WP 2.2 - Diagnosis of Food Dependent, Exercise Induced Anaphylaxis (FDEIA)

Background:

Wheat-Dependent, Exercise-Induced Anaphylasis (WDEIA) patients tolerate both intake of the offending food (wheat) and can perform high intensity exercise individually, but combining wheat and exercise can be fatal, even during low intensity workout. The pathogenesis of WDEIA is only vaguely understood, and the influence of food matrix and amount of offending food, exercise intensity, the kinetics and mechanisms, as well as facilitating factors such as alcohol and ASA need to be addressed .

 

Hypothesis:

WDEIA occur in patients sensitized to specific wheat proteins (gliadins). Five hypotheses for possible mechanisms have been proposed;  two of them are considered more reliable: 1) Exercise induces a change the gut permeability, thereby increasing the uptake of wheat proteins. 2) Exercise facilitates a redistribution of blood and thereby allergen to target organs/cells with higher allergen affinity. It is, however, unclear whether only a single mechanism is involved or multiple phenotypes of this disorder exist.

 

Methods:

This study contains of 6 subparts, incl. five parts in collaboration within the EU project, IFAAM (SWEAT protocol) – see detailed flow-chart online.

I) A standardization of challenge material with focus on gliadin/protein content and palatability.  In vitro allergen standardization with basophil histamine release.

II) Standardization of challenge/exercise including extrinsic and environmental factors. Measurement of temperature (skin + core) blood lactate and heart rate.

III) Reevaluation of the standard procedure found in part I and II to standardize challenge algorithm.

IV) Reevaluation of all existing + newly referred patients using the new algorithm from part III).

V) Influence of triggers and facilitators such as alcohol and Aspirin

VI) Absorption and mechanistic  studies using isotope-marked gliadin-proteins and whole-body in-vivo image scans.

 

 

Update 2016

Patterns of suspected wheat-related allergy: a retrospective single-centre case note review in 156 patients

AUTHORS:

Morten J. Christensen, Esben Eller, Carsten Bindslev-Jensen.

Odense Research Center for Anaphylaxis (ORCA), Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark.

 

BACKGROUND:

Allergy to wheat can present clinically in different forms: Sensitization to ingested wheat via the gastrointestinal tract can cause traditional food allergy or in combination with exercise, Wheat-Dependent Exercise-Induced Anaphylaxis (WDEIA). Sensitization to inhaled wheat flour may lead to occupational rhinitis and/or asthma.

 

METHODS:

We retrospectively reviewed the case notes of 156 patients (age 0.7 - 73.3 years) with a case history of wheat allergy. The population was divided into three groups, 1: Wheat allergy elicited by ingestion, 2: By inhalation and 3: WDEIA. All patients were examined with detailed case history, specific IgE (sIgE), Skin Prick Test (SPT) and wheat challenge (nasal or oral?±?exercise). Details of the case history were extracted from the patients´ case records.

 

RESULTS:

Group 1: Twenty one of 95 patients were challenge positive (15 children, 6 adults). All children had atopic dermatitis, and most (13/15) outgrew their wheat allergy. Most children (13/15) had other food allergies. Challenge positive patients showed significantly higher levels of sIgE to wheat and significantly more were SPT positive than challenge negative. Group 2: Eleven out of 13 adults with occupational asthma or rhinitis were challenge positive. None outgrew their allergy. Seven had positive sIgE and 10 had positive SPT to wheat. Group 3: Ten of 48 (adolescent/adults) were positive when challenged during exercise. Challenge positive patients showed significantly higher levels of sIgE to ?-5-gliadin. The natural course is presently unknown.

 

CONCLUSION:

Wheat allergy can manifest in different disease entities, rendering a detailed case history and challenge mandatory. Patient age, occupation, concomitant allergies (food or inhalant) and atopic dermatitis are important factors for evaluation.

 

 

Wheat-Dependent, Exercise-Induced Anaphylaxis Can Be Elicited Without Exercise

 

AUTHORS

Morten J. Christensen1, Esben Eller1, Charlotte G. Mortz1, Knut Brockow2, Carsten Bindslev-Jensen1

From 1 Department of Dermatology and Allergy Centre, Odense Research Center for Anaphylaxis

(ORCA), Odense University Hospital, 5000 Odense C, Denmark and 2 Department of Dermatology and Allergy Biederstein, Klinikum rechts der Isar, Technische Universität München, Munich.

 

BACKGROUND

The diagnosis of Wheat-Dependent, Exercise-Induced Anaphylaxis (WDEIA) is challenging and believed to be a distinct form of wheat allergy characteristically induced by exercise. We demonstrate that and exercise is merely an augmentation factor able to lower threshold.

 

METHODS

We prospectively investigated 38 patients (age 20.2 - 71.4 years) with a convincing case-history of WDEIA. All were examined with detailed case history, specific IgE (s-IgE), (ThermoFischer, Uppsala, Sweden), Skin Prick Test (SPT), (ALK-Abello, Copenhagen, Denmark), prior to a challenge with gluten (Jean Püzt Product, Cologne, Germany) at rest and combined with exercise on a treadmill.

 

RESULTS

WDEIA was confirmed by challenge in 38 of 38 patients (female=16, male=22) either at rest without cofactors (n=18) or with exercise as a co-factor (n=38), including 14 patients with prior negative wheat challenge combined with exercise.

Threshold for the clinical reaction was lowered (mean 65 %) when oral challenge was combined with exercise (n=38). Tryptase elevation was measured in 6 patients.

Concomitant with a lower threshold, severity score (Sampson 2003) was higher in the majority of the patients with addition of exercise (n=25) and unchanged (n=13)

Thirty-four out of 38 patients had positive s-IgE to omega-5 gliadin (mean 11.4 IU/L [1.14-46.7]) and 30 of 38 positive s-IgE to wheat (mean 2.6 IU/L [0.38-18.7]). SPT to wheat was positive in 36 of 38 patients (mean 6.1 mm [3.0-10.0]) and gluten 36 of 38 patients (mean 5.6 mm [3.0-11.5]).

 

CONCLUSION

Open oral gluten challenge at rest and/or in combination with exercise is a sensitive and specific test for the diagnosis of WDEIA. Reaction could be triggered at rest and therefore exercise is not an essential trigger but merely able to lower threshold and increase severity.

 

 

Patterns of suspected wheat-related allergy: a retrospective single-centre case note review in 156 patients

AUTHORS:

Morten J. Christensen, Esben Eller, Carsten Bindslev-Jensen.

Odense Research Center for Anaphylaxis (ORCA), Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark.

 

BACKGROUND:

Allergy to wheat can present clinically in different forms: Sensitization to ingested wheat via the gastrointestinal tract can cause traditional food allergy or in combination with exercise, Wheat-Dependent Exercise-Induced Anaphylaxis (WDEIA). Sensitization to inhaled wheat flour may lead to occupational rhinitis and/or asthma.

 

METHODS:

We retrospectively reviewed the case notes of 156 patients (age 0.7 - 73.3 years) with a case history of wheat allergy. The population was divided into three groups, 1: Wheat allergy elicited by ingestion, 2: By inhalation and 3: WDEIA. All patients were examined with detailed case history, specific IgE (sIgE), Skin Prick Test (SPT) and wheat challenge (nasal or oral?±?exercise). Details of the case history were extracted from the patients´ case records.

 

RESULTS:

Group 1: Twenty one of 95 patients were challenge positive (15 children, 6 adults). All children had atopic dermatitis, and most (13/15) outgrew their wheat allergy. Most children (13/15) had other food allergies. Challenge positive patients showed significantly higher levels of sIgE to wheat and significantly more were SPT positive than challenge negative. Group 2: Eleven out of 13 adults with occupational asthma or rhinitis were challenge positive. None outgrew their allergy. Seven had positive sIgE and 10 had positive SPT to wheat. Group 3: Ten of 48 (adolescent/adults) were positive when challenged during exercise. Challenge positive patients showed significantly higher levels of sIgE to ?-5-gliadin. The natural course is presently unknown.

 

CONCLUSION:

Wheat allergy can manifest in different disease entities, rendering a detailed case history and challenge mandatory. Patient age, occupation, concomitant allergies (food or inhalant) and atopic dermatitis are important factors for evaluation.

 

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