S5457 Sulfasalazine-Induced Liver Injury

Introduction: Sulfa drugs are one of the leading causes of drug-related, idiosyncratic fulminant hepatic failure. Most cases have mild elevations in alanine aminotransferase (ALT) levels, which resolve rapidly but may be accompanied by hepatic granulomas, usually within 2 to 4 weeks unless cholestasis is severe. Case Description/Methods: A 36-year-old woman with a history of ulcerative colitis presented with a 4-day history of viral-like symptoms, including fever and malaise. Laboratory evaluation revealed marked elevation of liver enzymes (aspartate aminotransferase 147 IU/L, alanine aminotransferase 461 IU/L) suggestive of hepatocellular injury. She had been initiated on sulfasalazine therapy for ulcerative colitis one month prior. Initial investigations, with hepatitis A antibody, hepatitis-B core Antibody, hepatitis-B surface Antigen, and hepatitis-C, ANA, LKM, anti-smooth muscle, and antimitochondrial antibody, which were negative, and imaging was unremarkable. Over subsequent days, the patient’s liver enzymes continued to rise despite supportive measures. The clinical suspicion for drug induced liver injury was heightened given the temporal relationship with sulfasalazine initiation and absence of alternative etiologies. On Day 5, liver biopsy confirmed drug-induced liver injury characterized by mild portal and lobular inflammation with rare mitotic figures. Following biopsy, sulfasalazine was promptly discontinued, and the patient was initiated on Solu-Medrol for a presumed drug hypersensitivity reaction. Liver function tests began to normalize within a week, with the resolution of symptoms. The patient was discharged with close outpatient follow-up to monitor liver function and ensure resolution of hepatotoxicity. Discussion: Sulfa-induced liver damage is idiosyncratic, an allergic reaction. Symptoms typically include sudden fever and rash, followed by jaundice within days or weeks of starting the medication. It often involves abnormal blood counts like eosinophilia or atypical lymphocytes. The liver injury pattern is usually cholestatic or mixed and can be severe at times. The severity of liver injury varies widely, from mild, non-jaundiced enzyme increases to severe hepatitis or even liver failure. Most cases improve quickly when the drug is stopped, usually within 2 to 8 weeks. Severe bile blockage can cause prolonged issues, and rare chronic liver damage cases of vanishing duct have been noted. Patients should avoid all sulfonamides and rechallenge is not advised. Prednisone may help in severe cases.