Disseminated histoplasmosis presenting as a pyrexia of unknown origin

Histoplasmosis is a systemic fungal infection caused by inhalation of spores of Histoplasma capsulatum . The disease is endemic in several geographical regions worldwide, including parts of India such as West Bengal, Assam, and selected areas of southern and northern India. Sporadic cases have also been reported from Gujarat and Rajasthan. However, being tropical countries with lots of other infections, histoplasmosis becomes a relatively rare infection and is often missed in routine clinical practice. In patients presenting with pyrexia of unknown origin, delayed diagnosis of disseminated histoplasmosis may result in catastrophic consequences. We report the case of a 29-year-old male, grain merchant by occupation, presented with a fever of 1-month duration. He had previously received empirical broad-spectrum antimicrobial therapy at another hospital without clinical improvement. At presentation, the patient was ill-appearing and hemodynamically unstable. On physical examination, mild splenomegaly was present, and the chest was clear on auscultation. Laboratory evaluation demonstrated bicytopenia, raising suspicion for hematological malignancy or overwhelming systemic infection. Fluorodeoxyglucose (FDG)-positron emission tomography computed tomography demonstrated diffuse marrow hypermetabolism and FDG-avid hepatosplenomegaly, further increasing suspicion for malignancy. Bone marrow aspiration and biopsy were planned, but due to hemodynamic instability could not be performed; however, peripheral blood smear examination revealed intra- and extracellular small oval yeast-like organisms morphologically suggestive of H. capsulatum . The patient was treated with an induction therapy dose of Liposomal amphotericin B 3 mg/kg/day for 7 days. Fever subsided within 24 h of therapy, accompanied by rapid clinical and hemodynamic improvement. Following induction therapy, maintenance treatment with oral itraconazole was initiated with a loading dose of 200 mg thrice daily for 3 days, followed by 200 mg twice daily, planned for 1 year. Disseminated histoplasmosis should be considered in patients with prolonged unexplained fever, even in the absence of apparent immunodeficiency. Peripheral blood smear examination may provide an important diagnostic clue and, in selected cases, may help avoid invasive procedures such as bone marrow examination. Early recognition and prompt initiation of antifungal therapy can result in rapid clinical improvement and may be lifesaving.