Vasculitides induced by TNFα antagonists: a study in 39 patients in France

TNFα antagonists are effective in the treatment of chronic inflammatory joint disease. Despite a good overall safety profile, they can induce a number of adverse effects, including autoimmunity and infections. A link between TNFα antagonists and vasculitides has been suggested.MethodsBetween December 2004 and January 2005, a nationwide survey was conducted among 1200 hospital-based rheumatologists and internists in France, who were asked to report cases of vasculitis in patients taking TNFα antagonists.ResultsThe survey identified 39 cases (32 women) of vasculitis during TNFα antagonist therapy. The joint disease was rheumatoid arthritis (RA) in 34 patients (including four without rheumatoid factor), juvenile idiopathic arthritis in two patients, ankylosing spondylitis in two patients, and psoriatic arthritis in one patient. Mean disease duration was 14.1 ± 8.7 years. The TNFα antagonist was etanercept in 21 patients, infliximab in 15, adalimumab in 2, and another drug in 1; mean treatment duration was 9.6 months. The manifestations of vasculitis involved the skin (n = 32); peripheral nervous system (n = 9); kidney (n = 7); central nervous system (n = 3); pleura (n = 2), pericardium (n = 2); and the lung, gallbladder, and heart (n = 1 each). Antinuclear factor (ANF) was present in 22 patients, hypocomplementemia in 6, and antineutrophil cytoplasmic antibody in 5. Histology (30 biopsies from 27 patients) showed nonnecrotizing vasculitis in 12 patients, necrotizing vasculitis in 7, an inflammatory dermal infiltrate without vasculitis in 3, extravascular necrotic granulomas in 2, chilblain lupus in 1, and cicatricial fibro-inflammatory changes in 1. Renal biopsy in three patients showed extracapillary glomerulonephritis with IgA deposits (n = 2) or active floccular necrosis against a background of glomerular sclerosis (n = 1). TNFα antagonist therapy was stopped in 33 patients, among whom 18 recovered without further treatment and 14 required high-dose glucocorticoids and/or immunosuppressant therapy, which ensured symptom resolution within a few weeks. The remaining patient died with multiple organ failures.DiscussionThe relative contributions of TNFα antagonist therapy and of the underlying disease to the development of vasculitis cannot be determined. Features that suggest a causal link between TNFα antagonists and vasculitis include the short time from TNFα antagonist initiation to vasculitis onset; the favorable response to discontinuation of TNFα antagonist therapy; and the development of systemic vasculitis in patients with rheumatoid factor-negative RA, in adults with juvenile-onset arthritis, and in patients with spondyloarthropathies.