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Background: Hymenoptera venom is one of the most frequent causes of anaphylaxis. Studies from adults indicate the clinical profiles and risk factors of Hymenoptera venom-induced anaphylaxis (VIA). Much less is known about pediatric VIA., Objective: To understand elicitor- and age-related factors determining pediatric VIA by analyzing data from the anaphylaxis registry., Methods: We selected pediatric VIA, pediatric food-induced anaphylaxis (FIA), and adult VIA cohorts from the anaphylaxis registry and performed a comparative data analysis regarding elicitors, symptoms, and management., Results: We identified 725 pediatric patients with VIA, 3,149 with pediatric FIA, and 5,534 with adult VIA. In pediatric VIA, boys were more frequently affected, atopy was not increased, and the onset of the reaction after exposure was fast (≤30 min; 91%) compared with pediatric FIA. Symptoms in pediatric VIA were age dependent, and although respiratory symptoms occurred most frequently besides skin symptoms in both pediatric patients with VIA and FIA, cardiovascular symptoms were more frequently reported in pediatric patients with VIA than pediatric patients with FIA. The analysis of pediatric versus adult VIA revealed clear differences in the frequency of involved organ systems (skin: 93% vs 78%; respiratory: 77% vs 64%; and cardiovascular: 61% vs 85%). For both pediatric and adult VIA, the rates of adrenaline application by a professional were low (29% vs 31%) but hospitalization rates were higher in children than in adults (61% vs 42%). Venom immunotherapy was frequently initiated regardless of age (78% each)., Conclusions: Pediatric VIA is more frequent in boys, symptoms are age dependent, and hospitalization is often required. Adrenaline should be applied according to current guidelines. Venom immunotherapy is an important treatment option in pediatric VIA and should be considered in severely affected children., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Food is one of the most common elicitors of anaphylaxis, with an increasing incidence over recent years., Objectives: To characterize elicitor-specific phenotypes and identify factors enhancing the risk or severity of food-induced anaphylaxis (FIA)., Methods: We analyzed data from the European Anaphylaxis Registry applying an age- and sex-matched analysis of associations (Cramer's V) for single food triggers and calculated odds ratios (ORs) for severe FIA., Results: We identified 3,427 cases of confirmed FIA showing an age-dependent elicitor ranking (for children: peanut, cow's milk, cashew, and hen's egg; and for adults: wheat flour, shellfish, hazelnut, and soy). The age- and sex-matched analysis revealed defined symptom patterns for wheat and cashew. Wheat-induced anaphylaxis was more frequently associated with cardiovascular symptoms (75.7%; Cramer's V = 0.28) and cashew-induced anaphylaxis with gastrointestinal symptoms (73.9%; Cramer's V = 0.20). Furthermore, concomitant atopic dermatitis was slightly associated with anaphylaxis to hen's egg (Cramer's V = 0.19) and exercise was strongly associated with anaphylaxis to wheat (Cramer's V = 0.56). Additional factors influencing the severity were alcohol intake in wheat anaphylaxis (OR = 3.23; CI, 1.31-8.83) and exercise in peanut anaphylaxis (OR = 1.78; CI, 1.09-2.95)., Conclusions: Our data show that FIA is age-dependent. In adults, the range of elicitors inducing FIA is broader. For some elicitors, the severity of FIA seems to be related to the elicitor. These data require confirmation in future studies considering a clear differentiation between augmentation and risk factors in FIA., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Co-occurring atopic conditions are common in children with peanut allergy. As such, it is important to examine the safety and efficacy of epicutaneous immunotherapy with Viaskin Peanut 250 μg patch (VP250) in peanut-allergic children with these conditions., Objective: We sought to compare efficacy and safety of VP250 versus placebo in peanut-allergic children with/without ongoing atopic conditions at baseline, including asthma, atopic dermatitis/eczema, or concomitant food allergy., Methods: A subgroup analysis of peanut-allergic children aged 4 to 11 years enrolled in PEPITES (12 months) and REALISE (6 months) randomized, placebo-controlled, phase 3 trials was conducted. The efficacy outcome measure was the difference in prespecified responder rate between placebo and VP250 groups at month 12 based on eliciting dose of peanut protein using double-blind, placebo-controlled food challenge in PEPITES. Safety profiles were evaluated by baseline concomitant disease subgroup in all randomized subjects who received 1 or more dose of the study drug in PEPITES and REALISE pooled data., Results: Responder rates were significantly ( P  < .05, all comparisons) greater with VP250 compared with placebo treatment regardless of whether subjects had other atopic conditions. Safety and tolerability profiles were generally similar across subgroups, with no new safety concerns detected. A trend for both higher responder rates and rates of local reactions was observed in subjects with baseline atopic dermatitis versus those without. In subjects with concomitant food allergy at baseline, higher rates of treatment-emergent adverse events, but not study discontinuations or overall rates of anaphylaxis, were observed., Conclusions: The results support the safety and efficacy of VP250 for treating peanut-allergic children with or without concomitant atopic conditions., (© 2022 The Authors.)

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergy mainly affecting infants and young children. Allergic FPIES reactions differ from IgE-mediated food allergies, for example, regarding elicitors and clinical course., Objective: The aim of our study was to describe causative agents and development of tolerance in German children with FPIES., Methods: We conducted a retrospective survey on children with FPIES from 14 centers in Germany assessing a 6-year period., Results: We analyzed 142 patients with 190 FPIES reactions, 130 of which met acute FPIES criteria and 60 were defined as chronic FPIES. The most frequent eliciting food for acute FPIES was cow's milk, followed by fish, vegetables (eg, potato, pumpkin), meats (eg, beef), and grains. A total of 119 children reacted to 1 food only, 16 children to 2 or 3 foods, and 7 children to ≥4 foods. In chronic FPIES, all but 4 exclusively breastfed infants reacted to cow's milk feeding. IgE sensitization to the triggering food was found in 21 of 152 (14%) cases. Two children developed additional IgE-mediated symptoms upon a food challenge. Time to proof of tolerance was shortest in cow's milk-induced FPIES, and it was shorter in chronic than in acute FPIES., Conclusion: In our national survey, we identified triggers for acute FPIES that partially differ from those reported internationally. Mainly foods introduced early in infant nutrition triggered acute reactions. Time to proven tolerance was shown to be contingent on FPIES symptomatology and on the triggering food. These data should be considered regarding nutritional advice for infants with FPIES., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Anaphylaxis is an immediate hypersensitivity reaction. However, a biphasic course with the second onset of symptoms can occur hours after the initial phase. Little is known about the causes of biphasic anaphylaxis making the identification of patients at risk difficult., Objective: To identify factors predisposing for biphasic anaphylaxis for the better understanding of these reactions., Methods: Data from the Anaphylaxis Registry (from 11 countries) including 8736 patients with monophasic and 435 biphasic anaphylaxis were analyzed., Results: The rate of biphasic reactions in this large cohort was 4.7%. The identified risk factors were reaction severity (grade III/IV vs grade II: odds ratio [OR] = 1.34; 95% confidence interval [CI]: 1.1-1.62); multiorgan involvement; skin, gastrointestinal, severe respiratory, and cardiac symptoms; anaphylaxis caused by peanut/tree nut (OR = 1.78; 95% CI: 1.38-2.23) or an unknown elicitor (OR = 1.96; 95% CI: 1.41-2.72); exercise as a cofactor (OR = 1.44; 95% CI: 1.17-1.78); chronic urticaria as a comorbidity (OR = 2.12; 95% CI: 1.19-3.78); a prolonged interval between the contact with the elicitor and start of primary symptoms (OR for >30 vs <30 min: 1.38; 95% CI: 1.08-1.76); and antihistamine treatment (OR = 1.52; 95% CI: 1.14-2.02)., Conclusion: A biphasic course of anaphylaxis occurs more frequently in severely affected patients with multiorgan involvement. However, we identified multiple additional predictors, suggesting that the pathogenesis of biphasic reactions is more complex than being a rebound of a severe primary reaction., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Walnut is an important elicitor of food allergy in children and adults with a high rate of severe reactions. Multicenter studies using a common clinical protocol and a comprehensive allergen are lacking., Objective: To investigate potential correlations between molecular sensitization patterns and clinical characteristics of walnut-allergic patients., Methods: A total of 91 walnut-allergic subjects and 24 tolerant controls from Switzerland, Germany, and Spain were included. Walnut allergy was established by food challenge in all but anaphylactic subjects. Specific IgE (sIgE) to walnut extract, rJug r 1 (2S albumin), rJug r 3 (nonspecific lipid transfer protein 1), nJug r 4 (11S globulin), rJug r 5 (PR-10 protein), 2 vicilin fractions, profiling, and cross-reactive carbohydrate determinant was determined by ImmunoCAP. A threshold of 0.10 kU A /L was used for positivity., Results: Sensitivity of sIgE to walnut extract was 87% and increased to 96% for the sum of all walnut components. sIgE to walnut extract and all walnut components, except rJug r 5, was significantly higher in patients younger than 14 years at inclusion. Stratification by age at onset of walnut allergy led to similar results. All patients younger than 14 years had severe reactions, whereas 38% of patients 14 years or older were mild reactors. Severe reactors (n = 70) had higher sIgE levels than did mild reactors (n = 21) to walnut extract (P < .0001), rJug r 1 (P < .0001), nJug r 4 (P = .0003), and both vicilin fractions (P < .0001), but not to Jug r 3 and Jug r 5., Conclusions: Sensitization to walnut storage proteins is acquired in childhood and correlates with severe reactions. sIgE levels to storage proteins Jug r 1 and Jug r 4 and vicilin fractions, but not to nonspecific lipid transfer protein and PR-10 proteins, correlate with systemic reactions to walnut., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. 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.)