Disseminated Histoplasmosis Presenting as Granulomatous Hepatitis in a Patient with Psoriatic Arthritis

Abstract

Histoplasma capsulatum(HC) is known to cause systemic infections in immunodeficient hosts. It most commonly originates in the lungs, and then may spread to involve the gastrointestinal tract, liver and bones. However, presentation as acute granulomatous hepatitis without preceding pulmonary symptoms is very rare. A 54-year-old woman with psoriatic arthritis, previously treated with methotrexate and adalimumab, was admitted for worsening jaundice, abdominal pain and 20-pound weight loss. Physical exam revealed tenderness in the upper quadrants of the abdomen, with no appreciable hepatosplenomegaly. Cell counts were normal. Total and direct bilirubin were 11 and 8.4 mg/dl respectively. Alkaline Phosphatase was high at 1064 mg/dl, with mildly elevated AST/ALT. Hepatitis panel was negative. Liver ultrasound showed a cirrhotic appearance, mild hepatomegaly and a few simple appearing cysts. There was no evidence of ascites, ductal dilatation or cholecystitis. She underwent a liver biopsy, which revealed well-formed portal and lobular caseating granulomas with small yeasts. In addition, bile duct proliferation, biliary infarcts and moderate macro vesicular steatosis involved 40% of the hepatic parenchyma. The Gomori's methenamine silver stained slide also revealed small yeasts in the areas of granulomatous inflammation. The morphology was consistent with HC. Urine HC antigen, and serum antibodies were also positive. Mycobacterium infection was ruled out by tissue polymerase chain reaction. Patient was started on 2 weeks of amphotericin B 4mg/kg with 12 months course of Itraconazole to follow. She was seen in clinic for follow-up and reported resolution of her symptoms. The pathogenesis behind early liver involvement and pulmonary sparing, remains unknown till date. Patients with immune suppression and extremes of age are known to have ten times higher the risk of HC, when compared to general population. Therefore, granulomatous hepatitis, as an initial manifestation of systemic histoplasmosis is only reported in patients with AIDS or renal transplants. A high index of suspicion is required for appropriate work up leading to this diagnosis. We report the first case of such a presentation in a patient with psoriatic arthritis. Interestingly, our patient had well-controlled disease and was not on immune-suppressive therapy for past year. She responded well to the anti-fungal treatment with normalization of her liver enzymes and marked improvement in her symptoms.