Histoplasmosis: Fever of Unknown Origin Disseminated to Bone Marrow

Abstract

Histoplasmosis capsulatum is a dimorphic fungus highly endemic to the Mississippi and Ohio River valleys of North America. Infection develops when Histoplasma microconidia are inhaled and transform into their yeast form inside the lungs. In this report, we highlight the importance of including histoplasmosis as a differential diagnosis for a fever of unknown origin. A 42-year-old female with a PMH of HIV presented to the ED in Southwest Indiana for a fever. Her last known CD4 count was 4 and viral load was 601,000. She was found to have pancytopenia. Her platelets were refractory to platelet transfusion and she had several episodes of epistaxis requiring packing. She failed IV antibiotics as her fever persisted. Blood cultures were initially negative, chest x-ray was insignificant, urinalysis was unremarkable, and a respiratory panel was negative, but a urine blastomyces antigen test came back positive and a month later the blood culture subsequently grew presumptive histoplasma capsulatum. She subsequently underwent a bone marrow biopsy as part of her pancytopenia workup which demonstrated histiocytes containing fungal organisms. Her pancytopenia was therefore declared to be secondary to disseminated mycosis. She was treated with IV amphotericin B per infectious disease with improvement. Extrapulmonary disease has been well reported in patients with blastomycosis and histoplasmosis, but bone marrow infiltration is rare. In fact, according to one epidemiological study, only 4% of cases have bone involvement. Our case report is unique as the patient had evidence of fungus in the bone, and it was only through inadvertently obtaining a bone marrow sample for hematologic testing that we were able to find the source for her fever. Although CT of the chest would later demonstrate lung involvement, the case of disseminated mycosis was made by both blood cultures and bone marrow aspirate, indicating osteomyelitis and, hence, disseminated disease that would have otherwise gone unnoticed. This case report highlights the importance of keeping histoplasmosis and other fungal infections on the list of differential diagnoses given the demographic and geographical region as it can potentially be the source for acute illness.