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Pathogenesis and clinical manifestations of disseminated histoplasmosis

Carol A Kauffman, MD
Section Editor
Kieren A Marr, MD
Deputy Editor
Jennifer Mitty, MD, MPH


Histoplasmosis is the most prevalent endemic mycosis in the United States [1]. While most infections are asymptomatic or self-limited, some individuals develop acute pulmonary infections or severe and progressive disseminated infection [2-5]. Progressive disseminated histoplasmosis occurs in about one in 2000 patients with acute infection [2,5,6].

Although hematogenous dissemination probably occurs in most patients during the acute infection before cellular immunity develops, progressive illness is unusual except in the host with altered immunity and those at the extremes of age [2,3,6]. The diagnosis of disseminated histoplasmosis requires a high index of suspicion, recognition of the common modes of presentation, and familiarity with the appropriate diagnostic tests.

The pathogenesis of disseminated histoplasmosis, risk factors for dissemination, and clinical features of the infection will be reviewed here. The diagnosis and treatment of this infection and the manifestations of localized pulmonary histoplasmosis are discussed separately. (See "Diagnosis and treatment of disseminated histoplasmosis in HIV-uninfected patients" and "Pathogenesis and clinical features of pulmonary histoplasmosis".)


Histoplasma capsulatum is a thermally dimorphic fungus, growing as a mold in the environment and as a yeast at 37ºC. Infection develops when Histoplasma microconidia are inhaled into the lungs, where they change into the yeast form. Neutrophils, macrophages, lymphocytes, and natural killer (NK) cells are attracted in response to the infection. As in tuberculosis, macrophages assist in spreading the organism via lymphatics and the blood to the adjacent lymph nodes and throughout the reticuloendothelial system (liver, spleen, lymph nodes, adrenal glands, and bone marrow).

In patients with progressive disseminated infection, macrophages are typically engorged with yeasts, supporting the important role of intracellular proliferation of the organism. Organisms are confined to macrophages but less commonly can be seen within the tissue spaces. The organisms can occasionally be seen in peripheral white blood cells in patients with disseminated infection (picture 1).

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Literature review current through: Nov 2017. | This topic last updated: Jul 18, 2016.
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