Drug-dependent exercise-induced anaphylaxis

Exercise-induced anaphylaxis (EIA) is well known and may be food-dependent. We describe a patient with a history of anaphylaxis during exercise after taking nafylpropion acid (Naprosyne®), a nonsteroidal anti-inflammatory drug. An exercise-challenge test after Naprosyne intake induced bronchoconstriction. The combination of history and challenge tests suggests that intolerance or allergy to drugs may present as EIA.     

Three cases of food-dependent exercise-induced anaphylaxis

A variety of systemic reactions associated with exercise are recognized. This article describes three cases of anaphylaxis induced by exercise within 2 hours after the ingestion of causative foods. Their symptoms were urticaria, angioedema, bronchial asthma, fall in blood pressure and syncope. Cases #1 and #3 showed exercise-induced anaphylaxis after ingestion of wheat. However, case #1 reacted only to toasted wheat. In case #2 the most likely responsible food was also wheat, although we could not definitely confirm this. Two subjects exhibited an elevation in plasma histamine level when symptoms developed. In addition, we observed inhibition of these symptoms by pretreatment with anti-allergic drugs. These observations suggest that type I allergic reaction is involved in the development of these symptoms. However, why exercise combined with ingestion of food is needed for this type of anaphylaxis still remains unknown.     

A case of food-dependent exercise-induced anaphylaxis

A 15-year-old man with food-dependent exercise-induced anaphylaxis is reported. The patient had begun to run 4 hours after he had lunch on fried shrimps. When running about 2000 m, he suffered from general cutaneous erythema with itching, urticaria, angioedema of face and dyspnea. He had experienced the similar episodes associated with postprandial exercise before. Skin test and IgE-RAST were positive for shrimp. Exercise challenge test after having 20 g boiled shrimp was conducted, and the elevation of plasma histamine level was recognised. 25 cases with food-dependent exercised-induced anaphylaxis have reported in Japan. 13 of 25 cases were related with wheat, and 10 cases were related with shrimp. 14 of 25 cases had experienced the similar episodes. Exercise as part of planned health program has virtually mushroom world-wide. Therefore, the fact that anaphylaxis can be a complication of such exercise must be recognised if appropriate prevention and treatment are to be administered.     

Frequency of food-dependent, exercise-induced anaphylaxis in Japanese junior-high-school students

BACKGROUND: Food-dependent, exercise-induced anaphylaxis (FEIAn) is classified among the physical allergies. The pathophysiology of FEIAn remains unknown, as does the frequency of FEIAn in the general population. OBJECTIVE: We sought to study the epidemiology of FEIAn, especially its frequency in junior-high-school students in Yokohama, Japan. METHODS: A questionnaire asking about the occurrence of FEIAn in school students was sent to all 145 public junior-high-school nurses in Yokohama. RESULTS: One hundred thirty-two junior-high-school nurses responded to the questionnaire, and 13 (11 boys and 2 girls) cases of FEIAn among 76,229 junior-high-school students were reported. In addition, 24 (12 boys and 12 girls) subjects with exercise-induced anaphylaxis (EIAn) were detected. From this survey, the frequency of FEIAn was 0.017% in this population, and its frequency was significantly higher in boys than in girls (P < .05). The frequency of EIAn was 0.031%, and there was no difference according to sex. Only one third of junior-high-school nurses had any knowledge of FEIAn. We also performed provocation tests in 5 of the 13 cases with FEIAn after obtaining informed consent from the students and their parents and were able to confirm the diagnosis. CONCLUSION: This study showed that FEIAn and EIAn are relatively rare diseases among junior-high-school students in Yokohama. To avoid serious outcomes, we believe it is important that not only physicians but also school nurses and teachers of physical education be aware of these diseases.     

Sensitivity and specificity of recombinant omega-5 gliadin-specific IgE measurement for the diagnosis of wheat-dependent exercise-induced anaphylaxis

Background:  A recent study has shown that the measurement of specific IgE antibodies to B-cell epitope peptides of wheat ω-5 gliadin (Pep A) and high molecular weight glutenin subunit (Pep B) are useful to diagnose wheat-dependent exercise-induced anaphylaxis (WDEIA).
Aims of the study:  We sought to compare the sensitivity and specificity of the in vitro tests for measuring the specific IgE antibodies to recombinant ω-5 gliadin (rω-5 gliadin) with those for wheat, gluten, Pep A, and Pep B in identification of patients with WDEIA.
Methods:  Fifty patients with WDEIA, 25 healthy subjects and 25 patients with atopic dermatitis with specific IgE antibodies to wheat but without experience of allergic reactions after ingestion of wheat products were enrolled in this study. The concentrations of specific IgE antibodies were measured using ImmunoCAP^TM. The empirical receiver operating characteristics curves (ROC) for each test were prepared and the areas under the ROC curve ( AUC ) were compared.
Results:  In patients with WDEIA, the sensitivities of the allergen-specific IgE tests for wheat, gluten, Pep A, Pep B and rω-5 gliadin were 48%, 56%, 76%, 22%, and 80%, respectively. The seven of 10 WDEIA patients with no specific IgE antibodies to rω-5 gliadin had specific IgE antibodies to Pep B. The highest AUC (0.850) was observed in the test for rω-5 gliadin.
Conclusions:  Measuring the concentration of specific IgE antibodies to rω-5 gliadin is more useful than to wheat, gluten, or Pep A in the identification of patients with WDEIA.     

Clinical courses of 18 cases with food-dependent exercise-induced anaphylaxis]

Eighteen cases (7 males and 11 females) of food-dependent exercise-induced anaphylaxis were observed for several years. The age of the patients at the first visit to our hospital ranged from 9 to 43 years (average 24.3 years). The offending foods were wheat in 9 cases, shrimp in 2 cases, shellfish in 1 case, fish in 1 case, and unknown foods in 5 cases. The inducing exercises were ball play games, running, riding a bicycle, swimming, kendo (Japanese fencing), walking, and so on. We advised these patients to avoid eating offending foods or taking exercises, or to take antiallergic medicine such as DSCG, and repirinast. We observed their clinical courses and laboratory data for 2 to 10 years. Only a few cases relapsed anaphylactoid reactions, but all cases have improved until now. In some cases, IgE RAST scores for wheat decreased. In other cases, the rate of histamine release on anti-IgE stimulation decreased after taking DSCG.     

Food-induced anaphylaxis

To date, there are no population-based epidemiologic studies providing information about the prevalence of food-induced anaphylaxis. However, statistics from the United Kingdom demonstrated an increase of anaphylaxis from 5.6 cases per 100000 hospital discharges in 1991–92 to 10.2 cases in 1994–95. The increase for the subcategory of food-induced anaphylaxis was above the overall increase in anaphylaxis. In the UK register of fatal anaphylactic reactions, all food-induced fatalities have been accompanied by respiratory problems with respiratory arrest. Atopic individuals with bronchial asthma and prior allergic reactions to the same food are at a particularly high risk. Not only peanuts, seafood and milk can induce severe, potentially lethal, anaphylaxis, but indeed a wide spectrum of foods, according to the different patterns of food sensitivity in different countries. Foods with "hidden" allergens and meals at restaurants are particularly dangerous for patients with food allergies. Similarly, schools, public places and restaurants are the major places of risk. However, the main factor contributing to a fatal outcome is the fact that the victims did not carry their emergency kit with adrenaline (epinephrine) with them. Therefore, we suggest that the pharmaceutical industry should reintroduce an adrenaline inhaler that is more effective, especially in asthmatic reactions.     

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 anaphylaxis

Anaphylaxis is a life-threatening allergic reaction, and food is one of the most common responsible allergens in the outpatient setting. The prevalence of food-induced anaphylaxis has been steadily rising. Education regarding food allergen avoidance is crucial as most of the fatal reactions occurred in those with known food allergies. The lack of a consensus definition for anaphylaxis has made its diagnosis difficult. Symptoms affect multiple organ systems and include pruritus, urticaria, angioedema, vomiting, diarrhoea, abdominal cramps, respiratory difficulty, wheezing, hypotension, and shock. Prompt recognition of anaphylaxis is essential as delayed treatment has been associated with fatalities. Although epinephrine is accepted as the treatment of choice, timely administration does not always occur, partly due to a lack of awareness of the diagnostic criteria. Several novel tools are currently being investigated, which will potentially aid in the diagnosis and treatment of food-induced anaphylaxis.     

The utility of the ISAC allergen array in the investigation of idiopathic anaphylaxis

A diagnosis of idiopathic anaphylaxis following a detailed clinical assessment remains very challenging for patients and clinicians. Risk reduction strategies such as allergen avoidance are not possible. This study investigated whether the (ISAC) allergen array with 103 allergens would add diagnostic value in patients with idiopathic anaphylaxis. We extended the specific immunoglobulin (Ig)E testing in 110 patients with a diagnosis of idiopathic anaphylaxis from five UK specialist centres using ISAC arrays. These were divided into three groups: score I identified no new allergen sensitization beyond those known by previous assessment, score II identified new sensitizations which were not thought likely to explain the anaphylaxis and score III identified new sensitizations felt to have a high likelihood of being responsible for the anaphylaxis. A proportion (50%) of score III patients underwent clinical reassessment to substantiate the link to anaphylaxis in this group. The results show that 20% of the arrays were classified as score III with a high likelihood of identifying the cause of the anaphylaxis. A wide range of major allergens were identified, the most frequent being omega‐5‐gliadin and shrimp, together accounting for 45% of the previously unrecognized sensitizations. The ISAC array contributed to the diagnosis in 20% of patients with idiopathic anaphylaxis. It may offer additional information where a careful allergy history and follow‐on testing have not revealed the cause of the anaphylaxis.