Disseminated histoplasmosis in a patient without identified immunodeficiency: A case report

Disseminated histoplasmosis, caused by Histoplasma capsulatum, is uncommon in immunocompetent individuals and more frequently associated with immunocompromised hosts. We report a case of a 48-year-old male with no known immunodeficiency who presented with persistent fever and night sweats lasting over a month, without respiratory symptoms or relevant exposure history. Laboratory tests revealed elevated inflammatory markers and liver enzymes, while HIV screening, autoantibodies, immunoglobulin levels, lymphocyte subsets (CD3⁺, CD4⁺, CD8⁺), rheumatoid factor, (1,3)-β-d-glucan (BDG), and galactomannan antigen test were all within normal limits. Chest and abdominal CT scans showed no abnormalities. Bone marrow examination revealed yeast-like organisms within macrophages, which were identified as H. capsulatum by next-generation sequencing (NGS), despite a negative BDG test. Initial treatment with posaconazole was ineffective; symptoms resolved after switching to amphotericin B combined with dexamethasone, followed by maintenance therapy with itraconazole. This case is notable for infection primarily confined to the bone marrow, in the absence of underlying immunodeficiency. The negative BDG test may be attributable to the masking of β-d-glucan by 1,3-α-glucan on the fungal cell wall, allowing immune evasion. This report underscores the potential for H. capsulatum to disseminate in patients without identified immunodeficiency and highlights the diagnostic value of bone marrow analysis and NGS in cases of fever of unknown origin with nonspecific systemic symptoms. Clinicians should consider disseminated histoplasmosis even in the absence of classical risk factors.