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Abstract: The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data‐driven method that is informed by clinical and patient experience and other stakeholders’ perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three‐grade‐based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice. [ABSTRACT FROM AUTHOR]

Abstract: Background: Consumption of oily fish or fish oil during pregnancy, lactation and infancy has been linked to a reduction in the development of allergic diseases in childhood. Methods: In an observational study, Icelandic children (n = 1304) were prospectively followed from birth to 2.5 years with detailed questionnaires administered at birth and at 1 and 2 years of age, including questions about fish oil supplementation. Children with suspected food allergy were invited for physical examinations, allergic sensitization tests, and a double‐blind, placebo‐controlled food challenge if the allergy testing or clinical history indicated food allergy. The study investigated the development of sensitization to food and confirmed food allergy according to age and frequency of postnatal fish oil supplementation using proportional hazards modelling. Results: The incidence of diagnosed food sensitization was significantly lower in children who received regular fish oil supplementation (relative risk: 0.51, 95% confidence interval: 0.32‐0.82). The incidence of challenge‐confirmed food allergy was also reduced, although not statistically significant (0.57, 0.30‐1.12). Children who began to receive fish oil in their first half year of life were significantly more protected than those who began later (P = .045 for sensitization, P = .018 for allergy). Indicators of allergy severity decreased with increased fish oil consumption (P = .013). Adjusting for parent education and allergic family history did not change the results. Conclusion: Postnatal fish oil consumption is associated with decreased food sensitization and food allergies in infants and may provide an intervention strategy for allergy prevention. [ABSTRACT FROM AUTHOR]

Environmental exposure to food allergens may be a risk factor for cutaneous sensitization. Previous studies could detect peanut allergen in house dust. In this pilot study, we wanted to investigate whether hen's egg allergen is detectable in house dust collected from different household areas and whether levels are increased after intentional hen's egg consumption. Hen's egg protein levels of dust samples were measured using ELISA. In 8 of 8 households, hen's egg was detectable in dust samples of eating area and bed. Forty-eight hours after intentional hen's egg consumption, hen's egg protein levels were significantly increased in both. Still, further research is necessary to investigate whether hen's egg allergen in house and bed dust plays a role in sensitization via skin. [ABSTRACT FROM AUTHOR]

Background Genetic variants for IgE-mediated peanut allergy are yet to be fully characterized and to date only one genomewide association study ( GWAS) has been published. Objective To identify genetic variants associated with challenge-proven peanut allergy. Methods We carried out a GWAS comparing 73 infants with challenge-proven IgE-mediated peanut allergy against 148 non-allergic infants (all ~ 1 year old). We tested a total of 3.8 million single nucleotide polymorphisms, as well as imputed HLA alleles and amino acids. Replication was assessed by de novo genotyping in a panel of additional 117 cases and 380 controls, and in silico testing in two independent GWAS cohorts. Results We identified 21 independent associations at P ≤ 5 × 10−5 but were unable to replicate these. The most significant HLA association was the previously reported amino acid variant located at position 71, within the peptide-binding groove of HLA- DRB1 ( P = 2 × 10−4). Our study therefore reproduced previous findings for the association between peanut allergy and HLA- DRB1 in this Australian population. Conclusions and Clinical Relevance Genetic determinants for challenge-proven peanut allergy include alleles at the HLA- DRB1 locus. [ABSTRACT FROM AUTHOR]

Anaphylaxis has been defined as a 'severe, life-threatening generalized or systemic hypersensitivity reaction'. However, data indicate that the vast majority of food-triggered anaphylactic reactions are not life-threatening. Nonetheless, severe life-threatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life-threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food-allergic children also have asthma, yet almost none will experience a fatal food-allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food-induced allergic reactions. [ABSTRACT FROM AUTHOR]

Background 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. Methods A standardised questionnaire was filled from 2008 to 2010 by the emergency physicians. Results A total of 333 cases of anaphylaxis were reported. 295 of these met the inclusion criteria for severity and were analysed. 13.9% ( n = 41) were reactions with respiratory symptoms, 25.4% ( n = 75) with cardiovascular, and in 60.7% ( n = 179) of cases, respiratory and cardiovascular symptoms were reported. Two reactions were fatal. The most common elicitors were food products (32.2%), drugs (29.2%) and insect venom (19.3%). The most frequently given drugs were corticoids and antihistamines, but not adrenaline. For 2008, the calculated incidence was 4.5 per 100 000. Conclusions Our data show that food products are frequent elicitors of severe allergic reactions in the general population including children and adults. It unravels a strong underuse of adrenaline by emergency physicians, not reflecting treatment protocols according to the current guidelines. As data obtained from allergists reveal a different rank order of elicitors, this study suggests that food-allergic adult patients may present a risk population and should receive more attention by allergists. [ABSTRACT FROM AUTHOR]

Background The measurement of specific serum immunoglobulin E ( sIgE) and the skin prick test (SPT) are accepted tools in the diagnostic work-up of suspected food allergy. Often only one of the methods is used to determine sensitization; however, it is still under debate whether these two methods can be used interchangeably. Objectives To investigate the concordance of SPT and sIgE serum assays with regard to suspected food allergy. Methods In 395 children referred to our clinic with suspected cow's milk allergy and in 268 children with suspected hen's egg allergy specific immunoglobulin E (IgE) was measured, a SPT and an oral food challenge performed. A weal size ≥ 3 mm and sIgE ≥ 0.35 kU/L were considered positive. The weal size of the SPT and the level of food-specific IgE were tested for correlation for each allergen. Results Of the 395 (23%) children orally challenged with cow's milk, 92 showed no corresponding results for SPT and sIgE as either positive or negative. For hen's egg, in 27 of 268 (10%) children differing test results for SPT and sIgE in serum were obtained. Moreover, regarding the quantitative values for sIgE and SPT in children with or without clinically relevant food allergy, sIgE and SPT correlated badly. Conclusions The concordance between SPT and sIgE is surprisingly low for cow's milk and hen's egg on an individual basis. Therefore, the tests should not be used interchangeably. Especially in children who receive a negative test result the alternative test should also be used. Furthermore, our data indicate again that oral food challenges are still the method of choice to diagnose food allergies. [ABSTRACT FROM AUTHOR]

Summary Background There is an emerging consensus that, as with other risks in society, zero risk for food-allergic people is not a realistic or attainable option. Food allergy challenge data and new risk assessment methods offer the opportunity to develop quantitative limits for unintended allergenic ingredients which can be used in risk-based approaches. However, a prerequisite to their application is defining a tolerable level of risk. This requires a value judgement and is ultimately a 'societal' decision that has to involve all relevant stakeholders. Objective The aim of the workshop was to bring together key representatives from the stakeholders (regulators, food industry, clinical researchers and patients), and for the first time ever discuss the definition of a tolerable level of risk with regard to allergic reactions to food. Results The discussions revealed a consensus that zero risk was not a realistic option and that it is essential to address the current lack of agreed action levels for cross-contamination with allergens if food allergen management practice is to be improved. The discussions also indicated that it was difficult to define and quantify a tolerable level of risk, although both the clinical and the industry groups tried to do so. A consensus emerged that doing nothing was not a viable option, and there was a strong desire to take action to improve the current situation. Conclusions and Clinical Relevance Two concrete actions were suggested: (1) Action levels should be derived from the data currently available. Different scenarios should be examined and further developed in an iterative process. On the basis of this work, a tolerable level of risk should be proposed. (2) 'One-dose' clinical trial with a low challenge dose should be performed in multiple centres to provide additional information about the general applicability of dose-distribution models and help validate the threshold levels derived. [ABSTRACT FROM AUTHOR]

Background: Hen's egg (HE) allergy is a common disease in childhood. HE-specific serum IgE has been correlated with the outcome of oral food challenge tests, and diagnostic decision points have been described as helpful but still not sufficient to reduce the requirement for oral food challenges. The aim of the study was to correlate HE-specific IgE, IgG and IgG4 levels with the outcome of double-blind, placebo-controlled food challenges (DBPCFC) in patients with suspected HE allergy to improve diagnostic procedures. Methods: HE-specific IgE, IgG, and IgG4 levels were compared between 150 children with suspected HE allergy based on sensitization and/or patient's history who underwent DBPCFC. Sixty-six patients were HE-allergic (HE-sensitized with a positive DBPCFC), 48 HE-sensitized but tolerant (negative DBPCFC), and 36 patients were nonsensitized and tolerant (negative DBPCFC). Prior to food challenge HE-specific serum IgE, IgG, and IgG4 were measured with the Phadia CAP-system. Results: HE-specific IgE was significantly higher in HE-allergic patients than in clinically tolerant ones. However, there was no difference in HE-specific IgG and IgG4 concentrations between the patient groups. Conclusion: A proposed cut-off level of 12 kU/l IgE would identify children above this level correctly as HE-allergic. The level of HE-specific IgG or IgG4 in serum of children with suspected HE allergy does not add any additional information in the diagnostic procedure of HE allergy. For diagnostic purposes, specific IgG or IgG4 should not routinely be tested. [ABSTRACT FROM AUTHOR]

The relationship between infant feeding patterns and the later development of food allergies has been the focus of much debate and research over the last decade. National recommendations have been made by many countries on how to feed infants to reduce the risk of food allergy but due to the lack of firm evidence the recommendations differ widely. This review has been developed as part of EuroPrevall, a European multicentre research project funded by the European Union, to document the differing feeding recommendations made across Europe, to investigate the current evidence base for any allergy prevention feeding recommendations and to identify areas where further research is needed. This review will also provide information which, when combined with the infant feeding data collected as part of EuroPrevall, will give an indication of compliance to national feeding guidelines which can be utilised to assess the effectiveness of current dissemination and implementation strategies. [ABSTRACT FROM AUTHOR]

Background: Component-resolved diagnostics using microarray technology has recently been introduced into clinical allergology, but its applicability in children with food allergy has hardly been investigated so far. The aim of this study was to evaluate the utility of microarray-based IgE detection in the diagnostic workup of food allergy and to compare this new diagnostic tool with established methods of allergen-specific IgE detection. Methods: We investigated 130 infants and children with suspected allergy to cow’s milk (CM) or hen’s egg (HE). Serum IgE measurements, skin prick tests, allergen microarray assays and controlled oral food challenges with HE and CM were performed. Results: We analyzed 145 oral challenges that served as reference parameters for assay performance assessment. On this basis, the panel of microarrayed allergen components was shown to represent a comprehensive repertoire of clinically relevant CM and HE proteins. Additionally, the implemented CM and HE components respectively sufficed for equivalent test performance as compared to the corresponding fluorescence enzyme immunoassay extract and skin testing. However, component-resolved diagnostics for HE and CM allergy did not make oral food challenges superfluous. Clinical IgE decision points predicting positive oral food challenges could be calculated for both in vitro test methods. Conclusions: Allergen microarrays provide a new tool to diagnose symptomatic CM and HE allergy. They show performance characteristics comparable to the current diagnostic tests and may be indicated in small children in whom only small blood volumes are obtainable. However, they are not capable of replacing double-blind, placebo-controlled food challenges in most cases. [ABSTRACT FROM AUTHOR]

Primary prevention strategies of allergy so far have been aimed to fight allergy causes, by avoiding risk factors and inhibiting their mechanisms of action. The results of trials testing food or airborne allergen avoidance as a prevention strategy were, however, rather disappointing. A reverse approach for primary prevention of allergies aims to facilitate exposure to protecting factors which promote the induction of immunologic tolerance against innocuous antigens. These factors are associated with farming environment and a ‘traditional lifestyle’, but identification of these factors is quite difficult. Major candidates include food-borne microbes, helminths or their components, which are able to stimulate mucosal immunity, particularly in the gut. Similarly, new preventive and therapeutic strategies are being tested to induce specific food-allergen oral tolerance through the ingestion of progressively increasing doses of the offending food. This shifting of allergy prevention research from avoidance to tolerance induction will hopefully allow us to reverse the epidemic trend of allergy diseases. [ABSTRACT FROM AUTHOR]

Although controlled oral food challenges are considered to be the gold-standard in the diagnosis of food related symptoms, especially if performed in a double-blind, placebo-controlled food challenges (DBPCFC) manner, there are still many unanswered questions and newer aspects, which may explain some pitfalls encountered during oral food challenges. For stopping an oral food challenge and declaring a challenge as positive or negative, symptoms should be objective and/or repetitive. The time interval between administering the food and observing the clinical reaction is an ambivalent factor. Possible reasons for false negative assessments include inadvertent drug use during oral challenges, and the fact that a short-term specific oral tolerance induction (SOTI) may be induced as increasing amounts of the offended food are administered during a titrated oral food challenge. Possible reasons for false positive assessments are the difficulty to maintain an appropriate strict diet throughout the oral challenge procedure, and that the elimination diet implemented before the oral food challenge in children with atopic eczema and suspected food related symptoms may itself be responsible for immediate type clinical symptoms, which had not been reported by the parents before. Finally augmentation factors are among the most plausible explanations for the inadequate reproducibility of an oral food challenge. Although a 100% standardization of the challenge procedure does not seem realistic, efforts should be made to improve the methodology used so far. On the contrary, the possible relation of DBPCFC and SOTI may offer potential advantages for future therapeutic approaches of food allergy. [ABSTRACT FROM AUTHOR]

Background: Approximately two-thirds of egg-allergic infants become tolerant within the first 5 years of life. Objective: We sought (1) to compare the recognition of sequential (linear) and conformational binding sites of ovomucoid, ovalbumin and ovotransferrin, by IgE antibodies of children with persistent and transient egg allergy, (2) to identify immunodominant IgE-and IgG-binding epitopes of ovomucoid, and (3) to compare epitope-specificity of IgE antibodies between patients with differing natural histories of egg allergy. Methods: Using immunodot-blots or ImmunoCAPs, IgE-antibodies against conformational (native) and sequential (reduced and alkylated) egg proteins were determined at the time of clinical reactivity in patients who retained their allergy and in those who developed clinical tolerance. IgE- and IgG-binding epitopes were mapped for ovomucoid using overlapping decapeptides on SPOTs membranes. Recognition of the major IgE-binding epitopes were compared between patients with differing natural histories of egg allergy. Results: The patients with long-lasting egg allergy had a higher concentrations of IgE antibodies against sequential and native ovomucoid and ovalbumin than the children who subsequently gained tolerance ( P < 0.01). Four major IgE-binding epitopes were identified in ovomucoid at amino acid 1–10, 9–20, 47–56, and 113–124. IgE antibodies of all seven patients with persistent egg allergy recognized these epitopes whereas none of the 11 children who outgrew their egg allergy did so. Conclusions: Patients with persistent egg allergy develop IgE antibodies against more sequential and conformational epitopes of ovomucoid and ovalbumin. The presence of serum IgE antibodies to specific sequential epitopes of ovomucoid may be used as a screening instrument for persistent egg allergy. [ABSTRACT FROM AUTHOR]

The development of effective management strategies to optimize the quality of life for allergic patients is currently hampered by a lack of good quality information. Estimates of how many individuals suffer from food allergy and the major foods involved vary widely and inadequacies of in vitro diagnostics make food challenges the only reliable means of diagnosis in many instances. The EuroPrevall project brings together a multidisciplinary partnership to address these issues. Cohorts spanning the main climatic regions of Europe are being developed in infants through a birth cohort, community surveys in school-age children and adults and an outpatient clinic study. Confirmatory double-blind placebo-controlled food challenge diagnosis is being undertaken using foods as they are eaten with titrated doses to allow no-effect and lowest-observable effect levels for allergenic foods to be determined. The cohorts will also facilitate validation of novel in vitro diagnostics through the development of the EuroPrevall Serum Bank. Complementary studies in Ghana, western Siberia, India and China will allow us to gain insights into how different dietary patterns and exposure to microorganisms affect food allergies. New instruments to assess the socioeconomic impact of food allergy are being developed in the project and their application in the clinical cohorts will allow, for the first time, an assessment to be made of the burden this disease places on allergy sufferers and their communities. [ABSTRACT FROM AUTHOR]

Specific serum IgE is considered as one of the important diagnostic measures in the diagnostic work-up of food allergy.To evaluate the role of specific serum IgE in predicting the outcome of oral food challenges, and to determine threshold concentrations of specific serum IgE that could render double-blind, placebo-controlled food challenges unnecessary.In 501 children (median age 13 months), 992 controlled oral challenges were performed with cow's milk (CM), hen's egg (HE), wheat and soy. 440/501 (88%) children suffered from atopic dermatitis. For all children, specific IgE concentrations in serum were determined. Sensitivity, specificity, positive and negative predictive values, receiver operator characteristics-curves as well as predictive decision points were calculated.Four hundred and forty-five out of 992 oral food challenges with allergens were assessed as positive. Sensitivity of specific serum IgE was 97% for HE, 83% for CM, 69% for soy, and 79% for wheat. Specificity was 51% for HE, 53% for CM, 50% for soy, and 38% for wheat. Calculating 90%, 95% and 99% predicted probabilities using logistic regression revealed predictive decision points of 6.3, 12.6, and 59.2 kU/L for HE, respectively. Subdividing our children in those of below or above 1 year of age resulted in a markedly different predicted probability for HE. For CM, only the 90% predicted probability (88.8 kU/L) could be calculated. No decision points could be determined for CM, wheat and soy.In general, specific serum IgE levels showed a correlation with the outcome of positive oral food challenges for CM and HE. Meaningful predictive decision points can be calculated for HE, which may help to avoid oral food challenges in some cases. However, data need to be ascertained for each allergen separately. Furthermore, the age of the patient population under investigation must also be taken into account. [ABSTRACT FROM AUTHOR]

It has been hypothesized that high environmental exposure to peanut allergens may be a potent risk factor for cutaneous sensitization. Therefore, we wanted to investigate whether peanut proteins are detectable in house dust of different household areas. Peanut levels of dust samples were measured with ELISA. Overall, peanut was detectable in 19 of 21 households in the eating area and/or in bed. The frequency of peanut consumption correlated with peanut levels. Forty-eight hours after intentional peanut consumption, peanut levels were highly increased. Nevertheless, further research is required to prove whether peanut allergen in house dust can cause sensitization via skin. [ABSTRACT FROM AUTHOR]

Background: The standard treatment of food allergy is elimination of the incriminated food from the diet. Specific oral tolerance induction (SOTI) seems to be a promising approach for a causal treatment; however, it is unclear whether the tolerance achieved is transient or persistent. We report on a subset of three patients of a larger ongoing study who were treated successfully with SOTI treatment, but experienced a secondary loss of tolerance after a period of allergen avoidance. Methods: The patients suffered from IgE-mediated allergy either to cow's milk (CM) (patient A) or hen's egg (HE) (patients B and C), confirmed by double-blind, placebo-controlled food challenge (DBPCFC). SOTI treatment was performed at home on a daily basis until tolerance to a maximum of 250 ml CM or 4.5 g lyophilized HE protein was achieved. The daily maintenance dose was 100 ml CM or 2.5 g HE protein. Results: Patients A, B and C reached tolerance to the maximum dose after 37, 41 and 52 weeks, respectively. According to the protocol, patients A and B performed a strict secondary elimination diet for 2 months prior to a follow-up DBPCFC after a maintenance phase of 27 and 39 weeks, respectively. Patient C discontinued treatment for 2 days after 4 weeks on the maintenance dose. Despite previous tolerance, on re-exposure to the allergen all patients experienced moderate systemic allergic reactions. Conclusions: We conclude that SOTI can induce transient tolerance in food allergy, but does not necessarily lead to its permanent abrogation. Regular allergen intake seems necessary to maintain the established tolerance. [ABSTRACT FROM AUTHOR]

The author offers information on an advanced grading system for allergic reactions. He discusses discovery of immunoglobulin E (IgE) that led to the understanding of differentiation between IgE- and non-IgE-mediated allergic reactions, grading allergic symptoms which include allergic reactions from skin and grading anaphylactic reactions which include life-threatening reactions, and key points of an advanced grading system such as suitable for use in daily practice and universally applicable.

The article presents a research on the effect of freezing foods for the skin prick tests outcome. A study is made on freezing fresh foods such as cow's milk and eggs prior to performing skin prick tests is undertaken to compare its reliability as compared against fresh foods. It is found out that freezing foods does not alter their allergenic characters.

A letter to the editor is presented in response to the previously published article about specific oral tolerance induction .