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Anaphylaxis is an acute, potentially fatal, systemic hypersensitivity reaction that warrants prompt diagnosis and management. It continues to be challenging to anticipate who may be at risk of a severe, life-threatening allergic reaction. Anaphylaxis can be caused by a range of allergens, such as certain foods, medications, latex, insect stings, etc. Cofactors that augment the severity of clinical symptoms and increase the risk of poor outcomes include exercise, stress, infectious diseases, underlying mast cell disease, active allergic disease such as asthma, advanced age, intake of certain medications, history of previous anaphylaxis, and delayed or missed administration of adrenaline. According to the European Anaphylaxis Registry, food is the major elicitor of anaphylaxis, especially eggs, cow milk, and nuts, in children and adolescents. Reaction to insect venom has also been noted in young adulthood. Early recognition of signs and symptoms and prompt treatment are crucial in anaphylaxis management to avoid serious and even fatal outcomes. It is crucial for both individuals and clinicians to identify the cause of anaphylaxis. Biomarkers of anaphylaxis, such as histamine, tryptase, platelet activation factor (PAF), chymase, carboxypeptidase A3, dipeptidyl peptidase I (DPPI), basogranulin, CCL-2, hsa-miR-451a, may be useful in diagnosis and management. The purpose of this review article is to present a comprehensive overview of current evidence and expert opinions regarding the risk factors that predispose individuals to anaphylaxis. Additionally, it provides insights into potential biomarkers and genetic markers for accurate diagnosis and management. This review underscores the significance of expert guidance in enhancing patient outcomes and enabling self-management of anaphylactic episodes.

Summary: Background: Spirometric obstruction and restriction are two patterns of impaired lung function which are predictive of poor health. We investigated the development of these phenotypes and their transitions through childhood to early adulthood. Methods: In this study, we analysed pooled data from three UK population−based birth cohorts established between 1989 and 1995. We applied descriptive statistics, regression modelling and data-driven modelling to data from three population−based birth cohorts with at least three spirometry measures from childhood to adulthood (mid-school: 8–10 years, n = 8404; adolescence: 15–18, n = 5764; and early adulthood: 20–26, n = 4680). Participants were assigned to normal, restrictive, and obstructive spirometry based on adjusted regression residuals. We considered two transitions: from 8–10 to 15–18 and from 15–18 to 20–26 years. Findings: Obstructive phenotype was observed in ∼10%, and restrictive in ∼9%. A substantial proportion of children with impaired lung function in school age (between one third in obstructive and a half in restricted phenotype) improved and achieved normal and stable lung function to early adulthood. Of those with normal lung function in school-age,

Background: While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a whole. Aim: To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally. Methods: Phase 1: We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts. Phase 2: Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from “strongly agree” to “strongly disagree”. Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as “strongly agree” to “agree” after the second round. Based on feedback, 2 additional online voting rounds were conducted. Results: We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score. Conclusions: The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an evaluation grid, which may help to rate the severity of food allergy. Phase 3 will involve validating the scoring system in research settings, and implementing it in clinical practice.

Food allergy affects approximately 2–4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy.

Background: Dental age estimation using the simple average method utilizing the Demirjian 8 stage tooth developments system has not previously been compared to the 14 stage system of Moorrees. Neither method has been previously used nor compared with the Atlas method in a Kuwaiti population. The recent development of a Kuwait reference data set provides the means to determine which of these methods is the most accurate for age estimation in Kuwaiti subjects. Patients, materials and methods: The sample was dental panoramic tomographs (DPTs) from the archives of Kuwait Ministry of Health Dental Hospitals comprising 375 healthy children aged between 5 and 15 years.Each of the anonymized DPT was assessed in random order and personal details masked from the observer. Results: Intra and inter examiner agreement were calculated using Cohen's Kappa with scores of 0.76 or above which is ‘good to excellent’ agreement.The chronological age (CA) minus dental age (DA) difference using the simple average method (SAM) is an overestimate of 0.39 years for females and an underestimate of 0.14 years for males. The London Atlas overestimated the chronological age by 0.60 years for females and 0.19 years for males. Moorrees technique gave an underestimate of 1.01 years for females and 0.89 years for males.Bland-Altman plots showed an even distribution of difference around the chronological age. The Bland Altman plots showed the spread of the differences between chronological age and dental age for each of the three methods. Conclusions: The simple average method was the most accurate within, 2–3 months of chronological age. The London Atlas and Moorrees methods were less accurate.This makes the simple average method the favoured technique for dental age estimation in a forensic science setting where ethnic specific reference data are important.

Background and aims: The term “Food Allergy” refers to a complex global health problem with a wide spectrum of severity. However, a uniform definition of severe food allergy is currently missing. This systematic review is the preliminary step towards a state-of-the-art synopsis of the current evidence relating to the severity of IgE-mediated food allergy; it will inform attempts to develop a consensus to define food allergy severity by clinicians and other stakeholders. Methods: We undertook a mixed-methods systematic review, which involved searching 11 international biomedical databases for published studies from inception to 31 December 2019. Studies were independently screened against pre-defined eligibility criteria and critically appraised by established instruments. The substantial heterogeneity of included studies precluded meta-analyses and, therefore, narrative synthesis of quantitative and qualitative data was performed. Results: We found 23 studies providing eligible primary data on symptom-specific severity of food allergic reactions, and 31 previously published symptom-severity scoring systems referred to food allergic reactions. There were seven studies which assessed quality-of-life measures in patients (and family members) with different food allergy severity and two studies that investigated the economic burden of food allergy severity. Overall, the quality and the global rating of all included studies were judged as being moderate. Conclusions: There is heterogeneity among severity scoring systems used and even outcomes considered in the context of severity of food allergy. No score has been validated. Our results will be used to inform the development of an international consensus to define the severity of food allergy. Systematic review registration: A protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) database with the registration number CRD42020183103 (https://www.crd.york.ac.uk/prospero/#recordDetails).

Background and aims: The term “Food Allergy” refers to a complex global health problem with a wide spectrum of severity. However, a uniform definition of severe food allergy is currently missing. This systematic review is the preliminary step towards a state-of-the-art synopsis of the current evidence relating to the severity of IgE-mediated food allergy; it will inform attempts to develop a consensus to define food allergy severity by clinicians and other stakeholders. Methods: We will undertake a systematic review, which will involve searching international biomedical databases for published studies. Studies will be independently screened against pre-defined eligibility criteria and critically appraised by established instruments. Data will be descriptively and, if possible and applicable, quantitatively synthesised. Ethics and dissemination: This study does not require any specific ethical approval since it is a systematic review. We plan to report results from this systematic review in a peer reviewed journal. These results will be used to inform the development of an international consensus to define severe food allergy. Author's potential conflicts of interest are clearly stated. PROSPERO registration number: CRD42020183103.

ICON: Anaphylaxis provides a unique perspective on the principal evidence-based anaphylaxis guidelines developed and published independently from 2010 through 2014 by four allergy/immunology organizations. These guidelines concur with regard to the clinical features that indicate a likely diagnosis of anaphylaxis -- a life-threatening generalized or systemic allergic or hypersensitivity reaction.They also concur about prompt initial treatment with intramuscular injection of epinephrine (adrenaline) in the mid-outer thigh, positioning the patient supine (semi-reclining if dyspneic or vomiting), calling for help, and when indicated, providing supplemental oxygen, intravenous fluid resuscitation and cardiopulmonary resuscitation, along with concomitant monitoring of vital signs and oxygenation. Additionally, they concur that H1-antihistamines, H2-antihistamines, and glucocorticoids are not initial medications of choice.For self-management of patients at risk of anaphylaxis in community settings, they recommend carrying epinephrine auto-injectors and personalized emergency action plans, as well as follow-up with a physician (ideally an allergy/immunology specialist) to help prevent anaphylaxis recurrences.ICON: Anaphylaxis describes unmet needs in anaphylaxis, noting that although epinephrine in 1 mg/mL ampules is available worldwide, other essentials, including supplemental oxygen, intravenous fluid resuscitation, and epinephrine auto-injectors are not universally available.ICON: Anaphylaxis proposes a comprehensive international research agenda that calls for additional prospective studies of anaphylaxis epidemiology, patient risk factors and co-factors, triggers, clinical criteria for diagnosis, randomized controlled trials of therapeutic interventions, and measures to prevent anaphylaxis recurrences. It also calls for facilitation of global collaborations in anaphylaxis research.In addition to confirming the alignment of major anaphylaxis guidelines, ICON: Anaphylaxis adds value by including summary tables and citing 130 key references. It is published as an information resource about anaphylaxis for worldwide use by healthcare professionals, academics, policy-makers, patients, caregivers, and the public. Keywords: Anaphylaxis, Acute systemic allergic reaction, Epinephrine (adrenaline), H1-antihistamines, H2-antihistamines, Glucocorticoids, Food allergy, Venom allergy, Drug allergy, Exercise-induced anaphylaxis, Idiopathic anaphylaxis