Linus Grabenhenrich

Anaphylaxis in children and adolescents: The European Anaphylaxis Registry.

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%). Cows milk and hens 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 hens egg, cows 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.

Incidence and natural history of challenge-proven cow's milk allergy in European children – EuroPrevall birth cohort

Cows milk allergy (CMA) is one of the most commonly reported childhood food problems. Community‐based incidence and prevalence estimates vary widely, due to possible misinterpretations of presumed reactions to milk and differences in study design, particularly diagnostic criteria.

First European data from the network of severe allergic reactions (NORA)

Occurrence, elicitors and treatment of severe allergic reactions are recognized and reported differently between countries. We aimed to collect standardized data throughout Europe on anaphylaxis referred for diagnosis and counselling.

Predictive values of component-specific IgE for the outcome of peanut and hazelnut food challenges in children.

Oral challenges are the gold standard in food allergy diagnostic, but time‐consuming. Aim of the study was to investigate the role of peanut‐ and hazelnut‐component‐specific IgE in the diagnostics of peanut and hazelnut allergy and to identify cutoff levels to make some challenges superfluous.

The EuroPrevall birth cohort study on food allergy: baseline characteristics of 12,000 newborns and their families from nine European countries

To cite this article: McBride D, Keil T, Grabenhenrich L, Dubakiene R, Drasutiene G, Fiocchi A, Dahdah L, Sprikkelman AB, Schoemaker AA, Roberts G, Grimshaw K, Kowalski ML, Stanczyk‐Przyluska A, Sigurdardottir S, Clausen M, Papadopoulos NG, Mitsias D, Rosenfeld L, Reche M, Pascual C, Reich A, Hourihane J, Wahn U, Mills ENC, Mackie A, Beyer K. The EuroPrevall birth cohort study on food allergy: baseline characteristics of 12,000 newborns and their families from nine European countries. Pediatric Allergy Immunology 2012: 23: 230–239.

Anaphylaxis in an emergency setting – elicitors, therapy and incidence of severe allergic reactions

Anaphylaxis is a severe potentially life‐threatening hypersensitivity reaction with an estimated lifetime prevalence of 0.5–2.0%. The prevalence and incidence of anaphylactic reactions in Germany are unknown. We therefore assessed anaphylactic patients seen by emergency physicians in the Berlin area covering 4 million people.

Outcome of oral food challenges in children in relation to symptom-eliciting allergen dose and allergen-specific IgE

Oral food challenge (FC) protocols are discussed with reference to starting doses, dose increments, safety, and predictability of results. The aim of this study was to evaluate the relation of eliciting allergen doses, specific IgE levels and predictive factors to the outcome of FCs in children.

Early-life determinants of asthma from birth to age 20 years: A German birth cohort study

BACKGROUND The lack of longitudinal data analyses from birth to adulthood is hampering long-term asthma prevention strategies. OBJECTIVE We aimed to determine early-life predictors of asthma incidence up to age 20 years in a birth cohort study by applying time-to-event analysis. METHODS In 1990, the Multicenter Allergy Study included 1314 newborns in 5 German cities. Children were evaluated from birth to age 20 years at 19 time points. Using a Cox regression model, we examined the associations between 36 early-life factors and onset of asthma based on a doctors diagnosis or asthma medication (primary outcome), typical asthma symptoms, or allergic asthma (including positive IgE measurements). RESULTS Response at 20 years was 71.6%. Two hundred eighteen subjects met the primary outcome criteria within 16,257 person years observed. Asthma incidence was lower in participants who were vaccinated (measles, mumps, and rubella vaccine/tick-borne encephalitis vaccine/BCG vaccine: adjusted hazard ratio [HR], 0.66 [95% CI, 0.47-0.93]). Up to age 20 years, asthma incidence was higher in subjects who had parents with allergic rhinitis (adjusted HR, 2.24 [95% CI, 1.67-3.02]), started day care early or late (before 18 months: adjusted HR, 1.79 [95% CI, 1.03-3.10]; after 3 years: adjusted HR, 1.64 [95% CI, 0.96-2.79]), had mothers who smoked during pregnancy (adjusted HR, 1.79 [95% CI, 1.20-2.67]), had poor parents (adjusted HR, 1.55 [95% CI, 1.09-2.22]), and had parents with asthma (adjusted HR, 1.65 [95% CI, 1.17-2.31]). Not associated with asthma were aspects of diet and breast-feeding, pet ownership, presence of older siblings, and passive smoking. CONCLUSION Parental asthma and nasal allergy increase asthma incidence in offspring up to adulthood. Avoiding tobacco smoke exposure during pregnancy, receiving vaccinations in early childhood, and starting day care between 1.5 and 3 years of age might prevent or delay the development of asthma.

Implementation of Anaphylaxis Management Guidelines: A Register-Based Study

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.

Allergic multimorbidity of asthma, rhinitis and eczema over 20 years in the German birth cohort MAS.

The occurrence of allergic multimorbidity (coexistence of asthma, allergic rhinitis and eczema) has not been evaluated longitudinally from early childhood up to adulthood in a population‐based study sample. We aimed to determine the prevalence of allergic multimorbidity up to age 20 stratified by parental allergies and sex/gender using extensive prospective follow‐up data from two decades of a birth cohort study.