RAPIDLY PROGRESSIVE AUTOIMMUNE HEPATITIS FOLLOWING PROLONGED THERAPY WITH MINOCYCLINE AND ERYTHROMYCIN

CJ Karvellas, H Idikio, LD Jewell and KS Gutfreund

Departments of Medicine and Pathology, University of Alberta, Edmonton, Alberta

INTRODUCTION: Drug induced autoimmune hepatitis (AIH) is an uncommon but well described entity. Minocycline has been reported to cause hypersensitivity-type reactions with hepatitis, fulminant hepatic failure (FHF) and AIH. Other autoimmune diseases including SLE have been associated with the use of minocyline. AIH typically occurs after a year or more of ongoing therapy with minocyline and the clinical course has been very variable in the published cases. Erythromycin has been reported to cause mainly cholestatic hepatitis which usually resolves within weeks to several months after discontinuation of the offending drug.
CASE REPORT: A 14-year old female was started on minocycline for acne in October 1999. Eleven months after initiation of therapy she developed fatigue, occasional episodes of fever and arthralgias which eventually resolved. Laboratory investigations including an ALT and ANA were normal and minocycline was continued until July 2001. Thereafter, she was switched to erythromycin, which was continued until May 2002. Both of these medications were stopped because of treatment failure rather than side effects. However, subsequently she developed pruritus and was found to have markedly elevated aminotransferases (ALT 1658 U/L, AST 1416 U/L, ALP 172 U/L, Bilirubin 20 mmol/L) in July 2002. Further testing revealed an elevated IgG (32.85 g/L) and a positive SMA and ANA consistent with type I AIH. Investigations for viral and metabolic causes of hepatitis were negative. A liver biopsy showed chronic hepatitis with bridging portal fibrosis. She was subsequently started on Prednisone and endured a marked biochemical improvement by September 2002 (AST 165 U/L, ALT 471 U/L, ALP 128 U/L, Bilirubin 8 mmol/L). Imuran was then added and she achieved a near biochemical remission by October 2002. HLA genotyping was negative for the classical alleles associated with AIH.
CONCLUSION: This case report suggests that minocycline may have caused a delayed-onset of type I AIH with rapid progression to bridging fibrosis. A contributing role of erythromycin cannot be excluded. Discontinuation of the offending drug was ineffective but immunosuppressive therapy resulted in a prompt biochemical remission.