Justine Maller1, Emily Fox2, K T Park3, Sarah Sertial Paul4, Kevin Baszis5, Charlotte Borocco6, Sampath Prahalad7, Pierre Quartier8, Adam Reinhardt9, Dieneke Schonenberg-Meinema10, Lauren Shipman-Duensing11, Maria Teresa Terreri12, Julia Simard13, Idit Lavi14, Elizabeth Chalom15, Joyce Hsu16, Devy Zisman17, Elizabeth D Mellins18. 1. J. Maller, MD, PhD, Department of Pediatrics, Division of Rheumatology, Stanford University School of Medicine, Stanford, California, USA. 2. E. Fox, MD, Department of Pediatrics, Division of Rheumatology, Stanford University School of Medicine, Stanford, California, and Department of Pediatrics, Division of Rheumatology, Children's Mercy Hospital, University of Missouri-Kansas City, Kansas City, Missouri, USA. 3. K.T. Park, MD, Department of Pediatrics, Division of Gastroenterology, Stanford University School of Medicine, Stanford, California, USA. 4. S. Sertial Paul, DO, Department of Pediatrics, Goryeb Children's Hospital, Morristown, New Jersey, USA. 5. K. Baszis, MD, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA. 6. C. Borocco, MD, Paris University, Imagine Institute and Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital, AP-HP, Paris, France. 7. S. Prahalad, MD, Department of Pediatrics and Department of Genetics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia, USA. 8. P. Quartier, MD, Paris University, Imagine Institute, RAISE Reference Centre and Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital, AP-HP, Paris, France. 9. A. Reinhardt, MD, Department of Pediatrics, Boys Town National Research Hospital, Omaha, Nebraska, USA. 10. D. Schonenberg-Meinema, MD, Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam Universitair Medische Centra, Amsterdam, the Netherlands. 11. L. Shipman-Duensing, MD, Department of Pediatrics, Division of Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA. 12. M.T. Terreri, MD, Department of Pediatrics, Pediatric Rheumatology Unit, Universidade Federal de São Paulo, São Paulo, Brazil. 13. J. Simard, ScD, Department of Health Research & Policy, Division of Epidemiology, and Department of Medicine, Division of Immunology & Rheumatology, Stanford University, Stanford, California, USA. 14. I. Lavi, MA, Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel. 15. E. Chalom, MD, Department of Pediatrics, Saint Barnabas Medical Center, Livingston, New Jersey, USA. 16. J. Hsu, MD, Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA. 17. D. Zisman, MD, Carmel Medical Center, Rheumatology Unit, The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel. 18. E.D. Mellins, MD, Department of Pediatrics, Division of Human Gene Therapy, Program in Immunology, Stanford University School of Medicine, Stanford, California, USA. mellins@stanford.edu.
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.
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.
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