Paradoxical gastrointestinal reactions in patients taking tumor necrosis factor inhibitors: a rare event that broadens the histologic spectrum of medication–associated injury

Tumor necrosis factor (TNF) inhibitors are widely used in the therapy of certain autoimmune disorders. Paradoxical immunologic reactions manifesting as new-onset autoimmune disease or exacerbation of the underlying condition have been reported in association with these drugs. In this study, we reviewed gastrointestinal biopsies and clinical findings in patients with rheumatologic disease on TNF inhibitor therapy and compared to patients with rheumatologic disease not on TNF inhibitors. Eighteen biopsies from 9 patients treated with TNF inhibitor therapy and 249 biopsies from 120 control patients not treated with TNF inhibitors were included. Among patients taking a TNF inhibitor, 55.6% were female, and the median age was 47 (range, 30-67 years). Four (44.4%) patients were taking etanercept, 4 (44.4%) adalimumab, and 1 (11.1%) certolizumab pegol. Of the 120 control patients, 75 (62.5%) were female and the median age was 62 (range, 26-85 years). Paradoxical reactions were observed in 3 (33.3%) of 9 patients on TNF inhibitors, including 2 (22.2%) with inflammatory bowel disease–like changes and 1 (11.1%) with sarcoid-like granulomas. All 3 patients showed symptomatic and histologic improvement or resolution after discontinuation of therapy. These reactions were not observed in any of the control patients (P =.0002). Our results indicate that among patients with rheumatologic disease, paradoxical reactions of the gastrointestinal tract are associated with TNF inhibitor therapy. Knowledge of this association is important because symptoms and histologic features may improve following medication switch.