Disseminated histoplasmosis of a liver transplant recipient complicated by histoplasmosis‑induced hemophagocytic (HLH) syndrome: A case report and clinical challenges

Histoplasma capsulatum is an uncommon but severe infection in solid organ transplant recipients. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome rarely reported after liver transplantation. We describe a 71-year-old man with hepatitis B virus-related hepatocellular carcinoma who underwent orthotopic liver transplantation with steroid induction and tacrolimus/mycophenolate maintenance. One-month post-transplant he developed biopsy-proven acute cellular rejection refractory to pulse steroids and was treated with thymoglobulin. Two months later he presented with fever, pancytopenia, and pleural effusion; microscopy and serum antigen testing confirmed disseminated histoplasmosis. Despite itraconazole, he progressed to ARDS, dialysis dependence, and liver dysfunction. Persistent fevers, extreme hyperferritinemia (>33,000 ng/mL), new splenomegaly, elevated soluble IL-2 receptor, and bone marrow biopsy with hemophagocytosis established secondary HLH (7/8 HLH diagnostic criteria). Antifungal therapy was escalated to amphotericin B then transitioned to isavuconazole. Tacrolimus and mycophenolate were withdrawn, with low-level tacrolimus reintroduced during recovery, and IVIG was administered for HLH. He gradually improved and was discharged on hospital day 85 with normalized bilirubin and declining Histoplasma antigen. This first detailed report of disseminated histoplasmosis complicated by HLH and rejection in a liver transplant recipient underscores diagnostic challenges and the need for carefully balanced, multidisciplinary immunosuppression management.