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Purpose of reviewIn this review, we sought to describe the most recent advances in the dietary and medical management of peanut and tree nut allergy, including selective introduction and immunotherapy.Recent findingsDietary updates include changes to labeling laws, improved information sources, and new apps for buying foods in shops and overseas to better protect individuals with nut allergies. There are still issues in the management of nut allergies in schools, such as parents having to resort to packed lunches instead of school meals and patients experiencing bullying. Air travel also poses concern, but additional resources are now available to travelers, and recent evidence suggest limited airborne exposure to nuts. The medical management of anaphylaxis is use of epinephrine; however, this remains underutilized. Needle length and administration devices have been recently debated considering the risk of bone penetration vs subcutaneous administration, and autoinjectors seem to deliver higher peak concentrations than syringes. Selective nut introduction has gained momentum in the last 5 years, demonstrating improved quality of life but with the need for motivated parents for continued consumption and available resources for challenges. Immunotherapy to nuts is also a rapidly developing field, with the balance of efficacy and safety being important considerations in the differing modes of administration.SummaryThe management of nut allergies is a rapidly developing field, and dietary and medical management have progressed significantly in the last 5 years. Future research directions include improving safety and efficacy of food immunotherapy and examining patients’ goals for therapy and treatment outcomes.

Food allergy is an increasingly prevalent disease driven by uncontrolled type 2 immune response. Currently, knowledge about the underlying mechanisms that initiate and promote the immune response to dietary allergens is limited. Patients with food allergy are commonly sensitized through the skin in their early life, later on developing allergy symptoms within the gastrointestinal tract. Food allergy results from a dysregulated type 2 response to food allergens, characterized by enhanced levels of IgE, IL-4, IL-5, and IL-13 with infiltration of mast cells, eosinophils, and basophils. Recent studies raised a possible role for the involvement of innate lymphoid cells (ILCs) in driving food allergy. Unlike lymphocytes, ILCs lack They represent a group of lymphocytes that lack specific antigen receptors. ILCs contribute to immune responses not only by releasing cytokines and other mediators but also by responding to cytokines produced by activated cells in their local microenvironment. Due to their localization at barrier surfaces of the airways, gut, and skin, ILCs form a link between the innate and adaptive immunity. This review summarizes recent evidence on how skin and gastrointestinal mucosal immune system contribute to both homeostasis and the development of food allergy, as well as the involvement of ILCs toward inflammatory processes and regulatory mechanisms.

BackgroundThe Coronavirus disease 2019 (COVID‐19) has evolved as a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐)2. Allergists and other health care providers (HCPs) in the field of allergies and associated airway diseases are in the front line, taking care of patients potentially infected with SARS‐CoV‐2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.MethodThe scientific information on COVID‐19 was analyzed by a literature search in Medline, Pubmed, national and international guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library and the Internet.ResultsBased on diagnostic and treatment standards developed by EAACI, on international information regarding COVID‐19, on guidelines of the World Health Organization (WHO) and other international organizations as well as on previous experience, a panel of experts including clinicians, psychologists, IT experts and basic scientists along with EAACI and the “Allergic Rhinitis and its Impact on Asthma (ARIA)” inititiative have developed recommendations for the optimal management of allergy clinics during the current COVID‐19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.ConclusionsThis international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients whilst ensuring necessary safety in the current COVID‐19 pandemic.

Peanut allergy is an important public health concern and causes substantial psychosocial comorbidity. Although fatal anaphylaxis is rare (occurring at 0·03-0·3 per million person-years in the general population), peanuts are one of the most frequent causes of food allergy mortality. The Learning Early About Peanut study transformed prevention of peanut allergy by showing that early introduction of peanut into the diet of children at high risk (ie, those with an egg allergy or severe eczema) reduced the relative risk of peanut allergy at age 5 years by 81%. Following publication of this study, the US National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, convened an expert panel, which recommended that, for infants with severe eczema or egg allergy, health professionals should strongly consider evaluation with peanut-specific serological IgE or skin prick test (or both) and, if necessary, an oral food challenge before peanut introduction. In the USA, depending on test results, peanut-containing foods are recommended to be introduced from age 4-6 months in infants with severe eczema or egg allergy. Early introduction to peanuts is also advocated for children with either mild to moderate or no eczema, and in children who are not allergic to egg, but without screening before peanut introduction. However, the NIAID addendum guidelines contrast with other international approaches that do not advocate for allergy screening at a population level before introducing peanuts into infants' diets. In this Review, we evaluate the advantages and disadvantages of a pre-emptive screening approach before the early introduction of peanuts in infants at high risk of peanut allergy.

While the world is facing an unprecedented pandemic with COVID‐19, patients with chronic diseases need special attention and if warranted adaptation of their regular treatment plan. In children, allergy and asthma are among the most prevalent non‐communicable chronic diseases, and healthcare providers taking care of these patients need guidance. At the current stage of knowledge, children have less severe symptoms of COVID‐19, and severe asthma and immunodeficiency are classified as risk factors. In addition, there is no evidence that currently available asthma and allergy treatments, including antihistamines, corticosteroids, and bronchodilators, increase the risk of severe disease from COVID‐19. Most countries affected by COVID‐19 have opted for nationwide confinement, which means that communication with the primary clinician is often performed by telemedicine. Optimal disease control of allergic, asthmatic, and immunodeficient children should be sought according to usual treatment guidelines. This statement of the EAACI Section on Pediatrics puts forward six recommendations for the management of childhood allergies and immunodeficiencies based on six underlying facts and existing evidence.

There is increasing evidence regarding the importance of allergic sensitization through the skin. In this review, we provide an overview of the atopic march and immune mechanism underlying the sensitization and effector phase of food allergy. We present experimental models and human data that support the concept of epicutaneous sensitization and how this forms one half of the dual-allergen exposure hypothesis. We discuss specific important elements in the skin (FLG and other skin barrier gene mutations, Langerhans cells, type 2 innate lymphoid cells, IL-33, TSLP) that have important roles in the development of allergic responses as well as the body of evidence on environmental allergen exposure and how this can sensitize an individual. Given the link between skin barrier impairment, atopic dermatitis, food allergy, allergic asthma, and allergic rhinitis, it is logical that restoring the skin barrier and prevention or treating atopic dermatitis would have beneficial effects on prevention of related allergic diseases, particularly food allergy. We present the experimental and human studies that have evaluated this approach and discuss various factors which may influence the success of these approaches, such as the type of emollient chosen for the intervention, the role of managing skin inflammation, and differences between primary and secondary prevention of atopic dermatitis to achieve the desired outcome.

Background: As in many fields of medical care, the coronavirus disease 2019 (COVID-19) resulted in an increased uncertainty regarding the safety of allergen immunotherapy (AIT). Therefore, the European Academy of Allergy and Clinical Immunology (EAACI) aimed to analyze the situation in different countries and systematically collect all information available regarding tolerability and possible amendments in daily practice of sublingual AIT (SLIT), subcutaneous AIT (SCIT) for inhalant allergies and venom AIT.Method: Under the framework of the EAACI, a panel of experts in the field of AIT coordinated by the Immunotherapy Interest Group (IT IG) set-up a web-based retrospective survey (SurveyMonkey®) including 27 standardized questions on practical and safety aspects on AIT in worldwide clinical routine. Results: 417 respondents providing AIT to their patients in daily routine answered the survey. For patients (without any current symptoms to suspect COVID-19), 60% of the respondents informed of not having initiated SCIT (40% venom AIT, 35% SLIT) whereas for the maintenance phase of AIT, SCIT was performed by 75% of the respondents (74% venom AIT, 89% SLIT). No tolerability concern arises from this preliminary analysis. 16 physicians reported having performed AIT despite (early) symptoms of COVID-19 and/or a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Conclusions: This first international retrospective survey in atopic diseases investigated practical aspects and tolerability of AIT during the COVID-19 pandemic and gave no concerns regarding reduced tolerability under real-life circumstances. However, the data indicate an undertreatment of AIT, which may be temporary, but could have a long-lasting negative impact on the clinical care of allergic patients. Keywords: COVID-19, allergen immunotherapy (AIT), SARS-CoV-2, practicability, survey, safety, pandemic

With the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS‐CoV‐2‐induced Coronavirus disease‐19 (COVID‐19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS‐CoV‐2 infection and COVID‐19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multi‐organ disease. The similarities of the human immune response to SARS‐CoV‐2 and the SARS‐CoV and MERS‐CoV are underlined. We also summarize known and potential SARS‐CoV‐2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender and age in development of COVID‐19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID‐19 studies., The authors would like to thank the European Academy of Allergy and Clinical Immunology (EAACI) for the financial support to the sections, interest groups and working groups enabling the development of this paper. The research of SM is supported by a SNSF grant 310039_189334; JSR is funded by Ministerio de Economía y Competitividad (IJCI-2016-27619); KKI is supported by the FWO Post doc mandate 12W2219N; BW and PF were supported by funding from the Istituto Italiano di Tecnologia, Fondazione Telethon (project GGP19103), and Ricerca Finalizzata Giovani Ricercatori 2016 - Ministero Salute Italia (project GR-2016-02362413); GCC is supported by a postdoctoral contract cofounded by the competitive Program “Attracting Talent,” Community of Madrid, Spain; the research of SWCB was funded by DFG (398577603), “ADAPT” EIT Health is a body of the EU receiving support from H2020 and BMBF “ESCAPE” 01KI20169A; the research of UE is supported by the H2020 grant 768641 and by the BMF grant 19056.

Peanut and tree nut allergies have become a public health problem over the last 2 decades. The diagnostic procedure relies on a suggestive history, as well as on evidence of sensitization (skin prick testing and/or specific IgE blood testing), followed in selected cases by a food challenge. Standard IgE tests may be positive to more than 1 nut, due to cross-reactivity (allergens common to several nuts) or cosensitivity (frequently associated positive test results without cross-reactivity). Thus, many patients with a peanut or a tree nut allergy avoid all nuts, relying on positive test results without clinical evidence of reactivity. In addition, coexisting pollen sensitivity may add to diagnostic uncertainty due to potential cross-reactivity between pollens and nuts. In this article, we discuss challenges in diagnosis and clinical management of peanut and tree nut allergy related to cross-reactivity and cosensitization, as well as the avoidance of nuts tested positive to reduce the risk of reactions by cross-contamination. Studies to provide more accurate characterization of genuine clinically relevant cross-reactivity or cosensitivity to multiple nuts are needed. (C) 2016 American Academy of Allergy, Asthma & Immunology.

Bonertz, Andreas/0000-0002-6846-9265; Brough, Helen/0000-0001-7203-0813; Hoffmann, Hans Jurgen/0000-0002-6743-7931; Hoffmann-Sommergruber, Karin/0000-0002-8830-058X; Schmid-Grendelmeier, Peter/0000-0003-3215-3370 WOS:000569864500002 PubMed: 32306414 Diagnostic allergens are defined as medicinal products in the EU. Marketing authorization by national authorities is necessary; however, diagnostic allergens are not homogeneously regulated in different EU member states. Allergen manufacturers argue with increasing costs forcing them to continuously reduce the diagnostic allergen portfolios offered to allergists. In contrast, EAACI and national European Allergy Societies see the need for the availability of a wide range of high-quality diagnostic allergens for in vivo diagnosis of IgE-mediated allergies not only covering predominant but also less frequent allergen sources. In a recent EAACI task force survey, the current practice of allergy diagnosis was shown to rely on skin tests as first option in almost 2/3 of all types of allergic diseases and in 90% regarding respiratory allergies. With the need to ensure the availability of high-quality diagnostic allergens in the EU, an action plan has been set up by EAACI to analyse the current regulatory demands in EU member states and to define possible solutions stated in this document: (a) simplification of authorization for diagnostic allergens; (b) specific regulation of special types of diagnostic allergens; (c) new models beyond the current model of homologous groups; (d) simplification of pharmacovigilance reporting; (e) reduction of regulation fees for diagnostic allergens; (f) reimbursement for diagnostic allergens. Joining forces of allergists, manufacturers and authorities are of high importance to ensure remaining relevant allergens in the EU markets to facilitate a sustainable and comprehensive service for the diagnosis and treatment of allergic diseases.

Background Nut allergic patients are often IgE sensitized to other nuts/seeds and need multiple oral food challenges (OFCs) before the safe nuts can be introduced in the diet. However, OFCs are time-consuming and risky procedures. Objective To assess the utility of the basophil activation test (BAT) to predict the allergic status and reduce the need for an OFC in children with 1 or more nut or seed allergies. Methods Participants in the Pronuts study recruited at the Geneva and the London centers were tested on the BAT to hazelnut, cashew nut, sesame, almond, and peanut, Ara h 1, Ara h 2, Ara h 6, using FlowCAST, a commercially available BAT kit, and flow cytometry. Results The BAT to hazelnut, cashew nut, sesame, almond, and peanut discriminated between allergic and nonallergic children, to the respective nut or seed. The optimal allergen concentration and their optimal, positive, and negative cutoffs were identified for the BAT and the other tests, for each nut and seed. Using the BAT as a second step in the diagnostic process, after equivocal skin prick test and IgE to extracts and components, reduced the number of total OFCs by 5% to 15% and positive OFCs by 33% to 75% (except for hazelnut) with 0% false-negatives and a diagnostic accuracy of 96% to 100%. Conclusion The BAT proved to be a useful diagnostic tool, used in a stepwise approach, to predict the allergic status and reduce the number of OFCs in the Pronuts study participants with at least 1 nut allergy willing to consume selected nuts.

The prevalence of food allergy has been on the rise in the UK over the last 30 years. Food allergy can be classified as Immunoglobulin E (IgE)-mediated, non-IgE mediated or mixed IgE and non-IgE mediated food allergy. Whilst the management of IgE-mediated food allergy is relatively well established with regards to investigations and treatment options, non-IgE mediated food allergy management is emerging. The role of the gastroenterologist in food allergy is in the management of non-IgE mediated gastrointestinal food allergy, which is performed closely alongside allergologists. The aim of this review is to discuss the common presentations of non-IgE mediated food allergy (i.e. cow's milk protein allergy, food protein-induced enterocolitis, eosinophilic gastrointestinal disorders) and describe current investigation and treatment options for these conditions. It focuses on the main management options available such as elimination diets, drug therapies, as well as gastroenterology-specific tests such as endoscopy. It also highlights the importance of both allergy and gastroenterology multi-disciplinary team support in order to ensure the best management of these children.

Antihistamines are commonly used in paediatric medicine mainly for the treatment of allergic conditions. First generation antihistamines have been in use for many years, despite limited research studies supporting their use. Second generation antihistamines have been investigated for both efficacy and safety in paediatrics. An optimal understanding of their effects and pharmacology are required for optimal use in each patient. In this review we discuss the indications for use, as well as efficacy and safety of both old and newer antihistamines for the paediatric population.

For food allergic individuals, the typical method of exposure to food proteins happens during ingestion; however, individuals may be exposed to foods in other ways. In addition to ingestion reactions, allergic patients may have reactions from cutaneous or mucosal exposures to food proteins with the classic example being a peanut allergic child touching a counter with peanut butter and then rubbing their eyes. Similar to hands, saliva can also act as a carrier for food proteins. Finally, there is a wealth of new research regarding the presence of food proteins in the environment, for example, within household floor dust. This review will focus on (1) cross­contact of food proteins and (2) environmental food protein exposures. Cross-contact occurs when one type of food comes into contact with another type of food resulting in the mixture of proteins. For food allergies, cross-contact is important when an allergen is inadvertently transferred to a food/meal that is thought to not contain that specific allergen. We will discuss the current literature regarding the presence of detectable food proteins in different locations, how and if these proteins are transferred or eliminated, and the clinical implications of exposures to food proteins under these different scenarios.

The environmental factors driving the increase in food allergies are unclear and possibly involve dual exposure to allergens, microbiome-driven effects or other mechanisms. Until they can be better understood, early intervention aiming at establishing oral tolerance provides an effective way to decrease the window-of-risk when children may develop allergic sensitisation to foods due to the absence of a protective immune response. Thus, the recent LEAP (Learning Early About Peanut allergy) and LEAP-On studies achieved a high level of peanut allergy prevention by early introduction of peanuts in the infants diet and conveyed more information regarding the evolution of IgE and IgG4 antibody responses to food antigens over time.

The prevalence of peanut allergy has increased over the years and still remains one of the most common causes of food-related anaphylaxis. The way in which peanut sensitization occurs has been explored, such as via maternal consumption in pregnancy, via breastmilk and through a disrupted skin barrier. It has previously been shown that environmental exposure to aeroallergens in household dust can be a risk factor for the development of allergic asthma. There is an increasing body of evidence that the combination of cutaneous sensitization via a disrupted skin barrier (ie children with eczema or with filaggrin mutations) and environmental peanut exposure influences the development of peanut allergy. This review aims to explore routes of peanut sensitization and the current evidence on how environmental exposure to peanut affects the development of peanut allergy.

This review is of the ‘Addendum guidelines for the prevention of peanut allergy in the United States: report of the National Institute of Allergy and Infectious Diseases–sponsored expert panel’. We aim to summarise the key recommendations for the prevention of peanut allergy (PA) for general paediatricians to use in their day-to-day practice. The prevalence of PA has risen significantly across the developed world over the past few decades, with a recent estimate of around 2% among UK children.1 Severe reactions to peanut are rare, but PA remains a leading cause of fatal food-related anaphylaxis. While there have been important advances in peanut desensitisation, primary prevention remains the most attractive strategy for addressing this rise. The guideline outlines current recommendations on the prevention of PA in infants at various risk levels in the USA. The guideline was developed by the National Institute of Allergy and Infectious Diseases alongside 25 professional organisations, federal agencies and patient advocacy groups and was overseen by an expert panel of 26 members. It was published in September 2016 following a landmark clinical trial suggesting that early introduction of peanut to infants can help prevent the development of PA2 (box 1).Box 1 ### Resources 1. http://www.jacionline.org/article/S0091-6749(16)31222-2/fulltext Link to full guideline: Addendum guidelines for the prevention of peanut allergy in the United States: report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel 2. Learning Early About Peanut (LEAP) study 3. Enquiring About Tolerance (EAT) study A previous national guideline for the diagnosis and management of food allergy in the USA was published in December 2010.3 This guideline did not offer any specific strategies for the prevention of food allergies due to a lack of evidence from studies at the time. It did state that …

The availability of allergen molecules ('components') from several protein families has advanced our understanding of immunoglobulin E (IgE)-mediated responses and enabled 'component-resolved diagnosis' (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low-abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross-reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE-mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross-reactive panallergens from plant (lipid transfer proteins, polcalcins, PR-10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE-mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients.

Background In a randomized trial, the early introduction of peanuts in infants at high risk for allergy was shown to prevent peanut allergy. In this follow-up study, we investigated whether the rate of peanut allergy remained low after 12 months of peanut avoidance among participants who had consumed peanuts during the primary trial (peanut-consumption group), as compared with those who had avoided peanuts (peanut-avoidance group). Methods: At the end of the primary trial, we instructed all the participants to avoid peanuts for 12 months. The primary outcome was the percentage of participants with peanut allergy at the end of the 12-month period, when the participants were 72 months of age. Results: We enrolled 556 of 628 eligible participants (88.5%) from the primary trial; 550 participants (98.9%) had complete primary-outcome data. The rate of adherence to avoidance in the follow-up study was high (90.4% in the peanut-avoidance group and 69.3% in the peanut-consumption group). Peanut allergy at 72 months was significantly more prevalent among participants in the peanut-avoidance group than among those in the peanut-consumption group (18.6% [52 of 280 participants] vs. 4.8% [13 of 270], PConclusions: Among children at high risk for allergy in whom peanuts had been introduced in the first year of life and continued until 5 years of age, a 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy. Longer-term effects are not known. (Funded by the National Institute of Allergy and Infectious Diseases and others; LEAP-On ClinicalTrials.gov number, NCT01366846 .).