Diagnostic Value of Skin Biopsy in Fatal Histoplasmosis-Associated Hemophagocytic Lymphohistiocytosis: A Case Report.

introductionHemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome most commonly triggered in adults by infection, malignancy, or autoimmune disease. Disseminated histoplasmosis is an uncommon but recognized infectious trigger, particularly in immunosuppressed patients. Its cutaneous manifestations may be subtle and nonspecific but can provide accessible tissue for diagnostic evaluation. CASE REPORT: A 41-year-old man with psoriasis treated with adalimumab presented with 5 months of progressive constitutional and abdominal symptoms followed by fever, shock, pancytopenia, hepatosplenomegaly, coagulopathy, hypertriglyceridemia, and extreme hyperferritinemia (>  89,000 ng/mL). Bone marrow biopsy demonstrated hemophagocytosis but was negative for fungal organisms on Grocott methenamine silver staining. Punch biopsy of scattered pink-to-violaceous acneiform papules on the forehead and scalp demonstrated numerous tissue-invasive microorganisms, and subsequent molecular testing identified Histoplasma capsulatum. He received dexamethasone, ruxolitinib, and liposomal amphotericin B; etoposide was withheld because of ongoing hemorrhage. Despite treatment, he succumbed to hemorrhagic shock and multiorgan failure and died. Autopsy demonstrated widespread histoplasmosis.

conclusionsIn patients with HLH, subtle skin lesions may provide accessible tissue for demonstrating invasive infection and obtaining organism-specific confirmation, even when fungal staining of another tissue is negative. Careful skin examination and targeted biopsy of new, atypical, or evolving lesions should be considered in immunocompromised adults with unexplained systemic inflammation, particularly those receiving tumor necrosis factor-alpha inhibitors.