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Over the years, a variety of abnormal immune reactions to minocycline have been reported including arthritis, systemic lupus erythematosus, and hepatitis. The current report describes the detailed clinical and pathologic features of 3 patients who presented with chronic/autoimmune hepatitis alone while on minocycline at our hospital over a 2-year period. Minocycline use in these patients was temporally related to onset of severe hepatitis. Adolescents with such a reaction to minocycline have been included in previous reports but have not been well described as a distinct entity. We have compared our cases with similar cases previously reported with a review of the literature and a discussion of the implications for prescribing physicians.

Background: A 47-year-old woman who presented with hip pain as a result of osteoarthritis was treated with indometacin. Ten days after beginning treatment she developed jaundice and ascites. All medications were discontinued, but her symptoms continued to worsen., Investigations: Physical examination, laboratory tests and radiologic examinations, including liver chemistry tests, viral serologies, serum iron studies, ceruloplasmin and alpha-fetoprotein analyses, autoimmune serologies, ascites studies, abdominal CT, liver ultrasound and liver biopsy., Diagnosis: Severe biopsy-proven hepatitis that progressed to chronic autoimmune hepatitis., Management: Treatment with prednisone 40 mg/day was initially successful. The dose of the therapy was tapered over 18 months and then discontinued, after which time the patient's liver chemistry test results worsened. Repeat liver biopsy samples showed evidence of chronic hepatitis, and her liver chemistry test results improved when prednisone was restarted. The patient was maintained on 750 mg twice-daily mycophenolate mofetil and prednisone was decreased to 5 mg every other day.

Background: Minocycline is an antibiotic commonly used in the treatment of adolescent acne., Objectives: To describe the clinical, laboratory, and histological features in 3 cases of minocycline-related autoimmune hepatitis and to review the literature of similar cases in the adolescent population., Design: Case series., Setting: Patients were cared for in the Division of Gastroenterology, Children's Hospital, Boston, Mass., Results: Three adolescents (age, 15-16 years), while being treated with therapeutic doses of minocycline for periods of 12 to 20 months, met the 1993 International Autoimmune Hepatitis Group criteria for autoimmune hepatitis. All had a positive antinuclear antibody titer. Other features included hypergammaglobulinemia and a positive anti-smooth muscle antibody titer. Two patients underwent liver biopsy that revealed severe chronic lymphoplasmacytic inflammation, necrosis, and fibrosis. All other causes of liver disease were excluded. One patient had resolution of symptoms with withdrawal of the drug, while 2 required immunosuppression therapy. A review of the literature yielded only 18 similar cases, none in the pediatric literature, the majority of which contained incomplete pertinent data., Conclusions: Minocycline is related to the development of autoimmune hepatitis in some adolescents. Pediatricians who use this drug for treatment of acne should be aware of this serious potential relation and stop the drug immediately when suspicion is raised.

Immune-related drug responses are one of the most common sources of idiosyncratic toxicity. A number of organs may be the target of such reactions; however, this review concentrates mostly on the liver. Drug-induced hepatitis is generally divided into two categories: acute hepatitis in which the drug or a metabolite destroys a vital target in the cell; immunoallergic hepatitis in which the drug triggers an adverse immune response directed against the liver. Their clinical features are: a) low frequency; b) dose independence; c) typical immune system manifestations such as fever, eosinophilia; d) delay between the initiation of treatment and onset of the disease; e) a shortened delay upon rechallenge; and f) occasional presence of autoantibodies in the serum of patients. Such signs have been found in cases of hepatitis triggered by drugs such as halothane, tienilic acid, dihydralazine and anticonvulsants. They will be taken as examples to demonstrate the recent progress made in determining the mechanisms responsible for the disease. The following mechanisms have been postulated: 1) the drug is first metabolized into a reactive metabolite which binds to the enzyme that generated it; 2) this produces a neoantigen which, once presented to the immune system, might trigger an immune response characterized by 3) the production of antibodies recognizing both the native and/or the modified protein; 4) rechallenge leads to increased neoantigen production, a situation in which the presence of antibodies may induce cytolysis. Toxicity is related to the nature and amount of neoantigen and also to other factors such as the individual immune system. An effort should be made to better understand the precise mechanisms underlying this kind of disease and thereby identify the drugs at risk; and also the neoantigen processes necessary for their introduction into the immune system. An animal model would be useful in this regard.