[Treatment of discoid lupus erythematosus with sulfasalazine: 11 cases]

Antimalaria agents and thalidomide are two reference drugs for discoid lupus erythematosus. In non-responders or after secondary resistance or contraindications, there are a number of alternative therapeutics which are less effective and more toxic. We therefore conducted an open study in patients with discoid lupus erythematosus treated with sulfasalazine.

Seven men and four women (mean age 40 years) with severe discoid lupus erythematosus (mean duration of disease 14 years) were treated with sulfasalazine (2 g/d). This treatment was initiated after a previous failure or contraindication of antimalarial drugs or thalidomide. The acetylation phenotype was predicted in all patients with N-acetyltransferase 2 genotyping. Genome DNA was tested for mutations causing an N-acetyltransferase deficiency. 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 sequence at the mutation sites were predicted rapid acetylators.

We had 7 complete responses, 1 partial response and 3 failures. Mean delay to efficacy was 7 weeks, longer for lesions involving the scalp (4 to 5 months). Six of the 8 responders were given sulfasalazine exclusively. The effect was suspensive and dose-dependent; the minimal effective dose was 1.5 g/d. Excepting light sensitization requiring discontinuation, there were no clinically significant side effects. Neutropenia occurred in one patient and moderate and transient live enzyme movements did not require treatment withdrawal. The only immunoallergic side effect (light sensitization) observed occurred in a slow acetylator. All responders except one were rapid acetylators.

Salazosulfapyridine, or sulfasalazine, is composed of a derivative of 5-aminosalicylic acid and a sulfamide fraction, sulfapyridine. It is only marginally used in dermatology except for psoriasis. Its efficacy in chronic lupus erythematosus has been reported in one case. We confirmed the role of this compound in the treatment of chronic lupus erythematosus. The rare observations of induced lupus and development of antinuclear antibodies are not a contraindication, but require close regular clinical and biological surveillance. The potential risk is that possible hypersensitivity could lead to reserving sulfasalazine for severe resistant chronic lupus erythematosus after failure with antimalarials and thalidomide. Nevertheless, our study demonstrates that the slow 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 propose sulfasalazine as a treatment for discoid lupus erythematosus in rapid acetylators.