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Delayed Systemic Toxicity from Minocycline for Acne

Minocycline is widely used as a safe and effective therapy for acne. Between 1986 and 1994, the Committee on Safety of Medicines in Great Britain received 11 reports of suspected drug-induced lupus erythematosus and 16 reports of hepatitis associated with minocycline therapy. This paper reviews these 27 cases and describes an additional 7 cases from the authors' clinical experience.

The clinical components of the reactions suggest that one occurs early and the other occurs late. The first reaction, an "acute" hypersensitivity syndrome, occurs 1 to 3 months after the start of therapy and is characterized by fever, malaise, and hepatitis with possible rash or anemia/pancytopenia. The second reaction occurs a median of 2 years after therapy, but may be delayed even up to 6 years. These patients, most of whom were female, presented with a symmetrical polyarthritis/arthralgia in the small joints of the hands and wrists. Serologic testing revealed that these patients were positive for antinuclear antibodies, and negative for anti-DNA antibodies and extractable nuclear antigen antibodies. Some of the patients with arthritis also had liver disease, and biopsies were compatible with chronic active hepatitis. These patients recovered within 3 months after withdrawal of minocycline. There were 13 cases of hepatitis uncomplicated by other systemic disease, 8 of these in males. Two patients who had hematologic and cutaneous symptoms died despite stopping the drug.

Approximately 800,000 mincocycline perscriptions were written in the United Kingdom in 1993; thus the reaction rate is exceedingly low. Still, the seriousness of the reactions raises concerns about the need for routine monitoring and the added costs to treatment with an already expensive drug.

Comment: Acne patients starting minocycline therapy should be told that there are rare but serious side effects from the medication. If the patients get a flu-like illness in the first few months, they should stop the drug. Otherwise they should keep coming in for follow-up. The risk of hepatitis is low, but because hepatotoxicity can be asymptomatic it is worth considering the routine use of liver-function tests on an annual basis. Are patients with known lupus erythematosus or previous hepatitis at higher risk? The answer is not known, but I would avoid using minocycline for such patients.

— NH Shear

Published in Journal Watch Dermatology March 1, 1996

Citation(s):

Gough A et al. Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome. BMJ 1996 312 169-172.

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