Study of immune reactivity of minocycline-induced chronic active hepatitis

Hepatotoxicity of minocycline, a semisynthetic tetracycline, leading to microsteatosis, allergic reactions, or a syndrome similar to autoimmune hepatitis has been described. We describe the case of a female adolescent with Hashimoto's thyroiditis, 18 months of minocycline intake for acne, who presented with an anti-nuclear antibody (ANA) -positive chronic active hepatitis. After cessation of minocycline therapy, the chronic active hepatitis subsided. Testing the patient's serum by immunoprecipitation against human hepatoma cells, antibodies against a 50- and a 90-kDa protein could be visualized. Furthermore, the patient's serum recognizes a 50-kDa protein of rat liver microsomes when tested by western blot, and different purified P-450 proteins by ELISA test. We speculate that there must be an antibody reaction against an as yet unknown metabolite of minocycline that cross-reacts with several microsomal cytochromes. Furthermore, this finding suggests that the hepatotoxicity of minocycline could be mediated by an immune response.