Development of lupus‐related side‐effects in patients with early RA during sulphasalazine treatment—the role of IL‐10 and HLA

Abstract

Objective. The development of systemic lupus erythematosus (SLE)‐related syndromes during treatment with sulphasalazine has been described and demonstrated to be influenced by genetic factors. The prevalence of this drug‐induced condition and the immunological mechanisms involved are less known. The aim of this study was to determine the prevalence of sulphasalazine‐induced lupus‐like reactions in a well‐defined early rheumatoid arthritis (RA) cohort and to analyse the roles of HLA haplotypes, autoantibodies and the B‐cell stimulating cytokine interleukin‐10 (IL‐10) as possible underlying risk factors.

Patients and methods. Forty‐one consecutive patients with early RA, in whom sulphasalazine was used as the first disease‐modifying anti‐rheumatic drug in single therapy and was maintained for at least 6 months, were investigated for the occurrence of lupus‐related events. Longitudinal analyses of rheumatoid factor (RF), antinuclear antibodies (ANA), anti‐double‐stranded DNA antibodies and serum IL‐10 (ELISA) and the typing of HLADR and DQ alleles were performed.

Results. Four of the 41 patients developed lupus‐like disease. Three of four patients who had lupus‐related events vs four of 37 patients without side‐effects had an HLA DR 0301 haplotype. The patients developing lupus‐related side‐effects had increased levels of serum IL‐10 and a high frequency of ANA in speckled patterns before the onset of therapy.

Conclusion. The development of SLE‐like symptoms and SLE‐related autoantibody production was observed more commonly than expected, with an increased risk in patients with SLE‐related HLA haplotypes, increased serum IL‐10 levels and ANA in speckled patterns. The data suggest that immunomodulation associated with sulphasalazine treatment may contribute to the development of lupus‐related reactions in genetically predisposed individuals.

Sulphasalazine, SLE, Rheumatoid arthritis, Drug‐induced lupus, HLA, IL‐10