Recurrent Disseminated Histoplasmosis in an Apparently Immunocompetent Older Adult

Disseminated histoplasmosis remains a significant diagnostic challenge in older adults, as immunosenescence can impair macrophage activation, T-cell-mediated fungal clearance, and cytokine signalling, predisposing individuals to severe infection despite apparent immunocompetence. We report a 74-year-old man with 4 months of fatigue, dyspnea, pedal edema, and intermittent fever, whose evaluation revealed pancytopenia and hepatosplenomegaly. Bone marrow and skin biopsy demonstrated intracellular Histoplasma capsulatum , confirming disseminated histoplasmosis. The clinical presentation frequently overlaps with hematologic malignancies and endemic infections such as visceral leishmaniasis or disseminated tuberculosis, leading to delayed diagnosis. Bone marrow examination remains a valuable diagnostic tool in patients with unexplained cytopenias, particularly in resource-limited settings where fungal antigen assays and molecular tests are unavailable. Recurrent disease after adequate therapy raises concerns regarding latent intracellular persistence of H. capsulatum , subtherapeutic itraconazole exposure due to variable gastrointestinal absorption, and progressive immunosenescence. Recognition of these mechanisms is essential to enable timely diagnosis, optimize antifungal pharmacokinetics, and ensure long-term surveillance to prevent relapse in older individuals.