Exercise and aspirin increase levels of circulating gliadin peptides in patients with wheat-dependent exercise-induced anaphylaxis

BACKGROUND: Food-dependent exercise-induced anaphylaxis (FDEIA) is an allergic reaction characteristically induced by intense exercise combined with the ingestion of causative food. Recent reports have shown that aspirin intake is a contributing factor in some patients with FDEIA. Wheat is known to be the most frequent causative food, and the IgE-binding epitopes of a major wheat allergen (omega-5 gliadin) in wheat-dependent exercise induced anaphylaxis (WDEIA) have already been clarified. However, the mechanism of eliciting the symptom in WDEIA remains not fully understood. OBJECTIVES: The aim of this study was to examine the relationship of serum gliadin levels and allergic symptoms induced by exercise or aspirin in patients with WDEIA. METHODS: Six patients with a history of recurrent anaphylaxis associated with wheat ingestion were diagnosed as having WDEIA by the provocation test, which included wheat ingestion, exercise, aspirin intake and a combination of these challenges. During the tests, serum levels of gliadins were monitored by gliadin-specific sandwich ELISA. The effects of exercise and aspirin on serum gliadin levels were also investigated in four healthy subjects. RESULTS: 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. Serum gliadin levels also increased under the two same challenge conditions in the healthy subjects, although they exhibited no allergic symptoms. However, low levels of gliadin were detected in the sera of both patients and healthy subjects when challenged with wheat alone. CONCLUSION: We demonstrated for the first time that blood gliadin levels correlate with clinical symptoms induced by exercise and aspirin in patients with WDEIA. These findings suggest that exercise and aspirin facilitate allergen absorption from the gastrointestinal tract.     

Food-dependent exercise-induced anaphylaxis that was difficult to evoke by a provocation test

As a result of ingesting wheat- and soybean-based food products in school meals, an 8-year-old boy repeatedly experienced dyspnea and urticaria while exercising. Based on the symptoms, he was assumed to have been experiencing a food-dependent exercise-induced anaphylactic reaction. Based on the Japanese pediatric guideline for oral food challenge in food allergy 2009, examination using various combinations of food products (wheat and soybeans), medicine (aspirin), and exercise was performed. However, the examination failed to elicit any symptoms. Although we eliminated the food products from the examination, dyspnea caused by exercising after ingesting only wheat products was observed again. Thereafter, we performed a provocation test using wheat products, but symptoms were observed only on increasing the amount of ingested food and the momentum of exercise, without administering aspirin. The possibility that wheat is a more potent inducing factor than aspirin in increasing the momentum of exercise and amount of ingestion in food-dependent exercise-induced anaphylaxis was suggested.     

Two cases of food-dependent exercise-induced anaphylaxis difficult to evoke symptoms by provocation test]

We report two cases of food-dependent exercise-induced anaphylaxis (FDEIA), which were hardly induced by provocation test in the hospital. Case 1: A 28-years-old Japanese female suffers repeated episodes of sternutation, nasal discharge and edema of eyelids after wheat ingestion of wheat followed by exercise. Case 2: A 14-years-old Japanese male suffers repeated episodes of wheal formation on whole body and dyspnea after lunch containing apple followed by exercise. Both of them had never developed symptoms by either ingestion or exercise alone. Provocation tests were performed on admission by combinations of the ingestion of suspected foods, exercise, and aspirin, but no symptoms were reproduced by any combination of them. After discharge, case 1 reproduced symptoms during exercise after the ingestion of wheat under prostration and cold climate. Case 2 reproduced symptoms during exercise after ingestion of apple when he suffered from common cold. Warm and comfortable condition in admission may make it harder to evoke symptoms by the provocation test. Frigidity, cold, prostration, and stress should be reckoned with in the provocation test to improve the accuracy of diagnosis for FDEIA.     

Life-threatening, recurrent anaphylaxis caused by allergy to gliadin and exercise

Background Exercise-induced urticaria or anaphylaxis is regarded as a distinct form of physical allergy. In some patients the symptoms occur only after ingestion of various food products in connection with exercise. We have come across patients with cereal dependent exercise-induced anaphylaxis. Objectives The purpose of the present study was to analyse the allergens in cereals responsible for the severe anaphylactic symptoms and to verify the test methods suitable for screening the patients with cereal dependent exercise-induced anaphylaxis. Methods The patients underwent skin-prick tests (SPT) with common inhalant and food allergens as well as with various cereal extracts. IgE-immunoblotting was used to identify the allergenic fractions. Results Five patients found positive in SPT with NaC1 wheat suspension had IgE antibodies to wheat, rye, barley and oats, especially directed against the ethanolsoluble protein fractions in immunoblotting. No IgE antibodies were detected against other cereals. The patients had been unaware of any cereal allergy since anaphylaxis occurred only in association with exercise postprandially. The patients were directed to follow a gluten-free diet and have been free from symptoms, being able to continue their outdoor physical activities. Conclusion Wheat gliadin and the corresponding ethanol-soluble proteins of taxonomically closely related cereals were found to be the allergens in cereal-dependent exercise-induced anaphylaxis. Skin-prick testing with NaC1 wheat suspension was a simple and practical test to screen patients with this kind of occult, possibly life-threatening, allergy to cereals.     

Wheat - Dependent Exercise-Induced Anaphylaxis Occurred With a Delayed Onset of 10 to 24 hours After Wheat Ingestion: A Case Report

Wheat-dependent exercise-induced anaphylaxis (WDEIA) usually occurs 1 to 4 hours after wheat ingestion and the pathophysiology of WDEIA remains unknown. It is recommended that WDEIA patients refrain from exercise for 4 to 6 hours after wheat ingestion. We report a case of a 51-year-old man who experienced 5 anaphylaxis attacks; two of which occurred 10 to 24 hours after wheat ingestion and exercise. He has a history of chronic gastroenteritis that responds well to antihistamine drugs but not proton pump inhibitors (PPIs) and prokinetic agents. Abdominal CT results implied the possibility of superior mesenteric artery syndrome. We suggest that WDEIA occurs 6 hours after wheat ingestion in cases compounded by obstructive gastrointestinal diseases.     

Enhancement of nonsteroidal, anti-inflammatory drugs and preventive effect of antihistamines and disodium cromoglycate on wheat allergy]

BACKGROUND: Aspirin has been known to be an enhancer to wheat allergy, including wheat-dependent, exercise-induced anaphylaxis. OBJECTIVE: To investigate whether nonsteroidal, anti-inflammatory drugs (NSAIDs) other than aspirin would enhance allergic reactions after wheat ingestion and whether antihistamines and disodium cromoglycate would prevent these reactions. METHODS: Seven cases, whose reactions after wheat ingestion were enhanced by aspirin on challenge tests, were enrolled. Skin prick tests (SPT) and CAP-RAST were undergone for wheat and gluten. We used challenge tests of wheat after pretreatment of NSAIDs and preventive drugs. RESULTS: Four cases were diagnosed with wheat allergy, 3 cases had wheat-dependent, salicylic acid-induced anaphylaxis. SPT and CAP-RAST were positive for wheat and gluten in 5 of 7 cases and 4 of 7 cases, respectively. Dicrofenac enhanced the allergic reactions after wheat ingestion in 1 of 2 cases, whereas etodolac failed to enhance the symptoms in all 5 cases performed. Furthermore, disodium cromoglycate could not completely prevent the allergic reaction in all 4 cases and even enhanced the reaction in 1 case of them. To see an inhibitory effect of antihistamines on the symptoms, fexofenadine (in 2, 1 and 1 case, respectively), olopatadine, and chlorpheniramine were administrated before the challenge test, and as a result these drugs were found to have inhibitory effects on the allergic reaction. CONCLUSION: In this study, it was suggested that etodolac might be a relatively safe anti-inflammatory drug on wheat allergy and antihistamines could prevent allergic reactions more than DSCG in patients with wheat allergy.     

Wheat-induced anaphylaxis

A 13 year old boy suffered two separate episodes of severe anaphylaxis after consuming sandwiches and a piece of bread. Prick skin testings with available food allergens only revealed a positive reaction to a 1:10 w/v of wheat flour extract. A diagnosis of wheat-induced anaphylaxis was made and a double blind food challenge was suggested however was declined by the family. The patient was instructed to avoid all wheat containing foods and to carry a kit containing an epinephrine pre-loaded syringe and an antihistamine tablet to be used in the event of inadvertant consumption with an instruction to seek medical assistance as soon as possible. Thus far, no further recurrence of anaphylaxis was encountered. A review of the current literature discloses that wheat-induced anaphylaxis is an uncommon event and could occur either immediately after the ingestion or with a concomitant exercise. The natural history of wheat allergy is currently not fully understood but may possibly be a life long event.     

Wheat anaphylaxis in children

Food anaphylaxis is now the leading known cause of anaphylactic reactions treated in emergency departments, and wheat is one of the most common causes of anaphylaxis. Wheat is an important source of food worldwide. Wheat anaphylaxis is increasingly observed in our clinic. The purpose of this study was to describe the clinical features of wheat-induced anaphylaxis in 19 children for better elucidation of this disease. Children with severe reactions after ingestion of small amounts of wheat were referred to our clinic during a 4-year period. A detailed clinical history was recorded for each of the patients and a skin prick test was performed with wheat allergen extracts. The wheat-specific IgE and total IgE were measured. Grading of anaphylaxis episodes was performed according to a specific grading system. We identified 36 episodes of wheat anaphylaxis in 19 patients. All of the first attacks of wheat anaphylaxis occurred in the first-time ingestion. The most frequent manifestations of the reactions were skin and respiratory symptoms. In this study 78.9% of reactions were moderate and 21.1% of them were severe. All of our patients had positive skin prick tests to wheat. Mean total IgE level was 853.4 ± 455.27 IU/ml, and mean wheat-specific IgE was 70 ± 14.61 Ucs/ml. We conclude that wheat-induced anaphylaxis is a disease that is sufficiently severe, and. prevention of first wheat-induced anaphylaxis episodes is almost impossible. It would, however, probably be good practice to educate physicians to recognize the common clinical manifestations of this disease for early management.     

Exercise-induced anaphylaxis (EIA)

Summary EIA is a unique physical allergy with increasing incidence as the exercising population increases. Clinical features are indistinguishable from IgE-mediated anaphylaxis in which the offending allergens are known (food or insect stings). Recognition of the association with exercise is crucial. A wide variety of exercises can induce the symptoms, including brisk walking. Symptoms may not be always reproduced by the same amount and type of exercise in a given patient suggesting that associated factors are also needed. Food is an associated factor recognized with increasing frequency, and in the last 5 yr, wheat has been the most frequently associated. Avoidance of the known associated factors, such as food of nonsteroidals, induces a long-lasting remission of EIA. Treatment does not differ from that of anaphylaxis of any other cause. General recommendations for patients with EIA include avoidance of exercise 4–6 h after eating, avoidance of aspirin and nonsteroidals before exercise, and avoidance of all associated conditions known to trigger attacks in each particular patient. Discontinuation of exercise at the earliest warning symptom is critical.     

Wheat Anaphylaxis in Children

Food anaphylaxis is now the leading known cause of anaphylactic reactions treated in emergency departments, and wheat is one of the most common causes of anaphylaxis. Wheat is an important source of food worldwide. Wheat anaphylaxis is increasingly observed in our clinic. The purpose of this study was to describe the clinical features of wheat-induced anaphylaxis in 19 children for better elucidation of this disease. Children with severe reactions after ingestion of small amounts of wheat were referred to our clinic during a 4-year period. A detailed clinical history was recorded for each of the patients and a skin prick test was performed with wheat allergen extracts. The wheat-specific IgE and total IgE were measured. Grading of anaphylaxis episodes was performed according to a specific grading system. We identified 36 episodes of wheat anaphylaxis in 19 patients. All of the first attacks of wheat anaphylaxis occurred in the first-time ingestion. The most frequent manifestations of the reactions were skin and respiratory symptoms. In this study 78.9% of reactions were moderate and 21.1% of them were severe. All of our patients had positive skin prick tests to wheat. Mean total IgE level was 853.4 ± 455.27 IU/ml, and mean wheat-specific IgE was 70 ± 14.61 Ucs/ml. We conclude that wheat-induced anaphylaxis is a disease that is sufficiently severe, and. prevention of first wheat-induced anaphylaxis episodes is almost impossible. It would, however, probably be good practice to educate physicians to recognize the common clinical manifestations of this disease for early management.     

Anaphylaxis: risk factors for recurrence

BACKGROUND: There are few studies on the incidence or recurrence of anaphylaxis. OBJECTIVE : To examine the incidence of anaphylaxis and risk factors for recurrence. METHODS: A prospective study of 432 patients referred to a community-based specialist practice in the Australian Capital Territory with anaphylaxis, followed by a survey to obtain information on recurrence. RESULTS: Of 432 patients (48% male, 73% atopic, mean 27.4 years, SD 19.5, median 26) with anaphylaxis, 260 patients were seen after their first episode; 172 experienced 584 previous reactions. fifty-four percent of index episodes were treated in hospital. Aetiology was identified in 91.6% patients: food (61%), stinging insects (20.4%) or medication (8.3%). The minimum occurrence and incidence of new cases of anaphylaxis was estimated at 12.6 and 9.9 episodes/100,000 patient-years, respectively. Follow-up data were obtained from 304 patients (674 patient-years). One hundred and thirty experienced further symptoms (45 serious), 35 required hospitalization and 19 administered adrenaline. Accidental ingestion of peanut/tree nut caused the largest number of relapses, but the highest risk of recurrence was associated with sensitivity to wheat and/or exercise. Rates of overall and serious recurrence were 57 and 10 episodes/100 patient-years, respectively. Of those prescribed adrenaline, 3/4 carried it, 2/3 were in date, and only 1/2 patients faced with serious symptoms administered adrenaline. Five patients each developed new triggers for anaphylaxis, or re-presented with significant psychiatric symptoms. CONCLUSION: In any 1 year, 1/12 patients who have suffered anaphylaxis will experience recurrence, and 1/50 will require hospital treatment or use adrenaline. Compliance with carrying and using adrenaline is poor. Occasional patients develop new triggers or suffer psychiatric morbidity.     

Wheat‐dependent exercise‐induced anaphylaxis

Wheat‐dependent exercise‐induced anaphylaxis (WDEIA) is a rare, but potentially severe food allergy exclusively occurring when wheat ingestion is accompanied by augmenting cofactors. It is clinically characterized by anaphylactic reactions ranging from urticaria and angioedema to dyspnoea, hypotension, collapse, and shock. WDEIA usually develops after ingestion of wheat products followed by physical exercise. Other cofactors are acetylsalicylic acid and other non‐steroidal anti‐inflammatory drugs, alcohol, and infections. The precise mechanisms of WDEIA remain unclear; exercise and other cofactors might increase gastrointestinal allergen permeability and osmolality, redistribute blood flow, or lower the threshold for IgE‐mediated mast cell degranulation. Among wheat proteins, ω5‐gliadin and high‐molecular‐weight glutenin subunits have been reported to be the major allergens. In some patients, WDEIA has been discussed to be caused by epicutaneous sensitization with hydrolysed wheat gluten included in cosmetics. Diagnosis is made based on the patient's history in combination with allergy skin testing, determination of wheat‐specific IgE serum antibodies, basophil activation test, histamine release test, and/or exercise challenge test. Acute treatment includes application of adrenaline or antihistamines. The most reliable prophylaxis of WDEIA is a gluten‐free diet. In less severe cases, a strict limitation of wheat ingestion before exercise and avoidance of other cofactors may be sufficient.     

Role of adverse reactions to food in urticaria and exercise-induced anaphylaxis

In urticaria, adverse reactions to food are only a frequent finding in the subset of patients with chronic continuous urticaria. Mostly these reactions are of pseudoallergic nature, directed against artificial additives as well as naturally occurring aromatic components. IgE-mediated allergic reactions are a rare cause in acute urticaria as well as in recurrent chronic urticaria. In other types of urticaria, e.g. physical urticaria, food plays hardly any role as an eliciting agent with the exception of ice-cold drinks in cold urticaria. By contrast, exercise-induced anaphylaxis is frequently food-dependent. Two subtypes are distinguished: unspecific food-dependent exercise-induced anaphylaxis (FDEIA), where the filling of the stomach independently of the kind of food ingested prior to exercise is responsible for the symptoms. In specific FDEIA, an IgE-mediated food allergy causes symptoms only in combination with exercise. In the latter group, wheat is an important allergen.     

Anaphylaxis to wheat beer.

BACKGROUND: Despite its worldwide and abundant consumption, beer has rarely been found to cause anaphylaxis. Barley malt contained in lager beers seems to be an important elicitor. OBJECTIVE: To report the unusual case of severe anaphylaxis following the ingestion of wheat beer. METHODS: A 59-year-old man experienced angioedema, generalized urticaria, and unconsciousness after ingestion of wheat beer. He tolerated lager beer well. For diagnostic evaluation, skin prick tests, oral challenge tests, and identification of specific IgE antibodies were performed. RESULTS: Skin prick test results with standard series of common aeroallergens and food allergens were negative with the exception of a 1 + reaction to wheat flour. The results of skin prick tests with native materials were positive for 2 brands of wheat beer and wheat malt shred but negative for baker's yeast, hops, and a brand of lager beer. Oral challenges with wheat beer or wheat flour elicited urticaria. By CAP-FEIA, specific IgE antibodies to wheat and barley flour but not to hops or baker's yeast were found in serum. Immunoblot analysis revealed that patient's IgE was bound to a protein of approximately 35 kDa in wheat extract. CONCLUSIONS: This is the first report, to our knowledge, on anaphylaxis to beer attributable to wheat allergy.     

Wheat omega-5 gliadin is a major allergen in children with immediate allergy to ingested wheat

BACKGROUND: Sensitization to wheat by ingestion can lead to food allergy symptoms and wheat-dependent, exercise-induced anaphylaxis. Sensitization by inhalation causes bakers' asthma and rhinitis. Wheat allergens have been characterized at the molecular level in bakers' asthma and in wheat-dependent, exercise-induced anaphylaxis, in which omega-5 gliadin (Tri a 19) is a major allergen. However, little information is available regarding allergens responsible for hypersensitivity reactions to ingested wheat in children. OBJECTIVE: The aim of this study was to examine whether children with allergy to ingested wheat have IgE antibodies to omega-5 gliadin. METHODS: Sera were obtained from 40 children (mean age, 2.5 years; range, 0.7-8.2 years) with suspected wheat allergy who presented with atopic dermatitis and/or gastrointestinal and/or respiratory symptoms. Wheat allergy was diagnosed with open or double-blinded, placebo-controlled oral wheat challenge. Wheat omega-5 gliadin was purified by reversed-phase chromatography, and serum IgE antibodies to omega-5 gliadin were measured by means of ELISA. In vivo reactivity was studied by skin prick testing. Control sera were obtained from 22 children with no evidence of food allergies. RESULTS: In oral wheat challenge, 19 children (48%) reacted with immediate and 8 children (20%) with delayed hypersensitivity symptoms. Sixteen (84%) of the children with immediate symptoms had IgE antibodies to purified omega-5 gliadin in ELISA. In contrast, IgE antibodies to omega-5 gliadin were not detected in any of the children with delayed or negative challenge test results or in the control children. The diagnostic specificity and positive predictive value of omega-5 gliadin ELISA were each 100% for immediate challenge reactions. Skin prick testing with omega-5 gliadin was positive in 6 of 7 children with immediate challenge symptoms and negative in 2 children with delayed challenge symptoms. CONCLUSION: The results of this study show that omega-5 gliadin is a significant allergen in young children with immediate allergic reactions to ingested wheat. IgE testing with omega-5 gliadin could be used to reduce the need for oral wheat challenges in children.     

Immediate type food hypersensitivity associated with atopic dermatitis in children]

Food allergy is frequently associated with atopic dermatitis (AD) in children. Appropriate elimination diet is necessary in the case of immediate food hypersensitivity, regardless it causes worsening of the chronic eczema or not. Here we report the prevalence of immediate type food allergy diagnosed by oral food challenge or the episodes of apparent acute allergic reaction in the AD patients (n=182, average age 4.9+/-5.1), who visited our clinic within one year. The prevalence of food allergy in the AD patients was 85.7% in age 0 years, 75.6% in age 1,65.4% in age 2, and declined to 13.9% in age 7 years old or more. The offending foods were egg, milk, wheat, fish and so on. The symptoms of food allergy included skin, gastrointestinal or respiratory manifestations, and also anaphylaxis. In conclusion, immediate type food allergy is frequently associated with childhood AD, and appropriate elimination of the offending food is necessary to avoid the acute allergic reaction including anaphylaxis.     

Wheat allergy: clinical and laboratory findings

BACKGROUND: Food allergy affects 6-8% of infants and wheat allergy is one of the common food allergies among children. The clinical and laboratory manifestations of wheat allergy were evaluated in this study. METHODS: Thirty-two children (< or =12 years old) with suspected wheat allergy were evaluated for wheat allergy. The patients underwent wheat skin prick test (SPT), measurement of wheat-specific IgE and wheat challenge test. The patients with a convincing history of anaphylaxis following ingestion of wheat or with a positive challenge test, and those with a history of immediate hypersensitivity reaction following ingestion of wheat in addition to a positive wheat SPT and/or positive wheat-specific IgE were considered wheat allergic. Then, the laboratory and clinical manifestations of their disease were studied. RESULTS: Among patients with suspected wheat allergy, 24 patients with definite wheat allergy were identified. Anaphylaxis was a dominant clinical feature, accounting for 54.1% of acute symptoms. Chronic allergy symptoms like asthma and eczema were noted in 50% of the patients. Wheat-specific IgE was higher in patients with anaphylaxis (p<0.02) and the risk of anaphylaxis was 14.4 times more in patients with wheat-specific IgE equal to or more than 3+. CONCLUSIONS: Anaphylaxis had occurred in a remarkable number of patients repeatedly, which demonstrates the severity of the reactions, poor knowledge of the disease and probable existence of more patients with mild reactions. Regarding the higher level of wheat-specific IgE in patients with anaphylaxis, wheat-specific IgE could be used to predict the severity of symptoms.     

Should children with a history of anaphylaxis to foods undergo challenge testing?

Background Data on the frequency of resolution of anaphylaxis to foods are not available, but such resolution is generally assumed to be rare. Objective To determine whether the frequency of negative challenge tests in children with a history of anaphylaxis to foods is frequent enough to warrant challenge testing to re‐evaluate the diagnosis of anaphylaxis, and to document the safety of this procedure. Methods All children (n=441) who underwent a double‐blind, placebo‐controlled food challenge (DBPCFC) between January 2003 and March 2007 were screened for symptoms of anaphylaxis to food by history. Anaphylaxis was defined as symptoms and signs of cardiovascular instability, occurring within 2 h after ingestion of the suspected food. Results Twenty‐one children were enrolled (median age 6.1 years, range 0.8–14.4). The median time interval between the most recent anaphylactic reaction and the DBPCFC was 4.25 years, range 0.3–12.8. Twenty‐one DBPCFCs were performed in 21 children. Eighteen of 21 children were sensitized to the food in question. Six DBPCFCs were negative (29%): three for cows milk, one for egg, one for peanut, and one for wheat. In the positive DBPCFCs, no severe reactions occurred, and epinephrine administration was not required. Conclusions This is the first study using DBPCFCs in a consecutive series of children with a history of anaphylaxis to foods, and no indications in dietary history that the food allergy had been resolved. Our study shows that in such children having specific IgE levels below established cut‐off levels reported in other studies predicting positive challenge outcomes, re‐evaluation of clinical reactivity to food by DBPCFC should be considered, even when there are no indications in history that anaphylaxis has resolved. DBPCFCs can be performed safely in these children, although there is a potential risk for severe reactions.     

Anaphylaxis induced by lentil inhalation

Anaphylaxis is a rapid onset serious allergic reaction which may be fatal. Foods are the most common allergens leading to anaphylaxis especially for childhood. Most of the food-induced anaphylactic reactions take place after ingestion of the allergic food and only a few cases exist with anaphylactic reactions induced by inhalation of foods such as peanut, soybean and lupine. The case we present is unusual in that an 8 1/2-year-old boy developed anaphylaxis with the inhalation of steam from boiling lentils.     

Clinical presentation,allergens, and management of wheat allergy

IgE-mediated allergy to wheat proteins can be caused by exposure through ingestion, inhalation, or skin/mucosal contact, and can affect various populations and age groups. Respiratory allergy to wheat proteins is commonly observed in adult patients occupationally exposed to flour, whereas wheat food allergy is more common in children. Wheat allergy is of growing importance for patients with recurrent anaphylaxis, especially when exercise related. The diagnosis of wheat allergy relies on a consistent clinical history, skin prick testing with well-characterized extracts and specific IgE tests. The accuracy of wheat allergy diagnosis may be improved by measuring IgE responses to several wheat components. However, a high degree of heterogeneity has been found in the recognition pattern of allergens among patient groups with different clinical profiles, as well as within each group. Thus, oral provocation with wheat or the implicated cereal is the reference test for the definitive diagnosis of ingested wheat/cereal allergy.