Exercise Lowers Threshold and Increases Severity, but Wheat-Dependent, Exercise-Induced Anaphylaxis Can Be Elicited at Rest

Background: Wheat-dependent, exercise-induced anaphylaxis (WDEIA) is a severe form of allergy in which exercise is being considered as mandatory. The diagnosis is often complex and the clinical reproducibility low. Objective: The aims of this study were to establish a standardized challenge method for the diagnosis of WDEIA and to investigate whether exercise is an essential trigger factor or alternatively an augmentation factor able to lower threshold and increase severity. Methods: We investigated 71 patients (age, 18.6-73.7 years) with a case history of WDEIA. Skin prick test (SPT) and measurement of specific IgE (sIgE) were followed by an oral food challenge with gluten at rest and in combination with treadmill exercise. Results: A clinical reaction was elicited in 47 of 71 (66%), and in 26 of these (37%) the reaction could be elicited at rest. The median dose required at rest was 48 g (8-80 g) and in combination with exercise 24 g (4-80 g). Severity was significantly higher with exercise (2.3) than at rest (1.1) using Sampson severity score. In the challenge, SPT was positive to wheat in 93.6% (44 of 47) and to gluten in 95.7% (45 of 47). sIgE to wheat, gliadin, and omega-5 gliadin was present in 78.7% (37 of 47), 76.5% (36 of 47), and 91.4% (43 of 47) of the patients. Receiver operating characteristic–curve analysis for sIgE to omega-5 gliadin, a component of the gluten fraction and the major allergen in WDEIA, showed best sensitivity (91%) and specificity (92%) when gluten was combined with exercise. Conclusions: A challenge test with gluten at rest and combined exercise is a safe confirmatory test for WDEIA. A reaction can be elicited at rest (without exercise), but exercise is able to lower the threshold and increase the severity.