IM Board Review

A 37-year-old man with a chronic cough

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A 37-year-old man presented to the emergency department with an 8-week history of a mildly productive cough and shortness of breath accompanied by high fevers, chills, and night sweats. He also had some nausea but no vomiting.

Four days earlier, he had been evaluated by his primary care physician, who prescribed a 14-day course of one double-strength trimethoprim-sulfamethoxazole tablet (Bactrim DS) every 12 hours for presumed acute bronchitis, but his symptoms did not improve.

He was unemployed, living in Arizona, married with children. He denied any use of tobacco, alcohol, or injection drugs. On further questioning, he disclosed that he had unintentionally lost 30 pounds over the past 2 to 3 months and had been feeling tired.

When asked about his medical history, he revealed that he had been diagnosed with human immunodeficiency virus (HIV) infection in 2008 and that recently he had not been taking his antiretroviral medication, a once-daily combination pill containing efavirenz, emtricitabine, and tenofovir (Atripla). He had no other significant medical history, and the only medication he was currently taking was the trimethoprim-sulfamethoxazole.

On examination, his temperature was 38.7°C (101.7°F), blood pressure 109/68 mm Hg, heart rate 60 beats per minute, respiratory rate 18 breaths per minute, and oxygen saturation 100% while breathing supplemental oxygen via nasal cannula at 2 L/min. He did not appear seriously ill.

His mucous membranes were moist, and he did not have oral candidiasis. He had a palpable 1-cm nontender lymph node above his left clavicle. His heart and lungs were normal on physical examination. He had normal bowel sounds and no signs of peritonitis. His liver and spleen did not seem enlarged. Neurologic examination demonstrated normal cranial nerves, strength, reflexes, and sensation in all four limbs.

Initial blood tests (Table 1) showed a normal white blood cell count, normal results on a complete metabolic panel, and a lactate dehydrogenase level of 539 IU/L (reference range 313–618). His serum lactate level was within normal limits.

Figure 1. The chest radiograph at the time of admission shows findings consistent with a diffuse interstitial process with a lingular consolidation (arrow).

A chest radiograph showed multiple pulmonary nodules and a cavity in the lingula (Figure 1). In view of these findings, the patient was admitted to the hospital for further evaluation and testing.

HIV-specific tests performed on the second day of hospitalization showed extreme immunosuppression, with a CD4 count of 5 cells/μL (normal 326–1,404 cells/μL).

WHICH ORGANISM IS CAUSING HIS LUNG INFECTION?

1. Which of the following organisms is the least likely to be associated with this patient’s condition?

  • Mycobacterium tuberculosis
  • Pneumocystis jirovecii
  • Coccidioides immitis
  • Candida albicans
  • Streptococcus pneumoniae
  • Cytomegalovirus

Bacterial, fungal, and viral lung infections are common in HIV-infected patients, especially if they are not on antiretroviral therapy and their CD4 lymphocyte counts are low. Clues to the cause can be derived from the history, physical examination, and general laboratory studies. For instance, knowing where the patient lives and where he has travelled recently provides insight into exposure to endemic infectious agents.

The complete blood cell count with differential white blood cell count can help narrow the differential diagnosis but rarely helps exclude a possibility. Neutrophilia is common in bacterial infections. Lymphocytosis can be seen in tuberculosis, in fungal and viral infections, and, rarely, in hematologic malignancies. Eosinophilia can be seen in acute retroviral syndrome, fungal and helminthic infections, adrenal insufficiency, autoimmune disease, and lymphoma.

A caveat to these clues is that in severely immunocompromised hosts, like this man, diagnoses should not be excluded without firm evidence. This patient has severe, active immunosuppression, and only one of the six answer choices above is not a possible causative agent: C albicans rarely causes lung infection, even in immunocompromised people.

Mycobacterium tuberculosis

Tuberculosis can be the first manifestation of HIV infection. It can occur at any CD4 count, but as the count decreases, the risk of dissemination increases.1 Classic symptoms are fever, night sweats, hemoptysis, and weight loss.

The CD4 count also affects the radiographic presentation. If the count is higher than 350 cells/μL, then infiltration of the upper lobe is likely; if it is lower than 200 cells/μL, then middle, lower, miliary, and extrapulmonary manifestations are likely.1,2 Cavitation is less common in HIV-infected patients, but mediastinal adenopathy is more common.1

Definitive diagnosis is via sputum examination, blood culture, nucleic acid amplification, or microscopic study of biopsy specimens of affected tissues to look for acid-fast bacilli.1

Interferon-gamma-release assays such as the QuantiFERON test (Cellestis, Valencia, CA) or a tuberculin skin test can be used to check for latent tuberculosis infection. These tests can also provide evidence of active infection in the appropriate clinical context.3

Interferon-gamma-release assays have several advantages over skin testing: they are more sensitive (76% to 80%) and specific (97%); they do not give false-positive results in people who previously received bacille Calmette-Guérin vaccine; they react only minimally to previous exposure to nontuberculous mycobacteria; and interpretation is not subject to interreader variability.4,5 However, concordance between skin testing and interferon-gamma-release assays is low. Therefore, either or both tests can be used if tuberculosis is strongly suspected, and a positive result on either test should prompt further workup.6,7

Of note, both tests may be affected by immunosuppression, making both susceptible to false-negative results as the CD4 count declines.3

In any case, a positive acid-fast bacillus smear, radiographic evidence of latent infection, or pulmonary symptoms should be presumed to represent active tuberculosis. In such a situation, directly observed treatment with the typical four-drug regimen—rifampin (Rifadin), isoniazid, pyrazinamide, and ethambutol (Myambutol)—is recommended while awaiting definitive results from culture or polymerase chain reaction (PCR) testing.1

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