Wheat Allergy: Clinical Phenotypes, Diagnostic Approaches, and Management Strategies

Wheat triggers a broad spectrum of allergic diseases, with prevalence varying across regions. In adults, it is the leading cause of food-induced anaphylaxis, most often as wheat-dependent exercise-induced anaphylaxis (WDEIA), while occupational exposure causes baker's asthma. In children, wheat allergy manifests as immediate-type reactions, including anaphylaxis, and contributes to atopic dermatitis. Recently, wheat is known as one of key triggers of eosinophilic esophagitis across all age groups. Wheat proteins are classified into water/salt-soluble and -insoluble fractions, with distinct physiochemical profiles. Among insoluble proteins, ω-5 gliadin and high- and low-molecular weight glutenins are well recognized as major allergens in WDEIA. Conversely, both gluten proteins and water-salt soluble allergens, such as α-amylase inhibitors and lipid-transfer proteins, are key allergens in pediatric wheat allergy and baker's asthma. Accurate diagnosis requires component-resolved diagnostics (CRD), given the complex physicochemical properties of wheat proteins. However, conventional skin prick testing and some multiplex specific immunoglobulin E assays lack full CRD integration, likely underestimating true prevalence. Management primarily relies on avoidance, but strict elimination is difficult due to wheat's ubiquity. In WDEIA, cofactors such as exercise, alcohol, or nonsteroidal anti-inflammatory drugs commonly precipitate reactions, with provoking doses varying widely, necessitating individualized strategies. Oral immunotherapy has been attempted for pediatric wheat allergy but demonstrated lower efficacy than for other foods, underscoring the need for patient-tailored strategies. Baker's asthma management focuses on work-place control, personal respiratory protective equipment, and pharmacotherapy. Overall, improved CRD-based diagnostics and novel therapeutic approaches are needed to enhance care for this diverse spectrum of wheat-related allergic diseases.