Wheat-Dependent Cofactor-Augmented Anaphylaxis: A Prospective Study of Exercise, Aspirin, and Alcohol Efficacy as Cofactors

BACKGROUND: Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a severe and potentially life-threatening allergy caused by wheat ingestion and most commonly in combination with exercise. OBJECTIVE: To investigate the role and impact of different cofactors (exercise, aspirin, and alcohol) in patients with WDEIA. METHODS: We studied 25 adult patients with WDEIA. Diagnostic workup included specific IgE to omega-5 gliadin and skin prick test with wheat flour and gluten. Titrated oral challenge was performed with gluten at rest, combined with treadmill exercise, aspirin, alcohol, or a combination of exercise and aspirin. RESULTS: A positive challenge to gluten was found at rest (without cofactors) in 48% (12 of 25), with exercise in 92% (23 of 25), with aspirin in 84% (21 of 25), with alcohol in 56% (9 of 19), and with a combination of exercise and aspirin in 82% (18 of 22) of the patients. With exercise as a cofactor, the median threshold was 24 g (range, 4.8-80 g), with aspirin 8 g (range, 2.4-80 g), and with alcohol 28 g (range, 0-45 g). The combination of 2 cofactors (exercise and aspirin) resulted in a median threshold of 4.3 g (range, 1.1-48 g). The threshold for the clinical reaction was lowered by 63%, 83%, 36%, and 87%, respectively, compared with at rest. The mean severity grade (scale 0-5) according to the Sampson severity score at rest was 0.8 (range, 0-2), and when combined with exercise 2.1 (range, 0-5), with aspirin 1.9 (range, 0-5), with alcohol 0.8 (range, 0-2), and with the combination of exercise and aspirin 1.5 (range, 0-2). CONCLUSION: Our results demonstrate that exercise and aspirin augment clinical reactions in WDEIA by lowering the threshold and increase the severity of the allergic reaction, whereas alcohol gives ambiguous results. Furthermore, a combination of 2 cofactors (exercise and aspirin) increases the risk of reactions. (C) 2019 American Academy of Allergy, Asthma & Immunology