Challenges in diagnosing IBD-like intestinal lesions in young children
DOI:
https://doi.org/10.15574/SP.2025.2(146).147156Keywords:
young children, inflammatory bowel diseases, immunodeficiency states, monogenic immune defects, diagnosticsAbstract
Among inflammatory bowel diseases (IBD) with very early onset, particularly in children under two years of age (Infantile Form IBD), monogenic IBD-like disorders account for a significant proportion — up to 35%. Most of these conditions are associated with congenital immunodeficiencies. Our research also suggests a possible link between IBD-like intestinal mucosal lesions and certain congenital gastrointestinal malformations (such as neuropathy and myopathy) as well as severe viral infections, including COVID-19.
Aim - using the example of a clinical case, to show the phenotypic features, difficulties of diagnosis and treatment of CKD-like diseases in young children.
This article discusses the characteristics of IBD-like intestinal lesions associated with other diseases in young children, based on an examination of 10 patients. Among them, six had primary immunodeficiency (including three with genetically confirmed monogenic immune defects), two had congenital gastrointestinal malformations (neuro-muscular dysplasia and primary ileocecal valve insufficiency), and two had a history of virus-identified coronavirus infection (COVID-19) - post-COVID syndrome. Additionally, we describe a clinical case of an IBD-like (Crohn’s disease-like) intestinal lesion in the context of a genetic predisposition caused by a pathogenic NOD2 mutation.
Conclusions. IBD-like intestinal lesions in young children, particularly in monogenic IBD-like diseases, almost always present with a phenotype similar to classic IBD. Therefore, the diagnosis and management of very early-onset IBD, especially in infantile-onset cases, require a personalized approach. This includes the involvement of a multidisciplinary team of specialists, comprehensive immunological assessment, and a careful, individualized treatment strategy for young children presenting with an IBD-like phenotype.
The study adhered to the Helsinki Declaration principle.
Authors report no conflicts of interest.
References
Al-Hussaini A, El Mouzan M, Hasosan M, Al-Mehaidid A. (2016). Clinical Pattern of Early-Onset Inflammatory Bowel Disease in Saudi Arabia: A Multicenter National Study. Inflamm Bower Dis. 22; 8: 1961-1970. https://doi.org/10.1097/MIB.0000000000000796; PMid:27104817 PMCid:PMC4949013
Bousfiha A, Jeddane L, Picard C et al. (2020). Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol. 40(1): 66-81. https://doi.org/10.1007/s10875-020-00758-x; PMid:32048120 PMCid:PMC7082388
Cleynen I, Boucher G, Jostins L et al. (2016). International IBD Genetics Consortium Inherited Determinants of Crohn's disease and ulcerationts colitis phenotipes: a genetic assotiation study. Lancet. 87(10014): 156-167. https://doi.org/10.1016/S0140-6736(15)00465-1; PMid:26490195
Crowley E, Warner N, Pan J, Khalouei S, Elkadri A, Fiedler K et al. (2020) Prevalence and clinical features of inflammatory bowel disese associated with monogenic variants, identified by whole exome sequencing in 1000 children at a single center. Gastroenterology. 158(8): 2208-2220. https://doi.org/10.1053/j.gastro.2020.02.023; PMid:32084423 PMCid:PMC7283012
De Lange K, Moutsianas L, Lee J, Lamb C. (2017). Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat Genet. 49(2):256-261. https://doi.org/10.1038/ng.3760; PMid:28067908 PMCid:PMC5289481
Ensari A, Kelsen J, Russo P. (2017). Newcomers in paediatric GI pathology: childhood enteropathies including very onset monogenic IBD. Virchows Arch. 472(1): 111-123. Epub 2017 Jul 17. https://doi.org/10.1007/s00428-017-2197-9; PMid:28718031 PMCid:PMC6171108
Gomollon F, Dignass F et al. (2017). 3rd European Evidence - based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 1-2: Diagnosis and Medical Management. Journal of Crohn's and Colitis. 11(1): 3-5. Epub 2016 Sep 22. https://doi.org/10.1093/ecco-jcc/jjw168; PMid:27660341
Harbord M, Eliakim R et al. (2017). 3rd European Evidence - based Consensus on the Diagnosis and Management of Ulcerative Colitis. Part 2: Current Management. Journal of Crohn's and Colitis. 1-24. https://doi.org/10.1093/ecco-jcc/jjx008; PMid:28158501
Kammermeier J, Dziubak R, Pescarin M, Drury S, Godwin H, Reeve K et al. (2017, Jan). Phenotypic and Genotypic Characterisation of Inflammatory Bowel Disease Presenting Before the Age of 2 years. J Crohns Colitis. 11(1): 60-69. Epub 2016 Jun 14. https://doi.org/10.1093/ecco-jcc/jjw118; PMid:27302973 PMCid:PMC5885808
Kelsen JR, Russo R, Sullivan KE. (2019). Early-Onset Inflammatory Bowel Disease. Immunology and Allergy.Clinics of North America. 39(1): 63-79. URL: https://www.sciencedirect.com/science/article/abs/pii/S0889856l. https://doi.org/10.1016/j.iac.2018.08.008; PMid:30466773 PMCid:PMC6954002
Kelsen JR, Sullivan KE, Rabizadeh S, Singh N, Snapper S et al. (2020). North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper on the Evaluation and Management for Patients With Very Early-onset Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr. 70(3): 389-403. https://doi.org/10.1097/MPG.0000000000002567; PMid:32079889 PMCid:PMC12024488
Lega S, Pin A, Arrigo S, Cifaldi C. (2020). Diagnostic approach to monogenic inflammatory bowel disease in clinical practice: A ten-year multicentric experience. Inflamm Bowel Dis. 26(5): 720-727. https://doi.org/10.1093/ibd/izz178; PMid:31375816
Malamut G, Simon M, Nachury N, Uzzan M, Serrero M, Fumery M. (2022). Review: Inflammatory bowel diseases associated with primary immunodeficiency: a multicenter study. Journal of Crohn's and Colitis. 1; Suppl l. URL: https://www.sciencedirect.eom/science/article/pii/Sl56899722l00l452#bb0l85.
Meyts I, Bousfiha A, Duff C, Singh S. (2021). Primary immunodeficiencies: A decade of Progress and a promising future. Front immunol. 11: 625753. https://doi.org/10.3389/fimmu.2020.625753; PMid:33679719 PMCid:PMC7935502
Mirkov M, Verstoct B. Cleynen I. (2017). Genetics of inflammatory bowel disese: beyond NOD2. Lancet Gastroenterol hepatol. 2: 224-234. https://doi.org/10.1016/S2468-1253(16)30111-X; PMid:28404137
Muise A. (2019). Very Early Onset Inflammatory Bowel Disease (VEOIBD). Textbook of Autoinflammation: 383-404. https://doi.org/10.1007/978-3-319-98605-0_21
Ouahed J, Spencer E, Kotlarz D, Shouval DS, Kowalik M, Peng K, Field M et al. (2020). Very Early Onset Inflammatory Bowel Disease: A Clinical Approach With a Focus on the Role of Genetics and Underlying Immune Deficiencies. Inflamm Bowel Dis. 26(6): 820-842. https://doi.org/10.1093/ibd/izz259; PMid:31833544 PMCid:PMC7216773
Sasahara Y, Uchida T. (2022). Primary Immunodeficiencies Associated With Early-Onset Inflammatory Bowel Disease inSoutheast and East Asia. Frontiers in Immunology MINI REVIEW article: Front. Immunol. 13 January 2022 Sec. Primary Immunodeficiencies. Autoimmunity. 12. URL: https://www.frontiersin.org/articles/10.3389/fimmu.2021.786538/full. https://doi.org/10.3389/fimmu.2021.786538; PMid:35095863 PMCid:PMC8792847
Serra E, Schwerd T, Moutsianas L, Cavounidis A. (2020). Somatic mosaicism and common genetic variation contribute to the risk of very-early0onset inflammatory bowel disease. Nat Commun. 11: article 995.
Shouval DS, Kowalik M, Snapper SB. (2018). The Treatment of Inflammatory Bowel Disease in Patients with Selected Primary Immunodeficiencies. Clin Immunol. 38(5): 579-588. https://pubmed.ncbi.nlm.nih.gov/29956079/. https://doi.org/10.1007/s10875-018-0524-9; PMid:29956079
Tangye SG, Al-Herz W, Bousfiha A, Chatila T. (2020). Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 40(1): 1-35. https://doi.org/10.1007/s10875-022-01289-3; PMid:35748970 PMCid:PMC9244088
Tegtmeyer D, Seidl M, Gerner P, Baumann U. (2017). Inflammatory bowel disease caused by primary immunodeficiencies-Clinical presentations, review of literature, and proposal of a rational diagnostic algorithm. Pediatr Allergy Immunol. 28(5): 412-29. https://doi.org/10.1111/pai.12734; PMid:28513998
Turner D, Ruemmele FM, Orlanski-Meyer E, Griffiths AM, de Carpi JM, Bronsky J et al. (2018). Management of pediatric ulcerative colitis, part 2: Acute severe colitis - evidence-based consensus. Guidelines from the European Crohn's and Colitis Union. Organization and European Society of Pediatrics. Gastroenterology, hepatology and nutrition. J Pediatr Gastroenterol Nutr. 67(2): 292-304. https://doi.org/10.1097/MPG.0000000000002036; PMid:30044358
Uhlig HH, Charbit-Henrion F, Kotlarz D et al. (2021). Clinical Genomics for the Diagnosis of Monogenic Forms of Inflammatory Bowel Disease: A Position Paper From the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 72(3): 456-473. https://doi.org/10.1097/MPG.0000000000003017; PMid:33346580 PMCid:PMC8221730
Uhlig HH, Schwerd T, Koletzko S, Shah N, Kammermeier J, Elkadri A et al. (2014). The diagnostic approach to monogenic very early onset inflammatory bowel disease. Gastroenterology. 147(5): 990-1007. https://doi.org/10.1053/j.gastro.2014.07.023; PMid:25058236 PMCid:PMC5376484
Verstockt B, Smith K, Lee J. (2018). Genome-wide association studies in Crohn's disease: Past, present and future. Clin Transl Immunol. 7(1): P.e.1001. https://doi.org/10.1002/cti2.1001; PMid:29484179 PMCid:PMC5822399
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Modern pediatrics. Ukraine
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The policy of the Journal “MODERN PEDIATRICS. UKRAINE” is compatible with the vast majority of funders' of open access and self-archiving policies. The journal provides immediate open access route being convinced that everyone – not only scientists - can benefit from research results, and publishes articles exclusively under open access distribution, with a Creative Commons Attribution-Noncommercial 4.0 international license (СС BY-NC).
Authors transfer the copyright to the Journal “MODERN PEDIATRICS. UKRAINE” when the manuscript is accepted for publication. Authors declare that this manuscript has not been published nor is under simultaneous consideration for publication elsewhere. After publication, the articles become freely available on-line to the public.
Readers have the right to use, distribute, and reproduce articles in any medium, provided the articles and the journal are properly cited.
The use of published materials for commercial purposes is strongly prohibited.
