This patient's clinical illness and laboratory findings are most consistent with acute progressive disseminated histoplasmosis. Histoplasma is the most common endemic mycosis in the United States (primarily in the Ohio and Mississippi river valleys) and is also prevalent in Central America. The causative agent, Histoplasma capsulatum, is typically found in soil contaminated with bird or bat droppings, which encourage spore formation. Infection is usually through inhalation of spores and, in immunocompetent patients, may be asymptomatic or cause mild, self-limited pulmonary symptoms. However, in patients who are severely immunosuppressed, especially those with AIDS or hematologic malignancies, disseminated histoplasmosis may occur. In persons with HIV infection, the risk factors for histoplasmosis are a CD4 cell count less 200/µL and a history of exposure. Clinical manifestations are nonspecific. Fever and weight loss are common. The most common findings on physical examination include hepatosplenomegaly and lymphadenopathy. Common laboratory abnormalities include anemia, thrombocytopenia and leukopenia, and elevated serum aminotransferases and alkaline phosphatase. Chest radiographs may be normal or show scattered nodular densities or a diffuse reticular pattern. Diagnosis is by detection of histoplasma antigen in body fluids, which is present in up to 90% of patients with acute progressive disseminated histoplasmosis, or by isolation of H. capsulatum from bodily fluids or tissues. Bone marrow and blood cultures may also be useful in establishing the diagnosis (blood smear shown). Therapy is typically with liposomal amphotericin B with long-term suppressive therapy following short-term treatment.

Disseminated blastomycosis most commonly manifests as skin lesions, which this patient does not have. Other sites of disseminated disease include bones, joints, and the male genitourinary tract. Blastomycosis has been reported as a late complication in patients with AIDS, in whom central nervous system complications of blastomycosis are common and manifest as abscess or meningitis. The yeast forms of Blastomyces dermatitidis have a distinct appearance with broad-based budding.

Although mucosal candidiasis is common in advanced HIV infection, candidemia and disseminated candidiasis are rare.

Disseminated coccidioidomycosis most commonly presents with skin lesions, which this patient does not have. Other common sites of dissemination include bones, joints, and the meninges. Spherules (large, round, thick-walled structures containing endospores), noted by cytologic or histopathologic evaluation, are the classic finding.