EAACI guidelines: Anaphylaxis (2021 update).

Anaphylaxis is a clinical emergency which all healthcare professionals need to be able to recognize and manage. The European Academy of Allergy and Clinical Immunology Anaphylaxis multidisciplinary Task Force has updated the 2014 guideline. The guideline was developed using the AGREE II framework and the GRADE approach. The evidence was systematically reviewed and recommendations were created by weighing up benefits and harms. The guideline was peer-reviewed by external experts and reviewed in a public consultation. The use of clinical criteria to identify anaphylaxis is suggested with blood sampling for the later measurement of tryptase. The prompt use of intramuscular adrenaline as first-line management is recommended with the availability of adrenaline autoinjectors to patients in the community. Pharmacokinetic data should be provided for adrenaline autoinjector devices. Structured, comprehensive training for people at risk of anaphylaxis is recommended. Simulation training and visual prompts for healthcare professionals are suggested to improve the management of anaphylaxis. It is suggested that school policies reflect anaphylaxis guidelines. The evidence for the management of anaphylaxis remains mostly at a very low level. There is an urgent need to prioritize clinical trials with the potential to improve the management of patients at risk of anaphylaxis.

Esophageal and Small Intestinal Mucosal Integrity in Eosinophilic Esophagitis and Response to an Elemental Diet.

OBJECTIVES: The esophageal mucosal integrity is impaired in eosinophilic esophagitis (EoE) and it has been suggested that the duodenal permeability is increased. The absence of food allergens may restore the integrity. The aims of this study were to assess duodenal permeability in EoE and to evaluate the effect of an elemental diet on the esophageal and duodenal integrity. METHODS: In this prospective study 17 adult EoE patients and 8 healthy controls (HC) were included. Esophageal biopsy specimens were sampled before and after 4 weeks of elemental diet to measure eosinophil counts and gene expression of tight junction and barrier integrity proteins. Esophageal and duodenal impedance were measured by electrical tissue impedance spectroscopy and Ussing chambers were used to measure transepithelial resistance (TER) and transepithelial molecule flux. Small intestinal permeability was measured using a test, measuring lactulose/mannitol (L/M) ratios. RESULTS: In EoE patients, the esophageal but not the duodenal integrity was impaired, compared with HC. We observed no significant difference between L/M ratios of HC and EoE patients. After diet, eosinophil counts decreased significantly, which was paralleled by normalization of esophageal impedance and transepithelial molecule flux. The esophageal TER improved significantly, but did not reach values seen in HC. Esophageal expression of genes encoding for barrier integrity proteins filaggrin and desmoglein-1 was impaired at baseline and restored after diet. CONCLUSIONS: An elemental diet restores esophageal integrity, suggesting that it is at least partly secondary to allergen exposure. Duodenal integrity seems not to be affected in EoE, and possibly plays a minor role in its pathophysiology.

Threshold dose distributions for 5 major allergenic foods in children.

BACKGROUND: For most allergenic foods, insufficient threshold dose information within the population restricts the advice on levels of unintended allergenic foods which should trigger precautionary labeling on prepackaged foods. OBJECTIVE: We wanted to derive threshold dose distributions for major allergenic foods and to elaborate the protein doses at which a proportion of the allergic population is likely to respond. METHODS: For 7 allergenic foods double-blind, placebo-controlled food challenges (DBPCFCs) with a positive outcome for allergic reactions were selected from the clinical database of children routinely tested to diagnose food allergy at the University Medical Center Groningen. For each allergen 2 population threshold distributions were determined with the individual minimal eliciting dose and the preceding dose of each DBPCFC for objective symptoms and any symptom (either subjective or objective). RESULTS: Individual positive DBPCFCs were available for peanut (n = 135), cow's milk (n = 93), hen's egg (n = 53), hazelnut (n = 28), and cashew nut (n = 31). Fewer children were challenged with soy (n = 10) or walnut (n = 13). Threshold dose distributions showed a good statistical and visual fit. The protein dose at which 5% of the allergic population is likely to respond with objective reactions was 1.6 mg for peanut, 1.1 mg for cow's milk, 1.5 mg for hen's egg, 7.4 mg for cashew nut, and 0.29 mg for hazelnut. Thresholds for any symptom were on average 2 to 6 times lower than for objective symptoms. The 95% upper and lower confidence intervals of the threshold distributions were overlapping. The peanut threshold distribution on objective symptoms was similar to the distribution of another European center. CONCLUSIONS: Threshold distribution curves and eliciting doses are a powerful tool to compare different allergenic foods and for informing policy on precautionary labeling.

[Prevention of food allergy: Shift from elimination to exposure of highly allergenic food]. / Preventie van voedselallergie.

Since 2015 the new insight has emerged that avoidance of food allergens increases the risk of food allergy, specifically in infants with atopic dermatitis through cutaneous sensitisation. The primary treatment of atopic dermatitis consists of treatment with topical steroids and emollients and not by dietary intervention. Today all children are advised to introduce peanut and egg before 8 months of age. Children with atopic dermatitis are advised to so between 4 and 6 months of age following weaning foods such as fruits and vegetables. Guidelines for early introduction of peanut and egg, including home introduction schedules are available use in primary and secondary care. Timely introduction of diverse and healthy complementary foods also seems to be preventive for the development of food allergy. Breastfeeding yields contradictory results on the prevention of allergic disease, but remains the preferred choice because of many other health benefits.

Parental eczema increases the risk of double-blind, placebo-controlled reactions to milk but not to egg, peanut or hazelnut.

BACKGROUND: While genetic factors are known to be important in the development of sensitization to foods, it is not known whether they also play a role in clinical allergic reactivity to foods. OBJECTIVE: We aimed to determine whether parental atopic diseases are associated with a higher risk of a reaction to common allergenic foods when tested in a double-blind, placebo-controlled food challenge (DBPCFC). METHODS: Parents of children suspected of being food allergic were interviewed about their own and their child's atopic history. Specific IgE and skin prick tests to food allergens and the outcome of food challenges in the child were recorded. RESULTS: Data from 553 double-blind food challenges performed in 396 children were analyzed. The foods tested were milk (n = 185), egg (n = 110), peanut (n = 198) and hazelnut (n = 60). Only parental eczema was significantly associated with positive outcomes for food challenges with milk after correction for age, sex, atopic comorbidity in the child and milk-specific IgE test results (odds ratio 3.1, 95% confidence interval 1.5-6.3). CONCLUSIONS: Children with a positive DBPCFC to milk more frequently have parents with eczema than children with a negative test. This effect of parental eczema was not seen in children challenged with egg, peanut or hazelnut. Clinical reactivity to milk may be caused by genetic factors which are shared with parental eczema to a greater extent than clinical reactivity to other foods.

The Habitual Diet of Dutch Adult Patients with Eosinophilic Esophagitis Has Pro-Inflammatory Properties and Low Diet Quality Scores.

We determined the nutritional adequacy and overall quality of the diets of adult patients with eosinophilic esophagitis (EoE). Dietary intakes stratified by sex and age were compared to Dietary Reference Values (DRV). Overall diet quality was assessed by two independent Diet-Quality-Indices scores, the PANDiet and DHD-index, and compared to age- and gender-matched subjects from the general population. Lastly, food and nutrient intakes of EoE patients were compared to intakes of the general population. Saturated fat intake was significantly higher and dietary fiber intake significantly lower than the DRV in both males and females. In males, the DRV were not reached for potassium, magnesium, selenium, and vitamins A and D. In females, the DRV were not reached for iron, sodium, potassium, selenium, and vitamins A, B2, C and D. EoE patients had a significantly lower PANDiet and DHD-index compared to the general population, although the relative intake (per 1000 kcal) of vegetables/fruits/olives was significantly higher (yet still up to 65% below the recommended daily amounts) and alcohol intake was significantly lower compared to the general Dutch population. In conclusion, the composition of the habitual diet of adult EoE patients has several pro-inflammatory and thus unfavorable immunomodulatory properties, just as the general Dutch population, and EoE patients had lower overall diet quality scores than the general population. Due to the observational character of this study, further research is needed to explore whether this contributes to the development and progression of EoE.

Food allergy: stakeholder perspectives on acceptable risk.

We have reached a point where it is difficult to improve food allergy risk management without an agreement on levels of acceptable risk. This paper presents and discusses the perspectives of the different stakeholders (allergic consumers, health professionals, public authorities and the food industry) on acceptable risk in food allergy. Understanding where these perspectives diverge and even conflict may help develop an approach to define what is acceptable. Uncertainty about food allergy, its consequences and how to manage them is the common denominator of the stakeholders' views. In patients, uncertainty is caused by the unpredictability of reactions and the concern about whether avoidance strategies will be effective enough. Variability of symptoms and the lack of markers do not allow stratification of patients according to their reactivity, and force health professionals to give the same advice to all patients despite the fact that the risk to each is not identical. Regulators and the food industry struggle with the fact that the lack of management thresholds forces them to make case-by-case decisions in an area of uncertainty with penalties for under- or over-prediction. As zero risk is not a realistic possibility, consensus on acceptable risk will be needed.

Development and validation of the self-administered Food Allergy Quality of Life Questionnaire for adolescents.

BACKGROUND: Food allergy can affect health-related quality of life (HRQL). Currently, no validated, self-administered, disease-specific HRQL questionnaire for adolescents with food allergy exists. OBJECTIVE: We sought to develop and validate the Food Allergy Quality of Life Questionnaire-Teenager Form (FAQLQ-TF) in the Dutch language. METHODS: Ten adolescents (13-17 years) with food allergy were interviewed and generated 166 HRQL items. The most important items were identified by 51 adolescents with food allergy by using the clinical impact method, resulting in the FAQLQ-TF containing 28 items (score range: 1 "no impairment" to 7 "maximal impairment"). The FAQLQ-TF, the Food Allergy Independent Measure, and a generic HRQL questionnaire (CHQ-CF87) were sent to 98 adolescents with food allergy for cross-sectional validation of the FAQLQ-TF. RESULTS: Construct validity was assessed based on the correlation between the FAQLQ-TF and the Food Allergy Independent Measure (rho = 0.57, P < .001). The FAQLQ-TF had excellent internal consistency (Cronbach alpha = .92) and discriminated between adolescents who differed in number of food allergies (1 vs >2 food allergies: total FAQLQ-TF score, 4.3 vs 3.5; P = 0.037) but did not discriminate between those who did or did not have reported anaphylaxis. The FAQLQ-TF correlated weakly with 6 of the 11 CHQ-CF87 scales, demonstrating convergent/discriminant validity. CONCLUSION: The FAQLQ-TF is the first self-administered, disease-specific HRQL questionnaire for adolescents with food allergy. It has good construct validity and excellent internal consistency and discriminates between adolescents who differ in the number of food allergies. The FAQLQ-TF is short and easy to use and might therefore be a useful tool in clinical research.

IgE-mediated food allergy diagnosis: Current status and new perspectives.

In June 2005, the work of the EU Integrated Project EuroPrevall was started. EuroPrevall is the largest research project on food allergy ever performed in Europe. Major aims of the project are to generate for the first time reliable data on the prevalence of food allergies across Europe and on the natural course of food allergy development in infants. Improvement of in vitro diagnosis of food allergies is another important aim of the project. The present review summarizes current knowledge about the clinical presentation of food allergy and critically reviews available diagnostic tools at the beginning of the project period. A major problem in diagnosis is a relatively poor 'clinical specificity', i. e. both positive skin tests and in vitro tests for specific IgE are frequent in sensitized subjects without food allergy symptoms. So far, no in vitro test reliably predicts clinical food allergy. EuroPrevall aims at improving the predictive value of such tests by proceeding from diagnosis based on allergen extracts to purified allergen molecules, taking into account the affinity of the IgE-allergen interaction, and evaluating the potential of biological in vitro tests such as histamine release tests or basophil activation tests including assays performed with permanently growing cell lines.

The development of a standardised diet history tool to support the diagnosis of food allergy.

The disparity between reported and diagnosed food allergy makes robust diagnosis imperative. The allergy-focussed history is an important starting point, but published literature on its efficacy is sparse. Using a structured approach to connect symptoms, suspected foods and dietary intake, a multi-disciplinary task force of the European Academy of Allergy and Clinical Immunology developed paediatric and adult diet history tools. Both tools are divided into stages using traffic light labelling (red, amber and green). The red stage requires the practitioner to gather relevant information on symptoms, atopic history, food triggers, foods eaten and nutritional issues. The amber stage facilitates interpretation of the responses to the red-stage questions, thus enabling the practitioner to prepare to move forward. The final green stage provides a summary template and test algorithm to support continuation down the diagnostic pathway. These tools will provide a standardised, practical approach to support food allergy diagnosis, ensuring that all relevant information is captured and interpreted in a robust manner. Future work is required to validate their use in diverse age groups, disease entities and in different countries, in order to account for differences in health care systems, food availability and dietary norms.

[One guideline for diagnosing cow milk allergy; for primary, secondary and tertiary care in the Netherlands]. / 1 richtlijn voor diagnostiek van koemelkallergie; voor de eerste, tweede en derde lijn in Nederland.

The aims of the new Dutch guideline 'Diagnosing Cow Milk Allergy in Children in the Netherlands' are to provide an evidence-based instrument for the reliable and safe diagnosis of cow milk allergy and to improve the collaboration between health care professionals at well-baby clinics, general practices and hospitals. The double-blind, placebo-controlled cow-milk provocation test is the only test available for establishing an allergy to cows' milk. The double-blind provocation test in children at a low risk of severe reactions may be performed at the better-equipped well-baby clinics and at all general practices, thereby shifting care from secondary to primary care. The use of extensively hydrolysed formulas based on whey protein as well as on casein can be advised for a cow-milk-free diet. The general practitioner and well-baby physician should collaborate in designating responsibilities during the diagnostic phase of cow milk allergy in primary care.

Test-retest reliability of the Food Allergy Quality of Life Questionnaires (FAQLQ) for children, adolescents and adults.

OBJECTIVE: The self-administered Food Allergy Quality of Life Questionnaire-Child Form (FAQLQ-CF), -Teenager Form (FAQLQ-TF) and -Adult Form (FAQLQ-AF) were recently developed within EuroPrevall, a multi-centred study of food allergy in Europe. The primary aim of this study was to evaluate the test-retest reliability of the FAQLQ-CF, -TF and -AF. METHODS: One hundred and one Dutch patients (31 children, 34 adolescents and 36 adults) completed the FAQLQ twice with a 10-14 day interval. The intraclass correlation coefficient (ICC), Lin's concordance correlation coefficient (CCC) and Bland-Altman plots were used to assess test-retest reliability. RESULTS: Test-retest reliability was excellent with ICCs and CCCs above 0.907, 0.975 and 0.951 for the FAQLQ-CF, -TF and -AF, respectively. Bland-Altman plots showed that the mean differences of the test and re-test were all close to zero for the FAQLQs. CONCLUSIONS: The FAQLQs are reliable over a short time interval. The FAQLQs are not only excellent tools for group comparison studies, but also for monitoring individual patients.

Assessment of the reduced allergenic properties of the Santana apple.

BACKGROUND: Approximately 2% of the Northern and Central European population is allergic to apples. Because of symptoms of oral allergy syndrome, many individuals avoid eating fresh apples. A strategy to allow apple allergic individuals to eat apples is the development of hypoallergenic apple varieties. OBJECTIVE: To investigate the allergenicity of a putatively hypoallergenic apple cultivar, the Santana apple, on apple allergic individuals using a method of challenge in which loss of allergenicity is minimized. METHODS: The study population consisted of 15 apple allergic individuals, who underwent an open oral challenge with 3 different apple cultivars: Santana, Golden Delicious, and Topaz. Food challenges were performed between February 1 and May 31, 2005, during the birch tree pollen season. Sensory perception during challenges was minimized by use of a blindfold and nose clip and randomization of challenge order. Subjective symptoms were scored by a visual analog scale. RESULTS: After challenge with the Santana apple, 8 of 15 study participants (53%) developed no symptoms, which was a significantly greater proportion than after challenge with the Topaz apple (1 participant) and Golden Delicious apple (1 participant) (P = .002). The visual analog scale scores for the Santana apple (dose 1) were significantly lower than that for the Golden Delicious and Topaz apples. A total of 73% of the participants stated they would eat Santana apples in the future. CONCLUSION: The Santana apple caused significantly fewer allergic symptoms in apple allergic individuals than the Golden Delicious and Topaz apples. The Santana apple may be a good choice for most apple allergic individuals who want to eat apples.

Dietary prevention of allergic disease in children: are current recommendations really based on good evidence?

We provide a critical appraisal of the literature on the effects of dietary prevention of atopic disease in children. In our view, currently available studies suffer from lack of blinding which is a major problem if the primary end point is subjective (such as the diagnosis of eczema). In addition, long-term follow-up suggests that atopic symptoms are delayed rather than truly prevented, and that only the mildest cases are prevented (or delayed). Although it has been reported that cow's milk allergy is truly prevented by dietary interventions in early life, this has never been demonstrated by double-blind placebo-controlled food challenges. No studies to date have shown effects of hypoallergenic formulae on objective markers of atopic sensitization, such as specific IgE levels. Finally, there is no universally accepted pathophysiological mechanism which could explain the usefulness of hypoallergenic formulae in allergy prevention. In conclusion, we feel that the currently available evidence on the allergy preventive effects of hypoallergenic formulae is insufficient to justify blanket advice being given to 'high risk' families. Such advice gives parents the hope that they can actually prevent allergy in their children which may not be justified. A cautious approach in advising interventions with hypoallergenic formulae to prevent allergy in high-risk infants is warranted.

Development and validation of challenge materials for double-blind, placebo-controlled food challenges in children.

BACKGROUND: The use of double-blind, placebo-controlled food challenges (DBPCFCs) is considered the gold standard for the diagnosis of food allergy. Despite this, materials and methods used in DBPCFCs have not been standardized. OBJECTIVE: The purpose of this study was to develop and validate recipes for use in DBPCFCs in children by using allergenic foods, preferably in their usual edible form. METHODS: Recipes containing milk, soy, cooked egg, raw whole egg, peanut, hazelnut, and wheat were developed. For each food, placebo and active test food recipes were developed that met the requirements of acceptable taste, allowance of a challenge dose high enough to elicit reactions in an acceptable volume, optimal matrix ingredients, and good matching of sensory properties of placebo and active test food recipes. Validation was conducted on the basis of sensory tests for difference by using the triangle test and the paired comparison test. Recipes were first tested by volunteers from the hospital staff and subsequently by a professional panel of food tasters in a food laboratory designed for sensory testing. Recipes were considered to be validated if no statistically significant differences were found. RESULTS: Twenty-seven recipes were developed and found to be valid by the volunteer panel. Of these 27 recipes, 17 could be validated by the professional panel. CONCLUSION: Sensory testing with appropriate statistical analysis allows for objective validation of challenge materials. We recommend the use of professional tasters in the setting of a food laboratory for best results.