels) + PO doxycyciine (14 days) ± PO metronidazole (14 days); or (3) IM cefo­ taxime or ceftizoxime (single dose) + PO doxycyciine (14 days) ± PO metronidazole (14 days). Note that metro­ nidazole can be added to any of the regimens if anaerobic organisms or bacterial vaginosis is suspected, as in this case. Once antibiotic therapy (oral or parenteral) is initiated, the patient should have significant clinical improvement within 72 hours. If a patient with PID does not respond to outpatient therapy, the patient should be admitted to the hospital for further management. The CDC recommends that admission to the hospital should be considered in pregnancy, TOAs, failure to respond to outpatient therapy, poor oral intake, noncompliance, severe illness (high fever, nausea, vomiting, intractable abdominal pain), or surgical emergencies that cannot be excluded (eg, appendicitis). If a patient with PID does not respond to inpatient therapy, additional diagnostic tests (eg, CT with contrast, diagnostic laparoscopy) and surgical intervention may be required. It should be noted that patients with PID may also be intra­ uterine device (IUD) users. Although IUD insertion poses a PID risk within the first 3 weeks of insertion, the CDC advises that there is insufficient evidence to recommend removal of IUDs in women diagnosed with acute PID, but close follow-up is mandatory if an IUD is left in place.
20) 62 y.o. white man presents to the ED with palpitations, dizziness, and fatigue. The patient is not sure when the symptoms started, but he believes that it has been 2 or 3 days. The patient states that he has never had palpitations before and is concerned about his heart. Past medical history includes asthma that is controlled with albuterol and hypertension that is controlled with benazepril. The patient denies any history of prior stroke. Vital signs include a temperature of 37°C (98.6°F), pulse 145 bpm.
APPENDIX B RAPID-FIRE CLINICAL JUDGMENTS 321

322
CLINICAL JUDGMENT USMLE STEP 3 REVIEW
blood pressure 140/82, and respiration 18/min. Physi­ cal exam reveals an irregularly irregular pulse, and aus­ cultation of the heart demonstrates an irregular rhythm with a rapid heartbeat. There is no JVD, carotid bruits, thyromegaly, wheezes, diminished breath sounds, hepa­ tomegaly, cyanosis, clubbing, or edema on exam. The resident physician orders the following STAT items\: IV access, pulse oximetry (96% oxygen saturation), con­ tinuous blood pressure (140/82), continuous cardiac monitor (irregular irregular rhythm, ventricular rate of 145 bpm), 12-lead EKG (no discrete P waves, chaotic f waves, irregular R-R intervals, atrial rate of 352 bpm, rapid ventricular response of 145 bpm, interpretation as atrial fibrillation). The resident orders a onetime bolus of IV diltiazem and waits 15 minutes to see if there is an adequate response. In the meantime the resident orders a CBC, electrolytes, BUN/creatinine, troponin-I, TSH, free T4, BNP, D-dimer, PT/INR, PTT, CXR, transtho­ racic echocardiography (TTE), and a toxicology screen. Fifteen minutes have passed, and the resident checks the cardiac monitor and reads an irregular irregular rhythm with a ventricular rate of 128 bpm. The resident decides to give one more bolus of IV diltiazem. Fifteen minutes later the cardiac monitor reads an irregular irregular rhythm with a ventricular rate of 98 bpm. The patient tells the resident physician, “I feel much better, doc.” Re­ sults of the labs and imaging are all within normal limits. What is your next step management in this patient with atrial fibrillation (AF)?
The patient is presenting with new-onset AF. The resi­ dent made the correct decision by initially controlling the ventricular rate to less than 110 bpm without necessarily converting to normal sinus rhythm. Conversion to sinus rhythm will eventually be addressed with cardioversion ± anticoagulation (depending on duration of AF). Acute rate control can be achieved by intravenous metoprolol, esmo- lol, diltiazem, or verapamil, which are all effective in slow­ ing the AV nodal conduction. Note that we used a calcium channel blocker (diltiazem) in this case instead of a beta- blocker because of his history of bronchospastic disease (asthma). In general, beta-blockers and calcium channel blockers should be avoided in patients with AV blocks and decompensated heart failure. Digoxin can also slow the AV nodal conduction, but it is not considered a first-line agent because it takes a longer time to achieve rate control. How­ ever, IV digoxin can be considered as the initial therapy for rate control in patients with significant hypotension or ad­ vanced heart failure. It should be noted that beta-blockers, calcium channel blockers, and digoxin should be avoided in patients with preexcited AF (eg, WPW syndrome) be­ cause these AV nodal blocking agents can actually encour­ age the conduction of impulses through the accessory pathway resulting in an increased ventricular rate and potentially ventricular fibrillation. Preexcited AF can be treated with IV procainamide in stable patients and syn­ chronized direct-current (DC) cardioversion in unstable patients. The next question that the resident has to consider
is the duration of the AF because there is an increased risk of embolization the longer the duration of AF. In this case, the patient was symptomatic for the past 48 to 72 hours, but there is no documented AF on EKG until he arrives in the ED, so he fits into the category of unknown duration. If AF is known to be greater than 48 hours or the AF is of unknown duration, then there are two options. The op­ tions include (1) TEE (look for atrial thrombus) + IV hepa­ rin (anticoagulation before cardioversion) + cardioversion (if no thrombus seen) + oral warfarin after cardioversion; (2) oralwarfarinfor4weeks(targetINRof2.5)+cardiover­ sion + oral warfarin after cardioversion for 4 weeks (target INR of 2.5). If AF is less than 48 hours, then there is a lower risk of embolization and it is acceptable to consider car­ dioversion by pharmacologic (eg, flecainide, propafenone, dofetilide, ibutilide) or electrical (direct-current) means. It should be noted that it can be difficult to determine the ac­ tual onset and duration of AF. However, keep in mind that if a patient is on the telemetry floor, the onset and duration of AF can easily be documented, but AF in the outpatient setting may prove to be more difficult to document unless a Holter monitor is used. The ACC/AHA/ESC guidelines recommend immediate synchronized DC cardioversion in patients with AF who do not respond promptly to a rapid ventricular response (RVR) with pharmacologic therapy and there is evidence of ongoing myocardial ischemia (eg, EKG evidence), chest pain (angina), heart failure, or symp­ tomatic hypotension. In addition, immediate DC cardio­ version can be performed in patients with preexcited AF who are hemodynamically unstable or in the presence of an extremely rapid ventricular rate secondary to an accessory bypass tract. DC cardioversion delivers electrical current in monophasic or biphasic waveforms that is synchronized to the QRS complex. An initial shock energy of 200 joules for monophasic devices or 120 to 200 joules for biphasic devices are recommended for AF. AF is characterized by rapid, disorganized electrical activity in the atria with unco­ ordinated atrial contraction. The ventricular response is al­ ways irregular, but the ventricular rate can be slow or rapid. A slow ventricular rate may be due to AV nodal disease, AV nodal blocking agents, or a long refractory period of the AV node (eg, aging, enhanced vagal parasympathetic tone, athlete). A rapid ventricular rate may be due to an acces­ sory bypass tract (preexcitation syndrome) or a shortened refractory period of the AV node (eg, sympathetic stimula­ tion, catecholamine excess). An easy way to estimate the ventricular rate is to count the number of QRS complexes in a 6-second EKG strip (ie, 30 big squares) and multiply by
10. AF is commonly associated with hypertension and cor­ onary artery disease. Other associated conditions include heart failure, rheumatic valvular disease, congenital heart disease, hyperthyroidism, heavy alcohol use, and cardiac surgery. There are several terms used to describe AF which include new onset (first detection of AF), paroxysmal (>2 episodes of AF that terminate within 7 days, typically <24 hours), persistent (AF >7 days that usually requires car­ dioversion), permanent (AF refractory to cardioversion),

and lone AF (absence of structural heart disease, typically <60 years old). The 3 essential elements to consider in AF management are (1) rate control, (2) rhythm control, and (3) anticoagulation to prevent a stroke. Once the patient re­ verts to sinus rhythm, the decision to undergo rate control or rhythm control for long-term management is addressed. It should be noted that either strategy (rate or rhythm con­ trol) results in similar overall mortality and morbidity. However, anticoagulation is still recommended with either strategy in patients at high risk for stroke. To determine the risk of stroke, the CHADS2 is a validated scoring system that has gained favor. Each letter in the CHADS2 (CHF,
HTN, Age >75 years old, Diabetes, Stroke) carries a single point except for stroke or TIA, which carries 2 points (ie, it is the strongest predictor of stroke). Patients with nonval- vular AF with a score of zero are considered low risk (no antithrombotic therapy necessary), those with a score of 1 are at intermediate risk (aspirin or oral anticoagulant ther­ apy recommended), and those with a score >2 are at rela­ tively high risk (oral anticoagulant therapy recommended).
Once you have read and understood the essence of each question in Appendix B, then you have sharpened your clinical judgment another sliver.
APPENDIX B RAPID-FIRE CLINICAL JUDGMENTS 323

Factoids
Factoids are another part ofyour armamentarium in conquer­ ing the Step 3 exam. The facts presented in this section will serve as building blocks to strengthen your knowledge base. Factoids should be viewed as another arsenal in your prepa­ ration because they will provide (1) “silver bullet” knowl­ edge (ie, ability to answer the question with 100% conviction
based on a fact); (2) improved deductive reasoning (ie, ability to eliminate wrong answers and make good educated choices based on facts); and (3) sharper analytical thinking on inference-type questions. The design of the following for­ mation is so that you will be able to absorb as many facts as possible without turning a page.
• Mini-Mental Status Exam (MMSE) has a total of 30 points. Cognitive im­ pairment is based on a score with <9 (severe), 10-20 (moderate), and >21 (mild). A score >24 is generally con­ sidered normal.
• Anion gap = Na - (Cl + HC03).
• High anion gap metabolic acidosis is MUDPILES (Methanol, Uremia, DKA, Propylene glycol, Isoniazid, Lactic acidosis, Ethylene glycol, Salicylates).
• Major depressive episode is >5 of the following symptoms (SIGECAPS + D) for 2 weeks that must include either depressed mood or loss of interest\: S-sleep changes, I-interest loss, G-guilt, E-energy loss, C-con- centration loss, A-appetite/weight changes, P-psychomotor agitation or retardation, S-suicide ideation + D- depressed mood most of the day.
• The following is the CDC recom­ mended immunization schedule (2014) for aged 0-18 years.
• Hepatitis A (2 doses)\: 12-23 months of age (2nd dose separated by 6-18 months).
• Hepatitis B (3 doses)\: Birth, 1-2 months, 6-18 months of age.
• MMR (2 doses)\: 12-15 months, 4-6 years of age.
• Varicella (2 doses)\: 12-15 months, 4-6 years of age.
• DTaP (5 doses)\: 2, 4, 6, 15-18 months, 4-6 years of age.
• Tdap (1 dose)\: 11-12 years of age.
• PCV (4 doses)\: 2, 4, 6, 12-15 months
ofage.
• Hib (3 or 4 doses depending on brand)\: 2,4, ±6,12-15 months of age.
• Phase 0 Clinical Trials\: Designed to evaluate the pharmacodynam­ ics (drug does to body) and phar­ macokinetics (body does to drug). Information is then used to refine the researchers’ study in the tradi­ tional phase 1 testing. Phase 0 stud­ ies usually recruit a small number of patients, has a short testing pe­ riod, and low dosages of the drug are given.
• Phase 1 Clinical Trials\: Evaluate the safety of the drug. Researchers learn how the drug should be given, deter­ mine a safe dosage range, and iden­ tify any side effects. Only a small number of patients are recruited.
• Phase 2 Clinical Trials\: Evaluate the effectiveness of the drug. Researchers continue to monitor side effects. A larger group of patients are recruited to the study.
325

326 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Apgar score performed at 1 and 5 min­ utes ofage and a score >7 points is gen­ erally considered normal, 4-6 is fairly low and requires dose attention, and a score 0-3 indicates a serious problem.
• Apgar stands for A-appearance/color, p-pulse, g-grimace/reflex response, a- activity/muscle tone, r-respiration/ lung maturity.
• Median survival is <1 month in untreat­ ed acute promyelocytic leukemia (APL).
• Hypovolemic shock\: 4 CO, t SVR, 4 PCWP.
• Cardiogenic shock\: 1 CO, t SVR, T pcwp.
• Distributive (vasodilatory) shock\:
t CO, 4 SVR, 4 or nl PCWP.
• Uncompensated metabolic acido­
sis\: 4 pH, 4 h C0 3“ (primary pro­ cess), nl pC02.
• Compensated metabolic acidosis\:
nl pH (ie, compensated), 4 HCO" 4 pC02 (ie, blowing off C02 through hyperventilation during compensation).
• Uncompensated respiratory acido­ sis\: 4 pH, t pC02 (primary process), nl HCO"
• Compensated respiratory acidosis\: nl pH (ie, compensated), T pC02, T HCO“ (ie, kidneys are reabsorbing more base during compensation).
• Uncompensated metabolic alka­ losis\: T pH, T HCOj (primary pro­
cess), nl pC02.
• Compensated metabolic alkalosis\: nl pH (ie, compensated), T HCO", T pC02 (ie, C02 is retained during compensation).
• Uncompensated respiratory alkalo­ sis\: TpH, 4pC02 (primary process), nl HCO'.
• Compensated respiratory alkalosis\: nl pH (ie, compensated), 4pC02, 4hCO“ (ie, kidneys excreting more base during compensation).
• In simple acid-base disorders, pC02 and HCOj will move in the same direction during compensation to re­ turn the pH to normal range.
• Mixed metabolic and respiratory acidosis\: 4 pH, t pC02,4 HCOj.
• Rotavirus (2 or 3 doses depending on brand)\: 2,4, ±6 months of age.
• IPV (4 doses)\: 2,4,6-18 months, 4-6 years of age.
• Meningococcal (1 dose + booster)\: Start at ages 11-12 years followed by a booster at age 16.
• HPV (3 doses)\: Start at ages 11-12 years. Second dose given 1-2 months after the first dose. Third dose given after 6 months from the first dose. Note that HPV2 vaccine protects from HPV types 16 and 18 and should be given to females only. The HPV4 vaccine protects from HPV types 6, 11, 16, and 18 and can be given to females and males.
• Influenza (annual)\: Ages6-23 months use only inactivated vaccine. Ages 2-18 years old can use inactivated or live attenuated vaccine.
• CDC recommends against the use of inactivated influenza vaccine (IIV) in patients with severe allergic reactions to egg.
• CDC recommends against the use of live attenuated influenza vaccine (LAIV) in patients with severe aller­ gic reactions to egg protein, gentami­ cin, gelatin, and arginine.
• LAIV should not be used concomi­ tantly with aspirin in children and adolescents.
• LAIV should not be used in pregnant women, children <2 years, adults >50 years, asthmatic patients, chil­ dren 2-4 years who had wheezing in the past 12 months, immunosup- pressed patients, and underlying medical conditions that would pre­ dispose patients to complications.
• Tanner Stage 1 (girls)\: Prepubertal; elevation of the papilla; no pubic hair.
• Tanner Stage 2 (girls)\: Breast bud stage; sparse pubic hair.
• Tanner Stage 3 (girls)\: Further en­ largement of breast and areola; pubic hair is darker, coarser, and curlier.
• Tanner Stage 4 (girls)\: Secondary mound formed above the level of the breast; adult hair covering most of the pubic region.
•
•
•
•
•
•
•
•
•
Phase 3 Clinical Trials\: Compare the efficacy and safety of the new treat­ ment with the current standard treat­ ment for that disease. Phase 3 stud­ ies usually include a large group of patients.
Phase 4 Clinical Trials\: Also referred to as postmarketing surveillance tri­ als. After the drug is approved and marketed, researchers will learn the effectiveness of the drug in various populations and identify unantici­ pated side effects that were not seen earlier in the clinical trials.
Patient Safety—A “time out” should occur prior to any surgical proce­ dure. During the time out, verifica­ tion ofthe correct patient, procedure, and site must be confirmed.
Glasgow coma scale (GCS)—Three domains that include eye opening (4 points is the best possible score re­ flecting spontaneous eye opening), verbal response (5 points is the best possible score reflecting oriented), and motor response (6 points is the best possible score reflecting obeys command).
GCS—The highest total score is 15 points and the lowest possible score is 3 points. A score >13 points reflects mild brain injury, a score 9 to 12 points reflects moderate brain injury, and a score <8 points reflects severe brain injury (ie, “less than 8 may be too late, so you better in­ tubate”).
Tanner Stage 1 (boys)\: Prepubertal; no pubic hair.
Tanner Stage 2 (boys)\: Enlargement of the scrotum and testes; scrotal skin reddens; sparse pubic hair.
Tanner Stage 3 (boys)\: Enlargement of the penis in length; further growth of the testes and scrotum; pubic hair is darker, coarser, and curlier.
Tanner Stage 4 (boys)\: The breadth of the penis enlarges; further growth of the testes and scrotum; scrotal skin becomes darker; adult hair covering most of the pubic region.

Mixed metabolic and respiratory alkalosis\: t pH, l pC02, THCOj.
Patient Safety—A sentinel event is an unanticipated outcome that may result in death or serious physical or psychological injury. Keep in mind that not all sentinel events are due to error because some diseases have a natural course of terminal illness that may not be the physician’s fault.
American mistletoe toxicity—Gas­ troenteritis.
Ginseng toxicity—Diarrhea, hyper­ tension, headache, nausea, insomnia.
Gingko toxicity—Headache, bleed­ ing, emesis.
Short stature is defined as a height that is >2 standard deviations (SD) below the mean for children of the same sex and age. The equivalent would be less than the third percen­ tile for height on the growth curve.
Constitutional delay of growth\: Variant of normal growth, normal size at birth, delay in height and weight velocity, resumes normal height and weight growth but may be at the lower growth percentiles or parallel to the third percentile, nor­ mal final height, normal TSH and T4, delayed skeletal age, delayed pu­ berty, timing of puberty dependent on bone age and not chronologic age, normal average height of the parents, family history of delayed growth or puberty is frequently present.
Familial short stature\: Variant of nor­ mal growth, normal size at birth, low- normal growth velocity throughout life, short final height, normal TSH and T4, bone age consistent with chrono­ logical age, normal puberty, normal onset of puberty since bone age is nor­ mal, short height of the parent(s).
Normal CSF\: Clear fluid, opening pressure 70-180 mmH20, glucose 40- 70 mg/dL, protein <40 mg/dL, cells 0-5/mm3 (lymphs).
Bacterial meningitis CSF\: Cloudy fluid, opening pressure >180 mm H20, glucose <40 mg/dL, protein >45 mg/dL, WBCs 10 pL-10,000 jiL (T neutrophils), Grams stain positive >60% of the time, culture positive >80% ofthe time.
• Tanner Stage 5 (girls)\: Mature ap­ pearing breast with recession of the areola; adult hair with extension onto thighs.
• Sequence of pubertal events in girls\: thelarche —» pubarche —> peak height velocity —> menarche.
• In a minority of girls, pubarche will be the first manifestation in pubertal maturation.
• The mean interval between the breast bud stage (Tanner Stage 2) and men­ arche is approximately 2.5 years.
• The mean age of onset of puberty is approximately 10.5 years of age in girls and 11.5 years of age in boys.
• Newborns will lose up to 10% of their birth weight in the first few days and then regain their weight in approximately 10 days.
• Approximate weight gain in babies is as follows\: 30 g/dy (for first 3 months of life) —» 20 g/dy (3 to 6 months of life) —> 10 g/dy (6 to 12 months oflife).
• Average weight gain from 2 years old to puberty is 2 kg/yr or 4.4 lbs/yr.
• To convert pounds (lbs.) to kilogram (kg), take the number in pounds and divide by 2.2.
• Birth weight should have doubled by 4 months of age and tripled by age 1.
• Cryptococcal meningitis CSF\: t opening pressure, normal to i glu­ cose, normal to T protein, T cell count (10-200 cells/mm3), mononuclear cell predominance (T lymphs), India ink preparation of CSF demonstrates a halo surrounding the encapsulated yeast, CSF cryptococcal antigen posi­ tive, Cryptococcus neoformans is a fungus and may present similarly to other fungal meningitides.
• Spina bifida occulta—Also referred to as closed spinal dysraphism; “oc­ culta” in Latin means hidden; mild­ est form of spina bifida; one or more vertebrae are malformed; meninges and spinal cord are normal and not exposed; dimpling of the skin or hairy patch may be seen at the site of the lesion.
• Tanner Stage 5 (boys)\: Adult size and shape of the genitalia; adult hair with extension onto thighs.
• Sequence of pubertal events in boys\:
testicular enlargement —» penile en­ largement —> pubarche —> peak height velocity.
• The peak height velocity (growth spurt) typically occurs 2 years earlier in girls than in boys.
• Nocturnal sperm emissions (wet dreams) are considered the male counterpart of menarche and typi­ cally occur shortly after peak height velocity.
• Precocious puberty occurs before the age of 8 in girls and 9 in boys.
• Delayed puberty is considered by age 13 in girls and 14 in boys.
• Drug Schedule I—Considered the most dangerous class of drugs, high abuse potential, no acceptable medi­ cal use, examples\: heroin, LSD, ecstasy (MDMA), mescaline, methaqualone, peyote, marijuana (certain states such as Colorado and Washington state al­ lows for medical marijuana use).
• Drug Schedule II—High abuse potential but less abuse potential compared to schedule I, accepted medical indications with severe restrictions, examples\: morphine, hy- dromorphone, oxycodone, codeine, fentanyl, methadone, meperidine, methamphetamine, methylphenidate, amphetamine, cocaine, pentobarbital.
• Drug Schedule III—Abuse poten­ tial less than schedule I and II, low to moderate potential for physical and psychological dependence, accepted medical indications, examples\: anabolic steroids, acetaminophen with codeine, acetaminophen with hydrocodone, ket­ amine, buprenorphine, dronabinol.
• Drug Schedule IV—Low potential for abuse, low risk for dependence, accepted medical indications, ex­ amples\: benzodiazepines, phenobar- bital, zolpidem, modafinil, pentazo­ cine, carisoprodol.
APPENDIX C FACTOIDS 327

328 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Viral meningitis CSF\: Clear fluid, normal to slightly elevated opening pressure, normal to slightly reduced glucose, normal to slightly elevated protein, WBC <500 cells/pL (mono­ nuclear cell predominance), some­ times polymorphonuclear (PMN) predominance within the first 48 hours, negative Grams stain, nega­ tive acid-fast, negative India ink.
• Aseptic meningitis refers to men­ ingeal inflammation not caused by pyogenic bacteria. The most common cause of aseptic meningitis is the en­ terovirus (eg, echovirus, coxsacki­ evirus, poliovirus). However, other viruses can still cause aseptic menin­ gitis (eg, HSV, HIV, EBV, CMV, VZV, mumps, measles, rubella) and other etiologic agents include bacteria (eg, Borrelia burgdorferi, Mycobacterium tuberculosis. Treponema pallidum), fungi (eg, Cryptococcus neoformans, Coccidioides immitis, Histoplasma capsulatum), parasite (eg, Toxoplasma gondii), malignancy (eg, leukemia, lymphoma, leptomeningeal cancer), systemic diseases (eg, SLE, sarcoid, Behcet’s disease), and drugs (eg, NSAIDs, TMP-SMX, IVIG, azathio- prine, vaccines).
• Milestone—fine motor (2 months)\: Holds hands together.
• Milestone—fine motor (4 months)\: Grasps rattle and brings to mouth.
• Milestone—fine motor (6 months)\: Transfers object from hand to hand.
• Milestone—fine motor (9 months)\: Pokes with forefinger, uses immature pincer grasp.
• Milestone—fine motor (12 months)\: Neatly picks up small objects with thumb and index finger (mature pin­ cer grasp).
• Milestone—fine motor (18 months)\: Makes 4 cube tower.
• Milestone—fine motor (2 years)\: Makes 6 cube tower, makes a “train” of cubes.
• Milestone—fine motor (3 years)\: Copies a circle.
• Milestone—fine motor (4 years)\: Copies a cross and square.
• Milestone—social (2 months)\: Smiles.
• Milestone—social (4 months)\: Vo­ calizes.
• Milestone—social (6 months)\: Strang­ er anxiety.
• Milestone—social (9 months)\: Sepa­ ration anxiety.
• DrugScheduleV—Least potential for abuse, preparations contain limited amounts of narcotics and stimu­ lants, accepted medical indications, examples\: antitussives (<200 mg of codeine), antidiarrheals (eg, diphenoxylate + atropine, difenoxin + atropine), pregabalin, decongestant (eg, propylhexedrine).
• Neurosyphilis CSF\: Reactive CSF- VDRL, f protein, lymphocytic CSF pleocytosis, ± CSF HIV genotype positive for the virus (keep in mind that patients at risk for syphilis are also at risk for HIV infection).
•
•
• • • •
•
• •
• •
•
•
TB meningitis CSF\: Cloudy fluid, opening pressure 180-300 mm H20, 4 glucose (usually <45 mg/dL), T pro­ tein (usually 100-500 mg/dL), mono­ nuclear cell predominance (T lymphs), but early in infection polymorphonu­ clear predominance (T neutrophils), CSF acid-fast stain positive.
Neoplastic CSF\: Positive CSF cytol­ ogy, 4 glucose, T protein, presence of mononuclear cells (<500 cells/mm3), negative Gram’s stain.
Milestone—gross motor (2 months)\:
Head up and chest up when lying prone.
Milestone—gross motor (4 months)\:
Holds head steady when held upright.
Milestone—gross motor (6 months)\:
Rolls over, sits with little to no support.
Milestone—gross motor (9 months)\:
Pulls to stand, crawls, gets into sitting position.
Milestone—gross motor (12 months)\:
Holds onto furniture when walking (“cruising”).
Milestone—gross motor (18 months)\:
Walks alone, may run well.
Milestone—gross motor (2 years)\:
Runs, dances, walks up and down stairs holding on, throws ball overhand.
Milestone—gross motor (3 years)\:
Pedals a tricycle, climbs well.
Milestone—gross motor (4 years)\:
Hops on one foot, stands on one foot for 2 seconds, catches a bounced ball.
Primary prevention—Prevents the disease from occurring (eg, immuni­ zations).
Secondary prevention—Early de­ tection of disease and treatment to stop progression of the disease (eg, routine Pap smears).
• Milestone—language
Coos.
• Milestone—language
Laughs.
• Milestone—language
Babbles.
• Milestone—language
(2 months)\:
(4 months)\:
(6 months)\:
(9 months)\:
Says mamma/dada (nonspecifically).
• Milestone—language (12 months)\:
Says mamma/dada (specifically), uses 1-2 true words.
• Milestone—language (18 months)\:
Says “no” a lot, names common ob­ jects.
• Milestone—language (2 years)\: Uses 2-word sentences, follows 2-step com­ mands.
• Milestone—language (3 years)\:
Uses 3-word sentences, plurals, and pronouns correctly (eg, I, me, you).
• Milestone—language (4 years)\: Tells stories, follows 3-step commands.
• Milestone—cognitive (2 months)\:
Recognizes parent.
• Milestone—cognitive (4 months)\:
Enjoys looking around.
• Milestone—cognitive (6 months)\:
Shows curiosity.
• Milestone—cognitive (9 months)\:
Waves bye-bye, plays pat-a-cake, plays peek-a-boo.

Root reflex—Stroking the baby’s cheek causes the baby to turn toward the stimulus and opens the mouth. Present at birth, and disappears by 3-6 months.
Sutures—Basic concepts in sutures include\: (1) Absorbable vs. Non­ absorbable\: Absorbable sutures typically lose their tensile strength in <60 days, but nonabsorbable su­ tures retain their tensile strength for at least 60 days. (2) Diam­ eter of the sutures is graded by the number of zeros (eg, 1-0, 2-0, 3-0, 4-0, 5-0, 6-0, 7-0, 8-0, 9-0, 10-0). There is an inverse relationship be­ tween the number of zeros and suture diameter plus suture strength. For example, a 10-0 suture has a high number of zeros, but a smaller diam­ eter and low suture strength, while a 1-0 suture has a low number of zeros, but a large diameter and high suture strength (think of the Golden Gate Bridge with an increase in the num­ ber of parallel wires in each of the main cables that increases the cable diameter). (3) Monofilament vs. Multifilament (eg, braided, twisted). Monofilament is more resistant to harboring bacteria and therefore less prone to infection. Multifilament is susceptible to harboring bacteria between the strands and therefore are more prone to infection. Multi­
filament sutures are easier to handle and provide greater knot security compared to monofilament sutures. (4) Tissue reactivity to the sutures is commonly seen in chromic gut, plain gut, and silk sutures. However, suture materials made of polydioxanone, polyglyconate, and polypropylene have the least tissue reactivity. (5) Location of the sutures\: Absorb­ able sutures are typically used for deeper structures such as the fascia. Nonabsorbable sutures are typically used for the outermost layer in which the sutures can be removed. Smaller caliber sutures (eg, 5-0, 6-0) are used for delicate tissues (eg, face, digits), larger caliber sutures (eg, 2-0, 3-0) are used for closure of deeper tissues, and tissues on the scalp, extremity, and torso are typically sutured with a 3-0 or 4-0 suture.
• Milestone—social (12 months)\: Imi­ tates actions or sounds to get attention.
• Milestone—social(18months)\: Plays in company with other children.
• Milestone—social (2 years)\: Parallel play.
• Milestone—social (3 years)\: Imagi­ native play, shares toys.
• Milestone—social (4 years)\: Coop­ erative or group play.
• Tertiary prevention—Reduce com­ plications of disease (eg, diabetic pa­ tients require glycemic control, foot and eye checkups, urine microalbu­ min test, lipid control, HTN control, i smoking, aspirin, vaccinations).
• Plantar grasp—Placing a finger in the baby’s palms causes the baby to grip the finger. Present at birth, and disappears by 9 months.
• Nonabsorbable sutures—Nylon, silk, polypropylene (Prolene), polyester (Mersilene), polybutester (Novafil).
• Absorbable sutures—Plain gut, chro­ mic gut, polydioxanone (PDS), poly­ glyconate (Maxon), polyglactin (Vicryl), polyglycolic acid (Dexon), poliglecaprone (Monocryl).
• Lead time bias is the bias that survival rates may be increased by a screening test when in fact the disease course is not altered by earlier detection. Pa­ tients do not necessarily live longer, but rather the perception of increased survival from the time of diagnosis. Researchers should avoid lead-time bias by comparing age-specific mor­ tality rates instead of survival rates.
• Length time bias is the bias that out­ comes appear better than the actual prognosis and is often discussed in the context of screening. For exam­ ple, most slow-growing tumors will be detected by screening, and those slow-growing tumors inherently have a better prognosis. However, faster-growing tumors may prompt patients to seek medical care because of symptoms and be diagnosed with­ out screening. As a result, screening appears to be more effective com­ pared to no screening.
• Milestone—cognitive (12 months)\: Copies gestures.
• Milestone—cognitive (18 months)\: Points to at least one body part.
• Milestone—cognitive (2 years)\: Sorts objects by color and shape.
• Milestone—cognitive (3 years)\: Kn­ ows own gender, age, and name; dresses and undresses self.
• Milestone—cognitive(4years)\:Sings a song from memory, draws a 4-part person, starting to count.
• Moro reflex (startle reflex)—A sudden, slight dropping of the head from a slightly raised supine posi­ tion causes the baby to open the palms of the hand and extension and abduction of the arms, followed by flexion and sometimes crying. Present at birth, and disappears by 3-6 months.
• Receiver operating characteristic (ROC) curve is a graphical illustra­ tion of the relationship between the sensitivity (ie, true positive rate) along the vertical axis (y-axis) and 1-specificity (ie, false positive rate) along the horizontal axis (x-axis). The ROC curve allows you to iden­ tify a cutoff value that would mini­ mize the false negatives and false positives. As you move from left to right on the ROC curve, the sensi­ tivity increases while the specificity decreases. Ideally, you would want a test that would give a near 100% sen­ sitivity and 100% specificity, which would reflect a curve closest to the far upper-left corner. On the board exam, there may be 2 or 3 curves on the graph that reflect 2 or 3 tests (eg, screening test). The curve that lies
near the far upper-left corner will usually prove to be the superior test of them all. The area under the ROC curve represents the accuracy of the test. A near perfect test is seen when the area under the curve approaches one.
APPENDIX C FACTOIDS 329

330 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Placenta accreta—Placenta attaches to the myometrium; think of Ac­ creta-Attachment; prior C-sections increases the risk of placenta ac­ creta; placenta previa after a prior C- section increase the risk of placenta accreta; consider placenta accreta in the setting of overt hemorrhage at the time of manual placental separation.
• Placenta increta—Placenta invades into the myometrium; think of Increta-Invades Internally.
• Placenta percreta—Placenta pen­ etrates through the myometrium to the uterine serosa; think of Percreta- Penetrates Powerfully; placenta accre­ ta (most common) > placenta increta > placenta percreta (least common).
• Placenta previa—Placenta is implant­ ed over or very near to the internal cervical os; think of Previa-Previous (in other words, the placenta is lying previous or in front of the internal cervical os, which is the gateway to the outside world); painless vaginal bleeding usually beyond 20 weeks gestation; risk factors include prior C- sections, multifetal gestations, multi­ parity, advanced maternal age, prior placenta previa, prior abortions, prior uterine surgery, infertility treatment, smoking, and cocaine; complete pla­ centa previa (placenta completely covers the internal os); partial pla­ centa previa (placenta partially cov­ ers the internal os); marginal placenta previa (placenta is at the margin of the internal os, but does not cover it); low-lying placenta (placenta is in close proximity to the internal os).
• Normal sequential primary tooth eruption\: lower (mandibular) central
• Enuresis—Repeated voiding of urine in an individual >5 years of age that may be involuntary or intentional and can occur during the night, day, or both. Enuresis occurs at least 2 times/wk for at least 3 consecutive months or in the presence of signifi­ cant distress or the disturbance im­ pairs functioning in important areas (eg, work, school, relationships). Enuresis is usually a self-limiting condition and children will typically be continent by adolescence. There are no significant changes from DSM-IV to DSM-5.
• Velamentous umbilical cord inser­ tion—Umbilical cord inserts into the fetal membranes (chorioamniotic membranes) rather than the placenta mass. Remember that the umbili­ cal cord has vessels and these vessels will continue to travel haphazardly through the chorioamniotic mem­ branes to the placenta. The reason why the vessels are running haphaz­ ardly is that they are vulnerable to rupture since they are unprotected from Whartons jelly. Whartons jelly is a gelatinous substance that is nor­ mally found in the umbilical cord, and it serves to protect the umbili­ cal vessels. Think of velamentous umbilical cord insertion as a defec­ tive insertion (ie, the umbilical cord should normally extend to the cho­ rionic plate) with exposed umbili­ cal vessels running from the end of the umbilical cord to eventually the placenta. The length of exposed um­ bilical vessels can be highly variable.
• Vasa previa—Fetal vessels crossing over the internal cervical os; think of Vasa Previa-Vessel Previous (in other words, vasa, which means ves­ sel in Latin, lies previous or in front of the internal cervical os, which is the gateway to the outside world); vasa previa may be associated with velamentous umbilical cord insertion or vessels that cross between lobes of the placenta (eg, bilobate placenta, succenturiate placenta); consider rupture of the vessels secondary to digital manipulation, artificial rup­ ture, or descent of the fetal head compressing the vessels during labor.
• Encopresis—Repeated fecal incon­ tinence in an individual >4 years of age that may be involuntary or intentional and may occur with constipation and overflow inconti­ nence or without constipation and overflow incontinence. Encopresis occurs at least 1 time/mo for at least 3 months. In the majority of cases, encopresis is usually a self-limiting condition, but intermittent exacer­ bations may persist for years. There are no significant changes from DSM-IV to DSM-5.
• Asymmetric tonic neck reflex— Rotating the baby’s head to one side causes extension of the arm and leg on the side to which the head is turned and at the same time flex­ ion of the arm on the opposite side, which gives the baby a fencing pos­ ture. Present at birth, and disappears by 4-9 months.
• Placenta abruption (abruptio pla­ centae)—An abruption at the decid­ ual-placental interface; consider pla­ centa abruption in patients beyond 20 weeks gestation; acute abruption may present with an acute onset of vaginal bleeding, back pain, abdomi­ nal pain, uterine contractions, uter­ ine tenderness, and a nonreassuring FHR pattern; chronic abruption may present with intermittent bleeding, retroplacental hematoma, IUGR, oligohydramnios, or preeclampsia; risk factors for placenta abruption include multifetal gestations, mul­ tiparity, advanced maternal age, prior abruption, smoking, cocaine, abdominal trauma, chronic hyper­ tension, preeclampsia, eclampsia, PROM, polyhydramnios, and low birth weight; DIC may be a complica­ tion of placental abruption, but DIC may also be seen in other pregnancy- related complications (eg, uterine rupture, placenta previa, placenta accreta, eclampsia, severe preeclamp­ sia, HELLP syndrome, septic abor­ tion, amniotic fluid embolism).
upper (maxillary) central lateral incisors —»first mo­
incisors
incisors
lars—>canines secondmolars.
• Patient Safety—Use appropriate an­ tibiotic prophylaxis to reduce surgi­ cal site infections.
• Ultraviolet B (UVB) radiation (280 to 320 nm) has a shorter wavelength compared to UVA radiation. UVB radiation damages the skin’s superfi­ cial epidermal layers. UVB radiation has a principal role in skin cancer but a contributory role in photoaging.

Ultraviolet A (UVA) radiation has a longer wavelength compared to UVB radiation. UVA radiation can be di­ vided into long-wavelength UVA1 (340 to 400 nm) and short-wavelength UVA2 (320 to 340 nm). UVA radia­ tion is able to penetrate deeper into the skin affecting the dermis. An easy way to remember that UVA goes deeper into the skin than UVB is that “UVA gets an A+ while UVB gets a B for penetration.” UVA radiation appears to be the principal player in the photo­ aging process, but it may still contrib­ ute to and initiate the development of skin cancers.
Sunburns are principally caused by UVB radiation, but UVA2 can also cause sunburns.
Psoralen plus UVA therapy (PUVA) used to treat skin disorders such as psoriasis can increase the risk of de­ veloping melanoma and nonmela­ noma skin cancer, particularly SCC.
Tanning beds, which primarily emit UVA radiation, have been implicated in increasing the risk of cutaneous SCC, BCC, and melanoma.
Lipoxygenase pathway\: Membrane phospholipids —> Enzyme phospho­ lipase A2 (PLA^) releases arachidonic acid from the membrane lipid —» Enzyme 5-lipoxygenase converts arac hidonic acid to leukotriene precur­ sors (HPETEs) —» Final products\: LTB4 (neutrophil chemotaxis), LTC4 (bronchoconstriction), LTD4 (bron- choconstriction), LTE4 (bronchocon­ striction).
Corticosteroids inhibit the synthesis of COX-2 enzyme and inhibit the enzyme PLA2.
Spina bifida aperta—Also referred to as open spinal dysraphism; “ap­ erta” in Latin means opening; hernia­ tion and exposure of the spinal cord and meninges (myelomeningocele) is the most severe form; protrusion of the meninges through an abnormal vertebral opening (meningocele).
• Palmar grasp—Placing a finger under the baby’s toes causes the toes to curl toward the finger. Present at birth, and disappears by 9 months.
• Uterine rupture—Life-threatening pregnancy complication; consider uterine rupture in a patient with a nonreassuring FHR pattern, fetal bradycardia, decelerations (variable, late, or prolonged), uterine contrac­ tion abnormalities, ± abdominal pain (ie, may be masked by analge­ sics), variable vaginal bleeding, loss of fetal station, and maternal he­ modynamic instability secondary to intraabdominal hemorrhage; higher risk of uterine rupture in a scarred uterus (eg, prior C-section, uterine surgery, myomectomy) compared to an unscarred uterus; type of pri­ or uterine incision confers a risk of uterine rupture (classic vertical inci­ sion [higher risk] > low vertical > low transverse [lower risk]); risk factors for a uterine rupture in the unscarred uterus includes multiple gestation, grand multiparity, malpresentation, abnormal placentation (eg, placenta accreta, increta, or percreta), labor dystocia, macrosomia, uterine over­ distension (eg, polyhydramnios), bicornuate uterus, connective tissue disorders, advanced maternal age, injudicious use of uterotonic agents, and trauma.
• Cyclooxygenase pathway\: Mem­ brane phospholipids —» Enzyme phospholipase A2 (PLA2) releases arachidonic acid from the membrane lipid —> Enzyme cyclooxygenase (COX-1, COX-2) converts arachi­ donic acid to prostaglandin precur­ sors (PGG2, PGH2) —» Final prod­ ucts\: PGE2 (T uterine contractions, relaxes smooth muscle of the cervix, induces fever, T sensitivity to pain), PGI2/prostacyclin (4 platelet aggre­ gation, 4 uterine tone, vasodilata­ tion), TXA2/thromboxane (T plate­ let aggregation, vasoconstriction).
• NSAIDs, including aspirin, inhibit cyclooxygenase enzymes (COX-1 and COX-2).
• Patient Safety—Root cause analysis is an assessment to identify the root cause of the underlying problems that may lead to an adverse outcome (eg, sentinel event). The analysis tries to correct the faculty process or systems in place, rather than an in­ dividual. The goal is to reduce simi­ lar occurrences in the future and to improve outcomes for patients.
• Trunk incurvation (Galant reflex)— While the baby is in the prone posi­ tion, the examiner strokes along one side of the spine and the baby will move the pelvis toward the side of the stimulus. Present at birth, and disap­ pears by 6 months.
• Patient Safety—Use pressure-reliev­ ing bedding materials to prevent pressure ulcers.
• Contraindications to MMR vaccine include pregnancy, current febrile illness with fever >101.3°F (38.5°C), active untreated TB, anaphylactic reaction to neomycin, hypersensitiv­ ity to gelatin, blood issues (eg, blood dyscrasias, lymphoma, leukemia, malignancy affecting bone marrow or lymphatic system), patients on immunosuppressive therapy (includ­ ing high-dose steroids), patients with AIDS, patients with HIV who are severely immunocompromised, and family history of immunodeficiency (until recipient of the vaccine shows immune competence). Breastfeed­ ing, positive PPD, PPD test given at the same time as the MMR vaccine, egg allergy, and immunodeficient family member, asymptomatic or mild symptomatic HIV infection are not contraindications to the MMR vaccine.
• Celecoxib is a COX-2 inhibitor that provides antipyretic, analgesic, and anti-inflammatory properties. Fea­ tures of COX-2 inhibitors include a 4 in gastroduodenal ulcers, 4 risk of GI bleeding, sulfonamide allergy, and they do not inhibit platelet aggrega­ tion. Since COX-2 inhibitors do not inhibit the COX-1 enzyme, COX-1 can provide gastric cytoprotection.
APPENDIX C FACTOIDS 331

332 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
•
IV drug users may develop infective endocarditis (IE). The most common cause of IE in IV drug users is Staph­ ylococcus aureus, but others may in­ clude Streptococci and Enterococci. Most cases of IE due to IV drug use are a right-sided IE. It should be noted that a murmur may not be de­ tectable, but it is possible that deep inspiration (T blood to right ven­ tricle) may accentuate a right-sided murmur (see Table 3-6).
Craniosynostosis is the prema­ ture fusion of one or more cranial sutures. Premature fusion of the sagittal suture (scaphocephaly or dol- ichocephaly) can cause the head to be elongated resulting in a narrow face. Premature fusion of the unilateral coronal suture (anterior plagioceph- aly) can result in flattening of the forehead with eyebrow elevation on the affected side. Premature fusion of bilateral coronal sutures (brachy- cephaly) can result in a short, wide, boxlike head.
Microcephaly—A head circumfer­ ence that is more than 2 standard de­ viations below the mean for age and gender.
Average head circumference at birth is 35 cm.
Compensated metabolic acidosis\: For every 1 mEq/L fall in HCOj, there is a respiratory compensation ofa fall of 1.25 mm Hg ofpCOr•
Compensated metabolic alkalosis\:
For every 1 mEq/L elevation in HC03-, there is a respiratory compensation of a raise of 0.75 mm Hg ofpC02.
Compensated acute respiratory aci­ dosis\: For every 1 mm Hg elevation in pC02, there is a bicarbonate compen­ sation of a raise of 0.1 mEq/L HCOj.
Compensated chronic respiratory ac­ idosis\: For every 1 mm Hg elevation in pC02, there is a bicarbonate compen­ sation of a raise of 0.4 mEq/L HCO ".
Compensated acute respiratory al­ kalosis\: For every 1 mm Hg fall in pC02, there is a bicarbonate compen­ sation of a fall of 0.2 mEq/L HCO~.
• A useful guideline in estimating the average plasma glucose is to assume that a HbAlc of 6.0% is equivalent to 120 mg/dL and that with an in­ crease in each percentage point of the HbAlc, there is a rise of 30 mg/ dL in the average glucose. For exam­ ple, a HbAlc of 9.0% is equivalent to an average glucose of 210 mg/dL (ie,
120 mg/dL + 90 mg/dL = 210 mg/dL).
• Blood group A\: A antigen on cell; anti-B in plasma; may receive blood from A and O; may give blood to A and AB.
• Blood group B\: B antigen on cell; anti-A in plasma; may receive blood from B and O; may give blood to B and AB.
• Blood group AB\: Universal recipi­ ent; A and B antigen on cell; no anti- A or anti-B in plasma (ie, reason for being the universal recipient); may receive blood from A, B, AB, or O; may give blood to AB only (ie, be­ cause A and B antigen on cell).
• Blood group O\: Universal donor; no A or B antigen on cell (ie, reason for being the universal donor); anti-A and anti-B in plasma; may receive blood from O only (ie, because anti-A and anti-B in plasma); may give blood to A, B, AB, or O; remember that “O” are good “d-O-n-o-r-s.”
• Vaccines contraindicated in preg­ nancy include varicella, MMR, live attenuated influenza vaccine (LAIV), and zoster vaccine.
• Patient Safety—Practice proper hand hygiene with the use ofantiseptic soap or alcohol-based gels. Remember it is still important to clean your hands before and after wearing gloves.
• Macrocephaly—A head circumference that is more than 2 standard deviations above the mean for age and gender.
• Saw palmetto toxicity—Hyperten­ sion, headache, nausea, diarrhea, constipation, urinary retention.
• Opioid intoxication—CNS depression, bradycardia, hypotension, depressed respirations, hypothermia, hyporeflex- ia, miosis, X bowel sounds, euphoria followed by apathy, slurred speech.
• NSAIDs (including aspirin) have the triple As (Antipyretic, Analgesic, Anti-inflammatory properties).
• Acetaminophen has antipyretic and analgesic effect, but has little to no anti-inflammatory properties.
• Zileuton is seen in the treatment of asthma and serves to inhibit the 5-lipoxygenase enzyme.
• Zafirlukast is seen in the treatment of asthma and serves as a leukotriene receptor antagonist.
• Montelukast is seen in the treatment of asthma and allergic rhinitis; it serves as a leukotriene receptor an­ tagonist.
• World Health Organization (WHO) analgesic ladder\: Mild pain (non­ opioid ± adjuvant) -» Mild to Mod­ erate pain (weak opioid ± non-opioid ± adjuvant) —> Moderate to Severe pain (stronger opioid ± non-opioid ± adjuvant).
• Non-opioids—Acetaminophen, aspi­ rin, and NSAIDs.
• Weak opioids—Codeine, hydroco- done, tramadol, and propoxyphene.
• Stronger opioids—Morphine, fen- tanyl, hydromorphone, oxycodone, methadone, and levorphanol.
• Inhalant intoxication—Toluene (eg, glues, paint thinners, marker pens, adhesives, acrylic paints, gasoline), nitrous oxide (eg, whipping cream canisters), hydrocarbons (eg, lighter fluid, aerosol propellants, propane, degreasers, dry-cleaning fluids, spot removers, Freons), euphoria, violent behavior, slurred speech, disorienta­ tion, ataxia, hallucinations, diplopia, headache, abdominal cramps, nau­ sea, vomiting, eczematoid dermatitis (“glue-sniffer’s rash”), arrhythmias, generalized muscle weakness, X re­ flexes, hand tremor, nystagmus, my­ driasis, unusual chemical odor on the breath.
•
•
•
•
•
•
•
•

Compensated chronic respiratory alkalosis\: For every 1 mm Hg fell in pC02, there is a bicarbonate compen­ sation of a fell of 0.4 mEq/L HCO3. (Note the ratios for all the compen­ sations. For example, in this case, if thereisafallof10mmHginpC02, then there should be a fall of4 mEq/L HCOj. In another example, if there isaraiseof10mmHginpC02in acute respiratory acidosis, then there should be a compensatory raise of 1 mEq/L HCO;.)
Amphetamine intoxication—Agita­ tion, paranoia, tachycardia, hyper­ tension, tachypnea, hyperthermia, hyperreflexia, mydriasis, perspira­ tion, hypervigilance, euphoria.
Amphetamine withdrawal—Hyper­ somnia, fatigue, T appetite, irritabil­
ity, delayed depression.
Methaqualoneintoxication—“Quaa- ludes,” drowsiness, ataxia, sexual arousal, slurred speech, headache.
First generation cephalosporins— Cefazolin (parenteral), cephalexin (oral); MOA—Inhibits bacterial cell wall synthesis by binding to the penicillin binding proteins (PBPs); Clinical use—Gram-positive cov­ erage (including staphylococci and streptococci, but not enterococci); minimal gram-negative coverage but can cover Proteus mirabilis, E coli, and Klebsiella pneumoniae (acronym PEcK); absent anaerobic coverage; cefazolin is commonly used for peri­ operative prophylaxis; Side effects— Abdominal pain, rash, eosinophilia, penicillin allergy, abnormal LFTs; Pregnancy drug rating—Cefazolin (category B), cephalexin (category B).
• Opioid withdrawal—Mydriasis, lac- rimation, nausea, vomiting, diarrhea, piloerection, insomnia, runny nose, yawning, muscle aches, abdominal cramping.
• Cannabis intoxication—Euphoria, impaired perception and motor skills, conjunctival injection, T appetite, dry mouth, decreased short-term memory.
• Cannabis withdrawal—Sleep distur­ bances, irritability, tremors, i appe­ tite, depressed mood, anxiety, head­ aches, mood swings.
• Alcohol intoxication—Slurred speech, mood lability, incoordination, vomit­ ing, stupor, confusion.
• Alcoholwithdrawal—Tremors, agita­ tion, insomnia, T heart rate, sweating,
clammy skin, GI distress, seizures, anxiety, delirium tremens.
• Benzodiazepine intoxication—Slurred speech, confusion, ataxia, somno­ lence, stupor.
• Benzodiazepine withdrawal—Anx­ iety, insomnia, sweating, irritability, nausea, vomiting, tremors, sweating, seizures, psychosis.
• Phencyclidine (PCP) intoxication—
“Angel dust,” belligerence, violence, psychomotor agitation, hallucinations, tachycardia, hypertension, tachypnea, hyperthermia, hyperacusis, nystag­ mus, muscle rigidity, catatonia.
• MDMA intoxication—“Ecstasy* eu­ phoria, excitement, tachycardia, hypertension, tachypnea, hyperther­ mia, mydriasis, bruxism.
• Lysergic acid diethylamide (LSD)—
“Acid,” hallucinations, tachycardia, hypertension, hyperthermia, mydri­ asis, anxiety, piloerection.
• Patient Safety—Handoffs are the transfer of essential information from one health-care provider to another. A good handoff includes clear lan­ guage, avoiding abbreviations, updat­ ed information, accurate information, tasks for the receiver must be clearly explained, minimize environmental distractions, allow receiver time to re­ view relevant summary, allow oppor­ tunity for questions, verify informa­ tion, denote severity of the patients, and outline contingency plans.
•
•
Tobacco withdrawal—Headache, ir­ ritability, difficulty concentrating, de­ pressed, T appetite, tobacco cravings,
insomnia, restlessness.
Macrolides—Azithromycin, clarithro­ mycin, erythromycin; MOA—Protein synthesis inhibitor by binding to the 50S ribosomal subunit; Clinical use— Upper respiratory tract infections, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoni­ ae, Legionella pneumophila, Chla- mydophila pneumoniae. Mycoplasma pneumoniae, Mycobacterium avium complex (MAC); Side effects—GI dis­ tress, rash, QT prolongation, torsades de pointes, hearing loss, pyloric steno­ sis, abnormal LFTs; Pregnancy drug rating—Azithromycin (category B), clarithromycin (category C), erythro­ mycin (category B).
Lincosamide—Clindamycin; MOA— Protein synthesis inhibitor by bind­ ing to the SOS ribosomal subunit; Clinical use—PID, acne, anaerobic infections, streptococcal infections, staphylococcal infections; Side ef­ fects—Diarrhea (including Clostridi­ um difficile colitis); Pregnancy drug rating—Clindamycin (category B).
•
APPENDIX C FACTOIDS 333

334 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• Second generation cephalospo­ rins—Cefuroxime (parenteral and oral), cefoxitin (parenteral), cefo- tetan (parenteral); MOA—Inhib­ its bacterial cell wall synthesis by binding to the penicillin binding pro­ teins (PBPs); Clinical use—Weaker activity against gram-positive or­ ganisms compared to the first gen­ eration, but extended gram-negative and anaerobic coverage; important distinctions in this generation is that cefuroxime has good activity against H influenzae and M catarrhalis while cefoxitin and cefotetan have good ac­ tivity against the anaerobe Bacteroi- des fragilis; Side effects—Diarrhea, penicillin allergy; Pregnancy drug rating—Cefuroxime (category B), cefoxitin (category B), cefotetan (cat­ egory B).
• Glycopeptide—Vancomycin; MOA— Inhibits bacterial cell wall synthesis by binding to the D-ala-D-ala portion of the cell wall precursor; Clinical use—Invasive gram-positive infections (including MRSA), Clos­ tridium difficile-associated diarrhea; Side effects—Ototoxic, nephrotoxic, red man syndrome; Pregnancy drug rating—Vancomycin (category B in the oral form, and category C in the intravenous form).
• Third generation cephalosporins— Ceftriaxone (parenteral), cefotaxime (parenteral), ceftazidime (paren­ teral); MOA—Inhibits bacterial cell wall synthesis by binding to the peni­ cillin binding proteins (PBPs); Clini­ cal use—Weaker activity against gram-positive organisms compared to the first generation, but increased activity against gram-negatives that are resistant to other beta-lactams; most third generations can cross the blood brain barrier; ceftriaxone (4 activity against P aeruginosa, used in gonococcal infections, empiric treatment in meningitis, used in community-acquired pneumonia, used in Lyme disease); cefotaxime (•l activity against P aeruginosa, used against penicillin-resistant pneumo­ cocci; used in spontaneous bacterial peritonitis); ceftazidime (T activity against P aeruginosa); Side effects— Diarrhea, rash, penicillin allergy, biliary pseudolithiasis (ceftriaxone can lead to ceftriaxone crystal for­ mation or “sludge” in the gallbladder mimicking a gallstone and causing colicky abdominal pain); Pregnancy drug rating—Ceftriaxone (category B), cefotaxime (category B), ceftazi­ dime (category B).
• Aminoglycosides—Gentamicin, to­ bramycin, streptomycin, neomycin, amikacin; MOA—Protein synthesis inhibitor by binding to the 30S ri- bosomal subunits; Clinical use— Aerobic gram-negative bacilli infec­ tion (including Pseudomonas aerugi­ nosa), synergistic with beta-lactams to cover gram-positives (streptococci, staphylococci, enterococci), resistant to anaerobic bacteria; Side effects— Ototoxic (usually irreversible), neph­ rotoxic (usually reversible); Pregnancy drug rating—Gentamicin (category D), tobramycin (category D), strep­ tomycin (category D), neomycin (cat­ egory D), amikacin (category D).
• Metronidazole\: MOA—Formation of toxic compounds that interact with the host cell DNA, resulting in DNA strand breakage and eventually into cell death; Clinical use—Anaer­ obic infections, protozoal infections (including amebiasis), Clostridium difficile-associated diarrhea, bacterial vaginosis, trichomoniasis, giardiasis, H pylori, abscess; Side effects—Me­ tallic taste, disulfiram-like reaction with alcohol, GI distress, peripheral neuropathy, headache, urine dark­ ening; Pregnancy drug rating— Metronidazole (category B).
• Synthetic cathinone intoxication— “Bath salts,” violent behavior, agita­ tion, self-mutilation, hallucinations, paranoia, panic attacks, tachycardia, hypertension, hyperthermia, mydria­ sis, sweating, seizures.
• Fourth generation cephalosporin— Cefepime (parenteral); MOA— Inhibits bacterial cell wall synthesis by binding to the penicillin bind­ ing proteins (PBPs); Clinical use- improved activity against gram-pos­ itive organisms that is comparable to the first generation; greater resis­ tance to beta-lactamases produced by gram-negative bacteria; active against streptococci and methicillin- susceptible staphylococci; T activity against P aeruginosa that is similar to ceftazidime; used in febrile neu­ tropenia; used in pneumonia (noso­ comial and community-acquired); Side effects—Diarrhea, rash, penicil­ lin allergy, seizure; Pregnancy drug rating—Cefepime (category B).

Fluoroquinolones—Ciprofloxacin, levofloxacin, norfloxacin, ofloxacin, moxifloxacin, gemifloxacin; MOA— Fluoroquinolones are direct inhibi­ tors of bacterial DNA synthesis. All fluoroquinolones can inhibit DNA gyrase (topoisomerase II), but gemi­ floxacin and moxifloxacin can also inhibit topoisomerase IV, which is another important enzyme in DNA replication; Clinical use—Broad- spectrum antibiotics with greatest activity against aerobic gram-neg­ ative bacilli; fluoroquinolones are used in gram-negative infections (including E coli, H influenzae, M catarrhalis, Klebsiella spp, Legionella spp, Salmonella spp, Shigella spp, P aeruginosa, Proteus spp, Neisseria meningitidis. Neisseria gonorrhoeae); CDC no longer recommends fluo­ roquinolones to treat gonococcal disease; only moxifloxacin has ad­ ditional coverage against anaerobes; fluoroquinolones are used to treat genitourinary infections, communi­ ty-acquired pneumonia, nosocomial pneumonia, acute exacerbations of chronic bronchitis, skin infec­ tions, acute sinusitis, and prostatitis; Side effects—GI distress (includ­ ing Clostridium difficile-associated diarrhea), headache, QT prolon­ gation, tendon rupture, tendinitis, rash, hyperglycemia, hypoglycemia, abnormal LFTs; avoid in patients <18 years old because of concerns of cartilage erosions in weight-bearing joints; avoid in pregnant women be­ cause safety in pregnancy has not been established; Pregnancy drug rating—Ciprofloxacin (category C), levofloxacin (category C), norfloxa­ cin (category C), ofloxacin (catego­ ry C), moxifloxacin (category C), gemifloxacin (category C).
• Tetracyclines—Doxycycline, mino­ cycline, tetracycline, demeclocycline; MOA—Protein synthesis inhibitor by binding to the 30S ribosomal subunit at a position that prevents attach­ ment of the aminoacyl-tRNA; Clini­ cal use—Broad-spectrum antibiot­ ics; tetracyclines are used against the spirochete Borrelia burgdorferi (Lyme disease), gram-negative Rickettsia rickettsii (Rocky mountain spotted fever), atypical pathogen Mycoplas­ ma pneumoniae (causes mycoplasma pneumonia), obligate intracellular bacteria Chlamydophila spp, Coxi- ella burnetii (Q fever), gram-negative Vibrio cholerae (cholera), gram-posi­ tive rod Bacillus anthracis (anthrax), H pylori eradication, and Ureaplasma urealyticum; Side effects—GI dis­ tress (including Clostridium difficile- associated diarrhea), photosensi­ tivity, hepatotoxicity, discoloration of the teeth and enamel hypoplasia in children <8 years old; avoid in pregnant women and children <8 years old if possible; Pregnancy drug rating—Doxycycline (cat­ egory D), minocycline (category D), tetracycline (category D), demeclo­ cycline (category D).
• Neutropenia is typically defined as an absolute neutrophil count (ANC) of <1500 cells/pL. An ANC <500 cells/pL would be considered se­ vere neutropenia. The percent seg­ mented neutrophils is part of the equation in calculating the ANC (ie, ANC = WBC x [PMN% + Bands%]/
100). Neutropenia may be seen in the setting of cancer chemotherapy, in­ fection, autoimmune disorders, and drug-induced conditions. When as­ sessing for neutropenia, remember not to just look at segmented neutro­ phil percentages in the lab report, but look at the absolute neutrophil count because it is absolutely better. The ANC is usually a component of the standard CBC report.
• Carbapenems—Imipenem-cilas- tatin, meropenem, doripenem, er- tapenem; MOA—Inhibits bacterial cell wall synthesis by binding to the penicillin binding proteins (PBPs); low susceptibility to beta-lactamases; Clinical use—Broad-spectrum an­ tibiotics that cover gram-negatives, gram-positives, and anaerobes; Side effects—GI distress, rash, headache, seizures, allergic cross-reactivity with beta-lactam antibiotics (ie, beta- lactam ring found in carbapenems, monobactams, penicillins, and cepha­ losporins); Pregnancy drug rating— Imipenem-cilastatin (category C), meropenem (category B), doripenem (category B), ertapenem (category B).
• Cilastatin is a compound that is usually added to imipenem therapy because imipenem is normally de­ graded in the kidney (proximal renal tubule) by an enzyme called renal de­ hydropeptidase I. Cilastatin inhibits renal dehydropeptidase I and there­ by prolongs the antibacterial effect of imipenem and also prevents the for­ mation of nephrotoxic metabolites if imipenem was degraded.
• Monobactam—Aztreonam; MOA— Inhibits bacterial cell wall synthesis by binding to the penicillin binding pro­ tein 3 (PBP-3); resistant to beta-lacta­ mases; Clinical use—Greatest activity against gram-negative bacteria (includ­ ing Enterobacteriaceae and P aerugino­ sa)-, no activity against gram-positive bacteria or anaerobes; synergistic with aminoglycosides; used in patients with penicillin allergies; cross-allergenicity with other beta-lactams are unlikely ex­ cept for ceftazidime (third generation cephalosporin) because ceftazidime and aztreonam both have a shared side chain; Side effects—GI distress, rash, abnormal LFTs; Pregnancy drug rat­ ing—Aztreonam (category B).
• St. John’s wort toxicity—Nausea.
• Ephedra (ma huang) toxicity—
Hypertension, tachycardia.
• Patient Safety—Appropriate use of prophylaxis (eg, LMWH, pneumatic compression devices) to prevent perioperative venous thromboembo­ lism (VTE).
APPENDIX C FACTOIDS 335

Key Lab Values
The key lab values are basic lab values that you should probably know prior to the exam to facilitate your understanding of the question when asked to analyze a set of lab values. Although the Step 3 exam will provide you with the laboratory values and the reference range, searching for the lab value and processing the information can be a multistep process. Knowing a few basic lab values before the exam can improve your efficiency, maintain
SERUM
Electrolytes
Sodium\: 135-146 mEq/L Potassium\: 3.5-5.0 mEq/L Chloride\: 95-105 mEq/L Bicarbonate\: 22-28 mEq/L Calcium (total)\: 8.4-10.2 mg/dL Magnesium\: 1.5-2.0 mEq/L Phosphorus\: 3.0-4.5 mg/dL
Liver Analytes
ALT\: 10-40 U/L
AST\: 15-40 U/L
Alkaline phosphatase (male)\: 30-100 U/L Alkaline phosphatase (female)\: 45-115 U/L Total bilirubin\: 0.1-1.0 mg/dL
Direct bilirubin\: 0.0-0.3 mg/dL
your rhythm, and allow for a smoother transition into your ana­ lytical thinking on the questions. Although memorizing these lab values may require extra storage space in your brain, you can use your short-term memory by memorizing these lab values 1 to 2 days prior to the exam. The payoff may well be worth it. Re­ member, passing Step 3 reflects the attitude you take during your preparation, and that includes not discounting the small things.
Endocrine Analytes
Fasting glucose\: 70-110 mg/dL
2-hour postprandial glucose\: <120 mg/dL TSH\: 0.5-5.0 pU/mL
T4\:5-12|ig/dL
T3RU\: 25%-35%
Lipids
Total cholesterol\: 150-240 mg/dL Triglycerides\: 35-160 mg/dL HDL\: 30-70 mg/dL
LDL\: <160 mg/dL
337

338 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
Enzymes
Amylase\: 25-125 U/L LDH\: 45-90 U/L
Renal Analvtes
BUN\: 7-18 mg/dL Creatinine\: 0.6-1.2 mg/dL
ABG
pH\: 7.35-7.45/ PC02\: 33-45/ P02\: 75-105
HEMATOLOGIC
CBC
WBC\: 4500-11,000/mm3
Hb (male)\: 13.5-17.5 g/dL
Hct (male)\: 4196-53%
Hb (female)\: 12.0-16.0 g/dL Hct (female)\: 36%-46% Platelets\: 150,000-400,000/mm3
Coagulation Analvtes
PT\: <12 seconds
PTT\: <28 seconds Bleeding time\: 2-7 minutes
URINE
Calcium\: 100-300 mg/24 hr
Total proteins\: <150 mg/24 hr
Specific gravity\: 1.003-1.030
Urine osmolality\: 50-1400 mOsmol/kg H20
BMI
BMI\: 19-25 kg/m2
Proteins
Total proteins\: 6.0-7.8 g/dL Albumin\: 3.5-5.5 g/dL
Solute Balance
Serum osmolality\: 275-295 mOsmol/kg H20
Differentials
Bands\: 3%-5%
Segmented neutrophils\: 54%-62% Lymphocytes\: 25%-33%

•
•
•
•
• • • •
•
Final Pearls
This is your last step in the USLME series, so give the test its due diligence so that you can move forward with your life.
Remember that a systematic, methodical approach to your preparation will usually lead to a higher percentage of pass­ ing any examination.
Be sure to track your progress throughout the course of your preparation and anticipate which chapters or sections of the chapter will be mastered by the end of each rotation (eg, car­ diology chapter by the end of the cardiology rotation, EKG review section by the end of the ICU/CCU service).
Be open-minded when reading the questions. Do not be too rigid and absolute with classic presentations. Sometimes atypical presentations may be integrated with a classic pre­ sentation. Other times, there may be associated features presented with the disease (eg, bacterial vaginosis presented with PID).
Make sure you answer all questions since unanswered ques­ tions are considered wrong answers.
Try not to skip too many questions because there is no guar­ antee that the next set of questions will be easier or shorter.
Try generating an answer after reading the question before looking at the option list.
On long narrative questions, try reading the last line of the question first because then you know what the question is asking. Then, read the question from the beginning. In this approach, you can read with more intention.
Take ownership of the exam by controlling the pace of each block and the tempo of the exam day. You should be able to
know how many blocks you have completed, what CCS case number you are on, and what quarter you are on in the quar­ ter method. Use the dry-erase board provided on the exam to help you with those three elements.
• Consider bundling all literature interpretation questions to­ ward the end of each block. In this approach, you maintain good rhythm with the other multiple-choice questions.
• Although it is nice to answer questions with “silver-bullet” knowledge (ie, you are 100% sure of answering the question correcdy), do not underestimate the power of deductive reason­ ing. Eliminating clearly wrong answers on the multiple-choice questions based on facts and medical concepts will increase your percentage of answering the question correctly.
• Good test takers can always spot key pieces of information. The pieces of information can then be collectively integrated to formulate the diagnosis and then make good management decisions.
• Remember to keep track of your time on the test (quarter method).
• Give each question an “equal opportunity” in terms of time.
• Caveat 1—Do not underestimate the exam.
• Caveat 2—Never spend too much time on any one question since some questions could be experimental or piloted ques­ tions (ie, consider ambiguous questions as land mines since they can damage your time).
• Caveat 3—Time can creep up on you when you least expect it, or it may occur at the end of the day when you are men­ tally exhausted.
339

340 CLINICAL JUDGMENT USMLE STEP 3 REVIEW
• •
•
•
• •
•
•
•
•
•
Caveat 4—You cannot expect to pass if you don’t put in the time.
One of the key elements to making sound clinical judgments is to always weigh pertinent facts carefully before making a decision.
Ifyoureadthisbookandunderstandthemajorityofthemedi­ cal information, then your clinical judgment should be sharper and you should have enough firepower to do well on the exam.
Remember that it is easy to know a lot if you understand a lot. Once you know a lot, then you have the tools to think with more depth and think critically.
The more depth you have in your knowledge base, the better you can position yourself at making sound clinical judgment.
Try to extract the essence of each chapter (not just purely memorizing information) because you ultimately want to sharpen your clinical judgment.
Once you have read this book and extracted the information from each chapter, try to make sense out of it on a global per­ spective by interrelating the chapters (ie, connecting points). This is when you tap into sound clinical judgment.
In your final review prior to the exam, you should be able to go through the book and know all the connecting points without hesitation.
Consider taking the examination on consecutive days or within 2 to 3 days after day 1. In this respect, you should feel more comfortable going into part 2 of the exam because you already know what to expect. If you prolong the latency period (eg, 1 month later), you might feel a little bit on edge going into part 2 of the exam.
Between day 1 and day 2, make sure you have time to decom­ press to get ready for part 2. It is not recommended to look up answers to the questions you remember. If you do, you might second-guess yourself on part 2 and you may shatter your confidence. You need to go into part 2 with a positive mind frame. Remember that the evaluation process is a sum total and not on several questions you remember.
Take inventory of your clinical judgment skills. Clinicians use their clinical judgment on a day-to-day basis, but they may not be aware of how strong or weak their skills are.
• Do your best to get a good nights rest the day before the exam. Ifyou don’t, however, that is okay. It is completely nor­ mal and part of the process of taking examinations. Know that the time and effort you put into your preparation cannot be stolen. You will still be able to function at a high level and make good decisions on the exam.
• On the CCS, practice the CCS component of the exam with each chapter review. You will be amazed to discover some­ thing new each time.
• On the CCS, never blow off any CCS cases on the actual exam. Even if you don’t know how to manage a patient on the CCS exam, you can always work up the patient based on a pertinent history, physical exam, and updated lab re­ ports. Remember that a thorough approach based on your clinical judgment may not necessarily deduct from your score.
• On the CCS, be aware of CCS cases in which you have to defer from further testing and treatment that would not be considered the standard of care. For example, you do not want to do further testing or treatment on a patient with a terminal illness. If you do further testing or treatment, that would be considered an aggressive approach and you will certainly have a low score.
• On the CCS, the initial vital signs are a clue to whether the patient is stable or unstable and whether or not the manage­ ment decisions need to be done expeditiously.
• On the CCS, remember to always “bridge” your ther­ apy. Think about what needs to be treated acutely (eg, pain) and what needs to treated in the long term (eg, prevention).
• On the CCS, remember to appropriately monitor your pa­ tients (eg, pulse oximetry, continuous cardiac monitoring, continuous blood pressure monitoring, pertinent physical exams after treatment, urine output, vital signs, ICU, fetal monitor, PFTs, neuro checks).
• On the CCS, if you ever feel overwhelmed with any CCS cases, hit the “refresh” button in your mind by (1) compos­ ing yourself, (2) quickly reading the case introduction, (3) identifying key aspects of the initial history, (4) glancing at the vital signs, and (5) asking yourself, “What are the neces­ sary steps in managing this patient?”