How Exercise Can Worsen Your Allergic Reactions to Food and What You Can Do About It

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Some people with food allergies find that exercise seems to worsen their allergic reactions. Some people don’t seem to have allergic reactions to food unless they exercise. The exercise in question can be anything from a more recognised version of physical activity like running or playing football, to doing household chores or crossing the street. For the latter group of unfortunates, the ‘exercise’ part of their reaction is so well hidden that it can take years before they are diagnosed. For most people, however, once a proper diagnosis is reached, exercise-induced reactions are quite manageable.

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Exercise as a cofactor; confusion and debate

For the past couple of decades, allergists have been increasingly aware that the presence of certain things like exercise, alcohol and medications—so-called ‘cofactors’—have the potential to make allergic reactions worse.

Physical exercise is the most commonly reported cofactor involved in food-induced allergic reactions, although the percentage of people it may affect varies widely per study and trying to sort through the data on the subject is not as simple as it should be.

For a long time, allergists have had 2 separate categories for allergic reactions to food involving exercise:

1. ‘Conventional’ cofactor-enhanced food allergy, in which a person who is allergic to food finds that their symptoms are worsened or more easily provoked when they engage in intense exercise
2. Food-Dependent Exercise-Induced Anaphylaxis (FDEIA), which is an allergic reaction to food which happens only when a person also exercises. In this case, the exercise in question can be any kind of activity, from crossing the street to climbing a mountain

However, there is currently a debate going on as to whether the two categories actually include people with two separate conditions, or whether they are all cases of people with ‘conventional’ food allergy and difference tolerance levels for their trigger food(s). More on that later.

And then there is the special case of wheat allergy. Because wheat is so frequently involved in FDEIA, allergists assigned wheat-based exercised-induced anaphylactic reactions their own category, giving the condition it’s own acronym: WDEIA, or Wheat-Dependent Exercise-Induced Anaphylaxis. But within this category, they also decided to include anaphylactic reactions to wheat that do not involve exercise at all (despite it actually being in the name) but other cofactors like aspirin and alcohol.

Additionally, because the protein in the wheat that seems to be responsible for the majority of cases of WDEIA is called omega-5-gliadin, WDEIA is also sometimes called ‘omega-5 gliadin allergy’. But other proteins can also cause exercise-induced anaphylaxis to wheat, including alpha/beta and gamma-gliadins, high-molecular-weight glutenin low-molecular-weight glutenin and lipid transfer proteins. And the term omega-5 gliadin allergy covers anyone allergic to that particular protein, including people who have ‘conventional’ food allergy and react without cofactors like exercise.

Finally, just because the word ‘anaphylaxis’ is included in the name of the two most well-studied conditions, food-dependent exercise-induced anaphylaxis and wheat-dependent exercise-induced anaphylaxis, does not mean that people with those conditions will necessarily have anaphylactic symptoms.

With all of that in mind, let’s dive in.

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How important is exercise as a cofactor?

Finally, just because the word ‘anaphylaxis’ is included in the name of the two most well-studied conditions, food-dependent exercise-induced anaphylaxis and wheat-dependent exercise-induced anaphylaxis, does not mean that people with those conditions will necessarily have anaphylactic symptoms.

Studies examining the importance of exercise as a cofactor in conventional food allergy are rare.

A review of all cases of anaphylaxis registered by a hospital in Hong Kong between January 2017 and August 2022 involving both children and adults reported that two-thirds (66%) of cases involving food-related anaphylaxis were associated with exercise.

An analysis of data from the European anaphylaxis registry which covers 90 study centres in 10 European countries (Germany, Switzerland, France, Italy, Austria, Poland, Spain, Ireland, Greece, and Bulgaria) shows that, between July 2007 and March 2015, exercise was a suspected cofactor in 1 of 5 (21%) anaphylactic reactions involving children and adolescents.

There are no studies looking into the proportion of adults with conventional food allergy who are affected by exercise (that I’ve found), but exercise is an important factor in food-allergic adults who develop serious symptoms; most cases of FDEIA involve adults. As a typical example, a Portuguese review of 62 food-allergic people seen at a hospital in Coimbra after suffering anaphylactic reactions reported that exercise was the most common cofactor, associated with 13 cases of FDEIA, 11 of which involved adults.

Most of the analyses of the effect of exercise on allergic reactions involve people who’ve had anaphylactic symptoms of some kind. In 2016, a team of Dutch researchers decided to examine how often cofactors were associated with more severe symptoms to food all in people with a doctor diagnosed food allergy, not just those with severe reactions. They examined the medical records of 496 Dutch patients over the age of 16 referred to one allergy centre in the city of Utrecht between November 2002 and August 2012, just over half (52%) of whom had a history of severe reactions.

They found that, while exercise was the most frequently reported cofactor, only 10% of patients thought that exercise had made their symptoms worse. It should be noted, however, that almost two thirds (65%) of the study’s subjects couldn’t saywhether any cofactors had beeninvolved in their reactions.

Whether you’re at risk of having worse reactions when you exercise may depend on the type of food you’re allergic to. Recent analysis of data from the European anaphylaxis registry (covering the same countries mentioned in the previous analysis and, somewhat oddly, Brazil) including people of all ages, has reported that exercise is often involved in severe reactions to wheat and it also worsens reactions to peanut. (Strangely, the researchers also found that exercise may make reactions to red meat or poultry milder.)

Controlled studies carried out to examine the impact of exercise and a lack of sleep in 73 and 71 peanut‐allergic adults, respectively, reported that exercise reduced the reaction threshold (putting the peanut-allergic subjects at greater risk of a reaction) but did not seem to impact severity.

Further analysis of the raw data from the experiment, however, found that the effect of exercise on the reaction threshold was more modest than initially reported; in fact, only 12% of the participants saw a significant drop in their threshold. In other words, the impact of exercise is probably not that important in the majority of peanut‐allergic individuals.

Ultimately, the consensus seems to be that exercise may lower reaction thresholds in 10–20% of people with food allergy, but it’s unlikely to make things worse for the majority of the food allergic, with the notable exception of two groups of people:

1. Those undergoing immunotherapy. Reports of people undergoing food desensitisation suddenly experiencing symptoms to an amount of allergen that they previously tolerated when they exercise around the time that they take their daily dose are quite common, especially when peanut or wheat are involved.

In rare cases, exercise has also been shown to reverse an acquired tolerance to milk; once, in a boy who had undergone successful immunotherapy to milk before then developing FDEIA to dairy and, another time, in a 16-year-old girl who had naturally acquired tolerance to milk by the age of 14 but still showed skin sensitisation to the allergen (as people who acquired tolerance often do) and later also developed FDEIA to milk. Her doctors thought that, eventually, when her sensitisation to milk disappeared, the FDEIA would disappear, too.

2. Those with a diagnosis of food-dependent exercise-induced anaphylaxis.

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Food-Dependent Exercise Induced Anaphylaxis (FDEIA)

There’s a lot more information on food-dependent exercise-induced anaphylaxis (FDEIA), and the rest of this page focus on this, more well-researched, condition.

The first case of FDEIA was reported in 1979 as a late allergic reaction to shellfish after jogging in a person who was tolerant to shellfish when not exercising and able to exercise freely without problems as long as they did not eat shellfish. As it turned out, this was to be the first of many similar reports, and the condition was later defined as a separate entity and given the name ‘food-dependent exercise-induced anaphylaxis’.

Studies on the prevalence of FDEIA in the general population are vanishingly rare. The prevalence of FDEIA among the general population worldwide is thought to be between 0.001% and 0.017% worldwide for all food.

Surveys of school nurses in Japan have reported a prevalence of FDEIA of 0.0047% among elementary school students and 0.018% among junior high school students.

People with FDEIA tend to be older than people with conventional food allergy when they have their first reaction, and cases of FDEIA are much more common in adolescents and adults. One analyses of cases in the literature reported that many people suffered their first episode between the age of 10 and 20 but other analyses of hospital patients have put the age of onset in the mid to late 30s.

That said, the age of onset varies widely and there are cases reports of patients having their first known attack between 7 and 82 years old.

According to data from Ireland and Japan, cases of FDEIA (like all cases of food allergy) may be on the increase, although at least some of the increase in numbers may be due to the fact that FDEIA is becoming more recognised and diagnosis is more frequent now than it used to be.

Cases are often associated with jogging, probably because it tends to be a popular pastime among people who like to exercise, but any type of physical activity can provoke a reaction. So far, FDEIA has been linked to various gym workouts, Zumba classes and school PE classes, Nordic walking, long distance running, cycling, skiing, floorball, golf, badminton, squash, tennis, racquetball, football, volleyball, basketball, swimming, kendo and mountain climbing.

It’s not just traditional exercise that some FDEIA sufferers have to worry about; several reactions have been provoked by dancing, as well as walking to school and walking home, carrying moving boxes and shopping, cleaning, sweeping, yard work and farm work. As people get older, even less activity is needed to provoke a reaction; crossing the street is enough. For one poor woman, eating a meat loaf and then doing the ironing was enough to trigger an anaphylactic attack.

In fact, reactions in response to low-intensity exercise may be the norm; an analysis of 283 Chinese adults and children with wheat-dependent exercise-induced anaphylaxis (WDEIA) revealed that 30% of the reactions occurred during relatively intense exercise (such as running, badminton, table tennis, basketball and mountaineering) and the remaining 70% took place during activity that can barely be counted as exercise, such as walking and doing housework.

The intensity of ‘exercise’ needed to provoke a reaction is so low that another group of researchers looking into the symptoms of WDEIA—which can be milder than anaphylaxis—suggested that an alternative name be adopted, namely ‘activity-dependent wheat allergy’.

And that’s not the only reason for a name change.

Conventional food allergy by another name?

The main thing that’s supposed to differentiate FDEIA from conventional, cofactor-induced food allergy is the idea that when a person has FDEIA, if they eat food without ‘exercising’ within hours of their meal/snack, they will not have an allergic reaction. And if they exercise without eating their trigger food, there is no allergic reaction. But when the two things are combined, they always bring on symptoms.

However, research has shown that some people with FDEIA can develop symptoms to a food without actually doing any exercise; they just have to eat a lot more of their trigger food—like someone with corn FDEIA eating a whole bag of taco chips for example—and maybe add another cofactor like aspirin and/or alcohol to the mix.

In the most quoted study of its kind, a team of Danish scientists gave 71 adults with a history of WDEIA controlled challenges, one involving just eating wheat, and another involving eating wheat and then exercising. They found that 26 (37%) of their subjects did not need exercise to have symptoms; they just needed to eat high doses of wheat. The primary impact of the exercise was to reduce the reaction threshold (average dose of gluten needed at rest was 48 g; average dose needed when combined with exercise was 24 g) and to increase the severity (there was a greater tendency to anaphylaxis with exercise).

On the basis of these results, the researchers suggested that many people with WDEIA might be allergic to wheat even without exercising but they can tolerate normal portions because their reaction thresholds are much higher than typical serving sizes. However, once exercise is added to the mix, there is a significant drop in their reaction thresholds which results in reactions to more typical portion sizes of wheat.

In a follow-up study, the researchers showed that aspirin may be a more powerful instigator of reactions in people with WDEIA than exercise; in their 25 adult subjects, aspirin was shown to decrease the average reaction threshold by 83%, compared with 63% observed for exercise and 36% for alcohol.

Additional support for the idea that people with WDEIA may simply be wheat-allergic people with very high thresholds can be found in a study set up to determine whether exercise is absolutely necessary to provoke reactions. In this study, 16 people with confirmed WDEIA were challenged challenged sequentially with and without exercise and other cofactors. 4 of them developed symptoms just by eating between 10 and 80 grams of gluten (for the record, eating 80 g of gluten is the equivalent of eating just under a kilo of bread). Another 10 participants needed to add between 500 to 1000 mg of aspirin and 10 to 30 millilitres of 95 percent ethanol to develop symptoms. The last 2 subjects required all of the above and exercise to develop symptoms.

There are also cases of people diagnosed with WDEIA who have a history of recurrent hives to wheat, suggesting that they may have had a milder form of wheat allergy before developing more serious symptoms in conjunction with cofactors like exercise and aspirin—and also implies a worsening form of conventional food allergy.

Similarly, there are also cases of people who have oral allergy syndrome to foods (such as walnut or cuttlefish) but only develop FDEIA when others cofactors—exercise, drugs and temperature—are involved.

Another interesting finding is that some people who are allergic to multiple foods seem to have a much higher tolerance to one of the foods that they are allergic to; they need the presence of a cofactor to lower their threshold for that particular food before they react. One case report, for example, describes the case of a 17-year-old who suffered from anaphylaxis when he ate food containing chickpeas at rest, but needed to exercise to provoke the same kind of reactions when he ate foods containing lentil.

In light of these types of revelations, some experts have suggested that the term ‘wheat allergy dependent on augmentation’ or a more general name like ‘cofactor-dependent food allergy’ would be more accurate and reflect the fact that these symptoms are not just seen in people with wheat allergy.

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How does exercise make reactions worse?

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Which foods are involved?

Wheat is the most common, well-known and well-studied instigator of exercise-induced reactions, linked to a veritable multitude of cases of anaphylaxis after eating things like baked goods, noodles, dumplings, pizza, pancakes, muesli and cereal bars.

That said, all kinds of food can provoke exercise-induced reactions, and there are case reports of FDEIA to a wide range of foods including: grains and cereals related to wheat, namely rye, barley and oats, corn, buckwheat, rice, cabbage, pumpkin, potato, tomato, celery, carrot, parsley, spinach, mushroom, onion, paprika, mustard, lentil, chickpea, soybean in hidden in processed foods and tofu, as well as apple, orange, strawberry, cherry, peach, nectarine, kiwi, mango and grape. And peanut, almond, walnut, hazelnut and pistachio.

Although the vast majority of FDEIA tends to be provoked by plant food, cases have also been reported to fish and shellfish including shrimp, crab, cuttlefish, oysters and snails, as well as chicken, egg, beef, pork, milk and cheese.

There are clear geographical differences when it comes to which foods are most commonly involved in FDEIA; for example, in Central Europe, wheat is the most common cause of FDEIA in adults whereas, in Southern Europe, tomatoes, cereals and peanut are the usual suspects when it comes to exercise-induced food allergy. In Japan, wheat is back as the primary provoker, closely followed by shrimp, which seems to be the most common instigator in people under 20.

Not only can people be triggered by more than one food, in some cases it actually requires multiple foods to trigger a reaction, such as a combination of peanut and egg, wheat and umeboshi (preservedJapanese plums), wheat and shrimp, wheat and apple or tomato, courgette and wheat.

Sometimes it seems to require a special combination of ingredients, as in the case of a 32-year-old man who suffered symptoms when exercising after eating foods made from wheat, sugar and butter, such as doughnuts and pancakes. And sometimes the food needs to be combined with food additives and alcohol to trigger an attack.

Sometimes, only certain forms of the food will trigger symptoms. One study reported the case of a person who could tolerate soy milk before exercising but who could not eat tofu and then exercise without having a reaction. The scientists discovered that the particular allergen that the person was allergic to was digested much more quickly when it came in the form of soy milk than when it was eaten in the form of tofu (20 minutes vs over 120 minutes). They concluded that the presence of undigested allergens in the digestive tract led to the development of FDEIA.

In another study, 3 people with WDEIA were described as developing anaphylaxis to the hydrolysed wheat protein (HWP) in a cake mix, but being able to tolerate regular wheat products like bread or pasta on a regular basis. Another case describes someone who only reacted to wheat if it was toasted.

Another report details the case of an 8-year-old boy who suffered from episodes of FDEIA after eating potato crisps, although eating unprocessed potatoes before exercise did not seem to provoke any symptoms.

There’s also a rare version of FDEIA called nonspecific food dependant exercise-induced anaphylaxis (NFDEIA) in which any food can induce anaphylaxis, without sensitisation or allergy being involved. In this case, it’s just the filling of the stomach that is responsible for inducing a reaction.

Reactions have been shown to be dose-dependent. Studies that have carried out challenges tests on people with WDEIA have found that reactions occur after a certain amount of wheat has been eaten (which makes sense if you consider that FDEIA might simply be a cofactor-induced reaction in people with a high tolerance to the food they’re allergic to). In one study, for example, a 24-year-old Japanese woman with WDEIA showed symptoms after eating 64g of bread but not after eating 45g, and after eating 200g of udon noodles, but not after eating smaller amounts.

In another study, levels of wheat allergen circulating in the blood of people diagnosed with WDEIA were shown to correlate with the severity of the symptoms that they showed after taking exercise and wheat challenges.

Sometimes, even eating food is not necessary. In the case of a 23- year-old professional cyclist, FDEIA was triggered by an inhaled antigen; he had an anaphylactic reaction during a race when the cyclists went through an almond orchard that was in full bloom.

And, since we have developed a predilection for putting food into our cosmetics, food-induced allergic reactions can also be provoked by beauty products; around 15 years ago, hundreds of Japanese people started reacting to wheat after using a certain HWP-containing brand of soap. Many of them first developed skin rashes when using the product and then went on to develop WDEIA; most suffered from swollen eyelids but many also from anaphylaxis after eating wheat products.

In 2022, the first European case was reported. Happily, the case of a teenager with suspected WDEIA provides hope for the afflicted: remission may be possible. In this case, a 16-year-old who had suffered several reactions during exercise after eating wheat-containing foods was initially diagnosed as having WDEIA and advised to avoid eating wheat before exercising. Then it was discovered that she had been using a HWP-containing soap which had probably kick-started her allergic reactions. She stopped using the soap and, after a few months, her lab tests showed vastly diminished immune reactivity to wheat, so she was able to start eating it again and exercising without provoking any significant reactions.

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What other factors may be involved?

People with food allergies made more likely by the involvement of exercise are vulnerable to the same kinds of (other) cofactors as anyone else with food allergy.

The most well-known of these are drugs and alcohol. Multiple studies from around the world have reported the influence of drugs—notably NSAIDs—and alcohol in serious reactions involving exercise.

Aspirin has been found to be so good at provoking reactions that it is considered a useful part of the diagnostic toolbox and is routinely used in provocation challenges (although not always successfully). Although aspirin is the most referenced NSAID, ibuprofen, naproxen and naprosyne have also been mentioned in conjunction with FDEIA.

NSAIDs are not the only type of medication suspected of involvement in FDEAI reactions; angiotensin converting enzyme (ACE) inhibitors, proton pump inhibitors, beta-blockers and antacids are frequently mentioned as potential cofactors, and other medication like calcium channel blockers have also been implicated.

Other types of cofactor likely to worsen reactions include infection and coexisting atopic conditions such as hay fever (allergic rhinitis), asthma, allergic conjunctivitis and atopic dermatitis.

Temperature can be the missing ingredient for some people, and has been cited in one case involving food, exercise and cold water, and another case that occurred only when the patient exercised during the winter. At the other end of the scale, there’s the case of a 19-year-old man who developed anaphylactic shock only when he exercised in temperatures of around 26°C.

Menstruation is also a cofactor that’s mentioned quite often in cases of exercise-adjacent reactions to food, often in combination with Ibuprofen or aspirin, which will come as no surprise to any woman who’s ever had menstrual cramps. In these types of cases, a woman will probably be able to eat her trigger foods and exercise quite strenuously without developing any symptoms, but if she also happens to be menstruating and/or takes a high dose of painkillers, then she will experience an episode of FDEIA.

Finally, cannabis has also been mentioned as causing severe symptoms in a man over two episodes involving eating wheat, walking and playing football.

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What are the symptoms?

As its name suggests, FDEIA is a serious allergic condition which often results in anaphylaxis. But not necessarily initially, and not all the time. If you have FDEIA, you will typically start off with episodes of warmth/flushing and hives during exercise which progress to involve more severe symptoms over time.

Early signs and symptoms often include:

• itchy skin (pruritus)
• diffuse warmth and/or flushing
• tingling in the extremities
• hives (urticaria)
• swelling of the face (angio-oedema) and/or throat and/or extremities (often the hands)
• sudden fatigue
• profuse sweating

You may also experience headaches that can last for several hours or even days.

You may experience these milder symptoms for several months or years before going through your first episode of anaphylaxis. The milder symptoms are also often the initial ones in an episode that then progresses to full anaphylaxis.

More severe symptoms include:

• wheezing
• shortness of breath (dyspnea) due to tightening of the air passages in the lungs (bronchospasm)
• a feeling of tightness in the chest
• a swollen throat (laryngeal oedema) that makes swallowing difficult (dysphagia) and/or can make the voice hoarse
• nausea
• stomach cramps
• diarrhoea

Some cases also describe blurred vision and temporary loss of vision.

Finally, the most severe cases end in anaphylaxis, which includes:

• trouble breathing
• rapid heartbeat
• feeling dizzy
• passing out

A review of cases described in the literature up to July 2021 identified 602 patients with food-dependent exercise-induced allergic reactions and reported that 120 (16.6%) had had skin symptoms only. Of those who had suffered anaphylaxis, just under two thirds (64%) had suffered respiratory symptoms, over half (57%) had suffered cardiovascular symptoms and around a quarter (24%) had suffered gastrointestinal symptoms.

A review of the medical records of patients treated in Hong Kong between January 2017 and August 2022 found that individuals with FDEIA were more likely to experience cardiovascular symptoms than patients with food-related anaphylaxis (90.9% vs. 46.4%) but less likely to experience respiratory symptoms (47.3% vs 75.0%).

In China, a similar review reported that people with the wheat-triggered version of this allergy were most likely to suffer from severe symptoms, finding the most common clinical features among this patient population were hives (urticaria, 100%), loss of consciousness (82.7%), shortness of breath (dyspnea, 50.8%), low blood pressure (hypotension, 47.2%), and blurred vision (39.1%).

Reassuringly, a small study of Italian children noted that young children seemed to be more likely than older children and adults to have wheezing and less likely to suffer from severe symptoms like collapse, possibly because early diagnosis prevents the progression to worse symptoms. A review of 231 FDEIA-related studies including 722 patients bolsters their observation, reporting that people with food-dependent exercise-induced allergic reactions who had anaphylaxis were older at the time of disease onset.

Timing of symptoms

In most cases of FDEIA, symptoms appear within half an hour of the onset of physical activity, but they can appear anywhere from 5 minutes after starting to exercise to 5 hours after the end of physical activity.

Rare cases show an even longer onset of symptoms. For example, one patient taking part in a study designed to evaluate the effectiveness of a test protocol for diagnosing WDEIA developed symptoms 24 hours after taking the exercise-food challenge test.

In another case, one 51-year-old man experienced anaphylactic attacks 10 hours and 24 hours after eating wheat-containing meals and doing some exercise. In his case, a history of chronic gastroenteritis and the associated intestinal blockage is thought to have exacerbated the delay.

In order to provoke a reaction, the offending food is generally eaten within minutes to a couple of hours before exercise, but food eaten up to 6 hours before exercising can cause problems.

In the original report of FDEIA caused by shellfish, the patient was reported to have suffered a reaction after going on a long distance run about 20 hours after eating 100 grams of smoked oysters.

There are also rare reports of people suffering from symptoms when eating their trigger food shortly after exercise. In one case, for example, a 39-year-old woman suffered from several episodes of itchiness, stomach cramps, dizziness and weakness when she ate celery within 2 hours of exercising. The episodes lasted between 1 and 3 hours and stopped happening when she stopped eating celery after exercising.

In another case, a 12-year-old Chinese boy experienced severe anaphylaxis requiring a trip to the hospital twice during exercise after eating wheat, and then another time before eating wheat, although in this case, the symptoms—generalised hives and shortness of breath—resolved after her took some antihistamines.

Intensity of reactions

There may be a dose–response relationship between the intensity of exercise and the corresponding intensity of symptoms, with vigorous physical exercise sometimes associated with more severe reactions.

A study investigating the characteristics of patients who had been treated at 2 allergic clinics in Sri Lanka described several cases of patients experiencing more severe symptoms after more strenuous exercise; one patient who had hives after climbing a couple of flights of stairs but had an anaphylactic attack after playing football, a second patient who had 2 episodes of hives after a couple of short walks and 2 episodes of anaphylaxis after playing badminton and dancing, and a third patient who developed hives after swimming and anaphylaxis after playing badminton.

A review of anaphylaxis cases in European adults has also identified an allergy to wheat as a risk factor for reaction severity, with adults suffering from wheat being 4 times more likely to have more serious symptoms (including cardiovascular symptoms and loss of consciousness) than people allergic to other foods.

These results were corroborated by results of an analysis into 906 Chinese patients seen at an allergy centre which found that 57% of the severe anaphylaxis episodes were triggered by wheat, and that fruits and vegetables were more likely to trigger mild or moderate reactions.

Pregnant women with a history of exercise-induced anaphylaxis are also at risk of suffering from worse symptoms when they exercise during their pregnancy (and afterwards) or from having anaphylactic reactions while they are in labour. This can be dealt with by a well-prepared medical team and a decent delivery plan.

Other complications

Sometimes, allergic reactions can involve more unusual symptoms.

There are several reports of Kounis Syndrome due to FDEIA. Kounis Syndrome, aka allergic angina, is a type of heart disease—acute coronary syndrome—that is brought on by an allergic reaction.

It requires treatment for both the heart problem and the allergic reaction, which is complicated by the fact that some of the medication used to treat one condition can aggravate the other. In one case involving a 62-year-old woman who had developed FDEAI by playing tennis after eating a mango, the use of adrenaline to treat the anaphylactic reaction worsened the heart condition, and the use of aspirin to treat the heart condition worsened the anaphylactic attack.

Although Kounis syndrome often involves people who are middle-aged and older, this is not always the case; one case report, for example, involves a 23-year-old who was undergoing physical rehabilitation and accidentally drank some milk that she was allergic to.

Originally considered a rare condition, it’s now thought of as not rare but a rarely diagnosed syndrome.

There is also a very unusual report of an otherwise healthy 42-year-old man who had a seizure while exercising at the gym. After a few minutes on the treadmill, he noticed an itching sensation all over this body and the beginnings of a rash. Then he had a seizure which lasted less than a minute and was limited to frothing from the mouth. The only difference in his usual routine was that he had had his dinner before exercising, rather than afterwards, and he was subsequently diagnosed with nonspecific FDEIA and given a warning not to exercise for at least 4 hours after eating, which put an end to his symptoms.

A person can also have more than one exercise-related allergy, like the case of this 15-year-old boy who suffered both from exercise-induced asthma—which, in his case, caused shortness of breath—and FDEIA to hazelnut, which added itchy skin, a rash and a swollen throat to his list of symptoms.

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How is FDEIA diagnosed?

The diagnosis of food-dependent exercise-induced anaphylaxis (or exercise-induced anaphylaxis) is heavily dependent on a detailed clinical history of the events surrounding the allergic reactions. The allergist will want to know:

• what was eaten and drunk in the hours prior to your allergic reactions
• what, exactly, were your symptoms, including their timing and progression (how long they lasted, whether they got worse)

• if exercise (or some form of physical exertion) was associated with each of the attacks
• if other cofactors—drugs, alcohol, heat, cold, emotional stress, menstruation, infection—were involved
• if you have a history of past reactions to foods, exercise, or environment (e.g. pollen, insects)
• whether your immediate family has a history of allergies

Skin and/or blood tests

Skin prick tests and allergen-specific immunoglobulin E (IgE) blood tests can reveal which food(s) you might be allergic to and exclude other suspected allergens. Skin or blood tests to environmental allergens like pollen may be done if your medical history indicates that they could be cofactors in your reactions (e.g. high pollen counts), but they are not routinely done.

If you have FDEIA, you may not be aware of the relationship of your allergic reaction to food because you can normally eat the food without reacting. If this is the case, the allergist may test for allergies to foods commonly associated with FDEIA, but the medical history is often good enough for more specific testing to be done.

Skin and blood tests do not provide a definitive diagnosis. For one, they often disagree with each other or give contradictory results and their results cannot be trusted in isolation.

Test results, when positive, often show low levels of specific antibodies to food triggers which, normally, would be considered too low to cause a reaction for someone with a classic food allergy, but in the case of FDEIA, will produce symptoms.

Being sensitised to a food does not mean that you’re necessarily allergic to it; a positive test does not mean that you will definitely develop symptoms when you eat that food and then exercise. In one case, for example, a 15-year-old girl with FDEIA to corn also had very high levels of IgE antibodies to wheat, but was able to eat wheat without experiencing any problems. This is actually very a common finding.

Conversely, sometimes people who react after eating specific foods have negative test results. This was the case for an 11-year-old girl who had an anaphylactic attack after eating a cookie before playing indoor basketball. Her skin and blood tests were negative for all the separate ingredients in the cookie, but a challenge which involved eating the same brand of cookie and then doing an exercise challenge produced symptoms.

Some people with FDEIA can have symptoms when they exercise after eating any kind of food (i.e. they have nonspecific food dependant exercise-induced anaphylaxis, NFDEIA); these people generally have negative test results.

The provocation challenge

Your clinical history and lab tests can only suggest the possibility that you have FDEIA to a certain food. The only way to be sure is to undergo a food and exercise and/or cofactor challenge.

The provocation challenge can be risky. One retrospective study of the challenges undertaken by 41 people with suspected FDEIA reported that adrenaline had to be administered to the patient in 1 in 5 of the positive challenges. In another study involving challenges in 14 adults and children with WDEIA, adrenaline had to be given to 6 of the 10 people who reacted, 3 of whom were children. Therefore this type of challenge should always be performed by allergy specialists who have the expertise, staff and equipment available to treat anaphylaxis.

In practice, because this type of testing requires a lot of time and resources and can be risky, it’s generally not performed as a matter of course. If you have a clinical history suggestive of FDEIA and a positive blood or and/skin test, you probably won’t be asked to undergo it.

Things that make such a test more likely to be recommended include:

• your clinical history and lab tests don’t match up (your history suggests a food allergy but your tests are negative, and vice versa)
• your symptoms are unusual or ambiguous
• you are planning on introducing a food into your diet that you’re sensitised to and are worried that it will cause reactions when you exercise
• you want to know whether your have outgrown a food allergy

The whole testing process can theoretically consist of 5 different parts, although people who take part in a provocation challenge are unlikely to have to undergo all five. Each part is normally carried out on a separate day.

Before testing begins, you will be asked to eliminate the suspect food from your diet for at least 2 weeks beforehand so that it doesn’t interference with the results of the tests.

Part 1: the food challenge

A diagnosis of FDEIA requires proof that you cannot eat the food and exercise without having an allergic reaction, but you can either exercise or eat the food without problem.

A food challenge is carried out when you cannot report having been able to eat normal portions of the suspect food without suffering reactions since your last episode of anaphylaxis, meaning that there is a need to rule out the possibility that what you have is a ‘classic’ food allergy which is simply aggravated by exercise. If you do have FDEIA, you should be able to eat (the maximum amount of) the food during this challenge without symptoms.

In practice, the medical history is generally clear enough that a food challenge alone is rarely needed.

Part 2: the aspirin challenge

Similar to the food challenge, the aspirin challenge is carried out in people who are thought to have a possible allergy to aspirin and consists of taking small doses of aspirin, generally ending with a cumulative dose of around 500 mg, to see whether that provokes a reaction.

Part 3: the exercise challenge

The exercise test is carried out after 12 hours of fasting, to make sure that you don’t have exercise-induced anaphylaxis (EIA).

The exercise challenge test is generally performed according to the Bruce protocol and often consists of running on a treadmill or using an exercise bike (aka bicycle ergometer) while trying to reproduce the duration and/or effort involved during the previous anaphylactic reaction. This is done under close observation and may include cardiopulmonary exercise testing to rule out exercise-induced asthma.

The exercise is varied according to the ability of the person taking the test. Children, for example, are often asked to run back and forth along a corridor for six minutes until they reach 80% maximum heart frequency for their age (or a heart rate of at least 170 beats/min). In one study, an elderly man with suspected FDEIA was asked to stomp his feet for 15 minutes.

Part 4: the food and exercise challenge

On this day. the food and exercise challenge are combined; you are asked to eat the suspected food (or any food, if this is a case of nonspecific FDEIA) and an exercise test is performed one hour later.

The gold standard of FDEIA diagnosis is a double-blind placebo-controlled food exercise challenge (DBPCFEC). During this type of challenge neither you nor the doctor knows whether you are eating the food you might be allergic to, or a placebo meal which contains food that you should not react to. The evaluation of FDEIA is not standardised, and a double-blind challenge is not required to diagnose FDEIA, and often not performed.

Part 5: a challenge with food and a cofactor with or without exercise

Sometimes, you may be given an NSAID (often aspirin) and/or alcohol before eating the suspected food and (perhaps) taking the exercise test.

It could be that drugs are a standard part of the protocol in a certain allergy centre or that your medical history suggests that cofactors may be needed to provoke an allergic reaction.

Or you may have to take this challenge if your previous challenge(s) produced no symptoms but your medical history strongly suggests that you have FDEIA.

Not an easy task…

Diagnosing FDEIA is not easy. Ultimately, the point of the challenge is to try and reproduce the setting, food and features (exercise intensity, heat, drugs…) involved in the previous allergic reaction as closely as possible.

But everyone is different, each individual needs a different amount of food to trigger a reaction, a different amount and intensity of exercise, a different amount of time between food and exercise, a different food or a combination of foods, an added cofactor or combination thereof.

Then there are the cofactors that aren’t considered like lying face down in the cold, which is not something that springs to mind when carrying out a challenge in a lab. Having an infection or experiencing emotional stress are also not tested, being ethically problematic, if not impossible to achieve.

All of these types of cofactors (and probably more which haven’t been identified yet) help to explain why reactions produced in people’s daily lives are often not reproduced during allergy testing and why many challenges produce false negative results.

So, a negative challenge test doesn’t necessarily mean that you don’t have FDEIA and allergists often find themselves having to work with ambiguous test results and uncertain diagnoses.

Arriving at a diagnosis for food-dependent exercise-induced anaphylaxis is such a complex and tricky process that the condition is often misdiagnosed and many people with FDEIA may suffer through several reactions and have a long wait before their condition is identified. A retrospective study of 132 British patients eventually diagnosed with WDEIA in four allergy centres around the UK reported that 2 in 5 people (40%) had to wait over a year for a diagnosis, and just under under a third (29%) had to wait over 5 years.

A similar study which analysed the medical records of 197 Chinese patients with WDEIA who had been seen at one hospital in Peking reported that the average time to diagnosis was 16 months, with the quickest diagnosis being made immediately and the longest taking 26 years. Another study of 80 Australians with omega 5 gliadin allergy seen at a hospital in Melbourne over an 8-year period reported an average wait of 2 years before being diagnosed, with one poor individual having to wait 30 years!

As well as the challenges for the allergists setting up the challenges for the patient, it can be difficult getting to the challenge in the first place; in many cases, FDEIA is simply not suspected. One of the most common reasons for a delay in diagnosis is that, for a lot of people, minimal exercise is needed to provoke a reaction; it’s difficult to suspect an exercise-induced allergy when someone shows symptoms after doing some ironing.

Another reason may be the fact that the initial symptoms are not deemed serious enough to warrant a referral. In a study comparing the differences between Chinese and British patients with omega 5 gliadin allergy, patients in Hong Kong were found to have more serious symptoms than patients in London, a difference that was put down to the higher referral threshold among physicians in HK, where people who do not shown ‘typical’ or severe signs of allergy, like hives or anaphylactic shock, tend not to be recognised and referred to an allergist.

In some people, another allergic condition, the absence of typical FDEIA triggers and ambiguous test results can conspire to conceal the underlying problem.

Sometimes a diagnosis is difficult to arrive at because the tools are not quite there yet. In this case, a 47-year-old woman went through several anaphylactic episodes and had to undergo two lots of testing before she was able to eliminate the right food from her diet because, the first time she went in for testing, her skin tests showed sensitivity to a suspect food that matched her medical history but that she could actually tolerate (shellfish) and the specific (wheat) allergen that she was allergic to was not yet available for testing.

And sometimes there are many possible factors involved and the most obvious ones—according to the patient’s history—produce negative test results. In these cases, the allergist just has to go with their gut feeling to make the diagnosis, as in the case of a 22-year-old woman who had 2 anaphylactic attacks while jogging that may or may not have been caused by a combination of spring pollen, seafood and exercise.

Differential diagnosis

If your symptoms and signs are not typical, the allergists will have to look for another cause.

The most obvious alternative is:

Exercise-induced anaphylaxis

Exercise-induced anaphylaxis (EIA) is basically exactly like food-dependent exercise-induced anaphylaxis, but without the need for food. It can be differentiated from FDEIA with an exercise challenge on an empty stomach that produces symptoms as well as negative lab tests for common food allergens.

EIA is generally either confirmed or ruled out during the exercise challenge part of the provocation test.

If you still don’t have a diagnosis, there’s a wide list of conditions to consider that can be associated with exercise and could either coincidentally occur when you eat a certain food (if, for instance, you have a particular meal you always eat on a certain day or before exercising) or can co-exist with a food allergy.

A food-induced allergy can be ruled out in the following cases if your medical history include reactions that are not linked to a particular food and/or by negative skin/blood tests.

Exercise-induced asthma

Exercise-induced bronchoconstriction (aka exercise-induced asthma, although this term is frowned upon because it implies that exercise causes asthma, which is not the case) is the name given to a condition in which exercise causes your airways to get smaller, producing symptoms of asthma. It often occurs in people who have asthma but up to 1 in 5 cases occur in people without an asthma diagnosis.

It can be differentiated from (food-dependent) exercise-induced anaphylaxis by an exercise challenge that produces a decrease in lung function and the associated respiratory symptoms (cough, wheezing, shortness of breath and/or chest tightness) but no skin or cardiovascular symptoms.

This can also either be confirmed or ruled out on during the exercise challenge part of the provocation test.

Cholinergic urticaria

Cholinergic urticaria (CU, aka cholinergic angio-oedema or heat bumps) is a reaction provoked by an increase in body temperature. This can happen during exercise, but it can also happen if you have a hot bath, feel angry, eat spicy food or leave a cool room to go outside on a hot day. People with CU can also develop anaphylaxis.

It can be differentiated from EIA when the medical history includes reactions that occurred when a person was not exercising and the fact that the hives provoked by CU are typically smaller (1 to 5 mm weals also referred to as ‘punctate’ hives) than the ones produced by FDEIA (weals usually 10 to 15 mm in diameter or larger) and surrounded by reddened skin.

Cold-induced urticaria

Cold urticaria (or cold hives) is a rare condition in which hives are triggered within minutes after exposure to cold air, fluids or objects. Someone with cold urticaria could be confused for someone with an exercise-induced allergy because they can develop a rash or hives after swimming or bathing in cold water or walking outside in cold weather.

Cold urticaria can be differentiated from EIA by a personal history that includes symptoms associated with cold but not exercise, and by using the ice cube challenge: an ice cube placed on the skin for up to 30 minutes (often 3 to 4 minutes) should induces hives during rewarming. (People with hereditary cold urticaria will generally take longer to develop symptoms than those with essential cold urticaria.)

… and other forms of urticaria, including exercise-induced urticaria (EIU) in which physical activity leads to the development of hives (with or without angio-oedema), dermatographic urticaria in which shearing forces such as rubbing produce hives, delayed pressure urticaria in which pressure to the skin by, for example, tightly fitting gym clothing, causes the development of hives, vibratory urticaria, in which vibrations, for example from a bike on the road, produces hives, solar urticaria which is hives caused by the sun and/or ultraviolet light and aquagenic urticaria (aka water allergy and water urticaria) in which contact with water provokes hives. This is regardless of the temperature although, it can be temperature dependant and involve anaphylaxis.

Other conditions

Other conditions which could mimic symptoms of exercise-induced allergies include exercise-associated reflux, which produces flushing, throat discomfort, and chest tightness/cough (but not itchy skin, hives or swelling) and hereditary angio-oedema, a rare genetic condition that causes swelling (but not hives) in different parts of the body.

Conditions that produce anaphylactic symptoms include mastocytosis, which makes sufferers susceptible to anaphylactic attacks from a variety of triggers, including exercise, and NSAID-induced urticaria/anaphylaxis, which is hives or anaphylaxis caused by NSAID medications like aspirin.

Another category of disorders that a doctor may looked into is cardiovascular events like arrhythmias which can cause sudden fatigue, shortness of breath and collapse during exercise (but not skin symptoms).

There are also allergies to things that are eaten but aren’t food.

Sometimes a reaction looks like a case of WDEIA but it’s actually a reaction to something hiding in wheat flour; dust mites. This allergy to hidden mites was initially discovered in people who had anaphylaxis after eating pancakes, hence its alternative name, pancake syndrome. As with other instances of FDEIA, the person has to exercise after eating the mites to show any symptoms.

Sometimes the reaction can be caused by mould on the food. This was the case for a 14-year-old boy who had three allergic reactions—starting off with just skin symptoms and a cough during the first episode but ending with loss of consciousness during the 3^rd episode—after 2 running events and during a football match. Before each episode of exercise, he had eaten meals containing a relatively wide range of foods, but skin tests and challenges with those foods produced negative results. However, someone was clever enough to consider the possibility of a food contaminant and discovered mould (P. lanoso-caeruleum) in the food, and subsequent testing showed that his allergic reactions required that particular strain of mould combined with exercise.

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What’s the prognosis?

Food-dependent exercise-induced anaphylaxis is rarely fatal and the number of case reports describing fatalities are still in the single digits.

That said, unless it’s associated with a childhood allergy which is outgrown, the condition generally stays with you for life. In a retrospective review of the medical records of 197 people with WDEIA, just one person reported achieving tolerance. That person had avoided exercising after eating wheat for 5 years after his diagnosis, until one day he accidentally found himself running to catch a train after eating a breakfast containing wheat and didn’t develop any symptoms. So he started eating wheat whenever he wanted to again and, at least by the time the study was carried out, suffered no more reactions.

Sometimes the opposite can happen, as in the case of a13-year-old boy who was diagnosed with FDEIA to apple and later developed a conventional food allergy (or, possibly, his reaction threshold simply decreased to a level where a ‘normal’ portion of apple produced symptoms).

The good news is that most people find that the frequency of attacks tends to stabilise or decrease over time, as long as they do they best to avoid their triggers.

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