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Objective: The self-administered Food Allergy Quality of Life Questionnaire-Child Form (FAQLQ-CF), -Teenager Form (FAQLQ-TF) and -Adult Form (FAQLQ-AF) were recently developed within EuroPrevall, a multi-centred study of food allergy in Europe. The primary aim of this study was to evaluate the test-retest reliability of the FAQLQ-CF, -TF and -AF.Methods: One hundred and one Dutch patients (31 children, 34 adolescents and 36 adults) completed the FAQLQ twice with a 10-14 day interval. The intraclass correlation coefficient (ICC), Lin's concordance correlation coefficient (CCC) and Bland-Altman plots were used to assess test-retest reliability.Results: Test-retest reliability was excellent with ICCs and CCCs above 0.907, 0.975 and 0.951 for the FAQLQ-CF, -TF and -AF, respectively. Bland-Altman plots showed that the mean differences of the test and re-test were all close to zero for the FAQLQs.Conclusions: The FAQLQs are reliable over a short time interval. The FAQLQs are not only excellent tools for group comparison studies, but also for monitoring individual patients. [ABSTRACT FROM AUTHOR]

Background: Precautionary Allergen ("may contain") Labelling (PAL) is used by industry to communicate potential risk to food-allergic individuals posed by unintended allergen presence (UAP). In 2014, the World Allergy Organization (WAO) highlighted that PAL use was increasing, but often applied inconsistently and without regulation - which reduces its usefulness to consumers with food allergy and those purchasing food for them. WAO proposed the need for a regulated, international framework to underpin application of PAL. In 2019, the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) of the United Nations convened an expert consultation to address the issue of PAL, the outputs of which are now being considered by the Codex Committee on Food Labelling (CCFL)., Objectives: To summarise the latest data to inform the application of PAL in a more systematic way, for implementation into global food standards., Methods: A non-systematic review of issues surrounding precautionary labelling and food allergens in pre-packaged products., Results: Approximately, 100 countries around the world have legislation on the declaration of allergenic ingredients. Just a few have legislation on UAP. Given the risks that UAP entails, non-regulated PAL creates inconvenience in real life due to its unequal, difficult interpretation by patients. The attempts made so far to rationalize PAL present lights and shadows., Conclusions: At a time when CCFL is considering the results of the FAO/WHO Expert Consultation 2020-2023, we summarise the prospects to develop an effective and homogeneous legislation at a global level, and the areas of uncertainty that might hinder international agreement on a regulated framework for PAL of food allergens., Competing Interests: Paul J Turner: Grants from UK Medical Research Council, UK Food Standards Agency, JM Charitable Foundation, NIHR/Imperial Biomedical Research Centre and End Allergies Together, outside the submitted work; personal fees from UK Food Standards Agency, DBV Technologies, Aimmune Therapeutics, Allergenis and ILSI Europe outside the submitted work. Antonio Bognanni: No conflicts to disclose. Stefania Arasi: Advisory board member, consultant, and/or speaker for Novartis, DBV, Ferrero, and Ulrich outside the submitted work. Ignacio J Ansotegui: Advisory board member, consultant, and/or speaker for Bayer, Bial, Cipla, Eurodrug, Faes Farma, Gebro, Glenmark, Menarini, MSD, Roxall and Sanofi outside the submitted work. Sabine Schnadt: Speaker honoraria and advisory panel consultancy outside the submitted work for Aimmune and DBV. Sébastien La Vieille: Employment: Health Canada (Government of Canada) - no conflict of interest. Jonathan O’B Hourihane: Research funding from Johnson& Johnson, DBV Technologies; Travel support Stallergenes; Speaker fees Nutricia; Consultancy Camallergy, Stallergenes; Board membership Clemens von Pirquet Foundation and Irish Food Allergy Network. Torsten Zuberbier: Institutional funding for research and/or honoria for lectures and/or consulting from Amgen, AstraZeneca, AbbVie, ALK, Almirall, Astellas, Bayer Health Care, Bencard, Berlin Chemie, FAES, HAL, Henkel, Kryolan, Leti, L'Oreal, Meda, Menarini, Merck, MSD, Novartis, Pfizer, Sanofi, Stallergenes, Takeda, Teva and UCB, Uriach; in addition, he is a member of ARIA, DGAKI, ECARF, GA2LEN and WAO. Philippe Eigenmann: Speaker and advisory board honoraria: DBV technologies, Novartis, ThermoFisher Scientific, Nestlé Health Sciences, Synlab, GSK,; Stocks and Stock options: DBV technologies. Motohiro Ebisawa: No conflicts to disclose. Mario Morais-Almeida: No conflicts to disclose. Julie Barnett: Funded research from Food Standards Agency, UK. Member of Food Standards Agency Advisory Committee for Social Science. Bryan Martin: No conflicts to disclose. Linda Monaci: Speaker honoraria and funded research project by Ferrero outside the submitted work. Graham Roberts: No conflicts to disclose. Gary Wong: Advisory panel consultancy outside the submitted work for Haleon, Nestle, Novartis, OM Pharma, Ferrero. Ruchi Gupta: Research support from the National Institutes of Health (NIH) (R21 ID # AI135705, R01 ID # AI130348, U01 ID # AI138907), Food Allergy Research & Education (FARE), Melchiorre Family Foundation, Sunshine Charitable Foundation, Novartis, and Genentech. Medical consultant/advisor for Genentech, Novartis, Food Allergy Research & Education (FARE), OWYN, Kaléo, Aquestive Therapeutics, and Byrn Pharma. Ownership interest in Yobee Care, Inc. Sophia Tsabouri: No conflicts to disclose. Clare Mills: No conflicts to disclose. Simon Brooke-Taylor: Consults to and receives payment from the Allergen Bureau of Australia & New Zealand. Consults on food regulation and compliance with Australian and New Zealand food standards to the food industry. Joan Bartra: Speaker honoraria outside the submitted work for Thermo Fisher Scientific, Novartis, Menarini. Michael Levin: Speaker honoraria and advisory panel consultancy outside the submitted work for Viatris, Novartis, Organon, Sanofi, Pfizer. Marion Groetch: No commercial interests to disclose. Royalties from UpToDate and Academy of Nutrition and Dietetics and consulting fees from Food Allergy Research Education; serves on the Medical Advisory Board of IFPIES, as a Senior Advisor to FARE, as a Health Sciences Advisor for APFED. Luciana Tanno: Speaker honoraria of Sanofi, DBV Technologies, Research grant from ANS (Agence Numerique de Santé), AllerGos. Elham Hossny: No conflicts to disclose. Barbara Ballmer Weber: Speaker honoraria and advisory panel consultancy outside the submitted work for Thermo Fisher Scientific, Novartis, ALK, Allergopharma, Menarini, Sanofi, MSD, Aiummune. Vincenzo Fierro: Speaker honoraria for Stallergenes, Sanofi, GSK. Benjamin C Remington: No conflicts to disclose. Jennifer Gerdts: Food Allergy Canada receives unrestricted funding support for educational programming from Pfizer, DBV, Sanofi, American Peanut Council and consultant fees from Novartis. M Hazel Gowland: Speaker honoraria: Food industry, technical and regulatory conferences, academic lecture fees Advisory panel consultancy: UK Food Standards Agency, Safefood, industry food technical and public health organisations. Funded research: FSA, UKRI, Safefood funded studies, UK Fatal Anaphylaxis Registry. Derek Chu: No conflicts to disclose. Marjan Van Ravenhorst: Employee, Allergenen Consultancy BV. Jennifer Koplin: No conflicts to disclose. Alessandro Fiocchi: Speaker honoraria and advisory panel consultancy outside the submitted work for Nutricia, Abbott, Danone, Stallergenes, DBV, Novartis. Funded research (Institution) from Sanofi, Novartis, Ferrero, DBV, GSK, Astrazeneca, Hipp GmBDH, Humana SpA., (© 2024 The Authors.)

Background: The Short-Term Topical Application for Prevention of Atopic Dermatitis (STOP AD) study, a randomized, open-label trial evaluating the effect of short-term (from the first 4 postnatal days to age 8 weeks) skin barrier protection using Aveeno Dermexa Fast & Long-Lasting Balm (Johnson & Johnson, New Brunswick, NJ) in infants with a parent with allergic disease, demonstrated decreased cumulative incidence and decreased prevalence of atopic dermatitis (AD) at age 12 months., Objective: In the STOP AD study, we aimed to identify skin biomarkers that are associated with risk of development of AD., Methods: Skin swabs were collected from the cheek and antecubital fossa (AF) at baseline, age 8 weeks, and age 12 months from subsets of study participants from the intervention arm (n = 43 of 119) and control arm (n = 43 of 138) and were analyzed for specific cytokines (CCL27, CXCL2, human β-defensin-1 [hBD-1], IL-18, IL-8, IL-1α, IL-1 receptor antagonist [IL-1RA], IL-1β, S100A8/9, and IL-36γ) by ELISA., Results: Higher titers of S100A8/9 at the AF at age 8 weeks in infants with the filaggrin wild-type genotype (FLGwt), but not in those with filaggrin loss-of-function mutation (FLGmut), predicted (1) development of AD in the first year of life (P = .033), (2) presence of AD at ages 6 or 12 months (P = .009 and .035, respectively), (3) persistence of AD between ages 6 and 12 months (P < .001), and (4) development of AD with the emollient intervention., Conclusion: Increased titers of S100A8/9 from skin swabs of the AF in high-risk infants at age 8 weeks with FLGwt were predictive of AD development in the first year of life and other AD features. These findings suggest that there are different molecular pathways leading to AD in individuals with FLGmut and in individuals with FLGwt. Early identification of infants who are likely to develop AD will allow more targeted interventions., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Invasive bacterial disease is associated with significant morbidity and mortality. In winter 2022, there was an apparent increased rate of invasive bacterial disease compared to preceding years. Cross-site retrospective analysis of the three Children's Health Ireland (CHI) hospitals looking at children admitted between 1st October 2022-31st December 2022 (Q4) with community-acquired invasive bacterial disease, defined as an abscess in a normally sterile site in the head, neck and chest or isolation or PCR detection of Streptococcus pneumoniae, Neisseria meningitidis, Streptococcus pyogenes (Group A streptococcus) or Haemophilus influenzae from a normally sterile site. Case numbers were compared to Q4 in each of 2018-2021. Eighty-two children met the case definition in Q4 2022 vs 97 (Q4 2018-2021). In 2022, 42/82 (51%) were female, median age 3.75 years (1.5-8.25 years). Only 2 (2%) were immunosuppressed and 2 others (2%) had underlying neurodisability. Fifty (61%) were admitted on second or subsequent presentation to a healthcare setting. Fifty-six (68%) had an abscess in a sterile site. Bloodstream infection (positive blood culture or PCR: 24 (29%)) was the most common site of infection, followed by neck 22 (27%) and intracranial 12 (15%). Group A streptococcus (GAS) 27 (33%) was the most common organism isolated. Seven cases (9%) died in 2022 compared to 2 patients (2%) from 2018 to 2021 (p < 0.05). More children had Paediatric Overall Performance Category (POPC) scores > 1 in 2022 than 2018-2021 (p = 0.003).  Conclusion: Invasive bacterial diseases increased in Q4 2022 with higher morbidity and mortality than in the preceding 4 years. Group A streptococcal infection was the most significant organism in 2022. What is known: • Invasive bacterial disease is the leading cause of childhood mortality globally. • There was an increase in cases of invasive Group A streptococcus infections reported in many countries (including Ireland) during the winter of 2022/23. What is new: • Head, neck and chest abscesses increased in Q4 of 2022 compared to the previous 4 years combined. • Invasive bacterial infections in Q4 of 2022 were associated with higher rates of mortality (9%), paediatric intensive care unit (PICU) admission (24%) and requirement for surgical drainage or intervention (67%) than in the preceding years., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: The CORAL study is a cohort of infants born during the first weeks of the first SARS-CoV-2 (COVID-19) lockdown. This cohort has had lower antibiotic exposure, higher breastfeeding rates and lower infection rates, especially in the first year of life. We hypothesized that the altered early-life environment of infants born during lockdown would change the incidence of allergic conditions., Methods: This longitudinal, observational study followed 365 infants born between March and May 2020 from enrolment to the age of 2 years. Infants attended three research appointments at 6-, 12-, and 24-months and completed detailed questionnaires. At research appointments, children had skin prick testing, and atopic dermatitis (AD) assessment. Statistical analysis focused on changes within the group at different time points, the influence of specific environmental factors on allergic risk and compared the incidence of atopic conditions with a pre-pandemic Irish infant cohort, BASELINE., Results: AD was more common in CORAL group at both 12 (26.5% vs. 15.5%; p < .001) and 24 months (21.3% vs. 15.9%; p = .02) compared with pre-pandemic BASELINE cohort. Within the CORAL group, those with AD at both 12- and 24-month appointments had a more severe AD phenotype associated with a higher risk of allergic sensitization. There was less milk (0% vs. 1%; p = .09), peanut (0.6% vs. 1.8%; p = .3), and egg allergy (0% vs. 2.9%; p < .001) in the CORAL group at 24 months compared with the BASELINE cohort. Aeroallergen sensitization increased between 12 and 24 months in the CORAL cohort (1.5% vs. 8.9%; p < .001), as did parent-reported wheezing episodes (9% vs. 24%; p < .001)., Conclusions: Despite higher AD incidence in the CORAL cohort, the incidence of food sensitization and allergy are lower than expected pre-pandemic rates possibly reflecting the early introduction and maintenance of dietary allergens enhanced by changes in infant infections, antibiotic use, and breastfeeding in the first 2 years of life in the group. These beneficial effects of the lockdown could be outweighing the expected risk of less early-life microbial encounters outlined by the hygiene hypothesis., (© 2023 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Background: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown., Methods: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo., Results: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group., Conclusions: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.)., (Copyright © 2023 Massachusetts Medical Society.)

In most countries, the use of precautionary allergen labeling (PAL) is not governed by regulation. PAL was initially identified as a judicious risk management measure to address instances of "unavoidable" cross-contact with priority food allergens during food processing. However, PAL has gradually been devalued in part due to overuse and inconsistent application by the food industry. Currently, most food products do not contain detectable allergen residue or contain only low concentrations of residue of the allergens declared using PAL; however, occasionally, high concentrations of allergen residue are reported, rendering it an ineffective risk communication tool for allergic consumers. In this context, several reasons exist that make the consumption of products bearing a PAL statement not advisable for people with food allergies. The main reason is that the risk is generally not correlated with the statement used by manufacturers. Because of the increased use of PAL on prepackaged food products, and to maximize food choices for allergic individuals, health care professionals increasingly advise some patients considered to be "not highly allergic" to consume products bearing a PAL statement. This article explains why the consumption of products with PAL is not advisable without having a full clinical evaluation and knowledge that an allergen risk assessment has been conducted. It also discusses the perspectives for a better use of PAL on the basis of the recent Food and Agricultural Organization/World Health Organization recommendations on food allergens., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Protecting the skin barrier in early infancy may prevent atopic dermatitis (AD). We investigated if daily emollient use from birth to 2 months reduced AD incidence in high-risk infants at 12 months., Methods: This was a single-center, two-armed, investigator-blinded, randomized controlled clinical trial (NCT03871998). Term infants identified as high risk for AD (parental history of AD, asthma or allergic rhinitis) were recruited within 4 days of birth and randomised 1:1 to either twice-daily emollient application for the first 8 weeks of life (intervention group), using an emollient specifically formulated for very dry, AD-prone skin, or to standard routine skin care (control group). The primary outcome was cumulative AD incidence at 12 months. AD <6 months was diagnosed based on clinical presence of AD. The UK Working Party Diagnostic Criteria were applied when diagnosing AD between 6 and 12 months., Results: Three hundred twenty-one were randomised (161 intervention and 160 control), with 61 withdrawals (41 intervention, 20 control). The cumulative incidence of AD at 12 months was 32.8% in the intervention group vs. 46.4% in the control group, p = 0.036 [Relative risk (95%CI): 0.707 (0.516, 0.965)]. One infant in the intervention group was withdrawn from the study following development of a rash that had a potential relationship with the emollient. There was no significant difference in the incidence of skin infections between the intervention and control groups during the intervention period (5.0% vs. 5.7%, p > 0.05)., Conclusions: This study has demonstrated that early initiation of daily specialized emollient use until 2 months reduces the incidence of AD in the first year of life in high-risk infants., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Clinical trials (PALISADE [ARC003], ARTEMIS [ARC010]) proving efficacy and safety of peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) have used double-blind, placebo-controlled food challenges (DBPCFCs) to screen for eligibility and to evaluate efficacy. In routine clinical practice, individuals with peanut allergy do not always undergo food challenges to confirm diagnosis or determine candidacy for treatment., Objective: To describe PTAH safety and tolerability in participants selected by clinical history and peanut sensitization parameters not undergoing DBPCFCs during trials and to compare findings with previously published data., Methods: RAMSES (ARC007) was a 6-month, phase 3, randomized, double-blind, placebo-controlled trial in children aged 4 to 17 years with physician-confirmed peanut allergy. ARC011 was the subsequent 6-month follow-on maintenance PTAH study. The primary end point for RAMSES and ARC011 was the frequency of treatment-emergent adverse events (AEs). We descriptively compared baseline characteristics and safety outcomes from RAMSES and ARC011 to participants undergoing DBPCFCs in phase 3 PALISADE and ARTEMIS trials., Results: In 506 patients randomized to study treatment, baseline characteristics appeared balanced among groups. Proportion of participants with at least 1 AE was 55% for PTAH vs 33.9% for placebo during initial dose escalation and 98.8% vs 94.0% during updosing, respectively. Most participants with AEs had mild or moderate events. The most common AEs were gastrointestinal. Comparisons to pooled PALISADE and ARTEMIS data revealed higher baseline median peanut-specific immunoglobulin E and skin prick test values for RAMSES participants. Safety outcomes during trial periods were comparable., Conclusion: Safety data from clinically selected children with peanut allergy receiving PTAH do not seem different from those in phase 3 trials requiring DBPCFC to enter trials., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cow's milk protein allergy (CMPA) is one of the most common food allergies in infancy. Most infants with CMPA tolerate baked milk from diagnosis and gradually acquire increased tolerance. Nevertheless, parents often display significant anxiety about this condition and a corresponding reluctance to progress with home introduction of dairy due to concerns about possible allergic reactions., Objective: To evaluate the impact on gradual home introduction of foods containing cows' milk after a supervised, single low-dose exposure to whole milk at time of diagnosis., Methods: Infants less than 12 months old referred with suspected IgE-mediated cow's milk allergy were recruited to an open-label randomized, controlled trial of intervention-a single dose of fresh cow's milk, using the validated dose of milk that would elicit reactions in 5% of CMPA subjects-the ED 05 - vs routine care. Both groups implemented graded exposure to CM (using the 12 step MAP Milk Tolerance Induction Ladder), at home. Parents completed food allergy quality of life questionnaires and State and Trait Anxiety Inventories (STAI). Main outcome measures were milk ladder position at 6 months and 12 months post-randomization., Results: Sixty patients were recruited, 57 (95%) were followed to 6 months. By 6 months, 27/37 (73%) intervention subjects had reached step 6 or above on the milk ladder compared to 10/20 (50%) control subjects (p = .048). By 6 months, 11/37 (30%) intervention subjects had reached step 12 (i.e. drinking unheated cow's milk) compared to 2/20 (10%) of the controls (p = .049). Twelve months post-randomization, 31/36(86%) of the intervention group and 15/19(79%) of the control group were on step 6 or above. However, 24/37 (65%) of the intervention group were at step 12 compared to 7/20 (35%) of the control group (p = .03). Maternal STAIs were significantly associated with their infants' progress on the milk ladder and with changes in skin prick test and spIgE levels at 6 and 12 months., Conclusion: This study demonstrates the safety and effectiveness of introduction of baked milk implemented immediately after diagnosis of cows' milk allergy in a very young cohort. A supervised single dose of milk at the ED 05  significantly accelerates this further, probably by giving parents the confidence to proceed. Maternal anxiety generally reflects infants' progress towards completion of the milk ladder, but pre-existing high levels of maternal anxiety are associated with poorer progress., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) is a commonly used patient-reported outcome measure in food allergy (FA) research. It was developed before FA treatment clinical trials were commonplace and is used as a secondary outcome measure in pivotal FA treatment trials. We examined the psychometric properties of the FAQLQ-PF and its relevance to children with peanut allergy engaged in an epicutaneous immunotherapy (EPIT) clinical trial., Methods: Analysis was performed on 26 universally answered items of the FAQLQ-PF, from assessments undertaken during the phase 3 PEPITES study (baseline, Month 12), which examined the safety and efficacy of EPIT for children with peanut allergy aged 4-11 years. Item response theory (IRT) was used to assess psychometric parameters of the FAQLQ-PF (i.e., discrimination, difficulty, and information). Confirmatory factor analysis was also employed; reliability was assessed using McDonald's omega (ω) and Cronbach's alpha (α)., Results: A total of 23 of 26 items presented very high discrimination levels (>1.7), and all 26 fell within the recommended difficulty threshold (between -1.5 and 1.5). The items contributed a reasonable information level for their respective factors/subdomains. The measure also presented a marginally acceptable model fit for the 3-factor structure (e.g., comparative fit index = 0.88, Tucker-Lewis index = 0.87) and good reliability levels across time points (ω and α > 0.90)., Conclusions: Herein, we present a novel reanalysis of the FAQLQ-PF items using IRT. The longitudinal performance of individual items and subscales was corroborated, and items with the highest discrimination were identified, showing that the tool is suitable for longitudinal measurements in FA treatment trials., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions., Methods: Following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated., Results: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87-0.92, specificity 0.73-0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10 -6 -1.23 × 10 -3 ). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians., Conclusion: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The benefit of daily administration of Peanut (Arachis hypogaea) Allergen Powder-dnfp (PTAH)-formerly AR101-has been established in clinical trials, but limited data past the first year of treatment are available. This longitudinal analysis aimed to explore the impact of continued PTAH therapeutic maintenance dosing (300 mg/day) on efficacy, safety/tolerability, and food allergy-related quality of life., Methods: We present a subset analysis of PALISADE-ARC004 participants (aged 4-17 years) who received 300 mg PTAH daily for a total of ~1.5 (Group A, n = 110) or ~2 years (Group B, n = 32). Safety assessments included monitoring the incidence of adverse events (AEs), accidental exposures to food allergens, and adrenaline use. Efficacy was assessed by double-blind, placebo-controlled food challenge (DBPCFC); skin prick testing; peanut-specific antibody assays; and Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) scores., Results: Continued maintenance with PTAH increased participants' ability to tolerate peanut protein: 48.1% of completers in Group A (n = 50/104) and 80.8% in Group B (n = 21/26) tolerated 2000 mg peanut protein at exit DBPCFC without dose-limiting symptoms. Immune biomarkers showed a pattern consistent with treatment-induced desensitization. Among PTAH-continuing participants, the overall and treatment-related exposure-adjusted AE rate decreased throughout the intervention period in both groups. Clinically meaningful improvements in FAQLQ and FAIM scores over time suggest a potential link between increased desensitization as determined by the DBPCFC and improved quality of life., Conclusions: These results demonstrate that daily PTAH treatment for peanut allergy beyond 1 year leads to an improved safety/tolerability profile and continued clinical and immunological response., (© 2021 Aimmune Therapeutics. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Few patients with food allergy are "highly allergic," meaning they always have severe reactions and always react to very small amounts of allergen. Standard medical approaches for allergy management have focused on the safety and lifestyle modifications this group truly needs, but consequently families with food allergy are typically advised to strictly avoid any exposure to their implicated allergens. Most food-allergic subjects are actually not reactive to very low doses, and many never experience severe reactions. There are also notable conditions where a different care plan is already commonly offered: patients with pollen-related food allergy syndrome, with food-associated exercise-induced anaphylaxis, and with resolving or mild milk or egg allergy might be advised to ingest the allergens in specific circumstances with detailed instructions. Because oral immunotherapy and allergy prevention by early exposure have emphasized alternatives to strict avoidance, there is increasing interest in prospects to forego strict avoidance in those with food allergy. For patients with a high threshold of reactivity (low-dose tolerant, high-dose mildly reactive), there may be options such as allowing the ingestion of products with precautionary allergen labels, allowing dietary indiscretions with small amounts of the allergen, or even encouraging ingestion of subthreshold amounts with therapeutic intent. These practices have not been extensively studied and could be considered controversial. If these approaches are considered, shared decision making is needed in discussing them with patients and families. This review considers the potential approaches to those who are "not highly allergic": the risks, benefits, shared decision making, and research needs., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Internationally, the COVID-19 pandemic severely curtailed access to hospital facilities for those awaiting elective/semi-elective procedures. For allergic children in Ireland, already waiting up to 4 years for an elective oral food challenge (OFC), the restrictions signified indefinite delay. At the time of the initiative, there were approx 900 children on the Children's Health Ireland (CHI) waiting list. In July 2020, a project was facilitated by short-term (6 weeks) access to an empty COVID stepdown facility built, in a hotel conference centre, commandeered by the Health Service Executive (HSE), Ireland. The aim of this study was to achieve the rapid roll-out of an offsite OFC service, delivering high throughput of long waiting patients, while aligning with existing hospital policies and quality standards, international allergy guidelines and national social distancing standards., Methods: The working group engaged key stakeholders to rapidly develop an offsite OFC facility. Consultant paediatric allergists, consultant paediatricians, trainees and allergy clinical nurse specialists were seconded from other duties. The facility was already equipped with hospital beds, bedside monitors (BP, pulse and oxygen saturation) and bedside oxygen. All medication and supplies had to be brought from the base hospital. Daily onsite consultant anaesthetic cover was resourced and a resuscitation room equipped. Standardized food challenge protocols were created. Access to the onsite hotel chef facilitated food preparation. A risk register was established., Results: After 6 weeks of planning, the remote centre became operational on 7/9/2020, with the capacity of 27 OFC/day. 474 challenges were commenced: 465 (98%) were completed and 9 (2%) were inconclusive. 135 (29%) OFCs were positive, with 25 (5%) causing anaphylaxis. No child required advanced airway intervention. 8 children were transferred to the base hospital. The CHI allergy waiting list was reduced by almost 60% in only 24 days., Conclusions: Oral food challenges remain a vital tool in the care of allergic children, with their cost saving and quality-of-life benefits negatively affected by a delay in their delivery. This project has shown it is possible to have huge impacts on a waiting list efficiently, effectively and safely with good planning and staff buy-in-even in a pandemic. Adoption of new, flexible and efficient models of service delivery will be important for healthcare delivery in the post-COVID-19 era., (© 2021 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Competing Interests: The authors declare no conflict of interests.

Background: There is increasing interest in the use of eliciting doses (EDs) to inform allergen risk management. The ED can be estimated from the distribution of threshold doses for allergic subjects undergoing food challenges within a specified population. Estimated ED 05 values for cow's milk (the dose expected to cause objective allergic symptoms in 5% of the milk-allergic population) range from 0.5 mg to 13.9 mg cow's milk protein. We undertook a single-dose challenge study to validate a predicted ED 05 for cow's milk of 0.5 mg protein., Methods: Participants were recruited from 4 clinical centres. Predetermined criteria were used to identify patients reacting to 0.5 mg cow's milk protein (approximately 0.015 mL of fresh cow's milk). Children over 1 year underwent formal challenge to cow's milk to confirm clinical reactivity., Results: 172 children (median age 6.0 (IQR 0.7-11) years, 57% male) were included in this analysis. Twelve (7.0%, 95% CI 3.7%-11.9%) children experienced objective symptoms that met the predetermined criteria. One participant had mild anaphylaxis that responded to a single dose of adrenaline, the remainder experienced only mild symptoms with no treatment required. We did not identify any baseline predictors of sensitization that were associated with objective reactivity to the single-dose challenge using 0.5 mg cow's milk protein., Conclusions: These data support an estimated ED 05 for cow's milk of 0.5 mg protein. Values for ED 05 above 0.5 mg for cow's milk protein proposed for allergen risk management need to be reviewed., (© 2021 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Risk is a concept inherent in every medical procedure. It can be defined as the probability of an adverse event in a defined population over a specified period of time. In the frame of food allergy management, it might be related to a diagnostic procedure, a treatment, or the consumption of foods. The risk of an adverse event can also be augmented by individual factors. This rostrum article discusses various aspects faced by children with food allergies in the light of risk, and their practical implications. Identifying personal risks for severe reaction, such as unstable asthma, and correcting them whenever possible also contribute to a reduction of the risk inherent to food allergy. Among the facets discussed, oral food challenges (OFC) are the most common diagnostic procedures implying an inherent risk. The risk of OFCs can be minimized by correct indication and timing of the test, a safe setting, as well as by ensuring that the patient is otherwise well without potential stressor potentially increasing the risk of a more severe reaction. Oral immunotherapy (OIT) has been studied as a potential treatment for increasing the threshold dose for reaction, and thus reducing the risk of accidental reaction. Nevertheless, the procedure is not devoid of risk as the patients may and do often react during the course of the procedure. Ingestion of trace amounts in processed foods, mainly in community settings such as restaurants, schools, or day care, represents a potential risk of reactions, although for a minority of patients. Precautionary allergen labeling (PAL) is a widespread strategy to reduce the potential risk of reactions due to traces. However, PAL is currently inefficient due to inconsistent labeling, also not indicating a clear maximum amount possibly present in the manufactured food. Finally, cost-effectiveness needs to be considered in risk management, as many risk reduction procedures are clearly not cost-effective., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Anaphylaxis is an immediate hypersensitivity reaction. However, a biphasic course with the second onset of symptoms can occur hours after the initial phase. Little is known about the causes of biphasic anaphylaxis making the identification of patients at risk difficult., Objective: To identify factors predisposing for biphasic anaphylaxis for the better understanding of these reactions., Methods: Data from the Anaphylaxis Registry (from 11 countries) including 8736 patients with monophasic and 435 biphasic anaphylaxis were analyzed., Results: The rate of biphasic reactions in this large cohort was 4.7%. The identified risk factors were reaction severity (grade III/IV vs grade II: odds ratio [OR] = 1.34; 95% confidence interval [CI]: 1.1-1.62); multiorgan involvement; skin, gastrointestinal, severe respiratory, and cardiac symptoms; anaphylaxis caused by peanut/tree nut (OR = 1.78; 95% CI: 1.38-2.23) or an unknown elicitor (OR = 1.96; 95% CI: 1.41-2.72); exercise as a cofactor (OR = 1.44; 95% CI: 1.17-1.78); chronic urticaria as a comorbidity (OR = 2.12; 95% CI: 1.19-3.78); a prolonged interval between the contact with the elicitor and start of primary symptoms (OR for >30 vs <30 min: 1.38; 95% CI: 1.08-1.76); and antihistamine treatment (OR = 1.52; 95% CI: 1.14-2.02)., Conclusion: A biphasic course of anaphylaxis occurs more frequently in severely affected patients with multiorgan involvement. However, we identified multiple additional predictors, suggesting that the pathogenesis of biphasic reactions is more complex than being a rebound of a severe primary reaction., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The PEPITES (Peanut EPIT Efficacy and Safety) trial, a 12-month randomized controlled study of children with peanut allergy and 4 to 11 years old, previously reported the safety and efficacy of epicutaneous immunotherapy (EPIT) for peanut allergy (250 μg, daily epicutaneous peanut protein; DBV712 250 μg)., Objective: We sought to assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) PEOPLE (PEPITES Open-Label Extension) study., Methods: Subjects who completed PEPITES were offered enrollment in PEOPLE. Following an additional 2 years of daily DBV712 250 μg, subjects who had received DBV712 250 μg in PEPITES underwent month-36 double-blind, placebo-controlled food challenge with an optional month-38 sustained unresponsiveness assessment., Results: Of 213 eligible subjects who had received DBV712 250 μg in PEPITES, 198 (93%) entered PEOPLE, of whom 141 (71%) had assessable double-blind, placebo-controlled food challenge at month 36. At month 36, 51.8% of subjects (73 of 141) reached an eliciting dose of ≥1000 mg, compared with 40.4% (57 of 141) at month 12; 75.9% (107 of 141) demonstrated increased eliciting dose compared with baseline; and 13.5% (19 of 141) tolerated the full double-blind, placebo-controlled food challenge of 5444 mg. Median cumulative reactive dose increased from 144 to 944 mg. Eighteen subjects underwent an optional sustained unresponsiveness assessment; 14 of those (77.8%) maintained an eliciting dose of ≥1000 mg at month 38. Local patch-site skin reactions were common but decreased over time. There was no treatment-related epinephrine use in years 2 or 3. Compliance was high (96.9%), and withdrawals due to treatment-related adverse events were low (1%)., Conclusions: These results demonstrate that daily EPIT treatment for peanut allergy beyond 1 year leads to continued response from a well-tolerated, simple-to-use regimen., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Carriers of loss-of-function mutations in the filaggrin gene (LoF FLG) have less natural moisturizing factor (NMF) in their stratum corneum (SC) and an increased risk of atopic dermatitis (AD). Natural moisturizing factor can be measured noninvasively by Raman spectroscopy. The use of Raman-derived NMF at birth to screen for FLG genotype could inform targeted AD prevention, but values in neonatal populations are largely unexplored., Objective: To examine the associations between Raman-derived neonatal NMF measurements and FLG genotype., Methods: Natural moisturizing factor was measured by Raman spectroscopy in the SC of the thenar eminence within 4 days of birth in 139 term neonates. Filaggrin genotyping was performed for 117 neonates (84%)., Results: The mean (SD) NMF was 0.37 (0.11) g/g protein, with values increasing across the first 3 days (day 1 vs 3: 0.29 [0.09] vs 0.43 [0.08, P < .001]). Twelve infants (10.3%) were carriers of LoF FLG, all heterozygous. Natural moisturizing factor was lower in LoF FLG carriers compared with wild-type (0.27 [0.08] vs 0.38 [0.11] g/g protein, P ≤ .001). Natural moisturizing factor had good discriminatory power for FLG genotype (area under the receiver operating curve [AUROC]: 0.79; 95% CI: 0.66, 0.91; P ≤ .001). This improved after correcting day 1 and 2 measurements to day 3 (AUROC: 0.83; 95% CI: 0.75, 0.92; P < .001)., Conclusion: This study suggests that Raman-derived NMF measured in the early postnatal period may have the potential to classify by FLG genotype. The full translational value of this needs to be determined., (Copyright © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Patients with a history of anaphylaxis are at risk of future anaphylactic reactions. Thus, secondary prevention measures are recommended for these patients to prevent or attenuate the next reaction., Methods: Data from the Anaphylaxis Registry were analyzed to identify secondary prevention measures offered to patients who experienced anaphylaxis. Our analysis included 7788 cases from 10 European countries and Brazil., Results: The secondary prevention measures offered varied across the elicitors. A remarkable discrepancy was observed between prevention measures offered in specialized allergy centers (84% of patients were prescribed adrenaline autoinjectors following EAACI guidelines) and outside the centers: Here, EAACI guideline adherence was only 37%. In the multivariate analysis, the elicitor of the reaction, age of the patient, mastocytosis as comorbidity, severity of the reaction, and reimbursement/availability of the autoinjector influence physician's decision to prescribe one., Conclusions: Based on the low implementation of guidelines concerning secondary prevention measures outside of specialized allergy centers, our findings highlight the importance of these specialized centers and the requirement of better education for primary healthcare and emergency physicians., (© 2019 The Authors. Allergy published by John Wiley & Sons Ltd.)