Minocycline-related lupus in childhood

Sir: Systemic lupus erythematosus (SLE) is a connective tissue disease whose specific cause or causes remain undetermined. However, drugs and other agents can produce a lupus-like syndrome, drug-related lupus [6]. We have cared for a 14-year-old girt with lupus-like syndrome caused by prolonged minocycline therapy for acne. A 14-year-old girl was admitted because of spiking fever for 8 days and arthralgia in the right elbow. Two months before admission, she had begun to receive minocycline 200 mg daily for facial acne. There was no history of hair loss or photosensitivity. Chest X-ray was normal. Laboratory data were as follows: Hb 11.6 g/dl, WBC 2900/mm 3, ESR 50 mm/h, serum GPT 284 IU/1 and CRP 0.9 mg/dl. IgG, A, M, C3, C4 and CH50 values were normal. Serum antinuclear antibody (ANA) was positive at 1 : 640 with a nucleolar pattern. Anti-DNA, anti-Sm, anti-histone antibodies and LE test were all negative. Administration of piperacillin was ineffective. On the 6th hospital day, her physician realized that she had no discontinued minocycline, and ordered that it be stopped. After the cessation of minocycline, she defervesced rapidly and the arthralgia disappeared. She was discharged from the hospital after 21 days. At home, she had a recurrence of fever and arthralgia when she took minocycline for 2 days. During follow-up for 8 months, the GTP level and ANA titre gradually normalized and the patient was asymptomatic without any special treatment. HLA study revealed that she had HLA-DR2, which is thought to be the common HLA antigen in Japanese and Caucasian patients with SLE [2]. Agents causing drug-related lupus have been classified into three groups: (1) those with definite proof of association, (2) those with possible association, and (3) those with unproved association. Tetracyclines fall into the third group [6]. The first possible case of drug-related lupus with minocycline was described by Matsuura et al. [5] in 1993. In this report, a 22-year-old Japanese woman showed lupus syndrome following administration of minocycline for 2 years for the treatment of acne [5]. The case of Matsuura and ours are very similar: both involved young woman with long histories of minocycline therapy for acne who possessed HLA-DR2, which is a marker for SLE. As ache therapy, tetracyclines are often administered for several months to a few years until the desired clinical improvement is evident. In addition to antimicrobial activity, tetracyclines have a number of anti-inflammatory actions such as inhibition of leucocyte chemotaxis [1] and enhancement of interleukin1 f3 release [31. Therefore, it is reasonable to assume that tetracyclines interact with host cell-mediated immune defenses, which may contribute to their efficacy in the treatment of inflammatory lesions, and that chronic exposure to tetracyclines could perturb the host immune system, resulting in autoimmune disorders. Furthermore, acne inflammation mainly involves T-cell mediated immunity [4], suggesting that acne may be a co-factor in the pathogenesis of minocycline-related lupus. We believe that the prolonged administration of minocycline to individuals who have a hereditary predisposition to develop SLE may induce lupus-like syndrome. We feel that physicians should be aware of this possibility, especially in the treatment of acne.