Causes and risk factors for anaphylaxis.

Anaphylaxis is in most cases an IgE-dependent immunologic reaction. Mast cells are activated and release several mediators. Recent data about possible triggers of anaphylaxis indicate a clear age-dependency. The most frequent triggers of anaphylaxis in children are foods; in adults venom and drugs predominate. In 2006 an anaphylaxis registry was established in German-speaking countries. In the registry the triggers, circumstances, and treatment measures are collected from patients with anaphylaxis. However, the registry cannot supply epidemiological data like prevalence or incidence rates since the registration of cases is based on collaboration with allergy centers only. Similarly, other approaches to obtain data on the epidemiology of anaphylaxis are problematic given that allergic reactions of varying severity are covered by a number of codes in the ICD-10. Research in the field of anaphylaxis is focused on the identification of risk factors. Several data indicate the relevance of co-factors and augmentation factors in well-defined patient groups. Among these factors physical activity, infection, alcohol and additives are relevant. In the future a unique coding system with a subtype analysis regarding the triggers and severity should help to provide data on the epidemiology of anaphylaxis. Furthermore the mechanisms of co-factors and identification of biomarkers for risk assessment are important research areas for the future.

Milk ladder as a therapeutic option for cow's milk allergy: Proposal for a step-by-step plan for cow's milk introduction in cow's milk allergy.

In regard to cow's milk allergy, the current option of avoiding can be expanded by (re-)introducing milk using a milk ladder. So-called "food ladders" are internationally well known and utilized for both non-IgE-mediated and IgE-mediated cow's milk allergy. Stepping up the stairs from highly processed baked goods with milk via cooked milk products to pasteurized fresh milk reflects the status of acquired tolerance of each level. The allergenicity of milk depends on processing and amount. By implementing the milk ladder, it can enhance the clinical process of tolerance development, lead to meeting nutrient requirements quickly, and involve parents actively in the therapeutical process. The milk ladder, for the first time being published and adapted for Germany, describes a structured framework that might be adapted individually regarding the time period on a certain level or other variations such as preparation/amount of milk products. From a safety perspective, healthcare professionals should pay great attention to patient selection and education prior to implementing the milk ladder. Detailed advice as well as recipes and a graphical presentation can be found in the supplemental material.

Cow's milk and hen's egg anaphylaxis: A comprehensive data analysis from the European Anaphylaxis Registry.

BACKGROUND: Cow's milk (CM) and hen's egg (HE) are leading triggers of anaphylaxis in early childhood. The aim of this study was to identify clinical phenotypes and therapeutic measures for CM anaphylaxis (CMA) compared to HE anaphylaxis (HEA) in children up to 12 years of age, based on a large pan-European dataset from the European Anaphylaxis Registry. METHODS: Data from 2007 to 2020 on clinical phenotypes and treatment from 10 European countries, as well as Brazil, were analysed. The two-step cluster analysis was used to identify the most frequent phenotypes. For each trigger, three clusters were extracted based on sex, age, and existence of symptoms in four vitally important systems. RESULTS: Altogether 284 children with CMA and 200 children with HEA were identified. They were characterised as male (69% vs. 64%), infants (65% vs. 61%), with a most frequent grade III of Ring&Messmer classification (62% vs. 64%), in CMA versus HEA, respectively. Respiratory symptoms occurred more often in CMA (91% vs. 83%, p = 0.010), especially in infants (89% vs. 79%, p = 0.008). Cardiovascular symptoms were less frequent in CMA (30% vs. 44%, p = 0.002), in both infants (33% vs. 46%, p = 0.027), and older children (25% vs. 42%, p = 0.021). The clusters extracted in the CMA group were characterised as: (1) mild dermal infants with severe GI (40%), 2. severe dermal (35%), 3. respiratory (25%). While in HEA group: 1. infants with severe GI and/or reduction of alertness (40%), (2) conjunctival (16%), (3) mild GI without conjunctivitis (44%). The severity of the reaction was independent from the amount of ingested allergen protein, regardless of trigger. The first-line adrenaline application differed between the countries (0%-92%, as well as the reasons for not administering adrenaline, p < 0.001). CONCLUSIONS: Despite the similarity of their age, sex, and severity grade, the clinical profiles differed between the CMA and HEA children. Adrenaline was underused, and its administration was country dependent. Further studies are needed to assess to what extent the differences in the clinical profiles are related to matrix and/or absorption effects, and/or the allergen itself.

Provoking allergens and treatment of anaphylaxis in children and adolescents--data from the anaphylaxis registry of German-speaking countries.

Anaphylaxis is the most severe reaction of an IgE-mediated hypersensitivity. Data about affected patients may help to improve our knowledge of anaphylaxis and its medical care. We analysed data from the anaphylaxis registry of German speaking countries with regard to the provoking allergens and treatment modalities of anaphylaxis in children and adolescents. Inclusion criteria were severe systemic allergic reactions with concomitant pulmonary and/or cardiovascular symptoms. The data are collected by a password-controlled online-questionnaire. For this analysis, data of 197 reported anaphylactic reactions from children and adolescents registered between 2006 and 2009 were included. The data show that within the registered cases the most frequently affected organ systems for children and adolescents were the skin (89%) and the respiratory tract (87%) followed by symptoms of the cardiovascular system (47%) and the gastrointestinal tract (43%). The most frequent elicitors were food allergens accounting for 58% of cases, followed by insect venom (24%) and drugs (8%). The most frequent food allergens were peanuts followed by tree nuts and animal related food products. In 18% aggravating factors such as physical exercise were noted by the clinicians. 26% of the analysed patients had experienced more than one reaction. The data regarding the emergency treatment show that antihistamines (87%) and corticosteroids (85%) were often used but that adrenaline was rarely used (22% of the registered cases). Taken together these data show that the analysis of anaphylaxis by registration of affected individuals can provide data about provoking allergens and treatment measures but also suggest the impact of aggravating factors on anaphylactic reactions. The under-represented usage of adrenaline indicates the need of educational measures for patients and their physicians.

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.

Elicitors and co-factors in food-induced anaphylaxis in adults.

Food-induced anaphylaxis (FIA) in adults is often insufficiently diagnosed. One reason is related to the presence of co-factors like exercise, alcohol, additives and non-steroidal anti-inflammatory drugs. The objective of this analysis was to retrospectively investigate the role of co-factors in patients with FIA. 93 adult patients with suspected FIA underwent double-blind, placebo-controlled food challenges with suspected allergens and co-factors.The elicitors of anaphylaxis were identified in 44/93 patients. 27 patients reacted to food allergens upon challenge, 15 patients reacted only when a co-factor was co-exposed with the allergen. The most common identified allergens were celery (n = 7), soy, wheat (n = 4 each) and lupine (n = 3). Among the co-factors food additives (n = 8) and physical exercise (n = 6) were most frequent. In 10 patients more than one co-factor and/or more than one food allergen was necessary to elicit a positive reaction.The implementation of co-factors into the challenge protocol increases the identification rate of elicitors in adult food anaphylactic patients.

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.