Invited review article
Food-dependent exercise-induced anaphylaxis

https://doi.org/10.1016/j.jdermsci.2007.03.004Get rights and content

Summary

Food-dependent exercise induced anaphylaxis (FDEIA) is a distinct form of food allergy induced by physical exercise. Symptoms are typically generalized urticaria and severe allergic reactions such as shock or hypotension. Whereas various food items are responsible for the development of FDEIA, wheat is reported to be the allergen with the highest frequency in Japan. Recently aspirin has been known to be an additional exacerbating factor. Skin tests and in vitro serum food-specific IgE assays are currently used, however their sensitivity and specificity are not always satisfactory. A challenge test consisting of ingestion of assumed food followed by intense physical exercise is the only reliable method to determine the causative food and to diagnose the disease. The challenge test is not always safe because in some cases the test induces an anaphylactic shock. So a reliable in vitro diagnostic method is necessary for the patients with FDEIA. We revealed that wheat omega-5 gliadin and high molecular weight glutenin subunit are major allergens in wheat-dependent exercise-induced anaphylaxis (WDEIA). A simultaneous detection of specific IgE to epitope sequences of both omega-5 gliadin and high molecular weight glutenin is found to achieve higher sensitivity and specificity compared with the in vitro serum food-specific IgE assays currently used for diagnosis of WDEIA. On the other hand, immunoreactive gliadins appeared in the sera of patients during the provocation test with both wheat-exercise and wheat-aspirin challenges in parallel with allergic symptoms. These findings suggest that FDEIA is IgE-mediated hypersensitivity reaction to foods and both exercise and aspirin facilitate allergen absorption from the gastrointestinal tract.

Introduction

Nowadays IgE-mediated hypersensitivity to foods is clearly recognized as food allergy. Limited numbers of life-threatening anaphylactoid reactions have been observed associated with exercise [1]. Within this clinical entity considerable numbers of cases show anaphylactic reactions during or in association with exercise after ingestion of foods. A case of exercise-induced anaphylaxis was first reported by Maulitz et al. in 1979 [2] as a previously undescribed late allergic reaction to shellfish induced by strenuous exercise. In 1983, Kidd et al. [3] reported four cases of exercise-induced anaphylaxis (EIA) occurring only in combination with the ingestion of food, and initially described as food-dependent exercise-induced anaphylaxis (FDEIA). Three of these four cases were proved as having celery-allergy. The first case of FDEIA in Japan was described by Kushimoto and Aoki in 1985 [4], and the cause of the food reaction was wheat. Since these initial reports, numerous foods have been implicated in FDEIA/anaphylaxis and further clinical features of the disease have been documented.

Section snippets

Epidemiology

Data regarding the incidence of FDEIA are limited. According to a study in Japanese children, 0.06% of the elementary school students, and 0.21% of the junior high school students suffer from FDEIA [5]. In a larger study the incidence in Japanese students was calculated to be 0.012% with a prevalence of 0.017% for junior high school students and 0.0086% for high school students [6].

In an analysis of 167 Japanese FDEIA cases [7], the disease was more frequent in children than in adults with a

Clinical manifestation

These anaphylactic symptoms are usually induced by physical exercise after food ingestion. The typical symptoms include skin manifestations, respiratory symptoms, abdominal pain, fatigue and loss of consciousness. The skin manifestations include generalized urticaria, angioedema, and/or erythema, and these are seen in most patients. Dyspnea is experienced by approximately 60% of patients. The dyspnea is characterized as a choking sensation in the throat: therefore, this is believed to be caused

Causative foods

A variety of foods have been described as causal allergy inducing foods in FDEIA. These include shellfish [2], [14], [17], [19], [21], wheat products [4], [14], [15], [16], [17], [18], [19], [20], vegetables [3], [14], [22], [23], fruits [14], [17], [24], nuts [14], egg [14], [25], mushrooms [26], corn [14], [27], garlic [14], meat including pork/beef [14], and rice [14]. In European countries, vegetables are the most common food allergens. Among them tomatoes were the most frequent [14].

Mechanisms

The main distinctive feature of FDEIA is that some foods cause a severe systemic anaphylactic reaction when followed by physical exercise, but are usually tolerated if not followed by exercise. The mechanisms by which exercise induces this reaction are controversial. Scheffer et al. demonstrated that exercise enhances the degranulation of mast cells in patients with exercise-induced anaphylaxis [11], and a considerable rise in plasma histamine concentration was observed during the exercise

Diagnosis

A detailed clinical history of exercise-induced anaphylactic symptoms, especially a preceding history of all food-intake, is of particular importance for the correct diagnosis of FDEIA. Following this procedure EIA as well as cholinergic urticaria can be ruled out, and candidate causative foods can be identified.

Currently, the most useful diagnostic tests for food allergy are skin tests, in vitro serum food-specific IgE assays, and oral food challenges. Skin tests (a skin prick test is usually

Patient education

Education regarding avoidance and management of accidental ingestion of the foods causing allergy is crucial because neither medications nor immunotherapy are presently available to continuously or consistently prevent the anaphylactic symptoms. When patients consume the causative foods either accidentally or intentionally, avoidance of exercise for 4 h after eating might be helpful to prevent the occurrence of symptoms in many cases, however this is not always safe because some patients

Concluding remarks

FDEIA is known as a distinct form of food allergy which is specifically induced by exercise, however our intensive investigations have revealed that exacerbating factors such as aspirin intake as well as exercise can facilitate allergen absorption from the gastrointestinal tract, indicating that FDEIA is not a special subtype of allergy but is a consequence of exercise-induced increased allergen intake and routine food allergy. Interestingly facilitation of allergen absorption into the blood

Acknowledgement

This work was supported by a Grant-in Aid for Scientific Research (Nos. 16790642 and 17790769) from the Japan Society for Promotion of Science.

Eishin Morita graduated and received the MD degree from Hiroshima University School of Medicine in 1982. He was at the Department of Dermatology Hiroshima University School of Medicine from 1982 to 1986. He was employed as a visiting research fellow at the Department of Dermatology, University of Kiel, the Federal Republic of Germany from 1986 to 1990. In 2002, he moved to Shimane Medical College, where he was an associate professor in the Department of Dermatology. In 2004, he was promoted to

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    Eishin Morita graduated and received the MD degree from Hiroshima University School of Medicine in 1982. He was at the Department of Dermatology Hiroshima University School of Medicine from 1982 to 1986. He was employed as a visiting research fellow at the Department of Dermatology, University of Kiel, the Federal Republic of Germany from 1986 to 1990. In 2002, he moved to Shimane Medical College, where he was an associate professor in the Department of Dermatology. In 2004, he was promoted to a chief professor in the Department of Dermatology, Shimane University School of Medicine. His research interests include allergic skin diseases and food allergy.

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