A systematic review and meta-analysis of nutritional and dietary interventions in randomized controlled trials for skin symptoms in children with atopic dermatitis and without food allergy: An EAACI task force report.

This systematic review and meta-analysis aimed to consolidate evidence on dietary interventions for atopic eczema/dermatitis (AD) skin symptoms in children without food allergies, following PRISMA 2020 guidelines. Systematic review updates were conducted in May 2022 and June 2023, focusing on randomized placebo-controlled trials (RCTs) involving children with AD but without food allergies. Specific diets or supplements, such as vitamins, minerals, probiotics, prebiotics, symbiotics, or postbiotics, were explored in these trials. Exclusions comprised descriptive studies, systematic reviews, meta-analyses, letters, case reports, studies involving elimination diets, and those reporting on food allergens in children and adolescents. Additionally, studies assessing exacerbation of AD due to food allergy/sensitization and those evaluating elimination diets' effects on AD were excluded. Nutritional supplementation studies were eligible regardless of sensitization profile. Evaluation of their impact on AD clinical expression was performed using SCORAD scores, and a meta-analysis of SCORAD outcomes was conducted using random-effect models (CRD42022328702). The review encompassed 27 RCTs examining prebiotics, Vitamin D, evening primrose oil, and substituting cow's milk formula with partially hydrolyzed whey milk formula. A meta-analysis of 20 RCTs assessing probiotics, alone or combined with prebiotics, revealed a significant reduction in SCORAD scores, suggesting a consistent trend in alleviating AD symptoms in children without food allergies. Nonetheless, evidence for other dietary interventions remains limited, underscoring the necessity for well-designed intervention studies targeting multiple factors to understand etiological interactions and propose reliable manipulation strategies.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update - XII - Recommendations on milk formula supplements with and without probiotics for infants and toddlers with CMA.

Background: Cow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders. Results: After reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as "conditional" following the GRADE approach due to the very low certainty about the health effects based on the available evidence. Conclusions: If breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers' values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable.

Prevention of IgE-Mediated Food Allergy: Emerging Strategies Through Maternal and Neonatal Interventions.

Whereas the early introduction of highly allergenic foods has been shown to be effective at preventing the onset of food allergy (FA) in high-risk infants, sensitization to food antigens can occur prior to complementary food introduction, and thus, additional earlier FA prevention strategies are urgently needed. Currently, aside from early introduction of peanut and egg, no therapies are strongly recommended by international professional allergy societies for the primary prevention of FA. This review focuses on maternal- and neonatal-directed interventions that are being actively investigated and developed, including maternal dietary factors and supplementation, specific elimination diets, breastfeeding, cow's milk formula supplementation, microbiome manipulations, bacterial lysate therapy, and skin barrier therapies. Evaluating how these factors and various prenatal/early life environmental exposures may impact the development of FA is crucial for accurately counseling caregivers in the prevention of FA.

Feeding difficulties in children with food allergies: An EAACI Task Force Report.

The term "feeding difficulties" refers to a spectrum of phenotypes characterized by suboptimal intake of food and/or lack of age-appropriate eating habits. While it is evident that feeding difficulties are prevalent within healthy children, no consensus has been reached for those with food allergies. The aim of this study was to systematically review all the available literature reporting the prevalence of feeding difficulties within food allergic children. We searched eight international electronic databases for all published studies until June 2022. International experts in the field were also contacted for unpublished and ongoing studies. All publications were screened against pre-defined eligibility criteria and critically appraised by established instruments. The substantial heterogeneity of included studies precluded meta-analyses, so narrative synthesis of quantitative data was performed. A total of 2059 abstracts were assessed, out of which 21 underwent full-text screening and 10 studies met the study criteria. In these, 12 different terms to define feeding difficulties and 11 diagnostic tools were used. Five papers included data of feeding difficulty prevalence in children with food allergies, ranging from 13.6% to 40%. Higher prevalence was associated with multiple food allergies. The current literature suggests that feeding difficulties are prevalent within food allergic children, particularly those with multiple food allergies. However, the heterogeneity of terminologies and diagnostic tools makes drawing conclusions challenging. Consensus guidelines for the diagnosis and management of feeding difficulties within food allergic children and further research on the development and perpetuation of feeding difficulties are needed to appropriately manage such patients.

Redefining the Role of Nutrition in Infant Food Allergy Prevention: A Narrative Review.

Pediatric food allergy remains commonplace, despite the advancement in our understanding of risk factors and prevention modalities for the condition. Early allergen introduction, a dietary intervention, has been endorsed by professional societies globally as an effective primary preventive measure, yet awareness among medical professionals and parents is lacking. Alongside food allergen introduction, overall nutrition, such as diet diversity, also plays an important role in allergy prevention. To address both food allergen introduction and overall nutrition, dietitians play a pivotal role in the dissemination and education of current guidelines to caregivers. This review addresses the particular role of the dietitian in food allergy prevention consultations, providing up-to-date information on food allergies, their development and prevalence, risk factors, dietary factors and an overview of the current guidelines in the United States. This has not been addressed in any of the current food allergy or nutrition guidelines.

The future of cow's milk allergy - milk ladders in IgE-mediated food allergy.

Cow's milk allergy (CMA) is one of the most common and complex presentations of allergy in early childhood. CMA can present as IgE and non-IgE mediated forms of food allergy. Non-IgE mediated CMA includes food protein-induced enterocolitis syndrome (FPIES), eosinophilic gastrointestinal disorders (EGIDs), and food protein-induced proctocolitis (FPIAP). There are recent guidelines addressing CMA diagnosis, management, and treatment. Each of these guidelines have their own strengths and limitations. To best manage CMA, individualized avoidance advice should be given. Cow's milk (CM) can be replaced in the diet by using hypoallergenic formulas or plant-based milk, depending on factors such as the child's age and their current food intake. Oral and epicutaneous immunotherapy is used to increase tolerance in children with CMA but is not without risk, and the long-term outcome of sustained unresponsiveness is still unclear. The allergenicity of CM proteins are affected differently by different forms of heating, leading to the use of baked milk or milk ladders in the management of CMA, most likely the most promising option for future management and treatment of CMA. Future management of children with CMA will also include discussion around the immunomodulatory potential of the child's dietary intake.

Age-Related Food Aversion and Anxiety Represent Primary Patient Barriers to Food Oral Immunotherapy.

BACKGROUND: Although oral immunotherapy (OIT) for food allergy is a reasonable treatment option, barriers to this procedure's implementation have not been extensively evaluated from a patient perspective. OBJECTIVE: We evaluated the barriers patients face during OIT administration, including anxiety and taste aversion, and the role of health care professionals, especially dietitians. METHODS: A survey in Canada and the United States involved families currently enrolled in food OIT programs. RESULTS: Of responses from 379 participants, fear of reaction was the most common barrier to OIT initiation, with 45.6% reporting it being a "very significant" barrier with other fears reported. However, taste aversion represented the prominent obstacle to continuation. Taste aversion was associated with a slower buildup (P = .02) and a reduction in dose (P = .002). Taste aversion was a strongly age-dependent barrier for initiation (P < .001) and continuation (P < .002), with older children over 6 years of age reporting it as a very significant barrier (P < .001). Boredom was reported as a concern for specific allergens such as peanut, egg, sesame, and hazelnuts (P < .05), emphasizing the need for diverse food options. Notably, 59.9% of respondents mixed OIT foods with sweet items. Despite these dietary concerns, dietitians were underutilized, with only 9.5% of respondents having seen a dietitian and the majority finding dietitian support helpful with greater certainty about the exact dose (P < .001). CONCLUSIONS: Taste aversion and anxiety represent primary patient-related barriers to OIT. Taste aversion was highly age dependent, with older patients being more affected. Dietitians and psychology support were underutilized, representing a critical target to improve adherence and OIT success.

Dietary management of IgE and non-IgE-mediated food allergies in pediatric patients.

Food allergies (FA) consist of both IgE and non-IgE-mediated entities, with varying phenotypes and overlapping and different considerations for each specific disease presentation. In general, all FAs place children at increased risk for inadequate nutritional intake and negative impacts on their nutritional status, as well as negative impacts on the quality of life for the entire family. To minimize these untoward effects, a multidisciplinary approach should be taken, including consultation and management with a dietitian trained in the varying presentations of FA. Families should be instructed on label reading as a first line of nutritional management. During a nutrition consultation, the age of the child, growth, and nutritional status should be considered. Food refusal should be assessed and addressed. Families should be educated on avoidance and appropriate substitutions. In the case of cow's milk allergy, a suitable specialized formula should be suggested if the infant is not breastfed or if breast milk supply is not sufficient. Other mammalian milk should be avoided and careful consideration should be given before plant-based milk is used in young children. Specific food allergies may differ in terms of advice provided on the level of avoidance required, whether precautionary advisory labels should be avoided, and if a maternal avoidance of the allergen during breastfeeding should be advised. The role of immunonutrition on overall health should be discussed.

Association between gut microbiota development and allergy in infants born during pandemic-related social distancing restrictions.

BACKGROUND: Several hypotheses link reduced microbial exposure to increased prevalence of allergies. Here we capitalize on the opportunity to study a cohort of infants (CORAL), raised during COVID-19 associated social distancing measures, to identify the environmental exposures and dietary factors that contribute to early life microbiota development and to examine their associations with allergic outcomes. METHODS: Fecal samples were sequenced from infants at 6 (n = 351) and repeated at 12 (n = 343) months, using 16S sequencing. Published 16S data from pre-pandemic cohorts were included for microbiota comparisons. Online questionnaires collected epidemiological information on home environment, healthcare utilization, infant health, allergic diseases, and diet. Skin prick testing (SPT) was performed at 12 (n = 343) and 24 (n = 320) months of age, accompanied by atopic dermatitis and food allergy assessments. RESULTS: The relative abundance of bifidobacteria was higher, while environmentally transmitted bacteria such as Clostridia was lower in CORAL infants compared to previous cohorts. The abundance of multiple Clostridia taxa correlated with a microbial exposure index. Plant based foods during weaning positively impacted microbiota development. Bifidobacteria levels at 6 months of age, and relative abundance of butyrate producers at 12 months of age, were negatively associated with AD and SPT positivity. The prevalence of allergen sensitization, food allergy, and AD did not increase over pre-pandemic levels. CONCLUSIONS: Environmental exposures and dietary components significantly impact microbiota community assembly. Our results also suggest that vertically transmitted bacteria and appropriate dietary supports may be more important than exposure to environmental microbes alone for protection against allergic diseases in infancy.

Systematic review of the association between short chain fatty acids and allergic diseases.

We performed a systematic review to investigate the current evidence on the association between allergic diseases and short chain fatty acids (SCFAs), which are microbially produced and suggested as one mechanism on how gut microbiome affects the risk of allergic diseases. Medline, Embase and Web of Science were searched from data inception until September 2022. We identified 37 papers, of which 17 investigated prenatal or early childhood SCFAs and the development of allergic diseases in childhood, and 20 assessed SCFAs in patients with pre-existing allergic diseases. Study design, study populations, outcome definition, analysis method and reporting of the results varied between papers. Overall, there was some evidence showing that the three main SCFAs (acetate, propionate and butyrate) in the first few years of life had a protective effect against allergic diseases, especially for atopic dermatitis, wheeze or asthma and IgE-mediated food allergy in childhood. The association between each SCFA and allergic disease appeared to be different by disease and the age of assessment. Further research that can determine the potentially timing specific effect of each SCFA will be useful to investigate how SCFAs can be used in treatment or in prevention against allergic diseases.

Immune Mechanisms Underpinning Long COVID: Collegium Internationale Allergologicum Update 2024.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in a prolonged multisystem disorder termed long COVID, which may affect up to 10% of people following coronavirus disease 2019 (COVID-19). It is currently unclear why certain individuals do not fully recover following SARS-CoV-2 infection. SUMMARY: In this review, we examine immunological mechanisms that may underpin the pathophysiology of long COVID. These mechanisms include an inappropriate immune response to acute SARS-CoV-2 infection, immune cell exhaustion, immune cell metabolic reprogramming, a persistent SARS-CoV-2 reservoir, reactivation of other viruses, inflammatory responses impacting the central nervous system, autoimmunity, microbiome dysbiosis, and dietary factors. KEY MESSAGES: Unfortunately, the currently available diagnostic and treatment options for long COVID are inadequate, and more clinical trials are needed that match experimental interventions to underlying immunological mechanisms.

A systematic review and meta-analysis on nutritional and dietary interventions for the treatment of acute respiratory infection in pediatric patients: An EAACI taskforce.

Acute respiratory infections are a major cause of morbidity and mortality in children worldwide. Dietary and nutritional interventions, including minerals and vitamin supplementation, have been explored as potential treatments for these infections. However, the evidence on their efficacy is limited and inconclusive. This systematic review and meta-analysis aim to provide a comprehensive summary of the available evidence on the effectiveness of dietary and nutritional interventions for treating acute respiratory tract infections in children. A systematic review was conducted according to the PRISMA 2020 guidelines in April 2022 and updated in April 2023. Clinical trials focusing on dietary or nutritional interventions, including supplementations, in children with acute respiratory tract infections were included. The selection of interventions and outcomes was based on biological plausibility. Data were extracted using a standardized form, and the risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta-analysis was performed using random-effect models. A total of 50 studies were included in the review. Four trials were conducted in low, 32 in lower-middle, 12 in upper-middle, and only two in high-income countries. The studies evaluated various dietary interventions, including zinc, vitamin A, vitamin E, vitamin D, and probiotics. The results of individual studies on the efficacy of these interventions were mixed, with some showing positive effects on clinical outcomes such as duration of symptoms, while others showed no significant impact. Meta-analysis was conducted for zinc supplementation in children with pneumonia, and the pooled results suggested a potential limited benefit in terms of reduced hospital length of stay but not time to recovery. Meta-analyses on vitamin D did not show any effect in children with pneumonia. This systematic review fills a critical gap in the literature by synthesizing the available evidence on the efficacy and safety of nutritional or dietary interventions for acute respiratory tract infections in children. The findings indicate no dietary or nutritional intervention can currently be recommended for the routine treatment of respiratory tract infections in children based on single supplement studies. The metanalysis suggests that zinc supplementation might have a beneficial effect on length of hospitalization in children with pneumonia. New studies are needed to establish more conclusive evidence for pediatric acute respiratory diseases especially for children living in a context of high-income countries.

Identifying Children at Risk of Growth and Nutrient Deficiencies in the Food Allergy Clinic.

BACKGROUND: Food allergies affect growth in children by decreasing the availability of nutrients through decreased dietary intake, increased dietary needs, food-medication interactions, and psychosocial burden. Guidelines on food allergy management frequently recommend nutrition counseling and growth monitoring of children with food allergies. OBJECTIVE: To provide clear guidance for clinicians to identify children with food allergies who are at nutritional risk and ensure prompt intervention. METHODS: We provide a narrative review summarizing information from national and international guidelines, retrospective studies, population studies, review articles, case reports, and case series to identify those with food allergy at greatest nutritional risk, determine the impact of nutritional interventions on growth, and develop guidance for risk reduction in children with food allergies. RESULTS: Children with food allergies are at increased risk of nutritional deficiencies and poor growth. Nutritional assessment and intervention can improve outcomes. Identifying poor growth is an important step in the nutrition assessment. Therefore, growth should be assessed at each allergy evaluation. Interventions to ensure adequate dietary intake for growth include appropriately prescribed elimination diets, breast-feeding support and assessment, supplemental formula, vitamin and/or mineral supplementation, appropriate milk substitutes, and timely introduction of nutrient-dense complementary foods. Access to foods of appropriate nutritional value is an ongoing concern. CONCLUSION: Nutrition intervention or referral to registered dietitian nutritionists with additional training and/or experience in food allergy may result in improved growth and nutrition outcomes.

Precautionary Allergen Labeling: Avoidance for All?

PURPOSE OF REVIEW: Precautionary allergen labeling (PAL) suggests the risk of unintended allergen presence (UAP) in food but is unregulated in most countries and inconsistently applied by food manufacturers. This review evaluates the current use of PAL, its relevance to allergic consumers, and weighs possible advantages and disadvantages of avoiding products with PAL. RECENT FINDINGS: In most countries, manufacturers are free to decide whether, when, and how to apply PAL resulting in inconsistencies and consumer confusion. Patients with food allergy often interpret PAL incorrectly and without guidance from their health care providers. Health care providers are also prone to misinterpreting PAL, indicating a need for better education. Consumers desire guidance on whether to avoid products with PAL or not. Until further regulatory guidance is available, shared decision-making between patient and provider is required to offer individualized, rather than one-size-fits-all, approaches to PAL.

Reported food-related symptoms and food allergen sensitization in a selected adult population in Hyderabad, India: A hospital-based survey.

Background: Research on reported food-related triggers of atopic disease in South Asian adults is lacking despite the region's large population and the global significance of allergic diseases. Objectives: The study aimed to identify prevalent local food items and assess allergic sensitization rates to potential trigger foods for atopic diseases via skin prick and specific IgE testing. Methods: The study began with a pilot survey of 100 subjects recruited from 4 hospitals in Hyderabad, India, focusing on foods perceived to relate to asthma, allergic rhinitis, atopic dermatitis, urticaria, and gastrointestinal allergic symptoms. A subsequent main study evaluated 2010 participants, 1754 of whom were diagnosed with an aforementioned atopic disease and who reported allergic symptoms related to any of 77 foods identified in the pilot study. Ultimately 1622 patients who consented to skin prick and specific IgE testing and who reported at least 1 food item triggering allergic diseases were included in the final analysis. Results: Among 1622 patients (average age, 42.6 ± 12.9 years; 55.5% male), asthma was the most commonly diagnosed atopic disease (26.4%), with itching and rash being frequently reported symptoms (22.7%). Notably, 94.9% of patients had total serum IgE > 144 kU/L. Chickpea, cabbage, eggplant, walnut, cumin, and betel leaf were the most commonly reported trigger foods. Conclusion: In this sample of South Indian adults diagnosed with allergic disease, reported food triggers were most commonly local dietary staples, while reported reactions to priority allergens like peanut and sesame were conspicuously absent. Observed concordance between patient-reported food triggers and sensitization to reported food triggers was low, highlighting the need for improved clinical evaluation of suspected triggers.

The Maternal Diet Index and Offspring Microbiota at 1 Month of Life: Insights from the Mediterranean Birth Cohort MAMI.

Background: Maternal diet during pregnancy may play a role in infant health outcomes via the maternal microbiota. We assessed the association of the maternal diet index for the Mediterranean area (MDI-med) with infant gut microbiota at 1 month of life. Methods: The MAMI study is a longitudinal birth cohort in the Mediterranean area. In this work, a cross-sectional study, including 120 mother-infant dyads with available maternal diet and infant microbiota at 1-month-old data, was undertaken. The MDI developed in the US (MDI-US) was adapted for the MAMI cohort (MDI-med). Stratification based on extreme values resulted (22 in the "lower" MDI-med group and 23 in the "upper" group from the mean). Relative microbial abundances and alpha (microbial richness and diversity indexes) and beta diversity (Bray-Curtis distance matrix) were compared between the groups. Results: Higher maternal daily vegetable intake and lower red meat intake were the characteristics of the "upper" MDI-med group. Significantly lower microbial diversity (Shannon and InvSimpson index (p = 0.01)), but no changes in richness (Chao1 index) nor in beta-diversity, using Bray-Curtis distance, were observed in the "upper" group, compared to the "lower" MDI-med group. A higher relative abundance of the Bifidobacterium genus (Actinomycetota phylum) was associated with maternal daily vegetable and yogurt intake. Conclusion: Reduced infant microbial diversity at 1 month of age was associated with "upper" MDI-med scores. Higher maternal intakes of vegetables and yogurt were associated with higher relative abundances of the Bifidobacterium genus in the infant gut. Further studies are needed to understand the link between pregnancy diet, infant microbiota, and health outcomes.

Nutrition in chronic inflammatory conditions: Bypassing the mucosal block for micronutrients.

Nutritional Immunity is one of the most ancient innate immune responses, during which the body can restrict nutrients availability to pathogens and restricts their uptake by the gut mucosa (mucosal block). Though this can be a beneficial strategy during infection, it also is associated with non-communicable diseases-where the pathogen is missing; leading to increased morbidity and mortality as micronutritional uptake and distribution in the body is hindered. Here, we discuss the acute immune response in respect to nutrients, the opposing nutritional demands of regulatory and inflammatory cells and particularly focus on some nutrients linked with inflammation such as iron, vitamins A, Bs, C, and other antioxidants. We propose that while the absorption of certain micronutrients is hindered during inflammation, the dietary lymph path remains available. As such, several clinical trials investigated the role of the lymphatic system during protein absorption, following a ketogenic diet and an increased intake of antioxidants, vitamins, and minerals, in reducing inflammation and ameliorating disease.

Prevalence of tree nut allergy in Europe: A systematic review and meta-analysis.

In 2014, the European Academy of Allergy and Clinical Immunology (EAACI) published the first systematic review that summarized the prevalence of food allergy (FA) and food sensitization in Europe for studies published 2000-2012. However, only summary estimates for tree nut allergy (TNA) were feasible in that work. In the current update of that systematic review, we summarized the prevalence of tree nut allergy/sensitization to individual tree nuts. Six databases were searched for relevant papers published 2012-2021 and 17 eligible studies were added to the 15 studies already identified between 2000 and 2012, giving a total of 32 studies. Of the investigated tree nuts, meta-analysis was possible for hazelnut, walnut, almond, and in few cases, for cashew, and Brazil nut. The lifetime self-reported prevalence was 0.8% (95% CI 0.5-1.1) for hazelnut and 0.4% (0.2-0.9) for walnut. The point self-reported prevalence was 4.0% (2.9-5.2) for hazelnut, 3.4% (2.0-4.9) for Brazil nut, 2.0% (1.1-2.9) for almond, and 1.8% (1.1-2.5) for walnut. Point prevalence of food challenge-confirmed TNA was 0.04% (0.0-0.1) for hazelnut and 0.02% (0.01-0.1) for walnut. Due to paucity of data, we could not identify any meaningful and consistent differences across age groups and European regions.