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Common food allergens

Food Allergy

Non-IgE-mediated Allergies

Douglas H. Jones, MD, FAAAAI, FACAAI 
Reviewed on June 20, 2024
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Diagnostic Approaches

Non-IgE-mediated allergies typically manifest with a delayed onset of symptoms, primarily affecting the gastrointestinal tract, although they may also involve the skin or lungs. Depending on which non-IgE-mediated food allergy is present, these symptoms may include nausea, vomiting, diarrhea, abdominal pain and bloody stools, further prompting dehydration, weight-loss, long-term malabsorption, failure to thrive and lethargy.

While IgE-mediated allergies dominate the clinical landscape and are well-understood, non-IgE-mediated allergies pose diagnostic and management challenges due to the variability in symptom manifestation, similarity between different medical conditions and absence of a definitive diagnostic test or biomarker. Some non-IgE-mediated allergies show typical histological changes that can confirm the diagnosis; however, obtaining samples through endoscopy can be challenging, especially in young children who need general anesthesia for the procedure.…

Diagnostic Approaches

Non-IgE-mediated allergies typically manifest with a delayed onset of symptoms, primarily affecting the gastrointestinal tract, although they may also involve the skin or lungs. Depending on which non-IgE-mediated food allergy is present, these symptoms may include nausea, vomiting, diarrhea, abdominal pain and bloody stools, further prompting dehydration, weight-loss, long-term malabsorption, failure to thrive and lethargy.

While IgE-mediated allergies dominate the clinical landscape and are well-understood, non-IgE-mediated allergies pose diagnostic and management challenges due to the variability in symptom manifestation, similarity between different medical conditions and absence of a definitive diagnostic test or biomarker. Some non-IgE-mediated allergies show typical histological changes that can confirm the diagnosis; however, obtaining samples through endoscopy can be challenging, especially in young children who need general anesthesia for the procedure. The diagnosis of acute Food Protein–Induced Enterocolitis Syndrome (FPIES) often relies solely on clinical history and identification of symptoms consistent with the diagnostic criteria for acute FPIES. On the other hand, chronic FPIES requires additional testing to confirm the diagnosis. The most commonly used techniques for the diagnosis of non-IgE-mediated allergies are elimination diets and oral food challenge (OFC).

References

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  • Chehade M, Jones SM, Pesek RD, et al. Phenotypic Characterization of Eosinophilic Esophagitis in a Large Multicenter Patient Population from the Consortium for Food Allergy Research. J Allergy Clin Immunol: In Practice. 2018;6(5):1534-1544.e5.
  • Connors L, O’Keefe A, Rosenfield L, Kim H. Non-IgE-mediated food hypersensitivity. Allergy Asthma Clin Immunol. 2018;14(S2):56.
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  • Iyngkaran N, Robinson MJ, Prathap K, Sumithran E, Yadav M. Cows’ milk protein-sensitive enteropathy. Combined clinical and histological criteria for diagnosis. Arch Dis Child. 1978;53(1):20-26.
  • Katzka 2020 Katzka DA. Eosinophilic Esophagitis. Ann Intern Med. 2020;172(9):ITC65-ITC80.
  • Kuitunen P, Visakorpi JK, Savilahti E, Pelkonen P. Malabsorption syndrome with cow’s milk intolerance. Clinical findings and course in 54 cases. Arch Dis Child. 1975;50(5):351-356.
  • Mathew M, Leeds S, Nowak-Węgrzyn A. Recent Update in Food Protein-Induced Enterocolitis Syndrome: Pathophysiology, Diagnosis, and Management. Allergy Asthma Immunol Res. 2022;14(6):587-603. doi:10.4168/aair.2022.14.6.587
  • Mehr S, Kakakios A, Frith K, Kemp AS. Food Protein-Induced Enterocolitis Syndrome: 16-Year Experience. Pediatrics. 2009;123(3):e459-e464
  • Mulé A, Prattico C, Al Ali A, et al. Diagnostic and Management Strategies of Food Protein-Induced Enterocolitis Syndrome: Current Perspectives. Pediatric Health Med Ther. 2023;14:337-345.
  • Nowak-Węgrzyn A, Chehade M, Groetch ME, et al. International consensus guidelines for the diagnosis and management of food protein–induced enterocolitis syndrome: Executive summary—Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2017;139(4):1111-1126.e4.
  • Nowak-Węgrzyn A, Katz Y, Mehr SS, Koletzko S. Non–IgE-mediated gastrointestinal food allergy. J Allergy Clin Immunol. 2015;135(5):1114-1124.
  • Zhang S, Sicherer S, Berin MC, Agyemang A. Pathophysiology of Non-IgE-Mediated Food Allergy. ImmunoTargets Ther. 2021;10:431-446.
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