Exercise-induced Anaphylaxis Research Articles

食物依存性運動誘発アナフィラキシーの診断におけるアレルゲンコンポーネントの有用性

「食物アレルギー診療ガイドライン2016」では, 食物依存性運動誘発アナフィラキシー (FDEIA) の診断に, 詳細な問診, 一般的血液検査, 各種アレルギー検査が有用で, 確定診断には誘発試験の実施が望ましいとされている. しかし誘発試験の再現性は高くはなく, アレルゲンコンポーネント (AC) が新たな診断ツールとして注目されている.

負荷試験の課題～アスピリンの有用性～

食物依存性運動誘発アナフィラキシー (FDEIA) を疑う症例では確定診断のため誘発試験を行うが, 原因食品と運動負荷のみでは誘発率が低い. 陰性の場合, 当科ではアスピリンと食品, アスピリン, 食品と運動負荷の2方法の検査を追加し行っている. アスピリンは非ステロイド系抗炎症薬として知られ, 成人では食物アレルギーやFDEIA症状を増強することが知られている. 小児において, アスピリンによる食品のアレルギー反応増強は低率であったが, アスピリンを加えることにより運動誘発試験陽性率を2倍に増加させた. 食物に運動やアスピリンなどの因子が加わることでの反応性には年齢や原因食物などによる個人差があると考えられ, そのメカニズムについて今後の検討が必要である.

食物依存性運動誘発アナフィラキシーの臨床経過と原因食品ごとの診断ポイント

食物依存性運動誘発アナフィラキシーの臨床経過と原因食品ごとの診断ポイント

Cross-reactive LTP sensitization in food-dependent exercise-induced urticaria/anaphylaxis: a pilot study of a component-resolved and in vitro depletion approach.

BackgroundChallenge tests for food-dependent exercise-induced anaphylaxis (FDEIA) carry some risk and have a high rate of false negatives. Our aim was to explore the usefulness of an in vitro immunodepletion assay and an allergen microarray test in the identification of IgE-mediated cross-reactive food allergens in patients with suspected FDEIA or food-dependent exercise-induced urticaria and panallergen sensitization.MethodsThree patients with a history of food dependent exercise induced urticaria/anaphylaxis and food panallergen sensitization in whom a food-exercise challenge was not feasible were selected: a 25-year-old man with cholinergic urticaria who experienced generalized urticaria and angioedema during a soccer match after drinking a peach-based soft drink; a 19-year-old woman with allergic rhinitis and controlled asthma who experienced anaphylactic shock while playing soccer, having eaten walnuts in the previous 90 min; and a 57-year-old man with baker’s asthma who experienced four episodes of anaphylaxis during exercise after ingesting wheat-containing food. All individuals underwent a diagnostic work-up with skin prick tests, specific IgE (sIgE) and ImmunoCAP ISAC test. For the in vitro immunodepletion procedure, patients’ serum was pre-incubated with the suspected native allergen (peach, walnut, or wheat) in solid phase (ImmunoCAP). The eluted serum, containing unbound IgE, was collected and samples were re-tested using Immunocap ISAC 112 and compared with baseline results.ResultsAll individuals were sensitized to lipid transfer proteins. The first patient was sensitized to Pru p 3, Cor a 8, Jug r 3, and Ara h 9; after pre-incubation with peach there was 100% depletion of sIgE to all components. The second patient was sensitized to Pru p 3, Cor a 8, Jug r 3, and Ara h 9; immunodepletion with walnut depleted sIgE to Ara h 9 by 67%, Pru p 3 and Pla a 3 (60%), Art v 3 (75%), Jug r 3 (88%), and Cor a 8 (100%). The third patient was sensitized to Pru p 3, Jug r 3, Ara h 9, and Tri a 14; immunodepletion with wheat depleted Tri a 14 only (100%).ConclusionsIn vitro immunodepletion might be a useful diagnostic tool in food dependent exercise induced urticaria/anaphylaxis with panallergen sensitization, particularly for identifying the culprit allergen and guiding dietary elimination recommendations.

Aspirin Intolerance: Experimental Models for Bed-to-Bench.

Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin intolerance) are also observed in patients with food-dependent exercise-induced anaphylaxis, a type I allergy disease, and aspirin-induced urticaria (AIU). However the target and the mechanism of the aspirin intolerance are still unknown. There is no animal or cellular model of AERD, because its pathophysiological mechanism is still unknown, but it is thought that inhibition of cyclooxygenase by causative agents leads to an increase of free arachidonic acid, which is metabolized into cysteinyl leukotrienes (cysLTs) that provoke airway smooth muscle constriction and asthma symptoms. As the bed-to-bench approach, to confirm the clinical discussion in experimental cellular models, we have tried to develop a cellular model of AERD using activated RBL-2H3 cells, a rat mast cell like cell line. Indomethacin (another NSAID and also causes AERD), enhances in vitro cysLTs production by RBL-2H3 cells, while there is no induction of cysLTs production in the absence of inflammatory activation. Since this suggests that all inflammatory cells with activation of prostaglandin and cysLT metabolism should respond to NSAIDs, and then I have concluded that aspirin intolerance should be separated from subsequent bronchoconstriction. Evidence about the cellular mechanisms of NSAIDs may be employed for development of in vitro AERD models as the approach from bench-to-bed.

Successful treatment with omalizumab in challenge confirmed exercise-induced anaphylaxis

Successful treatment with omalizumab in challenge confirmed exercise-induced anaphylaxis

Rye-dependent exercise-induced anaphylaxis

Rye-dependent exercise-induced anaphylaxis

Model development for prediction of the allergic response to the wheat proteins ω-5 gliadin and HMW-glutenin

As one of the eight foods that account for 90 % of food allergies, wheat must be excluded from the diet in patients suffering from wheat allergies. From studies of wheat-dependent exercise-induced anaphylaxis (WDEIA), which has been used as a model to develop hypoallergenic wheat, we now know that the gluten fraction of wheat protein, particularly ω-5 gliadin and high-molecular-weight (HMW)-glutenin, is responsible for the allergic response. However, studies of allergic responses with WDEIA have been performed with a single wheat cultivar. Thus, in an effort to provide more information for the development of hypoallergenic wheat, we compared various cultivars with different countries of origin and characteristics. For the first step, we compared the allergen contents (ω-5 gliadin and HMW-glutenin) in each cultivar and the allergic response caused by each cultivar. Domestic wheat cultivars had lower contents of ω-5 gliadin and HMW-glutenin than those of imported wheat cultivars. Additionally, some cultivars caused varying allergic responses due to their allergen components. From regression analysis of allergen contents and allergic responses in vivo, we suggest a prediction model to estimate the extent of allergic response based on the ω-5 gliadin and HMW-glutenin contents. Further studies are needed to analyze the biological interactions between allergens from various cultivars and allergic response factors.

Allergic reaction from fingerprint kit attributable to unlabeled gluten, probable wheat flour

Allergic reaction from fingerprint kit attributable to unlabeled gluten, probable wheat flour

Molecular characterization of the IgE-binding epitopes in the fast ω-gliadins of Triticeae in relation to wheat-dependent, exercise-induced anaphylaxis

Fast ω-gliadins were minor components of wheat storage proteins but a major antigen triggering allergy to wheat. Sixty-six novel full-length fast ω-gliadin genes with unique characteristics were cloned and sequenced from wheat and its relative species using a PCR-based strategy. Their coding regions ranged from 177bp to 987bp in length and encoded 4.28kDa to 37.56kDa proteins. On the base of first three deduced amino acids at the N-terminal, these genes could be classified into the six subclasses of SRL-, TRQ-, GRL-, NRL-, SRP- and SRM-type ω-gliadin genes. Compared by multiple alignments, these genes were significantly different from each other, due to the insertion or deletion at the repetitive domain. An analysis of the IgE-binding epitopes of the 66 deduced fast ω-gliadins demonstrated that they contained 0–24 IgE-binding epitopes. The phylogenetic tree demonstrated that the fast ω-gliadins and slow ω-gliadins were separated into two groups and their divergence time was 21.64millionyears ago. Sequence data of the fast ω-gliadin genes assist in the study of the origins and evolutions of the different types of ω-gliadins while also providing a basis for the synthesis of monoclonal antibodies to detect wheat antigen content.

The clinical spectrum of omega-5-gliadin allergy.

IgE-mediated allergy to the wheat protein omega-5-gliadin (O5G) is associated with wheat-dependent exercise-induced anaphylaxis (WDEIA), where exercise acts as a cofactor, triggering anaphylaxis after wheat ingestion. The wider application of O5G-specific IgE (sIgE) testing has revealed that the manifestations of O5G allergy extend beyond WDEIA. This study documents clinical manifestations in a large series of patients with sIgE to O5G. A retrospective clinical audit was performed on adult patients with a positive O5G sIgE (>0.35kU/L) between 2007 and 2013 compared with a group who had negative O5G sIgE. Clinical characteristics and skin prick test (SPT) results were examined. Sixty-seven patients were characterised, 26 of whom presented with food-dependent exercise-induced allergy, whilst others presented with exercise-induced symptoms without apparent food association (16/67), idiopathic anaphylaxis (10/67), food-induced allergic symptoms without exercise (10/67) or recurrent acute urticaria (5/67). Specific IgE to O5G had 91% sensitivity and 92% specificity for wheat-related allergic symptoms. SPT had sensitivity of 92% and specificity of 84%. WDEIA is the most common manifestation of O5G allergy, but patients may present with a variety of allergic manifestations, and wheat allergy is not always obvious on history. Non-exercise cofactors or a lack of cofactors were identified in many patients. A distinctive feature of this allergy is that despite regular wheat ingestion, allergic reactions to wheat occur infrequently. Testing for sIgE to O5G should be considered in patients presenting with exercise-induced urticaria/anaphylaxis, idiopathic anaphylaxis and recurrent acute (but not chronic) urticaria.

Clinical and laboratory features, and quality of life assessment in wheat dependent exercise-induced anaphylaxis patients from central China.

Wheat dependent exercise-induced anaphylaxis (WDEIA) is a rare but potentially severe food allergy caused by the combination of wheat ingestion and physical exercise. The impact of WDEIA on quality of life (QOL) is unclear. This study characterized the clinical and laboratory features and investigated the QOL in WDEIA patients from Central China. Twenty-eight WDEIA patients were analyzed, and QOL was measured by validated Chinese version Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF) and Food Allergy Independent Measure (FAIM) after obtaining the diagnosis. The results showed that half of the patients were females. The median onset age was 37 years old. The symptoms occurred within 1 h after wheat ingestion (26/28). Symptoms of anaphylaxis included cutaneous (26/28), respiratory (11/28), gastro-intestinal (5/28) and cardiovascular manifestations (27/28). Skin prick tests were positive to salt soluble (89.3%) and salt insoluble wheat allergen extracts (100%). Positive rate to wheat, gluten and omega-5 gliadin specific IgE was 64.3%, 92.9% and 92.9% respectively. Specific IgE to omega-5 gliadin with a cut-off value 0.83 KU/L offered highly efficient diagnostic criterion for WDEIA (sensitivity: 89.3%; and specificity: 88.9%). The mean scores of FAQLQ-AF and FAIM were 4.70 and 4.98 respectively and level of anti-omega-5 gliadin IgE had positive correlations with FAQLQ scores. Thereby, WDEIA is commonly found in mid-age adults. In most cases, multi-organs especially skin and cardiovascular systems are involved. Salt insoluble wheat allergen skin test and serum specific IgE to gluten and omega-5 gliadin help to diagnose WDEIA. QOL in WDEIA patients is severely impaired.

Characterization of a hypoallergenic wheat line lacking ω-5 gliadin

BackgroundThere is no curative treatment for wheat-dependent exercise-induced anaphylaxis (WDEIA). ω-5 Gliadin is one of the dominant allergens affecting WDEIA patients. The use of ω-5 gliadin-free wheat flour in the regular diet is considered one of the prophylactic approaches against the elicitation of allergic symptoms and sensitization to ω-5 gliadin. We sought to find hypoallergenic bread wheat (or common wheat) that lacked the genes encoding ω-5 gliadin and to evaluate its in vitro allergenicity. We also aimed to evaluate the sensitization ability of one of the selected hypoallergenic wheat lines by using a possible animal model of wheat allergy. MethodsWe screened the deletion lines of bread wheat by western blotting to ascertain common wheat lines lacking the ω-5 gliadin locus. The deletion lines we used have partial deficiency of chromosome 1B (Endo and Gill, 1996). To assess sensitization ability of gluten from the selected deletion line, guinea pigs were fed with either the gluten from the selected deletion line or commercially available gluten, and allergic score was evaluated after challenging the same gluten preparations. ResultsWe found that a deletion line 1BS-18 had the least deficiency of chromosome 1B among the deletion stocks lacking the ω-5 gliadin locus. The challenge test using the guinea pigs revealed that the symptoms induced by application of the 1BS-18 gluten were much less than that of commercially available gluten. ConclusionsThe deletion line 1BS-18, which lacked the ω-5 gliadin locus, is likely to have a low sensitization capacity in the guinea pig. The use of the wheat products of the 1BS-18 line in daily life may provide a feasible solution for the onset of wheat allergy.

Diagnostic and Therapeutic Approach in Patients with Exercise-Induced Anaphylaxis

The prevalence of exercise-induced anaphylaxis is estimated to be about 2.36-5 % of all cases of anaphylaxis. The clinical manifestations of exercise-induced anaphylaxis include flushing, increase warmth, diffuse pruritus, urticaria, angioedema, bronchospasm, gastrointestinal symptoms, hypotension, and laryngeal edema. The main differential diagnosis is with cholinergic urticaria. Exercise-induced anaphylaxis may display food-dependence, with or without specific IgE sensitivity. The most commonly implicated foods are wheat (omega-5 gliadin), shellfish (especially shrimps), celery, corn, cow’s milk, mite-contaminated wheat flour, and peanuts. Interestingly, in these patients aerobic exercises alone, as well as the sole ingestion of the allergenic foods without associated exercises, do not cause anaphylaxis. The synergistic effect of both inducing factors is necessary for the occurrence of the anaphylactic manifestations. There may be drug-dependence in exercise-induced anaphylaxis. Implicated drugs and chemicals include NSAIDS, aspirin, antibiotics (cephalosporins), and the so-called anti-catabolic energizer supplements, such as beta-hydroxymethylbutyrate. Avoidance of eating the triggering foods is recommended when possible, and in temperate areas of the planet an additional preventive measure is not to exercise when there is high environmental exposure to pollens (then exercising indoors). It is also advisable to avoid exercising in extreme weather conditions (too hot, cold, or humid environments). Monoclonal anti-IgE (omalizumab) as a mast cell stabilizer with downregulation of the high affinity IgE receptors (FceRI) can have a potential role preventing these anaphylactic episodes.

A study of cross-reactivity between citrus fruit and pollen allergens in oral allergy syndrome and food-dependent exercise-induced anaphylaxis in Japan

Objectives: Oral allergy syndrome (OAS) associated with citrus fruits has been previously reported. However, in Japan, although rare, citrus allergy is also associated with food-dependent exercise-induced anaphylaxis (FDEIA). This study was done to determine whether different allergens may be involved in these two responses, and to examine cross-reactivity between popular citrus fruits and local pollen allergens. Methods: Twelve patients were studied who had a history of OAS (8 cases) or FDEIA (4 cases), and had positive IgE antibody titers or tested positive with a skin prick test to citrus antigens. Serum immunodetection assays and immunoblot inhibition assays were performed with extracted Valencia orange (rCit s 2), selected antigens in white birch pollen (WBP) and orchard grass pollen (OGP). Results: Immunodetection assays demonstrated an allergen associated with OAS as the 14-kDa protein, Cit s 2. An as yet unidentified 54-kDa protein was demonstrated in FDEIA patients. Cross-reactivity between orange and pollen antigens was confirmed by the following results: 1) Significant correlations between serum specific IgE levels for orange and OGP, 2) Immunoblot inhibition with WBP and OGP pollen antigens against rCit s 2. In Immunoblot inhibition, WBP and OGP both pollen antigens inhibited against rCit s 2. Conclusion: The main allergen of OAS induced by orange was Cit s 2, which has cross-reactivity with WBP and/or OGP in Japanese patients with orange allergy. IgE-binding protein pattern in patients with FDEIA induced by orange were different from that in OAS. A 54-kDa protein was assumed to be a candidate for clinically relevant allergens in the development of the FDEIA.

Baseline CD63 Expression in Patients with Exercise Induced Anaphylaxis (EIA)

Baseline CD63 Expression in Patients with Exercise Induced Anaphylaxis (EIA)

Wheat-Dependent, Exercise-Induced Anaphylaxis Can be Elicited without Exercise (And With Other Co-factors)

Wheat-Dependent, Exercise-Induced Anaphylaxis Can be Elicited without Exercise (And With Other Co-factors)

Identification of Japanese Apricot Peamaclein As a New Allergen Related to Food-Dependent Exercise-Induced Anaphylaxis Due to Japanese Apricot: Cross-Reactivity to Pru p 7

Identification of Japanese Apricot Peamaclein As a New Allergen Related to Food-Dependent Exercise-Induced Anaphylaxis Due to Japanese Apricot: Cross-Reactivity to Pru p 7

Exercise-Induced Anaphylaxis Successfully Treated with Hydroxychloroquine

Exercise-Induced Anaphylaxis Successfully Treated with Hydroxychloroquine

Wheat allergy: diagnosis and management

Triticum aestivum (bread wheat) is the most widely grown crop worldwide. In genetically predisposed individuals, wheat can cause specific immune responses. A food allergy to wheat is characterized by T helper type 2 activation which can result in immunoglobulin E (IgE) and non-IgE mediated reactions. IgE mediated reactions are immediate, are characterized by the presence of wheat-specific IgE antibodies, and can be life-threatening. Non-IgE mediated reactions are characterized by chronic eosinophilic and lymphocytic infiltration of the gastrointestinal tract. IgE mediated responses to wheat can be related to wheat ingestion (food allergy) or wheat inhalation (respiratory allergy). A food allergy to wheat is more common in children and can be associated with a severe reaction such as anaphylaxis and wheat-dependent, exercise-induced anaphylaxis. An inhalation induced IgE mediated wheat allergy can cause baker’s asthma or rhinitis, which are common occupational diseases in workers who have significant repetitive exposure to wheat flour, such as bakers. Non-IgE mediated food allergy reactions to wheat are mainly eosinophilic esophagitis (EoE) or eosinophilic gastritis (EG), which are both characterized by chronic eosinophilic inflammation. EG is a systemic disease, and is associated with severe inflammation that requires oral steroids to resolve. EoE is a less severe disease, which can lead to complications in feeding intolerance and fibrosis. In both EoE and EG, wheat allergy diagnosis is based on both an elimination diet preceded by a tissue biopsy obtained by esophagogastroduodenoscopy in order to show the effectiveness of the diet. Diagnosis of IgE mediated wheat allergy is based on the medical history, the detection of specific IgE to wheat, and oral food challenges. Currently, the main treatment of a wheat allergy is based on avoidance of wheat altogether. However, in the near future immunotherapy may represent a valid way to treat IgE mediated reactions to wheat.