WDEIA

Hintergrund

Ein exemplarischer Weg zur Diagnose

• Woche 0
• Schwere Anaphylaxie, bis kurz vor der Intubation, da auch die Atmung mangels Kreislauf nicht mehr wollte. Nach Kopfschmerzen, Ibuprofen, BBQ Chicken Pizza und 2 std "Mittagsschlaf"
• Verdacht auf spontane Allergie gegen Ibuprofen -> Kein Ibu mehr
• Woche 5
• Nächste Anaphylaxie, durch Notfallset ausgebremst. Nach Pizza mit Mozzerella und Hähnchen. (Dummerweise am Flughafen im Urlaub) -> Ibu wackelt, da wieder Kopfschmerzen und etwas Erkältet geht ein schwammiger Verdacht in die Richtung./li>
• Ernährungstagebuch! (Yay . . .)
• Woche 8
• Nächste Anaphylaxie nach super leckerem Käsetoast und Brennholz schleppen. Notfallset hilft ganz gut.
• Es wäre langsam mal eine gute Idee zu einem Allergologen zu gehen? Tja. Tests auf Medikamente gibts nur Stationär und da gibt es 3 Monate Wartezeit für einen Termin für ein Vorgespräch... Pricktest beim Hautarzt ohne wirkliche Auffälligkeiten.
• Glücklicherweise gibt es Ärzte im Freundeskreis, die in Krankenhäusern arbeiten und meinen man soll mal Anrufen
• Woche 10
• Vorgespräch im Klinikum: Initial gleiche Irritation wie bisher. Leiterin der Ambulanz kündigt an zu wissen was es ist, hätte nur gerne etwas Blut. Verdacht auf WDEIA :)
• Woche 12
• Ein Tag im Klinikum: Bluttest auf WDEIA war negativ, Pricktest mit leichten Reaktion auf Weizen und Roggen und ein klein wenig auf Dinkel, aber nichts ausreichendes. Plan: Stationär ins Krankenhaus, bis was gefunden wird.
• Woche 14
• Nächste Anaphylaxie: Hähnchen vom Smoker und Semmelknödel + eine Runde Billard
• Woche 18
• Woche im Krankenhaus: Blut, Medizinisches Konzil. Donnerstags dann das positive Blutergebnis rTri a 19 -> Omega-5-Gliadian und WDEIA. Weizen so zum Essen vertragen. Planung für Provokation
• Woche 21
• Provokation: Brötchen, Nudelsuppe und ab aufs Trimmrad, bis die Reaktion los geht Diagnose fertig! :) Ärzte gratulieren dazu was ganz besonderes zu

Fazit

• Ganz auf Weizen verzichten? Am besten ja, aber sehr individuell von Patient zu Patient
• "Execise/Stress/Belastung? Bei dem anders. Triggermenge liegt zwischen Aufstehen und fleißig Joggen
• Keine NSAR mehr
• Dinkel? Ist bei den meisten ok, gibt aber auch Kreuzallergien -> Ausprobieren und vorsichtig sein
• Weizenbrand? Unbekannt :)
• Witzige Tipps: "Als erstes machen sie diesen Tropfendeckel aus dem Fenistil raus! Zum zählen haben sie dann eh kein Kopf. Nehmen sie einfach einen Teelöffel voll und wenn sie sich nicht sicher, nehmen sie zwei. Und im Zweifel einfach das ganze Fläschchen, wenn sie bei uns landen bekommen sie eh viel mehr"
• Der Beipackzettel vom EpiPen ist lesenswert. zB hier bei shop-apotheke.com

Nicht erwähnt sind hierbei

• Die durchgängigen Erkältungen und das abgeschlagen sein, da das Kortison, Fenistil und Adrenalin doch Spuren hinterlassen
• Frust mit dem Ernährungstagebuch, dass nachweist, dass man gegen nichts allergisch sein kann
• Der Versuch sich weizen- bzw. glutenfrei zu ernähren und Restaurants wo das Essen in der einen Woche ok ist, der Kellner in der nächsten aber sagt, dass Semmelbrösel in den Burgerpattys sind...
• Der MDK, der meint das Arbeiten und beruflich auf Reisen sein bevor man weis wogegen man allergisch ist gar kein Problem darstellt. Die Anaphylaxien seien ja nicht so schlimm, irgendwo im Hotel sein daher kein Problem und sich selbst Essen einpacken für eine Woche sei ja auch machbar
• Ärzte, die einem das Ganze nicht glauben, weil es komisch klingt. Wenn auch leider verständlich
• Ärzte, die trotz Allergieausweis und Unterlagen die Diagnose in Frage stellen, weil der Brief vom finalen Befund nicht in den Unterlagen liegt
• Ärzte die meinen man hätte nach der Diagnose absoluten Humbug über die Allergie erzählt bekommen. Schwer zu bewerten, aber...schade

3 Jahre mit WDEIA

• JEDER im Freundeskreis, der vom Adrenalin in der Tasche erfährt, zieht sofort eine Referenz zu Pulp Fiction
• 5 Reaktionen über 3 Jahre, die ersten schwach, danach wollte das Adrenalin auch genutzt werden
• Dinkelmehl wird soweit vertragen
• Gelernt, das Dinkel und Weizen durch die Anwesenheit von ω-5 Gliadin unterschieden werden. Im Gegenzug finden sich auch im Dinkel diverse Epitope des ω-5 Gliadin.
• Reaktionen auf selbstgemachtes Gebäck mit Dinkel und frisch-Hefe der einen Marke, keine Reaktionen bei einer anderen Marke. Beide gluten- und weizenfr.ei. Ggf. die Frage welche Teile des Mehls die Hefe frisst?
• Keine Reaktion mit der üblichen Trockenhefe
• Notaufnahmen mögen es nicht, wenn man ihnen sagt was man hat und brauch. Beim Hinweis auf eine Anaphylaxie und Notwendigkeit von Kortison und einem Antiallergikum sorgt für Verweis auf KV Notfallpraxis, die Std warten ist ok wenn man leuchtet wie ein Weihnachtsbaum (war allerdings auch zu Ostern)
• Notärzte und Sanis lieben es sich den Epi-Pen anzuschauen. Am besten den ausgelösten und einen frischen, damit sie den Mechanismus nachvollziehen können
• Viele junge Ärzte sind super neugierig und entschuldigen sich fürs stellen von sovielen Fragen über die Allergie
• Ältere Ärzte, tja "jaja, sowas hab ich noch nie gehört, das wird vielleicht auch einfach was ganz anderes sein", Vielleicht liegen sie damit sogar richtig...aber...bisher hält die Diagnose
• Der Stress den Leute um einen herum haben während einer Reaktion... Es ist anstregender die Leute zu beruhigen als sich selbst
• Es sorgt für reichlich Grinsen, wenn der Notarzt sich mit einem dermatologischen Notfall in der Notaufnahme vordrängelt
• Meist sind die Symptome weg, bevor man mit dem Krankenwagen das Krankenhaus erreicht hat....
• Die einen Ärzte wollen einen für 24Std in der Notaufnahme/KH behalten, die anderen lassen einen nach 3-4Std wieder gehen. Verlasse mich bisher auf meine Erfahrung, und gehe lieber, da ich daheim mehr Ruhe habe
• Es ist immer wieder beeindruckend wie anstrengend eine Anaphylaxie ist!

5 Jahre mit WDEIA

• Ein paar weitere Reaktion in den letzten 2 Jahren
• Je seltener die Reaktion, desto schlimmer erscheinen sie
• "Möchtest du das mal machen?" sagen Notärzte zu ihren Sanitätern, wenn sie es noch nie verabreicht haben
• Manchen Ärzten genügt der Allergipass nicht und sie bitten um den Brief mit Diagnose, weil sie nicht glauben, dass es eine WDEIA ist
• Jeder Arzt hat eine andere Lösung: Der Ansatz bei der Diagnose die Toleranzen zu Weizen auszutesten und nicht pauschal zu verzichten werden teils als Unmöglichkeit betrachtet. Gleichzeitig sind dann aber "Spuren von Weizen" irrelevant
• Bei kleineren Mengen kribbelt es einfach ein bischen, was vor Experimenten abschreckt.

Persönliche Tricks / Regeln

• Kein Dinkel auf leeren Magen.
• Keine Dinkel Produkte über 2 Tage. Ich habe Reationen oft erst am 2 Tag des genießens von frischem Brot oder Brötchen gehabt.
• Vorsicht mit der Hefe: Ich habe im Laufe der Zeit 2 Sorten Frischhefe und eine Trockenhefe probiert. Bei der Trockenhefe hatte ich bisher keine Reaktionen mit Dinkel, bei der einen Frischhefe jedes Mal, bei der anderen sporadisch. Alle drei Hefen sind laut Hersteller Gluten- und Weizenfrei. Auf Grund der Komplexität der Allergie ist es schwer mit dem Finger auf die Hefe zu zeigen und nicht Belastung, das Mehl...was auch immer... Im Gegenzug sind Entspannung und Vertrauen gut.
• Langsam, über lange Zeit geruhte Sauerteigprodukte scheinen kein Problem zu machen.
• Vllt sind diese Tricks auch einfach nur Kopfsache :)
• Keine Teigschüsseln ohne Handschuhe spühlen: Egal ob Dinkel oder Weizen, in Kombination mit Spühlmittel und warmen Wasser sind meine Hände nicht glücklich.
• Tatsächlich die Shampooflasche lesen. Ich habe nach 3 Tagen rotem Kopf und Stirn gesehen, dass das Shampoo tatsächlich Weizenprotein enthält. Mein Kopf mochte es nich!

Links

Andere Projekte zum Thema

WDEIA

• Wheat Allergy / Weizenallergie bei European Centre for Allergy Research Foundation
  
• WDEIA: An welchen Symptomen erkennt man sie? Wie sehen Diagnose und Therapie aus? bei MeinALLERGIEPortal
  
• Weizenabhängige anstrengungsinduzierte Anaphylaxie T78.0 bei ALTMEYERS ENZYKLOPÄDIE
  
• Nur mit Kofaktoren bei Die PTA
  
• Glutenintoleranz bei Ärzteblatt Sachsen 1/2014
  
• Lebensmittelallergene bei Verband Deutscher Mühlen
  
• rTri a 19 Omega-5 Gliadin, Wheat bei Thermo Scientific
  
• Präzisere Diagnostik für die IgE-vermittelte Weizen-Allergie bei ImmunoCAP Explorer
  

Getreide

• Vergleich von reinen Dinkeln und Dinkel/Weizen-Kreuzungen bei Arbeitsgemeinschaft Getreideforschung e.V.
  
• Weizenanteile in Dinkelprodukten bei Forschungskreis der Ernährungsindustrie e.V.
  
• Wieviel Weizen steckt im Dinkel? Die DNA und weizentypische Proteine geben Auskunft bei Forschungskreis der Ernährungsindustrie e.V.
  
• Classification of spelt cultivars based on differences in storage protein compositions from wheat bei Elsevier, science direct
  

Paper zum Thema

2023

Wheat-dependent exercise-induced anaphylaxis: Subtypen, Diagnostik und Management

Die wheat-dependent exercise-induced anaphylaxis (Anstrengungs-getriggerte Weizenallergie, WDEIA) ist eine IgE-vermittelte Nahrungsmittelallergie, bei der es nur zu allergischen Symptomen kommt – welche von intermittierender Urtikaria bis hin zu schweren Anaphylaxien reichen können –, wenn Weizen im zeitlichen Zusammenhang mit verstärkenden Kofaktoren wie körperlicher Bewegung, nichtsteroidalen Antirheumatika oder Alkohol verzehrt wird. In den meisten Fällen weisen die Patienten eine Sensibilisierung auf ω5-Gliadin in der Glutenfraktion des Weizens auf. ω5-Gliadin-negative Subtypen der WDEIA sind oft schwierig zu diagnostizieren und können durch Tri a 14 (Weizen-Lipid-Transferprotein), durch perkutane Sensibilisierung mit hydrolysierten Weizenproteinen oder, in seltenen Fällen, durch eine Gräserpollenkreuzreaktivität verursacht werden. Die Diagnose wird anhand der Anamnese in Kombination mit dem serologischen IgE-Profil, Hauttests, Basophilenaktivierungstests und einer Provokationstestung mit Weizengluten und Kofaktoren gestellt. Die individuelle Ernährungsberatung ist nach wie vor die zentrale Säule im Management von Patienten mit WDEIA. Eine komplett weizenfreie Diät stellt eine mögliche Option dar, jedoch scheint diese die Toleranz weniger zu fördern als der weitergeführte regelmäßige Verzehr glutenhaltiger Getreidesorten, dieses allerdings nur bei gleichzeitiger Meidung von Kofaktoren. Alle Patienten sollten ein Notfallset zur Selbstbehandlung inklusive einem Adrenalin-Autoinjektor erhalten und entsprechend geschult werden. Zur sublingualen Immuntherapie bei WDEIA, einer potenziell vielversprechenden therapeutischen Perspektive, werden weitere Daten benötigt. Dieser Artikel gibt einen Überblick über den aktuellen Wissensstand zur Diagnostik und zum Management bei WDEIA, einschließlich eines optimierten Provokationsprotokolls mit Weizengluten und Kofaktoren.

2022

Clinical features and outcomes of patients with wheat-dependent exercise-induced anaphylaxis: a retrospective study

Background
Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a serious and potentially life-threatening form of wheat allergy. Further episodes can only be prevented by avoiding wheat ingestion or avoiding exercise after wheat intake. Anaphylaxis may recur in some patients post-diagnosis. This study aimed to analyze the clinical features and management/outcomes of WDEIA in China.
Methods
We retrospectively analyzed the clinical characteristics, and laboratory testing of 197 patients with WDEIA. After diagnosis, the patients were followed up as outpatients to evaluate dietary/exercise choice and clinical outcomes.
Results
Among the 197 WDEIA patients (median age, 37 years), 53.8% were male and 28.4% had other allergic disorders. The median duration of anaphylaxis before diagnosis was 16 months. Significant delays in diagnosis (> 1 years) were recorded in 52.7% of the patients, which has not decreased by years (P = 0.064). Exercise (83.8%), alcohol (12.2%), and nonsteroidal anti-inflammatory drugs (7.1%) were the most common cofactors. The most common clinical features were urticaria (100%), loss of consciousness (82.7%), dyspnea (50.8%), and hypotension (47.2%). Of the 197 eligible patients, 155 responded (78.7%), and 124 (80.0%) of which had no anaphylaxis post-diagnosis. A wheat-free diet prevented future anaphylaxis in 91.7% of the patients, followed by the avoidance of wheat combined with exercise (87%) and reduced wheat intake combined with exercise avoidance (80.5%).
Conclusion
The diagnosis of WDEIA is frequently delayed. Therefore, when patients present with unexplained anaphylaxis, the possibility of WDEIA should be considered. A wheat-free diet or avoiding wheat combined with exercise or reduced wheat combined with exercise avoidance helps to significantly reduce the onset of future anaphylaxis. However, approximately one-fifth of patients continue to experience anaphylaxis post-diagnosis. Thus, these patients must always carry epinephrine autoinjectors.

2019

Wheat allergy in patients with recurrent urticaria

BACKGROUND: Clinical observation revealed that most of wheat-induced anaphylaxis (WIA)/wheat-dependent exercise-induced anaphylaxis (WDEIA) patients showed a history of recurrent urticaria. We aim to determine the association between recurrent urticaria and anaphylaxis in wheat allergy.
METHODS: Population-based cohort study involved patients with WIA (n = 193, including WDEIA n = 104), recurrent urticaria (n = 177), non-wheat-related anaphylaxis (n = 584), atopic disease (excluding anaphylaxis, n = 221) and healthy control (n = 95) from 2009 to 2016. Detailed course of urticaria and anaphylaxis were obtained from medical records and following-up questionnaire. Serum IgE specific to wheat, gluten and ω-5 gliadin and skin prick test to wheat were examined. Clinical and laboratory data were statistically analyzed.
RESULTS: In recurrent urticaria patients, wheat allergy was not rare, and 6.8% (n = 12) was diagnosed as wheat-induced urticaria. Patients with WIA/WDEIA had higher prevalence of recurrent urticaria history than those with non-wheat-related anaphylaxis (164/193, 84.9% vs 85/584, 14.5%), and 70.4% of them (136/193) had recurrent urticaria prior to their first anaphylactic attack. Among patients with WIA/WDEIA and previous urticaria, 46.3% experienced an exacerbation of urticaria. The value of serum specific IgE to ω-5 gliadin was significantly higher in patients with WIA/WDEIA than those with wheat-induced urticaria.
CONCLUSIONS: We recommend screening wheat allergy in recurrent urticaria to identify patients who have a potential risk to develop severe reactions earlier.

2018

An unusual case of wheat dependent exercise induced anaphylaxis (WDEIA) triggered by Tri a 14 in a pediatric patient: a case report

Anakinra, one of the novel biological agents, is a recombinant human IL-1 receptor antagonist. It is preferred as an alternative drug for familial Mediterranean fever cases where colchicine is not sufficient or cannot be used due to its side effects. Like all other biologics, hypersensitivity reactions to anakinra are quite rare. This is the first case which was successfully desensitized with anakinra after a severe immediate-type hypersensitivity reaction. We report a case of WDEIA in an asthmatic boy admitted to our Unit with suspected mushroom acute toxicity. The symptoms occurred during a gym session, approximately 2 hours after the ingestion of a meal based on pasta and cooked mushroom found in the family's garden. Acute toxicity due to mushroom ingestion was then excluded. Triptase serum levels resulted elevated in acute phase and normal after 24 hours. Food specific IgE showed a sensitization to lipid transfer protein Pru p 3 and to Tri a 14. This case highlights that WDEIA is underdiagnosed, especially when patients are firstly visited in Emergency Unit. Moreover, Tri a 14 is seldom described as responsible for WDEIA, compared to omega 5 gliadin.

2017

Occupational allergy to Triticum spelta flour

Poster :)

2016

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.

2015

SIX CASES OF WHEAT-DEPENDENT EXERCISE-INDUCED ANAPHYLAXIS IN CHILDREN

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is often reported in adults for whom the specific IgE to ω-5 gliadin can be a useful diagnostic test. However, few cases of WDEIA in children have been reported. We herein report six cases (aged 7-16 years) of children with WDEIA, who had no clinical history of immediate-type wheat allergy but who were diagnosed by a wheat ingestion + exercise provocation test. The specific IgE to wheat ranged <0.35-3.49 (median 1.64) UA/ml. Skin prick tests using wheat extract were performed on 3 patients who showed either a negative or low specific IgE titer to wheat, and all of them resulted in negative findings. The specific IgE to ω-5 gliadin was below the detection limit in all cases. Aspirin-supplemented provocation tests were performed to 4 cases who had negative results in the wheat + exercise test. All of these resulted in a positive reaction, and two of them provoked the occurrence of anaphylactic shock, which was relieved by the intramuscular injection of adrenaline. WDEIA in children cannot be ruled out by serological tests alone. On the other hand, severe symptoms might be provoked by the provocation test. Therefore, a safe procedure is warranted for the diagnosis of WDEIA in children.

Using a gluten oral food challenge protocol to improve diagnosis of wheat-dependent exercise-induced anaphylaxis

BACKGROUND: Oral wheat plus cofactors challenge tests in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) produce unreliable results.
OBJECTIVE: We sought to confirm WDEIA diagnosis by using oral gluten flour plus cofactors challenge, to determine the amount of gluten required to elicit symptoms, and to correlate these results with plasma gliadin levels, gastrointestinal permeability, and allergologic parameters.
METHODS: Sixteen of 34 patients with a history of WDEIA and ω5-gliadin IgE underwent prospective oral challenge tests with gluten with or without cofactors until objective symptoms developed. Gluten reaction threshold levels, plasma gliadin concentrations, gastrointestinal permeability, sensitivities and specificities for skin prick tests, and specific IgE levels were ascertained in patients and 38 control subjects.
RESULTS: In 16 of 16 patients (8 female and 8 male patients; age, 23-76 years), WDEIA was confirmed by challenges with gluten alone (n = 4) or gluten plus cofactors (n = 12), including 4 patients with previous negative wheat challenge results. Higher gluten doses or acetylsalicylic acid (ASA) plus alcohol instead of physical exercise were cofactors in 2 retested patients. The cofactors ASA plus alcohol and exercise increased plasma gliadin levels (P < .03). Positive challenge results developed after a variable period of time at peak or when the plateau plasma gliadin level was attained. Positive plasma gliadin threshold levels differed by greater than 100-fold and ranged from 15 to 2111 pg/mL (median, 628 pg/mL). The clinical history, IgE gliadin level, and baseline gastrointestinal level were not predictive of the outcomes of the challenge tests. The challenge-confirmed sensitivity and specificity of gluten skin prick tests was 100% and 96%, respectively.
CONCLUSION: Oral challenge with gluten alone or along with ASA and alcohol is a sensitive and specific test for the diagnosis of WDEIA. Exercise is not an essential trigger for the onset of symptoms in patients with WDEIA.

Diagnostik und Mechanismen der Anaphylaxie bei Patienten mit weizenabhängiger Anstrengungsanaphylaxie

Weizenabhängige Anstrengungsanaphylaxien sind Summationsanaphylaxien, bei denen allergische Soforttyp-Reaktionen zumeist durch körperliche Anstrengung nach dem Verzehr von Nahrungsmitteln ausgelöst werden. Häufige Symptome sind zunächst Urtikaria und Angioödem, jedoch können oft im Verlauf auch Kreislauf und Atemwege betroffen sein. Omega-5-Gliadin wurde als wesentliche spezifische Allergenstruktur bei der durch Weizen ausgelösten anstrengungsinduzierten Anaphylaxie identifiziert. Diagnostisch beweisend für die weizenabhängige Anstrengungsanaphylaxie ist die positive orale Provokationstestung unter kontrollierten Bedingungen. Der sichere Nachweis der Erkrankung durch herkömmliche Provokationstestungen mit Weizen oder Weizensemmeln ist schwierig. Aufgrund der Problematik häufig falsch-negativer Provokationstestungen, wurde ein neues Protokoll mit Verwendung von Gluten plus Augmentationsfaktoren etabliert. Dabei wurden unter ärztlicher Aufsicht schrittweise ansteigende Dosen von Gluten mit nachfolgend körperlicher Anstrengung bzw. anderen Kofaktoren verabreicht. Im Rahmen der Studie konnte damit bei 16 von 16 Patienten die Diagnose weizenabhängige Anstrengungsanaphylaxie bestätigt werden. Im Blut der Patienten wurden die Omega-5-Gliadin-Spiegel bestimmt. Die Reaktionen waren jeweils mit hohen Plasmagliadinwerten assoziiert. Zusätzliche Kofaktoren führten zu erhöhter gastrointestinaler Permeabilität. Die Reaktionsschwelle war nicht mit allergologischen Parametern korreliert. Weder die spezifischen IgE-Spiegel von ω5-Gliadin, noch das Verhältnis der spezifischen IgE am Gesamt-IgE, noch der Quaddel-Durchmesser des Prick-Tests auf Gluten, noch der maximale Schweregrad der Reaktionen in der Krankengeschichte, noch die Anzahl der Reaktionen konnten eine Prognose über die klinische Reaktionsschwelle geben.
In unserer Studie zeigte sich, dass die alleinige Gabe einer hohen Allergenmenge an Gluten bei Patienten zur Reaktionsauslösung führen kann, selbst wenn Kofaktoren nicht präsent sind. Deshalb muss die nahrungsmittelabhängige anstrengungsinduzierte Anaphylaxie, die nur dann auftritt wenn Kofaktoren wie Anstrengung präsent sind, unterschieden werden von einer Nahrungsmittelanaphylaxie, die durch Anstrengung verstärkt, jedoch auch ohne diese auftreten kann. Wie die Ergebnisse unserer Studie darstellen, ist körperliche Anstrengung für eine Reaktionsauslösung nicht immer obligat. Eine weizenabhängige Anstrengungsanaphylaxie könnte deshalb vielleicht treffender als „kofaktorgetriggerte Nahrungsmittelallergie“ (augmentation factor-triggered food allergy (AFTFA)) bezeichnet werden.
Haut-Prick-Testungen, die Bestimmung von spezifischen IgE-Antikörpern und orale Provokationstestungen mit Gluten können als guter Screening-und Bestätigungstest bei Patienten mit Verdacht auf weizenabhängige Anstrengungsanaphylaxie empfohlen werden. Es muss jedoch betont werden, dass die Patienten in unserer Studie während der Testungen auf supraphysiologische Dosen von Gluten reagierten, während in der Vergangenheit im realen Leben deutlich geringere Mengen an Gluten ausgereicht hatten, um eine Reaktion auszulösen. Dies deutet darauf hin, dass die Reaktionsschwelle durch zusätzliche Faktoren, die noch teilweise unerkannt sind, beeinflusst wird. Hier besteht weiterer Forschungsbedarf, denn nur die Identifikation der Allergene und der Triggerfaktoren sowie eine intensive ärztliche Schulung und Diätberatung der Patienten verhindert zukünftige Anaphylaxien. |

2014

Wheat-dependent exercise-induced anaphylaxis: a retrospective case review from a tertiary hospital

BACKGROUND: Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a specific form of wheat allergy caused by the combination of wheat ingestion and physical exercise and has been reported in other parts of Asia. At present, there are no published reports of WDEIA in Singapore. The objective of this study is to characterise the common local clinical and laboratory manifestations of WDEIA.
METHODS: This was a retrospective descriptive study of all WDEIA who presented to a tertiary Singaporean Hospital over a 5-year-period from 1 January 2009 to 30 June 2013.
RESULTS: Eight patients aged 9-41 years old were characterised. Six were males and the majority (5) was of Chinese ethnicity. An atopic history was found in four patients. The symptoms of anaphylaxis included cutaneous manifestations such as urticaria (n=7), angioedema (n=6), respiratory symptoms of dyspnoea and wheezing (n=5) and hypotension (n=5). The symptoms occurred 20-75 min after consumption of wheat-based products, often upon cessation of exercise [running (n=3), walking (n=4) and swimming (n=1)]. The WDEIA was recurrent in seven patients. The skin prick tests were positive to wheat in seven patients, and ω-5 gliadin test to wheat was positive in five patients.
CONCLUSIONS: With the emergence of wheat allergy in East Asian countries, WDEIA has become an important condition for physicians and Singapore is no exception. Under-recognition combined with life-threatening symptoms warrants better public awareness measures. In addition, further studies are necessary to identify possible unique genetic and environmental exposures that could explain the inter-regional differences of WDEIA.

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.

2013

Characterization of causative allergens for wheat-dependent exercise-induced anaphylaxis sensitized with hydrolyzed wheat proteins in facial soap

BACKGROUND: In Japan, hydrolyzed wheat proteins (HWP) have been reported to cause wheat-dependent exercise-induced anaphylaxis (WDEIA) by transcutaneous sensitization using HWP-containing soap. Patients develop allergic reactions not only with soap use, but also with exercise after the intake of wheat protein (WP). ω5-Gliadin and HMW-glutenin were identified as major allergens in conventional WP-WDEIA patients. However, the allergens in HWP-WDEIA have yet to be elucidated.
METHODS: Sera were obtained from 22 patients with HWP-sensitized WDEIA. The allergenic activities of HWP and six recombinant wheat gluten proteins, including α/β-, γ-, ω1,2- and ω5-gliadin and low- and high molecular weight (HMW)-glutenins, were characterized by immunoblot analysis and histamine releasing test. IgE-binding epitopes were identified using arrays of overlapping peptides synthesized on SPOTs membrane.
RESULTS: Immunoblot analysis showed that IgE antibodies (Abs) from HWP-WDEIA bound to α/β-, γ- and ω1,2-gliadin. Recombinant γ-gliadin induced significant histamine release from basophils in eight of 11 patients with HWP-WDEIA. An IgE-binding epitope "QPQQPFPQ" was identified within the primary sequence of γ-gliadin, and the deamidated peptide containing the "PEEPFP" sequence bound with IgE Abs more strongly compared to the native epitope-peptide. The epitope-peptide inhibited IgE-binding to HWP, indicating that the specific IgE to HWP cross-reacts with γ-gliadin.
CONCLUSIONS: HWP-WDEIA patients could be sensitized to HWP containing a PEEPFP sequence, and WDEIA symptoms after WP ingestion could partly be induced by γ-gliadin. These findings could be useful to help develop tools for diagnosis and desensitization therapy for HWP-WDEIA.

The sensitivity and clinical course of patients with wheat-dependent exercise-induced anaphylaxis sensitized to hydrolyzed wheat protein in facial soap - secondary publication

BACKGROUND: Recently, an increasing number of patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) have been reported in Japan. Most of them had developed this condition during or after using hydrolyzed wheat protein (HWP)-containing soap (HWP-WDEIA).
METHODS: To clarify the relation between WDEIA and HWP-containing soap and their prognosis, we retrospectively studied the patients who visited Hiroshima University Hospital and were diagnosed as WDEIA from January 2010 to June 2011. We took detailed clinical histories, performed skin prick tests, serum immunoassays for antigen-specific IgE and basophil histamine release test, and followed up their clinical courses after the diagnosis.
RESULTS: Among 36 patients with WDEIA, 30 patients had used only one type of HWP-soap. The patients with HWP-WDEIA were mainly women and had developed facial symptoms and angioedema. They suffered from blood pressure reductions less frequently than patients with conventional WDEIA. The levels of gluten-specific IgE were higher than those of omega-5 gliadin in patients with HWP-WDEIA (P < 0.05, One-way ANOVA). All patients with HWP-WDEIA were positive against HWP in histamine release test. Among the conventional wheat antigens, glutenins induced the highest histamine release from basophils of patients with HWP-WDEIA. The sensitivities of patients against glutens and glutenins were reduced over months along with the discontinuance of HWP-soap.
CONCLUSIONS: The development of HWP-WDEIA is associated with the use of HWP-soap. The sensitivity to HWP that cross reacts with non-processed wheat may be reduced or possibly cured after the discontinuation of HWP-soap.

Serum gliadin monitoring extracts patients with false negative results in challenge tests for the diagnosis of wheat-dependent exercise-induced anaphylaxis

BACKGROUND: Challenge testing with wheat plus exercise and/or aspirin is a gold standard for the diagnosis of wheat-dependent exercise-induced anaphylaxis (WDEIA); however, the test may often yield false-negative results. Our previous study suggested that an increase in serum wheat gliadin levels is required to induce allergic symptoms in patients with WDEIA. Based on this knowledge, we sought to extract the patients with false negative results in the challenge tests of WDEIA.
METHODS: Thirty-six patients with suspected WDEIA were enrolled. First, group categorizations-Group I, challenge tests were positive; Group II, challenge tests were negative and serum gliadin were undetectable; Group III, challenge tests were negative and serum gliadin were detectable-were given according to the results of wheat plus exercise and/or aspirin challenge testing and serum gliadin levels. Second, diagnoses were made using retests and/or dietary management in Group II and III.
RESULTS: Positive results for wheat plus exercise and/or aspirin challenge tests gave a diagnosis of definite WDEIA in 17 of 36 patients (Group I). Of the remaining 19 challenge negative patients, serum gliadin was undetectable in ten patients (Group II). Of the ten patients (Group II), three of them were diagnosed as definite WDEIA by retesting and six of them were diagnosed as probable WDEIA using a wheat elimination diet, whereas one patient was non-WDEIA. In the rest of the nine challenge negative patients, serum gliadin was detectable (Group III). No allergic episodes with a normal diet provided a diagnosis of non-WDEIA in seven of the nine patients, whereas the remaining two patients were probable WDEIA or had another food allergy because of repeated episodes.
CONCLUSIONS: Our study revealed that serum gliadin monitoring during challenge testing is useful.

2012

Wheat-dependent exercise-induced anaphylaxis sensitized with hydrolyzed wheat protein in soap

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a specific form of wheat allergy typically induced by exercise after ingestion of wheat products. Wheat ω-5 gliadin is a major allergen associated with conventional WDEIA, and detection of serum immunoglobulin E (IgE) specific to recombinant ω-5 gliadin is a reliable method for its diagnosis. Recently, an increased incidence of a new subtype of WDEIA, which is likely to be sensitized via a percutaneous and/or rhinoconjunctival route to hydrolyzed wheat protein (HWP), has been observed. All of the patients with this new subtype had used the same brand of soap, which contained HWP. Approximately half of these patients developed contact allergy several months later and subsequently developed WDEIA. In each of these patients, contact allergy with soap exposure preceded food ingestion-induced reactions. Other patients directly developed generalized symptoms upon ingestion of wheat products. The predominant observed symptom of the new WDEIA subtype was angioedema of the eyelids; a number of patients developed anaphylaxis. This new subtype of WDEIA has little serum ω-5 gliadin-specific serum IgE.

Recombinant high molecular weight-glutenin subunit-specific IgE detection is useful in identifying wheat-dependent exercise-induced anaphylaxis complementary to recombinant omega-5 gliadin-specific IgE test

BACKGROUND: Recently an increasing number of patients with wheat-dependent exercise-induced anaphylaxis (WDEIA), developed during or after using hydrolyzed wheat protein (HWP)-containing soap (HWP-WDEIA), were reported in Japan.
METHODS: To clarify the relation between WDEIA and HWP-containing soap and their prognosis, we investigated the patients who visited Hiroshima University Hospital and were diagnosed as WDEIA from January 2010 to June 2011. We took detailed clinical histories, performed skin prick tests, serum immunoassays for antigen-specific IgE and basophil histamine release test, and followed up their clinical courses after the diagnosis.
RESULTS: Among 36 patients with WDEIA, 30 patients had used only one type of HWP-soap. The patients with HWP-WDEIA were mainly women and had developed facial symptoms and angioedema. They suffered from blood pressure reductions less frequently than patients with conventional WDEIA. The levels of glutens-specific IgE were higher than those of ω-5 gliadin in patients with HWP-WDEIA (p<0.05, One-way ANOVA). All patients with HWP-WDEIA were positive against HWP in histamine release test. Among the conventional wheat antigens, glutenins induced highest histamine release from basophils of patients with HWP-WDEIA. The sensitivities of patients against glutens and glutenins were reduced over months along with the discontinuance of HWP-soap.
CONCLUSIONS: The development of HWP-WDEIA is associated with the use of HWP-soap. The sensitivities to HWP that cross reacts with non-processed wheat may be reduced or possibly cured after the discontinuation of HWP-soap.

2009

Food-dependent exercise-induced anaphylaxis -importance of omega-5 gliadin and HMW-glutenin as causative antigens for wheat-dependent exercise-induced anaphylaxis-

Food-dependent exercise-induced anaphylaxis (FDEIA) is a special form of food allergy where a food-intake alone does not induce any symptoms. However, allergic symptoms are elicited when triggering factors such as exercise or aspirin-intake are added after ingestion of the causative food. The most frequent causative foodstuff in Japan is wheat. The triggering factors, both exercise and aspirin-intake, facilitate allergen absorption from the gastrointestinal tract, resulting in allergic symptoms in the patients with wheat-dependent exercise-induced anaphylaxis (WDEIA). Analysis using purified wheat proteins revealed that approximately 80% of the patients with WDEIA have IgE reacting to omega-5 gliadin and the remaining of the patients to high molecular weight glutenin (HMW-glutenin). Simultaneous measurement of specific IgE to omega-5 gliadin and HMW-glutenin was found to be highly useful in diagnosing WDEIA compared with the routine diagnostic system for wheat.

The inhibition effect of a synthetic analogue of prostaglandin E1 to the provocation by aspirin in the patients of WDEIA

BACKGROUND: Exercise or aspirin intake enhances symptoms by increasing blood gliadin levels in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA). Misoprostol, a synthetic analogue of prostaglandin E1 (PGE1) compensates prostagrandins of which synthesis is inhibited by aspirin and protect the gastrointestinal mucosa. We projected to examine the effect of misoprostol in suppression the allergic symptom and elevation of blood gliadin levels in WDEIA induced by aspirin.
PATIENTS AND METHODS: Two patients with a history of recurrent anaphylaxis associated with wheat ingestion accompanied with exercise, positive specific IgE and/or skin test were enrolled in the provocation test. On the provocation test of WDEIA, wheat ingestion, exercise, aspirin intake were combined on various ways. During the test, the patients' symptom and serum gliadins levels were monitored.
RESULTS: Although wheat with exercise did not induce any symptoms, addition of aspirin induced urticaria and elevation of blood gliadin levels in both cases. In case 1, premedication of misoprostol suppressed the urticaria and elevation of blood gliadin levels which were induced by exercise, wheat and aspirin intake. In case 2, premedication of misoprostol suppressed the urticaria and elevation of blood gliadin levels which were induced by wheat and aspirin intake.
CONCLUSION: These findings suggest that a synthetic analogue of PGE1 may suppresses the absorption of the allergen levels and outbreak the allergic symptom induced by aspirin in the patients with WDEIA.

2008

Gliadin-specific IgE in wheat-dependent exercise-induced anaphylaxis

Food-dependent exercise-induced anaphylaxis is a unique form of food allergy. Recent studies indicate that gliadin is a major allergen in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA). We evaluated the value of serum gliadin-specific IgE in the diagnosis of WDEIA, as well as the characteristics and digestibilities of the IgE-binding components of gliadin. We analyzed 32 adult subjects sensitized to wheat; 26 were asymptomatic sensitizers and 6 had WDEIA. Wheat flour and gliadin-specific IgE levels were measured, and corresponding receiver operator characteristics (ROC) curves were determined. Patients with WDEIA had higher levels of gliadin-specific IgE than patients without WDEIA (p = 0.003). The area under the ROC curve for gliadin-specific IgE was 0.872, which suggested this assay could be used as a supplementary test for the diagnosis of WDEIA. IgE immunoblot analyses of reactions to wheat and gliadin extracts were compared both with and without simulated gastric fluid (SGF) and intestinal fluid incubation (SIF). All six WDEIA patients had high IgE binding signals to 50 kDa of gliadin extract on IgE immunoblots. This binding was suppressed by SGF, although minimal inhibition was noted with SIF incubation.

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 omega-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 omega-5 gliadin (romega-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. 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 romega-5 gliadin were 48%, 56%, 76%, 22%, and 80%, respectively. The seven of 10 WDEIA patients with no specific IgE antibodies to romega-5 gliadin had specific IgE antibodies to Pep B. The highest AUC (0.850) was observed in the test for romega-5 gliadin.
CONCLUSIONS: Measuring the concentration of specific IgE antibodies to romega-5 gliadin is more useful than to wheat, gluten, or Pep A in the identification of patients with WDEIA.

2005

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.

2004

Identification of the IgE-binding Epitope in ω-5 Gliadin, a Major Allergen in Wheat-dependent Exercise-induced Anaphylaxis

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a severe IgE-mediated allergic reaction provoked by the combination of wheat-ingestion with intensive physical exercise over the next few hours. Among wheat proteins, omega-5 gliadin, which is one of the components of fast omega-gliadin, has been reported as a major allergen in the anaphylaxis. In this study, we detected IgE-binding epitopes within the primary sequence of omega-5 gliadin using arrays of overlapping peptides synthesized on derivatized cellulose membranes. Sera from four patients with WDEIA having specific IgE to the fast omega-gliadin were used to probe the membrane. Seven epitopes, QQIPQQQ, QQLPQQQ, QQFPQQQ, QQSPEQQ, QQSPQQQ, QQYPQQQ, and PYPP, were detected within the primary sequence of omega-5 gliadin. By using sera of 15 patients, 4 of them, QQIPQQQ, QQFPQQQ, QQSPEQQ, and QQSPQQQ, were found to be dominant epitopes. Mutational analysis of the QQIPQQQ and QQFPQQQ indicated that amino acids at positions Gln(1), Pro(4), Gln(5), Gln(6), and Gln(7) were critical for IgE binding. These results will provide a useful tool for developing safer wheat products in addition to diagnostic and immunotherapy techniques for WDEIA.

2003

Fast omega-gliadin is a major allergen in wheat-dependent exercise-induced anaphylaxis.

BACKGROUND: Wheat-dependent exercise-induced anaphylaxis is an anaphylaxy induced by physical exercise after ingestion of wheat. An immediate-type hypersensitivity to water/salt-insoluble fraction of wheat proteins (gluten) has been considered to underlie in this disease.
OBJECTIVE: The aim of the study is to determine the major allergen in Japanese patients with wheat-dependent exercise-induced anaphylaxis by using a panel of purified wheat gliadins and glutenins.
METHODS: Water/salt-insoluble wheat proteins, alpha-gliadin, beta-gliadin, gamma-gliadin, fast omega-gliadin, slow omega-gliadin, high molecular weight glutenin and low molecular weight glutenin, were purified, and five patients with wheat-dependent exercise-induced anaphylaxis, whose diagnose had been determined by positive-challenge test, were evaluated for skin prick test, dot-blotting test and CAP-RAST inhibition test by using these purified wheat proteins.
RESULTS: The fast omega-gliadin was the most potent allergen among these water/salt-insoluble proteins when evaluated by skin prick test and dot-blotting test. Fast and slow omega-gliadin, and gamma-gliadin caused dose-dependent inhibition of the serum IgE-binding to solid-phase gluten in the patients. The incubation with fast omega-gliadin of the patient's serum caused dose-dependent inhibition in the IgE-binding to gamma-gliadin as well as slow omega-gliadin, indicating a cross-reactivity of these proteins in IgE-binding.
CONCLUSION: We concluded that fast omega-gliadin is a major allergen among these water/salt-insoluble proteins for wheat-dependent exercise-induced anaphylaxis in Japanese patients, and IgE against fast omega-gliadin cross-reacts to gamma-gliadin and slow omega-gliadin.

Humoral and cellular responses to gliadin in wheat-dependent, exercise-induced anaphylaxis

BACKGROUND: Wheat-dependent, exercise-induced anaphylaxis (WDEIA) is a severe allergy where wheat ingestion together with physical exercise induces anaphylaxis. We have previously shown that patients with WDEIA have IgE antibodies against gliadin proteins and identified omega-5 gliadin (Tri a 19) as a major allergen.
OBJECTIVE: The aim of this study was to examine gliadin-specific IgG subclass, IgA and IgE antibodies, basophil histamine release and cell-mediated responses in WDEIA.
METHODS: Sera and peripheral blood mononuclear cells (PBMC) were obtained from patients with WDEIA and from controls without wheat allergy. Serum antibodies to crude gliadin extract (CGE) and purified omega-5 gliadin were measured by ELISA and basophil reactivity by histamine-release test. Gliadin-induced cell-mediated responses were assessed by lymphocyte proliferation assay, and cytokine mRNA expression with real-time quantitative PCR.
RESULTS: All patients with WDEIA, but none of the controls, had IgE antibodies to CGE and omega-5 gliadin. Both allergens released high levels of histamine from the basophils of patients with WDEIA. Levels of IgA antibodies to CGE and omega-5 gliadin were significantly elevated in the patients, but the distribution of IgG subclass antibodies showed no statistically significant differences between the two groups. Proliferative responses of PBMC to CGE were increased in patients with WDEIA, and stimulation of PBMC with CGE caused, both in patients and in controls, a clear induction of IL-10 mRNA. Compared with the controls, induction of IL-10 mRNA expression in patients with WDEIA was significantly (P < 0.01) suppressed.
CONCLUSION: These results suggest that, in addition to IgE antibodies against omega-5 gliadin, specific IgA antibodies may be involved in the pathogenesis of WDEIA. Decreased expression of IL-10 mRNA in PBMC during gliadin stimulation may facilitate the development of gliadin-specific T cell responses.

2001

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

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. The aim of this study was to examine whether children with allergy to ingested wheat have IgE antibodies to omega-5 gliadin. 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. 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. 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.

Rye γ-70 and γ-35 secalins and barley γ-3 hordein cross-react with ω-5 gliadin, a major allergen in wheat-dependent, exercise-induced anaphylaxis

Patients with wheat-dependent, exercise-induced anaphylaxis experience severe allergic reactions when exercising after ingestion of wheat. The major wheat allergen associated with these reactions is a ω-5 gliadin, and patients following a gluten-free diet have remained free of symptoms. The aim of this study was to examine whether allergens cross-reacting with wheat ω-5 gliadin are present in rye, barley and oats. Sera from 23 adult patients with wheat-dependent, exercise-induced anaphylaxis were examined. Cereal allergens cross-reacting with wheat ω-5 gliadin were identified by immunoblot inhibition. The cross-reactive allergens were purified by gel filtration and reversed-phase chromatography and submitted to amino acid sequencing. Cross-reactivity was further studied by IgE ELISA and ELISA inhibition, and in vivo reactivity by skin prick testing. In immunoblotting rabbit anti-ω-5 gliadin antibodies bound to 70 kDa and 32 kDa proteins in rye and a 34-kDa protein in barley, but not to proteins in oats. N-terminal sequencing identified these proteins as rye γ-70 secalin, rye γ- 35 secalin and barley γ-3 hordein, correspondingly. In ELISA 21/23 (91%) patients with wheat-dependent, exercise-induced anaphylaxis showed IgE antibodies to purified γ-70 secalin, 19/23 (83%) to γ-35 secalin and 21/23 (91%) to γ-3 hordein. In ELISA inhibition ω-5 gliadin inhibited over 90% of the IgE binding of pooled patient sera to solid-phase γ-secalins and γ-3 hordein. Skin prick testing gave positive reactions to γ-70 secalin in 10/15 (67%) patients, to γ-35 secalin in 3/15 (20%) patients and to γ-3 hordein in 7/15 (47%) patients. The results of this study show that γ-70 and γ-35 secalins in rye and γ-3 hordein in barley cross-react with ω-5 gliadin, a major allergen in wheat-dependent, exercise-induced anaphylaxis. These findings suggest that also rye and barley may elicit symptoms in patients with wheat-dependent, exercise-induced anaphylaxis.

2000

Food-dependent exercise-induced anaphylaxis: a report of two cases and determination of wheat-gamma-gliadin as the presumptive allergen

Food-dependent, exercise-induced anaphylaxis is a severe form of allergy; the reaction is caused by ingestion of a specific food before exercise. This disorder often escapes diagnosis because neither the ingested food nor the exercise alone induces the symptoms. The aim of the study was to characterize the allergens involved in wheat-dependent, exercise-induced anaphylaxis and to describe the clinical outcome in a series of 18 adult patients. All 18 patients had experienced recurrent episodes of generalized urticaria during exercise, 17 patients in association with collapse and 15 patients with an anaphylactic reaction. The symptoms appeared only when the patients had eaten food containing wheat before exercise. Wheat allergens were detected by immunoblotting, purified by gel filtration and reversed-phase chromatography, and subjected to N-terminal sequencing. The IgE-binding ability of the purified proteins was studied by ELISA, and their in vivo reactivity was studied by skin prick testing. IgE antibodies from pooled patient sera were bound to 65-kd and 40-kd wheat proteins in immunoblotting. The 65-kd allergen was a previously undescribed wheat protein, showing 61% sequence identity to gamma-gliadin, whereas the 40-kd allergen had 100% identity to alpha-gliadin. In ELISA, all 18 patients showed elevated IgE levels to the novel gamma-like gliadin, and 13 of the patients showed elevated IgE levels to the alpha-gliadin. None of the 54 control subjects with wheat allergy, urticaria, or coeliac disease had IgE antibodies to the gamma-like gliadin. The in vivo reactivity of the gamma-like gliadin was verified by positive skin prick test responses in all of the 15 patients who were tested. During the follow-up on a gluten-free or wheat-free diet, 3 patients experienced reactions after having unknowingly eaten wheat before exercise, but all the other patients who were adhering to the diet remained symptom-free. This study shows that wheat is a frequent cause of food-dependent, exercise-induced anaphylaxis and suggests that the major allergen is a previously undescribed gamma-like gliadin. For screening of this life-threatening allergy, we recommend skin prick testing with crude gliadin and we recommend a gluten-free diet for treatment.

1997

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 NaCl 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 NaCl wheat suspension was a simple and practical test to screen patients with this kind of occult, possibly life-threatening, allergy to cereals.|

Exercise-Induced Anaphylaxis: Useful Screening of Food Sensitization

Exercise-induced anaphylaxis is a well-defined entity as described by Sheffer and Austen. Exercise-induced anaphylaxis can be associated with ingestion of a specific food. We report our experience with a series of cases of exercise-induced anaphylaxis in which anaphylaxis was considered to be associated with food allergy. We observed 19 patients in whom severe systemic signs of anaphylaxis occurred during or immediately after exercise, while the severity of reactions excluded challenge testing. The causal relationship with various foods was systematically investigated in all cases, even in the absence of any history of allergy. Sensitization to wheat flour was demonstrated in 12 patients, to peanut in seven, and to tree nuts in six cases with skin tests and/or RAST. Sensitivity to various other foods was found less often. Further, avoidance of specific foods according to results of skin tests and RAST was systematically observed during the five hours prior to exercise and no symptom occurred, suggesting a role of specific food intake in the pathogenesis of exercise-induced anaphylaxis. With such elimination diets, most of these young patients were able to engage in regular vigorous exercises (more than twice a week in some cases) without any clinical manifestation with a median followup of 2 years. In two patients, however, recurrence of exercise-induced anaphylaxis was subsequently explained by concomitant ingestion of other foods such as rice and peanut. Additional avoidance of these foods before exercise was then effective in 14 cases (median follow up: 2 years). Investigations to detect food sensitization, in particular to wheat, peanut and/or tree nuts, and specific avoidance of these foods five hours before exercise appear essential in cases of exercise-induced anaphylaxis. |

1996

IgA and IgG Binding Components of Wheat, Rye, Barley and Oats Recognized by Immunoblotting Analysis with Sera from Adult Atopic Dermatitis Patients

IgA and IgG antibody response of adult atopic dermatitis patients against neutral/ acidic fractions of wheat, rye, barley and oats was analyzed utilizing an immunoblotting method. Moreover, the antibody response against ethanol-soluble fraction of wheat was examined with serum pools of healthy donors, atopic dermatitis patients and patients with dermatitis herpetiformis or adult celiac disease. All patient sera revealed polymorphic IgA and IgG binding to cereal peptides with molecular weights of 11-97 kD. The antibody staining was essentially identical with atopic dermatitis patients and controls. Patients with dermatitis herpetiformis or celiac disease showed more intensive staining with the ethanol extract of wheat and showed more IgA-stained bands in immunoblotting. It seems that the presence of IgA and IgG antibodies to different cereal antigens is a result of natural exposure and in atopic dermatitis displays little diagnostic significance, in contrast to antigliadin antibody response in dermatitis herpetiformis and celiac disease.

1991

Fod-dependent, exercise-induced anaphylaxis: A study on 11 Japanese cases

Eleven patients with food-dependent, exercise-induced anaphylaxis were studied. Seven patients experienced anaphylactic symptoms only after eating certain foods, such as shellfish, wheat, and grape before exercise. In the remaining four patients, no specific food could be identified, but the act of eating itself predisposed to anaphylaxis. Their anaphylactic symptoms were all clearly distinguished from cholinergic urticaria by history. Patients who developed anaphylactic symptoms before 20 years of age (N = 7) were atopic themselves or had atopic first-degree relatives. Six patients had increased serum IgE levels, and IgE antibodies against the causative food allergens were detected by the skin prick test or RAST in four cases. In contrast, patients who developed the symptoms after 30 years of age (N = 4) appeared to have a less atopic background, and IgE levels were within normal range except in one case. Three of four patients in the latter group developed symptoms after ingesting food made of wheat followed by exercise. All patients were sensitive to wheat as determined by the skin prick test. In six of 11 patients, a considerable rise in plasma histamine concentration was observed after exercise challenge with treadmill alone, and food intake followed by exercise induced a further increase in one patient.

1985

Masked Type I Wheat Allergy: Relation to Exercise-Induced Anaphylaxis

Six patients had type I hypersensitivity to wheat. Three cases were exercise-induced anaphylaxis to wheat, one was exercise-induced urticarial reaction to wheat (with angioedema), and the remaining two were exercise-accentuated urticarial reaction to wheat. Elimination of wheat from the diet completely cleared these symptoms. Allergens were prepared from wheat, gluten, gliadin, and glutenin by simple extraction and enzyme digestion, and these preparations were used in skin tests. The allergens obtained from gluten, gliadin, and glutenin by pepsin digestion were qualitatively different from wheat and gluten allergens obtained by simple extraction and were more related to exercise-induced anaphylaxis. Trypsin digestion showed no such effect and abolished all these allergens. These results indicate that wheat allergens are reinforced in the stomach and destroyed in the jejunum.

1983

IgA antigliadin antibodies: A marker of mucosal damage in childhood coeliac disease

Antigliadin antibodies in serum samples of 31 children with coeliac disease were measured by an enzyme-linked immunosorbent technique. In young patients (less than 2 years) tested before gluten withdrawal IgA antigliadin antibody levels were invariably above the levels of 36 controls. The titres fell rapidly when gluten was eliminated from the diet and rose on its reintroduction. The titres were not always greater than the control level in older untreated patients. IgA antigliadin antibodies seem to be a good marker of the immune reaction in the jejunum triggered by gluten. In 2 IgA-deficient patients gluten challenge caused an increase in IgM antigliadin antibodies, and at the same time the number of IgM-containing cells increased in the jejunal mucosa. Rising IgG antigliadin antibody levels after gluten elimination were seen in 6 patients, 5 of whom had very low complement C3 levels before gluten elimination.

Fragen?

Formales