Clinical Management Review 2023-2024: Volume 1: USMLE Step 3 and COMLEX-USA Level 3

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, consider prophylactic tamoxifen (very strong family history 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 who have >30 pack-years of smoking (current smoker or have quit <15 years), screening with low dose CT (non-contrast) is recommended annually

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 best way to prevent 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.

Wear seatbelts and bicycle helmets

Do not drive after drinking alcohol

Be aware of the risks that firearms pose in the home

Another essential role for the physician is to identify those at increased risk of physical or sexual abuse. Simply asking patients 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 of 5 days duration

History and Physical Examination

A 32-year-old man comes to the emergency department with 5 days of fever, fatigue, shortness of breath, a cough productive of bloody sputum, and pleuritic chest pain. He is an active IV drug user and last used drugs yesterday. His past medical history is significant for skin abscesses. He uses no prescription drugs and has no allergies. A COVID test is performed and is negative. Blood pressure is 112/72 mm Hg, pulse 110/min, respirations 22/min, and temperature 39 C (102.2 F). 

He is a thin, weak-appearing man. Examination of the head, eyes, ears, nose, and throat shows no evidence of petechiae in the mouth or on the conjunctivae. Funduscopic examination is unremarkable. On chest auscultation there are rhonchi and wheezes throughout both lung fields. 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, extremities have no clubbing, and the fingernails/hands appear normal.

NOTE

Management is not yet clear for the COVID-19 virus, an infectious disease caused by a newly discovered coronavirus. Therefore, questions about COVID are unlikely to be seen on the exam at this time.

Symptoms can include fever, loss of taste or smell, cough, and shortness of breath, possibly leading to pneumonia.

Testing is PCR (best) or antigen-testing; chest x-ray (will show interstitial pneumonia mostly when it affects the lungs), and inflammatory markers (very elevated).

Treatment, while not yet definitive, should include respiratory isolation and anti-inflammatories such as steroids early in the course. Monoclonal antibody therapy has shown promise.

Prevention is best achieved with vaccination.

Differential Diagnosis

MRSA bacteremia

Infective endocarditis (IE)

Tuberculosis

Strep pneumonia

CCS NOTE

For the CCS be organized, address the chief complaint and stabilize the patient by addressing any abnormal vital signs first. In this case, make sure the heart (with an abnormal rate) is monitored on a monitor bed or EKG.

Initial Management

Setting: emergency department

Diagnostic/Therapeutic Plan

EKG and monitor bed

Chest x-ray

Blood cultures

Test Results

Chest x-ray: multiple nodular opacities are visible bilaterally

Blood cultures from peripheral sites, aerobic and anaerobic: results pending

Assessment

An IV drug user will be at increased risk of methicillin-resistant staph aureus (MRSA), which can cause skin abscess, endocarditis, pneumonia, and even osteomyelitis and septic arthritis. Suspect endocarditis in anyone with a fever and a murmur; blood cultures will be necessary. Furthermore, complaints of cough productive of bloody sputum plus fever with pleuritic chest pain in an IV drug user are suggestive of a typical pneumonia. 

Due to the acute presentation here, TB and malignancies are less likely in the differential diagnosis. When pneumonia is considered, only the typical pneumonias have pleuritic chest pain (because they affect the pleura), e.g., S. pneumoniae, S. aureus, K. pneumoniae, H. influenzae. In contrast, the atypical (non-typical) pneumonias affect the interstitial space only (do not affect the pleura and are not associated with pleuritic chest pain).

Diagnosis of IE requires use of the modified Duke criteria: 2 major and 1 minor criterion OR 1 major and 3 minor criteria OR 5 minor criteria.

Two major criteria: positive blood culture and imaging showing endocardial involvement with vegetations

Five minor criteria

Major risk factor, eg, IVDU

Fever >38 C (100.4 F)

Embolic phenomena including septic pulmonary embolization, Janeway lesions, or conjunctival hemorrhages

Osler nodes, Roth spots, or a positive rheumatoid factor

Blood cultures growing organism normally not causing endocarditis

Acute endocarditis, as the name suggests, is usually acute in onset. It is commonly caused by MRSA and mostly affects the right side of the heart. The vegetations—caused by staph—are very large and usually only embolize to the lungs. They will not cause the typical findings of microembolization seen in subacute endocarditis.

Subacute endocarditis is caused by an organism such as strep, which entering the body (e.g., through a contaminated procedure such as gingival manipulation) can seed previously damaged valves (usually valves affected by conditions like rheumatic fever, which mostly involve the left-sided valves). Subacute endocarditis produces microscopic embolization, and thus you will see the typical Roth spots in the retina, Osler’s nodes (pain in the palms of the hands), Janeway lesions, and splinter hemorrhage on the fingernails—none of which this patient has.

Further Management Plan/Results

Lab results: blood cultures positive for Staphylococcus aureus, antibiotic susceptibility pending 

Transthoracic echocardiogram (TTE): vegetation visible on tricuspid valve with tricuspid regurgitation

EKG: sinus tachycardia is seen but otherwise is unremarkable

Further Management

Empiric antibiotic (something that covers MRSA such as vancomycin) until the sensitivities are back reporting any other organism; then, adjust the antibiotic at that time (take 3 sets of blood cultures before starting the antibiotics)

TTE: if positive, nothing further needed for diagnosis but if negative, transesophageal echocardiogram (TEE) which is much more sensitive; further evaluation by TEE may be needed for those with significant valvular regurgitation (to determine need for surgery) and those with ≥1 risk factors for perivalvular abscess (including new conduction delay on EKG, aortic valve endocarditis, and persistent bacteremia/fever despite appropriate antimicrobial therapy).  IV antibiotic (e.g., nafcillin or oxacillin) for 4–6 weeks, with gentamicin for first week if it is methicillin-sensitive 

Possible surgical replacement of valve if there is acute decompensation, myocardial abscess, repeated emboli, very large vegetations, fungal endocarditis, or prosthetic valve endocarditis

Discussion

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 health care–associated bacteremia. Empiric therapy for IE includes:

Community-acquired native valve IE: vancomycin plus gentamicin 

Nosocomial-associated IE: vancomycin, gentamicin, rifampin, and an antipseudomonal beta-lactam (i.e., cefepime, meropenem)

Prosthetic valve IE: vancomycin, gentamycin, rifampin

Native valve subacute endocarditis is typically caused by Streptococci. 

Viridans streptococci (normal inhabitants of the mouth) (75% of cases)

Streptococcus bovis and Clostridium septicum (20%  of cases) (associated with neoplastic diseases of the colon)

Staphylococci (30% of cases, most S. aureus)

Enterococci (5–10% of cases)

Culture-negative endocarditis is caused by the HACEK organisms. 

Haemophilus (Haemophilus parainfluenzae), (Haemophilus aphrophilus), (Haemophilus paraphrophilus)

Actinobacillus

Cardiobacterium hominis

Eikenella corrodens

Kingella (Kingella kingae)

However, studies have found that the HACEK organisms can be easily isolated with current blood culture systems when incubated for at least 5 days.

Prosthetic valve endocarditis is typically caused by Staphylococci in the early postoperative period. Staphylococcus epidermidis is more common in the first 2 mos after the replacement. 

Complications of endocarditis include CHF (most common cause of death); embolic phenomena (seen in 25% of patients within 1 week of treatment); abscess/mycotic aneurysm/abscess; renal infarction/abscess; splenomegaly; valvular degeneration; and  glomerulonephritis if not treated.

The blood culture results for this patient eventually confirm methicillin-sensitive S. aureus (MSSA). Treatment is nafcillin (or oxacillin or cefazolin) for 4-6 weeks. Gentamicin or another aminoglycoside is often added for the first 5 days; these are bactericidal and must be used over vancomycin if the organism is methicillin-sensitive.

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

For Enterococcus, use a beta-lactam antibiotic such as penicillin or ampicillin, plus an aminoglycoside (gentamicin or streptomycin) for the entire 4-6 weeks.

For HACEK organisms, use ceftriaxone, ampicillin-sulbactam, or ciprofloxacin for 4 weeks.

For Q fever endocarditis, use hydroxychloroquine plus doxycycline.

For an urticarial rash to vancomycin or vancomycin MIC >2, use daptomycin to treat right-sided MRSA endocarditis.

Surgery is indicated under the following conditions: 

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 infection to involve the conduction system of the heart)

Acute heart failure (can indicate degeneration of the valves, papillary muscles, or chordae tendineae sufficient to cause evidence of CHF)

Valvular regurgitation

Recurrent embolic event while on antibiotics

Antibiotic prophylaxis is recommended for IE under the following conditions (high-yield):

Prosthetic cardiac valve or prosthetic material used in valve repair

Previous endocarditis

Congenital heart disease

Unrepaired cyanotic heart disease

Cardiac transplantation with cardiac valvular disease

Post-prosthesis surgery or surgical repair of a congenital heart disease (for 6 months, since endothelialization of prosthetic material occurs within that time period)

Unepithelialized prosthetic patch or prosthetic device 

Manipulation of gingival tissue or periapical region of the teeth or perforation of oral mucosa

Incision or biopsy of the respiratory tract mucosa (bronchial biopsy, tonsillectomy, and adenoidectomy)

When giving antibiotic prophylaxis, give 2 hours before the procedure (and possibly 2 hours after the procedure). Medications include amoxicillin (PO) (preferred) or ampicillin (IV) (alternates include clindamycin, azithromycin, and ceftriaxone/cefazolin (IM/IV).

Final Diagnosis

Acute bacterial endocarditis

CLINICAL PEARL

Start empiric antibiotics for all presumed infections after cultures have been drawn. The best antibiotics for MSSA are oxacillin, nafcillin, and cefazolin.

Basic Science Correlate

Streptococcus viridans (most common organism to cause endocarditis) 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.

NOTE

Q fever is a mild atypical pneumonia in patients exposed to livestock (e.g., farmers, large animal veterinarians, and slaughterhouse workers). Consider Q fever endocarditis in those who had Q fever from 2 months to 2 years after acute Q fever.

CLINICAL PEARL

In chronic rheumatic heart disease, the mitral valve is almost always involved. It leads to mitral stenosis, and gives patients a fish-mouth appearance. Patients are often immigrants from low-income countries.

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.)

CASE 2

Chief Complaint

Pain and swelling of left leg

History and Physical Examination

A 72-year-old 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 older adult 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 empiric.

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 put some 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.

Surgical drainage, along with incision of abscess and deeper infection, is crucial for adequate treatment. 

Antibiotics guidelines are as follows: 

Severe, invasive infection that requires IV antibiotics as inpatient: vancomycin (preferred), daptomycin, ceftaroline, tigecycline, telavancin, or linezolid

Mild infection: empiric oral antibiotic, e.g., trimethoprim-sulfamethoxazole, doxycycline, or linezolid (if cultures are sensitive, use clindamycin)

Small abscess with no surrounding erythema: no antibiotics needed

Antibiotics are also indicated for the following:

Patients who are very young/older adult or who have multiple infection sites, systemic illness/comorbidity/immunosuppression

Infection that quickly progresses and is associated with concomitant cellulitis

Abscess that does not respond well to incision/drainage or is too difficult to drain

Final Diagnosis

Cellulitis

CLINICAL PEARL

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

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 type 2 diabetes 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

Lactic acid

Chemistry profile

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

Broad spectrum IV antibiotics

Test Results

CBC: WBC 30,000 cells/mL, segments 90%, Hb 10 mg/dL, platelets 100,000

Lactate: 8.2 mmol/L

Chemistry profile: 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 has poorly controlled diabetes 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, tigecycline, ceftaroline, or linezolid (to cover MRSA) plus (coverage for gram-negative, including pseudomonas plus anaerobes)

Imipenem/meropenem

Piperacillin/tazobactam

Ticarcillin/clavulanate 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

Fever, headache, and neck stiffness for 3 days

History and Physical Examination

A 34-year-old man HIV positive is brought to the emergency department by his roommate because of high fever, headache, and neck stiffness for the last 3 days. Since yesterday he has started to become confused. Currently his medications are bictegravir, tenofovir alafenamide and emtricitabine. His last CD4 count was 945 cells/mm3.

The patient appears muscular, lying on the stretcher with his hands over his eyes. His temperature is 38 C (104 F). Examination of head, eyes, ears, nose, and throat shows no papilledema. There is moderate nuchal rigidity and marked photophobia. Heart, lung, and abdominal examination are normal. He is oriented to place but gets confused with the time. He knows his own name and can recognize his roommate. There are no focal motor or sensory deficits. The Babinski reflex shows toes that are down-going.

Differential Diagnosis

Cryptococcal meningitis

Tuberculous meningitis

Neisseria meningitidis

Streptococcus pneumoniae

Viral meningitis

Initial Management

Setting: emergency department

Diagnostic/Therapeutic Plan

Empiric antibiotic and dexamethasone

CT of the brain

CSF culture

Test Results

CT of the brain: unremarkable with no evidence of mass-occupying lesions

WBC 3,500/mm³ with 95% neutrophils, negative Gram stain, elevated protein, decreased glucose

CSF culture: Streptococcus pneumoniae

Assessment

Looking at the presenting symptoms, it takes very little time to realize that headache, nuchal rigidity, and photophobia are classic signs of meningitis. In the differential diagnosis we have viral meningitis, bacterial meningitis, fungal meningitis, and tuberculous meningitis. Because of the duration of symptoms here of only 3 days, the patient has either bacterial or viral meningitis; these can be differentiated with a lumbar puncture (LP). 

If the meningitis had lasted more than 10-14 days or was subacute, then conditions such as fungal or tuberculous meningitis should be considered. So the differential diagnosis can be narrowed down to N. meningitidis and S. pneumoniae. 

Brain abscess is unlikely here. That usually presents with only focal neurological signs and symptoms, but because this patient is confused a brain CT is needed before an LP. (Brain CT is always needed with focal neurological deficits, immunocompromised patients, altered mental status, new onset of seizures, history of CNS disease, and papilledema.)

Further Management Plan/Results

Lumbar puncture

CCS NOTE

Body fluid infections such as urine, CSF, and pleural effusion are initially diagnosed based on cell count, but because cultures are never available at the time a treatment decision must be made empiric therapy must be started. Because of the severe symptoms here plus a high CSF WBC count (most likely neutrophils), give ceftriaxone and vancomycin until the culture results are known.

Discussion

The timing of this patient’s symptoms (only lasting 3 days) points toward a viral or bacterial origin to his meningitis. The only concerning symptom is his confusion, which required a CR of the brain to rule out mass-occupying lesions prior to doing an LP. Once the LP is done, focus on the nature of the liquid:

Cloudy liquid indicates a high WBC >1000, and likely means a bacterial cause to the meningitis; in these cases, the differential will show mostly neutrophils (as in our case here).

When WBC <1000 (especially when <500), the cause is a likely virus, fungus, or mycobacterial infection.

Next, look at the blood glucose. In this case the glucose is decreased, which means the process is consuming glucose. Viruses are the only organisms whose process does not lead to the consumption of glucose.

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, and 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

Consider other types of meningitis:

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 and flucytosine, followed by 3 months of fluconazole until CD4 count >100/mm

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

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 has very low glucose (<50 mg/dL), very high LDH or neutrophil count >10,000, or is polymicrobial, suspect secondary peritonitis and proceed to imaging.

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.

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 of 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