Case 11 – A 45-year-old woman with disseminated disease

A 45-year-old woman from Cincinnati presents to her physician complaining of cough, dyspnea, fevers, and weight loss. She has been HIV positive for 20 years and has been using highly active antiretroviral therapy for the past decade. Although she continues to take her medications, this past year she lost her health insurance and has been unable to see her regular physician. Her temperature is 39°C (102.2°F), heart rate is 90/min, and respiratory rate is 20/min. Chest examination is notable for diffuse rales, while other physical examination findings include hepatosplenomegaly and lymphadenopathy. X-ray of the chest reveals reticulonodular infiltrates with a few calcified granulomas. Laboratory studies show:

CD4 count: 100/mm³
Hemoglobin: 10.0 g/dL
WBC count: 4000/mm³
Platelet count: 50,000/mm³

What is the most likely diagnosis?

Disseminated endemic fungal infection, likely histoplasmosis. The endemic fungi are soil-based fungi seen in particular geographic areas and include histoplasmosis and blastomycosis (Ohio and Mississippi River valleys), coccidioidomycosis (southwestern United States), and paracoccidioidomycosis (Latin America). In endemic areas, these fungi commonly cause asymptomatic infection in healthy patients. In patients with a large inoculum, an acute pulmonary infection is seen. Patients with underlying lung disease can develop chronic cavitary disease, which resembles tuberculosis. In immunocompromised patients, especially those with AIDS, disseminated disease can be life-threatening.

What is the differential diagnosis of this condition?

The differential diagnosis of a febrile wasting disease with lymphadenopathy in a patient with AIDS includes the Mycobacterium avium complex, lymphoma, or miliary tuberculosis. In acute pulmonary cases in patients without AIDS, the differential list also includes sarcoidosis, which can have a very similar clinical presentation.

What is the pathogenesis of this condition?

The endemic mycoses are dimorphic fungi that live in the soil. When the spores are aerosolized and inhaled, they revert to fungal forms and incite a T-cell response that usually clears the infection within 2 weeks. Immunocompromised patients can either develop disseminated disease immediately or as a reactivation of latent infection. Disseminated disease can demonstrate gastrointestinal involvement with ulcerations and polyp development, skin lesions, adrenal involvement, and central nervous system disease.

How is the diagnosis made?

Rapid antigen detection tests can identify the Histoplasma polysaccharide antigen in urine, blood, or bronchoalveolar lavage fluid. Direct visualization and culture of the fungus can be done with blood or tissue samples, although culture may take weeks.

What is the most appropriate management for this patient?

The current recommendation for disseminated histoplasmosis in patients with AIDS is liposomal amphotericin B, followed by itraconazole suppressive therapy for life. The majority of acute pulmonary histoplasmosis infections in immunocompetent patients do not require treatment.

By Melissa Rosenstein, MD, Resident in Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco Medical Center; in association with Le TT, Schabelman E, Shivaram A, and Klein J, eds: First Aid Cases for the USMLE Step 2 CK. New York: McGraw-Hill, 2007.