Modern View on Very Early Onset and Early Onset Inflammatory Bowel Diseases in Children
Anatoly I. Khavkin,
Anastasiya A. Permyakova,
Mariya O. Tsepilova,
Aleksandra V. Kaplina,
Stanislav I. Sitkin,
Andrey N. Surkov,
Stanislav D. Getmanov https://doi.org/10.15690/vsp.v23i3.2768
Abstract
Nowadays, an urgent problem of pediatric gastroenterology is the study of inflammatory bowel diseases with very early onset (VEO-IBD), which have unique genetic, clinical, immunological, morphological, and laboratory sings. Early VEO-IBD is usually considered as monogenic disease, especially in combination with congenital immune defects, which leads to difficulties in diagnosis and management this pathology. Despite this, systematization of information about this group of nosological forms of IBD is practically not carried out. This article presents a review of the available information on etiological factors, course variants, and therapeutic options for VEO-IBD.
Keywords
early onset inflammatory bowel disease,
very early onset inflammatory bowel disease,
Crohn's disease,
ulcerative colitis,
indeterminate colitis,
necrotizing enterocolitis
Supporting agencies: Not declared
About the Authors
Anatoly I. Khavkin
Research and Clinical Institute for Children; Belgorod State University
Russian Federation
Disclosure of interest:
Russian Federation
Mytishchi, Belgorod
Disclosure of interest:
Other authors confirmed the absence of a reportable conflict of interests
Anastasiya A. Permyakova
Saint Petersburg State Pediatric Medical University
Russian Federation
Disclosure of interest:
Russian Federation
Saint Petersburg
Disclosure of interest:
Other authors confirmed the absence of a reportable conflict of interests
Mariya O. Tsepilova
Saint Petersburg State Pediatric Medical University
Russian Federation
Disclosure of interest:
Russian Federation
Saint Petersburg
Disclosure of interest:
Other authors confirmed the absence of a reportable conflict of interests
Aleksandra V. Kaplina
Almazov National Medical Research Centre
Russian Federation
Disclosure of interest:
Russian Federation
Saint Petersburg
Disclosure of interest:
Other authors confirmed the absence of a reportable conflict of interests
Stanislav I. Sitkin
Almazov National Medical Research Centre; North-Western State Medical University named after I.I. Mechnikov
Russian Federation
Disclosure of interest:
Russian Federation
Saint Petersburg
Disclosure of interest:
Other authors confirmed the absence of a reportable conflict of interests
Andrey N. Surkov
Research Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery; Pirogov Russian National Research Medical University
Russian Federation
Disclosure of interest:
Russian Federation
Moscow
Disclosure of interest:
lecturing for pharmaceutical companies PTC Therapeutics, Swixx BioPharma, Sanofi Aventis Group, AstraZeneca, OTCPharm, Opella Healthcare, Leovit
Stanislav D. Getmanov
Pirogov Russian National Research Medical University
Russian Federation
Disclosure of interest:
Russian Federation
Moscow
Disclosure of interest:
Other authors confirmed the absence of a reportable conflict of interests
References
1. Ouahed J, Spencer E, Kotlarz D, et al. Very Early Onset Inflammatory Bowel Disease: A Clinical Approach With a Focus on the Role of Genetics and Underlying Immune Deficiencies. Inflamm Bowel Dis. 2020;26(6):820–842. https://doi.org/10.1093/ibd/izz259
2. Kuenzig ME, Fung SG, Marderfeld L, et al. Twenty-first Century Trends in the Global Epidemiology of Pediatric-Onset Inflammatory Bowel Disease: Systematic Review. Gastroenterology. 2022;162(4):1147–1159.e4. https://doi.org/10.1053/j.gastro.2021.12.282 2022 Jan 5
3. Nameirakpam J, Rikhi R, Rawat SS, et al. Genetics on early onset inflammatory bowel disease: An update. Genes Dis. 2019;7(1): 93–106. https://doi.org/10.1016/j.gendis.2019.10.003
4. Cananzi M, Wohler E, Marzollo A, et al. IFIH1 loss-of-function variants contribute to very early-onset inflammatory bowel disease. Hum Genet. 2021;140(9):1299–1312. https://doi.org/10.1007/s00439-021-02300-4
5. Uhlig HH, Schwerd T, Koletzko S, et al. The Diagnostic Approach to Monogenic Very Early Onset Inflammatory Bowel Disease. Gastroenterology. 2014;147(5):990–1007.e3. https://doi.org/10.1053/j.gastro.2014.07.023
6. Drabent P, Berrebi D. Pediatric very early onset inflammatory bowel disease: Role of pathology. Ann Pathol. 2023;43(3):202–212. https://doi.org/10.1016/j.annpat.2023.02.003
7. Shumilov PV, Shchigoleva AE. Features of very early-onset inflammatory bowel disease: the experience of the Federal Pediatric Center. Voprosy detskoi dietologii = Pediatric Nutrition. 2021;19(3):5–13. (In Russ). https://doi.org/10.20953/1727-5784-2021-3-5-13]
8. Shchigoleva AE, Shumilov PV, Shumilov AP. Inflammatory bowel diseases with very early onset. Pediatria. Journal n.a. G.N. Speransky. 2018;97(6):141–146. (In Russ). https://doi.org/10.24110/0031-403X-2018-97-6-141-146
9. Moran CJ. Very early onset inflammatory bowel disease. Semin Pediatr Surg. 2017;26(6):356–359. https://doi.org/10.1053/j.sempedsurg.2017.10.004
10. Gupta N, Bostrom AG, Kirschner BS, et al. Presentation and disease course in early-compared to later-onset pediatric Crohn’s disease. Am J Gastroenterol. 2008;103(8):2092–2098. https://doi.org/10.1111/j.1572-0241.2008.02000.x
11. Collen LV, Kim DY, Field M, et al. Clinical Phenotypes and Outcomes in Monogenic Versus Non-monogenic Very Early Onset Inflammatory Bowel Disease. J Crohns Colitis. 2022;16(9): 1380–1396. https://doi.org/10.1093/ecco-jcc/jjac045
12. Novikova VP, Khavkin AI, Prokopyeva NE. IBD-like gastrointestinal disorders in children. Experimental and Clinical Gastroenterology. 2021;(4):161–169. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-188-4-161-169
13. Usoltseva O.V., Surkov A.N., Movsisyan G.B., Potapov A.S., Kulebina E.A., Kulikov К.A., Chernikov V.V. Correlation of Inflammatory Bowel Diseases with Liver Involvement Severity in Autoimmune Hepatobiliary Pathology: Cross-Sectional Study. Current Pediatrics. 2022;21(2):105–112. (In Russ.) https://doi.org/10.15690/pf.v19i2.2407
14. Kelsen JR, Russo P, Sullivan KE. Early-Onset Inflammatory Bowel Disease. Immunol Allergy Clin North Am. 2019;39(1):63–79. https://doi.org/10.1016/j.iac.2018.08.008
15. Petrova NA, Kaplina AV, Khavkin AI, et al. Necrotizing enterocolitis: current concepts of etiopathogenesis with an emphasis on microbiome and metabolomics. Voprosy prakticheskoi pediatrii = Clinical Practice in Pediatrics. 2021;16(4):98–105. (In Russ). https://doi.org/10.20953/1817-7646-2021-4-98-105
16. Kaplina A, Kononova S, Zaikova E, et al. Necrotizing Enterocolitis: The Role of Hypoxia, Gut Microbiome, and Microbial Metabolites. Int J Mol Sci. 2023;24(3):2471. https://doi.org/10.3390/ijms24032471
17. Kaplina AV, Petrova NA, Nikiforov VG, et al. Necrotizing enterocolitis in newborns with congenital heart defects: incidence and risk factors. Voprosy prakticheskoi pediatrii = Clinical Practice in Pediatrics. 2022;17(6):62–73. (In Russ). https://doi.org/10.20953/1817-7646-2022-6-62-73
18. Hackam DJ, Sodhi CP. Toll-Like Receptor-Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing Enterocolitis. Cell Mol Gastroenterol Hepatol. 2018;6(2): 229–238.e1. https://doi.org/10.1016/j.jcmgh.2018.04.001
19. Ashton JJ, Ennis S, Beattie RM. Early-onset paediatric inflammatory bowel disease. Lancet Child Adolesc Health. 2017;1(2):147–158. https://doi.org/10.1016/S2352-4642(17)30017-2
20. Fuller MK. Pediatric Inflammatory Bowel Disease: Special Considerations. Surg Clin North Am. 2019;99(6):1177–1183. https://doi.org/10.1016/j.suc.2019.08.008
21. Levine AE, Mark D, Smith L, et al. Pharmacologic Management of Monogenic and Very Early Onset Inflammatory Bowel Diseases. Pharmaceutics. 2023;15(3):969. https://doi.org/10.3390/pharmaceutics15030969
22. Zheng HB, De la Morena MT, Suskind DL. The growing need to understand very early onset inflammatory bowel disease. Fron Immunol. 2021;12:675186. https://doi.org/10.3389/fimmu.2021.675186
23. Nambu R, Warner N, Mulder DJ, et al. A Systematic Review of Monogenic Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2022;20(4):e653–e663. https://doi.org/10.1016/j.cgh.2021.03.021
24. Arai K. Very Early-Onset Inflammatory Bowel Disease: A Challenging Field for Pediatric Gastroenterologists. Pediatr Gastroenterol Hepatol Nutr. 2020;23(5):411–422. https://doi.org/10.5223/pghn.2020.23.5.411
25. Shim JO. Recent Advance in Very Early Onset Inflammatory Bowel Disease. Pediatr Gastroenterol Hepatol Nutr. 2019;22(1): 41–49. https://doi.org/10.5223/pghn.2019.22.1.41
26. Chapuy L, Leduc B, Godin D, et al. Phenotype and outcomes of very early onset and early onset inflammatory bowel diseases in a Montreal pediatric cohort. Front Pediatr. 2023;11:1157025. https://doi.org/10.3389/fped.2023.1157025
27. Kelsen JR, Conrad MA, Dawany N, et al. The Unique Disease Course of Children with Very Early onset-Inflammatory Bowel Disease. Inflamm Bowel Dis. 2020;26(6):909–918. https://doi.org/10.1093/ibd/izz214
28. Nemati S, Teimourian S. An Overview of Inflammatory Bowel Disease: General Consideration and Genetic Screening Approach in Diagnosis of Early Onset Subsets. Middle East J Dig Dis. 2017;9(2):69–80. https://doi.org/10.15171/mejdd.2017.54
29. Beser OF, Conde CD, Serwas NK, et al. Clinical features of interleukin 10 receptor gene mutations in children with very early-onset inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2015;60(3):332–338. https://doi.org/10.1097/MPG.0000000000000621
30. Pigneur B, Escher J, Elawad M, et al. Phenotypic characterization of very early-onset IBD due to mutations in the IL10, IL10 receptor alpha or beta gene: a survey of the Genius Working Group. Inflamm Bowel Dis. 2013;19(13):2820–2828. https://doi.org/10.1097/01.MIB.0000435439.22484.d3
31. Moran CJ, Walters TD, Guo CH, et al. IL-10R polymorphisms are associated with very-early-onset ulcerative colitis. Inflamm Bowel Dis. 2013;19(1):115–123. https://doi.org/10.1002/ibd.22974
32. Watson A, Forbes Satter L, Reiland Sauceda A, et al. NOD2 Polymorphisms May Direct a Crohn Disease Phenotype in Patients With Very Early-Onset Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr. 2023;77(6):748–752. https://doi.org/10.1097/MPG.0000000000003846
33. Zeissig S, Petersen BS, Tomczak M, et al. Early-onset Crohn’s disease and autoimmunity associated with a variant in CTLA-4. Gut. 2015;64(12):1889–1897. https://doi.org/10.1136/gutjnl-2014-308541
34. Moazzami B, Moazzami K, Rezaei N. Early onset inflammatory bowel disease: manifestations, genetics and diagnosis. Turk J Pediatr. 2019;61(5):637–647. https://doi.org/10.24953/turkjped.2019.05.001
35. Shouval DS, Biswas A, Kang YH, et al. Interleukin 1β Mediates Intestinal Inflammation in Mice and Patients With Interleukin 10 Receptor Deficiency. Gastroenterology. 2016;151(6):1100–1104. https://doi.org/10.1053/j.gastro.2016.08.055
36. Lekbua A, Ouahed J, O’Connell AE, et al. Risk-factors Associated With Poor Outcomes in VEO-IBD Secondary to XIAP Deficiency: A Case Report and Literature Review. J Pediatr Gastroenterol Nutr. 2019;69(1):e13–e18. https://doi.org/10.1097/MPG.0000000000002297
37. Turner D, Levine A, Kolho KL, et al. Combination of oral antibiotics may be effective in severe pediatric ulcerative colitis: a preliminary report. J Crohns Colitis. 2014;8(11):1464–1470. https://doi.org/10.1016/j.crohns.2014.05.010
38. Bedoui Y, Guillot X, Selambarom J, et al. Methotrexate an Old Drug with New Tricks. Int J Mol Sci. 2019;20(20):5023. https://doi.org/10.3390/ijms20205023
39. Kelsen JR, Sullivan KE, Rabizadeh S, et al. 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. 2020;70(3):389–403. https://doi.org/10.1097/MPG.0000000000002567
40. Walker R, Kammermeier J, Vora R, Mutalib M. Azathioprine dosing and metabolite measurement in pediatric inflammatory bowel disease: Does one size fit all? Ann Gastroenterol. 2019;32(4): 387–391. https://doi.org/10.20524/aog.2019.0381
41. Wilkins BJ, Kelsen JR, Conrad MA. A Pattern-based Pathology Approach to Very Early-onset Inflammatory Bowel Disease: Thinking Beyond Crohn Disease and Ulcerative Colitis. Adv Anat Pathol. 2022;29(1):62–70. https://doi.org/10.1097/PAP.0000000000000327
42. Miró-González ÁA, Maldonado-Chaar SM, Zambrana-Valenzuela R, et al. Development of Very-Early-Onset Inflammatory Bowel Disease After Multiple Early-Life Antibiotic Exposures: A Case Report and Literature Review. Cureus. 2023;15(1):e33813. https://doi.org/10.7759/cureus.33813
43. Grove Z. A narrative review of pitfall and progress in management of inflammatory bowel disease in child. Pediatr Med. 2023;6:10. https://doi.org/10.21037/pm-21-11
44. Grove Z. Predicting and preventing complications in children with inflammatory bowel disease. Transl Pediatr. 2019;8(1):70–76. https://doi.org/10.21037/tp.2019.01.03
45. Klamt J, de Laffolie J, Wirthgen E, et al. Predicting complications in pediatric Crohn’s disease patients followed in CEDATAGPGE registry. Front Pediatr. 2023;11:1043067. https://doi.org/10.3389/fped.2023.1043067
46. Dahmus J, Rosario M, Clarke K. Risk of Lymphoma Associated with Anti-TNF Therapy in Patients with Inflammatory Bowel Disease: Implications for Therapy. Clin Exp Gastroenterol. 2020;13:339–350. https://doi.org/10.2147/CEG.S237646
47. Chen Y, Junlin H, Xiaowen H, et al. Risk of Lymphoma in Patients With Inflammatory Bowel Disease Treated With Antitumour Necrosis Factor Alpha Agents: A Systematic Review and Meta-analysis. J Crohns Colitis. 2018;12(9):1042–1052. https://doi.org/10.1093/ecco-jcc/jjy065
48. Lemaitre M, Kirchgesner J, Rudnichi A, et al. Association Between Use of Thiopurines or Tumor Necrosis Factor Antagonists Alone or in Combination and Risk of Lymphoma in Patients With Inflammatory Bowel Disease. JAMA. 2017;318(17):1679–1686. https://doi.org/10.1001/jama.2017.16071
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For citations:
Khavkin A.I., Permyakova A.A., Tsepilova M.O., Kaplina A.V., Sitkin S.I., Surkov A.N., Getmanov S.D. Modern View on Very Early Onset and Early Onset Inflammatory Bowel Diseases in Children. Current Pediatrics. 2024;23(3):145-151. (In Russ.) https://doi.org/10.15690/vsp.v23i3.2768
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