{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T02:44:31Z","timestamp":1785725071314,"version":"3.56.0"},"reference-count":36,"publisher":"Korean Association for the Study of Intestinal Diseases","issue":"3","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"MEXT Cooperative Research Project Program"},{"name":"Medical Research Center Initiative for High Depth Omics"},{"name":"CURE"},{"DOI":"10.13039\/501100004096","name":"Kyushu University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004096","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["irjournal.org"],"crossmark-restriction":true},"short-container-title":["Intest Res"],"published-print":{"date-parts":[[2026,7,30]]},"abstract":"<jats:p>Background\/Aims: Occasionally, pediatric Crohn\u2019s disease (CD) may develop after diagnosis of orofacial granulomatosis (OFG), which is characterized by chronic granulomatous lesions of the oral mucosa, lips, and perioral area. This study aimed to clarify clinical characteristics, treatment responses, and potential genetic contributors in pediatric patients with CD complicating OFG. Methods: We studied pediatric patients with CD complicating OFG who were treated from 2013 to 2022 at 7 Japanese institutions specializing in pediatric inflammatory bowel disease. Their clinical courses were analyzed retrospectively, and analyses of 71 genes associated with monogenic inflammatory bowel disease were performed. Results: Among 13 patients, 8 were girls. Median ages at diagnosis of OFG and CD were 9.2 (3.8\u201315.3) and 10.3 (6.4\u201315.3) years old, respectively. Upper gastrointestinal lesions were frequent in 8 cases (62%), while perianal lesions were present in 7 (54%). OFG failed to improve or relapsed despite remission of intestinal lesions in about half of the patients (n = 7, 54%). During follow-up, OFG went into remission in 7 patients, including 6 of the 9 who were treated with biologics (66%) and 1 of the 4 who were not (25%). In 8 patients, the &lt;i&gt;NCF1&lt;\/i&gt; p.Arg90His allele was detected by genetic analysis; 7 were heterozygous and 1 homozygous, a higher prevalence than in the general Japanese population. Conclusions: Clinical features of OFG associated with pediatric CD are diverse, and biologic agents were beneficial for OFG patients. &lt;i&gt;NCF1&lt;\/i&gt; p.Arg90His mutation may contribute to the pathogenesis of pediatric CD complicating OFG.<\/jats:p>","DOI":"10.5217\/ir.2025.00109","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T01:20:16Z","timestamp":1766712016000},"page":"571-582","update-policy":"https:\/\/doi.org\/10.5217\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Orofacial granulomatosis in pediatric Crohn\u2019s disease: clinical outcomes and genetic background in the era of biologics: a retrospective study in Japan"],"prefix":"10.5217","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7206-7111","authenticated-orcid":true,"given":"Ryusuke","family":"Nambu","sequence":"first","affiliation":[{"name":"Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology and Hepatology, Saitama Children\u2019s Medical Center, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9744-7946","authenticated-orcid":true,"given":"Takeo","family":"Naito","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9185-9402","authenticated-orcid":true,"given":"Mei","family":"Haruyama","sequence":"additional","affiliation":[{"name":"Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology and Hepatology, Saitama Children\u2019s Medical Center, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0191-8529","authenticated-orcid":true,"given":"Junichi","family":"Hosokawa","sequence":"additional","affiliation":[{"name":"Kazusa DNA Research Institute, Kisarazu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7173-0420","authenticated-orcid":true,"given":"Hirotaka","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2198-913X","authenticated-orcid":true,"given":"Ichiro","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2713-1329","authenticated-orcid":true,"given":"Shin-ichiro","family":"Hagiwara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nutrition and Endocrinology, Osaka Women\u2019s and Children\u2019s Hospital, Izumi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2943-7068","authenticated-orcid":true,"given":"Tatsuki","family":"Mizuochi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3191-0192","authenticated-orcid":true,"given":"Yugo","family":"Takaki","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Hepatology, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2409-7359","authenticated-orcid":true,"given":"Takashi","family":"Ishige","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Gunma University Graduate School of Medicine, Maebashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2515-3508","authenticated-orcid":true,"given":"Takuya","family":"Nishizawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Gunma University Graduate School of Medicine, Maebashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4708-8049","authenticated-orcid":true,"given":"Takahiro","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6415-9753","authenticated-orcid":true,"given":"Natsuki","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, 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