Evaluation of antineutrophil cytoplasmic antibody seroconversion induced by minocycline, sulfasalazine, or penicillamine

Objective, Case reports have suggested that minocycline, sulfasalazine, and penicillamine are associated with antineutrophil cytoplasmic antibody (ANC A)-positive vasculitis, This study evaluated ANCA seroconversion due to the se agents in serum samples prospectively collected in randomized, double-bl ind, controlled trials. Methods, The sources of study sera were 3 clinical trials: 1) a 48-week tri al of minocycline for early rheumatoid arthritis, with 64 patients receivin g minocycline compared with 68 receiving placebo; 2) a 37-week trial of sul fasalazine for rheumatoid arthritis, with 51 receiving sulfasalazine compar ed with 38 receiving placebo; and 3) a 104-week trial of penicillamine for early systemic sclerosis, with 15 undergoing high-dose penicillamine treatm ent versus 12 receiving low-dose penicillamine, ANCA were measured in the b aseline and study-end serum samples by indirect immunofluorescence (IIF) fo r perinuclear ANCA (pANCA) and cytoplasmic ANCA (cANCA) patterns, and by an tigen-specific enzyme-linked immunosorbent assay (ELISA) for antibodies to myeloperoxidase (anti-MPO) and proteinase 3 (anti-PR3), Laboratory personne l were blinded to the group identity of the samples. ANCA results were inte rpreted using an ANCA scoring system that combines the results of IIF and E LISA testing, Results. No patient in any of the active study drug groups demonstrated ANC A seroconversion according to the final interpretation of the combined IIF and ELISA results. Twelve of the 248 patients (5%) were positive for anti-M PO with pANCA at baseline. No subject was positive for anti-PR3 with cANCA, There were no findings suggestive of vasculitis in any of these patients. Conclusion. From our study results, there was no suggestion of ANCA serocon version induced by minocycline, sulfasalazine, or penicillamine, However, t hese findings do not rule out the possibility of rare, sporadic cases of ei ther ANCA seroconversion or true drug-induced vasculitis with these drugs.