S3675 Azithromycin-Induced Acute Liver Injury

Abstract

Introduction: Idiosyncratic drug-induced liver injury (DILI) is a subtype of drug-induced liver injury that is typically variable in presentation and independent of medication dose or duration. A great number of commonly used medications and herbal supplements have been associated with idiosyncratic drug-induced liver injury. DILI is of clinical significance due to the potential for progression to chronic liver disease or acute liver failure, and may be caused by drugs not commonly associated with liver injury. Case Description/Methods: A 60 year old female was admitted after presenting with sore throat, fever, cough, diarrhea, rash and generalized malaise for 4 days prior to admission. Her past medical history was significant for mixed connective tissue disease, rheumatoid arthritis, and a remote history of alcohol abuse. She was on day two of an outpatient Azithromycin course prescribed for community acquired pneumonia. Physical exam showed diffuse, blanching, maculopapular rash along chest wall and dorsum of her upper extremities. Hepatic panel showed AST 64, ALT 42, Total bilirubin 1.1, and alkaline phosphatase of 68. Liver chemistries peaked during admission to AST 607, ALT 936, Total Bilirubin 20.8, ALP 739. MRCP demonstrated gallbladder adenomyomatosis and multiple simple hepatic cysts. Azithromycin was discontinued, and patient was started on N-acetylcysteine infusion. Workup for viral hepatitis was negative, as were EBV, CMV, HSV and HIV serologies. Immunologic workup showed positive ANA with chromatin of 6.5, SMRNP >8, and RNP of 8. AMA and ASMA were < 1:20. Given rising liver chemistries and history of autoimmune disease, a liver biopsy was obtained and revealed mild chronic hepatitis with minimal periportal activity, moderate bile duct injury with marked cholestasis, pseudoxanthomatous degeneration, and mild anisonucleosis consistent with DILI. Liver chemistries began improving on day 11 of admission. Patient’s maculopapular rash was largely cleared prior to discharge. Discussion: Azithromycin is recognized as a common agent in DILI. In this case, Azithromycin was recognized early as a potential cause of the patient’s worsening liver chemistries. Cessation of the offending agent will resolve most cases of DILI. This case demonstrates how a commonly prescribed medication may cause DILI with risk of progression to acute liver failure. Medications not typically associated with hepatic injury should be assessed when considering DILI.Figure 1.: Portal area with reactive atypia in bile ducts consistent with cholestasis. Mixed inflammatory infiltrate surrounding portal area.