Exercise can be replaced in food-dependent exercise-induced anaphylaxis


Published Online: September 27, 2014

Many patients react with anaphylaxis only if in addition to allergenic foods further specific cofactors are present. Wheat-dependent exercise-induced anaphylaxis (WDEIA) is the best studied model of “cofactor-induced” anaphylaxis (summation anaphylaxis). However, oral wheat plus cofactors challenge tests in wheat dependent exercise-induced anaphylaxis (WDEIA) have produced unreliable results. Now, in a study recently published in The Journal of Allergy and Clinical Immunology, K. Brockow and colleagues present a provocation protocol for WDEIA and show that utilizing gluten alone or in combination with other cofactors is a sensitive and specific test for the diagnosis of WDEIA and that exercise is not an obligatory trigger factor for this disease.

The authors of this study analyzed 34 patients with a clear history of WDEIA and presence of IgE to the wheat allergen ω5-gliadin. Sixteen patients underwent prospective oral challenge tests with gluten +/- cofactors until objective symptoms developed. Gluten reaction threshold levels, plasma gliadin concentrations, gastrointestinal permeability, the sensitivity and specificity for skin prick test and specific IgE were ascertained in patients and in 38 controls.

With this design the authors were able to confirm WDEIA in all 16 challenged patients (100%) utilizing gluten alone or gluten plus cofactors, including four patients with previous negative wheat challenges. Higher gluten doses or acetylsalicylic acid (ASA) + alcohol substituted for physical exercise as cofactors in the patients. Cofactors ASA with alcohol or exercise increased plasma gluten gliadin levels (p<0.03). Positive challenge always developed at peak or plateau plasma gliadin levels. Symptom-eliciting plasma gliadin thresholds differed by >100 fold from patient to patient. Unfortunately, clinical data was not predictive of the outcome of the challenge test. For screening, challenge-confirmed sensitivity and specificity of skin prick test with gluten were high: 100% and 96%, respectively.

This study provides proof of concept that skin prick test with gluten flour is helpful for screening and that oral challenge with high doses of gluten alone or together with augmentation factors ASA and alcohol is a sensitive and specific test for the diagnosis of “WDEIA”. Despite the term “exercise” being in the name of the acronym, exercise is not an essential trigger in “WDEIA”. Thus, augmentation factor-triggered food allergy (AFTFA) may be a more appropriate term for this under-diagnosed disease entity.


The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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