anaphylaxis is defined as a very serious systemic hypersensitive allergic reaction involving the skin , respiratory tract , gastrointestinal ( gi ) tract , and cardiovascular system .
this spontaneous and severe reaction is often accompanied by various signs and symptoms such as dyspnea , angioedema , and hypotension .
previous studies found that the rate of food anaphylaxis is between 0.008 to 0.05% per year with a lifetime prevalence of 0.05 to 2.0% . according to another previous investigation
, the prevalence of food anaphylaxis has been underestimated while the occurrence has dramatically increased .
other scientific data have indicated that up to 2% of the western population might be affected by food anaphylaxis .
the difference between anaphylaxis and food - dependent exerciseinduced anaphylaxis ( fdeian ) is the inclusion of physical activity as a causative factor .
fdeian arises from a combination of allergenic food and exercise , especially high - intensity regimens . in other words ,
an individual who has fedian will present signs and symptoms during exercise a few hours after ingesting allergenic food .
fdeian is a subtype of exercise - induced anaphylaxis ( eia ) characterized by the onset of symptoms of anaphylaxis during or following physical exertion .
it has been reported that fdeian symptoms include urticaria , respiratory disturbances ( e.g. , dyspnea , coughing , and wheezing ) , angioedema , gi manifestations , and even hypotension . the symptoms of eia can be observed at any moment during or after physical activity
. however , approximately , 90% of patients develop symptoms within 30 min after exercise cessation . in cases of fdeian ,
however , some research has indicated that fdeian may also occur if the patient ingests allergenic food soon after the completion of exercise .
although not all the food allergens have been identified , stellato et al .   suggested that exercising after consuming of shellfish can produce allergic reactions .
there are some studies indicating that omega-5 gliadin and gluten are common allergens involved in wheat - dependent fdeian .
the prevalence of fdeian has not been accurately reported although this condition is thought to be an infrequent phenomenon .
while the cause of fdeian remains unknown , it has been surmised that allergic anaphylaxis can be initiated by the onset of exercise in patients who have low - grade type i allergies to specific foods .
exercise helps increase the absorption of food allergens in the gi tract and the degranulation of mast cells .
it has also been reported that ige production is increased in patients with allergies because isotype switching from type i to type ii cytokines occurs during physical exercise .
dermatological tests and in vitro serum food - specific ige assays are not sensitive enough to detect ige - mediated hyperreactivity . the importance of fdeian should not be overlooked because this is a life - threatening disorder .
this syndrome can be categorized into two distinctive forms : systemic cholinergic urticarial ( cu ) and eia .
various forms of exercise - related allergies have been described including a random rash associated with cu , a conventional form of eia , and variant eia . in this review ,
we describe three types of eia along with the diagnosis , pathophysiology , and treatment of this disorder .
this reaction is mainly caused by active heat generation or passive heating , but is rarely associated with angioedema , bronchospasm , or hypotension .
the characteristics of cu are well known ; however , the specific mechanism underlying this condition has not been elucidated in detail .
exercise - induced cu has to be distinguished from eia , which is a potential life - threatening condition and a challenge for medical providers .
the subtypes of urticaria most commonly seen in athletes are acute forms induced by exercise , temperature , sunlight , water , or certain levels of external pressure .
figure skaters , skiers , ice hockey players , and speed skaters exposed to a cold environment frequently suffer from dermatological injuries .
cold urticaria is another type of physical urticaria defined as urticaria and angioedema arising after exposure to the cold .
effective management of cold urticarial includes patient education , antihistamine administration , and avoidance of precipitating triggers such as hot showers , strenuous exercise , or prolonged exercise .
exercise modification such as changing exercise type , duration , intensity , and frequency is commonly recommended for patients with anaphylaxis .
cases of urticaria or angioedema and hypotension induced by intense physical activity are classified as conventional eia .
eia is associated with other disorders including atopic eczema , atopic asthma , exercise - induced asthma , and seasonal rhinitis .
exercise - induced asthma that is related to exercise and allergenic food intake is associated with typical asthma symptoms , but these symptoms are limited to the lower airways .
vigorous exercise such as jogging and running have been identified as activities that can trigger eia .
other high- and/or low - intensity exercises such as soccer , tennis , swimming , basketball , snowboard , and walking have also been identified as activities linked to eia .
signs and symptoms generally last at least 30 min and up to 4 h after exercising .
eia occurs as a result of mast cell degranulation leading to the release of histamine and other mediators into the circulation .
an exaggerated pathologic response to increased temperature seems to provoke mast cell degranulation in individuals with cu . in cases of conventional eia ,
exercise is considered a physical stimulus that induces mast cell degranulation through an unknown mechanism .
in addition , airway maintenance and preserving normal cardiovascular function is very important for preventing further complications .
prophylactic treatment includes exercise avoidance , abstinence from specific foods and medications , pretreatment with antihistamines , caffeine , and cromolyn ( used to prevent exercise - induced asthma ) ; and the induction of tolerance to cu through regular physical activity .
the typical signs of variant eia are punctate erythematous papules and symptoms similar to those of cu .
anaphylaxis can occur when patients consume a particular food and participate in exercise within a few hours of eating . during physical activity
, cardiovascular problems such as sudden cardiac death can be an unique sign or symptom of exercise - induced food allergies .
however , it is expected that food allergens , exercise , and subsequent ige action reduce the mast cell release threshold .
fdeian is provoked by the combination of allergenic food and physical exercise whereas for eia is caused by exercise alone while cu is induced by stress , heat , and exercise .
severity of an allergic reaction can be determined based on the amount of allergenic food that has been consumed .
the most common trigger foods for fdeian are eggs , milk , wheat products , cheese , tomatoes , peaches , and shellfish .
epinephrine is the most common treatment for allergy anaphylaxis while h1 antagonists and salbutamol can be used to relieve secondary symptoms .
it is well known that the clinical symptoms of eia include pruritus , urticaria , angioedema , respiratory distress , and syncope . to diagnose fdeian , the medical history of the patient is first reviewed to find a specific cause of the symptoms and/or signs .
physical allergies are a group of reactions caused by physical stimuli such as low temperature , heat , exercise , sunlight , and mechanical pressure . it has also been reported that alcohol consumption can provoke a variety of hypersensitive reactions . furthermore , alcohol intake may increase total serum ige levels .
ige specific for different foods can be detected by either an immediate skin test or radioallergosorbent test ( rast ) in these patients .
the other group consists of patients who do not respond to a specific food allergen .
fdeian is marked by the onset of anaphylaxis during or soon after exercise preceded by the intake of allergenic foods .
as previously stated , fdeian is a rare disease in which postprandial exercise causes anaphylaxis .
however , several other factors such as physical and mental stress , fatigue , dry air , insufficient sleep , the common cold , humid weather , low temperature , and non - steroidal anti - inflammatory drugs ( nsaids ) are reported to aggravate anaphylaxis . if a patient is suspected to suffer from fdeian , a diagnostic physical stress test can be performed .
this can be accomplished on a treadmill or cycle ergometer in a manner similar to graded exercise testing .
previous animals studies demonstrated that exercise intensity and duration is positively correlated with fdeian severity .
the fdeian score is increased with high exercise intensity and duration compared to low intensity and duration .
this is because intense and prolonged exercise converts th1 lymphocytes into th2 lymphocytes caused by th2 cytokine production [ 32 - 34 ] .
therefore , more intense and prolonged episodes of exercise provoke a more severe allergic reaction . moreover , vigorous exercise facilitates allergen absorption from the gi tract , leading to fdeian .
skin vasoactive mediators are major factors that cause eia symptoms . additionally , increased plasma histamine levels are a typical indicator of variant and conventional forms of eia and cu .
other research indicated that physical exercise disrupts the digestion and absorption of allergenic food , leading to a rise in allergenic proteins in the blood .
this results in ige - mediated mast cell sensitization , and the release of heparin and histamine in response to the allergenic food that was consumed .
histamine also induces vasodilation , and leads to urticaria and angioedema , decreased blood pressure , and syncope .
the best treatment for fedian is to prevent the intake of causative foods and reduce exercise intensity . for cases of specific fdeian
, patients should not consume causative foods before physical activity . for cases of non - specific fdeian
, individuals should not participate in exercise within 1 - 6 h after consuming allergenic food .
patients who participate in exercise are also encouraged to have an individualized emergency kit that includes epinephrine , antihistamines , and corticosteroids .
the use of cromolyn , a mast cell stabilizer and antihistamine , has been shown to be effective for the prophylactic treatment of fdeian .
this reagent prevents the degranulation of mast cells , plasma histamine efflux , and the production of pro - inflammatory factors .
modification of exercise regimes , detraining , and cross - training are also important for treating patients suffering from fdeian .
individuals with fdeian should avoid causative allergenic foods and not exercise until 4 to 6 h after eating .
if patients have any signs or symptoms while exercising , they should stop their exercise and seek medical aid if the symptoms persist .
this reaction is mainly caused by active heat generation or passive heating , but is rarely associated with angioedema , bronchospasm , or hypotension .
the characteristics of cu are well known ; however , the specific mechanism underlying this condition has not been elucidated in detail .
exercise - induced cu has to be distinguished from eia , which is a potential life - threatening condition and a challenge for medical providers .
the subtypes of urticaria most commonly seen in athletes are acute forms induced by exercise , temperature , sunlight , water , or certain levels of external pressure .
figure skaters , skiers , ice hockey players , and speed skaters exposed to a cold environment frequently suffer from dermatological injuries .
cold urticaria is another type of physical urticaria defined as urticaria and angioedema arising after exposure to the cold .
effective management of cold urticarial includes patient education , antihistamine administration , and avoidance of precipitating triggers such as hot showers , strenuous exercise , or prolonged exercise .
exercise modification such as changing exercise type , duration , intensity , and frequency is commonly recommended for patients with anaphylaxis .
cases of urticaria or angioedema and hypotension induced by intense physical activity are classified as conventional eia .
eia is associated with other disorders including atopic eczema , atopic asthma , exercise - induced asthma , and seasonal rhinitis .
exercise - induced asthma that is related to exercise and allergenic food intake is associated with typical asthma symptoms , but these symptoms are limited to the lower airways . vigorous exercise such as jogging and running have been identified as activities that can trigger eia .
other high- and/or low - intensity exercises such as soccer , tennis , swimming , basketball , snowboard , and walking have also been identified as activities linked to eia .
signs and symptoms generally last at least 30 min and up to 4 h after exercising .
eia occurs as a result of mast cell degranulation leading to the release of histamine and other mediators into the circulation .
an exaggerated pathologic response to increased temperature seems to provoke mast cell degranulation in individuals with cu . in cases of conventional eia ,
exercise is considered a physical stimulus that induces mast cell degranulation through an unknown mechanism .
in addition , airway maintenance and preserving normal cardiovascular function is very important for preventing further complications .
prophylactic treatment includes exercise avoidance , abstinence from specific foods and medications , pretreatment with antihistamines , caffeine , and cromolyn ( used to prevent exercise - induced asthma ) ; and the induction of tolerance to cu through regular physical activity .
the typical signs of variant eia are punctate erythematous papules and symptoms similar to those of cu .
anaphylaxis can occur when patients consume a particular food and participate in exercise within a few hours of eating . during physical activity
, cardiovascular problems such as sudden cardiac death can be an unique sign or symptom of exercise - induced food allergies .
however , it is expected that food allergens , exercise , and subsequent ige action reduce the mast cell release threshold .
fdeian is provoked by the combination of allergenic food and physical exercise whereas for eia is caused by exercise alone while cu is induced by stress , heat , and exercise .
severity of an allergic reaction can be determined based on the amount of allergenic food that has been consumed .
the most common trigger foods for fdeian are eggs , milk , wheat products , cheese , tomatoes , peaches , and shellfish .
epinephrine is the most common treatment for allergy anaphylaxis while h1 antagonists and salbutamol can be used to relieve secondary symptoms .
it is well known that the clinical symptoms of eia include pruritus , urticaria , angioedema , respiratory distress , and syncope . to diagnose fdeian
, the medical history of the patient is first reviewed to find a specific cause of the symptoms and/or signs .
physical allergies are a group of reactions caused by physical stimuli such as low temperature , heat , exercise , sunlight , and mechanical pressure .
it has also been reported that alcohol consumption can provoke a variety of hypersensitive reactions .
ige specific for different foods can be detected by either an immediate skin test or radioallergosorbent test ( rast ) in these patients .
the other group consists of patients who do not respond to a specific food allergen .
fdeian is marked by the onset of anaphylaxis during or soon after exercise preceded by the intake of allergenic foods .
as previously stated , fdeian is a rare disease in which postprandial exercise causes anaphylaxis .
however , several other factors such as physical and mental stress , fatigue , dry air , insufficient sleep , the common cold , humid weather , low temperature , and non - steroidal anti - inflammatory drugs ( nsaids ) are reported to aggravate anaphylaxis . if a patient is suspected to suffer from fdeian , a diagnostic physical stress test can be performed .
this can be accomplished on a treadmill or cycle ergometer in a manner similar to graded exercise testing .
previous animals studies demonstrated that exercise intensity and duration is positively correlated with fdeian severity .
the fdeian score is increased with high exercise intensity and duration compared to low intensity and duration .
this is because intense and prolonged exercise converts th1 lymphocytes into th2 lymphocytes caused by th2 cytokine production [ 32 - 34 ] .
therefore , more intense and prolonged episodes of exercise provoke a more severe allergic reaction .
moreover , vigorous exercise facilitates allergen absorption from the gi tract , leading to fdeian .
skin vasoactive mediators are major factors that cause eia symptoms . additionally , increased plasma histamine levels are a typical indicator of variant and conventional forms of eia and cu .
other research indicated that physical exercise disrupts the digestion and absorption of allergenic food , leading to a rise in allergenic proteins in the blood .
this results in ige - mediated mast cell sensitization , and the release of heparin and histamine in response to the allergenic food that was consumed .
histamine also induces vasodilation , and leads to urticaria and angioedema , decreased blood pressure , and syncope .
the best treatment for fedian is to prevent the intake of causative foods and reduce exercise intensity . for cases of specific fdeian
, patients should not consume causative foods before physical activity . for cases of non - specific fdeian
, individuals should not participate in exercise within 1 - 6 h after consuming allergenic food .
patients who participate in exercise are also encouraged to have an individualized emergency kit that includes epinephrine , antihistamines , and corticosteroids .
the use of cromolyn , a mast cell stabilizer and antihistamine , has been shown to be effective for the prophylactic treatment of fdeian .
this reagent prevents the degranulation of mast cells , plasma histamine efflux , and the production of pro - inflammatory factors .
modification of exercise regimes , detraining , and cross - training are also important for treating patients suffering from fdeian .
individuals with fdeian should avoid causative allergenic foods and not exercise until 4 to 6 h after eating .
if patients have any signs or symptoms while exercising , they should stop their exercise and seek medical aid if the symptoms persist .
for management of acute anaphylaxis , an open airway should be maintained . vascular collapse and angioedema
fdeian is a clinically distinct form of anaphylaxis in which symptoms occur only when the patient exercises within a few hours of eating allergenic food .
the precise mechanism underlying this disease remains unclear and has been reported to have a wide variety of factors .
fdeian is characterized by symptoms of anaphylaxis due to the consumption of allergenic foods that manifest during or soon after exercising .
these include running , tennis , basketball , soccer , swimming , and even brisk walking .
numerous foods ( e.g. certain fruits , shrimp , shellfish , chicken , wheat , nuts , eggs , and vegetables ) have been identified as allergens associated with fdeian .
individuals may be diagnosed with eia if a reaction occurs with physical exertion alone without any food intake .
however , cu should be distinguished from eia . to prevent the occurrence of fdeian , patients should not eat any causative food within 4 h before exercising and should avoid vigorous physical activities .
however , limited intake of causative food has been found to be a reliable method for preventing fdeian . in this review
further research on the specific mechanisms underlying fdeian along with the development of effect treatment and diagnosic techniques are urgently needed .
 food - dependent exercise - induced anaphylaxis ( fdeian ) is induced by different types and various intensities of physical activity , and is distinct from food allergies . 
 it has been shown that consumption of allergenic food followed by exercise causes fdeian symptoms . 
 intake of allergenic food or medication before exercise is a major predisposing factor for fdeian . 
 urticaria and severe allergic reactions are general symptoms of fdeian . 
 dermatological tests and serum ige assays are the typical prescreening methods , and have been used for several decades . however , these screening tests are not sufficient for detecting or preventing fdeian . it has been found that exercise may stimulate the release of mediators from ige - dependent mast cells that can result in fdeian when a certain threshold level has been exceeded . 
 mast cell degradation might be a major factor to induce fdeian but this has not been determined . 
 a number of foods have been reported to be involved in the onset of fdeian including wheat , eggs , chicken , shrimp , shellfish , nuts , fruits , and vegetables . 
 it is also known that aspirin increases the occurrence of type i allergy symptoms when combined with specific foods . moreover , high intensity and frequent exercise are more likely to provoke an attack than low intensity and less frequent exercise . in this paper , we present the current views of the pathophysiological mechanisms underlying fdeian within the context of exercise immunology 
 . we also present a detailed fdeian definition along with etiologic factors and medical treatment for cholinergic urticaria ( uc ) and exercise - induced anaphylaxis ( eia ) . 
Introduction
The main discourse
CU
Conventional EIA
Variant EIA and FDEIAn
Diagnosis, pathophysiology, and treatment of FDEIAn
Conclusions