Pathophysiology of Non-IgE-Mediated Food Allergy

Abstract

Non-IgE-mediated food allergies are a group of disorders characterized by subacute or chronic inflammatory processes in the gut. Unlike IgE mediated food allergies that may result in multi-organ system anaphylaxis, the non-IgE mediated food allergies primarily affect the gastrointestinal tract. This review outlines the clinical manifestations, epidemiology, pathophysiology, and management of non-IgE-mediated food allergies. An updated literature search of selected non-IgE-mediated food allergies was conducted for this review using PubMed database to the current year (2021). Reviewed disorders include food protein-induced enterocolitis syndrome (FPIES), food-protein enteropathy (FPE), food protein-induced allergic proctocolitis (FPIAP), and eosinophilic gastrointestinal disorders (EGIDs) such as eosinophilic esophagitis (EoE). While extensive gains have been made in understanding FPIES, FPIAP, FPE, and EoE, more information is needed on the pathophysiology of these food allergies. Similarities among them include involvement of innate immunity, T-lymphocyte processes, alteration of the intestinal lumen at the cellular level with the appearance of inflammatory cells and associated histologic changes, and specific cytokine profiles suggesting food-specific, T-cell, and immune-mediated responses. While FPIES and FPIAP typically resolve in early childhood, EGIDs typically do not. Emerging new therapies for EoE offer promise of additional treatment options. Further studies identifying the immunopathogenesis, associated biomarkers, and mechanisms of tolerance are needed to inform prevention, diagnosis and management.

Keywords:

• food protein-induced enterocolitis syndrome
• FPIES
• food protein-induced enteropathy
• FPE
• food protein-induced allergic proctocolitis
• FPIAP
• eosinophilic gastrointestinal disorders
• EGIDs
• eosinophilic esophagitis
• EoE
• pathophysiology

Abbreviations

FPIES, food protein-induced enterocolitis; FPE, food-protein enteropathy; FPIAP, food protein-induced allergic proctocolitis; EGIDs, eosinophilic gastrointestinal disorders; EoE, eosinophilic esophagitis; EG, eosinophilic gastritis; EGE, eosinophilic gastroenteritis; EC, eosinophilic colitis; CM, cow’s milk; FTT, failure to thrive; OFC, oral food challenge.

Disclosures

Scott Sicherer – Reports royalty payments from UpToDate and from Johns Hopkins University Press; grants to his institution from the National Institute of Allergy and Infectious Diseases, from Food Allergy Research and Education; and personal fees from the American Academy of Allergy, Asthma and Immunology, outside of the submitted work.

M Cecilia Berin – Reports grants to her institution from the National Institute of Allergy and Infectious Diseases, outside of the submitted work.

The authors report no other conflicts of interest in this work.

Additional information

Funding

There is no funding to report.