Immunocompromised patients e.g. patients with acquired immune deficiency syndrome (AIDS), hematologic malignancies, and prolonged steroid/immunosuppressant treatment such as transplant recipients are at higher risk of developing acute disseminated histoplasmosis with an aggressive course.[1,2] As per The Center for Disease Control (CDC), the incidence of histoplasmosis in adults aged 65 years and older in the U.S. is 3.4 cases per 100,000 population. In the Midwest, the rates were highest (estimated 6.1 cases per 100,000 population). The estimated crude mortality rate is approximately 5% for children and 8% for adults among those who were hospitalized for histoplasmosis in the U.S. For patients with symptomatic histoplasmosis, the six-month mortality rate is 4%.[2] Endemic areas include the central and eastern United States, particularly areas around the Ohio and Mississippi River Valleys.[1,2,3] Histoplasma capsulatum exists as a mold with aerial hyphae in the environment. The hyphae produce macroconidia and microconidia spores that are aerosolized by activities like spelunking, cleaning chicken coops, construction and disturbing the soil heavily contaminated with bird or bat droppings. Histoplasmosis is acquired via inhalation of airborne microconidia. After the spores enter the lungs, they are transformed into yeasts due to higher temperature of the body. From there the yeast can travel to lymph nodes and other parts of the body through the bloodstream.[2] The severity of illness is determined by the host immunity and the intensity of the exposure. Symptomatic infections usually present 3 to 17 days after exposure. Acute pulmonary histoplasmosis is often self-limiting. The symptoms include fever, malaise, cough, headache, chest pain, chills, and myalgia. Chronic pulmonary histoplasmosis can develop in patients with a history of pulmonary disease. Immunosuppressed persons are at risk for developing disseminated histoplasmosis.[1,2,4]

Microscopic diagnosis has low sensitivity, but if positive it can provide a quick diagnosis. Histoplasma capsulatum appears as 1-5 µm, oval, narrow-based budding yeasts. Predominantly the yeasts are usually within macrophages, but can also be seen free in tissues. In patients with disseminated infection, it can be seen in the neutrophils of peripheral blood smear. When the yeasts are present in small numbers, it is difficult to identify it on hematoxylin and eosin stain; in those cases periodic acid Schiff (PAS) or Grocott-Gomori methenamine silver (GMS) stains can be used to visualize the organisms. The yeast-like organisms typical of H. capsulatum are few in number or absent in biopsy material in cases of granulomatous mediastinitis containing caseous material from necrotic nodes or fibrotic tissue from fibrosing mediastinitis.[4] Other tests available for the diagnosis of Histoplasmosis are antigen detection test [Enzyme immunoassay (EIA)], antibody tests [Immunodiffusion (ID) assay and Complement Fixation (CF) assay], culture, and Polymerase Chain Reaction (PCR). For antigen detection, preferred specimen is urine and/or serum, but it can also be performed on cerebrospinal fluid or bronchoalveolar lavage fluid. The antibody tests are not as useful as antigen detection tests in diagnosing acute histoplasmosis as the development of antibodies to Histoplasma can take two to six weeks. CF is more sensitive but less specific than ID. Culture may take up to 6 weeks to become positive. The sensitivity of respiratory cultures is much lower in localized disease or acute disease.[2,4,5] Polymerase chain reaction (PCR) for detection of Histoplasma is still experimental.[2]

Itraconazole is generally preferred for mild to moderate histoplasmosis, and amphotericin B has a role in the treatment for moderately severe and severe infections.[4]