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An infectious disease caused by Histoplasma capsulatum, characterized by a primary pulmonary lesion and occasional hematogenous dissemination, with ulcerations of the oropharynx and GI tract, hepatomegaly, splenomegaly, lymphadenopathy, and adrenal necrosis. The disseminated form is a defining disease for AIDS.
Etiology, Incidence, and Pathology
H. capsulatum in tissue is an oval budding cell 1 to 5 mu in diameter. Infection follows inhalation of dust that contains the spores. Severe disease is more frequent in men and in patients who have received a heavy (prolonged) inoculum.
Chest film surveys in certain geographic areas have shown many residents with symptomless, nontuberculous, occasionally calcified pulmonary lesions; delayed cutaneous hypersensitivity reactions to histoplasmin suggest widespread but subclinical infection. The highest incidence of such hypersensitivity is in the Ohio and Mississippi river valleys. The largest single outbreak, affecting over 100,000, occurred in Indianapolis.
Symptoms and Signs
There are 3 forms of the disease. The primary acute form is manifested by symptoms (fever, cough, malaise) indistinguishable in endemic areas (except by culture) from otherwise undifferentiated URI or grippe-like disease. The progressive disseminated form follows hematogenous spread from the lungs and is characterized by hepatomegaly, lymph-adenopathy, splenomegaly, and less frequently, oral or GI ulceration. Addison's disease is an uncommon but serious manifestation. The lesions in the liver are granulomatous, show the intracellular fungus, and may lead to hepatic calcification. Addison's disease from other causes, lymphoma, Hodgkin's disease, leukemia, and sarcoidosis must be differentiated. The chronic cavitary form is characterized by pulmonary lesions indistinguishable, except by culture, from cavitary TB. The principal manifestations are cough, increasing dyspnea, and eventually disabling respiratory dysfunction. Fibrosing mediastinitis is another manifestation. It has been postulated but not proved that histoplasmosis is a cause of uveitis.
Diagnosis
Culture of H. capsulatum is diagnostic. Specimens for culture may be sputum, lymph nodes, bone marrow, liver biopsy, blood, urine, or oral ulcerations. Lysis-centrifugation or use of buffy coat improves the yield from blood specimens. Tissues may be examined microscopically after staining with Gomori's methenamine-silver, periodic acid-Schiff, or Gridley's stain. The diagnosis may be suspected in AIDS patients when fungal forms suggestive of H. capsulatum are seen in polymorphonuclear or mononuclear leukocytes in Wright- or Giemsa-stained peripheral blood. Delayed cutaneous hypersensitivity and serologic tests are of no diagnostic value, since they are usually negative early in the disease.
Prognosis and Treatment
The acute primary form is usually benign; it is fatal only in rare cases with massive infection. The progressive disseminated form has a 90% fatality rate. In the chronic cavitary form, death results from severe respiratory insufficiency. In patients with AIDS, the disease is frequently and rapidly fatal.
Primary acute disease rarely requires chemotherapy (see General Therapeutic Principles, above). The disseminated form responds to amphotericin B; in the chronic cavitary form, the fungi disappear with therapy, but fibrotic lesions show little change.
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