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Histoplasmosis, also known as Cave disease, Darling's disease, Ohio valley disease, Reticuloendotheliosis, Spelunker's lung, and Caver's disease, is a fungal infection caused by Histoplasma capsulatum. This disease primarily affects the lungs but can disseminate to other organs, potentially becoming fatal if untreated.

H. capsulatum is commonly found in soil enriched with bat guano or bird droppings. Disruption of such soil releases infectious spores that can be inhaled by humans. The disease has a 1-2 week incubation period and is common among immunocompromised individuals, such as AIDS patients.

Histoplasma capsulatum. Methenamine silver stain showing histopathologic changes in histoplasmosis
Histoplasma capsulatum. Methenamine silver stain showing histopathologic changes in histoplasmosis

Signs and Symptoms

Symptoms of histoplasmosis can appear 3-17 days after exposure, typically around 12-14 days. Most individuals remain asymptomatic. When symptoms do appear, they often mimic nonspecific respiratory ailments like cough or flu-like symptoms. In severe cases, it can resemble tuberculosis. Disseminated histoplasmosis affects multiple organs and can be fatal without treatment.

Skin lesion on the upper lip due to H. capsulatum infection
Skin lesion on the upper lip due to H. capsulatum infection

Severe infections can cause hepatosplenomegaly, lymphadenopathy, and adrenal enlargement. Presumed ocular histoplasmosis syndrome (POHS) causes chorioretinitis, leading to vision loss similar to macular degeneration.


Without proper treatment, complications can arise, especially in immunocompromised individuals. These include recurrent pneumonia, respiratory failure, fibrosing mediastinitis, superior vena cava syndrome, pulmonary vessel obstruction, and progressive fibrosis of lymph nodes. Fibrosing mediastinitis is particularly serious and can be fatal.


H. capsulatum grows in soil contaminated with bird or bat droppings. It is thermally dimorphic, changing from a mycelium in the environment to a yeast at human body temperature. Infection occurs through the inhalation of microconidia, which reach the alveoli and are ingested by macrophages. Inside the macrophages, the fungus transforms into yeast, multiplies, and can disseminate to various organs.


Diagnosing histoplasmosis involves detecting the fungus in samples from sputum, blood, or infected organs. ELISA or PCR tests can detect antigens in blood or urine. Antigen tests can cross-react with other fungal infections, so culturing the fungus directly is often necessary for confirmation. Sabouraud agar is a growth medium used for this purpose.

Chest X-ray of a patient with acute pulmonary histoplasmosis
Chest X-ray of a patient with acute pulmonary histoplasmosis


Histoplasmosis can be classified into primary pulmonary histoplasmosis, progressive disseminated histoplasmosis, primary cutaneous histoplasmosis, and African histoplasmosis.

Histopathology of Histoplasma capsulatum, H&E stain, showing organisms surrounded by halos, in a granuloma of epithelioid histiocytes.
Histopathology of Histoplasma capsulatum, H&E stain, showing organisms surrounded by halos, in a granuloma of epithelioid histiocytes.
Histopathology of Histoplasma capsulatum, GMS stain, showing narrow budding yeast
Histopathology of Histoplasma capsulatum, GMS stain, showing narrow budding yeast
Histoplasma capsulatum var. duboisii, methenamine silver stain
Histoplasma capsulatum var. duboisii, methenamine silver stain
Macroconida form of Histoplasma capsulatum
Macroconida form of Histoplasma capsulatum


Preventing histoplasmosis involves avoiding areas with high bird or bat droppings. The US National Institute for Occupational Safety and Health provides guidelines for reducing occupational exposure risks.


In immunocompetent individuals, histoplasmosis often resolves without treatment. Severe cases require antifungal medications like amphotericin B followed by oral itraconazole. Liposomal preparations of amphotericin B are preferred due to lower nephrotoxicity risks. Alternatives to itraconazole include posaconazole, voriconazole, and fluconazole.


About 90% of patients with normal immune systems recover without intervention, while less than 5% require serious treatments.


H. capsulatum is found worldwide, with endemic areas in the United States, particularly around the Ohio River valley and the lower Mississippi River. It is also common in caves in Southern and East Africa. In Canada, the St. Lawrence River Valley has frequent infections. In India, West Bengal is a notable area for infections. In non-endemic countries, histoplasmosis is often diagnosed in immunocompromised patients.

Histoplasmosis in Workplaces

Histoplasma presents a significant occupational hazard, especially in industries like construction, demolition, agriculture, and mining. The CDC recommends preventive measures like protective equipment and safety plans to reduce exposure risks.


Histoplasma was first discovered in 1905 by Samuel T. Darling. Initially, many cases were mistaken for tuberculosis, leading to misdiagnosis and inappropriate treatment.

Society and Culture

Histoplasmosis has been referenced in popular culture, including songs by Johnny Cash and medical diagnoses in TV series like House M.D. and New Amsterdam.

Self-assessment MCQs (single best answer)

What is histoplasmosis primarily caused by?

Which of the following is NOT a common name for histoplasmosis?

What is the primary mode of infection for histoplasmosis?

Which population is most at risk for severe histoplasmosis?

What is a hallmark sign of disseminated histoplasmosis?

What type of stain is used to identify Histoplasma capsulatum in histopathologic samples?

How is histoplasmosis most commonly diagnosed?

Which antifungal medication is preferred for severe cases of histoplasmosis due to lower nephrotoxicity?

Where in the United States is histoplasmosis most commonly found?

Who first discovered Histoplasma capsulatum?


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