Randomised controlled trial of a baked egg intervention in young children allergic to raw egg but not baked egg

Consumption of baked egg by raw egg allergic children is associated with immune changes suggesting development of tolerance. However, causation has not been tested using a double blind randomized controlled trial (RCT). We aimed to compare clinical and immunological outcomes after baked egg (BE) consumption in young BE tolerant egg allergic children.In a double blind RCT, BE tolerant egg allergic children consumed 10 g BE (1.3 g protein) 2 to 3 times per week for 6 months (n = 21 intervention group) or similar egg free baked goods (n = 22 control group) while maintaining an otherwise egg free diet. The final assessment was a raw egg oral food challenge (OFC) 1 month after ceasing the intervention product. Egg specific IgE and IgG4 were assessed at baseline and 7 months.After the intervention there was no difference in raw egg tolerance between groups, (23.5% (4/17) intervention group and 33.3% (6/18) control group). This was independent of age and amount of BE consumed (aOR 0.50 CI 0.11-2.40 p = 0.39). Both groups demonstrated decreased egg specific serum IgE titres and decreased whole egg specific IgE/IgG4 ratios.We conducted this trial because inclusion of baked egg protein in the diet of egg allergic children appears to move children towards a more tolerant immune profile. Strengths of our study include design of the blinded intervention, the consistent dosing protocol and the regular monitoring of symptoms and intake. However, the study was limited by small sample size resulting in insufficient power to show statistically significant results.Our study suggests that short term, regular consumption of BE by BE tolerant 1 to 5 year old children with IgE mediated raw egg allergy may not induce, accelerate or slow development of tolerance to raw egg in this selected population. Trials with larger sample sizes are required to further test this hypothesis.The trial was registered on 7th February 2012 with the Australian New Zealand Clinical Trials Registry (ACTRN 12612000173897).Merryn Netting, Michael Gold, Patrick Quinn, Adaweyah El-Merhibi, Irmeli Penttila and Maria Makride

An algorithm for diagnosing IgE-mediated food allergy in study participants who do not undergo food challenge.

BACKGROUND: Food allergy diagnosis in clinical studies can be challenging. Oral food challenges (OFC) are time-consuming, carry some risk and may, therefore, not be acceptable to all study participants. OBJECTIVE: To design and evaluate an algorithm for detecting IgE-mediated food allergy in clinical study participants who do not undergo OFC. METHODS: An algorithm for trial participants in the Barrier Enhancement for Eczema Prevention (BEEP) study who were unwilling or unable to attend OFC was developed. BEEP is a pragmatic, multi-centre, randomized-controlled trial of daily emollient for the first year of life for primary prevention of eczema and food allergy in high-risk infants (ISRCTN21528841). We built on the European iFAAM consensus guidance to develop a novel food allergy diagnosis algorithm using available information on previous allergenic food ingestion, food reaction(s) and sensitization status. This was implemented by a panel of food allergy experts blind to treatment allocation and OFC outcome. We then evaluated the algorithm's performance in both BEEP and Enquiring About Tolerance (EAT) study participants who did undergo OFC. RESULTS: In 31/69 (45%) BEEP and 44/55 (80%) EAT study control group participants who had an OFC the panel felt confident enough to categorize children as "probable food allergy" or "probable no food allergy". Algorithm-derived panel decisions showed high sensitivity 94% (95%CI 68, 100) BEEP; 90% (95%CI 72, 97) EAT and moderate specificity 67% (95%CI 39, 87) BEEP; 67% (95%CI 39, 87) EAT. Sensitivity and specificity were similar when all BEEP and EAT participants with OFC outcome were included. CONCLUSION: We describe a new algorithm with high sensitivity for IgE-mediated food allergy in clinical study participants who do not undergo OFC. CLINICAL RELEVANCE: This may be a useful tool for excluding food allergy in future clinical studies where OFC is not conducted

Oral immunotherapy for food allergy in children: is it worth it?

Introduction: Oral immunotherapy (OIT) is effective at inducing desensitization in food-allergic individuals, and is a valid therapeutic option for those allergic to peanut, cow’s milk and egg. However, there is a high rate of dose-related adverse events, and at least one fatality to OIT has been reported. Areas covered: We provide an update on the broader framework of issues which will impact on the availability and uptake of OIT. Expert opinion: The need for standardized products remains controversial. A licensed product exists for peanut-OIT, but OIT can also be safely achieved using peanut-containing foods at much lower cost. For other allergens, OIT can only be done with non-pharma products – something which has been done safely for over 2 decades. There is a need to develop personalized protocols for OIT, particularly for the 20% of patients unable to tolerate standard OIT. Cost-effectiveness is dependent on improved quality of life, but evidence for this is currently lacking, and is a key evidence gap. OIT is likely to be cost-effective, particularly if noncommercial products are used. There may be a trade-off: in patients with lower reaction thresholds, a commercial product may be needed for initial updosing, until a level of desensitization is achieved when they can be switched to natural food products

The potential effect of dietary changes on the management of food allergies

Food allergy (FA) is a significant public health problem with symptoms ranging from mild urticaria up to severe anaphylaxis. The frequency of food allergy has been rising in the last decades particularly in children where nutritional compromise can ensue together with possible development of other allergic diseases. With the developing technology and knowledge, there has been improvement in the treatment of FA. Diet is a very important factor in the management and changes in the diet of both the child and mother affect the risk of developing food allergies. Consumption of some nutrients such as omega-3 fatty acids, vitamin D, folic acid may be beneficial in preventing FA. The mechanisms proposed are mainly related to their effects on regulating the immune system. Regulatory changes in the intestinal flora, such as dietary consumption and probiotic use, are also on the agenda and show promising results approaches. Although, it has been advised to remove the allergenic food from the diet, yet recently, it has been shown that processing of allergenic foods and early consumption of allergenic foods between 4th -6th months can cause food tolerance in infants. This review aims to provide updates on the effect of adding some nutrients and dietetic changes on the management of FA

Managing food allergy: GA2LEN guideline 2022

Food allergy affects approximately 2–4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy. + Graphical abstrac

Managing food allergy: GA2LEN guideline 2022

Food allergy affects approximately 2-4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy

Managing food allergy:GA²LEN guideline 2022

Food allergy affects approximately 2–4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy

Managing food allergy : GA(2)LEN guideline 2022

Food allergy affects approximately 2-4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA(2)LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy.Peer reviewe

The Gut Microbiome and the Big Eight

Food allergies are increasing at an alarming rate, with 6.5% of the general population affected. It has been hypothesized that the increase in allergies stems from the “hygiene hypothesis”. The gut microbiome, a collection of microbiota and their genetic contents from the gastrointestinal tract, has been shown to play a part in the development of food allergies. The Food and Drug Administration requires all regulated food companies to clearly state an inclusion of the major, or “big eight” food allergens on packaging. This review is to provide information on the significant advancements related to the gut microbiome and each of the eight major food allergies individually. Establishment of causal connection between the microbiome and food allergies has uncovered novel mechanisms. New strategies are discussed to prevent future sensitization and reaction through novel treatments involving functional additives and dietary changes that target the microbiome

Strategies and Future Opportunities for the Prevention, Diagnosis, and Management of Cow Milk Allergy

The prevalence of food allergy has increased over the last 20-30 years, including cow milk allergy (CMA) which is one of the most common causes of infant food allergy. International allergy experts met in 2019 to discuss broad topics in allergy prevention and management of CMA including current challenges and future opportunities. The highlights of the meeting combined with recently published developments are presented here. Primary prevention of CMA should start from pre-pregnancy with a focus on a healthy lifestyle and food diversity to ensure adequate transfer of inhibitory IgG- allergen immune complexes across the placenta especially in mothers with a history of allergic diseases and planned c-section delivery. For non-breastfed infants, there is controversy about the preventive role of partially hydrolyzed formulae (pHF) despite some evidence of health economic benefits among those with a family history of allergy. Clinical management of CMA consists of secondary prevention with a focus on the development of early oral tolerance. The use of extensive Hydrolysate Formulae (eHF) is the nutrition of choice for the majority of non-breastfed infants with CMA; potentially with pre-, probiotics and LCPUFA to support early oral tolerance induction. Future opportunities are, among others, pre- and probiotics supplementation for mothers and high-risk infants for the primary prevention of CMA. A controlled prospective study implementing a step-down milk formulae ladder with various degrees of hydrolysate is proposed for food challenges and early development of oral tolerance. This provides a more precise gradation of milk protein exposure than those currently recommended