MKSAP quiz on HIV


The following cases and commentary, which focus on HIV, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 16).

Case 1: Dyspnea, cough, chest pain, and fever

A 28-year-old man is admitted to the hospital for 3 weeks of increasing dyspnea on exertion, dry cough, pleuritic chest pain, and fever. The patient has been in a monogamous relationship with a male partner for the past 3 years but had multiple partners of both sexes previously.

On physical examination, temperature is 38.6 °C (101.5 °F), blood pressure is 110/66 mm Hg, pulse rate is 112/min, and respiration rate is 24/min. The oropharynx demonstrates scattered white plaques. Lung auscultation discloses diffuse crackles bilaterally. The remainder of the examination is normal.

Arterial blood gas levels with the patient breathing ambient air show a pH of 7.48, Pco2 of 30 mm Hg (4.0 kPa), and Po2 of 62 mm Hg (8.2 kPa). A rapid HIV test is positive. Sputum Gram stain shows few neutrophils, pseudohyphae, and mixed bacteria. A chest radiograph shows bilateral diffuse reticular infiltrates.

Which of the following is the most likely diagnosis?

A. Cytomegalovirus pneumonia
B. Mycobacterium avium complex infection
C. Pneumocystis jirovecii pneumonia
D. Pulmonary candidiasis

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Case 2: Arthralgia, rash, and burning eyes

A 32-year-old man is evaluated in the emergency department for a 1-week history of arthralgia, rash over the hands, burning sensation in the eyes, sore lips and tongue, and fever. Three months ago, he was diagnosed with HIV infection. Medications are efavirenz, emtricitabine, and tenofovir.

On physical examination, temperature is 38.1 °C (100.5 °F), blood pressure is 140/80 mm Hg, pulse rate is 100/min and regular, and respiration rate is 16/min. Bilateral conjunctival hyperemia is present; there is no change in visual acuity. Cracked, red lips and a strawberry tongue are present. The radial and dorsalis pedis pulses are normal, and there are no pleural or pericardial rubs. An erythematous rash is noted on the palms and digits of both hands with signs of desquamation around the nailfolds. There is tenderness to palpation of the wrists, knees, and ankles.

Laboratory studies show hematocrit 28%, leukocyte count 18,000/µL (18 × 109/L), platelet count 540,000/µL (540 × 109/L), erythrocyte sedimentation rate 76 mm/h, C-reactive protein 1.6 mg/dL (16 mg/L), rheumatoid factor negative, antinuclear antibodies negative. Urinalysis shows trace protein, 0-4 erythrocytes/hpf, 15-20 leukocytes/hpf, and no bacteria.

Which of the following is the most likely diagnosis?

A. Disseminated gonococcal infection
B. Kawasaki disease
C. Psoriatic arthritis
D. Toxic shock syndrome

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Case 3: Headaches, fever, sweats

A 40-year-old woman is admitted to the hospital for headaches, fever, and sweats of 3 weeks' duration as well as diplopia and increased somnolence that began yesterday. She was diagnosed with HIV infection 2 months ago with a CD4 cell count of 166/µL and an HIV RNA viral load of 66,923 copies/mL, and she immediately began taking antiretroviral therapy. She had been tolerating her medications and felt well until her current symptoms started. Medications are tenofovir, emtricitabine, efavirenz, and trimethoprim-sulfamethoxazole.

On physical examination, temperature is 38.2 °C (100.8 °F), blood pressure is 154/96 mm Hg, pulse rate is 64/min, and respiration rate is 18/min. She is awake but drowsy and is oriented to person and place but not time. The left eye cannot move laterally with leftward gaze. The rest of the neurologic examination is unremarkable.

CT scan of the head shows mildly increased ventricle size and mild cerebral atrophy, which is confirmed by MRI of the brain. Lumbar puncture is performed.

Cerebrospinal fluid analysis shows leukocyte count 122/µL (122 × 106/L) with 18% polymorphonuclear cells and 82% mononuclear cells, glucose 62 mg/dL (3.4 mmol/L), and protein 433 mg/dL (4330 mg/L).

The CD4 cell count is 251/µL, and the HIV RNA viral load is 675 copies/mL.

Infection with which of the following is the most likely cause of this patient's clinical presentation?

A. Cryptococcus neoformans
B. Cytomegalovirus
C. Histoplasma capsulatum
D. Toxoplasma gondii

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Case 4: Increasing back pain

A 38-year-old man is evaluated in the emergency department for fever and night sweats, as well as severe mid back pain, which has gradually increased over 6 months. The pain is now constant, independent of motion, and not relieved at night. The patient emigrated from Ghana 1 month ago. He has a 3-year history of HIV infection and takes no medications.

On physical examination, the patient appears cachectic and uncomfortable. Temperature is 38.2 °C (100.8 °F), blood pressure is 112/74 mm Hg, pulse rate is 78/min, and respiration rate is 14/min. BMI is 19. Limitation of flexion, extension, and rotation of the spine is noted. The mid thoracic back is tender. Neurologic examination is normal. The remainder of the examination is normal.

Radiographs of the spine reveal disk-space narrowing at the T12-L1 disk with destruction of the inferior surface of the T12 and the superior surface of the L1 vertebrae. MRI of the spine reveals a large irregular intervertebral and paraspinal mass. Chest radiograph is normal.

Which of the following is most likely to provide a diagnosis?

A. CT myelography
B. Technetium-99m bone scan
C. Tuberculin skin test
D. Vertebral biopsy

View correct answer for Case 4


Answers and commentary

Case 1

Correct answer: C. Pneumocystis jirovecii pneumonia.

The most likely diagnosis is Pneumocystis jirovecii pneumonia. This patient with known HIV risk factors and a reactive rapid HIV test very likely has HIV infection, although confirmation with Western blot testing still must be performed. He is most likely presenting with Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii. His subacute presentation with dry cough and dyspnea and chest radiograph findings of diffuse interstitial disease constitute the typical presentation of PCP in patients with AIDS, which is also the most common opportunistic infection in patients not taking Pneumocystis prophylaxis. Bronchoscopy with lavage can be done with special stains to confirm the diagnosis. Because this patient's arterial Po2 level is less than 70 mm Hg (9.3 kPa), treatment would include corticosteroids plus trimethoprim-sulfamethoxazole.

Although it can cause pneumonia in transplant recipients, cytomegalovirus (CMV) is an unusual cause of pneumonia in patients with AIDS. In such patients, CMV is more likely to present as retinitis or gastrointestinal disease, with CD4 cell counts less than 50/microliter.

Mycobacterium avium complex usually causes disseminated disease in patients with AIDS and CD4 cell counts less than 50/microliter who present with systemic symptoms, such as fevers, sweats, weight loss, and involvement of the liver, spleen, and lymph nodes, not as pulmonary disease.

Candida is generally a very rare cause of pulmonary infection, even in immunocompromised hosts. The presence of pseudohyphae in this patient's sputum is most likely a result of his oral candidiasis as demonstrated by his examination findings and is not evidence of pulmonary involvement.

Key Points

  • In patients with AIDS, Pneumocystis pneumonia is the most common opportunistic infection in patients not taking Pneumocystis prophylaxis and is typically characterized by a subacute presentation with dry cough and dyspnea and chest radiograph findings of diffuse interstitial disease.

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Case 2

Correct answer: B. Kawasaki disease.

This patient most likely has Kawasaki disease. Although most commonly seen in young children, Kawasaki disease may occur in adults, in particular those with HIV infection such as this patient. His initial findings, including fever with nonexudative conjunctivitis, pleomorphic erythematous rash, and oral mucositis, are consistent with this disorder. Other clinical features include cervical lymphadenopathy and an oligoarticular or polyarticular inflammatory arthritis. Laboratory abnormalities include anemia, leukocytosis, thrombocytosis, and sterile pyuria. As the disease evolves, the rash desquamates, initially in the periungual areas and then proximally over the hands and feet. Recognition of the typical features associated with Kawasaki disease is important to prevent possible coronary artery complications. The preferred initial treatment is administration of intravenous immune globulin, and salicylates are used to manage associated articular symptoms. Moderate doses of corticosteroids can be used for patients with more severe constitutional symptoms who are unresponsive to intravenous immune globulin and salicylates.

Although pyuria and arthralgia can occur with gonococcal infection, the skin lesions associated with disseminated infection are typically papular with central pustules and not a desquamating distal rash as seen in this patient.

Patients with HIV infection may develop severe variants of psoriasis and psoriatic arthritis. However, this patient's skin lesions are not the papular or pustular lesions associated with psoriasis.

Toxic shock syndrome (TSS) is an infrequent, but life-threatening, infection in which bacterial toxins are produced and lead to septic shock. Patients are febrile, hypotensive, have a diffuse malar rash with subsequent desquamation, and have at least three of the following manifestations: nausea, vomiting, or diarrhea; severe myalgia or elevated serum creatine kinase level; hyperemia of the vagina, conjunctiva, or pharynx; acute kidney injury; acute liver injury; thrombocytopenia; or disorientation without focal findings. This patient does not meet the diagnostic criteria for TSS.

Key Points

  • Although most commonly seen in young children, Kawasaki disease may occur in adults, in particular in those with HIV infection.

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Case 3

Correct answer: A. Cryptococcus neoformans.

The most likely diagnosis is Cryptococcus neoformans infection. This patient with AIDS has developed symptoms of meningitis after initiation of antiretroviral treatment, which is consistent with immune reconstitution inflammatory syndrome (IRIS), most likely from cryptococcal meningitis. With the initiation of combination antiretroviral therapy, viral load levels decrease sharply, CD4 cell counts increase, and immune responses improve. In the presence of an opportunistic infection, which may not have been clinically recognized previously, this process can lead to dramatic inflammatory responses as the newly revived immune system reacts to high burdens of antigens. IRIS usually occurs a few weeks to a few months after initiation of antiretrovirals in the setting of various opportunistic infections, most commonly mycobacterial or disseminated fungal infections, including cryptococcal meningitis. This patient's prolonged duration of symptoms, including headache, mental status changes, and cranial nerve involvement, are typical of cryptococcal meningitis as are the lumbar puncture results showing evidence of inflammation. Fungal cultures of cerebrospinal fluid may eventually grow the organism, but results of cryptococcal serum or cerebrospinal fluid antigen testing will be available more quickly and have a sensitivity of more than 95%. Acute treatment consists of intravenous amphotericin B followed by long-term oral fluconazole, with special attention to management of increased intracranial pressure.

Cytomegalovirus infection can cause encephalitis, but it is much less common, especially in patients with CD4 cell counts greater than 100/microliter; the MRI would also likely show periventricular involvement.

Histoplasmosis is caused by Histoplasma capsulatum, a thermal dimorphic fungus endemic to the midwestern states of the Ohio and Mississippi river valleys. Patients may have acute or chronic pulmonary disease, and immunocompromised patients, especially, may present with disseminated disease. Central nervous system involvement can occur, but usually as part of obvious dissemination including pulmonary disease, which is not consistent with this patient's presentation.

Toxoplasmosis can cause encephalitis in patients with AIDS, usually in those with CD4 cell counts less than 100/microliter and headache, mental status changes, and focal deficits. But the MRI findings in affected patients would show the characteristic multiple ring-enhancing lesions of the toxoplasmic abscesses, which are not present in this patient.

Key Points

  • In patients with HIV infection, immune reconstitution inflammatory syndrome can occur a few weeks to a few months after initiation of antiretroviral therapy and results in a dramatic inflammatory response to opportunistic infections.

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Case 4

Correct answer: D. Vertebral biopsy.

A vertebral biopsy is appropriate for this patient to evaluate for tuberculous arthritis of the spine. He is immunosuppressed, comes from an area in which tuberculosis is endemic, and has fever, night sweats, and radiographic findings indicating vertebral destruction. In this setting, spinal tuberculosis is the most likely diagnosis; the presence of a normal chest radiograph, as in this case, does not eliminate the possibility of tuberculous skeletal involvement. However, other diagnoses are possible, including other forms of infection, tumors, and occasionally, tophaceous gout. A vertebral biopsy (whether a percutaneous needle biopsy under CT visualization or, in some cases, an open surgical biopsy) can help to establish the diagnosis and eliminate other possibilities to initiate treatment in a timely manner.

CT myelography can further delineate the area of the vertebral damage but would not advance the search for a diagnosis, particularly in the setting of a condition sufficiently advanced to be recognized on plain radiographs, as seen in this case. MRI or CT myelography is valuable in demonstrating compression of the spinal cord and may be considered in the future, particularly if the patient develops neurologic signs, but neither will establish the diagnosis.

Technetium-99m bone scan identifies areas of inflammation but does not provide a microbiologic diagnosis and is less accurate than either CT myelography or MRI in documenting spinal cord compression.

Tuberculin skin testing can be performed as a routine matter, but its interpretation would be difficult in this case—the results may be positive owing to prior exposure rather than active disease; conversely, the patient may be anergic owing to HIV infection.

Key Points

  • A vertebral biopsy is indicated to diagnose tuberculous spinal osteomyelitis.