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The use of eliciting doses (EDs) for food allergens is necessary to inform individual dietary advice and food allergen risk-management. The Eliciting Dose 01 (ED01) for milk and egg, calculated from populations of allergic subjects undergoing oral food challenges (OFCs), are 0.2 mg total protein. The respective Eliciting Dose 05 (ED05) is 2.4 mg for milk and 2.3 mg for egg. As about 70% children allergic to such foods may tolerate them when baked, we sought to verify the EDs of that subpopulation of milk and egg-allergic children.We retrospectively assessed consecutive OFC for fresh milk and egg between January 2018 and December 2020 in a population of baked food-tolerant children.Among 288 children (median age 56 - IQR 36-92.5 months, 67.1% male) included, 87 (30.2%) returned positive OFC results, 38 with milk and 49 with egg. The most conservative ED01 was 0.3 mg total protein (IQR 0.03-2.9) for milk and 14.4 mg total protein (IQR 3.6-56.9) for egg. The respective ED05 was 4.2 (IQR 0.9-19.6) mg for milk and 87.7 (IQR 43-179) mg for egg. Such thresholds are, respectively, 1.5 (milk ED01), 1.75 (milk ED05), 72 (egg ED01), and 38.35 (egg ED05) times higher than the currently used thresholds.The subpopulation of children allergic to milk and egg, but tolerant to baked proteins, displays higher reactivity thresholds than the general population of children allergic to milk and egg. Their risk stratification, in both individual and population terms, should consider this difference. In baked milk-tolerant children, milk causes reactions at lower doses than egg in our group of egg-tolerant children. This could be associated with the relative harmlessness of egg compared with milk in the determinism of fatal anaphylactic reactions in children.

PURPOSE OF REVIEW To perform a nonsystematic review of the literature on the microbiota in the different types of non-IgE-mediated food allergy. RECENT FINDINGS The commonest non-IgE-mediated disorders managed by allergists include: eosinophilic esophagitis, food protein-induced enteropathy, food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis. The review of the literature describes how at phylum level we observe an increase of Proteobacteria in eosinophilic esophagitis esophageal microbiota and in food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis gut microbiota, while we observe an increase of Bacteroidetes in healthy controls. Several studies endorse the concept that a bloom of Proteobacteria in the gut reflects dysbiosis or an unstable gut microbial community structure. In several studies, the type of diet, the use of probiotics and in a single experience the use of fecal microbiota transplantation has produced significant variations of the microbiota. SUMMARY Genetic factors alone cannot account for the rapid rise in food allergy prevalence and the microbiome might be contributing to allergy risk. Our review showed that common features of the pathological microbiota among different types of non-IgE-mediated food allergy can be identified. These evidences suggest a possible role of the microbiota in the pathogenesis and non-IgE-mediated food allergies and the need to understand the effects of its modulation on the disorders themselves.

Objectives Infants with cow's milk allergy (CMA) are in need of a substitute formula up to 2 years. The are three requisites for a substitute of milk in CMA: tolerability, nutritional adequacy, and cost‐effectiveness. We evaluate here the tolerability of a new amino acid–based infant formula for the management of CMA. Methods In a phase III/IV prospective, multicentre, open‐label, international study, infants and children with immunoglobulin E‐mediated CMA were exposed to a diagnostic double‐blinded, placebo‐controlled food challenge with a new amino acid formula by Blemil Plus Elemental using Neocate as the placebo. If tolerant to it, the study formula was integrated into the patients’ usual daily diet for 7 days. Efficacy on day 7 was assessed in terms of symptoms associated with CMA, amount of formula consumed, nutritional and energy intake, and anthropometric data. Results Thirty children (17 M and 13 F; median age, 1.58; range, 0.08‐12.83 years) completed the open challenge and were able to consume the study formula for at least 7 days. No signs or symptoms of allergic reactions were recorded among children assuming either the test or the control formula, with a lower 95% one‐sided confidence interval for the proportion of subjects who did not experience allergic reactions above 90%. Sixteen patient under the age of two continued with the optional extension phase. Conclusions The study formula meets the American Academy of Pediatric criteria for hypoallergenicity and is well tolerated in short‐term use. During optional phase, growth of the patients was not hindered by the study formula., This study provides data on a new amino acid formula, documenting the hypoallergenicity of such a preparation in a cohort of children with milk allergy. These children are in need of a substitute formula especially up to 2 years. We designed a study in compliance with the rules and procedures indicated by the American Academy of Pediatric regarding studies on new special formulas to be included in the therapeutic options.

Background. The use of eliciting doses (EDs) for food allergens is necessary to inform individual dietary advice and food allergen risk-management. The Eliciting Dose 01 (ED01) for milk and egg, calculated from populations of allergic subjects undergoing diagnostic Oral Food Challenges (OFCs), are 0.2 mg total protein. The respective Eliciting Dose 05 (ED05) are 2.4 mg for milk and 2.3 mg for egg. As about 70% children allergic to such foods may tolerate them when baked, we sought to verify the EDs of that subpopulation of milk and egg-allergic children. Methods. We retrospectively assessed consecutive diagnostic OFC for fresh milk and egg between January 2018 and December 2020 in a population of baked food-tolerant children. Results. Among 288 children (median age 56 - IQR 36-92.5 months, 67.1% male) included, 87 (30.2%) returned positive OFC results, 38 with milk and 49 with egg. The most conservative ED01 were 0.3 mg total protein (IQR 0.03-2.9) for milk and 14.4 mg total protein (IQR 3.6-56.9) for egg. The respective ED05 were 4.2 (IQR 0.9-19.6) mg for milk and 87.7 (IQR 43-179) mg for egg. Such thresholds are respectively 1.5 (milk ED01), 1.75 (milk ED05), 72 (egg ED01), and 38.35 (egg ED05) times higher than the currently used thresholds. Conclusions The subpopulation of children allergic to milk and egg, but tolerant to baked proteins, displays higher reactivity thresholds than the general population of children allergic to milk and egg. Their risk stratification, in both individual and population terms, should consider this difference. In baked milk-tolerant children, milk causes reactions at lower doses than egg in our group of egg-tolerant children. This could be associated with the relative harmlessness of egg compared to milk in the determinism of fatal anaphylactic reactions in children

Down syndrome (DS) is one of the most common chromosomal anomalies. Gastrointestinal disorders in DS are predominantly related to anatomical anomalies and celiac disease. In 2015, the first two cases of non-IgE-mediated food allergy in patients with DS were described. However, gastrointestinal symptoms experienced by subjects with DS have never been related to a possible non-IgE-mediated food allergy and a Food Protein-induced Enterocolitis syndrome (FPIES). A retrospective descriptive single-center study was conducted. Subjects included were children with acute FPIES who entered our institutional follow-up protocol between January 2013 and January 2020. Among the 85 patients (forty-nine boys—57.6%), ten (11.76%) were children with DS. In our population, the FPIES triggers included different foods (such as milk, egg, fruit, fish, wheat, soy, beef, etc.). Nine patients with DS showed FPIES reactions after ingesting cow’s milk (one even with beef and three with soy), while the last one was affected by FPIES to fish. Considering the subgroup of patients affected by cow’s milk FPIES (40 subjects overall), 22.5% had a diagnosis of DS. Patients with DS experienced acute FPIES reactions with a severity degree slightly higher than that reported in other patients, ranging from mild-moderate to severe or very severe. During the acute reactions, the patients with DS showed increased white blood cell production, absolute neutrophil count and C-reactive protein levels. This series provides a starting point for novel hypothesis-testing clinical research and possible specific immunological alterations in FPIES children with or without DS.

Extremely sensitive food-allergic patients may react to very small amounts of allergenic foods. Precautionary allergen labelling (PAL) warns from possible allergenic contaminations. We explored the ability of proteomic methods to identify minute amounts of milk/egg allergens in a brand of PAL-labelled milk- and egg-free biscuits. We evaluated the reactivity of children with severe milk and egg allergy, by oral food challenge. Traces of milk and/or egg allergens in biscuits were measured by two different liquid-chromatography-mass spectrometry methods. The binding of patient's serum with egg/milk proteins was assessed at immunoblotting. None of the patients reacted to biscuits. Egg and milk proteins were found under the limit of detection of 0.6 µg/g for milk and egg (method A), and of 0.1 and 0.3 µg /g for milk and egg, respectively (method B). The immunoblots did not show milk/egg proteins in the studied biscuits. Our biscuits did not contain allergens of clinical significance. Their milk/egg content is far lower than 4 µg of milk or egg protein per gram of product, the minimal doses considered theoretically capable of causing reactions. With high sensitivity, proteomic assessments predict the harmlessness of very small amount of allergenic foods and can be used to avoid unnecessary PAL.

To provide an update of the studies concerning the diagnosis and management of food additives allergy.Additives improve specific characteristics of food products, but they may induce allergic even life-threatening reactions. Physical examination and medical history are basic to assess specific in-vivo and in-vitro tests. The only treatment for allergic patients consists in avoiding the food containing culprit additives. High-risk patients should be able to recognize severe reactions and self-manage them.The prevalence of adverse reactions to food additives is low, and it may depend on comorbidities, like asthma or chronic idiopathic urticaria. Food labels may help the correct identification of ingredients. Natural additives like spices should cause immediate reactions because of a pollen-sensitization or panallargen proteins presence. Additive-free diets may help the patient care, but the authors suggest assessing an oral food challenge with the culprit substance if there are no contraindications.

Purpose of review Allergic diseases are increasing worldwide and are considered an important public health problem causing severe and even life-threatening reactions. The creation of guidelines aims to help clinicians improving the quality of diagnosis and management of such diseases. Clinical practice guidelines alone are not sufficient and there is a need for implementation strategies for their introduction into daily practice. We report here the main international allergy guidelines with a more focused look on the Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines and their effect on clinical practice. Recent findings DRACMA guidelines have clearly modified the approach to cow's milk allergy (CMA) from its diagnosis to treatment tailoring the choices for each patient. Although they strongly recommend oral food challenge for diagnosing CMA, they also indicate that it may not be necessary in many cases with the introduction of the pretest probability of CMA. Studies on the implementation of DRACMA guidelines show how they influenced the formula market, making appropriate treatments more affordable. Summary DRACMA reconciled international differences in the diagnosis and management of CMA. They introduced the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology in the field of food allergy and highlighted the importance for meta-analyses to be able to adapt recommendations to the local context.

Food allergy (FA) and, in particular, IgE-mediated cow’s milk allergy is associated with compositional and functional changes of gut microbiota. In this study, we compared the gut microbiota of cow’s milk allergic (CMA) infants with that of cow’s milk sensitized (CMS) infants and Healthy controls. The effect of the intake of a mixture of Bifidobacterium longum subsp. longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 on gut microbiota modulation of CMA infants and probiotic persistence was also investigated. Gut microbiota of CMA infants resulted to be characterized by a dysbiotic status with a prevalence of some bacteria as Haemophilus, Klebsiella, Prevotella, Actinobacillus and Streptococcus. Among the three strains administered, B.longum subsp. infantis colonized the gastrointestinal tract and persisted in the gut microbiota of infants with CMA for 60 days. This colonization was associated with perturbations of the gut microbiota, specifically with the increase of Akkermansia and Ruminococcus. Multi-strain probiotic formulations can be studied for their persistence in the intestine by monitoring specific bacterial probes persistence and exploiting microbiota profiling modulation before the evaluation of their therapeutic effects.

Food allergy carries high importance and responsibility, affecting an estimated 220 million people worldwide. It is a frequent cause of food-induced anaphylaxis, a life-threatening condition requiring a toll of about one death per 50 million people a year worldwide. In order to help patients to identify allergenic foods and thus avoid anaphylactic reactions, 66 countries over the 5 continents require by law that allergenic ingredients must be declared when used in prepackaged foods. Unfortunately, the mandatory allergen list is not uniform, but varies among different countries. The widespread adoption of Precautionary Allergen Labeling (PAL) results in a proliferation of unregulated PALs with different informative statements. In this situation, the need of a scientific consensus on the definition of food allergy and the identification of a tolerable risk with routinely used detection assays, considering not only the eliciting dose but also the food source, is urgent. The aim of this manuscript is: 1) to draw a picture of the global situation in terms of PALs, and 2) to highlight new approaches that could aid in tackling the problem of regulating the labeling of allergens. These include the Voluntary Incidental Trace Allergen Labelling (VITAL) system, which intersects reference doses and labelling decisions, and a direct quantification of trace amounts of allergens at lower limit of detection (LOD) levels in the food itself through proteomics. We here highlight how, although with some limitations, the steady advances in proteomic approaches possess higher sensitivity than the recommended VITAL reference doses, allowing the identification of allergens at much lower LOD levels than VITAL. Considering that each assay used to detect allergen in food products carries method-specific issues, a more comprehensive and harmonized approach implementing both quantitative and qualitative methods could help overcoming the risk stratification approach and the overuse of PALs, offering promise as the field moves forward towards improving consumers' quality of life.

Background In some countries of the world, peanut allergy represents an important source of anaphylactic reactions. Traditionally treated with the avoidance of responsible allergens, this condition can also be targeted by oral peanut immunotherapy. Methods In this study, we review the beneficial and side effects of currently available forms of peanut oral immunotherapy (POIT). We report the discussions resulting from the publication of a meta-analysis that brought to light the downsides of oral immunotherapy for peanuts. Results In some clinical situations, the risk-benefit ratio can favor peanut oral immunotherapy over avoidance. In many other situations, this is not the case. The decision must be based on the values and preferences of clinicians and patients. Those not ready to accept serious adverse effects from POIT are likely to continue the elimination diet; those motivated to achieving desensitization, and prepared to accept serious adverse effects, may choose to undergo POIT. Conclusions Without being prejudiced against peanut oral immunotherapy, we indicate the possible evolution of treatment for this condition is in a rapidly evolving broader scenario. Among the future options, sublingual immunotherapy, parenteral immunotherapy with modified allergens, transcutaneous immunotherapy, and the use of biologics will become important options.

The development of oral tolerance or food allergy is an active process, related to dynamic interactions between host immune cells, microbiome, dietary factors, and food allergens. Oral tolerance is the default immune response in the gut. A food allergy occurs when this process fails and a pathologic Th2 response is activated. Oral food immunotherapy (OIT) aims to restore immune tolerance in food-allergic individuals. The stimulation of Tregs production seems to represent a crucial step in inducing long-term tolerance, but other mechanisms (e.g., the suppression of mast cell and basophil reactivity, changes in allergen-specific cells with regulatory markers) are involved. Several studies reported the efficacy of OIT in terms of "sustained unresponsiveness" (SU), an operational definition of immune tolerance. In successfully treated subjects, the ability to pass an oral food challenge 2 to 8 weeks after stopping the food allergen exposure seems to be conditioned by the treatment starting age, frequency, amount or type of food consumed, and by the duration of the maintenance phase. Based on the available data, the percentage of milk- and egg-allergic subjects achieving sustained unresponsiveness after an OIT ranges from 21% to 58,3%. A comprehensive understanding of mechanisms underlying the induction of oral tolerance with OIT, or natural tolerance to food allergens in healthy individuals, could potentially lead to advances in development of better treatment options for food allergic patients.

The epidemiology of food allergy did inspire theories on the reasons for the recent surge of the disease. We offer here a reasoned review on the relationships between the trajectories of human development and the trend of the food allergy epidemics.The exponential trend of the frequency of food allergy paralleled the explosive acceleration of the human development over the last few decades. Dietary factors have been indicated as responsible for these trends and targeted for potential preventive strategies. Other socio-economic factors have been related to this evolution: solar exposure, climate changes, structure of societies, reproductive choices and societal inequalities.The epidemiologic associations of food allergy suggest different causal theories. Future prevention strategies may be predicated not only on dietary interventions, but on wider programmes aimed to restore a human ecology promoting food tolerance.

Severe cases of food allergy account for the majority of the burden in terms of risks, quality of life, and resource expenditure. The traditional approach to these forms has been strict avoidance. More recently, Oral ImmunoTherapy (OIT) has gained a role in their management. However, in severe food allergies OIT is often infeasible.Case reports, observational, and prospective studies have recently proposed different approaches to severe food allergy. The majority of them include the use of biologics. Omalizumab has been the most studied drug for severe food allergies, and its role as adjuvant treatment to OIT is well established. Interest has been raised on other biologics, as dupilumab, reslizumab, and mepolizumab. Toll-like receptor agonists, and gene therapy using adeno-associated virus coding for Omalizumab are promising alternatives.The recent studies are deeply influencing the clinical practice. We review the modifications of the clinical approach to severe food allergies so far available. We indicate the possible evolutions of treatment with biologics in severe food allergies.

Purpose of review We review the laws on labeling in the international community, the difficulties they pose to the food manufacturers to prepare the food labels and the methodologies to determine the concentration of potential allergens in foods. Recent findings European Food Safety Authority and International Life Sciences Institute Europe are evaluating strategies to identify the threshold level of allergen that can trigger a reaction in individuals. The most used techniques to detect the presence of protein in food are Enzyme-linked immunosorbent assay, polymerase chain reaction and real time polymerase chain reaction. Researchers are now trying to apply proteomics to estimate the amount of protein within the food.In order to protect the health of consumers, the Codex Alimentarius Commission updates constantly the list of allergens. In response to these regulations, some industries have also added some precautionary allergen labeling (PAL). It was generally agreed that PAL statements needed to be visible, simple, and safe. It was suggested that PAL be standardized, an action that would occur if the 'Voluntary Incidental Trace Allergen Labelling' process was made mandatory. Summary So far, no laboratory technique is able to reassure the consumers about the composition of foods found on the packaging. International authorities produced increasingly stringent laws, but more is still to do.

The Diagnosis and Rationale for Action Against Cow’s Milk Allergy (DRACMA) guidelines were issued by World Allergy Organization (WAO) using the Grading of Recommendations Assessment, Development an...

The effects of omalizumab on food allergy thresholds have been little studied.To assess the real-life effects of omalizumab on food threshold tolerability in children treated for severe asthma.In this observational, real-life, efficacy study, we reviewed the food allergen thresholds of patients with severe asthma, as well as their immediate reactions to 2+ foods before and after a 4-month treatment with omalizumab. We also evaluated their control of asthma and their quality of life, as measured by Pediatric Quality of Life Inventory (PedsQL).Fifteen children, allergic to 37 foods, were evaluated. Omalizumab induced an increase in the allergen threshold for milk, egg, wheat, and hazelnut from a mean 1012.6 ± 1464.5 mg protein to 8727 ± 6463.3 eliciting dose (P.001). A total of 70.4% of subjects tolerated the complete challenge dose after 4 months of treatment with omalizumab. These foods were reintroduced in the patients' diet without the need for any oral immunotherapy procedures. The remaining foods were partially tolerated. The number of reactions to the unintended ingestion of allergenic foods over 4 months dropped from 47 to 2. The PedsQL increased from 61 ± 5.32 to 87 ± 7.33 (parental judgment; P.001) and from 65 ± 7.39 to 90 ± 4.54 (patients' judgment; P.001). The mean cost of omalizumab was €1311.63 per month.During treatment with omalizumab for severe uncontrolled asthma, the food allergen threshold increases to 8.6 times its original value. The quality of life of patients also increased, due to a better asthma control and a reduction in dietary restrictions. The cost/benefit ratio of such treatment for selected cases of food allergy remains to be evaluated.

Background In 2010, the diagnosis and treatment of IgE-mediated CMA were systematized in a GRADE guideline.Objectives & methods After 6 years, the state of the knowledge in diagnosis and treatment of CMA has largely evolved. We summarize here the main advances, and exemplify indicating some specific points: studies aimed at better knowledge of the effects of breastfeeding and the production of new special formulae intended for the treatment of CMA. The literature (PubMed/MEDLINE) was searched using the following algorithms: (1) [milk allergy] AND diagnosis; (2) [milk allergy] AND [formul*] OR [breast*], setting the search engine [6-years] time and [human] limits. The authors drew on their collective clinical experience to restrict retrieved studies to those of relevance to a pediatric allergy practice.Results Several clinical studies did address the possibility to diagnose CMA using new tools in vitro and in vivo, or to diagnose it without any evaluation of sensitization. Some studies also addressed the clinical role of formulae based on milk hydrolysates, soy, or rice hydrolysates in the treatment of CMA. Many studies have elucidated the effects of selective nutrients in breastfed infants on their immunologic and neurologic characteristics.Conclusions Evidence-based diagnostic criteria should be identified for non-IgE-mediated CMA. Debate is ongoing about the best substitute for infants with CMA. In particular, Hydrolyzed Rice Formulae have been widely assessed in the last six years. In the substitute choice, clinicians should be aware of recent studies that can modify the interpretation of the current recommendations. New systematic reviews and metanalyses are needed to confirm or modify the current DRACMA recommendations. Keywords: Cow’s milk allergy, Infants, DRACMA guidelines

Purpose of review In the last years, food allergy treatment is moving away from food avoidance to interventional treatments. We review here the recent developments on immunotherapy with food allergens. Recent findings Oral immunotherapy remains the best studied form of food immunotherapy. In 2017, further evidence has been added to its efficacy. Its mechanisms of action are under scrutiny. To reduce its side effects, studies have been dedicated to the simultaneous use of biologics, in particular omalizumab. Among the other forms of food immunotherapy that are being developed, the epicutaneous application of food allergens is promising. Summary The immunologic trajectories of the development of food tolerance may be intercepted by different forms of food immunotherapy. Research efforts aim to make these therapies feasible at the clinical level.

Purpose of review The prevalence of food allergy is increasing. More children are being diagnosed with food allergies, and it is taking longer to outgrow them, among those who develop tolerance. The aim of this review is to draw the profile of the persistent food allergic, so that prevention strategies can be developed and active treatment set up. Recent findings Many determinants are involved in food allergy prognosis: ethnicity and sex, type of food, innate immune system, eliciting dose, sensitization status and other biomarkers determination, gut microbiome composition, and the presence of comorbidities. Once identified, a persistent food allergy could be conveyed to active treatments, such as oral immunotherapy or the use of biologics, always taking into account their experimental nature. Summary A better understanding of prognostic factors and phenotypes of food allergy is crucial in decision-making when it comes to food allergy prevention and management. A good classification of the allergic patient allows to determine the degree of exclusion diets and the timing of the reintroduction of avoided food when possible. In the cases of persistent and severe food allergy, many promising interventions are emerging which could improve prognosis and quality of care.

Objective: The aim of this study was to determine the kinetics of true ileal protein digestion and digestible indispensable amino acid score (DIAAS) of a goat milk-based infant formula (GIF), a cow milk-based infant formula (CIF), and human milk (HM). Methods: The GIF, CIF, and HM were investigated in an in vitro gastrointestinal model simulating infant conditions. Digested compounds were dialyzed from the intestinal compartment as bioaccessible fraction. Dialysate was collected in 15 to 60-minute periods for 4 hours. True ileal protein digestibility and DIAAS were determined as bioaccessible nitrogen (N) and amino acids. Results: N bioaccessibility from the GIF showed similar kinetics to that of HM. The CIF showed a delay in N bioaccessibility versus the GIF and HM. In the 1st hour of digestion, N bioaccessibility was 19.9% ± 3.5% and 23.3% ± 1.3% for the GIF and HM, respectively, and 11.2% ± 0.6% for CIF (P

Background:Increased thyroid stimulating hormone (TSH) serum concentration can be a marker of subclinical hypothyroidism (SCH) or transient hyperthyrotropinemia. The aim of our study was to evaluate whether high serum TSH concentrations in allergic children could represent true SCH or isolated and transient hyperthyrotropinemia.Methods:We enrolled 620 allergic children (1.11–12.8 years) consecutively attending to our department. They were classified as atopics and non-atopics on the basis of the atopy work-up and, at baseline, they were investigated for thyroid function and low-grade inflammation state. Further, TSH was evaluated after 6 (T1) and 12 (T2) months.Results:Both atopics and non-atopics showed higher SCH prevalence compared to controls (p=0.0055 and p=0.02, respectively), and a significant association between atopy and SCH (OR 10.11, 95% CI 1.36–75.12) was found. Both at T1 and T2, atopics had a significant risk of developing severe SCH compared to non-atopics (RR 1.8, 95% CI 1.39–2.34 and 1.61, 95% CI 1.21–2.14; respectively).Conclusions:Our data may suggest that hyperthyrotropinemia in atopic children could be used as a marker of true SCH.

Background: The epidemiological decrease of Helicobacter pylori (Hp) infection has been recently associated to the increase of several extra-intestinal allergic disorders. Objective: We investigated the role of specific Hp IgG production in the development of IgE or not IgE mediated food allergy (FA) in children affected by atopic dermatitis (AD). Methods: From January 2010 to July 2013, 290 South Italian children, aged between 26 and 142 months, were consecutively referred to the Pediatric Clinic of the Pediatric Department at Second University of Naples and were diagnosed as affected by AD. The patients were classified in two groups on the basis of diagnosis of food allergy (88 FA affected and 202 not FA affected) and further divided on the basis of the diagnosis of atopy (63 IgE mediated and 23 not IgE mediated). Hp serum IgG was detected using an enzyme linked immunosorbent assay (ELISA) kit (Wampole Helicobactor pylori IgG ELISA II, Wampole Laboratories, Cranbury, NJ) and Hp stool antigens using enzyme immunoassay (Premier Platinum HpSa plus, Cincinnati OH). Results: We found a statistically significant higher prevalence of Hp serology positivity in not FA vs. FA AD-affected children (p ¼0.032) and a significant inverse association between FA and Hp immunization (1/OR 0.32 95% CI 0.11–0.95). Further, we identified an absolute prevalence Hp serology positivity in not-IgE-mediated rather than in IgE-mediated FA AD-affected patients (p ¼0.0006). Conclusion: We hypothesize that specific Hp IgG production could protect against the development of both FA and atopy in AD-affected children.

Food allergic individuals are exposed to unnecessary dietary restrictions due to precautionary food allergy labelling (PFAL). Two forms of PFAL exist: type I identifies the possible presence of allergenic contaminaion in foods (‘may content…’), type II indicates as potentially dangerous ingredients or contaminants that do no belong to official list of food allergens. PFAL type II is based on the fear of cross-reactivity with foods belonging to that list. PFAL type II is less known, but may be tempting for the legal offices of food companies, for clinicians in a ‘defensive medicine’ key, and even for legislators. We identify here a case of PFAL type II, allergy to rapeseed (belonging to the family of Brassicaceae). Increasingly used for their nutritional and nutraceutic value in asthma prevention, rapeseed has been indicated by regulatory authorities in Canada and Europe as potential cross-reactor with mustard. In this review, we provide the elements for a risk assessment of cross-reactivity of rapeseed/mustard allergy in the general population both clinically and from the point of view of the molecular allergy. Three findings emerge: 1. Allergic reactions to rapeseed are exceptional 2. The allergens identified in rapeseed and mustard are similar, but not identical 3. Reactions to rapeseed have never been described in mustard-allergic patients. On the ground of existing evidence, a precautionary labeling for rapeseed as potentially dangerous for patients allergic to mustard is not justified. In the interest of patients with multiple food allergy, PFAL type II must be avoided.

To verify the prevalence of thyroid autoimmunity (TA) and the possible association between atopy and TA in children affected by skin disease.Three hundred and twenty-four children consecutively referred due to skin disease symptoms to our Pediatric Department were enrolled. One hundred and eighty-seven were diagnosed with atopic dermatitis (AD), 95 with acute urticaria, 40 with chronic urticaria (CU), and 2 with alopecia areata (AA). According to the work-up for atopy, the children were divided into two groups: Atopics and non-atopics. TA was diagnosed by serum thyroid peroxidase autoantibodies and/or thyroglobulin autoantibodies levels more than twice normal values over a period of two months by immunoassay.In all children with skin disease, a significant prevalence of TA in atopics compared with non-atopics (13.67% vs 2.67%, P = 0.0016) and a significant association between TA and atopy (OR = 5.76, 95%CI: 1.71-19.35) were observed. These findings were confirmed as significant in children with AD: TA in atopics was 11.5%, while TA in non-atopics was 2.7% (P = 0.03, OR = 4.68, 95%CI: 1.02-21.38). In addition, atopics with CU showed a significantly higher prevalence of TA (26.9%), but none of the non-atopics showed CU (P = 0.0326). On the other hand, atopics with AA showed a 100% (2 out of 2) prevalence of TA, compared with none of the non-atopics.In children with skin disease, atopy seems to be associated with an increased risk of TA.

Aim To verify if subclinical hypothyroidism (SCH) could be associated to atopy in children. Methods Seven hundred and thirty-two Caucasian children from South Italy presenting symptoms of allergic disease were enrolled and submitted to atopy, obesity, chronic low grade inflammation, and SCH work up. Results Four hundred and forty-five out of 705 (63.12%) children affected by allergic disease were diagnosed as atopic and 260 (36.88%) as not atopic. The SCH prevalence was 6.3%. Significant higher prevalence of SCH among atopic children with average (group 2) and high (group 3) low grade chronic inflammation compared to atopic children with mild (group 1) low grade chronic inflammation was present. Moreover, group 1 and group 2 presented an OR to show SCH of 2.57 (95%CI: 1.55-6.26) and 2.96 (95%CI: 1.01-8.65), respectively. Both in atopic and not atopic children we found C3 serum levels significantly higher in group 3 respect to group 2 and group 1. Noteworthy, among atopic patients, also total immunoglobulin E (IgE) serum levels, were significantly higher in group 3 compared to group 2 and group 1 children. In atopic children, C3 and total IgE serum values increased in parallel with the increase of C-reactive protein values, while in not atopic children this phenomenon was not evident. Conclusion The possibility exists that an increasing atopic inflammation contributes to SCH occurrence. So far this is the first report in literature showing an association between SCH and atopy but further studies are needed to confirm our data.

Background As a result of several clinical reports addressing coincidence or coprevalence of atopy and autoimmune disease such as multiple sclerosis and type I diabetes mellitus, there has been considerable interest in defining the relationship between the expression of allergic and autoimmune disease in populations of patients. Although thyroid autoimmunity has been regularly associated with chronic urticaria in children, the cofrequency of thyroid autoimmunity and atopic dermatitis has not yet been investigated. The aim of the study was to describe our experience with children affected by atopic dermatitis and associated thyroid autoimmunity. Methods From January 2010 to December 2012, 147 children affected by atopic dermatitis were consecutively referred to the Pediatric Clinic of the Pediatric Department at the Second University of Naples. Seventy healthy children of comparable ages, unaffected by atopic dermatitis, atopy or thyroid disease, served as a control group. Results On the basis of skin prick test results we selected 54 IgE-mediated (36.7%) and 93 non-IgE-mediated AD (63.3%) children. Fourteen of 147 patients (9.52%) showed increased levels of antithyroid antibodies. Conclusions Our results therefore suggest that atopy, especially food allergy, and autoimmunity are two potential outcomes of dysregulated immunity.