title: Using a gluten oral food challenge protocol to improve diagnosis of wheat-dependent exercise-induced anaphylaxis.
abstract: BACKGROUND
  Oral wheat plus cofactors challenge tests in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) produce unreliable results.
  
  
  OBJECTIVE
  We sought to confirm WDEIA diagnosis by using oral gluten flour plus cofactors challenge, to determine the amount of gluten required to elicit symptoms, and to correlate these results with plasma gliadin levels, gastrointestinal permeability, and allergologic parameters.
  
  
  METHODS
  Sixteen of 34 patients with a history of WDEIA and ω5-gliadin IgE underwent prospective oral challenge tests with gluten with or without cofactors until objective symptoms developed. Gluten reaction threshold levels, plasma gliadin concentrations, gastrointestinal permeability, sensitivities and specificities for skin prick tests, and specific IgE levels were ascertained in patients and 38 control subjects.
  
  
  RESULTS
  In 16 of 16 patients (8 female and 8 male patients; age, 23-76 years), WDEIA was confirmed by challenges with gluten alone (n = 4) or gluten plus cofactors (n = 12), including 4 patients with previous negative wheat challenge results. Higher gluten doses or acetylsalicylic acid (ASA) plus alcohol instead of physical exercise were cofactors in 2 retested patients. The cofactors ASA plus alcohol and exercise increased plasma gliadin levels (P < .03). Positive challenge results developed after a variable period of time at peak or when the plateau plasma gliadin level was attained. Positive plasma gliadin threshold levels differed by greater than 100-fold and ranged from 15 to 2111 pg/mL (median, 628 pg/mL). The clinical history, IgE gliadin level, and baseline gastrointestinal level were not predictive of the outcomes of the challenge tests. The challenge-confirmed sensitivity and specificity of gluten skin prick tests was 100% and 96%, respectively.
  
  
  CONCLUSIONS
  Oral challenge with gluten alone or along with ASA and alcohol is a sensitive and specific test for the diagnosis of WDEIA. Exercise is not an essential trigger for the onset of symptoms in patients with WDEIA.
authors.affiliation: Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany. Electronic address: knut.brockow@lrz.tu-muenchen.de.
authors.forename: Knut
authors.initials: K
authors.lastname: Brockow
authors.affiliation: Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kneissl
authors.affiliation: Department of Gastroenterology and Hepatology, Section of Nutritional Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Luzia
authors.initials: L
authors.lastname: Valentini
authors.affiliation: Department for Prevention, Rehabilitation and Sports Medicine, Technische Universität München, Munich, Germany.
authors.forename: Otto
authors.initials: O
authors.lastname: Zelger
authors.affiliation: Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany.
authors.forename: Martine
authors.initials: M
authors.lastname: Grosber
authors.affiliation: Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kugler
authors.affiliation: Department of Gastroenterology and Hepatology, Section of Nutritional Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Werich
authors.affiliation: Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Darsow
authors.affiliation: Department of Pathophysiology and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsuo
authors.affiliation: Department of Dermatology, Faculty of Medicine, Shimane University, Izumo, Japan.
authors.forename: Eishin
authors.initials: E
authors.lastname: Morita
authors.affiliation: Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Ring
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology; D000707:Anaphylaxis / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology*; D052179:Antigens, Plant / Q000276:immunology; D015444:Exercise; D005260:Female; D005903:Gliadin / Q000097:blood / Q000276:immunology; D005983:Glutens / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010539:Permeability; D012720:Severity of Illness Index; D012882:Skin Tests; D021182:Wheat Hypersensitivity / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology*; D055815:Young Adult
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D007073:Immunoglobulin E; D005983:Glutens; D005903:Gliadin
keywords: Wheat-dependent exercise-induced anaphylaxis; anaphylaxis; cofactors; gluten; omega-5-gliadin; oral challenge test; plasma gliadin levels; threshold levels