A Rare Cause of Cholestatic Hepatitis in an Immunocompetent Male

Abstract

Introduction: Histoplasmosis has been rarely reported in the literature in immunocompetent patients, much less in a disseminated fashion. A 69-year-old male with history of end-stage renal disease (ESRD), hypertension, and diabetes presented with 3 weeks of progressive abdominal swelling and jaundice with worsening colicky abdominal pain, nausea, and diarrhea. Review of symptoms revealed several months of non-productive cough and intermittent low-grade fevers and chills. He was found to be febrile with icteric sclera and a mildly distended abdomen. Initial laboratory evaluation revealed a total bilirubin of 8.6 mg/dL, a direct bilirubin of 5.4 mg/dL, elevated ALP of 424 units/L, and normal AST and ALT. A miliary pattern was seen on chest x-ray. Investigation of the cholestatic labs, including a right upper quadrant ultrasound and CT abdomen, showed no intra or extrahepatic biliary duct dilation. MRI was remarkable only for iron deposition in the liver. These findings raised suspicion for a process involving both the lungs and liver. A bronchoscopy was completed with unrevealing initial cultures and pathology. HIV ELISA, fungal blood cultures, a viral hepatitis panel, and urine histoplasma antigen were negative. His fevers, hyperbilirubinemia, and elevated ALP persisted, and ultimately, a liver biopsy was completed, which revealed mixed inflammatory infiltrate with severe granulomatous hepatitis. Numerous well-formed granulomas were present, lacking overt caseating features but having fibrinoid material identified within them as well as areas of hepatic necrosis. There were no organisms detected on GMS fungal stain or acid-fast bacillus (AFB) stain, and liver biopsy cultures were negative as well. Final bronchoscopy cultures grew mold consistent with histoplasmosis. The patient was promptly started on itraconazole, after which he quickly defervesced with marked improvement in bilirubin and ALP. The myriad causes of hepatic granulomas can be broadly categorized into immunologic disorders, infiltrative bacterial and fungal infections, neoplasia, and hypersensitivity to drugs or metals. This case highlights the challenges in identifying a fungal etiology of granulomatous hepatitis based on histopathology alone, and underscores the importance of tissue microbiology in making the diagnosis. The patient’s liver histopathology did not have classic features of caseating granulomas typical of histoplasmosis, and neither GMS fungal stain nor liver biopsy identified any organism. It was not until the bronchoscopy culture grew mold that the diagnosis was reached. Histoplasmosis as a cause of unexplained cholestatic jaundice and fever must be considered even in immunocompetent patients from nonendemic areas.