Background: The Food and Agriculture Organization (FAO) of the United Nations and the World Health Organization (WHO) recently convened an expert consultation to address the increasing but inconsistent use of Precautionary Allergen (“may contain”) Labelling (PAL). Objectives: We conducted a Delphi study to explore the perspectives of clinicians, patient representatives, and other interest-holders on PAL practice. Methods: We followed previous guidance on Delphi study development and reporting. A narrative review exploring the FAO/WHO Expert Consultation informed the Delphi process. The working group generated 35 items based on the review of FAO/WHO consultation, categorized into 7 domains: (i) Importance of the issue, (ii) Informing use of PAL, (iii) Action level cut-offs, (iv) Communication, (v) Liability considerations, (vi) Free From statements, and (vii) Areas for further research. Items underwent 3 iterative Delphi rounds involving a panel of 35 experts who rated their agreement narratively and on a 5-point Likert scale. Consensus was defined as ≥70% consistency in agreement or disagreement (excluding neutral responses); stability was defined as <10% variation in average scores across rounds. A public consultation was held to collect different viewpoints arising from the consensus activity. Results: The Delphi was concluded after 3 rounds with consensus achieved for 33/35 items. Response rate was 100% across all 3 rounds. The panel strongly agreed that PAL should only be applied when an unintended allergen may be present above a cut-off (action level) and that it should always be based on a formal risk assessment, preferably quantitative, and mandated through legislation. Furthermore, action levels should be based on “reference doses” (amount of total allergenic protein), rather than on a concentration (eg, 10 ppm), and more specifically on population-adjusted eliciting doses ED05 (amount of allergen expected to elicit an objective reaction in no more than 5% of the allergic population). To achieve a balance between protection and the risk of PAL overuse, ED05 was deemed preferable to ED01. There was 70% agreement that consumers should be informed of residual risk (ie, unintended allergen presence below the reference dose), but no consensus as to how this might be done. Finally, PAL should not be used for an allergen declared to be absent with a “free from” statement, nor should a PAL appear for an allergen listed as an ingredient. Conclusions: This Delphi explored a comprehensive set of statements across multiple aspects of PAL development, application, and communication. On the one hand, it provides systematically derived considerations, aligned with the FAO/WHO consultation recommendations, to support future harmonization of practices. On the other, it highlights several areas of uncertainty to prioritize for future research.

"Primary Atopic Disorders (PAD) are a recently recognized group of inborn errors of immunity characterized by severe allergic manifestations. Due to their overlapping features with common atopic diseases, PAD diagnosis is often delayed. This consensus provides a standardized work-up and a core set of clinical and laboratory red flags to differentiate PAD from polygenic multifactorial allergic conditions."

Pediatric immunological and allergic conditions represent a broad spectrum, ranging from highly prevalent polygenic disorders (e.g., food allergy, atopic dermatitis, asthma, and allergic rhinitis) to rarer monogenic primary atopic disorders. The management of these conditions has undergone a paradigm shift in recent years. Moving away from a "one-size-fits-all" approach, precision medicine aims to deliver the right treatment to the right patient at the right time. By integrating clinical phenotypes with molecular endotypes and using specific biomarkers and "Omics" techniques, scientists and clinicians can now employ targeted biological therapies that significantly improve patient outcomes. By identifying early therapeutic windows and specific biomarkers, pediatric specialists can implement personalized interventions that halt the atopic march and mitigate the global burden of chronic allergic diseases. By shifting the focus from symptom management to the neutralization of specific molecular pathways, it is now possible to achieve better disease control, reduce side effects associated with broad-spectrum treatments such as systemic corticosteroids, and improve the quality of life for patients with refractory allergic diseases. This review, generated during a seminar funded by the Clemens von Pirquet Foundation, aims to delineate the "rare to common" pipeline, illustrating how precision medicine tools, including multi-omics, biomarkers, and artificial intelligence methods, can connect mechanistic pathways across the immunological spectrum.

BACKGROUND:Food allergy (FA) is one of the most common chronic conditions in children. Diagnostic delays and errors in FA are relevant problems in clinical practice. Non-invasive and accessible tools for FA diagnosis are highly required. We aimed to develop an easy-to-use clinical score to facilitate the diagnostic approach for pediatric FA (i.e. the NAPFA score). METHODS:Subjects with suspected FA aged 0-14 years were prospectively evaluated at a tertiary center for pediatric allergy, gastroenterology, and nutrition. Upon completing the diagnostic workup, the subjects were diagnosed with FA based on the oral food challenge result, or with other conditions. Bootstrapped multivariable logistic regression was employed to construct two models that estimate the probability of having FA, one (M1) without the results of the allergy screening tests, while the other (M2) including them. RESULTS:Six hundred and twenty-seven pediatric subjects were included in the study. The median (interquartile interval) age at symptom onset was 8 (3;27) months. M1 employed the following predictors: sex, age at symptoms onset, cesarean delivery, occurrence of atopic dermatitis before FA onset, first degree family members with allergy, symptoms occurrence after ingestion of specific food, and skin, gastrointestinal, respiratory, and systemic symptoms. M2 replaced the occurrence of symptoms after ingestion of specific food with the results of allergy tests. The c-statistic was 0.915 (95% bootstrapped CI: 0.895-0.937) for M1 and 0.977 (95% CI: 0.969-0.992) for M2. Both models demonstrated good internal calibration and a favorable decision analysis curve. CONCLUSION:The NAPFA score could be an easy-to-use tool holding the potential to streamline the FA diagnostic process in pediatric age, reducing unnecessary testing, and improving patient outcomes in a variety of healthcare settings. Its external validation will possibly enable a standardized approach for identifying children with FA.

The trajectories of allergic diseases represent one of the most currently debated topics both when referred to childhood and likewise adulthood. Data from cohorts show their heterogeneity as well as the key role of genetic and environmental factors. More insight has been recently provided in the pathophysiological mechanisms underlying the development and amplification of T2 (hyper)inflammation. Recent data support the hypothesis of associated allergic diseases (multimorbidity) reflecting, at a given time and in given organ(s)/tissue(s), the expression of the same favorable predisposition. In particular, the impairment of the epithelial barrier, especially in subjects genetically predisposed, and the dysregulation of the host's microbiome promote the onset of allergic diseases and multimorbidity, their persistence and/or severity. These findings challenge the classical theory of the atopic march with a temporal sequence characterized by the transition from one disease (eczema) to another (food allergy, airway allergic diseases). A better understanding of the diversity of disease trajectories and the underpinning mechanisms is crucial for prevention and identification of children at risk of a "unfavorable trajectory" (early intervention, i.e., early primary or secondary prevention), for a personalized therapeutic approach based on identification of specific endotypes, and, therefore, addressing specific pathophysiological pathways (treat to target strategies). In the perspective of the so-called "remission" and "treatment-induced-remission", the whole spectrum of the long-term consequences of the disease(s) including their treatment has to be considered. The concept of disease modifying treatment able to interfere with their trajectories and overall long-term induced morbidity is emerging.

The pathophysiology of atopic dermatitis (AD) involves cutaneous inflammation, predominantly mediated by innate immunity and T cells, in which IgE has a marginal role in most patients. Over previous decades, however, there has been an ongoing debate regarding the relevance of IgE-mediated allergy testing in patients with AD. Patients with AD have a defective skin barrier that facilitates a high inflammatory response to environmental antigens, placing them at greater risk for food allergies. Nevertheless, because these patients often produce high levels of IgE, the positive predictive value of skin prick tests and specific IgE measurements is low; such tests should be performed only when there is a concordant immediate hypersensitivity reaction (ie, urticaria or angioedema) rather than eczema. In recent years, numerous studies have emphasized the importance of maintaining oral exposure to foods to prevent the development or progression of food allergies in atopic patients. Although it is acknowledged that food allergens may contribute to AD in certain cases, it is critical that patients understand the risk of developing IgE-mediated food allergies if they exclude allergenic foods from the diet. Ultimately, controlling AD while retaining these foods in the diet should be the goal for all patients.