Inflammatory Bowel Disease in Children With Systemic Juvenile Idiopathic Arthritis

Abstract

Objective: The incidence of inflammatory bowel disease (IBD) in juvenile idiopathic arthritis (JIA) is higher than in the general pediatric population. However, reports of IBD in the systemic JIA (sJIA) subtype are limited. We sought to characterize sJIA patients diagnosed with IBD and to identify potential contributing risk factors.

Methods: Using an internationally distributed survey, we identified 16 patients with sJIA who were subsequently diagnosed with IBD (sJIA-IBD cohort). Five hundred twenty-two sJIA patients without IBD were identified from the CARRA Legacy Registry and served as the sJIA-only cohort for comparison. Differences in demographic, clinical characteristics, and therapy were assessed using chi-square test, Fisher exact test, t-test, and univariate and multivariate logistic regression, as appropriate.

Results: Of the patients with sJIA-IBD, 75% had a persistent sJIA course and 25% had a history of macrophage activation syndrome. sJIA-IBD subjects were older at sJIA diagnosis, more often non-White, had a higher rate of IBD family history, and were more frequently treated with etanercept or canakinumab compared to sJIA-only subjects. Sixty-nine percent of sJIA-IBD patients successfully discontinued sJIA medications following IBD diagnosis, and sJIA symptoms resolved in 9 of 12 patients treated with tumor necrosis factor-α (TNF-α) inhibitors.

Conclusion: IBD in the setting of sJIA is a rare occurrence. The favorable response of sJIA symptoms to therapeutic TNF-α inhibition suggests that the sJIA-IBD cohort may represent a mechanistically distinct sJIA subgroup. Our study highlights the importance of maintaining a high level of suspicion for IBD when gastrointestinal involvement occurs in patients with sJIA and the likely broad benefit of TNF-α inhibition in those cases.

Keywords: autoinflammation; cytokine inhibitors; inflammatory bowel disease; pediatric rheumatology; systemic juvenile idiopathic arthritis.

FIGURE 1.. Medication regimens of the sJIA-IBD cohort before and after IBD diagnosis.

Bars reflect the number of patients receiving one or more class-specific therapy in the six months before IBD diagnosis (black) and after (gray). DMARDs used before IBD diagnosis included the following (number of patients indicated in parentheses): cyclosporine (1), methotrexate (7), and tacrolimus (2); DMARDs after IBD diagnosis included methotrexate (5), sulfasalazine (2), and azathioprine (4). TNF-α inhibitors used before IBD diagnosis included adalimumab (1) and etanercept (5); TNF-α inhibitors after IBD diagnosis included adalimumab (4) and infliximab (10). IL-1 inhibitors used before IBD diagnosis included anakinra (2) and canakinumab (6); one patient remained on canakinumab after IBD diagnosis. IL-6 inhibitor was tocilizumab. 2 subjects were treated with mesalamine monotherapy after IBD diagnosis. Regimens in the 6 months before IBD diagnosis do not necessarily reflect medications initiated within this timeframe; data on specific timing and duration of therapy were not collected. DMARD, disease-modifying anti-rheumatic drug; NSAID, non-steroidal anti-inflammatory drug.