Adverse Food Reactions from Mechanisms to Management: A PRISMA Systematic Review of IgE-Mediated Allergies, Autoimmune Enteropathies, and Non-Immune Intolerances

Abstract

Background: Adverse reactions to food represent one of the most prevalent and clinically consequential issues in modern medicine. They encompass two fundamentally distinct categories: food allergy, an immune-mediated hypersensitivity, and food intolerance, driven by non-immune enzymatic, pharmacological, or metabolic mechanisms. As the global burden of both conditions continues to rise, driven primarily by environmental and lifestyle factors, a comprehensive and evidence-based synthesis of the literature is urgently needed.
Objectives: This systematic review aims to identify and synthesize the full spectrum of foods known to cause allergy or intolerance, characterize their underlying immunological and biochemical mechanisms, summarize current diagnostic criteria, and appraise the evidence base for management strategies.
Methods: A comprehensive search of PubMed/MEDLINE, Embase, Scopus, and Cochrane Library was conducted. Studies from January 2015 to May 2026 were prioritized, with seminal earlier publications included where essential. Search terms included: food allergy, food hypersensitivity, food intolerance, IgE-mediated, celiac disease, lactose intolerance, FODMAP, anaphylaxis, allergen, combined with specific food categories. PRISMA 2020 guidelines were followed throughout.
Results: Food allergy affects approximately 8% of children and 10% of adults globally, with the prevalence rising in developed nations. Nine major food allergens account for over 90% of reactions: peanut, tree nuts, milk, egg, wheat, soy, fish, shellfish, and sesame. Food intolerances, including lactose intolerance (affecting ~68% of the world population), non-celiac gluten sensitivity, fructose malabsorption, FODMAP sensitivity, and histamine intolerance, are distinct from true allergy in their non-immune mechanisms. Celiac disease, a gluten-triggered autoimmune enteropathy, occupies a unique intermediate category. Current diagnostic gold standards include oral food challenge (OFC) for allergy and hydrogen breath testing for carbohydrate intolerances.
Conclusions: A clear mechanistic distinction between food allergy and intolerance is essential for accurate diagnosis and effective management. Patient morbidity—physical, psychological, and nutritional—is substantial. Unvalidated commercial tests contribute to unnecessary dietary restriction. Evidence-based diagnosis and multidisciplinary management remain the cornerstone of care.