Epigenomic variability is associated with age-specific naïve CD4 T cell response to activation in infants and adolescents.

Childhood is a critical period of immune development. During this time, naïve CD4 (nCD4) T cells undergo programmed cell differentiation, mediated by epigenetic changes, in response to external stimuli leading to a baseline homeostatic state that may determine lifelong disease risk. However, the ontogeny of epigenetic signatures associated with CD4 T cell activation during key developmental periods are yet to be described. We investigated genome-wide DNA methylation (DNAm) changes associated with nCD4 T activation following 72 h culture in media+anti-CD3/CD28 beads in healthy infants (aged 12 months, n = 18) and adolescents (aged 10-15 years, n = 15). We integrated these data with transcriptomic and cytokine profiling from the same samples. nCD4 T cells from both age groups show similar extensive epigenetic reprogramming following activation, with the majority of genes involved in the T cell receptor signaling pathway associated with differential methylation. Additionally, we identified differentially methylated probes showing age-specific responses, that is, responses in only infants or adolescents, including within a cluster of T cell receptor (TCR) genes. These encoded several TCR alpha joining (TRAJ), and TCR alpha variable (TRAV) genes. Cytokine data analysis following stimulation revealed enhanced release of IFN-γ, IL-2 and IL-10, in nCD4 T cells from adolescents compared with infants. Overlapping differential methylation and cytokine responses identified four probes potentially underpinning these age-specific responses. We show that DNAm in nCD4T cells in response to activation is dynamic in infancy and adolescence, with additional evidence for age-specific effects potentially driving variation in cytokine responses between these ages.

TreEAT trial: Protocol for a randomized controlled trial investigating the efficacy and safety of early introduction of tree nuts for the prevention of tree nut allergy in infants with peanut allergy.

INTRODUCTION: Children with peanut allergy are at increased risk of developing tree nut allergies, which can be severe and for most lifelong. Introduction of peanut in the first year of life can reduce the risk of peanut allergy; however, prevention strategies for tree nut allergies have not been established. We aimed to test the efficacy and safety of a novel strategy, a supervised multi-nut oral food challenge (OFC) compared with standard care for tree nut allergy prevention in infants at high risk of developing tree nut allergy, TreEAT. METHODS AND ANALYSIS: TreEAT is a 2-armed, open-label, randomized, controlled trial (RCT). Infants (n = 212) aged 4-11 months with peanut allergy will be randomized 1:1 at peanut allergy diagnosis to either a hospital-based multi-tree nut (almond, cashew, hazelnut, and walnut) OFC using multi-nut butter or standard care (home introduction of individual tree nuts). All infants will be assessed at age 18 months, with questionnaires and SPT to peanut and tree nuts. Peanut and tree nut OFCs will be performed as required to determine the allergy status for each nut. The primary outcome is tree nut allergy at age 18 months. Secondary outcomes include peanut allergy resolution, proportion, and severity of adverse events related to tree nut ingestion, number and frequency of tree nuts ingested, quality of life and parental anxiety, and allergy-related healthcare visits from randomization to 18 months of age. Analyses will be performed on an intention-to-treat basis. ETHICS AND DISSEMINATION: TreEAT was approved by the Royal Children's Hospital Human Research Ethics Committee (#70489). Outcomes will be presented at scientific conferences and disseminated through publication. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT04801823.

Early peanut introduction: To test or not to test?

OBJECTIVE: To review recent evidence and international guidelines on early peanut introduction for preventing peanut allergy and provide an update on the status of the debate around testing before early peanut introduction. DATA SOURCES: Review of published literature documenting: infant feeding guidelines; impact of early peanut introduction on peanut allergy; risk factors for peanut allergy; and impact of early peanut introduction guidelines on infant feeding practices and allergy. STUDY SELECTION: We used a narrative approach and present both pro and con arguments for testing before peanut introduction. Data from randomized controlled trials and post-hoc analyses of these trials and observational studies were included. RESULTS: Allergy prevention guidelines around the world now consistently recommend introducing peanut into an infant's diet before 12 months of age for countries with high peanut allergy prevalence. In the US, guidelines recently shifted away from recommending allergy testing before introduction for those at risk of peanut allergy. There is evidence primarily from Australia that recommending early introduction without prior testing is safe and effective in increasing early peanut introduction for both high and low-risk infants, although the subsequent reduction in peanut allergy prevalence at the population level was less than expected. CONCLUSION: Current evidence supports recommending early peanut introduction without routinely testing for peanut allergy. If testing is offered, this should be based on shared decision making between families and practitioners and only be undertaken where there is provision for rapid access to definitive diagnosis including oral food challenges.

Ana o 3 sIgE and diagnostic algorithms reduce cost of cashew allergy diagnosis in children compared with skin prick test: A cost comparison analysis.

BACKGROUND: In the absence of a clear clinical history of reaction, diagnosis of cashew allergy using skin prick tests (SPT) or cashew-specific IgE requires a high number of oral food challenges (OFC). By using Ana o 3 sIgE alone, or a two-step diagnostic algorithm using cashew sIgE followed by Ana o 3 sIgE, there is a reduced need for OFC. We aimed to perform a cost comparison for both of these approaches compared with cashew SPT alone. METHODS: Pooled individual-level data from 6 studies were used to determine diagnostic accuracy and OFC rate. Two studies used cashew SPT (n = 567, 198 allergic), with 95% positive and negative predictive values of ≥12 mm and <3 mm. Four studies were included in the pathways for Ana o 3 sIgE alone or a 2-step algorithm incorporating cashew and Ana o 3 sIgE (n = 271, 156 allergic). Cut-offs used were ≥8.5kUA/L and ≤0.1kUA/L for cashew sIgE and ≥0.35kUA/L and ≤0.1kUA/L for Ana o 3 sIgE. Costs were constructed based on unit prices from hospital inpatient admissions, expenses incurred by families, individual patient data on allergic reaction types and rates, and adrenaline autoinjector carriage, applying a health system perspective. RESULTS: Modeled data through the Ana o 3 pathway resulted in a 46.43% cost reduction (€307,406/1000 patients) compared with using cashew SPT alone (€573,854/1000 patients). The 2-step algorithm resulted in a 44.94% cost reduction compared with SPT alone (€315,952.82/1000 patients). Both the Ana o 3 pathway and 2-step algorithm resulted in a 79%-80% reduction in OFCs compared with SPT. CONCLUSIONS: Using Ana o 3 as a standalone test for cashew allergy diagnosis or a 2-step algorithm incorporating cashew sIgE and Ana o 3 sIgE is accurate and results in a large reduction in both OFCs and health system costs compared with cashew SPT alone.

A pragmatic approach to infant feeding for food allergy prevention.

Early introduction of allergenic foods into an infant's diet is currently the most promising strategy to prevent food allergy, with infant guidelines around the world shifting from promoting avoidance to actively encourage the introduction of allergenic foods in the infant diet. Infant feeding guidelines vary according to regional public health priorities, and knowledge gaps remain, resulting in ongoing challenges for clinicians and families to translate guidelines into practical strategies for the introduction of complementary foods for food allergy prevention. Evidence from Australia demonstrates high community support and uptake of revised guidelines with most parents introducing allergenic foods in the first year of life, although this has not had the expected impact on substantially reducing food allergy prevalence. To uptake of guidelines from other countries is less clear, and several barriers have been noted in infant feeding RCTs, which may warrant intervention strategies. Further research is needed to understand additional strategies for food allergy prevention, particularly in infants who develop food allergy prior to when they are developmentally ready to commence solids. Several RCTs are underway investigating preventative strategies that target the window before allergen ingestion, such as vitamin D supplementation, emollient use, and immunizations that prime the immune response away from a Th2-driven allergic phenotype. Further research is also needed to understand the role of the environment and the host environment in the development of tolerance to foods.

Ana o 3 sIgE testing increases the accuracy of cashew allergy diagnosis using a two-step model.

BACKGROUND: Measurement of cashew-specific IgE (sIgE) is often used to confirm sensitization but does not reliably diagnose clinical allergy. Ana o 3 is the dominant cashew allergen detected in 75-100% of patients with cashew allergy but not currently used in clinical practice. OBJECTIVES: To determine if component-resolved diagnostics using specific IgE to the 2 S albumin from cashew, Ana o 3, improves the accuracy of diagnosing cashew allergy, thereby circumventing the need for an oral food challenge (OFC) in some patients. METHODS: A population-based sample of 5276 children was recruited at age 1 year and followed up at age 6 years. Children with positive cashew skin prick test at age 6 underwent an OFC to clarify allergy status. Forty-seven children (mean age 5.02 ± 0.2) (33 cashew-allergic and 14 cashew-tolerant) had cashew sIgE and Ana o 3 sIgE quantified by ImmunoCAP System FEIA. RESULTS: A cutoff of >0.32 kUA/L for Ana o 3 sIgE provided 95% specificity and 90% sensitivity and correctly identified 90% of clinical cashew allergy. At the same specificity, the sensitivity for cashew sIgE (>8.5 kUA/L) was only 26%. Sequential measurement of cashew sIgE followed by Ana o 3 sIgE diagnosed 90% of children with cashew allergy without the need for an OFC. CONCLUSION: Ana o 3 sIgE testing provides higher diagnostic accuracy than cashew sIgE. Sequential measurement of cashew sIgE followed by Ana o 3 removed the need for a food challenge from 66% down to 12.8% (5-fold) of children compared with cashew sIgE testing alone.

Immuno-epigenomic analysis identifies attenuated interferon responses in naïve CD4 T cells of adolescents with peanut and multi-food allergy.

BACKGROUND: IgE-mediated food allergies have been linked to suboptimal naïve CD4 T (nCD4T) cell activation in infancy, underlined by epigenetic and transcriptomic variation. Similar attenuated nCD4T cell activation in adolescents with food allergy have also been reported, but these are yet to be linked to specific epigenetic or transcriptional changes. METHODS: We generated genome-wide DNA methylation data in purified nCD4 T cells at quiescence and following activation in a cohort of adolescents (aged 10-15 years old) with peanut allergy (peanut only or peanut + ≥1 additional food allergy) (FA, n = 29), and age-matched non-food allergic controls (NA, n = 18). Additionally, we assessed transcriptome-wide gene expression and cytokine production in these cells following activation. RESULTS: We found widespread changes in DNA methylation in both NA and FA nCD4T cells in response to activation, associated with the T cell receptor signaling pathway. Adolescents with FA exhibit unique DNA methylation signatures at quiescence and post-activation at key genes involved in Th1/Th2 differentiation (RUNX3, RXRA, NFKB1A, IL4R), including a differentially methylated region (DMR) at the TNFRSF6B promoter, linked to Th1 proliferation. Combined analysis of DNA methylation, transcriptomic data and cytokine output in the same samples identified an attenuated interferon response in nCD4T cells from FA individuals following activation, with decreased expression of several interferon genes, including IFN-γ and a DMR at a key downstream gene, BST2. CONCLUSION: We find that attenuated nCD4T cell responses from adolescents with food allergy are associated with specific epigenetic variation, including disruption of interferon responses, indicating dysregulation of key immune pathways that may contribute to a persistent FA phenotype. However, we recognize the small sample size, and the consequent restraint on reporting adjusted p-value statistics as limitations of the study. Further study is required to validate these findings.

Altered immune cell profiles and impaired CD4 T-cell activation in single and multi-food allergic adolescents.

BACKGROUND: Approximately 5% of adolescents have a food allergy, with peanut and tree nut allergies the most common. Having two or more food allergies in adolescence also doubles the risk of any adverse food reaction, and is associated with increased dietary and social burden. Investigations of immune function in persistently food allergic children are rare. OBJECTIVE: In the present study, we aimed to investigate the immune mechanisms that underlie food allergy in adolescence. METHODS: We used high-dimensional flow cytometry, unsupervised computational analysis and functional studies to comprehensively phenotype a range of non-antigen-specific immune parameters in a group of well-characterized adolescents with clinically defined single peanut allergy, multi-food allergy and aged-matched non-food allergic controls. RESULTS: We show that food allergic adolescents have higher circulating proportions of dendritic cells (p = .0084, FDR-adjusted p = .087, median in no FA: 0.63% live cells, in FA: 0.93%), and higher frequency of activated, memory-like Tregs relative to non-food allergic adolescents (p = .011, FDR-adjusted p = .087, median in no FA: 0.49% live cells, in FA: 0.65%). Cytokine profiling revealed that CD3/CD28 stimulated naïve CD4 T cells from food allergic adolescents produced less IL-6 (p = .0020, FDR-adjusted p = .018, median log2 fold change [stimulated/unstimulated] in no FA: 3.03, in FA: 1.92) and TNFα (p = .0044, FDR-adjusted p = .020, median in no FA: 9.16, in FA: 8.64) and may secrete less IFNγ (p = .035, FDR-adjusted p = .11, median in no FA: 6.29, in FA: 5.67) than naïve CD4 T cells from non-food allergic controls. No differences between clinical groups were observed for LPS-stimulated monocyte secretion of cytokines. CONCLUSIONS: These results have important implications for understanding the evolution of the immune response in food allergy throughout childhood, revealing that dendritic cell and T-cell signatures previously identified in early life may persist through to adolescence.

Prevalence and natural history of tree nut allergy.

OBJECTIVE: Tree nuts are common causes of food-related allergic reactions and anaphylaxis. Resolution of tree nut allergy is thought to be low, yet studies of the natural history of tree nut allergy are limited. This review summarizes the available literature regarding tree nut allergy prevalence and natural history and discusses emerging diagnostic and prognostic developments that will inform clinical management of tree nut allergy. DATA SOURCES: A comprehensive literature search using PubMed was performed. STUDY SELECTIONS: Peer-reviewed publications relating to tree nut allergy prevalence, resolution, and diagnosis were selected, and findings were summarized using a narrative approach. RESULTS: Tree nut allergy prevalence varies by age, region, and food allergy definition, and ranges from less than 1% to approximately 3% worldwide. Reports on the natural history of tree nut allergy data are limited to retrospective clinical data or cross-sectional survey data of self-reported food allergy, with reported resolution ranging from 9% to 14%. Component-resolved diagnostics and basophil activation testing offer the potential to improve the diagnostic accuracy and predicted prognosis of specific tree nut allergy, but studies are limited. CONCLUSION: Tree nut allergy remains an understudied area of food allergy research with limited region-specific studies based on robust food allergy measures in population cohorts with longitudinal follow-up. This currently limits our understanding of tree nut allergy prognosis.

Patterns of tree nut sensitization and allergy in the first 6 years of life in a population-based cohort.

BACKGROUND: Longitudinal population-based data regarding tree nut allergy are limited. OBJECTIVES: We sought to determine the population prevalence of tree nut allergy at age 6 years and explore the relationship between egg and peanut allergy at age 1 year and development of tree nut allergy at age 6 years. METHODS: A population-based sample of 5276 children was recruited at age 1 year and followed up at age 6 years. At age 1 year, allergies to egg and peanut were determined by means of oral food challenge, and parents reported their child's history of reaction to tree nuts. Challenge-confirmed tree nut allergy was assessed at age 6 years. RESULTS: At age 1 year, the prevalence of parent-reported tree nut allergy was 0.1% (95% CI, 0.04% to 0.2%). Only 18.5% of infants had consumed tree nuts in the first year of life. At age 6 years, challenge-confirmed tree nut allergy prevalence was 3.3% (95% CI, 2.8% to 4.0%), with cashew the most common (2.7%; 95% CI, 2.2% to 3.3%). Of children with peanut allergy only at age 1 year, 27% (95% CI, 16.1% to 39.7%) had tree nut allergy at age 6 years compared with 14% (95% CI, 10.4% to 17.9%) of those with egg allergy only and 37% (95% CI, 27.2% to 47.4%) of those with both peanut and egg allergy. CONCLUSIONS: Tree nut allergy is uncommon in the first year of life, likely because of limited tree nut consumption. At age 6 years, tree nut allergy prevalence is similar to peanut allergy prevalence. More than a third of children with both peanut and egg allergy in infancy have tree nut allergy at age 6 years. Understanding how to prevent tree nut allergy should be an urgent priority for future research.

The global incidence and prevalence of anaphylaxis in children in the general population: A systematic review.

BACKGROUND: Despite an increasing number of publications from individual countries and regions, there is still no systematic review of the global epidemiology of anaphylaxis in the general paediatric population. METHODS: We conducted a systematic review, using a protocol registered and published with the international prospective register of systematic reviews (PROSPERO). Results were reported following PRISMA guidelines. The search strategy was designed in Medline (ovid) and modified for Embase (ovid) and PubMed. Papers were screened by two independent reviewers following selection and exclusion criteria. Data extraction and risk of bias assessment were completed by the same two reviewers. Studies in adults only or those that did not report data in children separately were excluded. RESULTS: A final total of 59 articles were included. Of these, 5 reported cumulative incidence, 39 reported incidence rate and 17 reported prevalence data. The incidence of anaphylaxis in children worldwide varied widely, ranging from 1 to 761 per 100 000 person-years for total anaphylaxis and 1 to 77 per 100 000 person-years for food-induced anaphylaxis. The definition of anaphylaxis from NIAID/FAAN was the most commonly used. Gender and ethnicity were demographic risk factors associated with anaphylaxis in children. Increasing total or food-induced anaphylaxis incidence over time was reported by 19 studies. CONCLUSION: The reported incidence of anaphylaxis in children varied widely. Studies in developing countries are underrepresented. To accurately compare anaphylaxis incidence between countries and investigate the time trends, further studies using a standardized definition across different countries are required.

Anaphylaxis management in Australian schools: Review of guidelines and adrenaline autoinjector use.

Food allergy and anaphylaxis is increasing in Australian children, and anaphylaxis is relatively common in Australian schools. This review aims to provide an overview of current policies and practices for anaphylaxis management in Australian schools, including approaches to risk mitigation and anaphylaxis training. We reviewed literature related to anaphylaxis training in the school setting published between 2010 and 2018. Current anaphylaxis policies/guidelines were obtained from Australian education and health departments, and reports of suspected anaphylaxis and adrenaline autoinjector (AAI) use for 2016-2017 were obtained from education departments where available. Our review of policies/guidelines across Australian jurisdictions indicates inconsistent approaches to anaphylaxis management training. Almost half of Australian school anaphylaxis events required a general-use AAI, administered to students not identified as at risk of anaphylaxis. Development of clear, evidence-based, consistent guidelines related to anaphylaxis management and training in the school setting is imperative to minimise risk.

Self-reported adverse food reactions and anaphylaxis in the SchoolNuts study: A population-based study of adolescents.

BACKGROUND: Adolescents are at the highest risk of death from anaphylaxis, yet few population-based studies have described the frequencies and risk factors for allergic reactions caused by accidental allergen ingestion in this group. METHODS: We describe the prevalence, frequency, and associated risk factors for recent adverse food reactions in 10- to 14-year-olds in Melbourne, Australia, recruited from a stratified, random, population-based sample of schools (SchoolNuts, n = 9663; 48% response rate). Self-reported food allergy and adverse reaction details, including anaphylaxis, were identified by using a student questionnaire over the past year. RESULTS: Of 547 students with possible IgE-mediated food allergy, 243 (44.4%; 95% CI, 40.3% to 48.7%) reported a reaction to a food. Fifty-three (9.7%; 95% CI, 7.2% to 12.2%) students reported 93 anaphylaxis episodes. Peanut and tree nuts were the most common food triggers. Among students with current IgE-mediated food allergy, those with resolved or current asthma (adjusted odds ratio [aOR], 1.9 [95% CI, 1.1-1.3] and 1.7 [95% CI, 1.1-2.6]) and those with more than 2 food allergies (aOR, 1.9 [95% CI, 1.1-3.1]) were at greatest risk of any adverse food reaction, and those with nut allergy were most at risk of severe reactions (aOR, 2.9 [95% CI, 1.1-4.4]). Resolved or current asthma was not associated with increased risk of severe reactions (aOR, 0.8 [95% CI, 0.3-2.2] and 1.6 [95% CI, 0.7-3.7]). CONCLUSIONS: Adolescents with food allergy are frequently exposed to food allergens. Those with asthma and more than 2 food allergies were at the greatest risk for adverse food reactions. Those with nut allergies were most at risk of severe reactions.

Prevalence of clinic-defined food allergy in early adolescence: The SchoolNuts study.

BACKGROUND: Rising rates of food-induced anaphylaxis have recently been shown in the adolescent age group, following earlier descriptions of a rise in children younger than 5 years. However, few population-based studies have examined the prevalence of food allergy in adolescence using objective measures such as oral food challenge (OFC). OBJECTIVE: We sought to determine the prevalence of food allergy among a population-based sample of 10- to 14-year-old adolescents using clinical evaluation including OFC to confirm the diagnosis. METHODS: Schools were randomly selected from greater metropolitan Melbourne, Australia. Students aged 10 to 14 years, and their parents, were asked to complete a questionnaire regarding the adolescent's food allergy or food-related reactions. Clinic evaluation, which consisted of skin prick tests and OFC where eligible, was undertaken if students were suspected to have current food allergy from parent response. Among 9816 students assessed, 5016 had complete parent response and clinic evaluation when eligible. An additional 4800 students had student questionnaires only. RESULTS: The prevalence of clinic-defined current food allergy based on history, sensitization data, and OFC results was 4.5% (95% CI, 3.9-5.1), with the most common food triggers being peanut, 2.7% (95% CI, 2.3-3.2), and tree nut, 2.3% (95% CI, 1.9-2.8). Among the additional group of 4800 adolescents who had only self-reported food allergy status available, the prevalence of self-reported current food allergy was 5.5% (95% CI, 4.9-6.2), with peanut, 2.8% (95% CI, 2.3-3.3), and tree nut, 2.3% (95% CI, 1.9-2.8), the most common. CONCLUSIONS: Approximately 1 in 20 10- to 14-year-old school students in Melbourne has current food allergy. This high prevalence suggests that the previously reported rise in food-induced anaphylaxis in this age group may reflect an increasing prevalence of food allergy rather than simply increased reporting of anaphylaxis.

The Prevalence of Tree Nut Allergy: A Systematic Review.

Tree nuts are one of the most common foods causing acute allergic reactions and nearly all tree nuts have been associated with fatal allergic reactions. Despite their clinical importance, tree nut allergy epidemiology remains understudied and the prevalence of tree nut allergy in different regions of the world has not yet been well characterised. We aimed to systematically review the population prevalence of tree nut allergy in children and adults. We searched three electronic databases (OVID MEDLINE, EMBASE and PubMed) from January 1996 to December 2014. Eligible studies were categorised by age, region and method of assessment of tree nut allergy. Of the 36 studies identified most were in children (n = 24) and from Europe (n = 18), UK (n = 8) or USA (n = 5). Challenge-confirmed IgE-mediated tree nut allergy prevalence was less than 2 % (although only seven studies used this gold standard) while probable tree nut allergy prevalence ranged from 0.05 to 4.9 %. Prevalence estimates that included oral allergy syndrome (OAS) reactions to tree nut were significantly higher (8-11.4 %) and were predominantly from Europe. Prevalence of individual tree nut allergies varied significantly by region with hazelnut the most common tree nut allergy in Europe, walnut and cashew in the USA and Brazil nut, almond and walnut most commonly reported in the UK. Monitoring time trends of tree nut allergy prevalence (both overall and by individual nuts) as well as the prevalence of OAS should be considered given the context of the overall recent rise in IgE-mediated food allergy prevalence in the developed world.

Australian Infant Food Allergy Emergency Presentations Following Updated Early Food Introduction Guidelines.

BACKGROUND: The Australasian Society of Clinical Immunology and Allergy food allergy prevention guidelines were updated in 2016 to recommend home introduction of allergenic foods actively in the first year of life, including to infants at high risk of allergy. An important consideration for parents and providers is whether this practice increases food allergy reactions or anaphylaxis. OBJECTIVE: We aimed to determine whether the 2016 update of food allergy prevention guidelines was associated with an increase in food allergy or anaphylaxis emergency department (ED) presentations. METHODS: We obtained hospital electronic medical records for infants aged 4 to 12 months who attended the Royal Children's Hospital Melbourne ED in 2015 or in 2018 with a presenting problem or an encounter diagnosis of food allergy or anaphylaxis. RESULTS: Emergency department presentations owing to food allergy increased from 1.0% (95% CI, 0.85-1.23) in 2015 to 1.4% (95% CI, 1.22-1.67) in 2018 (P = .006). There was no increase in the number of anaphylaxis presentations (28 in 2015 and 22 in 2018) or peanut anaphylaxis presentations (three in 2015 and three in 2018). Overall, the proportion of food allergy presentations attributed to IgE-mediated food allergy was similar (82.1% in 2015 and 84.1% in 2018), whereas peanut allergy presentations increased slightly, although not statically significantly, from 14.6% to 21.2% (P = .09). Food protein-induced enterocolitis syndrome ED presentations were five in 2015 (4.3%) and 12 in 2018(7.6%), although not statistically significant (P = .25). CONCLUSIONS: Changes to food allergy prevention guidelines recommending the earlier introduction of allergenic food may have led to a small increase in ED presentations for food allergy but not anaphylaxis.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines update - X - Breastfeeding a baby with cow's milk allergy.

Cow's milk allergy is rare in exclusively breastfed infants. To support the continuation of breastfeeding an infant after diagnosis with a cow's milk allergy, it is critical to examine the evidence for and against any form of cow's milk elimination diet for lactating mothers. In this narrative review, we highlight the lack of high-quality evidence, hence subsequent controversy, regarding whether the minuscule quantities of cow's milk proteins detectable in human milk cause infant cow's milk allergy symptoms. Current clinical practice recommendations advise a 2-4 week trial of maternal cow's milk dietary elimination for: a) IgE-mediated cow's milk allergy only if the infant is symptomatic on breastfeeding alone; b) non-IgE-mediated associated symptoms only if the history and examination strongly suggest cow's milk allergy; and c) infants with moderate to severe eczema/atopic dermatitis, unresponsive to topical steroids and sensitized to cow's milk protein. There should be a clear plan for home reintroduction of cow's milk into the maternal diet for a period of 1 week to determine that the cow's milk elimination is responsible for resolution of symptoms, and then subsequent reoccurrence of infant symptoms upon maternal cow's milk reintroduction. The evidence base to support the use of maternal cow's milk avoidance for the treatment of a breastfed infant with cow's milk allergy is of limited strength due to a lack of high-quality, adequately powered, randomised controlled trials. It is important to consider the consequences of maternal cow's milk avoidance on reducing immune enhancing factors in breast milk, as well as the potential nutritional and quality of life impacts on the mother. Referral to a dietitian is advised for dietary education, along with calcium and vitamin D supplementation according to local recommendations, and a maternal substitute milk should be advised. However, for most breastfed infants with cow's milk allergy maternal cow's milk dietary elimination will not be required, and active support of the mother to continue breastfeeding is essential.

Systematic Review of the Incidence and/or Prevalence of Eating Disorders in Individuals With Food Allergies.

BACKGROUND: Chronic diseases involving strict dietary adherence have been associated with an increased risk of eating disorders (EDs). This is the first systematic review investigating the rate of EDs among individuals with food allergies (FAs). OBJECTIVE: To report the incidence, prevalence, and types of EDs in individuals with FAs. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched 4 databases for studies published to January 2022 that reported the prevalence or incidence of EDs in samples with immunoglobulin E (IgE) or non-IgE-mediated allergy. Risk of bias was assessed and evidence qualitatively synthesized. RESULTS: From 1,180 papers identified, 9 met inclusion criteria. There were 4,161 adult and pediatric participants with IgE-mediated FAs or eosinophilic esophagitis. Avoidant/Restrictive Food Intake Disorder (ARFID) or anorexia nervosa/bulimia nervosa were the main EDs identified. The prevalence of EDs in samples with FA ranged from 0.8% to 62.9%. Among studies investigating IgE-mediated FA (n = 6), the prevalence of anorexia nervosa and/or bulimia nervosa ranged from 17.6 to 61%, ARFID was 62.9%, and unspecified EDs was 0.8% to 6%. Among samples with eosinophilic esophagitis (n = 3), ARFID prevalence ranged from 4.5% to 51%. Most studies were limited by small sample size, possible selection bias, and lack of diagnostic EDs tools validated for food allergic populations. CONCLUSIONS: Eating disorders appear prevalent in individuals with FA; however, prevalence estimates varied widely. Large studies with healthy control groups and validated measures to identify EDs in individuals with FA are needed to accurately determine the prevalence of EDs.

Cashew Allergy Prevalence and Sensitization in 1-Year-Old Infants.

BACKGROUND: Cashew allergy is the most common tree nut allergy in Australia, but there are limited data on the population-level prevalence and risk factors. OBJECTIVE: Describe the prevalence of cashew sensitization and allergy in 12-month-old infants and identify risk factors. METHODS: Data were from the EarlyNuts cohort, a population-based sample of infants recruited in Melbourne, Australia. Families completed a questionnaire and infants underwent a skin prick test (SPT) to cashew. Infants with positive SPTs were offered food challenges. Questionnaires collected demographic data and allergy risk factors. Allergy outcomes were determined by challenge outcomes or a convincing history of an allergic reaction. We used weights to adjust estimated prevalence to reflect the distribution of risk factors among the combined sample of participants and nonparticipants. RESULTS: We recruited 1,933 participants and identified 1,414 cashew allergy outcomes. Of these, 1.96% (95% CI, 1.28-2.99) had an SPT result of 3 mm or greater and 1.49% (95% CI, 0.91-2.44) were allergic to cashew. Infants with eczema or peanut allergy in the first year of life were more likely to be allergic to cashew (adjusted odds ratio = 5.75; 95% CI, 2.08-15.88; P = .001; and adjusted odds ratio = 19.30; 95% CI, 5.44-68.43; P < .001, respectively). Twenty-five percent of participants had cashew introduced before 12 months (95% CI, 22.7-27.8). There was no association between the timing of cashew introduction and cashew allergy. CONCLUSIONS: To our knowledge, this is the first study describing the prevalence of and risk factors for cashew allergy in a population-based infant cohort. Eczema and peanut allergy were associated with an increased risk of cashew allergy. Few infants were introduced to cashew before age 12 months, which suggests that infant feeding guidelines have not yet translated to the earlier introduction of all allergens.