{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T18:40:09Z","timestamp":1748630409451,"version":"3.41.0"},"reference-count":62,"publisher":"Colegio Mexicano de Inmunologia Clinica y Alergia, A. C.","issue":"1","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":["revistaalergia.mx"],"crossmark-restriction":false},"short-container-title":["Rev. Alergia Mex"],"abstract":"<jats:p>Background: Non-IgE-mediated gastrointestinal food allergy includes adverse reactions to food mediated by the innate immune system and cellular immunity. It is characterized by subacute or chronic gastrointestinal symptoms after ingestion of a relevant food allergen, making diagnosis difficult.\n\nObjective: To carry out an updated bibliographic review of non-IgE-mediated gastrointestinal food allergy, that summarizes incidence, pathophysiology, clinical manifestations, diagnostic tools and treatment.\n\nMethods: A search was conducted in the databases Medline, EMBASE, Scielo, Google Scholar and the Advanced Medicine Informatics Network (RIMA) using the keywords: non-IgE-mediated food allergy, allergic proctocolitis; cow\u2019s milk-induced anemia; food protein-induced enteropathy; food protein-induced enterocolitis syndrome; Celiac disease and Heiner syndrome. The search was limited to articles published in English and Spanish from January 2015 to May 2024.\n\nResults: While progress has been made in the recognition of these diseases, the prevalence and pathophysiology remain uncertain. Involvement of the innate immune system and cellular immunity in gastrointestinal inflammation has been found, but further studies are needed to clarify the immunopathogenesis and associated biomarkers.\n\nConclusions: Non-IgE-mediated gastrointestinal food allergy account for an unknown proportion of food allergies. Since there are no biomarkers or non-invasive confirmatory tests, the diagnosis relies on clinical features and is confirmed when the symptoms improve with elimination of the offending food. Management includes avoidance of the causative food from the diet, supportive treatment in case of accidental exposure, and nutritional counseling.\n\nKeywords: Non-IgE-mediated food allergy; Food protein-induced enterocolitis syndrome; Celiac disease; Allergic proctocolitis; Cow\u2019s milk-induced anemia; Food protein-induced enteropathy; Heiner syndrome.<\/jats:p>","DOI":"10.29262\/ram.v72i1.1420","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T15:54:10Z","timestamp":1744214050000},"page":"35-51","update-policy":"https:\/\/doi.org\/10.29262\/ram.crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Non-IgE-mediated gastrointestinal food allergy. Updated literature review by the CMICA Food Allergy Committee"],"prefix":"10.29262","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8359-3790","authenticated-orcid":false,"given":"Ileana","family":"Madrigal Beas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"11808","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"60386","doi-asserted-by":"crossref","unstructured":"1. Yu W, Freeland DMH, Nadeau KC. Food allergy: immune mechanisms, diagnosis and immunotherapy. Nat Rev Immunol 2016; 16 (12): 751-765. doi: 10.1038\/nri.2016.111","DOI":"10.1038\/nri.2016.111"},{"key":"60387","doi-asserted-by":"crossref","unstructured":"2. Anvari S, Miller J, Yeh C-Y, et al. IgE-mediated food allergy. Clin Rev Allergy Immunol 2019; 57 (2): 244-260. doi: 10.1007\/s12016-018-8710-3","DOI":"10.1007\/s12016-018-8710-3"},{"key":"60388","doi-asserted-by":"crossref","unstructured":"3. Kim EH, Wesley B. Immunological basis of food allergy. IgE-mediated, non- IgE mediated, and tolerance. In: Ebisawa M, Ballmer-Weber B, Vieths S, et al, editores. Food Allergy: Molecular Basis and Clinical Practice. Chemical Immunology and Allergy. 1a ed. Basilea, Suiza: Karger; 2015 (101): 8-17.","DOI":"10.1159\/000371646"},{"key":"60389","doi-asserted-by":"crossref","unstructured":"4. Shoemaker AA, Sprikkelman AB, Grimshaw KE, et al. Incidence and natural history of challenge-proven cow\u00b4s milk allergy in European children- EuroPrevall Birth cohort. Allergy 2015; 70: 963-972. doi: 10.1111\/all.12630","DOI":"10.1111\/all.12630"},{"key":"60390","doi-asserted-by":"crossref","unstructured":"5. Al-Iede M, Sarhan L, Alshrouf MA, et al. Perspectives on Non-IgE-Mediated Gastrointestinal Food Allergy in Pediatrics: A review of current evidence and guidelines. J Asthma Allergy 2023; 16: 279-291. doi: 10.2147\/JAA.S284825.","DOI":"10.2147\/JAA.S284825"},{"key":"60391","doi-asserted-by":"crossref","unstructured":"6. Sj\u00f6lund J, Kull I, Bergstr\u00f6m A, et al. Allergy-related diseases in childhood and risk for abdominal pain-related functional gastrointestinal disorders at 16 years - a birth cohort study. BMC Med 2021; 19 (1): 214. doi: 10.1186\/s12916-021-02069-3","DOI":"10.1186\/s12916-021-02069-3"},{"key":"60392","doi-asserted-by":"crossref","unstructured":"7. D\u00b4Auria E, Salvatore S, Acunzo M, et al. Hydrolysed formulas in the management of cow\u00b4s milk allergy: New insigths, pitfalls and tips. Nutrients 2021; 13 (8): 2762. doi: 10.3390\/nu13082762.","DOI":"10.3390\/nu13082762"},{"key":"60393","doi-asserted-by":"crossref","unstructured":"8. Nowak-Wegrzyn A, Katz Y, Shoeil MS, et al. Non-IgE mediated gastrointestinal food allergy. J Allergy Clin Immunol 2015; 135 (5): 1114-1124. doi: 10.1016\/j.jaci.2015.03.025","DOI":"10.1016\/j.jaci.2015.03.025"},{"key":"60394","doi-asserted-by":"crossref","unstructured":"9. Meyer R, Chebar LA, Fleischer DM, et al. Diagnosis and management of non-IgE gastrointestinal allergies in breastfed infants-an EAACI position paper. Allergy 2020; 75 (1): 14-32. doi: 10.1111\/all.13947","DOI":"10.1111\/all.13947"},{"key":"60395","doi-asserted-by":"crossref","unstructured":"10. Martin VM, Virkud YV, Seay H, et al. Prospective assessment of pediatrician-diagnosed food-protein induced allergic proctocolitis by gross or occult blood. J Allergy Clin Immunol 2020; 8 (5): 1692-1699. doi: 10.1016\/j.jaip.2019.12.029.","DOI":"10.1016\/j.jaip.2019.12.029"},{"key":"60396","doi-asserted-by":"crossref","unstructured":"11. Mennini M, Fiocchi AG, Cafarotti A, et al. Food protein-induced allergic proctocolitis in infants: Literature review and proposal of a management protocol. 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Allergy Asthma Proc 2015; 36 (3): 172-184. doi: 10.2500\/aap.2015.36.3811.","DOI":"10.2500\/aap.2015.36.3811"},{"key":"60400","doi-asserted-by":"crossref","unstructured":"15. Connors L, O'Keefe A, Rosenfield L, et al. Non-IgE-mediated food hypersensitivity. Allergy Asthma Clin Immunol 2018; 14 (Suppl 2): 83-91. doi: 10.1186\/s13223-018-0285-2.","DOI":"10.1186\/s13223-018-0285-2"},{"key":"60401","doi-asserted-by":"crossref","unstructured":"16. Mathew M, Leeds S, Nowak-W\u0119grzyn A. Recent Update in Food Protein- Induced Enterocolitis Syndrome: Pathophysiology, diagnosis, and management. Allergy Asthma Immunol Res 2022; 14 (6): 587-603. doi.org\/10.4168\/aair.2022.14.6.587","DOI":"10.4168\/aair.2022.14.6.587"},{"key":"60402","doi-asserted-by":"crossref","unstructured":"17. Heine RG. Gastrointestinal Food Allergies. In: Ebisawa M, Ballmer- Weber B, Vieths S, et al, editores. Food Allergy: Molecular Basis and Clinical Practice. Chemical Immunology and Allergy. 1a ed. 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Pediatr Neonatol 2018; 59 (1): 48-52. doi: 10.1016\/j.pedneo.2017.01.004.","DOI":"10.1016\/j.pedneo.2017.01.004"},{"key":"60406","doi-asserted-by":"crossref","unstructured":"21. Moscheo C, Licciardello M, Samperi P, et al. New insights into iron deficiency anemia in children: a practical review. Metabolites 2022; 12 (4): 289. doi: 10.3390\/metabo12040289","DOI":"10.3390\/metabo12040289"},{"key":"60407","doi-asserted-by":"crossref","unstructured":"22. Esp\u00edn JB, D\u00edaz MJ, Blesa BL, et al. Alergia a las Prote\u00ednas de leche de vaca no mediada por IgE. An Pediatr 2019; 90 (3): 191. doi: 10.1016\/j.anpedi.2018.11.007","DOI":"10.1016\/j.anpedi.2018.11.007"},{"key":"60408","doi-asserted-by":"crossref","unstructured":"23. Venter C, Brown T, Meyer R, et al. Better recognition, diagnosis and management of non-IgE-mediated cow\u2019s milk allergy in infancy. Clin Transl Allergy 2017; 7: 26. doi: 10.1186\/s13601-017-0162-y","DOI":"10.1186\/s13601-017-0162-y"},{"key":"60409","doi-asserted-by":"crossref","unstructured":"24. Ortega-Espinosa A, Mart\u00ednez-Benaiges MA, Rojas-Pineda NA, et al. Hematemesis en un neonato con s\u00edndrome de Heiner. Informe de caso. Rev Alerg M\u00e9xico 2021; 68 (3): 209-213. doi: 10.29262\/ram.v68i3.901","DOI":"10.29262\/ram.v68i3.901"},{"key":"60410","doi-asserted-by":"crossref","unstructured":"25. Liu XY, Huang XR, Zhang JW, et al. Hematochezia in one boy with syndrome of Heiner. Pediatr Front 2019; 7: 551-555. doi: 10.3389\/fped.2019.00551","DOI":"10.3389\/fped.2019.00551"},{"key":"60411","doi-asserted-by":"crossref","unstructured":"26. Anvari S, Ruffner MA, Nowak-Wegrzyn A. Current and future perspectives on the consensus guideline for food protein-induced enterocolitis syndrome (FPIES). 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Food protein\u2013induced enterocolitis syndrome in Australia: A population-based study, 2012-2014. J Allergy Clin Immunol 2017; 140 (5): 1323-30. doi: 10.1016\/j.jaci.2017.03.027","DOI":"10.1016\/j.jaci.2017.03.027"},{"key":"60415","doi-asserted-by":"crossref","unstructured":"30. Ocak M, Akarsu A, Sahiner UM, et al. Food protein-induced enterocolitis syndrome: Current practices in oral food challenge. Allergy Asthma Proc 2021; 42 (4): 343-349. doi: 10.2500\/app.2021.42.210042","DOI":"10.2500\/aap.2021.42.210042"},{"key":"60416","doi-asserted-by":"crossref","unstructured":"31. Akashi M, Kaburagi S, Kajita N, et al. Heterogeneity of food protein-induced enterocolitis syndrome (FPIES). Allergol Int 2024; 73 (2): 196-205. doi: 10.1016\/j.alit2024.02.001","DOI":"10.1016\/j.alit.2024.02.001"},{"key":"60417","doi-asserted-by":"crossref","unstructured":"32. Wang KY, Lee J, Cianferoni A, et al. Food Protein\u2013Induced Enterocolitis Syndrome Food Challenges: Experience from a Large Referral Center. J Allergy Clin Immunol Pract 2019; 7 (2): 444-450. doi: 10.1016\/j.jaip.2018.09.009","DOI":"10.1016\/j.jaip.2018.09.009"},{"key":"60418","doi-asserted-by":"crossref","unstructured":"33. Akashi M, Hayashi D, Kajita N, et al. Recent dramatic increase in patients with food protein\u2013induced enterocolitis syndrome (FPIES) provoked by hen\u2019s egg in Japan. J Allergy Clin Immunol Pract 2022; 10 (4): 1110-1112.e2. doi: 10.1016\/j.jaip.2021.11.007","DOI":"10.1016\/j.jaip.2021.11.007"},{"key":"60419","doi-asserted-by":"crossref","unstructured":"34. Nowak-Wegrzyn A, Warren CM, Brown-Whitehorn T, et al. Food protein\u2013 induced enterocolitis syndrome in the US population\u2013based study. J Allergy Clinical Immunol 2019; 144 (4): 1128-1130. doi: 10.1016\/j.jaci.2019.06.032","DOI":"10.1016\/j.jaci.2019.06.032"},{"key":"60420","doi-asserted-by":"crossref","unstructured":"35. Gonz\u00e1lez-Delgado P, Muriel J, Jim\u00e9nez T, et al. Food Protein\u2013Induced Enterocolitis Syndrome in Adulthood: Clinical characteristics, prognosis, and risk factors. J Allergy Clin Immunol Pract 2022; 10 (9): 2397-2403. doi: 10.1016\/j.jaip.2022.05.006","DOI":"10.1016\/j.jaip.2022.05.006"},{"key":"60421","doi-asserted-by":"crossref","unstructured":"36. Lange L, Gernert S, Berger M, et al. Different patterns of foods triggering FPIES in Germany. J Allergy Clin Immunol Pract 2022; 10 (4): 1063-1069. doi: 10.1016\/j.jaip.2021.11.033","DOI":"10.1016\/j.jaip.2021.11.033"},{"key":"60422","doi-asserted-by":"crossref","unstructured":"37. Bulsa K, Standowicz M, Bary\u0142a-Pankiewicz E, et al. Chronic Milk-dependent food protein-induced enterocolitis syndrome in children from West Pomerania region. Nutrients 2021; 13 (11): 4137. doi: 10.3390\/nu13114137","DOI":"10.3390\/nu13114137"},{"key":"60423","doi-asserted-by":"crossref","unstructured":"38. Kim YI, Joo JY, Jung YH, et al. Differentiation of food protein-induced enterocolitis syndrome misleading to necrotizing enterocolitis. Ann Allergy Asthma Immunol 2022; 128 (2): 193-198. doi: 10.1016\/j.anai.2021.09.024","DOI":"10.1016\/j.anai.2021.09.024"},{"key":"60424","doi-asserted-by":"crossref","unstructured":"39. Lenfestey MW, de la Cruz D, Neu J. Food Protein\u2013Induced Enterocolitis Instead of Necrotizing Enterocolitis? A Neonatal Intensive Care Unit Case Series. J Pediatr 2018; 200: 270-273. doi: 10.1016\/j.jpeds.2018.04.048","DOI":"10.1016\/j.jpeds.2018.04.048"},{"key":"60425","doi-asserted-by":"crossref","unstructured":"40. Suzuki H, Morisaki N, Nagashima S, et al. A nationwide survey of non-IgE- mediated gastrointestinal food allergies in neonates and infants. Allergol Int 2024; 73 (2): 264-274. doi: 10.1016\/j.alit.2023.10.003","DOI":"10.1016\/j.alit.2023.10.003"},{"key":"60426","doi-asserted-by":"crossref","unstructured":"41. Suzuki H, Tsutsumi Y, Morita H, et al. 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