S5781 A Rare Case of TMP-SMX Induced Idiosyncratic Drug-Induced Liver Injury

Introduction: Drug-induced liver injury (DILI) is a rare but potentially serious adverse reaction, ranging from asymptomatic liver enzyme elevation to fulminant hepatic failure. DILI is broadly classified into direct and idiosyncratic types. Direct DILI (dDILI) is dose-dependent, predictable, and commonly linked to agents such as acetaminophen, aspirin, tetracyclines, and vitamin A. In contrast, idiosyncratic DILI (iDILI) is dose-independent, unpredictable, and difficult to replicate in preclinical models. iDILI has been associated with various drug classes, including antibiotics, NSAIDs, herbal supplements, CNS agents, cardiovascular medications, and some chemotherapeutics. Agents such as amoxicillin-clavulanate, isoniazid, ciprofloxacin, and trimethoprim-sulfamethoxazole (TMP-SMX) have been implicated among antibiotics. Case Description/Methods: We present a case of a 59-year-old woman with no significant medical history who developed iDILI following a short course of TMP-SMX. One week prior to presentation, she was treated with TMP-SMX for a urinary tract infection. Three days into therapy, she developed generalized fatigue, weakness, nausea, migratory arthralgias, myalgias, and a diffuse red rash. Imaging revealed hepatic steatosis, and labs showed aspartate aminotransferase (AST) 1,492, alanine aminotransferase (ALT) 1,147, and ALK 73. Upon admission, AST was 1,351, ALT 1,386, ALK 74, CK 548, and LDH 2198. Physical exam showed erythema over the face, chest, and upper back. Notably, the patient recalled a similar reaction 2 years prior but was unsure of the offending agent. TMP-SMX was discontinued, and she was treated with prednisone, famotidine, and diphenhydramine. She was discharged the following day with improvement in symptoms and downtrending liver enzymes (AST 325, ALT 797). Discussion: This case highlights the importance of recognizing TMP-SMX as a potential cause of iDILI. Although rare, TMP-SMX-induced liver injury can be severe. DILI accounts for up to 16% of acute liver failure cases, with antibiotics comprising nearly half. Given the widespread use of TMP-SMX, clinicians should maintain a high index of suspicion for iDILI, particularly in patients presenting with systemic symptoms after recent drug exposure. Prompt identification, cessation of the offending agent, and supportive care are essential to prevent progression to severe liver damage.