Abstract
BACKGROUND—Sulphasalazine (SSZ) has been reported to cause drug induced systemic lupus erythematosus (SLE), but diagnosis of this complication in the context of rheumatoid arthritis (RA) is difficult. OBJECTIVE—To determine prospectively: (1) if patients become seropositive for antinuclear antibodies (ANA) during prolonged treatment with SSZ without clinical evidence of SLE; (2) if ANA positive patients develop more adverse reactions than ANA negative patients; (3) if drug induced SLE was identified in this cohort. METHODS—200 patients enrolled in a randomised prospective trial of SSZ and auranofin (AUR) were followed up for five years. Baseline and annual ANA results were collected along with information on drug toxicity and reasons for discontinuation of treatment. RESULTS—Over five years 24 patients stopped taking SSZ and 49 AUR because of side effects. Of the features common to SLE, rash developed in nine SSZ patients and 11 AUR treated patients and mouth ulcers in three and four patients respectively. Six SSZ treated patients and three treated with AUR developed leucopenia, which promptly resolved with drug withdrawal. No adverse event was ascribed to drug induced SLE. Of the 72 SSZ treated patients who were ANA negative or weakly positive at outset, 14 (19%) became strongly ANA positive compared with 11 (14%) of 80 AUR patients. Patients ANA positive at baseline or who became ANA positive were not more likely to develop drug toxicity or to withdraw from treatment than those ANA negative throughout. CONCLUSION—ANA positivity is common in patients with RA, but the presence or development of ANA did not increase the likelihood of withdrawing from treatment. No case of drug induced SLE was seen over five years in this study.
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Selected References
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- Alarcón-Segovia D., Kraus A. Drug-related lupus syndromes and their relationship to spontaneously occurring systemic lupus erythematosus. Baillieres Clin Rheumatol. 1991 Apr;5(1):1–12. doi: 10.1016/s0950-3579(05)80292-4. [DOI] [PubMed] [Google Scholar]
- BARNETT E. V., NORTH A. F., Jr, CONDEMI J. J., JACOX R. F., VAUGHAN J. H. ANTINUCLEAR FACTORS IN SYSTEMIC LUPUS ERYTHEMATOSUS AND RHEUMATOID ARTHRITIS. Ann Intern Med. 1965 Jul;63:100–108. doi: 10.7326/0003-4819-63-1-100. [DOI] [PubMed] [Google Scholar]
- Carr-Locke D. L. Sulfasalazine-induced lupus syndrome in a patient with Crohn's disease. Am J Gastroenterol. 1982 Sep;77(9):614–616. [PubMed] [Google Scholar]
- Caulier M., Dromer C., Andrieu V., Le Guennec P., Fournie B. Sulfasalazine induced lupus in rheumatoid arthritis. J Rheumatol. 1994 Apr;21(4):750–751. [PubMed] [Google Scholar]
- Caulier M., Dromer C., Andrieu V., Le Guennec P., Fournie B. Sulfasalazine induced lupus in rheumatoid arthritis. J Rheumatol. 1994 Apr;21(4):750–751. [PubMed] [Google Scholar]
- Clementz G. L., Dolin B. J. Sulfasalazine-induced lupus erythematosus. Am J Med. 1988 Mar;84(3 Pt 1):535–538. doi: 10.1016/0002-9343(88)90279-3. [DOI] [PubMed] [Google Scholar]
- Deboever G., Devogelaere R., Holvoet G. Sulphasalazine-induced lupus-like syndrome with cardiac tamponade in a patient with ulcerative colitis. Am J Gastroenterol. 1989 Jan;84(1):85–86. [PubMed] [Google Scholar]
- Drayer D. E., Reidenberg M. M. Clinical consequences of polymorphic acetylation of basic drugs. Clin Pharmacol Ther. 1977 Sep;22(3):251–258. doi: 10.1002/cpt1977223251. [DOI] [PubMed] [Google Scholar]
- Hess E. Drug-related lupus. N Engl J Med. 1988 Jun 2;318(22):1460–1462. doi: 10.1056/NEJM198806023182209. [DOI] [PubMed] [Google Scholar]
- Hobbs R. N., Clayton A. L., Bernstein R. M. Antibodies to the five histones and poly(adenosine diphosphate-ribose) in drug induced lupus: implications for pathogenesis. Ann Rheum Dis. 1987 May;46(5):408–416. doi: 10.1136/ard.46.5.408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laversuch C. J., Collins D. A., Charles P. J., Bourke B. E. Sulphasalazine-induced autoimmune abnormalities in patients with rheumatic disease. Br J Rheumatol. 1995 May;34(5):435–439. doi: 10.1093/rheumatology/34.5.435. [DOI] [PubMed] [Google Scholar]
- Linn J. E., Hardin J. G., Halla J. T. A controlled study of ANA+ RF- arthritis. Arthritis Rheum. 1978 Jul-Aug;21(6):645–651. doi: 10.1002/art.1780210606. [DOI] [PubMed] [Google Scholar]
- McEntegart A., Porter D., Capell H. A., Thomson E. A. Sulfasalazine has a better efficacy/toxicity profile than auranofin--evidence from a 5 year prospective, randomized trial. J Rheumatol. 1996 Nov;23(11):1887–1890. [PubMed] [Google Scholar]
- Mielke H., Wildhagen K., Mau W., Zeidler H. Follow-up of patients with double stranded DNA antibodies induced by sulfasalazine during the treatment of inflammatory rheumatic diseases. Scand J Rheumatol. 1993;22(6):299–301. doi: 10.3109/03009749309095143. [DOI] [PubMed] [Google Scholar]
- Mongey A. B., Hess E. V. Sulphasalazine-induced systemic lupus erythematosus. Br J Rheumatol. 1994 Aug;33(8):789–790. doi: 10.1093/rheumatology/33.8.789-a. [DOI] [PubMed] [Google Scholar]
- Porter D. R., McInnes I., Hunter J., Capell H. A. Outcome of second line therapy in rheumatoid arthritis. Ann Rheum Dis. 1994 Dec;53(12):812–815. doi: 10.1136/ard.53.12.812. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Skaer T. L. Medication-induced systemic lupus erythematosus. Clin Ther. 1992 Jul-Aug;14(4):496–495. [PubMed] [Google Scholar]
- Stratton M. A. Drug-induced systemic lupus erythematosus. Clin Pharm. 1985 Nov-Dec;4(6):657–663. [PubMed] [Google Scholar]
- Veale D. J., Ho M., Morley K. D. Sulphasalazine-induced lupus in psoriatic arthritis. Br J Rheumatol. 1995 Apr;34(4):383–384. doi: 10.1093/rheumatology/34.4.383. [DOI] [PubMed] [Google Scholar]
