Does sulphasalazine cause drug induced systemic lupus erythematosus? No eVect evident in a prospective randomised trial of 200 rheumatoid patients treated with sulphasalazine or auranofin over five years

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 diYcult. 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 eVects. 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. (Ann Rheum Dis 1999;58:288–290) Systemic lupus erythematosus (SLE) is a multifactorial disease. Since the 1970s, almost 50 drugs have been reported to be associated with drug related lupus. Hydralazine, penicillamine and procainamide are most commonly implicated, and several case reports have also established sulphasalazine (SSZ) as a causative agent. Diagnosis in the context of rheumatoid arthritis (RA) is diYcult as the side eVects of several disease modifying drugs (DMARDs) share features of SLE. In addition, “overlap” between RA and SLE is occasionally reported. Antinuclear antibodies (ANAs) may develop during long term treatment with a number of drugs, and ANAs are invariably detected in those who progress to develop a drug induced lupus syndrome. While the occurrence of antibodies is common, (detected in 50–90% of patients treated), the frequency of associated disease is rare. The exact incidence of drug induced lupus and of asymptomatic serological abnormalities has not been clearly established. The aim of this study was to determine if treatment with SSZ is associated with: (1) the development of ANA; (2) clinical evidence of drug induced SLE; (3) if there is a relation between ANA status and drug toxicity. Methods Two hundred patients with RA considered to require second line treatment were enrolled in a prospective, randomised trial comparing SSZ and auranofin (AUR) and followed up for five years. One hundred patients were randomised to each group. If the patient had previously been taking SSZ (25 patients) or AUR (four patients), they were allocated to receive the other drug. SSZ was started at 500 mg/day and increased if tolerated to a target dose of 40 mg/kg/day. AUR was introduced at 3 mg twice daily, increasing to 3 mg thrice daily if necessary. Patients were assessed at weeks 0, 12, 24, 48 and then annually until year 5. Full blood count, erythrocyte sedimentation rate, C reactive protein, biochemistry were performed at each visit with measurements of Ritchie articular index, pain score on 10 cm visual analogue scale and morning stiVness. Baseline and annual ANA results were collected with information on drug toxicity, concomitant medication and reasons for withdrawal from treatment. Results There was no significant diVerence between the groups with regard to patient details, with a Ann Rheum Dis 1999;58:288–290 288 Centre for Rheumatic Diseases, Glasgow Royal Infirmary, Glasgow