Indiana University School of Medicine Indianapolis, Indiana
Introduction: Histoplasmosis is the most prevalent endemic mycosis in the United States. While most infections are asymptomatic or self-limiting, some individuals develop acute pulmonary infections or severe and progressive disseminated infections. Disseminated histoplasmosis (DH) is a progressive extra-pulmonary infection. Liver is rarely the primary site of infection without evidence of pulmonary disease. Most patients who develop DH are immunosuppressed (eg, AIDS, solid organ transplantation, treatment with tumor necrosis factor-alpha inhibitors) or are at the extremes of age. DH very rarely presents with severe acute liver injury or hemophagocytic lymphohistiocytosis (HLH).
Case Description/Methods: Our subject is a 61 year old female with past medical history significant for rheumatoid arthritis treated with a TNF-alpha inhibitor who presented with few weeks history of fatigue, night sweats and fever. The patient was found to be in acute liver failure on admission to the hospital. She also developed cytopenias and was found to have elevated elevated IL-2 receptor levels raising the concern for HLH. A liver biopsy was obtained and showed acute hepatitis and marked steatosis. Scattered foci of lobular inflammation were also noted and with vaguely granulomatous appearance. Special stains for fungal organisms (PAS, GMS) showed numerous budding yeasts, consistent with histoplasmosis (Figures A&B). A bone marrow biopsy was noted with frequent hemophagocytic histiocytes and rare monocytic cells with intracytoplasmic inclusion bodies consistent with presumed HLH and histoplasmosis (Figures C&D). The patient was started on treatment with antifungals soon after diagnosis, with gradual improvement in liver function and blood counts and eventual normalization.
Discussion: Disseminated histoplasmosis presenting as granulomatous liver disease is rare. Hepatic histoplasmosis as the primary manifestation of disseminated disease and with no evidence of pulmonary involvement is rarely seen. Patients may present with stigmata of chronic liver disease, portal hypertension, ascites, varices, and occasionally with severe liver injury leading to acute failure as shown in this patient. Histoplasmosis-associated HLH is an uncommon disorder for which data are limited regarding the optimal treatment and clinical outcomes in adults. Providers should keep a high index of suspicion for this uncommon manifestation of fairly common infections in patients who present with cryptogenic liver injury and fever, specially in endemic areas.
