TREATMENT OF DISCOID LUPUS-ERYTHEMATOSUS BY SULFASALAZINE - 11 OBSERVATIONS

Introduction : Antimalaria agents and thalidomide are two reference dr ugs for discoid lupus erythematosus. In non-responders or after second ary resistance or contraindications, there are a number of alternative therapeutics which are less effective and more toxic. We therefore co nducted an open study in patients with discoid lupus erythematosus tre ated with sulfasalazine. Patients and methods : Seven men and four wom en (mean age 40 years) with severe discoid lupus erythematosus (mean d uration of disease 14 years) were treated with sulfasalazine (2 g/d). This treatment was initiated after a previous failure or contraindicat ion of antimalarial drugs or thalidomide. The acetylation phenotype wa s predicted in all patients with N-acetyltransferase 2 genotyping. Gen ome DNA was tested for mutations causing an N-acetyltransferase defici ency. Homozygous individuals or those with heterozygous composites for the tested mutations were predicted slow acetylators and those with a homozygous or heterozygous genotype for an allele carrying a normal s equence at the mutation sites were predicted rapid acetylators. Result s : We had 7 complete responses, 1 partial response and 3 failures. Me an delay to efficacy was 7 weeks, longer for lesions involving the sca lp (4 to 5 months). Six of the 8 responders were given sulfasalazine e xclusively The effect was suspensive and dose-dependent; the minimal e ffective dose was 1.5 g/d. Excepting light sensitization requiring dis continuation, there were no clinically significant side effects. Neutr openia occurred in one patient and moderate and transient liver enzyme movements did not require treatment withdrawal. The only immunoallerg ic side effect (light sensitization) observed occurred in a slow acety lator. All responders except one were rapid acetylators. Discussion : Salazosulfapyridine, or sulfasalazine, is composed of a derivative of 5-aminosalicylic acid and a sulfamide fraction, sulfapyridine. It is o nly marginally used in dermatology except for psoriasis. Its efficacy in chronic lupus erythematosus has been reported in one case. We confi rmed the role of this compound in the treatment of chronic lupus eryth ematosus. The rare observations of induced lupus and development of an tinuclear antibodies are not a contraindication, but require close reg ular clinical and biological surveillance. The potential risk is that possible hypersensitivity could lead to reserving sulfasalazine for se vere resistant chronic lupus erythematosus after failure with antimala rials and thalidomide. Nevertheless, our study demonstrates that the s low acetylator phenotype predicts immunoallergic events,as observed by other authors, and would be a factor predicting nonresponse. If these results are confirmed by other studies, it would be possible to propo se sulfasalazine as a treatment for discoid lupus erythematosus in rap id acetylators.