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The only official Kaplan Lecture Notes for USMLE Step 3 cover the comprehensive information you need to ace the exam. This 2-volume set is the perfect companion for Kaplan’s USMLE courses.

Up-to-date. Updated biannually by Kaplan’s all-star faculty. This updated edition reflects the 2014 test change and includes more foundational medicine and systems-based practice/patient safety.
Complete. Includes basic science correlates likely to be tested on the exam, patient management from the experts, patient safety, and population health.
Learner-efficient. Case-based content (250+ in-depth cases) organized in outline format presents material for both the Foundations of Independent Practice (FIP) and Advanced Clinical Medicine (ACM) components of the exam
Trusted. Used by thousands of students each year to succeed on the USMLE Step 3.

Two volumes in set:
Internal Medicine, Neurology, Psychiatry, Ethics
Pediatrics, Obstetrics/Gynecology, Surgery, Epidemiology, Patient Safety

This collection of books assumes mastery of both Step 1 pre-clinical discipline-based and Step 2 CK clinical sciences content, both of which are covered in Kaplan's other Lecture Notes bundles.
Jahr:
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english
ISBN 13:
9781506250021
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USMLE® Step 3


Lecture Notes 2019–2020


Internal Medicine

Psychiatry

Ethics





Table of Contents


USMLE® Step 3 Lecture Notes: Internal Medicine Neurology Psychiatry Ethics Cover

Title Page

Copyright

Editors

Feedback Page





Part I: Internal Medicine Chapter 1: Preventive Medicine Cancer Screening

Travel Medicine

Immunizations

Smoking Cessation

Osteoporosis Prevention

Prevention of Alcohol Abuse

Prevention of Violence and Injury





Chapter 2: Infectious Disease Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9

Case 10

Case 11

Case 12

Case 13

Case 14

Case 15





Chapter 3: Cardiology Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9

Case 10

Case 11

Case 12





Chapter 4: Pulmonology Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9





Chapter 5: Emergency Medicine Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9

Case 10

Case 11





Chapter 6: Hematology Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9

Case 10





Chapter 7: Oncology Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9





Chapter 8: Endocrinology Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9

Case 10

Case 11





Chapter 9: Gastroenterology Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9





Chapter 10: Nephrology Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9

Case 10





Chapter 11: Rheumatology Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9

Case 10





Part II: High-Yield Images: Dermatology, Radiology, and Ophthalmology Chapter 12: Dermatology Inflammatory Conditions

Fungal Infections

Viral Infections

Bacterial Infections

Sexually Transmitted Diseases

Malignant Lesions

Scaling Disorders/Papulosquamous Dermatitis





Chapter 13: Radiology Appearances of Common Disorders on Chest X-Ray





Chapter 14: Ophthalmology Retinal Diseases

Keratitis





Part III: Neurology Cha; pter 15: Neurology Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9

Case 10

Case 11

Case 12

Case 13

Case 14





Part IV: Psychiatry Chapter 16: Psychiatry Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9

Case 10

Case 11

Case 12

Case 13

Case 14

Case 15

Case 16





Part V: Ethics Chapter 17: Ethics Case 1

Case 2

Case 3

Case 4

Case 5

Case 6

Case 7

Case 8

Case 9





Part VI: Medical Abbreviations Chapter 18: Medical Abbreviations Medical Abbreviations





Guide


Cover

Table of Contents

Start of Content





USMLE® is a joint program of the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME), which neither sponsor nor endorse this product.

This publication is designed to provide accurate information in regard to the subject matter covered as of its publication date, with the understanding that knowledge and best practice constantly evolve. The publisher is not engaged in rendering medical, legal, accounting, or other professional service. If medical or legal advice or other expert assistance is required, the services of a competent professional should be sought. This publication is not intended for use in clinical practice or the delivery of medical care. To the fullest extent of the law, neither the Publisher nor the Editors assume any liability for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this book.

© 2019 by Kaplan, Inc.

Published by Kaplan Medical, a division of Kaplan, Inc.

750 Third Avenue

New York, NY 10017

All rights reserved under International and Pan-American Copyright Conventions. By payment of the required fees, you have been granted the non-exclusive, non-transferable right to access and read the text of this eBook on screen. No part of this text may be reproduced, transmitted, downloaded, decompiled, reverse engineered, or stored in or introduced into any information storage and retrieval system, in any form or by any means, whether electronic or mechanical, now known or hereinafter invented, without the express written permission of the publisher.

10 9 8 7 6 5 4 3 2 1

ISBN: 978-1-5062-5002-1





Editors


Internal Medicine


Joseph J. Lieber, MD

Director of Medicine

Elmhurst Hospital Center





Associate Professor of Medicine

Associate Program Director of Medicine for Elmhurst Site

Icahn School of Medicine at Mount Sinai

New York, NY



Frank P. Noto, MD Assistant Professor of Internal Medicine

Department of Hospital Medicine



Associate Program Director of Education for Elmhurst Site



Icahn School of Medicine at Mount Sinai

New York, NY





Internal Medicine Clerkship and Sub-Internship Site Director



Icahn School of Medicine at Mount Sinai

New York, NY



Manuel A. Castro, MD, AAHIVS

Diplomate of the American Board of Internal Medicine

Certified by the American Academy of HIV Medicine

Wilton Health Center (Private Practice)

Wilton Manors, FL



Nova Southeastern University

Clinical Assistant Professor of Medicine

Fort Lauderdale-Davie, FL



LECOM College of Osteopathy

Clinical Assistant Professor of Medicine

Bradenton, FL



Raj Dasgupta, MD, FACP, FCCP, FAASM

Assistant Professor of Clinical Medicine

Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine

Keck School of Medicine of USC, University of Southern California

Los Angeles, CA





Psychiatry and Ethics


Alina Gonzalez-Mayo, M.D.

Psychiatrist

Dept. of Veteran’s Administration

Bay Pines, FL





We want to hear what you think. What do you like or not like about the Notes? Please email us at medfeedback@kaplan.com.





Part I





Internal Medicine





1





Preventive Medicine





Cancer Screening


Regular screening is recommended for cancers of the colon, breast, cervix, and lung.





Colon Cancer


Patients with no significant family history of colon cancer should begin screening at age 50. The choices are:

Colonoscopy every 10 years (preferred screening modality)

Fecal occult blood testing every year

Sigmoidoscopy with barium enema every 5 years



Patients who have a single first-degree relative with colorectal cancer diagnosed age <60 or multiple first-degree relatives with colon cancer diagnosed at any age should undergo colonoscopy starting at one of the following, whichever age occurs earlier:

Age 40

Age that is 10 years younger than the age at which the youngest affected relative was diagnosed



In this group of high-risk patients, colonoscopy should be repeated every 5 years.





Breast Cancer


The 3 tests used to screen for breast cancer are mammogram, manual breast exam, and self-breast exam. The American Cancer Society no longer recommends monthly self-breast exam alone as a screening tool.

Patients age ≥50, screen with mammogram (with or without clinical breast exam) every 1–2 years



Patients with very strong family history should consider prophylactic tamoxifen “Very strong family history” is defined as multiple first-degree relatives





Cervical Cancer


The screening test of choice for the early detection of cervical cancer is the Papanicolaou smear (“Pap” test). In average risk women, Pap screening should be started at age 21—regardless of onset of sexual activity—and performed every 3 years until age 65.

As an alternative, women age 30–65 who prefer to screen every 5 years can do so by co-testing with Pap and HPV.

In higher risk women, e.g., HIV positive, more frequent screening or screening after age 65 may be required.





Lung Cancer


Current lung cancer screening guidelines recommend the following:

Patients age 55–80 with >30 pack-years of smoking, screen annually with low dose CT (non-contrast) Must be current smoker or has quit <15 years





Patients age >80, have quit >15 years, or have other medical problems (e.g., severe COPD) significantly limiting life expectancy or ability to undergo surgery, no screening is recommended





Travel Medicine


Hepatitis


Hepatitis A infection is travelers’ most common vaccine-preventable disease. Hepatitis A infection is possible wherever fecal contamination of food or drinking water may occur. If a patient is leaving within 2 weeks of being seen, both the vaccine and immune serum globulin are recommended.

A booster shot given 6 months after the initial vaccination confers immunity for approximately 10 years.

Hepatitis B vaccination is recommended for patients who work closely with the indigenous population. Additionally, patients who plan to engage in sexual intercourse with the local populace or to receive medical or dental care, and those who plan to remain abroad for >6 months, should be vaccinated.





Malaria


For malaria prophylaxis, mefloquine is used, although doxycycline is an acceptable alternative. For pregnant patients requiring malaria chemoprophylaxis, chloroquine is preferred.





Rabies


Rabies vaccination is recommended for travel to areas where rabies is common among domesticated animals (India, Asia, Mexico). Chloroquine can blunt the response to the intradermal form of rabies vaccine. Therefore, when both malaria prophylaxis and rabies prophylaxis are required, the intramuscular form of the vaccine should be administered.

Rabies vaccination is not considered a routine vaccination for most travelers.





Yellow Fever


Yellow fever vaccine is required for travel to sub-Saharan Africa and certain South American countries.





Typhoid


Typhoid vaccination is recommended for patients who are traveling to developing countries and will have prolonged exposure to contaminated food and water.





Polio


Adults who are traveling to developing countries and have never received a polio vaccine should receive 3 doses of the inactivated polio vaccine. Patients who have been previously immunized should receive a one-time booster. The live attenuated polio vaccine is no longer recommended because of the risk of vaccine-associated disease.





Meningitis


Patients traveling to areas where meningococcal meningitis is endemic or epidemic (Nepal, sub-Saharan Africa, northern India) should be immunized with the polysaccharide vaccine. Additionally, Saudi Arabia requires immunization for pilgrims to Mecca. Patients with functional or actual asplenia and patients with terminal complement deficiencies should also receive the vaccine. Meningococcal vaccine is now routine to give at age 11.





Diarrhea


To prevent traveler’s diarrhea, patients should be educated regarding the advisability of avoiding salads and unwashed fruit and drinking tap/ice water. Patients who experience loose stools without fever or blood can safely take loperamide. Treatment with a fluoroquinolone or azithromycin is reserved for patients with moderate to severe symptoms (bloody diarrhea).





Immunizations


Influenza Vaccine


Influenza vaccination is recommended annually for all adults, regardless of age. Additionally, those who have a history of cardiopulmonary disease, DM, or hemoglobinopathy, or who are residents of a chronic care facility should receive an annual influenza vaccination, regardless of age.

Pregnant women who will be in their second or third trimester during the influenza season should also receive the vaccine.





Pneumococcal Vaccine


Pneumococcal vaccination with the pneumococcal polysaccharide vaccine (PPSV23) is indicated for all adults age >65. Additionally, the following should receive the vaccine at any age:

Those with history of sickle-cell disease or splenectomy

Those with history of cardiopulmonary disease, alcoholism, or cirrhosis

Alaskan natives and certain Native American populations

Those who are immunocompromised (hematologic malignancy, chronic renal failure, nephrotic syndrome, HIV-positive; or taking immunosuppressive medications)



Additionally:

Those age >65 who received PPSV23 earlier than age 65 also need a booster shot if it has been more than 5 years since being vaccinated

Those with high risk of fatal infection (asplenic patients, immunocompromised patients, kidney disease, chemotherapy, long-term steroids, cancer including leukemia and lymphoma, organ transplant) should be revaccinated 1x after 5 years

No one gets more than 1 booster shot per lifetime





Varicella Vaccine


Varicella vaccine is a live, attenuated vaccine recommended for use in all adults who lack a history of childhood infection with varicella virus. Being a live, attenuated vaccine, varicella vaccine should not be given to immunocompromised patients, HIV-positive patients when symptomatic, those with <200 CD4 cells, or pregnant women.





Shingles Vaccine


The shingles (zoster) vaccine is recommended routinely in order to reduce the risk of shingles and its associated pain in people ≥60. Only one dose of zoster vaccine is typically given. Persons who report a previous episode of zoster and persons with chronic medical condition (chronic kidney disease, diabetes) can be vaccinated.

Zoster vaccination is not indicated to treat acute zoster, to prevent those with acute zoster from developing post-herpetic neuralgia, or to treat ongoing post-herpetic neuralgia. Before routine administration of zoster vaccine, it is not necessary to ask patients about their history of varicella (chickenpox) or to conduct serologic testing for varicella immunity. The zoster vaccine is a lyophilized preparation of live, attenuated VZV.





HPV Vaccine


The quadrivalent human papilloma virus (HPV) vaccine prevents against 4 types of HPV (types 6, 11, 16, 18) that are associated with genital warts and cervical cancer. It is given in 3 doses and it is recommended for those age 11–12, but can be given at age 9.

It is also recommended for those who did not complete the series or were never vaccinated from age 13–26. Males age 9–26 might get the vaccine to prevent genital warts. Cervical cancer screening with Pap smear should continue after vaccination.





Smoking Cessation


Smoking cessation is the most preventable cause of disease. Smoking is responsible for 1 in every 5 deaths in the United States. There are 5 steps a physician can take to help patients stop smoking.

ASK about smoking at every visit.

ADVISE all smokers to quit at every visit.

ATTEMPT to identify those smokers willing to quit.

ASSIST smokers in quitting by setting a quit date (usually within 2 weeks) and using nicotine patches/gum or the oral antidepressant bupropion as supportive therapy. Varenicline, a nicotinic receptor partial agonist, can also be used to treat nicotine addiction.

ARRANGE follow-up. Provide positive reinforcement if the quit attempt was successful. If the quit attempt was not successful, then determine why the patient smoked and elicit a recommitment to smoking cessation. Most patients will require several attempts before being successful.



U/S should be given once in male smokers age >65 in order to screen for abdominal aortic aneurysm. There are no screening recommendations in male nonsmokers and women, regardless of smoking history.





Osteoporosis Prevention


All women age >65 should be given a DEXA scan. Screening should begin at age 60 if there is low body weight or increased risk of fractures.





Prevention of Alcohol Abuse


Physicians should screen for alcohol abuse by using the CAGE questionnaire:

Have you ever felt the need to: Cut down on your drinking?

Have you ever felt: Annoyed by criticism of your drinking?

Have you ever felt: Guilty about your drinking?

Have you ever taken a morning: Eye opener?



A positive screen is 2 “yes” answers. One “yes” should raise the possibility of alcohol abuse.





Prevention of Violence and Injury


Injuries are the most common cause of death age <65. The role of the physician is to advise patients about safety practices that can prevent injury. Advising the patient about the importance of seat belts, bicycle helmets, not driving after one drinks alcohol, and understanding the risks that firearms pose in the home can all reduce the risk of serious injury.

Identifying women who are at increased risk of physical or sexual abuse is an essential role for physicians. Simply asking women if they have been hit, kicked, or physically hurt can increase identification by more than 10%.





2





Infectious Disease





Case 1


Chief Complaint


Fever, cough, and chest pain





History and Physical Examination


A 32-year-old man comes to the emergency department with 5 days of fever, a cough that is sometimes productive of blood, and pleuritic chest pain. He is an active IV drug user and last used yesterday. He denies being HIV positive. Past medical history is significant for skin abscesses in the past, but recently he has been quite well. He uses no medications and has no allergies. His T is 39 C (102.2 F), BP is 112/72 mm Hg, and pulse is 110/min.

Physical examination reveals a thin, weak-appearing man lying on his side in the stretcher. Examination of the head, eyes, ears, nose, and throat shows petechiae in his mouth and in the conjunctivae. Eye grounds are normal. The chest is bilaterally clear to auscultation. A 2/6 systolic ejection murmur is audible over the lower left sternal border. There is no radiation of the murmur. The abdomen is benign and the extremities have no clubbing, but thin red lines are visible under the fingernails in the distal 1/3.





Differential Diagnosis


Pneumonia

Infective endocarditis (IE)

Sepsis

Bronchiectasis





CCS Note


Many cases that appear on the CCS are not diagnostically difficult. The diagnosis is often obvious, with the emphasis on testing and treatment.





Initial Management


Setting: emergency department

Diagnostic/Therapeutic Plan

Chest x-ray

Blood cultures





Test Results


Methicillin-sensitive Staphylococcus aureus

Multiple nodular lesions visible bilaterally





CCS Note


You will not be given the results of cultures at the beginning of your ID cases. Treatment is empiric.





Assessment


Any active IV drug abuser presenting with fever may have acute endocarditis. This patient also has a cough, hemoptysis, and pleuritic chest pain. IV drug users are also at risk for pneumonia. However, this patient has a heart murmur, and the pulmonary symptoms combined with multiple, bilateral nodular lesions on chest x-ray most likely represent septic emboli to the lungs from the right side of the heart. The tricuspid valve is most commonly involved in drug abusers (50% of the time), with aortic valve involved 25% and mitral valve 20%.

The conjunctival petechiae and splinter hemorrhages are also indicative of endocarditis in both the acute and subacute forms. Roth spots (retinal lesions), Janeway lesions (flat, painless, purplish lesions on the hands and feet), and Osler nodes (pea-sized, painful nodules that usually occur on the pads of the fingers and toes and on the palms) are usually associated with subacute endocarditis. Most of the embolic phenomena are quite rare, and their absence should never dissuade you from suspecting endocarditis. Embolic phenomena arise from the left side of the heart.





Further Management Plan/Results


Echocardiogram: vegetation visible on tricuspid valve with tricuspid regurgitation, and atrial septal defect





Further Management


IV antibiotics (e.g., nafcillin or oxacillin) for 4–6 wks, with gentamicin for first week

If acute decompensation occurs, surgical replacement of valve; also consider surgery for myocardial abscess, repeated emboli, very large vegetations, fungal endocarditis, or prosthetic valve endocarditis





note


Start empirical antibiotics for all presumed infections after cultures have been drawn.





Discussion


Any IV drug user presenting with unexplained fever should be placed on IV antibiotics upon admission. The concern is for suspected endocarditis, because of the rapid decompensation that can occur with acute endocarditis. This should be done even in the absence of a murmur. Always take 3 sets of blood cultures before starting the antibiotics within 1 hr.

A transthoracic echocardiogram (TTE), with sensitivity of only 60%, should be done first. Detection of a vegetation is a positive test. If it is negative, then perform a transesophageal echocardiogram (TEE), with sensitivity of 95%.

Patients with abnormal findings on TTE who may require further evaluation by TEE include those with significant valvular regurgitation to determine need for surgery, and those with ≥1 risk factors for perivalvular abscess including new conduction delay on ECG, aortic valve endocarditis, and persistent bacteremia or fever despite appropriate antimicrobial therapy.

S. aureus accounts for 60–90% of endocarditis in IV drug abusers, and, depending on local conditions, a large percentage of this may be methicillin-resistant. A large portion of S. aureus endocarditis cases are attributed to healthcare-associated bacteremia. Vancomycin and gentamicin is good empiric coverage until the results of blood cultures are known.

Native valve subacute endocarditis is caused by Streptococci 50–60% of the time. Viridans streptococci, which are normal inhabitants of the mouth, account for 75% of these. Streptococcus bovis accounts for 20% and is particularly associated with neoplastic diseases of the colon. Staphylococci account for about 30% of native valve subacute endocarditis, and 90% of this is S. aureus. Enterococci account for 5–10% of cases.

Culture-negative endocarditis is caused by the HACEK organisms. The name is formed from their initials:

Haemophilus (Haemophilus parainfluenzae), (Haemophilus aprophilus), (Haemophilus paraprophilus)

Actinobacillus

Cardiobacterium hominis

Eikenella corrodens

Kingella (Kingella kingae)



Prosthetic valve endocarditis is caused most often by Staphylococci in the early postoperative period. Staphylococcus epidermidis is more common in the first 2 mos after the replacement. Currently, CHF is the most common cause of death. As time goes on, Streptococcus viridans becomes more common.

Other complications of endocarditis are embolic phenomena to the brain, causing abscess and mycotic aneurysm; renal infarction and abscess; and splenomegaly. The most common complication is CHF from valvular degeneration. In the pre-antibiotic era, glomerulonephritis was far more common. Strokes and major systemic embolic events are present in about 25% of patients within 1 week of therapy.

This patient has methicillin-sensitive S. aureus, and nafcillin (or oxacillin or cefazolin) should be used for 4 wks; it is usually used with gentamicin or another aminoglycoside for the first 5 days (optional).

These are bacteriocidal and must be used over vancomycin if the organism is methacillin-sensitive.

This patient will likely need 6 wks of antibiotics because of the vegetation and evidence of septic emboli in the lungs.

For patients with native valve subacute endocarditis from a sensitive S. viridans, penicillin G or ceftriaxone for 4 wks alone is often sufficient. Alternatively, use gentamicin plus either aqueous crystalline penicillin G or ceftriaxone for 2 wks, in the absence of renal insufficiency.

Enterococcus is best treated with a beta-lactam antibiotic such as penicillin or ampicillin, in combination with an aminoglycoside (gentamicin or streptomycin) for the entire 4 to 6 wks.

HACEK organisms are treated with ceftriaxone, ampicillin-sulbactam, or ciprofloxacin for 4 wks.

If the patient has urticarial rash to vancomycin or MIC for vancomycin is >2, use daptomycin to treat right-sided MRSA endocarditis. Daptomycin is used for MRSA skin and soft tissue infection, right-sided endocarditis, and bacteremia, usually due to line sepsis. Do not use daptomycin for pneumonia, as it is inactivated by surfactants.





Clinical Pearl


Oxacillin, nafcillin, and cefazolin are the best antibiotics for MSSA.

Daptomycin inserts into the cell membrane, where it then aggregates. The aggregation of daptomycin creates holes that leak ions. This causes rapid depolarization, resulting in a loss of membrane potential leading to inhibition of protein, DNA and RNA synthesis, which results in bacterial cell death.

Indications for surgery are the following:

Evidence of uncontrolled infection can mean persistence of positive blood cultures while already on therapy, recurrent emboli formation of myocardial or valvular ring abscesses, or spread of the infection to involve the conduction system of the heart

Acute heart failure indicates degeneration of the valves, papillary muscles, or chordae tendinea sufficient to cause evidence of CHF

Valvular regurgitation

Recurrent embolic event because of a large vegetation



Infective endocarditis prophylaxis is recommended for patients with the following (high-yield):

Prosthetic cardiac valve



Previous episode of infective endocarditis



Congenital heart disease characterized by unrepaired cyanotic congenital heart disease, including palliative shunts and conduits; a completely repaired congenital heart defect with prosthetic material or device during the first 6 months after the procedure; and repaired congenital heart disease with residual defects



Cardiac transplantation recipients in whom cardiac valvulopathy develops





Other rules to follow:

Antibiotic prophylaxis is recommended for all dental procedures which involve manipulation of gingival tissue or periapical region of the teeth or perforation of oral mucosa; limit to patients with the cardiac conditions mentioned above.

Antibiotic prophylaxis is no longer recommended for any GI or GU procedure.

Antibiotic prophylaxis is reasonable for procedures on the respiratory tract which involve incision or biopsy (e.g., tonsillectomy, bronchoscopic biopsy), and on infected skin, skin structures and musculoskeletal tissue; limit to patients with the cardiac conditions mentioned above.

For those who need prophylactic antibiotics, give amoxicillin 30–60 minutes before the procedure.

In cases of penicillin-allergy, give clindamycin, cephalexin, or a macrolide.





Final Diagnosis


Acute bacterial endocarditis





Basic Science Correlate


Streptococcus viridans is the most common overall organism to cause endocarditis. It is a low-virulence organism that infects previously damaged valves (MVP or chronic rheumatic heart disease because of valve scarring). Subacute endocarditis is typically associated with small vegetations that do not destroy the valve.

Staphylococcus aureus is a high virulence organism associated with IV drug use. It results in large vegetations which rapidly destroy the valve.

Staphylococcus epidermidis is associated with endocarditis of prosthetic valves within 2 months after surgery.

Streptococcus bovis is associated with colorectal cancer.





Clinical Pearl


Libman-Sacks endocarditis is due to sterile vegetations which arise in association with SLE. Vegetations are present on and under the surface of the mitral valve, and result in mitral regurgitation. (Think of this in a young female with rash, joint pain and MR without fever!)





Clinical Pearl


In chronic rheumatic heart disease, patients are often immigrants from developing countries. The mitral valve is almost always involved and causes mitral stenosis with “fish-mouth” appearance.





Case 2


Chief Complaint


Pain and swelling of left leg





History and Physical Examination


A 72-year-old white man with a history of prostatic cancer metastatic to bone and the lymphatic system comes to the emergency department because of a several-day history of increasing swelling and erythema of left leg from the knee down. He denies shortness of breath or chest pain. The patient feels warm. His T is 38.4 C (101.1 F).

Physical examination reveals a left leg that is swollen and erythematous below the knee, moderately tender and warm to touch; there is no palpable fluid collection or skin breakdown.





Differential Diagnosis


Cellulitis

Deep venous thrombosis

Lymphangitis





Initial Management


Setting: outpatient or emergency department

Diagnostic/Therapeutic Plan

Duplex U/S scan of venous system of the leg





Test Results


No evidence of thrombosis





Assessment


With a unilateral red, tender, warm, swollen leg without evidence of deep venous thrombosis, cellulitis is the most likely possibility. No further diagnostic tests are required. The primary means of diagnosing cellulitis is by clinical examination and history.

Venography is not the first test to exclude a thrombosis, even though it is slightly more sensitive and specific than U/S. This is because of the risk of renal toxicity in the elderly or allergic reaction from exposure to the required contrast agent. Venogram is done if the suspicion for a clot is very high and U/S is negative.

Specific microbiologic diagnosis is not routinely indicated. This is sometimes done in unresponsive cases by injecting a small amount of saline subcutaneously into the leading edge of the infection. Then, aspirate and send the sample for culture.





CCS Note


A specific microbiologic diagnosis is almost never obtained in the clinical management of a skin infection. Treatment is initiated and continued on an empiric basis.





Treatment Plan


IV antibiotics with oxacillin or nafcillin

Elevation of leg and warm soaks

Oral dicloxacillin (mild cases); if mild penicillin allergy such as rash, use oral cephalexin; if life-threatening penicillin allergy such as anaphylaxis, use clindamycin, macrolides, and new fluoroquinolones





Discussion


The most likely organisms in cellulitis are group A streptococci (S. pyogenes) and S. aureus.

Mild infections can be treated in the outpatient setting with oral dicloxacillin or oral cephalosporins.

For moderate cellulitis or cellulitis that does not resolve with oral treatment, a first-generation IV cephalosporin such as cefazolin or cephalexin is appropriate.

In cases of severe penicillin allergy (e.g., anaphylaxis), vancomycin or clindamycin is used.

Rates of cross-reaction between penicillin and cephalosporins are <5%. For reactions that were originally just a rash, cephalosporins are safe to use.

Antibiotics are continued until symptoms have resolved. Duration of treatment varies depending on how long it takes to improve.

Vancomycin cannot be used orally to treat cellulitis because it is not absorbed.



The magnitude of CA-MRSA infections has reached epidemic proportions in the United States. Certain risk factors have been described which put certain groups at higher risk:

Household contacts of patients with proven CA-MRSA infection

Children

Men who have sex with men (MSM)

Injection drug users

Athletes engaged in contact sports

Certain racial and ethnic groups such as Native Americans and Pacific Islanders



However, most patients with MRSA have none of these risk factors.

Remember that for severe, invasive infections requiring inpatient therapy with IV antibiotics, the drug of choice is vancomycin, but daptomycin, ceftaroline, tigecycline, telavancin, and linezolid can also be used.





Clinical Pearl


Cellulitis with abscess formation or purulent drainage is most likely MRSA.

In the last few years there has been a dramatic increase in skin and soft-tissue (and other site) infections due to community-acquired strains of MRSA (unlike hospital-associated isolates of MRSA, patients with CA-MRSA infection are relatively young and healthy, having had no recent contact with the health care system).

Surgical drainage, along with incision of abscess and deeper infection, is crucial for adequate treatment. A small abscess with no surrounding erythema needs no antibiotics.

In addition to incision and drainage, antibiotics are needed for the following:

Patients who are very young or elderly

Cases where multiple sites of infection, systemic illness, comorbidities, or immunosuppression are present

Cases where infection quickly progresses and is associated with concomitant cellulitis

There is poor response to incision and drainage

Abscesses that are in locations where they are difficult to drain





Final Diagnosis


Cellulitis





Case 3


Chief Complaint


Right leg pain





History and Physical Examination


A 45-year-old woman presents to the emergency department with 2 days of severe right lower extremity pain and swelling. The pain has been getting progressively worse and is now so intense that she cannot walk on her leg. The pain started over the shin and has now spread rapidly from the ankle to just below the knee. She is currently in extreme pain. She also complains of fevers. She has a past medical history of diabetes type 2 and is non-compliant. The diabetes is poorly controlled and her last Hb A1C about 1 year ago was 10%.

Physical examination reveals T 103° F, pulse 120/min, and BP 100/50 mm Hg. She is diaphoretic, lethargic, and toxic-appearing. The lungs are clear. Cardiac exam is normal except for tachycardia. Her right lower extremity shows tense edema with erythema and dark purple bullae expanding from the ankle to the knee. Warmth and tenderness are noted.





Differential Diagnosis


Cellulitis

Deep venous thrombosis

Necrotizing fasciitis





Clues


History and physical exam findings are very concerning for necrotizing fasciitis.

Extreme pain and tense edema with dark bullae with fevers and systemic toxicity on examination are very worrisome for necrotizing fasciitis.





Initial Management


Setting: emergency department

Diagnostic/Therapeutic Plan

CBC

Chemistry profile

Lactic acid

Immediate surgical debridement (consult surgery); if there is clinical suspicion and the physical exam is consistent with diagnosis, okay to send patient to the operating room without imaging

Broad spectrum IV antibiotics





Test Results


WBC 30,000 cells/mL

Segments 90%

Hb 10 mg/dL

Platelets 100,000

Lactate 8.2 mmol/L

Bicarbonate 12 mmol/L

Glucose 400 mg/dL

Creatinine 2.5 mg/dL

BUN 35 mg/dL





Assessment


This presentation is consistent with necrotizing fasciitis. The patient is a poorly controlled diabetic with a very serious skin and soft tissue infection that is rapidly progressing.

Cellulitis involves the skin and subcutaneous tissue. Patients with cellulitis very rarely have high fever or leukocytosis. If a cellulitis spreads rapidly or has tense edema or discoloration or blister formation, one must consider necrotizing fasciitis. If the PE is uncertain, CT may be helpful by showing gas formation, though clinical judgment is still the most important element in diagnosis.

The gold standard for diagnosis is tissue biopsy obtained during surgical exploration. Nothing else can rule out the diagnosis.

Best initial management is early aggressive surgical exploration and debridement of necrotic tissue, together with broad spectrum empiric antibiotic therapy, and hemodynamic support

Surgery is indicated in the setting of severe pain, toxicity, fever, and elevated serum creatine kinase, with or without radiographic evidence of fasciitis

Antibiotic therapy without debridement is associated with mortality rate approaching 100%

Aggressive supportive care with IV fluids and vasopressors may be needed for hemodynamic instability





Further Diagnostic Testing


CT (or plain x-ray) shows gas formation in different areas of the right leg, as well as swelling and necrosis of various muscle groups





Basic Science Correlate


Necrotizing fasciitis is a destruction of the fascia and muscle through the release of toxins (virulence factors), which include streptococcal pyogenic exotoxins. Most cases are polymicrobial including anaerobes and aerobes. Common organisms include group A streptococcus (Streptococcus pyogenes), staphylococcus aureus, clostridium perfringens, Bacteroides fragilis, and Aeromonas.

Clindamycin inhibits production of exotoxins by binding to and inhibiting the 50S subunit of the bacterial ribosome.

Penicillin inhibits the formation of peptidoglycan cross-links in the bacterial cell wall. Its 4-membered β-lactam ring binds to the enzyme DD-transpeptidase. As a consequence, DD-transpeptidase cannot catalyze formation of these cross-links, and an imbalance between cell wall production and degradation develops, causing the cell to rapidly die.





Clinical Pearl


Any serious skin and soft tissue infection caused by group A streptococcus—specifically necrotizing fasciitis—is treated with immediate surgical debridement and penicillin with clindamycin. Most cases are caused by a mixed flora and require one of the following in addition to surgical debridement:

Vancomycin, daptomycin, tigacycline, ceftaroline, or linezolid (to cover MRSA) plus (coverage for gram negative, including pseudomonas plus anaerobes)

Imipenem/meropenem

Pipercillin/tazobactam

Ticarcillin/clavulinate plus clindamycin for toxin production



Clostridium perfringens is a rare cause from deep stab wounds or black tar heroin abuse (skin popping is when people inject heroin into subcutaneous tissue). Treat with penicillin plus clindamycin.





Discussion


Necrotizing fasciitis has a high mortality. Clinical judgment is still the most important element in diagnosis. Signs include:

Tense edema

Grayish, purplish or other discolored wound drainage

Vesicles or bullae

Necrosis

Ulcers

Crepitus



Pain may be out-of-proportion to findings.

CT or MRI finding may be helpful but may be non-specific. Leukocytosis, thrombocytopenia, and elevated creatinine with lactic acidosis may also be seen. CT may show fascia edema and subcutaneous gas.

If the suspicion is there, immediate surgical exploration is the correct answer. The gold standard for diagnosis is tissue biopsy obtained during surgical exploration. Nothing else can rule out the diagnosis. Time-to-first-debridement and its adequacy are predictors of survival.





Final Diagnosis


Necrotizing fasciitis





Case 4


Chief Complaint


“I’ve had a fever, headache, and neck stiffness for 2 days.”





History and Physical Examination


A 14-year-old boy, who is in generally excellent health, is brought to the emergency department by his parents because of high fever, headache, and neck stiffness for the last 2 days. He has become more ill over the morning. He uses no medications, has no allergies, and is not sexually active.

Physical examination reveals a thin and muscular boy lying on the stretcher with his hands over his eyes. His T is 38° C (104° F). Examination of the head, eyes, ears, nose, and throat is normal, and fundoscopic examination shows no papilledema. There is moderate nuchal rigidity and marked photophobia. Heart, lung, and abdominal examinations are normal. He is oriented to time and place. He knows his own name and he can recognize his parents. There are no focal motor or sensory deficits. Babinski reflex shows toes that are down-going.





Differential Diagnosis


Bacterial meningitis

Viral meningitis

Viral encephalitis

Arboviral encephalitis





Initial Management


Setting: emergency department

Diagnostic/Therapeutic Plan

Lumbar puncture





Test Results


WBC 3500/mm3 with 95% neutrophils

Negative Gram stain

Elevated protein

Decreased glucose

CSF culture: Streptococcus pneumoniae





Assessment


The acute onset and high fever with disorientation point toward an infectious etiology. The pronounced meningeal symptoms (headache, neck stiffness, photophobia) all point toward a meningitis rather than an encephalitis, though it can be difficult to distinguish them clinically. The patient is awake and has a nonfocal neurologic examination.

A clinical diagnosis of encephalitis requires more than a headache. The absence of papilledema, confusion, and focal neurologic findings point away from any evidence of CNS mass lesion and generally indicate that it is safe to perform a lumbar puncture without CT scan of the head first. The differential on the cell count showing neutrophils and the high total WBC count are quite characteristic of a bacterial etiology.

CT head should be done before the LP only if the patient has altered mental status, papilledema, seizures, focal deficits, severely immunocompromised status (HIV or transplant). If head CT is required, do not hold antibiotics. Send blood cultures and then start antibiotics.





Further Management Plan/Results


Start empiric antibiotics





CCS Note


All body fluid infections such as urine, CSF, ascites, pleural effusion, and joint fluid are initially diagnosed based on cell count. Cultures are never available at the time a treatment decision must be made.

Because of this patient’s severe symptoms combined with a high CSF WBC count (most likely neutrophils), empiric therapy must be started before knowing the culture results. Ceftriaxone, with vancomycin, should be used until the culture results are known.





Discussion


There is no predetermined length of treatment; that will depend on the clinical response and whether the CSF clears of organisms. Listeria is a consideration in neonates or patients age >50, or patients with diabetes, lymphoma, HIV, and in steroid use. Remember that Listeria is resistant to all cephalosporins. Add penicillin or ampicillin to empiric ceftriaxone if the patient is immunocompromised and you suspect Listeria.

Although viral meningitis can give neutrophilic predominance in the CSF in the first 24 hours, it usually has a much lower total WBC count compared with bacterial meningitis. Viral meningitis generally gives hundreds of cells, whereas bacterial can give thousands. The Gram stain is only 60–80% sensitive in the detection of the pathogen in bacterial meningitis, so the negative stain does not rule out a bacterial etiology. Without a specific organism seen, the patient should receive coverage for the most common organisms. Add vancomycin to the empiric ceftriaxone until culture results are known.

S. pneumoniae and Neisseria meningitis are most common in this patient’s age group. Listeria does not need to be covered empirically unless the patient is an infant or otherwise immunocompromised with cancer (lymphoma most common) or steroid use. Ceftriaxone is excellent empiric coverage until the culture results of the CSF are known. Vancomycin is always added.

In the United States, 25,000 cases of bacterial meningitis occur each year; 70% of cases occur in children age <5 years.

In adult meningitis, H. influenzae accounts for only 1–3% of cases, due to the introduction of the haemophilus B vaccine.

S. pneumoniae is the most common cause of meningitis in children beyond the neonatal period, as well as in adults.

In the neonatal period, gram-negative bacilli and group B streptococci are the most common causes of meningitis.



The most common complication from bacterial meningitis is hearing loss. Mental retardation, cerebral palsy, seizures, and language problems may also occur.





Follow-up Management and Prevention


Initial empiric therapy is ceftriaxone and vancomycin until results of the sensitivities are known

If organism is penicillin-sensitive, change the antibiotic to penicillin or ampicillin Corticosteroid (dexamethasone) therapy is now considered standard empiric therapy for most cases of bacterial meningitis; benefits are greatest in patients with pneumococcal meningitis, resulting in decreased morbidity (deafness) and mortality

Dexamethasone should be given immediately before, or with, the first dose of antibiotic and continued for 4 days

Steroids can be discontinued if etiology of meningitis turns out to be non-pneumococcal





Repeat lumbar puncture after a few days to ensure that infection has cleared, necessary only if prompt clinical resolution does not occur

Examine for otitis, mastoiditis, sinusitis to try to identify the origin of the meningitis

For brain abscess, do surgical drainage PLUS empiric coverage with metronidazole AND ceftriaxone with or without vancomycin (polymicrobial, including anaerobes, most importantly, B. fragilis)

For post-neurosurgical or post-head traumatic patients, give vancomycin PLUS cefepime or meropenem or ceftazidime to cover MRSA and pseudomonas





Final Diagnosis


Pneumococcal meningitis





Clinical Pearl


Other types of meningitis to consider are:





Cryptococcal Meningitis


History of HIV with <100 CD4 cells. India ink positive in 50–70%, antigen test positive in >90%

More gradual in onset, less severe

Initial therapy with amphotericin, then lifelong fluconazole





Rocky Mountain Spotted Fever


Rash on wrists and ankles that moves toward the body

Confirm with serology specific for Rickettsia; treat with doxycycline until results of testing are known





Lyme Disease


Endemic area such as the Northeast; history of rash

Diagnose with positive enzyme-linked immunosorbent assay or Western blot; treat with ceftriaxone





Case 5


Chief Complaint


“My belly is swollen, and it hurts.”





History and Physical Examination


A 59-year-old woman comes to the emergency room with 2 days of increasing abdominal pain and distension. She has a history of alcoholism and biopsy-proven cirrhosis of the liver. Her ascites had been controlled in the past with a low-sodium diet and spironolactone, but she has been noncompliant with her medications recently.

Vital signs are T 38.4 C (101.1 F), BP 105/70 mm Hg, and pulse 120/min. Physical examination shows a few spider angiomata visible on the face. Her extremities have a 2+ pitting edema in the legs to the mid-thigh. Her abdomen is moderately distended with the presence of a fluid wave; it is diffusely tender but soft. There is no guarding or rebound tenderness. The liver and spleen are not palpable secondary to the ascites. There are normal bowel sounds. The remainder of the physical examination is unremarkable.





Differential Diagnosis


Spontaneous bacterial peritonitis

Secondary peritonitis (bowel perforation)

Pancreatitis

Cholangitis

Diverticulitis





Initial Management


Setting: emergency department

Initial Diagnostic Plan Results

CBC WBC 14,500/mm3 with 77% polymorphonuclear leukocytes, platelets 118,000/mm3

Prothrombin time 14.7 seconds (normal: <13 seconds)

Albumin 2.7 g/dL (normal: 3.5–5 g/dL)

AST/ALT Normal

Abdominal x-ray No obstruction, no air-fluid levels

Chest x-ray No infiltrates, no air under the diaphragm





Assessment


The ascites that accumulates from alcoholic cirrhosis is especially predisposed to spontaneous peritonitis. Spontaneous peritonitis presumably occurs from hematologic seeding in the absence of perforation of an abdominal organ or trauma, such as a knife wound. Although this patient’s complaints (pain and distension) and physical exam (fever, tenderness) are clearly indicative of peritonitis, these findings do not have to be present for spontaneous bacterial peritonitis to occur. Ultimately, the only certain diagnostic method is a paracentesis of the ascitic fluid. Patients may also present with hepatic encephalopathy.

A paracentesis must be performed in new-onset ascites even in the absence of symptoms because spontaneous bacterial peritonitis can still be present. Criteria for diagnosis are a polymorphonuclear leukocyte count of >250/mm3 or total WBC count >500/mm3 in the ascitic fluid. The elevation of the prothrombin time and the decreased albumin are indicative of the decreased synthetic function of the liver with far advanced cirrhosis. The transaminases are normal because eventually the liver becomes so destroyed that the transaminases return to normal. If the ascitic fluid had very low glucose (<50 mg/dL), very high LDH or neutrophil count >10,000 or is polymicrobial, secondary peritonitis should be suspected and imaging should be done.





Clinical Pearl


The Gram stain is relatively specific if it is positive, but it lacks sensitivity and cannot exclude infection if it is negative. This is also true for the culture of the paracentesis fluid.

Further Diagnostic Plan Results

Paracentesis WBC count 750/mm3 with 90% polymorphonuclear leukocytes

Culture yields E. coli

Fluid albumin 2.2 mg/dL





Treatment Plan


Antibiotics for gram-negative bacilli and S. pneumoniae (cefotaxime or ceftriaxone) plus infusion of IV albumin; in this case we know the cause is E. coli, but most cases are culture-negative, thus the need to cover S. pneumoniae with cephalosporins

Diuretics and repeated abdominal paracenteses to remove larger volumes of fluid if patient becomes uncomfortable or respiratory function is compromised





Discussion


Although spontaneous bacterial peritonitis implies that all abdominal organs are intact, the most common organisms are the bowel flora. Most often it is caused by a single agent. Polymicrobial infections generally indicate perforation of a viscus. Aerobic gram-negative bacilli (Enterobacteriaceae) such as E. coli are the most common. Gram positives such as S. pneumoniae, group A streptococci (pyogenes), and enterococci are also common. It is caused by translocation of enteric bacteria across the bowel wall.

Studies have shown that giving IV albumin infusion on days 1 and 3 of antibiotic treatment increases the effective arterial circulating volume and renal perfusion, thus decreasing the incidence of hepatorenal syndrome and improving mortality.

IV cefotaxime has evolved as the drug of choice, however. Cefotaxime will cover E. coli as well as S. pneumoniae. Anaerobes are rarely the causative organism in spontaneous bacterial peritonitis. When a specific organism is identified, as with this patient, the choice depends upon the specific sensitivities of the organism.





Prevention


Around 70% of patients who survive spontaneous bacterial peritonitis will have another episode within 1 year. Oral norfloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole have been shown to reduce the rate of recurrent infections to <20%. Therefore, any patient with a history or spontaneous bacterial peritonitis should take one of these agents for prophylaxis indefinitely.

When patients with cirrhosis have bleeding esophageal varices, they are at an increased risk of developing spontaneous bacterial peritonitis. Studies show that giving these patients ceftriaxone or ciprofloxacin for 1 week during the bleed reduces the risk. Therefore, during a variceal bleed, patients with cirrhosis should receive antibiotics, even if they do not have clinically apparent ascites.





Final Diagnosis


Spontaneous bacterial peritonitis





Case 6


Chief Complaint


“I’m here to see what medications I need.”





History and Physical Examination


A 47-year-old woman who has recently found that she is HIV-positive comes to your office for an initial evaluation. She has always been healthy and took the test only because an old boyfriend died of AIDS. She has no other medical problems and is currently on no medications.

Her only tests done so far are CD4 (T-cell) count 47 cells/mL (normal 600–1,200 cells/mL), polymerase chain reaction-RNA viral load 180,000 (normal <50 to >750,000), a genotype resistance test (pending), and PPD skin test with 8 mm in duration. She has no symptoms. Her last Pap smear was 4 years ago. Vital signs and examination, including pelvic examination, are normal.





note


Genotype resistance testing is done at initial diagnosis to determine if resistance to antiviral therapy exists. It is used to select treatment medications.





Initial Management


Setting: outpatient

Diagnostic/Therapeutic Plan

Rapid plasma reagin or venereal disease; normal research laboratory tests for syphilis

Toxoplasmosis antibody test

CBC

Chemistries

Pap smear

Chest x-ray

Hepatitis A, B, and C serology





Test Results


Rapid plasma reagin or venereal disease: normal

Toxoplasmosis antibody test: normal

CBC: normal

Chemistries: normal

Pap smear: normal

Chest x-ray: normal

Hepatitis A, B, and C serology: negative





Assessment


All patients who present for initial evaluation of HIV should have a set of routine lab evaluation tests to determine the need for prophylactic medications and determine prognosis. T-cell subsets (CD4 count) are the primary indicator for the need to initiate antiretroviral therapy and for making decisions about prophylactic medications. CD4 count tells us what diseases the patient is at risk for now, and it is the major clinical marker of the immunocompetence of the patient.

Viral load testing tells us how aggressive a person’s disease is, i.e., the magnitude of replication of the virus in the body. A high viral load implies a more aggressive disease in which the CD4 count will drop more rapidly. Viral load testing gives a numerical value to the amount of HIV in the patient’s blood. Viral load is like a glucose level in a diabetic patient: Higher viral load implies the need for more medication. The viral load is the most important test to monitor response to therapy. The aim of therapy is to have an undetectable HIV viral load in the serum after 6–12 mos of therapy (<50 copies/µL).

The other routine tests in HIV—syphilis serology, toxoplasmosis serology, TB skin testing with PPD, and Pap smear—determine the likelihood of common opportunistic infections. This patient’s PPD is considered positive because the induration is >5 mm in diameter (erythema without induration is not considered a positive test).

Induration of ≥15 mm is considered positive for the general population that is at low risk of developing active TB

Cutoff ≥5mm is considered for those patients at the highest risk of disease, e.g., HIV-positive patients, recent contact of TB patients, patients with fibrotic changes on chest x-ray consistent with prior disease, and organ transplant recipients or immunosuppressed patients

Cutoff ≥10 mm is used for those at intermediate risk of the disease, e.g., recent immigrants from endemic countries [within 5 years], health care personnel, injection drug users and mycobacteriology laboratory personnel, children age <4, and infants/children/adolescents exposed to adults with active TB



Further Diagnostic Plan Results

Repeat viral load testing 150,000





Treatment Plan


Pneumocystis jirovecii (formerly carinii) pneumonia prophylaxis with trimethoprim/sulfamethoxazole

Mycobacterium avium complex prophylaxis with azithromycin weekly

Antiretroviral therapy with 2 nucleosides and either 1 protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI)

Isoniazid 300 mg/d for 9 mos with pyridoxine (vitamin B6) to prevent peripheral neuropathy associated with isoniazid

Pneumococcal pneumonia vaccination

Hepatitis A and B vaccination

Influenza vaccination yearly





Discussion


Pneumocystis pneumonia prophylaxis must be initiated in all patients with <200 CD4 cells/mL. The most effective therapy is trimethoprim/sulfamethoxazole. If the patient is allergic to sulfa drugs, dapsone or atovaquone may be used as an alternative. Aerosolized pentamidine is only used in patients who cannot tolerate either trimethoprim/sulfamethoxazole or dapsone. Pentamidine is less efficacious than trimethoprim/sulfamethoxazole, dapsone, or atovaquone and is rarely used. For treatment of pneumocystis in patients with sulfa allergy, the options include IV pentamidine, clindamycin with primaquine, or atovaquone. Pentamdine has many side effects including, hypoglycemia, hyperglycemia, acute pancreatitis, ATN, hepatotoxicity.

M. avium complex prophylaxis is indicated in all patients with <50 CD4 cells/mL. Azithromycin or clarithromycin are the best medications. Because azithromycin is used only 1x/week, it is easier to take than clarithromycin, which is used 2x/day. Rifabutin is less efficacious than either of these and has frequent side effects, such as uveitis. In addition, rifabutin has numerous interactions with other medications that are metabolized through the hepatic p450 system. Treatment of MAC is macrolide with ethambutol with or without rifabutin.

Antiretroviral therapy initiation is now recommended with the diagnosis of HIV irrespective of CD4 count.



In pregnancy, always treat with combination therapy, even if CD4 >500, to prevent perinatal transmission. Start treatment immediately, i.e., do not wait for second trimester, and always use at least 3 drugs.



Never use efavirenz in pregnancy.

Give the baby zidovudine during delivery and for 6 weeks after.



The starting regimen is a combination of 2 nucleoside medications and at least 1 protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI).

Nucleoside medications: zidovudine, lamivudine, abacavir, didanosine, emtricitabine, stavudine, DDC, tenofovir

Protease inhibitors: indinavir, ritonavir, nelfinavir, saquinavir, amprenavir, lopinavir/ritonavir, fosamprenavir, atazanavir, tipranavir, darunavir

NNRTIs: efavirenz, etravirine rilpivirine, nevirapine





note


All of the protease inhibitors end in -navir.



The most common regimen for therapy today is emtricitabine-tenofovir or abacavir-lamivudine + an integrase inhibitor.





Clinical Pearl


HIV patients with CD4 count >200 can get any vaccination.

If there is resistance to first-line agents, use a second-line agent: integrase inhibitor raltegravir, entry inhibitors, enfuvirtide (penetration), or maraviroc (attachment).

Most protease inhibitors are now ‘boosted’ with ritonavir, another protease inhibitor. Ritonavir by itself is not an effective antiretroviral because of poor efficacy and side effects. However, when given in low doses with other protease inhibitors, it boosts serum levels by inhibiting patients’ metabolism by inhibiting on the cytochrome P450 system. This allows for higher serum levels of the boosted protease inhibitor, which decreases the probability of the HIV virus developing resistance. In addition, a lower dose of the boosted protease inhibitor can be given, which decreases adverse effects and improves compliance, also contributing to the decreased likelihood of developing resistance.

HIV-positive patients should be treated at any age if their PPD is >5 mm in size. The usual length of therapy in an HIV-negative patient is 9 months. Patients with HIV are treated for 9 months as well. Pneumococcal vaccination is indicated for most patients with significantly compromised immune systems, such as HIV-positive patients. Vaccination is indicated whenever you encounter the patient, regardless of T-cell count.

Let’s say a 19-year-old man is evaluated in the emergency department for a 10-day history of fever, cervical lymphadenopathy, malaise and fatigue, sore throat, headache, and nausea, but no vomiting, diarrhea, abdominal pain, nasal congestion, or cough. He had a rash a few days ago that has resolved. He is sexually active with both men and women, and does not use condoms. What is the next step?

The next step is the HIV nucleic acid amplification test. These symptoms may represent infectious mononucleosis or syphilis, but this may also be acute HIV syndrome. It presents within 2–4 wks of infection and lasts for a few weeks. Symptoms usually resolve without treatment.

HIV nucleic acid amplification test is the test of choice. The ELISA/Western blot will be false negative at this point because antibodies have not yet formed.





CCS Note


On the CCS, knowledge of preventive medicine in an ambulatory setting is more important than knowledge of complex exotic diseases. Similarly, knowing when to start prophylaxis in HIV is more important than knowing specific antiretrovirals.





Final Diagnosis


Acquired immunodeficiency syndrome (AIDS)





Basic Science Correlate


Presumptive diagnosis is made with ELISA (sensitive, high false-positive rate and low threshold, rule out test); results are then confirmed with Western blot assay (specific, high false-negative rate and high threshold, rule in test).

HIV PCR/viral load tests determine the amount of viral RNA in the plasma.

ELISA/Western blot tests look for antibodies to viral proteins; these tests often are falsely negative in the first 1–2 months of HIV infection.





Case 7


Chief Complaint


Elevated liver enzymes





History and Physical Examination


A 39-year-old man with a history of IV drug use 20 years ago presents for evaluation of elevated liver enzymes. He offers no complaints and feels well. He has no history of anorexia, nausea or vomiting, malaise, fatigue, dark urine, or upper abdominal discomfort. He denies blood transfusions or alcohol intake. He denies light-colored stools. He is taking isoniazid for treatment of positive PPD. He went for routine screening tests and his doctor told him that he has elevated liver enzymes.

His temperature is 37.4° and BP 150/80 mm Hg. Physical examination shows no scleral icterus or jaundiced skin. The liver is non-palpable and non-tender; the spleen is not palpable. There is no right upper quadrant tenderness.





Differential Diagnosis


Chronic viral hepatitis (B or C)

Drug-induced hepatitis

Wilson’s disease, hemochromatosis, autoimmune hepatitis

Choledocholelithiasis

Fatty liver



Initial Diagnostic Plan Results

LFTs



Bilirubin (total)1.0 mg/dL;

AST (SGOT) 50 u/L (normal: 5–45 units);

ALT (SGPT) 150 u/L (normal: 5–45 units);

albumin 2.7 mg/dL (normal: 3.5–5.5 mg/dL)





PT



13.2 seconds (normal: <13 seconds)

CBC



Normal





Assessment


This patient has elevated liver enzymes which has many causes. Alcohol is not a likely factor because the ratio of AST:ALT is not 2:1.

Acute hepatitis is not likely because he is asymptomatic and he has a mild elevation in his transaminiases. The symptoms of acute hepatitis include malaise, anorexia, jaundice, abdominal pain, and tenderness and they are all identical. In acute viral hepatitis the transaminase would be very high, maybe over a thousand.

Hepatitis B and C are characterized occasionally by extrahepatic manifestations such as rash, arthralgias, glomerulonephritis, cryoglobulinemia (hepatitis C), and polyarteritis nodosa (hepatitis B) in a small number of cases.

Drug-induced or toxin-induced hepatic injury, such as from the patient’s isoniazid or other medications, is also indistinguishable from acute viral hepatitis. Acetaminophen, halothane, alpha-methyldopa, erythromycin, and allopurinol are among the most common causes of drug-induced hepatitis. Wilson disease, hemochromatosis, primary biliary cirrhosis, and so-called “autoimmune” or lupoid hepatitis are other forms that can often only be distinguished by a liver biopsy.

The initial step for determining the cause is to check hepatitis serologies. CT scan offers little help. MRI scan shows increased iron and sonography shows fat infiltration.

This patient needs a workup for chronic hepatitis that includes transferrin saturation for hemochromatosis, hepatitis serologies, anti-smooth muscle and anti-LKM for autoimmune hepatitis. Wilson's is less likely due to the lack of CNS symptoms.





Further Diagnostic Plan/Results


Hepatitis serologies

(including A, B, and C):



Hepatitis A: IgM negative

Hepatitis B: anti-HB core: IgM negative anti-HB core: IgG positive: HBsAg positive; HBe Ag-positive; anti-HBs antibody-negative

Hepatitis C: Ab negative HBV DNA high





CCS Note


As you advance the clock, you can use the “INTERVAL HISTORY” button at the top of the physical examination screen to give you a progress report on the patient.





Treatment Plan


Tenofovir





Discussion


This patient has chronic active hepatitis B and should be treated. The goal of antiviral treatment is ideally to convert hepatitis B surface antigen (HBsAg)–positive status to HBsAg-negative status, though a more common goal is to induce suppression of viral replication without necessarily obtaining clearance of virus. Diagnosis is made by HB core: IgG positive: HBsAg positive with the surface antigen. The elevated HBV DNA and elevated liver enzyme indicate that the hepatitis B is active and replicating.

Patients with chronic active HBV infection, defined by elevated hepatic aminotransferases or active inflammation on liver biopsy, should receive antiviral therapy. Clinical outcomes are improved in patients with chronic active HBV with effective viral suppression. For all forms of acute viral hepatitis, there is no specific treatment; rest and avoidance of hepatotoxic medications are generally recommended.

The HBe Ag is a measure of active viral replication and potential infectivity. These are the patients that are most likely to benefit from treatment. The anti-hepatitis B IgM core is an antibody that is also a measure of acute hepatitis B. Hepatitis B is treated with interferon or a reverse transcriptase inhibitor, such as lamivudine, telbivudine, or adefovir. The limiting factor with lamivudine is the development of high rates of resistance. Tenofovir and entecavir are newer, preferred agents because of lower rates of resistance. Patients should also be monitored for hepatocellular carcinoma (HCC) with regular liver U/S. Alpha-feto protein has poor sensitivity and should not be used for HCC screening.

The major differences between hepatitis A and B are their sources, methods of transmission, and incubation times.

Hepatitis A is predominantly food- and water-borne, with a 2–4 week incubation period. It can be transmitted by sex.

Hepatitis B is transmitted by sex, transfusion, needle sharing, and vertically from mother to child. Incubation period can be 1–6 mos

First test to become abnormal is surface antigen, which becomes abnormal before the development of symptoms or an increase in LFTs

Chronic hepatitis B is defined as the persistence of hepatitis B surface antigen for >6 mos.





Chronic hepatitis C is the most common cause of cirrhosis and hepatoma in the United States. It is transmitted via exposure to blood and blood products.

As of recently, there are effective drugs that provide >90% cure of chronic hepatitis C. FDA-approved drugs include sofosbuvir (Sovaldi) and simeprevir (Olysio). When either of these drugs is combined with peginterferon and ribavirin, hepatitis C can be cleared from the liver in >90% of the most common form of the virus (genotype 1).

If the PCR-RNA viral load is elevated, patients should be treated.

If there is fibrosis on the liver biopsy, treatment is even more urgent to prevent progression to cirrhosis, which is irreversible.



Acute hepatitis E is found mostly in Asia. It has the same acute presentation as acute hepatitis A or B. Hepatitis E is particularly associated with increased severity in pregnant women.





Final Diagnosis


Chronic hepatitis B





Case 8


Chief Complaint


“I’ve had a pain in my leg for the last several weeks.”





History and Physical Examination


A 54-year-old man with a history of diabetes mellitus and peripheral vascular disease comes to your office with an ulcer on his left leg below the knee for the last week. He has been on aspirin alone as treatment for his peripheral vascular disease for several years and has a stable pattern of leg claudication after he walks more than several blocks or a few flights of stairs. He has had ulcerations of the skin on his legs intermittently for several years, which have all resolved with local care. Generally, these ulcerations have not been painful. The area at the site of the ulcer has been painful for the last 2 weeks.

Vital signs are T 37.4 C (99.3 F), BP 130/80 mm Hg, and pulse 72/min. He appears to be pleasant and in no distress. Examination of the extremities shows a 3-cm ulceration on the medial surface of proximal left tibia. The area is erythematous, mildly swollen, and tender with a small sinus tract that drains a tiny amount of purulent material. The remainder of the physical examination is normal.





Differential Diagnosis


Aseptic ulceration

Osteomyelitis

Cellulitis

Skin abscess





Initial Management


Setting: outpatient; emergency department if symptoms are severe

Diagnostic/Therapeutic Plan

Plain x-rays of leg

ESR

CBC





Test Results


X-rays of leg normal

ESR elevated at 90 mm/h (normal <20 mm/h)

CBC normal





CCS Note


The CCS values an orderly and sequential evaluation over a jump straight to a single most accurate diagnostic test.

When patient is short of breath, do chest x-ray before chest CT.

When patient has leg ulcer, do x-ray before bone scan or MRI, even if the x-ray comes back negative.





Assessment


This patient is at increased risk of infection because of the poor circulation from his peripheral vascular disease. Diabetes gives a similar risk. Other risks for osteomyelitis also include bacteremia from any source with seeding of the bone, although this is more common in children, and the presence of a prosthetic device (e.g., total knee replacement).

An overlying ulceration and cellulitis can often be difficult to tell apart from an underlying osteomyelitis. This patient’s symptoms are worse than usual with his ulcers in the past. In addition, the area is tender with a draining sinus tract, which is more consistent with osteomyelitis. The ESR is also quite elevated, which is consistent with osteomyelitis as well.

A normal x-ray of the bone does not rule out osteomyelitis; it can take many weeks for it to become abnormal because >50% of the bone must become demineralized first. A technetium bone scan is more sensitive, and will detect an osteomyelitis after several days. However, an overlying infection can obscure the definitive diagnosis, and CT or MRI is superior for localizing the infection to the bone itself. CT or MRI is also superior for identifying the precise amount of bony destruction. MRI is superior to CT in terms of sensitivity. The MRI becomes abnormal within 2 days after the onset of osteomyelitis. This is equal in sensitivity to bone scan but with far greater specificity. MRI is excellent at distinguishing bone involvement from overlying soft tissue infection. Bone biopsy prior to starting antibiotics is mandatory to identify a specific organism.





CCS Note


The status of your patient can come up spontaneously as a “nurse’s note,” telling you how the patient is doing. You can’t predict when this will happen. These notes come up spontaneously as the clock is moved forward.

Further Diagnostic Plan Results

MRI scan of the leg Mild bony destruction of the proximal tibia

Biopsy of the tibia Neutrophils visible on Gram stain. S. aureus grows in culture





Treatment Plan


IV antibiotics for 6–12 wks; oxacillin or nafcillin if the organism is sensitive, vancomycin if it is MRSA

Surgical debridement as necessary





Discussion


The most common organism causing osteomyelitis is still S. aureus. In diabetics or in osteomyelitis contiguous to decubitus ulcers, gram-negative bacilli such as E. coli or Pseudomonas are also common.

Bone biopsy is essential because there is no other definitive way to know the specific agent causing the infection. Culture of the wound or draining sinus tract does not correlate well with the organism causing the bone infection. Empiric treatment should be discouraged.

Oxacillin (or nafcillin) and ciprofloxacin or oxacillin and a third-generation cephalosporin are adequate empiric treatment before knowing the results of the bone biopsy. Vancomycin to cover the Gram-positive organisms can be used if the patient has had an anaphylactic reaction to penicillin. Cephalosporins can be used if the penicillin allergy is only a rash. Other options for empiric osteomyelitis therapy before knowing the results of bone biopsy are carbapenems or the beta lactam/beta lactamase combinations, such as piperacillin/tazobactam or ampicillin/sulbactam.

Biopsy is essential because gram-negative osteomyelitis can be treated with oral ciprofloxacin. You cannot adequately treat the patient without the biopsy.





Final Diagnosis


Acute osteomyelitis





Case 9


Chief Complaint


“I’m having fever, cough, body aches, and chest pain.”





History and Physical Examination


A 77-year-old man comes to the emergency department complaining of an episode of shaking chills earlier that night. He has since developed right-sided pleuritic chest pain, fever, sweats, malaise, and purulent sputum with mild hemoptysis. He has osteoarthritis, but his past medical history is otherwise unremarkable. He has smoked 1 pack of cigarettes per day for 30 years.

Vital signs are T 39.8 C (103.6 F), BP 90/60 mm Hg, pulse 106/min, and respirations 32/min. The patient is diaphoretic but alert. Lung examination reveals right basilar rales. Examination of skin, heart, joints, and nervous system are normal.





Differential Diagnosis


Pneumococcal pneumonia

Legionella pneumonia

Haemophilus pneumonia

Aspiration pneumonia

Tuberculosis

Postobstructive pneumonia from lung cancer

Bronchitis

Mycoplasma pneumonia





Initial Management


Setting: emergency department

Diagnostic/Therapeutic Plan

Chest x-ray

Sputum Gram stain

Sputum culture

Pulse oximeter

CBC

Blood culture





CCS Note


Shaking chills suggest bacteremia and should always result in ordering blood cultures.





CCS Note


For dyspneic patients, an oximeter is very accurate in the assessment of hypoxia. ABG is necessary when CO2 retention is a possibility, such as in COPD.





Test Results


Right lower lobe, infiltrate with blunting of right costophrenic angle

Abundant polymorphonuclear leukocytes with gram-positive, lancet-shaped diplococci in pairs and chains

Sputum culture grows pneumococcus

Pulse oximeter 92% saturation

WBC count 23,000/mm3

Blood culture negative





Assessment


The history, physical examination, and chest x-ray confirm that this is pneumonia. The history of shaking chills is indicative of the bacteremia that can accompany bacterial pneumonia. The other symptoms, such as fever, cough, sputum, and hemoptysis, could present with bronchitis as well. Chest x-ray is done to distinguish between pneumonia and bronchitis; with bronchitis, chest x-ray is generally normal.

If the sputum did not reveal a specific organism then bronchoscopy with biopsy could be done to confirm a specific bacteriologic diagnosis. Bronchoscopy is only necessary if the patient does not respond to empiric therapy and is worsening.

Further Diagnostic Plan Results

Decubitus x-rays of chest Fluid in chest is free-flowing (i.e., presence of an effusion)





Clinical Pearl


Clinical improvement in pneumonia may not be apparent for up to 72 hours after the initiation of antibiotics. If symptoms do not improve after 72 hours, potential issues include resistant organisms, metastatic foci, effusions, or non-infectious etiology. In this case, chest CT and possible bronchoscopy should be considered.





Clinical Pearl


Consider community-acquired MRSA in IV drug users; concurrent or recent influenza (high yield), severe pneumonia requiring intubation and ICU admission, and necrotizing (cavitary) pneumonia.





Treatment Plan


Hospitalize patient

IV antibiotics (ceftriaxone or fluoroquinolones)

Thoracocentesis of the parapneumonic effusion (may need drainage if complicated parapneumonic effusion)





Discussion


Outpatient therapy of pneumonia is best with the new fluoroquinolones: levofloxacin, gatifloxacin, or moxifloxacin. These agents cover most penicillin-insensitive pneumococcus. The fluoroquinolones can be used for inpatient therapy as well. Ciprofloxacin should not be used for pneumonia. Other outpatient treatments include azithromycin and clarithromycin.





CCS Note


Admission criteria for pneumonia are based on the severity of the illness, not the x-ray findings. Culture results will not be given at the time you must make this triage decision.

Pneumococcal pneumonia is still the most common cause of hospitalization for community-acquired pneumonia. The history of cough and pleuritic chest pain with purulent sputum that grows streptococcal pneumonia is confirmatory.

In this patient with a specific organism seen on the Gram stain and the results of culture known, treatment with penicillin alone is sufficient if the culture indicates that the pneumococcus is sensitive. This patient should be admitted for IV medications because of increased WBC count, hypoxia, fever, older age, and chills.

For patients admitted with this presentation in whom a specific organism is not identified, penicillin alone is too narrow an agent. Second-generation cephalosporins (e.g., cefuroxime) or a third-generation cephalosporin (e.g., ceftriaxone) in combination with a macrolide could be used. Ticarcillin/clavulanate or ampicillin/sulbactam are good choices as well and should be combined with a macrolide or doxycycline to cover Mycoplasma, Chlamydia, and Legionella.





CCS Note


The regular hospital ward is the location for most pneumonia patients who are admitted. The ICU should be chosen only in the persistently hypoxic or hypotensive.

In patients with community-acquired pneumonia, the CURB-65 score is used as a mortality clinical prediction tool. It assigns 1 point for each positive indicator:

Confusion

Blood urea nitrogen level >19.6 mg/dL (7.0 mmol/L)

RR ≥30/min

Systolic BP <90 mm Hg or diastolic BP ≤60 mm Hg

Age ≥65



A score of 0–1 indicates consideration for outpatient management, while ≥2 indicates the need for hospitalization.

If the patient has heart disease and a prolonged QT interval on EKG, use doxycycline. Avoid macrolides and fluoroquinolones.

All older patients (age >70) with serious co-morbid conditions such as cancer, CHF, or liver/renal disease should be strongly considered for admission to the hospital. The main criteria for hospitalization are:

Older age

Tachycardia

Hypoxia

High fever

Leukocytosis

Inability to take oral medications

Hypotension

Confusion





Final Diagnosis


Community-acquired pneumonia





Clinical Pearl


Make sure you know what covers Pseudomonas and when you need to cover it:

Hot tub folliculitis

Malignant otitis externa in diabetics

Septicemia

Burn victims

Cystic fibrosis

Severely neutropenic patients (<500 neutrophils/mm3) presenting with fever, usually those on chemotherapy

Ventilator-associated pneumonia



Beta-lactams that cover Pseudomonas include:

Cefepime

Ceftazidime

Piperacillin/tazobactam

Ticarcillin/clavulanate

Imipenem/meropenem (not ertapenem)

Aztreonam (no Gram-positive coverage)

Non-beta-lactam include aminoglycosides and ciprofloxacin





Case 10


Chief Complaint


Fever and increasing headache for 1 week





History and Physical Examination


A 38-year-old man with AIDS comes to your office with a week of fever, ranging from 38.6–38.8 C (101.4–101.8 F) and an increasing headache. He also complains of sunlight hurting his eyes, nausea, and weakness. His past medical history is significant for Pneumocystis pneumonia and total CD4 count 89 cells/μL. He was just started on trimethoprim/sulfamethoxazole, tenofovir, emtricitabine, and efavirenz.

Vital signs are T 39 C (102.2 F), BP 110/70 mm Hg, pulse 95/min. Physical examination shows photophobia and slight nuchal rigidity. The rest of the examination is normal.





Differential Diagnosis


Cryptococcal meningitis

Bacterial meningitis

Viral meningitis

Toxoplasmosis

Lymphoma





Initial Management


Setting: emergency department

Diagnostic/Therapeutic Plan

Lumbar puncture

Serum and CSF cryptococcal antigen





Test Results


Lumbar puncture: 4 WBCs, opening pressure 32 cm H2O (normal: <20 cm H2O), India ink positive, VDRL tests negative

Serum titer 1:1,024; CSF titer 1:512; CSF fungal culture grows cryptococcus





Discussion


Cryptococcus is spread via soil and pigeon droppings via a respiratory route. Most patients will have mild or no respiratory symptoms. Mucicarmine staining will show round budding yeast with peripheral clearings or halos which are thick polysaccharide capsules. Initiation of treatment with conventional amphotericin B plus flucytosine must start immediately. Flucytosine may act synergistically with the amphotericin. Flucytosine must never be given alone because of the likelihood of the development of resistance.





Clinical Pearl


An important element of CCS is the sequence and timing of when to do things. The results of either the antigen test or the culture at the point of initial triage will not be presented. Treatment in infectious diseases is started empirically and modified later.

In addition to an elevated opening pressure, other factors associated with a worse prognosis in cryptococcal meningitis are low WBC count in CSF, low glucose level in CSF, positive India ink, and high cryptococcal antigen titer. Titers >1:8 or 1:16 are generally considered positive. Therefore, although a normal WBC count in CSF is <5, this patient’s count of 4 indicates a worse prognosis rather than a better one.

Amphotericin is given in any life-threatening fungal illness, such as cryptococcal meningitis. Although some patients will be successfully treated from the beginning with fluconazole alone, an unacceptably high percentage will fail treatment. Despite the factors listed above that are associated with poor prognosis, it is difficult to reliably predict who has mild enough disease to be treated with fluconazole alone. Hence, all patients should be started initially on amphotericin. After the acute treatment with amphotericin is complete, fluconazole must be continued orally lifelong in the AIDS patient if the CD4 cells do not increase. Discontinuation of fluconazole may be considered in some patients who have had an excellent response to HAART (highly active antiretroviral therapy), as defined as sustained increase in CD4 cells to >100/µl for more than 6-12 mos and who are asymptomatic.

In patients who have an elevated opening CSF pressure on initial LP (>20 cm H2O), daily repeat lumbar puncture to lower the CSF pressure is an important adjunctive treatment that substantially lowers the morbidity and mortality associated with this disease. Elevated CSF pressure is not appreciably lowered by medical therapy or corticosteroids.

Immune reconstitution inflammatory syndrome (IRIS) refers to a spectrum of inflammatory disorders that develops in patients with AIDS upon initiation of antiretroviral therapy. There is a paradoxical worsening of underlying opportunistic infections, undiagnosed or treated earlier, related to rapid restoration of immune function after commencement of HAART. IRIS typically develops within the first 3 mos after starting HAART, though it may occur much later. It occurs more often in patients with a low pretreatment CD4 count (usually <100/µl) and those who have a rapid improvement in CD4 counts and suppression of viral load.

For example, a patient with AIDS in whom HAART is initiated may have undiagnosed underlying cryptococcal meningitis. The patient may have no symptoms of the disease (headache, fever) in the absence of any immune cells. Once HAART is initiated, and if there is a rapid recovery of CD4 cells, the patient’s immune cells are able to mount an immunologic response against cryptococcus and the patient will present with worsening headaches and fever and other symptoms consistent with an inflammatory response.

IRIS can be seen with most opportunistic infections, including pulmonary tuberculosis. In most cases, unless the illness is life-threatening, HAART may be continued and the patient can be symptomatically treated with NSAIDS or corticosteroids. If a known opportunistic illness (OI) exists prior to starting HAART and CD4 count is very low, it is suggested to start treating the infection and begin HAART 2-4 wks later.





Clinical Pearl


If a ring-enhancing lesion is seen on CT in an HIV patient with CD4 <100, presume toxoplasmosis and start pyrimethamine with sulfadiazine. Repeat the CT in 2 wks to confirm that there is improvement.





Further Management Plan


IV amphotericin followed by oral fluconazole





Final Diagnosis


Cryptococcal meningitis





Case 11


Chief Complaint


“I have a burning sensation in my penis when I urinate.”





History and Physical Examination


A 28-year-old man comes to your office with several days of burning on urination and a yellowish penile discharge. He reports a history of a similar illness a year ago for which he received some medication but cannot describe. He is otherwise healthy and uses no medications. He is sexually active but denies HIV risk factors. He is adamant that all of his sexual partners have been completely healthy because he hates using condoms and makes sure his partners have no symptoms.

He is afebrile, and there is no adenopathy. Except for a yellow discharge coming from the urethra, the remainder of the examination is normal.





Differential Diagnosis


Gonococcal urethritis

Nongonococcal urethritis (chlamydia, herpes, Mycoplasma hominis, Ureaplasma)

Trichomoniasis

Reiter syndrome





Initial Management


Setting: outpatient

Diagnostic/Therapeutic Plan

Urethral swab with Gram stain and wet mount





Test Results


Urethral swab: negative for organism





Assessment


A sexually active person with urethral discharge is most consistent with a sexually transmitted urethritis. A urethral swab can frequently identify intracellular gram-negative diplococci, which are consistent with gonococcus. Their absence on Gram stain does not exclude the diagnosis. Although visualization of intracellular gram-negative diplococci on a cervical or urethral smear has a high specificity for N. gonorrhoeae, the absence of this finding is not sensitive enough to exclude infection. Nucleic acid amplification urine tests therefore are preferred. If gram-negative cocci are visible, culture is not necessary.

The swab should be inserted 1.5–2 cm into the urethra and rotated. The insistence by the patient that his partners have been asymptomatic does not exclude gonorrhea. In fact, the major source of infection seems to be from asymptomatic people who are colonized with the organism. The endocervix is the most common site of asymptomatic colonization.





Further Management Plan/Results


Culture of urethral swab on Thayer-Martin medium



Positive for N. gonorrhoeae

DNA probe for both chlamydia and gonorrhea



Positive for gonorrhea

VDRL test



Negative

HIV test



Negative





Treatment Plan


Ceftriaxone 125 mg intramuscularly once and single-dose azithromycin

Doxycycline (orally for a week) or azithromycin (1 dose)

Oral cefixime can be substituted for ceftriaxone to treat gonorrhea. Fluoroquinolones are NO longer recommended for the treatment of gonococcal infections in the United States because fluroquinolone-resistant N. gonorrhoeae are now widespread throughout the country.





CCS Note


Therapy for urethritis has to be ordered before the results of the tests are known.





Discussion


Gonorrhea is one of the most common reportable bacterial infections in the United States. Only 50% of all cases are reported. Gonorrhea can cause a wide variety of infections, ranging from an asymptomatic carrier to urethritis, pharyngitis, cervicitis, pelvic inflammatory disease, conjunctivitis, proctitis, and disseminated disease. Some untreated cases (1–2%) will eventually disseminate. The most common site of infection in men is the urethra.

An increasing amount of gonorrhea is resistant to penicillin; thus, ceftriaxone is now the treatment of choice. A single dose is effective. Azithromycin or doxycycline is used to treat C. trachomatis. Because Chlamydia is an intracellular organism, it is not seen on a Gram stain of the urethral swab. Immunofluorescence staining can be done if required to diagnose chlamydiae because they do not culture easily. Ligase chain reaction (a nucleic acid amplification test) is a test done on urine with a very high sensitivity and specificity. Doxycycline or azithromycin is added to the treatment of all patients with gonorrhea because of the very high rates of co-infection and because confirming a diagnosis of chlamydia requires a relatively expensive test and follow-up in several days.

Other effective regimens for gonorrhea are spectinomycin, and third-generation cephalosporins such as cefotaxime, ceftizoxime, and cefixime.

Neisseria bacteria, including Neisseria gonorrhoeae and Neisseria meningitidis, will grow on a Thayer-Martin agar, which is 5% chocolate sheep blood and antibiotics.

It contains vancomycin, which is able to kill most Gram-positive organisms

Colistin, which is added to kill most gram-negative organisms except Neisseria

Nystatin, which can kill most fungi

Trimethoprim, which inhibits gram-negative organisms, especially swarming Proteus





Clinical Pearl


Classic findings of DGI are:

Migratory polyarthralgia evolving into frank arthritis. N. gonorrhoeae infection should be considered in the differential diagnosis of monoarticular septic arthritis in a sexually active patient.

Tenosynovitis involving ≥1 joints.

Skin lesions in 75% of patients. The classic lesion is characterized by a small number of necrotic vesicopustules on an erythematous base.



Remember, blood and synovial fluid cultures are often negative. A high index of clinical suspicion for DGI should prompt the collection of specimens from the cervix or urethra, pharynx, and rectum for culture to make a presumptive diagnosis.





Treatment


Ceftriaxone plus doxycycline





Clinical Pearl


Terminal complement deficiency (C5 to C9) can cause recurrent Neisseria infection.





Final Diagnosis


Gonococcal urethritis





Case 12


Chief Complaint


“I’ve got some blisters on my penis.”





History and Physical Examination


A 37-year-old ambitious executive for a local health maintenance organization comes to your office because he developed multiple blister-like lesions on his penis over the last 1–2 days. They are somewhat painful, and he is worried that he has AIDS. He denies unprotected sex and IV drug abuse and had an HIV test before his marriage 3 years ago. He reports several similar episodes several years ago when he worked as a photographer in Nepal. He was never told what they were, and they resolved over several days without any treatment.

He is afebrile, is pleasant, and does not appear to be in distress. Heart, lung, and abdomen are normal. Examination of genitals shows 6–8 vesicular lesions 3–4 mm in diameter on the glans of the penis. There is no crusting, drainage, or bleeding. They are moderately tender. There is also mild inguinal adenopathy bilaterally.





Differential Diagnosis


Herpes simplex type 1

Herpes simplex type 2





Initial Management


Setting: outpatient

Diagnostic/Therapeutic Plan

Wright’s or Giemsa stain of an unroofed lesion





Test Results


Stain: multinucleated giant cells visible lesion (Tzanck prep)





Assessment


Multiple small, tender vesicular lesions of the genitals or mouth are very characteristic of herpes simplex, and the differential diagnosis is small. Occasionally, if the lesions have unroofed or become confluent, they may be confused with chancroid, which is also painful. Most often herpetic lesions have such a characteristic appearance that no further diagnostic tests are required. If there is any doubt of the diagnosis, however, perform an HSV PCR, as that is the most sensitive and specific test.

The Tzanck prep has low sensitivity and specificity and would not be the correct test. Viral culture may also be used. Serology on blood testing is not useful in confirming the diagnosis because 85–90% of the population is positive. Herpes simplex 1 is found in 70% of the population, and herpes simplex 2 in 20%.





Further Management Plan/Results


Viral culture or HSV PCR: herpes simplex grows after 72 hours





Treatment Plan


Acyclovir; famciclovir and valacyclovir are also acceptable alternatives.





Discussion


This patient should be reassured that a recurrent episode of genital herpes is not indicative of AIDS. A confirmatory clue that this patient’s infection is a recurrence and not a primary infection is the absence of systemic symptoms. Initial infections of both oral and genital herpes are often associated with fever, headache, malaise, and adenopathy. These symptoms are generally absent from recurrences. Recurrent herpetic lesions only need 5 days of treatment, though primary lesions may need 10 days.

Topical acyclovir is worthless for oral lesions and of very limited use in genital lesions. As with this man’s original episodes several yrs ago, most episodes resolve spontaneously anyway, and the acyclovir treatment is solely to shorten the duration of the outbreak. Although oral lesions are more often caused by type 1 virus and genital lesions by type 2 virus, either one may cause oral or genital lesions. There is a clinical benefit of distinguishing between the two because viral shedding and recurrent ulcers are less likely with HSV-1 than HSV-2.

Herpes encephalitis is the most common cause of viral encephalitis.

Herpetic infections can recur at any time and with any frequency after the original infection from as infrequent as several yrs apart to as short as several wks apart. Any form of physical or emotional stress, intercurrent infection, or immunosuppression (such as with AIDS or steroid use) can cause recurrences.

Frequent recurrences of genital herpes can be suppressed with a regular dose of acyclovir 400 mg 2x/day, valacyclovir 1x/day, or famciclovir 2x/day on a chronic basis.





CCS Note


The options to move the clock forward also include an “as needed” option. This is for patients like this one, in which there is a brief, self-inflicted problem. See them once after the initial visit to make sure the lesions have resolved. Then click on “RETURN AS NEEDED.” This is done for patients in whom the problem has resolved.





Final Diagnosis


Herpes simplex of the genitals





Case 13


Chief Complaint


Diarrhea for the past 2 days





History and Physical Examination


Eighteen fellows and attending doctors from the department of medicine have come unexpectedly to the employee health service over the past 36 hours with a history of 1–2 days of diarrhea. All of them were present at a large dinner party given by one of the hospital’s gastroenterologists several days ago. They all complain of multiple episodes of watery diarrhea. Some have blood visible in their stool, and some have profound abdominal cramping and fever. They all ate multiple dishes at the party including chicken, lamb, beef, salads, sauces, and an excellent tiramisu (sponge cake with eggs, espresso, wine, sugar, melted chocolate, and cheese).

Their temperatures range from 37.6 to 38.6 C (99.6 to 101.4 F). Chest, heart, head, eyes, ears, nose, and throat are all normal. Abdominal examination shows some distention with generalized, mild tenderness.





Differential Diagnosis


Salmonella

Campylobacter

Shigella

Norwalk virus

Yersinia

Enteroinvasive E. coli





Initial Management


Setting: outpatient

Diagnostic/Therapeutic Plan

Stool examination for blood and leukocytes

Blood culture

Stool culture





Test Results


Stool exam: positive blood in the stool; positive leukocytes with methylene blue staining of the stool

Blood culture: positive for Campylobacter

Stool culture: positive for Campylobacter





Assessment


Salmonella, Shigella, Campylobacter, Yersinia, and E. coli can all present with a dysentery syndrome of multiple watery bowel movements, fever, abdominal pain, and blood in the stool. It is generally not possible to distinguish the causative agents on the basis of the history alone. S. aureus and Bacillus cereus tend to present with a more acute onset of 2–6 hours after ingestion of the contaminated food with more upper GI symptoms. Viral diarrhea is seldom accompanied by blood or WBCs in the stool. Almost all of them are benign and self-limited.

The definitive diagnosis of bacteria-related food poisoning depends upon stool culture. Campylobacter and Salmonella are the most common causes of bacterial food poisoning. Giardia and cryptosporidiosis are uncommon in this setting in which the water supply is presumably safe. In addition, Giardia and cryptosporidiosis do not give red or white cells in the stool. Giardia is treated with metronidazole.





Treatment Plan


Supportive with hydration alone in the majority of cases

Spontaneous resolution expected in 3–7 days

Avoidance of antimotility agents such as diphenoxylate and loperamide

Severe cases of infectious diarrhea with signs of sepsis, such as hypotension, fever, and tachycardia, are treated empirically with ciprofloxacin.





Discussion


Gastrointestinal infections are an enormous source of illness worldwide and rank second only to respiratory infections as a cause of death. They are the number-one cause of death in children worldwide, with >12,000 deaths per day.

The vast majority of cases of food poisoning resolve spontaneously without antibiotics and with the use of hydration alone. The rehydration solutions are a combination of water, salt, potassium, and sugar. Antimotility agents are avoided because they may lead to toxic megacolon and buildup of the infectious agent. For instance, when diphenoxylate is used in Shigella, there can be prolonged fever and shedding of the organism. In Salmonella, they can increase the risk of bacteremia. If a patient is extremely ill or if the diarrhea is not resolving, antibiotics may be used. In the absence of a specific etiology, ciprofloxacin is a good choice. Trimethoprim/sulfa may also be adequate.

Although almost all food poisoning in the United States is self-limited, there are some occasional complications. In cases where the diarrhea is <24 hrs, there is no need to send stool studies.





Final Diagnosis


Infectious diarrhea secondary to Campylobacter





Case 14


Chief Complaint


Dyspnea and dizziness





History and Physical Examination


A 45-year-old man presents to the emergency department with 3 days of dizziness and dyspnea. He denies chest pain or palpitations. He has no cough or fever. His past medical history is unremarkable. He lives in Massachusetts and works as a lawyer. He goes camping on the weekends with his children, but has not noticed any tick bites or rashes.

On physical examination he appears well. Temperature is normal, BP is 100/60 mm Hg, and pulse 35/min. Other than bradycardia, the remaining physical examination findings are unremarkable. Results of initial lab studies show a normal CBC, metabolic panel, and cardiac enzyme measurements.

EKG is shown. Relevant findings are complete heart block.





Differential Diagnosis


Bradycardia with heart block can be due to:

Hypothyroidism

Lyme disease

Beta-blocker or calcium channel blocker use

Ischemic heart disease





Clinical Pearl


With patients from the northeast United States, camping/tick exposure, and bradycardia, always consider Lyme disease.





Initial Management


Setting: emergency department

Diagnostic/Therapeutic Plan

Immediate treatment with IV ceftriaxone

Serologic testing for Borrelia burgdorferi; enzyme-linked immunosorbent assay is the initial test and a Western blot assay is used for confirmation





Discussion


Lyme disease is the most common arthropod-borne infection in the United States, with around 26,000 confirmed cases reported in 2014. The incidence varies geographically, and hyperendemic areas in the northeast and north central United States reflect the geographic density of the vector deer tick, Ixodes scapularis, in these areas. The causative spirochete is Borrelia burgdorferi sensu stricto, which is transmitted to humans following vector tick attachment and feeding. Deer ticks may also serve as vectors for other tick-borne infection, and coinfection may occur.

The clinical manifestations of Lyme disease depend on the stage of infection.

Early localized Lyme disease typically occurs 1–2 wks following infection.

The initial clinical manifestation is erythema migrans, an erythematous skin lesion at the site of tick attachment (noted in 70–80% of patients with confirmed infection).

Classically, the border of erythema migrans expands over several days, and the lesion develops central clearing, leading to the description of a “target” or “bull’s-eye” appearance.



If erythema migrans is seen, there is no need to send serology because a measurable antibody response may not have had time to develop and will be negative. If you're given erythema migrans on the exam, the answer is to treat with doxycycline.

Neurologic manifestations of early disseminated Lyme disease include cranial nerve palsy (unilateral or bilateral), aseptic meningitis, and radiculopathy.

Late-stage Lyme occurs in as many as 60% of untreated patients. Lyme arthritis is characterized by migratory monoarticular or oligoarticular inflammation, which often improves spontaneously and then recurs in the same joint or another joint months to year later. The knee is involved in 85% of patients.

The finding of B. burgdorferi antibodies in patients who have nonspecific symptoms of fatigue or myalgia or who are unlikely to have been exposed to a vector tick likely represents a false-positive test result for Lyme disease.

Therefore, serologic testing for Lyme disease should be restricted to patients with clinically suggestive signs or symptoms who either reside in or have traveled to an endemic area.

Patients who have nonspecific symptoms such as fatigue, myalgia, or arthralgia but a low pretest probability for Lyme disease should not be tested for this disease.

Patients with erythema migrans, Bell’s palsy, or joint involvement should be treated with doxycycline or amoxicillin. Although amoxicillin covers Lyme disease, doxycycline is also active against Anaplasma phagocytophilum and is the preferred agent for patients age ≥8 who are not pregnant or breast-feeding. Anaplasma phagocytophilum is also transmitted via the Ixodes scapularis and there is commonly co-infection.

IV ceftriaxone is the recommended therapy for patients with Lyme myocarditis associated with second- or third-degree heart block or Lyme meningitis or encephalitis.





Final Diagnosis


Lyme disease





Case 15


Chief Complaint


Fever, urgency, and dysuria





History and Physical Examination


A 25-year-old woman comes to the office with a 3-day history of lower abdominal pain that is beginning to radiate to her right flank. She de