Histoplasmosis is caused by Histoplasma capsulatum, a dimorphic fungus that has been isolated from soil contaminated with bird or bat droppings in endemic areas (central and eastern United States, eastern Canada, Mexico, Central America, South America, Africa, and southeast Asia). Infection presumably takes place by inhalation of conidia. These convert into small budding cells that are engulfed by phagocytic cells in the lungs. The organism proliferates and is carried hematogenously to other organs.
Symptoms and signs.
Most cases of histoplasmosis are asymptomatic or mild and thus go unrecognized. Past infection is recognized by the development of a positive histoplasmin skin test and occasionally by pulmonary and splenic calcification noted on incidental x-rays. Symptoms and signs of pulmonary involvement are usually absent even in patients who subsequently show areas of calcification on chest x-ray. Symptomatic infection may present with mild influenza-like illness, often lasting 1–4 days. Moderately severe infections are frequently diagnosed as atypical pneumonia. These patients have fever, cough, and mild central chest pain lasting 5–15 days.
Clinically evident infections occur in several forms:
1) Acute histoplasmosis frequently occurs in epidemics, often when soil containing infected bird or bat droppings is disturbed. It is a severe disease manifested by marked prostration, fever, and relatively few pulmonary complaints even when x-rays show diffuse pneumonia. The illness may last from 1 week to 6 months but is almost never fatal.
2) Progressive disseminated histoplasmosis is usually fatal within 6 weeks or less. Symptoms usually consist of fever, dyspnea, cough, loss of weight, and prostration. Ulcers of the mucous membranes of the oropharynx may be present. The liver and spleen are nearly always enlarged, and all the organs of the body are involved, particularly the adrenal glands, though this infrequently results in adrenal insufficiency.
3) Chronic progressive pulmonary histoplasmosis is usually seen in older patients with chronic obstructive lung disease. The lungs show chronic progressive changes, often with apical cavities.
4) Disseminated disease in the profoundly immunocompromised host often represents reactivation of prior infectious foci or may reflect acute infection. This form is commonly seen in patients with underlying HIV infection—with CD4 cell counts usually < 100 cells/mcL—and is characterized by fever and multiple organ system involvement. Chest x-rays may show a miliary pattern. Presentation may be fulminant, simulating septic shock, with death ensuing rapidly unless treatment is provided.
Most patients with progressive pulmonary disease show anemia of chronic disease. Bone marrow involvement may be prominent in disseminated forms with occurrence of pancytopenia. Alkaline phosphatase and marked lactate dehydrogenase (LDH) and ferritin elevations are also common.
In pulmonary disease, sputum culture is rarely positive except in chronic disease; antigen testing of bronchoalveolar lavage fluid may be helpful in acute disease. Blood or bone marrow cultures from immunocompromised patients with acute disseminated disease are positive more than 80% of the time but may take several weeks. A urine antigen assay has a sensitivity of greater than 90% for disseminated disease in AIDS patients and can be used to follow response to therapy. The sensitivity of screening immunodiffusion is 70% in acute pulmonary histoplasmosis, and complement fixation titers are positive in about 80% of cases. A combination of these two methods yields a sensitivity of up to 80% in immunodeficient adults.