Recent reports indiciate that the prevelance of food allergy is increasing, but accurate estimates remain a challenge due to cross-reactivity and limited use of precise diagnostic methods. Component-resolved diagnostics (CRD), in which sensitization to individual molecular components of whole food allergen extracts is measured, is emerging as a promising tool for evaluation of sensitization profiles. In this systematic review, we summarized estimates of prevalence of sensitization to food allergen components in the general population in Europe. We searched seven databases with no restrictions on publication date or language. Two reviewers independently screened the literature and appraised the risk of bias in the included studies. From 4,776 de-duplicated records, five studies, with low to moderate overall risk of bias, were included and narratively synthesized. Forty-six components from 18 foods were investigated. Overall, the prevalence of sensitization was low, particularly for major allergens, and non-existent for 10 components (0% [95% CI 0-0.8]). The highest prevalence was seen for PR-10 proteins, such as Cor a 1.04 (13.6% [95% CI 10.9-16.9]). There were not enough studies to discern regional differences or perfom meta-analysis, highlighting the need for more population-representative studies in order to elucidate patterns of sensitization to food allergen components in Europe.

To the EditorReply to Stefano Miceli SopoFirst of all we want to thank for giving us an opportunity to reply to this correspondence (1), acknowledging the correspondence authors important point about the recommendation of introducing well-cooked, but not raw or uncooked pasteurized hen’s egg as part of complementary feeding.We agree that the evidence-base is sparse, with just two trials about cooked egg contributing to the low to moderate certainty evidence in our review (2) and guideline (3). These studies were in different populations (4, 5). We highlighted these points in the guideline, and the subgroup analysis from the Perkin study (6) was used only as supporting material, and for estimating the amount of egg that could be used. It is correct that the Natsume study included infant at higher risk due to eczema, but that was the case for both groups, and outcome was assessed by controlled challenges as described in the systematic review (2).As set out in the guideline, the process took into account expert insight weighing up benefits and harms, costs, feasibility, standard practice and patient preferences, in addition to published evidence. Weighing up all of these factors, the task force decided that the potential benefits outweighed potential harms in the case of well-cooked egg. One relatively large study found a 29% absolute decrease in the proportion of high risk infants with egg allergy at 1 year when very small amounts of egg were introduced (RR 0.22, 95% CI 0.08 to 0.54) (4). And two trials found no adverse effects (4, 5). It is likely feasible for many families to introduce well-cooked egg as part of complementary feeding, including in baked goods. The potential benefits do not outweigh the harms for uncooked egg, so the task force did not suggest trying this approach.The task force included representatives from many countries and specialties, and followed a robust process when reviewing evidence and debating potential recommendations. As the correspondence authors note, this recommendation is in line with other key guidelines. Whilst the correspondence authors may not agree with specific recommendations, the process used to debate and vote on them was systematic and took into account perspectives from across the world, including those from organisations representing patients and their families. Furthermore, a public consultation process sought feedback prior to publication, which further reinforced consensus about this recommendation.As is the case with all guidelines, the EAACI food allergy prevention guideline provides suggestions for clinicians to consider, alongside the needs of individual patients and local contexts and customs. The guideline is not prescriptive and does not override clinical judgement ad individual circumstances. Given the lack of likely harm, the convenience of this approach and best available evidence to date, the task force stands by its suggestion that clinicians in countries where egg allergy is an issue discuss with families the potential and desire to introduce small amounts of well-cooked egg into the infant diet when appropriate as part of complementary feeding. This need not be from the beginning of complementary therapy and the amounts may be very small.The guideline suggests half of a well-cooked, small egg twice a week, which may be in the form of a hard-boiled egg, well-cooked egg pasta, bread or baked goods, for example (p. 850). There is no evidence of significant harm, and it is likely that infants in many parts of the world may be exposed to egg in their diet anyway. There is no need to avoid this to prevent egg allergy, and in the opinion of the EAACI task force, introducing it may have benefits.Susanne Halken, Professor a, ProfessorAntonella Maria Muraro b, ProfessorGraham Roberts c, ProfessorDebra de Silva d, ProfessorOn behalf of On behalf of the EAACI Prevention Guideline Task Forcea Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, DenmarkbDepartment of Women and Child Health, Food Allergy Referral Centre Veneto Region, Padua University Hospital, Padua, Italyc Clinical and Experimental Sciences and Human Development in Health, Faculty of Medicine, University of Southampton, Southampton, UK. NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK. The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Newport, UKdThe Evidence Centre Ltd, London, UKReferencesStefano Miceli Sopo, Dario Sinatti, Francesco Mastellone, Giulia Bersani, Mariannita Gelsomino. Comment on Halken et al. Pediatr Allergy Immunol . 2022de Silva D, Halken S, Singh C, et al. Preventing food allergy in infancy and childhood: systematic review of randomised controlled trials. Pediatr Allergy Immunol . 2020;31(7):813-826Halken S, Muraro A, de Silva D, et al. EAACI guideline: Preventing the development of food allergy in infants and young children (2020 update). Pediatr Allergy Immunol. 2021;32(5):843-858.Natsume O, Kabashima S, Nakazato J, et al. Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial. Lancet. 92 2017;389(10066):276-286.Perkin MR, Logan K, Tseng A, et al. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374(18):1733-1743.Perkin MR, Logan K, Bahnson HT, et al. Efficacy of the enquiring About Tolerance (EAT) study among infants at high risk of developing food allergy. J Allergy Clin Immunol. 2019;144(6):1606-1614.

Background There is substantial interest in allergen-specific immunotherapy in food allergy. We systematically reviewed its efficacy and safety. Methods We searched six bibliographic databases from 1946 to 30 April 2021 for randomised controlled trials about immunotherapy alone or with biologicals in IgE-mediated food allergy confirmed by oral food challenge. We pooled the data using random-effects meta-analysis. Results We included 36 trials with 2,126 participants, mainly children. Oral immunotherapy increased tolerance whilst on therapy for peanut (RR 9.9, 95% CI 4.5. to 21.4, high certainty); cow’s milk (RR 5.7, 1.9 to 16.7, moderate certainty) and hen’s egg allergy (RR 8.9, 4.4 to 18, moderate certainty). The number needed to treat to increase tolerance to a single dose of 300mg or 1000mg peanut protein was 2. In peanut allergy, oral immunotherapy did not increase adverse reactions (RR 1.1, 1.0 to 1.2, low certainty) or severe reactions (RR 1,6, 0.7 to 3.5, low certainty). It may increase adverse reactions in cow’s milk (RR 3.9, 2.1 to 7.5, low certainty) and hen’s egg allergy (RR 7.0, 2.4 to 19.8, moderate certainty), but reactions tended to be mild and gastrointestinal. Epicutaneous immunotherapy increased tolerance whilst on therapy for peanut (RR 2.6, 1.8 to 3.8, moderate certainty). Results were unclear for other allergies and administration routes. Conclusions Oral immunotherapy improves tolerance whilst on therapy and is probably safe in peanut, cow’s milk and hen’s egg allergy. However, our review found little about whether this improves quality of life, is sustained or cost-effective.

Background Biological therapies relieve symptoms in allergic and inflammatory diseases so may also benefit people with IgE-mediated food allergy. We systematically reviewed the highest quality published evidence to inform forthcoming GA 2LEN guidelines. Methods We searched six bibliographic databases from 1946 to 30 September 2021 for randomised controlled trials, controlled clinical trials and quasi-randomised trials about biological monotherapy in people with IgE-mediated food allergy confirmed by oral food challenge. We found 3 trials with 118 participants. We used the GRADE approach. We summarised the findings narratively because studies were too heterogeneous to conduct meta-analysis. Results We included one randomised trial about etokimab, one about omalizumab and one about the discontinued TNX-901. All were in people with peanut allergy in the USA, mostly aged 13+ years. There were trends towards improved tolerance of peanut during treatment, with no increase in adverse events compared to placebo. However, we have very low certainty about the evidence. No trial reported on quality of life or cost-effectiveness. Conclusions Our review of the highest quality research found that there is not yet enough certainty of evidence to support offering etokimab or omalizumab widely for food allergy. Clinicians may consider the merits for individuals, but large randomised trials with standardised measures need to confirm the safety and efficacy and the most suitable candidates, doses and durations of treatment.

Background This systematic review used the GRADE approach to compile evidence to inform an anaphylaxis guideline from the European Academy of Allergy and Clinical Immunology (EAACI). Methods We searched five bibliographic databases from 1946 to 20 April 2020 for studies about the diagnosis, management and prevention of anaphylaxis. We included 50 studies with 18,449 participants: 29 randomised controlled trials, seven controlled clinical trials, seven consecutive case series and seven case-control studies. Findings were summarised narratively because studies were too heterogeneous to conduct meta-analysis. Results It is unclear whether the NIAID/FAAN criteria or Brighton case definition are valid for immediately diagnosing anaphylaxis due to the very low certainty of evidence. Adrenaline is the cornerstone of first-line emergency management of anaphylaxis but, due to ethical constraints, little robust research has assessed its effectiveness . Newer models of adrenaline autoinjectors may slightly increase the proportion of people correctly using the devices and reduce time to administration. Face-to-face training for laypeople may slightly improve anaphylaxis knowledge and competence in using autoinjectors. Adrenaline prophylaxis prior to snake bite anti-venom may reduce anaphylaxis but the impact of prophylactic corticosteroids and antihistamines is uncertain. There was insufficient evidence about the impact of other anaphylaxis management strategies. Conclusions Anaphylaxis is a potentially life-threatening condition but, due to practical and ethical challenges, there is a paucity of robust evidence about how to diagnose and manage it.

The International Classification of Diseases (ICD) provides a common language for use worldwide as a diagnostic and classification tool for epidemiology, clinical purposes and health management. Since its first edition, the ICD has maintained a framework distributing conditions according to topography, with the result that some complex conditions, such as allergies and hypersensitivity disorders (A/H) including anaphylaxis, have been poorly represented. The change in hierarchy in ICD-11 permitted the construction of the pioneer section addressed to A/H, which may result in more accurate mortality and morbidity statistics, including more accurate accounting for mortality due to anaphylaxis, strengthen classification, terminology and definitions. The ICD-11 was presented and adopted by the 72nd World Health Assembly in May 2019 and the implementation is ongoing worldwide. We here present the outcomes from an online survey undertaken to reach out the allergy community worldwide in order to peer review the terminology, classification and definitions of A/H introduced into ICD-11 and to support their global implementation. Data are presented here for 406 respondents from 74 countries. All of the sub-sections of the new A/H section of the ICD-11 had been considered with good accuracy by the majority of respondents. We believe that, in addition to help during the implementation phase, all the comments provided will help to improve the A/H classification and to increase awareness by different disciplines of what actions are needed to ensure more accurate epidemiological data and better clinical management of A/H patients.

Since the first description of anaphylaxis in 1902, its clinical importance as an emergency condition has been recognized worldwide. Anaphylaxis is a severe, potentially life-threatening systemic hypersensitivity reaction characterized by rapid onset and the potential to endanger life through respiratory or circulatory compromise. It is usually, although not always, associated with skin and mucosal changes. Although the academic/scientific communities have advocated to promote greater awareness and protocols for management of anaphylaxis based on best evidence, there are few efforts documenting feedback as to the success of these efforts. In this document, we review the key unmet needs related to the diagnosis and management of anaphylaxis, propose a public health initiative for prevention measures and a timetable action plan which intends to strengthen the collaboration among health professionals and especially primary care physicians dealing with anaphylaxis that can encourage enhanced quality of care of patients with anaphylaxis. More than calling for harmonized action for best management of anaphylaxis to prevent undue morbidity and mortality, the Montpellier World Health Organization Collaborating Centre here proposes an action plan as a baseline for a global initiative against anaphylaxis. We strongly believe these collaborative efforts are a strong public health and societal priority that is consistent with the overarching goals of providing optimal care of allergic patients and best practices of allergology.