Diagnosis and management of food allergy-induced constipation in young children-An EAACI position paper.

The recognition of constipation as a possible non-Immunoglobulin E (IgE)-mediated allergic condition is challenging because functional constipation (unrelated to food allergies) is a common health problem with a reported worldwide prevalence rate of up to 32.2% in children. However, many studies in children report challenge proven cow's milk allergy and constipation as a primary symptom and have found that between 28% and 78% of children improve on a cow's milk elimination diet. Due to the paucity of data and a focus on IgE-mediated allergy, not all food allergy guidelines list constipation as a symptom of food allergy. Yet, it is included in all cow's milk allergy guidelines available in English language. The Exploring Non-IgE-Mediated Allergy (ENIGMA) Task Force (TF) of the European Academy for Allergy and Clinical Immunology (EAACI) considers in this paper constipation in the context of failure of standard treatment and discuss the role of food allergens as culprit in constipation in children. This position paper used the Delphi approach in reaching consensus on both diagnosis and management, as currently published data are insufficient to support a systematic review.

Referral Pathways for Children with Atopic Diseases in Denmark.

Atopic diseases such as atopic dermatitis, food allergy, allergic rhinoconjunctivitis, and/or asthma are common. In Denmark, however, there are multiple referral pathways for these diseases in the healthcare system and they are poorly understood. To describe how children with atopic diseases navigate their way through the Danish healthcare system, a questionnaire was distributed to children aged ≤ 17 years, who were being treated for atopic diseases between August 2020 and June 2021, either by a practising specialist or a hospital department, in the Capital Region of Denmark. A total of 279 children completed the questionnaire and most were referred to a specialist or to a hospital by their general practitioner. No "common track" to hospital existed for patients with ≥ 3 atopic diseases. These patients were more often referred to a hospital compared with children with 2 atopic diseases or fewer (odds ratio [OR] 3.79; 95% CI 2.07-7.24). The primary determinants for hospital treatment were food allergy (OR 4.69; 95% CI 2.07-10.61) and asthma (OR 2.58; 95% CI 1.18-5.63). In conclusion, children with multiple atopic diseases were more likely to be referred to hospital departments than to practising specialists, mainly due to food allergies.

Prevalence and Severity of COVID-19 among Pediatric Patients with Atopy: A Cross-sectional Study in Kerman, Southeast Iran.

The tragic COVID-19 pandemic affected many children worldwide. Among the factors that may influence the course of viral infections including COVID-19, it is still uncertain whether atopy has a protective or predisposing role. The study aims to address the knowledge gap by investigating the prevalence and severity of COVID-19 among atopic children in Kerman, in 2022. A descriptive-analytical cross-sectional study on children with a history of atopy was performed in Kerman Medical University. Demographic information, type of atopy (including allergic rhinitis, Hyper-Reactive Airway Disease (HRAD) or asthma, eczema, urticaria, anaphylaxis, and food allergy), history of COVID-19 infection, and disease severity were recorded. A total of 1007 children and adolescents, (boys: 56.4%, girls: 43.6%, age:5.61±2.64 years) were included in the study. History of COVID-19 infection was positive in 53.5%, with 75.9% of the cases exhibiting mild disease severity. The frequency of atopies was HRAD or asthma (67.2%), allergic rhinitis (42.6%), and food allergy (27.4%). The frequency of COVID-19 cases was significantly higher among patients with HRAD or asthma, whereas it was significantly lower among those with food allergies, anaphylaxis, and eczema. Among atopic individuals, COVID-19 severity was significantly lower in those with allergic rhinitis, while the opposite trend was observed among food-allergic individuals. This study sheds light on the relationship between atopy and COVID-19 among pediatric patients. It seems specific types of atopies may influence the risk and severity of COVID-19 infection differently. A better understanding of these associations can inform clinical management and preventive measures for vulnerable pediatric populations.

Psychometric properties of disease-specific health-related quality of life instruments for food allergy: A COnsensus-based Standards for the selection of health Measurement INstruments-based systematic review.

Food allergies severely impact the health-related quality of life (HRQoL) of patients and their caregivers (family or informal caregivers). Currently there is no comprehensive review to provide an overview and critical assessment of the instruments in the field. Six databases were searched from inception until 10 August 2023, and a combination of subject terms and free words was used to search the literature. We used the COnsensus-based Standards for the selection of health Measurement INstruments methodology (COSMIN) to evaluate the measurement properties of the instruments. Forty-one studies reported on ten eligible instruments. Based on COSMIN guidelines, one instrument was recommended for Grade A, and the remaining nine instruments were recommended for Grade B. The Grade A instrument identified, the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF), can help researchers assess the effectiveness of treatment for patients with food allergy and to understand the psychosocial impact of the disease on patients.

Group 2 innate lymphoid cells are key in lipid transfer protein allergy pathogenesis.

Background: Immunopathology in food allergy is characterized by an uncontrolled type 2 immune response and specific-IgE production. Recent studies have determined that group 2 innate lymphoid cells (ILC2) participate in the food allergy pathogenic mechanism and their severity. Our objective was to investigate the role of ILC2 in peach-allergic patients due to non-specific lipid transfer protein (Pru p 3) sensitization. Methods: The immune response in peripheral blood mononuclear cells was characterized in lipid transfer protein-allergic patients and healthy controls. We have analyzed the Pru p 3 uptake on ILC2, the expression of costimulatory molecules, and their involvement on the T-cell proliferative response and cytokine production under different experimental conditions: cytokines involved in group 2 innate lymphoid cell activation (IL-33 and IL-25), Pru p 3 as main food allergen, and the combination of both components (IL-33/IL-25+Pru p 3) using cell sorting, EliSpot, flow cytometry, and confocal microscopy. Results: Our results show that Pru p 3 allergen is taken up by group 2 innate lymphoid cells, regulating their costimulatory molecule expression (CD83 and HLA-DR) depending on the presence of Pru p 3 and its combination with IL-33/IL-25. The Pru p 3-stimulated ILC2 induced specific GATA3+Th2 proliferation and cytokine (IL-4, IL-5, and IL-13) production in lipid transfer protein-allergic patients in a cell contact-dependent manner with no changes in Tbet+Th1- and FOXP3+Treg cell differentiation. Conclusions: The results indicate that in lipid transfer protein-allergic patients, the responsible allergen, Pru p 3, interacts with group 2 innate lymphoid cells, promoting a Th2 cell response. Our results might be of interest in vivo, as they show a role of group 2 innate lymphoid cells as antigen-presenting cells, contributing to the development of food allergy. Consequently, group 2 innate lymphoid cells may be considered as potential therapeutic targets.

Metabolomic pathways in food allergy.

Food allergy (FA) is a widespread issue, affecting as many as 10% of the population. Over the past two to three decades, the prevalence of FA has been on the rise, particularly in industrialized and westernized countries. FA is a complex, multifactorial disease mediated by type 2 immune responses and involving environmental and genetic factors. However, the precise mechanisms remain inadequately understood. Metabolomics has the potential to identify disease endotypes, which could beneficially promote personalized prevention and treatment. A metabolome approach would facilitate the identification of surrogate metabolite markers reflecting the disease activity and prognosis. Here, we present a literature overview of recent metabolomic studies conducted on children with FA.

[Mast Cell-Neutrophil Communication Regulates Allergic Diseases].

Allergic diseases (e.g., food allergies) are a growing problem, with increasing numbers of individuals experiencing them worldwide. Congruently, the adverse reactions (e.g., anaphylaxis) associated with the administration of vaccines against emerging infectious diseases such as coronavirus disease 2019 (COVID-19) have become a familiar problem. Allergic diseases, which have a wide variety of symptoms, are difficult to prevent or cure; treatment is currently limited to therapeutic drugs or allergen immunotherapy. Therefore, elucidating new allergic regulatory factors that control the allergic (i.e., mast cell) responses is important. While investigating the regulatory mechanisms of the wide range of allergic responses of mast cells, we found that the affinity of allergens to immunoglobin E (IgE) regulates allergic inflammation through the differences in the secretory responses of mast cells and the types and interactions of the cells infiltrating the tissues. Here, we present our recent findings regarding the affinity of allergens to IgE in regulating allergic inflammation, heterogeneous secretory granules inducing diverse secretory responses, and mast cells interacting with neutrophils, thereby regulating the various allergic responses.

[A CHILD CASE OF EGOMA (PERILLA FRUTESCENS) ALLERGY DUE TO SCHOOL LUNCH, PROBABLY CAUSED BY PERCUTANEOUS SENSITIZATION].

Herein, we report the case of a 7-year-old girl with a history of atopic dermatitis because of infancy. Her grandfather grew Egoma (Perilla frutescens), and her family frequently consumed food items prepared using Egoma; however, she never consumed them because she did not enjoy these food items; she experienced vomiting, facial swelling, and oral discomfort upon ingesting Egoma during school lunch for the first time. Her food oral challenge test was positive, as well as a skin-prick test with sesame powder. Egoma antigen protein was extracted and reacted with patient serum by immunoblotting, which detected a positive band of approximately 26kDa. She was brought up in an environment with high exposure to Egoma; hence, she most likely developed an allergy to Egoma because of percutaneous sensitization. This is the first time an Egoma allergen analysis has been conducted in Japan, and we consider it to be a valuable case.

Three cases of scombroid syndrome in Italy: clinical and preventive considerations.

Background: Foodborne diseases are common sources of morbidity and mortality worldwide. Scombroid syndrome represents a particular condition since it is not directly related to the ingestion of spoiled food but is determined by high levels of histamine, a chemical mediator naturally produced within the human body under particular conditions. In these cases, histamine is formed as a result of the bacterial activity from histidine, an amino acid present at high levels in some fish species. The resulting symptomatology can range from mild symptoms such as headache and skin rash to more severe manifestations such as hypotension and coronary spasms. Reference regulations in Italy set maximum levels of histamine in food at 200 mg/kg. Cases description: The cases described involve a family of three who, following the ingestion of a tuna dish, started to exhibit symptoms typical of an allergic reaction. In one case, hypotension, tachycardia, and electrocardiographic changes in the ST-tract suggestive of myocardial ischemia also appeared with negative myocardionecrosis enzyme dosage. All three cases experienced complete remission of symptoms in the absence of sequelae. Histamine concentrations in fish sampled three days later were 169 mg/kg. Conclusion: The cases described emphasize the importance of proper differential diagnosis as well as the importance of implementing specific controls in food hygiene.

Extracellular adenosine triphosphate skews the T helper cell balance and enhances neutrophil activation in mice with food allergies.

Exposure to food allergens elicits fast changes in the intestinal microenvironment, which guides the development of allergic reactions. Investigating the key information about these changes may help in better understanding food allergies. In this research, we explored the relationship between a food allergy and extracellular adenosine triphosphate (ATP), a danger molecule that has been proved to regulate the onset of allergic asthma and dermatitis but has not been studied in food allergies, by developing a unique animal model through allergen-containing diet feeding. After consuming an allergen-containing diet for 7 days, the allergic mice exhibited severe enteritis with elevated luminal ATP levels. The dysregulated luminal ATP worsened food-induced enteritis by enhancing Th17 cell responses and increasing mucosal neutrophil accumulation. In vitro experiments demonstrated that ATP intervention facilitated Th17 cell differentiation and neutrophil activation. In addition, the diet-induced allergy showed noticeable gut dysbiosis, characterized by decreased microbial diversity and increased diet-specific microbiota signatures. As the first, we show that food-induced enteritis is associated with an elevated concentration of luminal ATP. The dysregulated extracellular ATP exacerbated the enteritis of mice to a food challenge by manipulating intestinal Th17 cells and neutrophils.

Study protocol: The role of milk matrix lipids in programming the immunoreactivity of proteins derived from lactic acid bacteria.

Food allergy is widely recognized as a significant health issue, having escalated into a global epidemic, subsequently giving rise to the development of numerous additional complications. Currently, the sole efficient method to curb the progression of allergy is through the implementation of an elimination diet. The increasing number of newly identified allergens makes it harder to completely remove or avoid them effectively. The immunoreactivity of proteins of bacterial origin remains an unexplored topic. Despite the substantial consumption of microbial proteins in our diets, the immunologic mechanisms they might induce require thorough validation. This stands as the primary objective of this study. The primary objective of this study was to evaluate the effects of bacterial proteins on the intestinal barrier and immune system parameters during hypersensitivity induction in both developing and mature organisms. The secondary objective was to evaluate the role of lipids in the immunoreactivity programming of these bacterial proteins. Notably, in this complex, comprehensively designed in vitro, in vivo, and ex vivo trial, the immunoreactivity of various bacterial proteins will be examined. In summary, the proposed study intends to address the knowledge gaps regarding the effects of Lactobacillus microbial proteins on inflammation, apoptosis, autophagy, and intestinal barrier integrity in a single study.

Animal-derived food allergen: A review on the available crystal structure and new insights into structural epitope.

Immunoglobulin E (IgE)-mediated food allergy is a rapidly growing public health problem. The interaction between allergens and IgE is at the core of the allergic response. One of the best ways to understand this interaction is through structural characterization. This review focuses on animal-derived food allergens, overviews allergen structures determined by X-ray crystallography, presents an update on IgE conformational epitopes, and explores the structural features of these epitopes. The structural determinants of allergenicity and cross-reactivity are also discussed. Animal-derived food allergens are classified into limited protein families according to structural features, with the calcium-binding protein and actin-binding protein families dominating. Progress in epitope characterization has provided useful information on the structural properties of the IgE recognition region. The data reveals that epitopes are located in relatively protruding areas with negative surface electrostatic potential. Ligand binding and disulfide bonds are two intrinsic characteristics that influence protein structure and impact allergenicity. Shared structures, local motifs, and shared epitopes are factors that lead to cross-reactivity. The structural properties of epitope regions and structural determinants of allergenicity and cross-reactivity may provide directions for the prevention, diagnosis, and treatment of food allergies. Experimentally determined structure, especially that of antigen-antibody complexes, remains limited, and the identification of epitopes continues to be a bottleneck in the study of animal-derived food allergens. A combination of traditional immunological techniques and emerging bioinformatics technology will revolutionize how protein interactions are characterized.

Emerging Trends in Information-Seeking Behavior for Alpha-Gal Syndrome: Infodemiology Study Using Time Series and Content Analysis.

BACKGROUND: Alpha-gal syndrome is an emerging allergy characterized by an immune reaction to the carbohydrate molecule alpha-gal found in red meat. This unique food allergy is likely triggered by a tick bite. Cases of the allergy are on the rise, but prevalence estimates do not currently exist. Furthermore, varying symptoms and limited awareness of the allergy among health care providers contribute to delayed diagnosis, leading individuals to seek out their own information and potentially self-diagnose. OBJECTIVE: The study aimed to (1) describe the volume and patterns of information-seeking related to alpha-gal, (2) explore correlations between alpha-gal and lone star ticks, and (3) identify specific areas of interest that individuals are searching for in relation to alpha-gal. METHODS: Google Trends Supercharged-Glimpse, a new extension of Google Trends, provides estimates of the absolute volume of searches and related search queries. This extension was used to assess trends in searches for alpha-gal and lone star ticks (lone star tick, alpha gal, and meat allergy, as well as food allergy for comparison) in the United States. Time series analyses were used to examine search volume trends over time, and Spearman correlation matrices and choropleth maps were used to explore geographic and temporal correlations between alpha-gal and lone star tick searches. Content analysis was performed on related search queries to identify themes and subcategories that are of interest to information seekers. RESULTS: Time series analysis revealed a rapidly increasing trend in search volumes for alpha-gal beginning in 2015. After adjusting for long-term trends, seasonal trends, and media coverage, from 2015 to 2022, the predicted adjusted average annual percent change in search volume for alpha-gal was 33.78%. The estimated overall change in average search volume was 627%. In comparison, the average annual percent change was 9.23% for lone star tick, 7.34% for meat allergy, and 2.45% for food allergy during this time. Geographic analysis showed strong significant correlations between alpha-gal and lone star tick searches especially in recent years (ρ=0.80; P<.001), with primary overlap and highest search rates found in the southeastern region of the United States. Content analysis identified 10 themes of primary interest: diet, diagnosis or testing, treatment, medications or contraindications of medications, symptoms, tick related, specific sources of information and locations, general education information, alternative words for alpha-gal, and unrelated or other. CONCLUSIONS: The study provides insights into the changing information-seeking patterns for alpha-gal, indicating growing awareness and interest. Alpha-gal search volume is increasing at a rapid rate. Understanding specific questions and concerns can help health care providers and public health educators to tailor communication strategies. The Google Trends Supercharged-Glimpse tool offers enhanced features for analyzing information-seeking behavior and can be valuable for infodemiology research. Further research is needed to explore the evolving prevalence and impact of alpha-gal syndrome.

Nanosized Additives: Silicon Dioxide's Potential Role in Development of Food Sensitivities in Mice.

The anticaking agent, used in a wide variety of powdered food products, interfered with immune tolerance of ovalbumin, a model antigen; and it worsened gut inflammation in a mouse model of celiac disease.

Food Allergy.

Food allergy is a growing health problem affecting both pediatric and adult patients. Food allergies are often immunoglobulin E (IgE) mediated but other food-induced non-IgE-mediated diseases exist. Diagnosis of food allergy relies on the combination of clinical and reaction history, skin and IgE testing as well as oral food challenges. Although oral immunotherapy has been able to achieve sustained unresponsiveness in some patients, no cure for food allergies has been found to date. Avoidance of the inciting food as well as availability of epinephrine autoinjectors remains the mainstay of treatment.