Food-Dependent Exercise-Induced Anaphylaxis

Although still a relatively rare condition Food-Dependent Exercise-Induced Anaphylaxis, along with other forms of anaphylaxis, is growing.
Dr Janice Joneja explains what it is, what tends to cause it and how best to manage it.

Food-dependent exercise-induced anaphylaxis (FDEIA) is a relatively rare condition and occurs only when an allergic person eats a food that contains an allergen to which he or she is hypersensitive and exercises within 3 to 4 hours after eating. Eating the same food alone, without exercise, does not cause them to react.

FDEIA is considered to be subtype of exercise-induced anaphylaxis, which  causes asthma and wheezing, urticaria, and a drop in blood pressure following exercise. (1) Other symptoms may include angioedema or swelling, gastrointestinal symptoms, bronchial constriction or difficulty in breathing, and vascular collapse. (2)

In most cases, specific foods do not cause any problems when they are eaten, except when eating them is followed by exercise when they can cause anaphylaxis. This is called specific FDEIA. In other cases, EIA results from exercise following consumption of any meal, regardless of the food eaten (called nonspecific FDEIA).

In specific FDEIA, there is usually an IgE-mediated reaction; skin-prick tests are positive and IgE food-specific antibodies can be detected in the patient’s blood. (3) Serum histamine and tryptase levels are increased during attacks, suggesting the release of inflammatory mediators from mast cells induced by IgE-mediated degranulation. (4)

Incidence of FDEIA

There is very little data available about the frequency of FDEIA, but reports of incidents of the condition have increased over the past 20 years, possibly reflecting an increased popularity of exercise in the general population (5) as well as an increased awareness of the condition.
The first published case report of FDEIA appeared in 1979. A 31-year-old male developed anaphylaxis after consuming shrimp or oysters up to 24 hours before long-distance running events. Since then, numerous other case reports of FDEIA have been published. (6)

FDEIA seems to be twice as common in females than in males and is especially prevalent in individuals 25 to 35 years of age. Individuals experiencing this type of reaction typically have asthma and other allergic conditions. (7)

Foods Associated With FDEIA

Although any food may contribute to this form of anaphylaxis, foods that have been reported most frequently as triggers of FDEIA include wheat, shellfish, fruit, milk, celery, and fish. However, there appear to be national differences in the most common trigger foods. For example, European and Japanese reports indicate wheat to be the most common food involved (1), whereas wheat accounts for only 5% of cases in the United States, with shellfish being highest at 16%, followed by alcohol (11%); tomato (8%); cheese (8%); celery (7%); strawberries (5%), wheat (5%), peach (5%); and milk (4%). (8) See below for list of foods most commonly associated with FDEIA.

Allergens in Food Associated With FDEIA

A few recent studies have sought to identify the specific allergens in foods that trigger FDEIA. It seems that the relevant allergens in the foods FDEIA may be different from those that cause other forms of allergy, including anaphylaxis.

For example, soluble proteins in wheat have been identified as allergens in baker’s asthma, whereas insoluble proteins (gluten) are allergens for wheat-dependent exercise-induced anaphylaxis. (8) Meanwhile, wheat-gamma-gliadin appeared to be the allergen in two cases of wheat-associated exercise-induced anaphylaxis (WAEIA) (9), but wheat-omega-5-gliadin in four cases of WAEIA25 in separate Japanese studies. There is increasing evidence for the important role of omega-5-gliadin in WAEIA to the extent that the allergen is being suggested as a marker in the differential diagnosis of the condition. (9)

In addition to the native allergen, the ability of gluten to cause an allergic response seems to be increased during digestion in sufferers ffrom WAEIA. When the wheat is digested with pepsin, the antigenicity, or ability to cause an allergic response, of the gluten was increased, but it decreased when digested with trypsin. This suggests that the antigenicity of gluten is enhanced in the stomach and attenuated in the duodenum.

Based on these observations, it is hypothesized that exercise might induce an increase in mucosal absorption of food peptides, including pepsin-digested gluten, in the small intestine before trypsin in the duodenum has an opportunity to act on the protein. This situation would then result in an enhanced allergen entering the circulation and triggering IgE-mediated allergy in sensitised individuals. (10)

Mechanism Responsible for FDEIA

The physiological and immunological mechanisms responsible for FDEIA are presently only partially understood. It appears that exercise triggers an anaphylactic reaction in those who have IgE-mediated allergy specific for certain foods. In addition to the presence of the allergen, several other factors may be involved in the reaction  (11):

  • Involvement of the autonomic nervous system
  • Intake of certain drugs
  • Weather conditions
  • Humidity
  • Stress
  • Inherited factors
  • Menstruation cycle
  • General physical condition of the individual
  • Concomitant intake of aspirin, nonsteroidal anti-inflammatory drugs (NSAID), and some other medications. (12)

It has also been suggested that exercise might change the efficiency of absorption of the allergen as a result of changes in blood flow through the major vessels and organs. (13) A dysfunction of the autonomic nervous system and the ability of gastrin to increase cutaneous mast cell mediator release have also been hypothesized as contributing to the onset of symptoms. (13)

Diagnosis of FDEIA

The diagnosis of FDEIA is usually made on the basis of the individual’s history. Development of signs of anaphylaxis during exercise, often starting with urticaria (hives), pruritus (itching), and erythema (reddening) that may be followed by breathing difficulty, and/or digestive tract symptoms in a food-allergic individual suggests FDEIA. (13)

Some studies have attempted to identify individuals who are likely to develop FDEIA by determining their sensitisation to specific foods by allergen-specific IgE and skin tests and subjecting the test-positive individuals to treadmill stress tests. However, because other variables not included in the test protocols may be contributing to the development of symptoms, most studies have been only partially successful in predicting which food-allergic subjects are likely to develop anaphylaxis while exercising. (14)

Directives for People Who Exhibit Anaphylactic Reactions to Foods

The most important preventive measure is to take every precaution possible to avoid exposure to the anaphylaxis-inducing food. The first requirement for prevention is
accurate identification of the food trigger. People who have experienced an anaphylactic reaction or who are deemed at risk as a result of their reaction to highly allergenic foods in the past are prescribed a kit for use when accidental exposure to the allergen occurs. The kit contains injectable adrenaline (epinephrine) and sometimes an oral antihistamine. The directives include:

  • Inject the adrenaline.
  • Take the antihistamine if available.
  • Proceed immediately to the nearest hospital emergency department.

After the injection of the adrenaline, it is extremely important that the person is taken to the hospital, even if the symptoms appear to be improving; it is sometimes a secondary phase of the response that can prove fatal. Specific instructions for the use of injectable adrenaline (epinephrine) should be obtained from the allergic person’s doctor or health care provider.

Anaphylaxis-prone individuals are also advised to wear a medic-alert bracelet to expedite appropriate treatment if they become unconscious.

People most at risk for anaphylaxis include:

  • Adolescents and young adults
  • Individuals with known food allergy, especially those with a prior history of anaphylaxis
  • People with asthma, especially severe asthma
  • Individuals with cardiovascular disease
  • People with mastocytosis

General Guidelines for Avoiding Food Allergens Associated With Anaphylaxis

  • Avoid all sources of the offending food; become familiar with all potential sources of the food, especially when eating in restaurants and other places where ingredients may not be obvious.
  • Become familiar with every term on food labels that indicates the presence of the allergen. Many terms bear little resemblance to the original name of the food, so there must be careful education about these terms, especially with children of reading age.
  • Make sure that the food does not enter the home, and make as many meals as possible from scratch from basic ingredients.
  • When manufactured foods are used, make sure that all ingredients are known.
  • When eating outside the home, make sure that the ingredients in every meal are known.
  • Inquire about ingredients in recipes used in restaurants

 

Foods most frequently associated with FAEIA

Beverages
Alcohol

Egg
Chicken egg

 

 

Fruit
Apple
Grape
Kiwi
Lychee
Orange
Peach
Pear
Strawberries

Grains
Barley
Buckwheat
Corn
Oats
Rice
Rye
Wheat

 

Legumes
Soy bean
Peanuts

Milk
Cheese
Milk

Nuts and seeds
Hazelnut
Almond
Mustard
Poppy seed
Walnut

Other
Snail

Poultry
Chicken

Shellfish and seafood
Crab
Cuttlefish
Octopus
Oyster
Shrimp
Squid

Vegetables
Cabbage
Celery
Fennel
Garlic (15)
Lettuce
Matsutake mushrooms
Onion (16)
Potato
Tomato
   
     

REFERENCES

1. Chong SU, Worm M, Zuberbier T. Role of adverse reactions to food in urticaria and exercise-induced anaphylaxis. Int Arch Allergy Immunol. 2002;129:19-26.
2. Aihara M, Miyazawa M, Osuna H, et al. Food-dependent exercise-induced anaphylaxis: influence of concurrent aspirin administration on skin testing and provocation. Br J Dermatol. 2002;146:466-472.
3. Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States: an investigation into its epidemiology. Arch Intern Med. 2001;161(1):15-21.
4. Castells MC, Horan RF, Sheffer AL. Exercise-induced anaphylaxis. Curr Allergy Asthm R. 2003;3:15-21.
5. Aihara Y, Kotoyori T, Takahashi Y, Osuna H, Ohnuma S, Ikezawa Z. The necessity for dual food intake to provoke food-dependent exercise-induced anaphylaxis (FEIAn): a case report of FEIAn with simultaneous intake of wheat and umeboshi. J Allergy Clin Immunol. 2001;107:1100-1105.
6. Perkins DN, Keith PK. Food- and exercise-induced anaphylaxis: importance of history in diagnosis. Ann Allergy Asthma Immunol. 2002;89:15-23.
7. Shadick NA, Liang MH, Partridge AJ, et al. The natural history of exercise-induced anaphylaxis: survey results from a 10-year follow-up study. J Allergy Clin Immunol. 1999;104(1):123-127.
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8. Morita E, Yamamura Y, Mihara S, Kameyoshi Y, Yamamoto S. Food-dependent exercise-induced anaphylaxis: a report of two cases and determination of gamma-gliadin as the presumptive allergen. Br J Dermatol. 2000;143:1059-1063.
9. Jacquenet S, Morisset M, Battais F, et al. Interest of ImmunoCAP system to recombinant omega-5 gliadin for the diagnosis of exercise-induced wheat allergy. Int Arch Allergy Immunol. 2009;149:74-80.
10. Romano A, Di Fonso M, Giuffreda F, et al. Food-dependent exercise-induced anaphylaxis: clinical and laboratory findings in 54 subjects. Int Arch Allergy Immunol. 2001;125:264-272.
11. Chong S-U, Worm M, Zuberbier T. Role of adverse reactions to food in urticaria and exercise-induced anaphylaxis. Int Arch Allergy Immunol. 2002;129:19-26.
12. Aihara M, Miyazawa M, Osuna H, et al. Food-dependent exercise-induced anaphylaxis: influence of concurrent aspirin administration on skin testing and provocation. Br J Dermatol. 2002;146:466-472.
13. Hosey RG, Carek PJ, Goo A. Exercise-induced anaphylaxis and urticaria. Am Fam Physician. 2001;64(8):1367-1372.
14. Chen W, Mempel M, Schober W, Behrendt H, Ring J. Gender difference, sex hormones, and immediate type hypersensitivity reactions. Allergy. 2008;63:1418-1427.
15. Perez-Pimiento AJ, Moneo I, Santaolalla M, de Paz S, Fernandez-Parra B, Dominguez-L. Anaphylactic reaction to young garlic. Allergy. 1999;54(6):626-629.
16. Perez-Calderon R, Gonzalo-Garijo MA, Fernandez de Soria R. Exercise-induced anaphylaxis to onion. Allergy. 2002;57:752-753.

June 2014

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If you found this article interesting, you will find many more articles on anaphylaxis here, and reports of research into anaphylaxis here.
You can also find articles on peanut and tree-nut allergy here, cow's milk allergies here, egg allergy here, histamine intolerance hereand articles on a wide range of other allergic and intolerance reactions to a wide range of other foods here.

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