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Original Articles
- Characteristics of monogenic inflammatory bowel disease in very early-onset cases: a Japanese multicenter registry study
- Natsuki Ito, Takahiro Kudo, Keisuke Jimbo, Ryusuke Nambu, Fumihiko Kakuta, Tatsuki Mizuochi, Takeshi Saito, Shin-ichiro Hagiwara, Naomi Iwata, Nao Tachibana, Hideki Kumagai, Takashi Ishige, Toshifumi Yodoshi, Mikihiro Inoue, Shigeo Nishimata, Hitoshi Tajiri, Eitaro Hiejima, Mika Sasaki, Sawako Kato, Hirotaka Shimizu, Yuri Hirano, Toshiaki Shimizu, Katsuhiro Arai, Japanese Pediatric Inflammatory Bowel Disease Registry (JPIBD-R)
- Received September 1, 2025 Accepted December 22, 2025 Published online February 24, 2026
- DOI: https://doi.org/10.5217/ir.2025.00203 [Epub ahead of print]
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Abstract
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ePub - Background/Aims
Very early-onset inflammatory bowel disease (VEO-IBD), defined as IBD diagnosed before 6 years of age, is highly influenced by genetic factors. Monogenic IBD is a type of enterocolitis caused by a single pathogenic variant. However, information on Asian patients with VEO-IBD and monogenic IBD is limited. This study investigated real-world data on VEOIBD and monogenic IBD in Japan.
Methods
We evaluated patients with VEO-IBD registered in the Japanese Pediatric Inflammatory Bowel Disease Registry, a multicenter prospective registry study conducted between 2012 and 2021. We categorized patients into monogenic and non-monogenic IBD groups and compared their clinical characteristics and outcomes.
Results
Among 703 pediatric patients with IBD, 68 (9.7%) had VEO-IBD. Of these, 26 (38.2%) had ulcerative colitis, 16 (23.5%) had Crohn’s disease, 23 (33.8%) had unclassified IBD (IBD-U), and 3 (4.4%) had Behçet’s disease. Genetic testing was performed in 25 patients (36.8%), and monogenic IBD was identified in 5 of the 23 patients with IBD-U (7.4% of the VEO-IBD cohort). All 5 monogenic cases presented with an IBD-U phenotype. Monogenic IBD included A20 haploinsufficiency, interleukin-10 receptor subunit alpha deficiency, chronic granulomatous disease, Wiskott–Aldrich syndrome, and Hermansky–Pudlak syndrome. Monogenic IBD was significantly associated with IBD-U phenotype (P= 0.015) and severe infections before 1 year of age (P= 0.004).
Conclusions
Patients with VEO-IBD who present an IBD-U phenotype and have a history of severe infections during infancy should be prioritized for genetic analysis to investigate the possibility of monogenic IBD.
- 1,805 View
- 87 Download
- Orofacial granulomatosis in pediatric Crohn’s disease: clinical outcomes and genetic background in the era of biologics: a retrospective study in Japan
- Ryusuke Nambu, Takeo Naito, Mei Haruyama, Junichi Hosokawa, Hirotaka Shimizu, Ichiro Takeuchi, Shin-ichiro Hagiwara, Tatsuki Mizuochi, Yugo Takaki, Takashi Ishige, Takuya Nishizawa, Takahiro Kudo, Natsuki Ito, Yosuke Kawai, Yoichi Kakuta, Masao Nagasaki, Toshiaki Shimizu, Itaru Iwama, Katsuhiro Arai
- Received June 18, 2025 Accepted September 1, 2025 Published online January 2, 2026
- DOI: https://doi.org/10.5217/ir.2025.00109 [Epub ahead of print]
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Abstract
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Supplementary MaterialPubReaderePub - Background/Aims
Occasionally, pediatric Crohn’s 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 (3.8–15.3) and 10.3 (6.4–15.3) 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 NCF1 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. NCF1 p.Arg90His mutation may contribute to the pathogenesis of pediatric CD complicating OFG.
- 2,592 View
- 141 Download
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