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.

Allergy, Anaphylaxis, and Nonallergic Hypersensitivity: IgE, Mast Cells, and Beyond

“…Besides immediate hypersensitivity responses induced by mast cells, basophils, and other cells, similar symptoms may also be due to other inflammatory processes. For example, various types of food allergies such as eosinophilic esophagitis or eosinophilic gastrointestinal disorders are characterized by esophageal/intestinal dysfunction and hypersensitivities with a predominant infiltration of eosinophils [ 132 , 133 ]. The pathophysiology remains poorly understood and multifactorial and is thought to involve type 2 immunity fostered by a combination of genetic, host, and environmental factors [ 133 , 134 , 135 ].…”

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - III - Cow's milk allergens and mechanisms triggering immune activation

“…24 The symptoms, both acute (emesis, diarrhea, lethargy, pallor) and chronic (intermittent, progressive vomiting and diarrhea), are triggered in an antigen-specific manner which can be exploited in diagnosis using food challenges. 104 In the absence of the causative food the symptoms resolve. Thus, fast and correct diagnosis is important for optimal management strategies to allow thriving of the infant.…”

Eosinophilic Esophagitis due to Aeroallergens: A Systematic Review and Update

“…GERD, FA, and alterations of the epithelial barrier and possibly of the microbiota combine to allow FA or AAs to penetrate the epithelium and activate receptors and inflammatory cells, including eosinophils. The latter secrete toxic granules and cytokines, inducing chronic inflammation, tissue damage, and fibrosis [59,60].…”