A clinical reaction can be elicited without cofactors in Wheat dependent exercise induced anaphylaxis

Background: Wheat-Dependent, Exercise- Induced Anaphylaxis (WDEIA) is believed to be a distinct form of wheat allergy characteristically induced by exercise as recently demonstrated by Brockow et al (2014). We investigated whether exercise is a mandatory cofactor for elicitation of a reaction. Method: We prospectively investigated 19 patients (age 20.2 - 71.0 years) with a convincing case-history of WDEIA. All were examined with detailed case history, specific IgE (s-IgE), (Thermo Fischer, Uppsala, Sweden), Skin Prick Test (SPT), (ALKAbello, Copenhagen, Denmark and prick to prick with foods), prior to a challenge with commercially available gluten at rest and in combination with physical exercise. Patients were administered gluten in increasing doses to a maximum of 80 gram cumulated with 60 min interval. When objective signs occurred, further challenge was terminated and the threshold noted. At the second session (> 1 week apart) standardised physical exercise on a treadmill was interspersed between the each dose administered. Seventeen out of 19 patients had positive s-IgE to omega-5 gliadin (mean 8.2 IU/L [<0.35-33.7]) and 14 of 19 positive s-IgE to wheat (mean 1.4 IU/L [<0.35-5.2]). SPT to wheat was positive in 18 of 19 patients (mean 5.5 mm [0-9.5]) and gluten 17 of 19 patients (mean 5.3 mm [0-11.5]). Results: Twelve of 19 patients reacted to oral challenge with gluten at rest with thresholds between 8 and 80 gram cumulated. All 19 patients reacted to oral challenge with gluten together with physical exercise with thresholds ranging from 3 to 48 gram cumulated. All patients demonstrated a lower threshold during exercise than at rest (mean threshold at rest [n=12,] 56.4 gram, compared to 16.3 gram during exercise, P <0.05) and the seven negative patients at rest became positive during exercise. Severity Score according to Sampson (2003) was increased during exercise in 12 patients, despite elicited at a lower challenge dose. Conclusion: Physical exercise is not a mandatory prerequisite for elicitation of an allergic reaction in patients with WDEIA but rather an important cofactor lowering clinical threshold and increasing severity.