{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:19:45Z","timestamp":1788221985902,"version":"build-2803163510"},"reference-count":18,"publisher":"American Academy of Pediatrics (AAP)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,1]]},"abstract":"<jats:p>Juvenile idiopathic arthritis is a common chronic childhood disease, with a prevalence of \u223c1 per 1000 children. Arthritis can also be a manifestation of other inflammatory conditions, such as inflammatory bowel disease (IBD). Studies suggest a genetic influence in IBD, including mutations in CARD8. CARD8 is a negative regulator of the NLRP3 inflammasome, and mutations in this gene are hypothesized to induce gastrointestinal inflammation. However, few studies have evaluated this association and most have included a limited number of patients. We present a case of a pediatric patient with IBD-associated arthritis and a CARD8 mutation. Our patient is a 7-year-old female who was initially evaluated by rheumatology for right leg pain and an intermittent rash. She had clinically active arthritis on exam and was started on methotrexate with only slight improvement. Additional workup revealed sacroiliitis by imaging, elevated inflammatory markers, no anemia, and a variant of unknown significance in CARD8. Adalimumab was recommended but before medication initiation, our patient\u2019s symptoms progressed to worsening joint pain, fatigue, fevers, nausea, vomiting, diarrhea, and hematochezia. Infectious testing was negative. Fecal calprotectin was &amp;gt;8000 \u00b5g\/g. A colonoscopy revealed IBD most consistent with Crohn\u2019s disease. Adalimumab was ultimately added, and she has responded well to combination therapy. This case report highlights the association between CARD8 mutations and IBD, especially in the setting of IBD-associated arthritis.<\/jats:p>","DOI":"10.1542\/peds.2022-058964","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T08:10:55Z","timestamp":1695111055000},"source":"Crossref","is-referenced-by-count":8,"title":["Juvenile Idiopathic Arthritis With Associated Inflammatory Bowel Disease and CARD8 Mutation"],"prefix":"10.1542","volume":"152","author":[{"given":"Victoria L.","family":"Gennaro","sequence":"first","affiliation":[{"name":"aChildren\u2019s of Alabama, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanine","family":"Maclin","sequence":"additional","affiliation":[{"name":"bDepartment of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Weiser","sequence":"additional","affiliation":[{"name":"bDepartment of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L.","family":"Stoll","sequence":"additional","affiliation":[{"name":"bDepartment of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily A.","family":"Smitherman","sequence":"additional","affiliation":[{"name":"bDepartment of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"issue":"2","key":"2023111414481084400_B1","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jbspin.2013.09.003","article-title":"Prevalence and incidence of juvenile idiopathic arthritis: a systematic review","volume":"81","author":"Thierry","year":"2014","journal-title":"Joint Bone Spine"},{"issue":"2","key":"2023111414481084400_B2","first-page":"390","article-title":"International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001","volume":"31","author":"Petty","year":"2004","journal-title":"J Rheumatol"},{"issue":"12","key":"2023111414481084400_B3","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.3390\/healthcare9121683","article-title":"Juvenile idiopathic arthritis: a review of novel diagnostic and monitoring technologies","volume":"9","author":"Garner","year":"2021","journal-title":"Healthcare (Basel)"},{"issue":"3","key":"2023111414481084400_B4","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s12178-011-9085-8","article-title":"Inflammatory bowel disease associated arthropathy","volume":"4","author":"Arvikar","year":"2011","journal-title":"Curr Rev Musculoskelet Med"},{"issue":"2","key":"2023111414481084400_B5","first-page":"33","article-title":"Evaluation and treatment of enthesitis-related arthritis","volume":"32","author":"Weiss","year":"2013","journal-title":"Curr Med Lit Rheumatol"},{"key":"2023111414481084400_B6","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3390\/gastroent11020008","article-title":"Inflammatory bowel diseases and coexisting spondyloarthritis: a neglected and too often under-reported association by radiologists. A multicenter study by an Italian research group of imaging in rheumatology","volume":"11","author":"Mazzei","year":"2020","journal-title":"Gastroenterol Insights"},{"issue":"5","key":"2023111414481084400_B7","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1172\/JCI98642","article-title":"Loss-of-function CARD8 mutation causes NLRP3 inflammasome activation and Crohn\u2019s disease","volume":"128","author":"Mao","year":"2018","journal-title":"J Clin Invest"},{"key":"2023111414481084400_B8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1471-2350-14-35","article-title":"The CARD8 p.C10X mutation associates with a low anti-glycans antibody response in patients with Crohn\u2019s disease","volume":"14","author":"Vasseur","year":"2013","journal-title":"BMC Med Genet"},{"issue":"6","key":"2023111414481084400_B9","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1002\/ibd.21493","article-title":"Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification","volume":"17","author":"Levine","year":"2011","journal-title":"Inflamm Bowel Dis"},{"issue":"1","key":"2023111414481084400_B10","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3748\/wjg.v20.i1.45","article-title":"Current issues in pediatric inflammatory bowel disease-associated arthropathies","volume":"20","author":"Cardile","year":"2014","journal-title":"World J Gastroenterol"},{"key":"2023111414481084400_B11","doi-asserted-by":"crossref","first-page":"650619","DOI":"10.3389\/fmed.2021.650619","article-title":"The increased levels of fecal calprotectin in children with active enthesitis related arthritis and MRI signs of sacroiliitis: the results of a single center cross-sectional exploratory study in juvenile idiopathic arthritis patients","volume":"8","author":"Lamot","year":"2021","journal-title":"Front Med (Lausanne)"},{"issue":"6","key":"2023111414481084400_B12","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1136\/annrheumdis-2013-203854","article-title":"Degree of bone marrow oedema in sacroiliac joints of patients with axial spondyloarthritis is linked to gut inflammation and male sex: results from the GIANT cohort","volume":"73","author":"Van Praet","year":"2014","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"2023111414481084400_B13","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1007\/s00431-021-04269-8","article-title":"Increasing rate of a positive family history of inflammatory bowel disease (IBD) in pediatric IBD patients","volume":"181","author":"Ruban","year":"2022","journal-title":"Eur J Pediatr"},{"issue":"11","key":"2023111414481084400_B14","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1111\/j.1572-0241.2003.08673.x","article-title":"NOD2\/CARD15 variants are associated with lower weight at diagnosis in children with Crohn\u2019s disease","volume":"98","author":"Tomer","year":"2003","journal-title":"Am J Gastroenterol"},{"issue":"3","key":"2023111414481084400_B15","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/j.1572-0241.2007.01661.x","article-title":"Association between genetic variants in the IL-23R gene and early-onset Crohn\u2019s disease: results from a case-control and family-based study among Canadian children","volume":"103","author":"Amre","year":"2008","journal-title":"Am J Gastroenterol"},{"key":"2023111414481084400_B16","doi-asserted-by":"crossref","first-page":"666772","DOI":"10.3389\/fmed.2021.666772","article-title":"Juvenile spondyloarthritis: what more do we know about HLA-B27, enthesitis, and new bone formation?","volume":"8","author":"Tay","year":"2021","journal-title":"Front Med (Lausanne)"},{"issue":"6","key":"2023111414481084400_B17","doi-asserted-by":"crossref","first-page":"465","DOI":"10.3109\/03009742.2013.779020","article-title":"Genetic variants in CARD8 but not in NLRP3 are associated with ankylosing spondylitis","volume":"42","author":"Kastbom","year":"2013","journal-title":"Scand J Rheumatol"},{"issue":"4","key":"2023111414481084400_B18","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1136\/ard.2008.106989","article-title":"CARD8 p.C10X polymorphism is associated with inflammatory activity in early rheumatoid arthritis","volume":"69","author":"Kastbom","year":"2010","journal-title":"Ann Rheum Dis"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/doi\/10.1542\/peds.2022-058964\/1567684\/peds.2022-058964.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/doi\/10.1542\/peds.2022-058964\/1567684\/peds.2022-058964.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T14:51:46Z","timestamp":1699973506000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/152\/4\/e2022058964\/193961\/Juvenile-Idiopathic-Arthritis-With-Associated"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,19]]},"references-count":18,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,9,19]]},"published-print":{"date-parts":[[2023,10,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2022-058964","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,19]]},"article-number":"e2022058964"}}