Workup for Elevated Liver Function Tests Unmasks Life-Threatening Disseminated Histoplasmosis Infection

Introduction: Histoplasmosis is an infectious disease caused by the fungus Histoplasma capsulatum that may manifest in a variety of clinical presentations. Many immunocompetent individuals who are exposed to the fungal spores remain asymptomatic; however, life-threatening disseminated infection may occur in immunosuppressed individuals. Although disseminated disease may involve extrapulmonary sites, the lung is usually the primary site of infection. Histoplasmosis that manifests primarily as hepatic infection without the involvement of lung tissue is rare. CASE REPORT: A 68-year-old male patient with a history of common variable immunodeficiency, non-Hodgkin's lymphoma in remission, and diabetes was admitted to the hospital with a two-week history of generalized weakness, intermittent fevers, and non-bloody diarrhea. Initial laboratory workup revealed elevated liver enzymes with total bilirubin of 1.6 mg/dl, AST 83 and ALT 62 mg/dl and ALP of 370 U/L. CT abdomen showed colitis and hepatomegaly and the patient was started on empiric antibiotics with no improvement. Lab parameters worsened with bilirubin increasing to 2.8 mg/dl, AST 114 and ALT 80 mg/dl and ALP to 779 U/L. Extensive liver workup including histoplasmosis serologic testing was negative and liver biopsy was performed as the etiology of progressive liver dysfunction was unclear. Liver biopsy with GMS stain showed yeast forms diagnostic of histoplasmosis. The patient was started on Amphotericin B with normalization of liver function tests to his baseline over the course of few days and complete resolution of symptoms within a few weeks. DISCUSSION: Disseminated histoplasmosis represents an infrequent form of this fungal infection, occurring in approximately 1 in 2000 patients with acute infection. Patients who develop diffuse disease are usually either immunosuppressed or are at extremes of age. Elevations in serum aminotransferases, alkaline phosphatase, and/or bilirubin may suggest hepatic involvement. Traditional laboratory testing modalities often have low sensitivities; therefore, a high degree of suspicion is required to diagnose disseminated Histoplasmosis. Biopsy of the involved organ may be needed for confirmation in-order to promptly initiate lifesaving treatment. Clinicians should recognize that unexplained elevation of liver function tests in patients at risk for disseminated histoplasmosis may represent life threatening liver involvement of this infection.