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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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PubReader
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.
- 1,808 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
PDF
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.
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- 141 Download
- Inflammatory bowel diseases
- Phenotypic characteristics of pediatric inflammatory bowel disease in Japan: results from a multicenter registry
- Katsuhiro Arai, Reiko Kunisaki, Fumihiko Kakuta, Shin-ichiro Hagiwara, Takatsugu Murakoshi, Tadahiro Yanagi, Toshiaki Shimizu, Sawako Kato, Takashi Ishige, Tomoki Aomatsu, Mikihiro Inoue, Takeshi Saito, Itaru Iwama, Hisashi Kawashima, Hideki Kumagai, Hitoshi Tajiri, Naomi Iwata, Takahiro Mochizuki, Atsuko Noguchi, Toshihiko Kashiwabara, Hirotaka Shimizu, Yasuo Suzuki, Yuri Hirano, Takeo Fujiwara
- Intest Res 2020;18(4):412-420. Published online August 18, 2020
- DOI: https://doi.org/10.5217/ir.2019.00130
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Abstract
PDFPubReaderePub
- Background/Aims
There are few published registry studies from Asia on pediatric inflammatory bowel disease (IBD). Registry network data enable comparisons among ethnic groups. This study examined the characteristics of IBD in Japanese children and compared them with those in European children.
Methods
This was a cross-sectional multicenter registry study of newly diagnosed Japanese pediatric IBD patients. The Paris classification was used to categorize IBD features, and results were compared with published EUROKIDS data.
Results
A total of 265 pediatric IBD patients were initially registered, with 22 later excluded for having incomplete demographic data. For the analysis, 91 Crohn’s disease (CD), 146 ulcerative colitis (UC), and 6 IBD-unclassified cases were eligible. For age at diagnosis, 20.9% of CD, 21.9% of UC, and 83.3% of IBD-unclassified cases were diagnosed before age 10 years. For CD location, 18.7%, 13.2%, 64.8%, 47.3%, and 20.9% were classified as involving L1 (ileocecum), L2 (colon), L3 (ileocolon), L4a (esophagus/stomach/duodenum), and L4b (jejunum/proximal ileum), respectively. For UC extent, 76% were classified as E4 (pancolitis). For CD behavior, B1 (non-stricturing/non-penetrating), B2 (stricturing), B3 (penetrating), and B2B3 were seen in 83.5%, 11.0%, 3.3%, and 2.2%, respectively. A comparison between Japanese and European children showed less L2 involvement (13.2% vs. 27.3%, P< 0.01) but more L4a (47.3% vs. 29.6%, P< 0.01) and L3 (64.8% vs. 52.7%, P< 0.05) involvement in Japanese CD children. Pediatric perianal CD was more prevalent in Japanese children (34.1% vs. 9.7%, P< 0.01).
Conclusions
Upper gastrointestinal and perianal CD lesions are more common in Japanese children than in European children. -
Citations
Citations to this article as recorded by
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- Diagnosis of Pediatric Inflammatory Bowel Disease (PIBD)–Implications for the Asia-Pacific Region: A Position Paper from the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition PIBD Working Group
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- 234 Download
- 34 Web of Science
- 38 Crossref
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