Food-Dependent Exercise-Induced Wheals, Angioedema, and Anaphylaxis: A Systematic Review

Background: Food-dependent exercise-induced wheals, angioedema, and anaphylaxis remain insufficiently characterized. Objective: We systematically reviewed the literature on clinical manifestations, laboratory investigations, culprit foods, triggering exercise, comorbidities, and treatment outcomes. Methods: Using predefined search terms and Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) recommendations, we searched 3 electronic databases to identify relevant literature published before July 2021. Results: Of 722 patients (median age 25 years; 55.4% male) from 231 studies (43 cohort studies, 15 cases series, and 173 case reports), 79.6% and 3.7% had anaphylaxis with and without wheals and/or angioedema, respectively. The remaining 16.6% had wheals and/or angioedema without anaphylaxis. The duration from eating to exercising and from exercising to symptom onset ranged from 5 minutes to 6 hours (median 1 hour) and from 5 minutes to 5 hours (median 30 minutes), respectively, and virtually all patients exercised within 4 hours after eating and developed symptoms within 1 hour after exercising. Wheat was the most common culprit food. Running was the most common trigger exercise. Most patients were atopic, and 1 in 3 had a history of urticaria. Aspirin and wheat-based products were the most frequent augmenting factors. On-demand antihistamines, corticosteroids, and epinephrine were commonly used and reported to be effective. Patients who stopped eating culprit foods before exercise no longer developed food-dependent exercise-induced allergic reactions. Conclusions: Food-dependent exercise-induced allergic reactions are heterogeneous in their clinical manifestations, triggers, and response to treatment. Patients benefit from avoidance of culprit foods before exercise, which highlights the need for allergological diagnostic workup and guidance.