Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE‐mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE‐mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well‐defined, highly pure molecules for component‐resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the “EAACI Molecular Allergology User's Guide” (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state‐of‐the‐art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.

In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21^stcentury.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients’ Associations (EFA) is a non‐profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients’ organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re‐categorize clinical syndromes into more coherent, uniform and treatment‐responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient‐oriented diagnostic and treatment protocols. Several allergic diseases require well‐controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult‐to‐manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.

Background: European legislators and wine producers still debate on the requirement for labeling of wines fined with potentially allergenic food proteins (casein, egg white or fish‐derived isinglass). We investigated whether wines fined with known concentrations of these proteins have the potential to provoke clinical allergic reactions in relevant patients.Methods: In‐house wines were produced for the study, fined with different concentrations of casein (n = 7), egg albumin (n = 1) and isinglass (n = 3). ELISA and PCR kits specific for the respective proteins were used to identify the fining agents. Skin prick tests and basophil activation tests were performed in patients with confirmed IgE‐mediated relevant food allergies (n = 24). A wine consumption questionnaire and detailed history on possible reactions to wine was obtained in a multinational cohort of milk, egg or fish allergic patients (n = 53) and patients allergic to irrelevant foods as controls (n = 13).Results: Fining agents were not detectable in wines with the available laboratory methods. Nevertheless, positive skin prick test reactions and basophil activation to the relevant wines were observed in the majority of patients with allergy to milk, egg or fish, correlating with the concentration of the fining agent. Among patients consuming wine, reported reactions were few and mild and similar with the ones reported from the control group.Conclusion: Casein, isinglass or egg, remaining in traces in wine after fining, present a very low risk for the respective food allergic consumers. Physician and patient awareness campaigns may be more suitable than generalized labeling to address this issue, as the latter may have negative impact on both non‐allergic and allergic consumers.

Background: Food protein‐induced allergic proctocolitis (FPIAP) is the leading cause of rectal bleeding in infants. Tolerance is presumed to develop until the first year of age, although natural history studies are scarce, making the determination of the ideal duration for any intervention, challenging. Intestinal microbiota (IM) is crucial in food allergy development; however, data for FPIAP remain limited. This study aimed to assess FPIAP remission after 3 months of milk avoidance and its correlation with IM longitudinal changes.Methods: A prospective observational study of infants aged ≤6 months with a diagnosis of FPIAP. After 3 months of management according to a clinical algorithm, infants were subjected to a milk challenge using either a cow (CM) or a goat (GM) milk formula in a random order. Stool samples were collected longitudinally for microbiome analysis.Results: Out of 61 infants, 57 were challenged (29 with CM, 28 with GM). Of these, 55 (96.5%) achieved tolerance, with no difference in tolerance rates between CM (28/29) and GM (27/28). The average age of tolerance development was 6.3 months. Enterobacteriaceae clusters (Klebsiella‐ and Shigella‐dominated) were most often represented in samples from symptomatic infants. In contrast, Bacteroides and Bifidobacteria clusters emerged later, in apparently healthy infants.Conclusion: A 3‐month intervention was sufficient for almost all infants to achieve tolerance. GM was tolerated equally well to CM. Symptomatic FPIAP is associated with immature enterotypes, while disease remission coincides with microbiome changes in time.

Background: Immunoglobulin-E(IgE)-mediated hypersensitivity to cow’s milk allergens is a frequent cause of severe and life-threatening anaphylactic reactions. Besides case histories and controlled food challenges, the detection of the IgE antibodies specific to cow’s milk allergens is important for the diagnosis of cow-milk-specific IgE sensitization. Cow´s milk allergen molecules provide useful information for the refined detection of cow-milk-specific IgE sensitization. Methods: A micro-array based on ImmunoCAP ISAC technology was developed and designated milk allergen micro-array (MAMA), containing a complete panel of purified natural and recombinant cow’s milk allergens (caseins, α-lactalbumin, β-lactoglobulin, bovine serum albumin-BSA and lactoferrin), recombinant BSA fragments, and α-casein-, α-lactalbumin- and β-lactoglobulin-derived synthetic peptides. Sera from 80 children with confirmed symptoms related to cow’s milk intake (without anaphylaxis: n = 39; anaphylaxis with a Sampson grade of 1–3: n = 21; and anaphylaxis with a Sampson grade of 4–5: n = 20) were studied. The alterations in the specific IgE levels were analyzed in a subgroup of eleven patients, i.e., five who did not and six who did acquire natural tolerance. Results: The use of MAMA allowed a component-resolved diagnosis of IgE sensitization in each of the children suffering from cow’s-milk-related anaphylaxis according to Sampson grades 1–5 requiring only 20–30 microliters of serum. IgE sensitization to caseins and casein-derived peptides was found in each of the children with Sampson grades of 4–5. Among the grade 1–3 patients, nine patients showed negative reactivity to caseins but showed IgE reactivity to alpha-lactalbumin (n = 7) or beta-lactoglobulin (n = 2). For certain children, an IgE sensitization to cryptic peptide epitopes without detectable allergen-specific IgE was found. Twenty-four children with cow-milk-specific anaphylaxis showed additional IgE sensitizations to BSA, but they were all sensitized to either caseins, alpha-lactalbumin, or beta-lactoglobulin. A total of 17 of the 39 children without anaphylaxis lacked specific IgE reactivity to any of the tested components. The children developing tolerance showed a reduction in allergen and/or peptide-specific IgE levels, whereas those remaining sensitive did not. Conclusions: The use of MAMA allows for the detection, using only a few microliters of serum, of IgE sensitization to multiple cow’s milk allergens and allergen-derived peptides in cow-milk-allergic children with cow-milk-related anaphylaxis.

Water is a vital nutrient with innumerable functions for every living cell. The functions of human skin include protection against dehydration of the body. Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease that presents with dry skin, erythematous and eczematous lesions, and lichenification. This paper discusses the question of whether extra water intake in children with AD affects skin hydration and the skin barrier function. Among the methods used to treat dry skin, topical leave-on products are the first-line treatment, intended to improve hydration and the skin barrier function. The effectiveness of adequate water intake as a measure to treat dry skin is still under debate. Normal skin hydration increases with dietary water intake, particularly in those with prior lower water consumption. Skin dryness in AD is instrumental to the itch and inflammation cycle, contributing to barrier impairment and aggravating disease severity and flares. Certain emollients provide significant hydration to AD skin, with relief of dryness and reduction in barrier impairment, disease severity, and flares. Further investigations are needed to evaluate the optimum water intake levels in children with AD, as important questions remain unanswered, namely, does oral hydration provide relief of skin dryness and reduce barrier impairment, disease severity, and flares; is there any additional benefit from using mineral or thermal spring water; or is there a need to specifically study the fluid/water intake in children with AD and food allergy (FA) restrictions?