Peanut-induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry.

BACKGROUND: Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. METHODS: Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre. RESULTS: 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004). CONCLUSIONS: The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition.

Risk Factors and Characteristics of Biphasic Anaphylaxis.

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.

Secondary prevention measures in anaphylaxis patients: Data from the anaphylaxis registry.

BACKGROUND: Patients with a history of anaphylaxis are at risk of future anaphylactic reactions. Thus, secondary prevention measures are recommended for these patients to prevent or attenuate the next reaction. METHODS: Data from the Anaphylaxis Registry were analyzed to identify secondary prevention measures offered to patients who experienced anaphylaxis. Our analysis included 7788 cases from 10 European countries and Brazil. RESULTS: The secondary prevention measures offered varied across the elicitors. A remarkable discrepancy was observed between prevention measures offered in specialized allergy centers (84% of patients were prescribed adrenaline autoinjectors following EAACI guidelines) and outside the centers: Here, EAACI guideline adherence was only 37%. In the multivariate analysis, the elicitor of the reaction, age of the patient, mastocytosis as comorbidity, severity of the reaction, and reimbursement/availability of the autoinjector influence physician's decision to prescribe one. CONCLUSIONS: Based on the low implementation of guidelines concerning secondary prevention measures outside of specialized allergy centers, our findings highlight the importance of these specialized centers and the requirement of better education for primary healthcare and emergency physicians.

Epinephrine in Severe Allergic Reactions: The European Anaphylaxis Register.

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.

Triggers and treatment of anaphylaxis: an analysis of 4,000 cases from Germany, Austria and Switzerland.

BACKGROUND: Anaphylaxis is the most severe manifestation of a mast cell-dependent immediate reaction and may be fatal. According to data from the Berlin region, its incidence is 2-3 cases per 100 000 persons per year. METHOD: We evaluated data from the anaphylaxis registry of the German-speaking countries for 2006-2013 and data from the protocols of the ADAC air rescue service for 2010-2011 to study the triggers, clinical manifestations, and treatment of anaphylaxis. RESULTS: The registry contained data on 4141 patients, and the ADAC air rescue protocols concerned 1123 patients. In the registry, the most common triggers for anaphylaxis were insect venom (n = 2074; 50.1%), foods (n = 1039; 25.1%), and drugs (n = 627; 15.1%). Within these groups, the most common triggers were wasp (n = 1460) and bee stings (n = 412), legumes (n = 241), animal proteins (n = 225), and analgesic drugs (n = 277). Food anaphylaxis was most frequently induced by peanuts, cow milk, and hen's egg in children and by wheat and shellfish in adults. An analysis of the medical emergency cases revealed that epinephrine was given for grade 3 or 4 anaphylaxis to 14.5% and 43.9% (respectively) of the patients in the anaphylaxis registry and to 19% and 78% of the patients in the air rescue protocols. CONCLUSION: Wasp and bee venom, legumes, animal proteins, and analgesic drugs were the commonest triggers of anaphylaxis. Their relative frequency was age-dependent. Epinephrine was given too rarely, as it is recommended in the guidelines for all cases of grade 2 and above.

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.

Exhaled nitric oxide decreases after positive food-allergen challenge.

BACKGROUND: Exhaled nitric oxide (FeNO) is a well described marker of airway inflammation in asthma and is also known to increase after chronic exposure to inhaled allergens. It is not known whether monitoring FeNO could be useful during food challenges to detect early or subclinical reactions. METHODS: Forty children aged 3 to 16 years undergoing an allergen-food challenge at two centres were prospectively recruited for this study. FeNO was assessed before and repeatedly after the food-challenge. RESULTS: Data were obtained from a total of 53 challenges (16 positive, 37 negative) and were compared between the two groups. Half of the patients with a positive food challenge exhibited clinical upper respiratory symptoms. The FeNO significantly decreased in 7 of 16 patients with a positive challenge test within 60 to 90 minutes after the first symptoms of an allergic reaction. CONCLUSION: Our results show a significant decrease in FeNO after a positive food challenge suggesting involvement of the lower airways despite absence of clinical and functional changes of lower airways. Prospective blinded studies are needed to confirm these results.