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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.
- 1,806 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.
- 2,592 View
- 141 Download
- Fecal surrogate markers strongly correlate with endoscopic findings in pediatric onset inflammatory bowel disease: a retrospective study in Japan
- Ryoko Yoshimura, Takahiro Kudo, Masanori Toda, Kosuke Kashiwagi, Masumi Nagata, Kaori Aoki, Natsuki Ito, Kazuhide Tokita, Nobuyasu Arai, Reiko Kyodo, Masamichi Sato, Eri Miyata, Keisuke Jimbo, Yoshikazu Ohtsuka, Toshiaki Shimizu, Hiromichi Shoji
- Received January 5, 2025 Accepted April 2, 2025 Published online December 12, 2025
- DOI: https://doi.org/10.5217/ir.2025.00103 [Epub ahead of print]
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Abstract
PDFPubReaderePub
- Background/Aims
Endoscopy serves as the gold standard for assessing disease activity in inflammatory bowel disease (IBD). Noninvasive biomarkers have been under exploration as potential alternatives. This study aims to examine the diagnostic effectiveness of fecal immunochemical tests, along with levels of fecal calprotectin (FC) and fecal lactoferrin (FL), in stool samples from patients with early-onset IBD.
Methods
Children with childhood-onset IBD who visited the Department of Pediatrics and Adolescent Medicine at Juntendo University Hospital between August 2019 and July 2023 were included. FC levels, FL levels, and fecal immunochemical test results were measured using a colloidal gold agglutination assay. Fecal biomarker results and endoscopic findings were reviewed retrospectively.
Results
Sixty-five patients had ulcerative colitis (UC), 20 had Crohn’s disease (CD), and 3 had unclassified IBD. The participants, aged 3–27 years (median, 18.0 years), included 56 males and 32 females. Stool samples (n = 1,105) were analyzed, from 803 with UC, 251 with CD, and 51 with IBD. Endoscopic evaluations were conducted in 45 UC patients and 18 CD patients. A significant correlation was found between the FC and FL. These biomarkers were significantly correlated with the endoscopic activity index in both UC and CD patients.
Conclusions
FC is valuable for diagnosing endoscopic inflammation and predicting recurrence. A significant correlation was observed between FC and FL. In patients with UC and CD, both markers strongly correlated with endoscopic activity. Thus, FC and FL can serve as a reliable alternative to endoscopic evaluation in pediatric patients with childhood-onset IBD.
- 1,405 View
- 128 Download
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