Paradoxical arthritis occurring during anti-TNF in patients with Inflammatory Bowel Disease: histological and immunological features of a complex synovitis.

Objective: Paradoxical arthritis under TNF-inhibitor (TNF-i) for Inflammatory Bowel Disease (IBD) has been described. This study aims to evaluate the histological features of paired synovial (ST) and colonic mucosa (CM) tissues in IBD patients developing paradoxical arthritis under TNF-i. Methods: IBD patients without history of co-existing joint involvement who developed arthritis under TNF-i, were enrolled. Each patient underwent ST biopsy and ileo-colonoscopy with CM biopsies. ST and CM paired samples were stained through immunohistochemistry(IHC) for CD68, CD21, CD20, CD3 and CD117. Clinical and immunological parameters [Anti-citrullinated peptides antibodies(ACPA)-IgM/IgA Rheumatoid Factor(RF)] were collected. Psoriatic Arthritis(PsA) and ACPA/IgM-RF/IgA-RF negative Rheumatoid Arthritis(RA) were enrolled as comparison. Results: 10 patients with IBD [46.0 +- 9.7 years old, 13.2 +- 9.9 years of disease duration, 2.5 +- 1.6 years of TNF-i exposure, 6 with Crohn’s Disease and 4 with Ulcerative Colitis respectively] were studied. At ST level, IHC revealed that IBD patients with paradoxical arthritis showed more similar histological findings in terms of synovial CD68+, CD21+, CD20+, CD3+ and CD117+ cells compared to PsA than ACPA/IgM-RF/IgA-RF negative RA. Analysing the CM specimens, IBD patients showed presence of CD68+, CD3+, CD117+ and CD20+ cells in 100%, 70%, 60% and 50% of cases, respectively, despite endoscopic remission. Finally, addition of c-DMARDs and switch to Ustekinumab were more effective than swapping into different TNF-i in IBD patients with paradoxical arthritis. Conclusion: IBD patients may develop histologically proven synovitis during TNF-i, comparable to PsA. The inhibition of inflammatory pathways alternative to TNF (IL12/1L23) may be an effective therapeutic option for severe paradoxical articular manifestations.