Case Presentation:

A 27-year-old man with recently diagnosed human immunodeficiency virus (HIV) not on antiretroviral therapy presents with several months of cough, fever, abdominal pain, weight loss, gait imbalance, and hallucinations. On presentation, he was febrile and tachycardic. He was cachectic-appearing with bibasilar rales and diffuse lymphadenopathy. His labs revealed a leukopenia, hyponatremia, elevated lactate dehydrogenase, and hyperferritinemia. A computed tomography of the chest showed diffuse bilateral nodular opacities and lymphadenopathy. He was persistently febrile and became hyponatremic to 120 mmol/L and was subsequently transferred to the intensive care unit. Confirmation from his previous hospitalization revealed an HIV viral load of 4.7 million copies/mL, CD4 count of 90 cells/cubic milliliter, and a positive M band on the histoplasma antibody serologies. He was promptly started on efavirenz/emtricitabine/tenofovir and broad spectrum antibiotics including sulfamethoxazole/trimethoprim and azithromycin. A bronchoscopy was performed revealing Histoplasma capsulatum on culture and budding yeast on pathology. His urine Histoplasma galactomannan antigen level was positive at >20 ng/mL. He was started on liposomal amphotericin for disseminated histoplasmosis. Due to the addition of amphotericin as well as documented gene mutations in his HIV genotype testing, his antiretroviral regimen was changed to abacavir-lamivudine and dolutegravir. After two weeks of amphotericin, he was transitioned to oral itraconazole. 


Histoplasma capsulatum is an endemic, dimorphic fungus in North, Central, and South America. Infection occurs when microconidia of H. capsulatum are aerosolized from soil or areas contaminated with bat or bird excrement. Histoplasmosis is usually self-limited in immunocompetent patients however it can manifest as the following in immunosuppressed patients: acute pulmonary histoplasmosis, progressive disseminated histoplasmosis, mediastinal lymphadenitis, or chronic cavitary pulmonary histoplasmosis, all of which are indications for antifungal therapy. Diagnosis is made by testing for Histoplasma antigen in urine or serum, direct examination of respiratory secretions by microscopy and Grocott’s methenamine silver (GMS) stain, and serology. For immunosuppressed patients with moderately-severe or severe histoplasmosis, initial therapy with two weeks of intravenous amphotericin B is warranted followed by itraconazole for up to 12 months. Secondary prophylaxis with antifungal therapy is warranted if immunosuppression persists. 


Histoplasmosis is an AIDS-defining illness.  Although uncommon, particularly with decreasing incidence of fulminant AIDS, disseminated histoplasmosis should be included in the differential for opportunistic infections in immunocompromised patients with respiratory, abdominal, central nervous system (CNS), or ocular symptoms.  Hospitalists should be aware that elevated LDH and ferritin levels are early indicators of disseminated disease.  Early treatment with amphotericin B is the treatment of choice for patients with severe infection.