NON-IMMUNOGLOBULIN E-MEDIATED FOOD ALLERGY WITH GASTROINTESTINAL MANIFESTATIONS IN CHILDREN: A CLINICAL PRACTICE REVIEW
##plugins.themes.vojs.article.main##
Abstract
Non-immunoglobulin E (IgE)-mediated gastrointestinal food allergy in children comprises a group of allergic gastrointestinal disorders without evidence of specific IgE sensitization. The most commonly recognized entities are food protein-induced allergic proctocolitis (FPIAP), food protein-induced enterocolitis syndrome (FPIES), and food protein-induced enteropathy (FPE); cow’s milk protein is the most frequently reported trigger across all three phenotypes. References were collected from guidelines, consensus statements, and updated reviews from international professional societies, mainly published between 2020 and 2026. The diagnosis of these disorders is essentially clinical, based on symptom improvement after elimination of the suspected food and recurrence upon re- challenge, as no specific biomarker has yet been validated as sufficiently reliable for routine clinical use. This review presents the concepts, classification, pathophysiology, phenotype- specific clinical manifestations, principles of diagnostic approach, treatment, and follow- up, while also systematizing common pitfalls in practice that may lead to overdiagnosis or unnecessary elimination diets. A balanced approach—not missing potentially severe phenotypes such as FPIES, while avoiding the attribution of all gastrointestinal symptoms in infants solely to food allergy is a fundamental principle of management.
##plugins.themes.vojs.article.details##
Keywords
Non-IgE-mediated food allergy with gastrointestinal manifestations, Food protein-induced allergic proctocolitis, Food protein-induced enterocolitis syndrome, Food protein-induced enteropathy, Cow’s milk protein allergy
References
2. Labrosse R, Graham F, Caubet JC. Non-IgE-mediated gastrointestinal food allergies in children: an update. Nutrients 2020;12(7):2086. https://doi.org/10.3390/nu12072086
3. Vandenplas Y, Broekaert I, Domellöf M et al. An ESPGHAN position paper on the diagnosis, management, and prevention of cow’s milk allergy. J Pediatr Gastroenterol Nutr 2024;78(2):386-413. https://doi.org/10.1097/mpg.0000000000003897
4. Nowak-Wegrzyn A, Sicherer SH, Akin C et al. Current status and future directions in food protein-induced enterocolitis syndrome: an NIAID workshop report of the June 22, 2022, virtual meeting. J Allergy Clin Immunol 2025;155(2):336-356. https://doi.org/10.1016/j.jaci.2024.10.022
5. Mennini M, Fiocchi AG, Cafarotti A et al. Food protein-induced allergic proctocolitis in infants: literature review and proposal of a management protocol. World Allergy Organ J 2020;13:100471. https://doi.org/10.1016/j.waojou.2020.100471
6. D’Auria E, Ferrigno C, Pellicani S et al. Neonatal food protein-induced enterocolitis: current insights and knowledge gaps. J Clin Med 2025;14(7):2461. https://doi.org/10.3390/jcm14072461
7. Barni S, Mori F, Pecoraro L et al. Food protein-induced enteropathy: a revision for the clinician. Front Pediatr 2024;12:1417391. https://doi.org/10.3389/fped.2024.1417391
8. Meyer R, Venter C, Bognanni A et al. World Allergy Organization (WAO) DRACMA Guideline update - VII - Milk elimination and reintroduction in the diagnostic process of cow’s milk allergy. World Allergy Organ J 2023;16:100785. https://doi.org/10.1016/j.waojou.2023.100785
9. Cuomo B, Anania C, D’Auria E et al. The role of the atopy patch test in the diagnostic work-up of non-IgE gastrointestinal food allergy in children: a systematic review. Eur J Pediatr 2023;182(8):3419-3431. doi:10.1007/s00431-023-04994-2.
10. 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
11. Levine A, Koletzko S, Turner D et al. ESPGHAN revised Porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J Pediatr Gastroenterol Nutr 2014;58(6):795-806. https://doi.org/10.1097/mpg.0000000000000239
12. Shields TM, Lightdale JR. Vomiting in children. Pediatr Rev 2018;39(7):342-358. https://doi.org/10.1542/pir.2017-0053
13. National Institute for Health and Care Excellence. Food allergy in under 19s: assessment and diagnosis. Clinical guideline CG116. Published February 23, 2011.
14. NENC Medicines Optimisation Team. Guidelines for the recognition and management of non-IgE mediated cow’s milk allergy (CMA) in infants. Version 1.2. NENC Clinical Effectiveness and Governance Subcommittee; 2026.
15. Le Thi Bich Phuong, Nguyen Thi Kim Oanh, Nguyen Thi Ngoc, Nguyen Anh Tuan. Implementation of home-based oral food challenge in children with non-IgE-mediated cow’s milk protein allergy: safety and feasibility. Vietnam J Pediatr 2025;18(6). https://doi.org/10.52724/tcnk.v18i6.470
16. Barni S, Pessina B, Fioretti L et al. Food protein-induced allergic proctocolitis: real-world experience from an Italian cohort. Nutrients 2025;17(1):98. https://doi.org/10.3390/nu17010098
17. Ullberg J, Ullberg D, Fech-Bormann M, Fagerberg UL. Resolution of food protein-induced enterocolitis syndrome-a long-term follow-up study of 113 Swedish children. J Allergy Clin Immunol Pract 2024;12(8):2127-2134.e1. https://doi.org/10.1016/j.jaip.2024.04.039.