Hepatitis, autoimmune minocycline

Minocycline is associated with a relatively high incidence of hepatotoxicity. In many cases it is quite distinct from minocycline-induced lupus, occurs earlier in the course of treatment (about 1 month), and the mechanism is unknown [62], However, in some cases the liver toxicity merges with the lupus-like syndrome, occurring after about a year of therapy, and is associated with ANA. This form is indistinguishable from idiopathic autoimmune hepatitis [63], and antibodies against Cyp 3A6 and Cyp 2C4 have been reported [64], Diclofenac has also been reported to cause hepatitis with autoimmune features such as ANA [65],... 

Gough, A. et al., Minocycline induced autoimmune hepatitis and systemic lupus erythe-matosus-like syndrome, Br. Med. J., 312, 169, 1996. 

Goldstein, N.S. et al., Minocycline as a cause of drug-induced autoimmune hepatitis. Report of four cases and comparison with autoimmune hepatitis, Amer. J. Clin. Pathol., 114, 591,2000. 

The authors stated that they did not have any clear information about the absolute and relative risks of hepatitis, whether these were hypersensitivity reactions or autoimmune hepatitis, in patients taking minocycline for varying lengths of time, and that a study of the comparative rates of hepatitis in people exposed to minocycline compared with those not exposed is required. In the meantime, new reports of severe hepatic reactions to minocycline continue to appear (15-17), including one case of autoimmune hepatitis requiring liver transplantation in a woman who had used minocychne 50-200 mg/ day for 3 years (17). Another case of liver transplantation has previously been reported in patients with hepatic failure after minocycline therapy (18). 

Immunoallergic reactions have been reported with minocycline and include lupus-like syndrome, autoimmune hepatitis, eosinophilic pneumonia, hypersensitivity syndrome, a serum sickness-like illness (29), and Sweet s syndrome (SEDA-21, 262) (SEDA-22, 271). Over 60 minocycline-induced cases of lupus-like syndrome and 24 cases of minocycline-induced autoimmune hepatitis were found in a review of the literature (30). In 13 patients, both disorders co-existed. These patients had symmetrical polyarthralgia/polyarthritis, raised liver enzymes, and positive antinuclear antibodies they were also generally antihistone-negative, and only two patients had p-ANCA antibodies. Minocycline-related lupus can also occur in adolescents (31). 

Three adolescents taking therapeutic doses of minocycline for 12-20 months met the 1993 International Autoimmune Hepatitis Group criteria for autoimmune hepatitis. All had hypogammaglobulinemia and positive antinuclear antibody and antismooth muscle antibody titers. Two underwent liver biopsy that showed severe chronic lymphoplasmocytic inflammation, necrosis, and fibrosis. All other causes of liver disease were excluded. One patient had resolution of symptoms after withdrawal of the drug, while two required immunosuppressive therapy. 

Angulo JM, Sigal LH, Espinoza LR. Coexistent minocycline-induced systemic lupus erythematosus and autoimmune hepatitis. Semin Arthritis Rheum 1998 28(3) 187-92. 

Teitelbaum JE, Perez-Atayde AR, Cohen M, Bousvaros A, Jonas MM. Minocycline-related autoimmune hepatitis case series and literature review. Arch Pediatr Adolesc Med 1998 152(ll) 1132-6. 

Liver In a review of 261 cases of autoimmune hepatitis, drugs were suspected in 24 cases (9.2%) [81. Nitrofurantoin and minocycline were most commonly impUcated (11 cases each). Comparison with minocychne, nitrofurantoin-induced hepatitis occurred in older patients, who had more inflammatory changes on histology, more radiological imaging abnormalities (73% versus 0%) and were more likely to have jaundice at presentation. Short-term immunosuppression was generally successful and cirrhosis did not develop. 

Liver Autoimmune hepatitis has been reported in a 20-year-old woman who had taken minocycline for 1 year [140 ], in a 17-year-old-woman who had taken minocycline 50 mg/day and an oral contraceptive for about 2 years [141 ], and in three other patients [142 ]. 

Healy J, Alexander B, Eapen C, Roberts-Thomson IC. Minocycline-induced autoimmune hepatitis. Intern Med J 2009 39 (7) 487-8. 

Ramakrishna J, Johnson AR, Banner BF. Long-term minocycline use for acne in healthy adolescents can cause severe autoimmune hepatitis. J Clin Gastroenterol 2009 43(8) 787-90. 

---