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

Rheumatology (Oxford). 2000 Aug;39(8):886-93. doi: 10.1093/rheumatology/39.8.886.


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 HLA DR 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Antinuclear / analysis
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy*
  • C-Reactive Protein / analysis
  • Cohort Studies
  • Female
  • HLA Antigens / classification
  • HLA Antigens / physiology*
  • HLA-DR Antigens / genetics
  • Haplotypes
  • Humans
  • Interleukin-10 / blood
  • Interleukin-10 / physiology*
  • Lupus Erythematosus, Systemic / chemically induced*
  • Lupus Erythematosus, Systemic / epidemiology
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / physiopathology
  • Male
  • Middle Aged
  • Prevalence
  • Reference Values
  • Sulfasalazine / adverse effects*
  • Time Factors


  • Antibodies, Antinuclear
  • Antirheumatic Agents
  • HLA Antigens
  • HLA-DR Antigens
  • Interleukin-10
  • Sulfasalazine
  • C-Reactive Protein