Inflammatory Bowel Disease in Children With Systemic Juvenile Idiopathic Arthritis

Justine Maller; Emily Fox; K T Park; Sarah Sertial Paul; Kevin Baszis; Charlotte Borocco; Sampath Prahalad; Pierre Quartier; Adam Reinhardt; Dieneke Schonenberg-Meinema; Lauren Shipman-Duensing; Maria Teresa Terreri; Julia Simard; Idit Lavi; Elizabeth Chalom; Joyce Hsu; Devy Zisman; Elizabeth D Mellins; CARRA Legacy Registry Investigators

doi:10.3899/jrheum.200230

Inflammatory Bowel Disease in Children With Systemic Juvenile Idiopathic Arthritis

J Rheumatol. 2021 Apr;48(4):567-574. doi: 10.3899/jrheum.200230. Epub 2020 Jun 15.

Authors

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; CARRA Legacy Registry Investigators

Collaborators

CARRA Legacy Registry Investigators:
L Abramson, E Anderson, M Andrew, N Battle, M Becker, H Benham, T Beukelman, J Birmingham, P Blier, A Brown, H Brunner, A Cabrera, D Canter, D Carlton, B Caruso, L Ceracchio, E Chalom, J Chang, P Charpentier, K Clark, J Dean, F Dedeoglu, B Feldman, P Ferguson, M Fox, K Francis, M Gervasini, D Goldsmith, G Gorton, B Gottlieb, T Graham, T Griffin, H Grosbein, S Guppy, H Haftel, D Helfrich, G Higgins, A Hillard, J R Hollister, J Hsu, A Hudgins, C Hung, A Huttenlocher, N Ilowite, A Imlay, L Imundo, C J Inman, J Jaquith, R Jerath, L Jung, P Kahn, A Kapedani, D Kingsbury, K Klein, M Klein-Gitelman, A Kunkel, S Lapidus, S Layburn, T Lehman, C Lindsley, M Macgregor-Hannah, M Malloy, C Mawhorter, D McCurdy, K Mims, N Moorthy, D Morus, E Muscal, M Natter, J Olson, K O'Neil, K Onel, M Orlando, J Palmquist, M Phillips, L Ponder, S Prahalad, M Punaro, D Puplava, S Quinn, A Quintero, C Rabinovich, A Reed, C Reed, S Ringold, M Riordan, S Roberson, A Robinson, J Rosette, D Rothman, D Russo, N Ruth, K Schikler, A Sestak, B Shaham, Y Sherman, M Simmons, N Singer, S Spalding, H Stapp, R Syed, E Thomas, K Torok, D Trejo, J Tress, W Upton, R Vehe, E von Scheven, L Walters, J Weiss, P Weiss, N Welnick, A White, J Woo, J Wootton, A Yalcindag, C Zapp, L Zemel, A Zhu

Affiliations

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.

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

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Juvenile* / complications
Arthritis, Juvenile* / drug therapy
Arthritis, Juvenile* / epidemiology
Child
Etanercept
Humans
Inflammatory Bowel Diseases* / complications
Inflammatory Bowel Diseases* / drug therapy
Inflammatory Bowel Diseases* / epidemiology
Macrophage Activation Syndrome*
Registries

Substances

Etanercept

Abstract

Publication types

MeSH terms

Substances

Grants and funding