S5114 Leptospirosis in Disguise: A Case of Cholestatic Jaundice and Multiorgan Involvement Without Classic Risk Factors

Introduction: Leptospirosis is a rare but potentially life-threatening zoonotic infection caused by Leptospira interrogans, with an annual incidence of fewer than 200 reported cases in the United States. It typically presents as a biphasic illness, beginning with nonspecific symptoms such as fever, myalgias, and headache in the initial leptospiremic phase, followed by the leptospiruric phase with immune-mediated multiorgan involvement. Weil’s disease, the severe form, is characterized by jaundice, renal dysfunction, and hemorrhagic manifestations, but can often present atypically, especially in non-endemic settings. Case Description/Methods: We report a diagnostically challenging case of Weil’s disease in a young adult man with no recent travel or identifiable exposure risk. The patient presented with constitutional symptoms and developed multiorgan dysfunction including severe cholestatic liver injury, acute kidney injury, myocarditis, and myositis. Notably, liver function testing demonstrated a striking cholestatic pattern, with a peak total bilirubin of 52.2 mg/dL (predominantly direct), minimal transaminitis, and a normal alkaline phosphatase—raising concern for biliary obstruction, drug-induced liver injury, or infiltrative disease. Imaging and serologic workup were unrevealing. Given a rising bilirubin and elevated INR, acute liver failure was considered, and the patient was started on intravenous N-acetylcysteine (NAC) while undergoing serial INR monitoring every 6–12 hours. Liver biopsy later revealed nonspecific acute hepatitis with cholestasis, leading to NAC discontinuation after stabilization of synthetic function. The hospital course was further complicated by cardiac involvement, with atrial fibrillation, elevated troponin, and reduced ejection fraction on echocardiography—all of which resolved with supportive care. Neurologic symptoms prompted evaluation for myositis, confirmed by MRI and elevated creatine kinase, and managed successfully with corticosteroids. The diagnosis of leptospirosis was ultimately confirmed by positive IgM serology. Empiric doxycycline was initiated early and resulted in marked clinical improvement. Discussion: This case underscores the importance of considering leptospirosis in the differential diagnosis of unexplained multiorgan dysfunction, even in the absence of classic epidemiologic risk factors. Prompt recognition and empiric treatment can be lifesaving in patients presenting with severe manifestations of this rare infection.