WDEIA case series: Do unique clinical presentations suggest mechanistic differences?

Background: Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a rare but potentially severe delayed-onset food allergy occurring exclusively when wheat ingestion is accompanied by augmenting cofactors. Objective: This study aimed to characterize WDEIA, understand its varied clinical presentations, and propose mechanistic differences from classic food allergy. Methods: A retrospective chart review of patients diagnosed with WDEIA between 2017 and 2024 was performed in accordance with the Declaration of Helsinki. The clinical presentation, diagnosis, management strategies, and clinical course were analyzed. Results: The cohort consisted of 7 patients, aged 21 to 46 years (6 male and 1 female). All patients had multiple episodes of severe/Brown grade III anaphylaxis before presentation. As expected with WDEIA, all patients tolerated exercise/other cofactors and wheat independently, although they all reported rare, mild intermittent urticaria that was correlated with wheat ingestion and resolved with antihistamines. Predominant cardiovascular symptoms (including loss of consciousness) with minimal respiratory involvement was noted in all patients. The severity of the anaphylactic shock appeared consistent across all patients regardless of the intensity of exercise, and amongst the different cofactors including alcohol, nonsteroidal anti-inflammatory drugs, and menstruation. Exercise was the most common cofactor in 7 of 7 patients. No correlation of omega-5 gliadin, wheat, or gluten IgE levels with anaphylaxis severity was noted. In all patients, a gluten-free diet prevented both intermittent urticaria and anaphylaxis, whereas separation of gluten from exercise and other cofactors prevented anaphylaxis only, and not intermittent urticaria in those patients. Conclusion: The study confirms the varied presentations of WDEIA, which are distinct from those of classic food allergies, suggesting a different mechanism. The differential effectiveness of the 2 preventive strategies was examined, with a gluten-free diet being the most effective in preventing anaphylaxis and intermittent urticaria.