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Background: Wheat is one of the most commonly consumed foods and a known elicitor of anaphylaxis in children and adults. Reactions in adults are often cofactor dependent and characterized by a prolonged time between food intake and the onset of symptoms making the diagnosis of wheat anaphylaxis challenging., Objective: To characterize a cohort of patients with the history of wheat anaphylaxis to better understand this atypical phenotype of anaphylaxis., Methods: Data from the European Anaphylaxis Registry from 2007 to 2019 (n = 10,636) including 250 patients (213 adults and 37 children) with a history of anaphylaxis caused by wheat were analyzed., Results: Wheat was the most common food elicitor of anaphylaxis in adults in the registry in Central Europe. Reactions to wheat in adults were frequently associated with exercise as a cofactor (82.8%) and partially delayed (57.5%). Only 36.9% of patients had atopic comorbidities, which was uncommonly low for adult patients allergic to other kinds of foods (63.2%). Anaphylaxis to wheat presented frequently with cardiovascular symptoms (86.7%) including severe symptoms such as loss of consciousness (41%) and less often with respiratory symptoms (53.6%). The reactions to wheat were more severe than reactions to other foods (odds ratio [OR] = 4.33), venom (OR = 1.58), or drugs (OR = 2.11)., Conclusions: Wheat is a relevant elicitor of anaphylaxis in adults in Central Europe. Wheat anaphylaxis is highly dependent on the presence of cofactors and less frequently associated with atopic diseases compared with other food allergies. More data on mechanisms of wheat-induced anaphylaxis are required to develop preventive measures for this potentially life-threatening disease., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Venom-induced anaphylaxis (VIA) is a common, potentially life-threatening hypersensitivity reaction associated with (1) a specific symptom profile, 2) specific cofactors, and 3) specific management. Identifying the differences in phenotypes of anaphylaxis is crucial for future management guidelines and development of a personalized medicine approach., Objective: This study aimed to evaluate the phenotype and risk factors of VIA., Methods: Using data from the European Anaphylaxis Registry (12,874 cases), we identified 3,612 patients with VIA and analyzed their cases in comparison with sex- and age-matched anaphylaxis cases triggered by other elicitors (non-VIA cases [n = 3,605])., Results: VIA more frequently involved more than 3 organ systems and was associated with cardiovascular symptoms. The absence of skin symptoms during anaphylaxis was correlated with baseline serum tryptase level and was associated with an increased risk of a severe reaction. Intramuscular or intravenous epinephrine was administered significantly less often in VIA, in particular, in patients without a history of anaphylaxis. A baseline serum tryptase level within the upper normal range (8-11.5 ng/mL) was more frequently associated with severe anaphylaxis., Conclusion: Using a large cohort of VIA cases, we have validated that patients with intermediate baseline serum tryptase levels (8-11 ng/mL) and without skin involvement have a higher risk of severe VIA. Patients receiving β-blockers or angiotensin-converting enzyme inhibitors had a higher risk of developing severe cardiovascular symptoms (including cardiac arrest) in VIA and non-VIA cases. Patients experiencing VIA received epinephrine less frequently than did cases with non-VIA., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Current guidelines recommend intramuscular administration of epinephrine as the first-line drug for the emergency treatment of severe allergic reactions (anaphylaxis), but no randomized trial evidence supports this consensus., Objective: We aimed to assess anaphylaxis treatment practices over 10 years, covering several European regions, all allergen sources, and all age groups., Methods: The European Anaphylaxis Register tracks elicitors, symptoms, emergency treatment, diagnostic workups, and long-term counseling for anaphylaxis incidents through web-based data entry from tertiary allergy specialists, covering information from the emergency respondent, patient, tertiary referral, and laboratory/clinical test results., Results: We analyzed 10,184 anaphylaxis incidents. In total, 27.1% of patients treated by a health professional received epinephrine and, in total, 10.5% received a second dose. Successful administration was less frequent in German-speaking countries (minimum 19.6%) than in Greece, France, and Spain (maximum 66.7%). Over the last decade, epinephrine administration from a health professional almost doubled to reach 30.6% in 2015-2017, half of which was applied intramuscularly. A total of 14.7% of lay- or self-treated cases were treated with an autoinjector. Of those without treatment, 22.4% carried a device for administration. No change in successful administration by lay emergency respondents was found over the last 10 years. Of the reaction and patient characteristics analyzed, only clinical severity considerably influenced the likelihood of receiving epinephrine, with 66.9% of successful administrations in near-fatal (grade IV) reactions., Conclusions: Despite clear recommendations, only a small proportion of anaphylaxis incidents are treated with epinephrine. We demonstrated a slight increase in treated patients when handled by professionals, but stagnation in lay- or self-treated anaphylaxis. The reaction circumstances, the respondent's professional background, and patient characteristics did not explain which reactions were treated., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Anaphylaxis in children and adolescents is a potentially life-threatening condition. Its heterogeneous clinical presentation and sudden occurrence in virtually any setting without warning have impeded a comprehensive description., Objective: We sought to characterize severe allergic reactions in terms of elicitors, symptoms, emergency treatment, and long-term management in European children and adolescents., Methods: The European Anaphylaxis Registry recorded details of anaphylaxis after referral for in-depth diagnosis and counseling to 1 of 90 tertiary allergy centers in 10 European countries, aiming to oversample the most severe reactions. Data were retrieved from medical records by using a multilanguage online form., Results: Between July 2007 and March 2015, anaphylaxis was identified in 1970 patients younger than 18 years. Most incidents occurred in private homes (46%) and outdoors (19%). One third of the patients had experienced anaphylaxis previously. Food items were the most frequent trigger (66%), followed by insect venom (19%). Cow's milk and hen's egg were prevalent elicitors in the first 2 years, hazelnut and cashew in preschool-aged children, and peanut at all ages. There was a continuous shift from food- to insect venom- and drug-induced anaphylaxis up to age 10 years, and there were few changes thereafter. Vomiting and cough were prevalent symptoms in the first decade of life, and subjective symptoms (nausea, throat tightness, and dizziness) were prevalent later in life. Thirty percent of cases were lay treated, of which 10% were treated with an epinephrine autoinjector. The fraction of intramuscular epinephrine in professional emergency treatment increased from 12% in 2011 to 25% in 2014. Twenty-six (1.3%) patients were either admitted to the intensive care unit or had grade IV/fatal reactions., Conclusions: The European Anaphylaxis Registry confirmed food as the major elicitor of anaphylaxis in children, specifically hen's egg, cow's milk, and nuts. Reactions to insect venom were seen more in young adulthood. Intensive care unit admissions and grade IV/fatal reactions were rare. The registry will serve as a systematic foundation for a continuous description of this multiform condition., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Anaphylaxis management guidelines recommend the use of intramuscular adrenaline in severe reactions, complemented by antihistamines and corticoids; secondary prevention includes allergen avoidance and provision of self-applicable first aid drugs. Gaps between recommendations and their implementation have been reported, but only in confined settings. Hence, we analysed nation-wide data on the management of anaphylaxis, evaluating the implementation of guidelines., Methods: Within the anaphylaxis registry, allergy referral centres across Germany, Austria and Switzerland provided data on severe anaphylaxis cases. Based on patient records, details on reaction circumstances, diagnostic workup and treatment were collected via online questionnaire. Report of anaphylaxis through emergency physicians allowed for validation of registry data., Results: 2114 severe anaphylaxis patients from 58 centres were included. 8% received adrenaline intravenously, 4% intramuscularly; 50% antihistamines, and 51% corticoids. Validation data indicated moderate underreporting of first aid drugs in the Registry. 20% received specific instructions at the time of the reaction; 81% were provided with prophylactic first aid drugs at any time., Conclusion: There is a distinct discrepancy between current anaphylaxis management guidelines and their implementation. To improve patient care, a revised approach for medical education and training on the management of severe anaphylaxis is warranted.

Objective: To identify the concentration of the fragrance compound hydroxyisohexyl 3-cyclohexene carboxaldehyde (INCI) (HICC) that is sufficiently low not to cause an allergic reaction in patients with proven sensitization., Methods: Repeated open application testing (ROAT) in 64 subjects with 2 preparations (perfume and cream) in different concentration (0.005-2.5%). Confirmatory patch testing with four preparations in two different concentrations (2.5% and 5%)., Results: The concentrations of HICC being tolerated by 90% of those sensitized to HICC are estimated as <88.2 ppm (cream) and <270 ppm (perfume) equivalent to 1.2 microg/cm(2) (perfume) and 4.9 microg/cm(2) (cream). Patch test preparations differed with regard to sensitivity (88.5-98.1%) and specificity (37.5-87.5%) against the ROAT result as external criterion. ROAT concentrations and the reaction strength in patch testing were inversely correlated (Kendall's tau-b: 0.69), both indicating the existence of different degrees of susceptibility., Conclusion: To protect 90% (50%) of people sensitized, the use concentration should be in the range of 0.009-0.027% (0.18-0.34%), depending on the product type. Taking into account these results, excessive concentrations should be avoided, as this would continue to sensitize people. Close monitoring is indispensable to prove the efficacy of any recommendations aiming to prevent induction.