2408 Carbamazepine-Induced Immuno-Allergic Hepatitis!

Abstract

INTRODUCTION: Drug induced liver injury (DILI) is an uncommon cause of abnormal liver tests. It is suspected based on clinical and chronological criteria and is usually a diagnosis of exclusion. Carbamazepine (CMZ) is a commonly prescribed medication for the treatment of epilepsy, trigeminal neuralgia and bipolar disorder. It is a well-known cause of transient liver tests elevation but is only rarely associated with severe hypersensitivity reactions that involve the liver. We present a case of a patient who developed CMZ-induced immuno-allergic hepatitis. CASE DESCRIPTION/METHODS: A 66 year-old Chinese man with history of trigeminal neuralgia presented with several days of fever, asthenia and generalized rash. He had been on CMZ 100 mg daily for trigeminal neuralgia for 8 weeks. Three weeks prior to admission he returned from a 2 week trip to China. He denied herbal remedies, alcohol intake or exposure to farm animals. Physical examination was notable for diffuse confluent maculopapular rash involving his palms and soles (Figure 1). Blood tests were significant for an alkaline phosphatase of 350 IU/L (30-115 IU/L), alanine aminotransferase of 165 U/L (0-41 U/L), aspartate aminotransferase of 84 U/L (0-41 U/L) (Graph 1). Blood tests for viral hepatitis and infectious organisms were negative (Table 1). CMZ was discontinued and the patient was managed conservatively. Three days afterwards, notable improvement in the patient's rash, constitutional symptoms and labs was noted. The patient was discharged uneventfully. DISCUSSION: DILI affects up to 22% of patients exposed to CMZ. It usually occurs within the first 6 months of medication use. The pattern of liver test elevation can be hepatocellular, cholestatic or mixed. CMZ-induced immune-allergic hepatitis affects 16 out of 10,000 individuals per year and mostly presents as part of drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). Although hypersensitivity reaction has been suggested as the most common mechanism of liver injury, reactive metabolites of CMZ have been shown to induce direct cytotoxicity. A direct association between CMZ-induced hepatitis and HLA-B X1502 has been specifically found in Southeast Asian population. After stopping the medication, symptoms resolve within 5-7 days but normalization of the liver enzymes may take up to 4 weeks. CMZ reuse may cause rapid severe recurrence. Heightened awareness of drug toxicity is advised in view of its non-specific symptoms, commonly delayed diagnosis and potentially fatal outcomes.