Food-Dependent Exercise-Induced Wheals/Angioedema, Anaphylaxis, or Both: A Systematic Review of Phenotypes

Abstract

Background: Food-dependent exercise-induced allergic reactions can manifest with wheals, angioedema, and anaphylaxis, alone or in combination. Objective: To systematically review the clinical manifestation, culprit foods and exercise, augmenting factors, comorbidities, and treatment options of each phenotype. Methods: Using predefined search terms, we assessed and analyzed the relevant literature until June 2021. Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations were applied to this systematic review. Results: A total of 231 studies with 722 patients were included. The most common phenotype was anaphylaxis with wheals, angioedema, or both, reported in 80% of patients. This was associated with a higher number of anaphylactic episodes, augmenting factors, and use of on-demand antihistamine compared with the least common phenotype, anaphylaxis without wheals or angioedema, reported in 4% of patients. Anaphylaxis with wheals/angioedema was also associated with distinct characteristics compared with stand-alone wheals, angioedema, or both, in 17% of patients. Patients with anaphylaxis were older at the time of disease onset, less often had a history of atopy, showed more positive results in response to food and exercise provocation tests, had a more restricted spectrum of culprit foods, and more often used on-demand epinephrine. Conclusions: The three phenotypes of allergic reactions to food and exercise differ in clinical characteristics, triggers, and response to treatment. Knowledge of these differences may help with patient education and counseling as well as disease management.