Lymphadenitis caused by infection with the fungus Histoplasma capsulatum.

Histoplasmosis is endemic in Central America and in the river valleys of the midwestern and south-central United States (1). In areas of high endemicity, such as the central valleys of the Mississippi and Ohio rivers, more than 80% of the population is sensitized (2). It has been estimated on the basis of histoplasmin skin tests that occult infection with H. capsulatum is three to four times more frequent in the U.S. population than occult infection with Mycobacterium tuberculosis (3). About 250,000 individuals are infected annually (1). Because of the high infectivity rate, disseminated histoplasmosis may occur in as many as 5% of acquired immune deficiency syndrome (AIDS) patients in Ohio and Mississippi and 6.7% of those in Guatemala (4,5).

Histoplasma capsulatum is a thermally dimorphic fungus. Its natural habitat is the soil, contaminated by excreta of chickens, birds, and bats (6). In endemic areas, the acidic soil with high organic content is favorable to growth. The birds are not infected and do not transmit the disease but contaminate the soil with excretions (1). In the soil, the organism exists in the mycelial phase at ambient temperature. Infection occurs when spores or hyphae are inhaled into the lungs. At the higher temperature of the body, H. capsulatum converts to its intracellular yeast form, which in immunocompetent persons has little potential for infection (6,7). Plated on Sabouraud dextrose agar, it forms large, cottony mycelial colonies with prominent, cross-walled hyphae. The yeasts have rigid cell walls and average 3 μm in diameter. Tissue fixatives cause the protoplasm to retract from the rigid walls and leave a clear space, which gives the erroneous impression of an unstained capsule (6).

In the normal population, infections with Histoplasma organisms remain occult, although occasionally, in special circumstances of heavy infection, outbreaks of histoplasmosis do occur (8). During an outbreak in Indiana, disseminated histoplasmosis developed in 4.2% of immunocompetent persons and 55.2% of patients who were immunosuppressed (9). Widely disseminated histoplasmosis may occur in patients with Hodgkin lymphoma and acute leukemias treated with corticosteroids and cytotoxic drugs (10). In endemic areas, AIDS patients are at high risk for acquiring histoplasmosis, and virulent forms of disease with dissemination are frequent (9). In normal, immunocompetent persons, infection with airborne spores of Histoplasma usually results in the formation of a minute (5-mm), subpleural, caseated, calcified nodule in the lower lobe of lung and a calcified area in the regional hilar lymph node; these form a primary complex entirely similar to the one commonly seen in tuberculosis (11,12). As the host immunity develops, the yeast growth ceases and 90% of individuals develop a positive skin reaction to Histoplasma antigen (1). In contrast, extensive lesions involving most organs develop in immunodeficient persons, particularly patients with AIDS. The lymph nodes and other components of the mononuclear phagocyte system (bone marrow, spleen, and liver) are the usual locations. The number of CD4+ T cells is greatly decreased in disseminated histoplasmosis, usually to below 75/mL (4). In their absence, macrophages become engorged with yeasts, which remain intact and are transported to various organs to disseminate the disease (13). Histoplasma yeasts may remain occult in healed granulomas and become reactivated years later under conditions of severe immune deficiency (1).

About 90% of pulmonary infected patients are asymptomatic (1). When symptoms occur, usually 3 to 14 days after a more massive exposure, they are nonspecific, manifesting as fever and chills, headaches, myalgia, and weight loss. Because the fungi are transported by histiocytes, the reticuloendothelial system is primarily affected, and therefore the bone marrow, lymph nodes, spleen, and liver are most likely to be involved (13). In a summary of reported series of cases of disseminated histoplasmosis in AIDS patients, bone marrow cultures were positive for organisms in 83% of cases, and bone marrow histologic sections were positive in 40% of cases in the form of discrete granulomas or lymphohistiocytic aggregates (14). Reports of disease in children documented cervical abscess (15) and mediastinal lymphadenopathies eroded in the bronchial tree (16) or compressing the esophagus with stricture and dysphagia (17). The adrenal gland is also frequently involved—80% in one series of cases—with necrosis and Addison disease in 10% (10,13,18). Any organ can be affected. Whereas pulmonary histoplasmosis in immunocompetent people is generally benign, in immunodeficient persons, severe and often fatal disease results from extension to the lungs, heart, and brain (13).