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A food allergy is an immunoglobulin E (IgE)-mediated hypersensitive reaction to food, which consists in the appearance of allergic symptoms; it can vary from common urticaria to even fatal anaphylaxis. The prevalence of food allergies has been increasing in the past twenty years and it represents a major public health problem in industrialized countries. The mechanism that leads to food allergies is the lack of immunologic and clinical tolerance to food allergens. The diagnosis of IgE-mediated food allergies is based on the combined use of a detailed medical history, in-vivo, and in-vitro research of specific IgE, the elimination diet, and the double-blind placebo-controlled food challenge. The only currently available treatment for allergies is the strict elimination diet. This type of attitude, which we could define as “passive”, does not overcome the risk of accidental reactions due to involuntary intake of the culprit food. For food allergy management, an “active” approach is urgently needed, such as specific allergen immunotherapy, which is currently under development and only used for research purposes. This article aims to give an updated review of IgE-mediated food allergies in pediatric populations in terms of epidemiology, pathogenesis, prevention, diagnosis, and management.

Fish allergy constitutes a severe problem worldwide. Its prevalence has been calculated as high as 7% in paediatric populations, and in many cases, it persists into adulthood with life-threatening signs and symptoms. The following review focuses on the epidemiology of Immunoglobulin E (IgE)-mediated fish allergy, its pathogenesis, clinical manifestations, and a thorough approach to diagnosis and management in the paediatric population. The traditional approach for managing fish allergy is avoidance and rescue medication for accidental exposures. Food avoidance poses many obstacles and is not easily maintained. In the specific case of fish, food is also not the only source of allergens; aerosolisation of fish proteins when cooking is a common source of highly allergenic parvalbumin, and elimination diets cannot prevent these contacts. Novel management approaches based on immunomodulation are a promising strategy for the future of these patients.

Google Trends (GT) data have shown promising results as a complementary tool to classical surveillance approaches. However, GT data are not necessarily provided by a representative sample of patients and may be skewed toward demographic and clinical groups that are more likely to use the internet to search for their health. In this study, we aimed to assess whether GT-based models perform differently in distinct population subgroups. To assess that, we analyzed a case study on asthma hospitalizations. We analyzed all hospitalizations with a main diagnosis of asthma occurring in 3 different countries (Portugal, Spain, and Brazil) for a period of approximately 5 years (January 1, 2012-December 17, 2016). Data on web-based searches on common cold for the same countries and time period were retrieved from GT. We estimated the correlation between GT data and the weekly occurrence of asthma hospitalizations (considering separate asthma admissions data according to patients' age, sex, ethnicity, and presence of comorbidities). In addition, we built autoregressive models to forecast the weekly number of asthma hospitalizations (for the different aforementioned subgroups) for a period of 1 year (June 2015-June 2016) based on admissions and GT data from the 3 previous years. Overall, correlation coefficients between GT on the pseudo-influenza syndrome topic and asthma hospitalizations ranged between 0.33 (in Portugal for admissions with at least one Charlson comorbidity group) and 0.86 (for admissions in women and in White people in Brazil). In the 3 assessed countries, forecasted hospitalizations for 2015-2016 correlated more strongly with observed admissions of older versus younger individuals (Portugal: Spearman ρ=0.70 vs ρ=0.56; Spain: ρ=0.88 vs ρ=0.76; Brazil: ρ=0.83 vs ρ=0.82). In Portugal and Spain, forecasted hospitalizations had a stronger correlation with admissions occurring for women than men (Portugal: ρ=0.75 vs ρ=0.52; Spain: ρ=0.83 vs ρ=0.51). In Brazil, stronger correlations were observed for admissions of White than of Black or Brown individuals (ρ=0.92 vs ρ=0.87). In Portugal, stronger correlations were observed for admissions of individuals without any comorbidity compared with admissions of individuals with comorbidities (ρ=0.68 vs ρ=0.66). We observed that the models based on GT data may perform differently in demographic and clinical subgroups of participants, possibly reflecting differences in the composition of internet users' health-seeking behaviors.

The prevalence of food allergy has increased in recent years, especially in children. Allergen avoidance, and drugs in case of an allergic reaction, remains the standard of care in food allergy. Nevertheless, increasing attention has been given to the possibility to treat food allergy, through immunotherapy, particularly oral immunotherapy (OIT). Several OIT protocols and clinical trials have been published. Most of them focus on children allergic to milk, egg, or peanut, although recent studies developed protocols for other foods, such as wheat and different nuts. OIT efficacy in randomized controlled trials is usually evaluated as the possibility for patients to achieve desensitization through the consumption of an increasing amount of a food allergen, while the issue of a possible long-term sustained unresponsiveness has not been completely addressed. Here, we evaluated current pediatric OIT knowledge, focusing on the results of clinical trials and current guidelines. Specifically, we wanted to highlight what is known in terms of OIT efficacy and effectiveness, safety, and impact on quality of life. For each aspect, we reported the pros and the cons, inferable from published literature. In conclusion, even though many protocols, reviews and meta-analysis have been published on this topic, pediatric OIT remains a controversial therapy and no definitive generalized conclusion may be drawn so far. It should be an option provided by specialized teams, when both patients and their families are prone to adhere to the proposed protocol. Efficacy, long-term effectiveness, possible role of adjuvant therapies, risk of severe reactions including anaphylaxis or eosinophilic esophagitis, and impact on the quality of life of both children and caregivers are all aspects that should be discussed before starting OIT. Future studies are needed to provide firm clinical and scientific evidence, which should also consider patient reported outcomes.

Shellfish, including various species of mollusks (e.g., mussels, clams, and oysters) and crustaceans (e.g., shrimp, prawn, lobster, and crab), have been a keystone of healthy dietary recommendations due to their valuable protein content. In parallel with their consumption, allergic reactions related to shellfish may be increasing. Adverse reactions to shellfish are classified into different groups: (1) Immunological reactions, including IgE and non-IgE allergic reactions; (2) non-immunological reactions, including toxic reactions and food intolerance. The IgE-mediated reactions occur within about two hours after ingestion of the shellfish and range from urticaria, angioedema, nausea, and vomiting to respiratory signs and symptoms such as bronchospasm, laryngeal oedema, and anaphylaxis. The most common allergenic proteins involved in IgE-mediated allergic reactions to shellfish include tropomyosin, arginine kinase, myosin light chain, sarcoplasmic calcium-binding protein, troponin c, and triosephosphate isomerase. Over the past decades, the knowledge gained on the identification of the molecular features of different shellfish allergens improved the diagnosis and the potential design of allergen immunotherapy for shellfish allergy. Unfortunately, immunotherapeutic studies and some diagnostic tools are still restricted in a research context and need to be validated before being implemented into clinical practice. However, they seem promising for improving management strategies for shellfish allergy. In this review, epidemiology, pathogenesis, clinical features, diagnosis, and management of shellfish allergies in children are presented. The cross-reactivity among different forms of shellfish and immunotherapeutic approaches, including unmodified allergens, hypoallergens, peptide-based, and DNA-based vaccines, are also addressed.

Available guidelines for asthma management represent an important and suitable tool to make the entire medical process evidence-based, effective, and safe for patients. Their purpose is to help doctors and patients formulate the best decisions in regard to asthma management by choosing the most appropriate strategies in each specific clinical situation. The Global Initiative for Asthma (GINA) document, together with other national and international recommendations, is one of the main documents used for asthma prevention and management in Italy, but several studies reported that these recommendations are often not applied in real-life clinical practice, which consequently results in inadequate asthma control. In this context, a substantial simplification of the GINA document and asthma guidelines may represent a feasible strategy to be pursued to ameliorate the knowledge among GPs, primary care pediatricians, and specialists taking care of children and adults with asthma. On the other hand, another critical factor that may explain unsatisfactory control of asthma is the limited importance that all recommendations place on asthma heterogeneity. In the era of personalized medicine and target therapies, phenotype-driven asthma management may become a desirable approach for optimizing the management of asthmatic patients. In addition, digital health strategies have been investigated in the literature to improve asthma monitoring and may represent a promising tool in the future from this point of view. Relevant stakeholders should continue to investigate how to optimize real-life asthma control to propose novel solutions to translate into clinical practice.

Alternaria alternata is one of the most clinically relevant fungal allergens in pediatric patients with respiratory allergies. Sensitization to this mold has increased in recent decades and is influenced by environmental exposure, geographic location, climate change, and genetic predisposition. In children, Alternaria spp. are strongly associated with the development and worsening of asthma and allergic rhinitis, often contributing to severe and difficult-to-control forms of the disease. The major allergen, Alt a 1, plays a central role in the immunopathogenesis of Alternaria-induced allergies and exhibits molecular features that allow cross-reactivity with other fungal species. Although Alternaria allergy is clinically relevant, its diagnosis remains challenging due to the variability and lack of standardization of fungal extracts. Therefore, it may be necessary to complement traditional diagnostic tools, such as skin prick testing and specific IgE measurement, with component-resolved diagnostics or, in selected cases, nasal provocation tests. Allergen immunotherapy (AIT) has shown promising results in the treatment of Alternaria allergy, particularly with the use of standardized Alt a 1-based extracts or chemically modified allergoids, which offer clinical benefits and immunological modulation. However, AIT is still underused in this context, partly because of the lack of widely available commercial products and long-term efficacy data in the pediatric population. This review provides a comprehensive overview of the current knowledge on the epidemiology, mechanisms, clinical implications, and treatment options related to Alternaria allergy in children, with the aim of supporting early recognition and tailored therapeutic strategies for this important, yet often underestimated, allergen.

Introduction T1DM is the most frequent form of diabetes in children. It has a multifactorial pathogenesis in which genetic, environmental and immunological factors are involved. Among genetic explanations a major role is attributed to second class HLA genes, with the greatest risk associated with the simultaneous presence of the haplotypes DR3DQ2 and DR4DQ8. Based on results obtained in other countries, the aim of this research is to verify a possible association between the haplotype DRB1 * 04: 05-DQA1 * 03-DQB1 * 02 and the onset of T1DM among Italian children with possible genotype-phenotype correlations. Greater knowledge of genes which increase or decrease susceptibility is important for genome analysis. Materials and methods 165 patients with type 1 diabetes treated at the Diabetology Unit of the Meyer Children’s University Hospital, were clinically analyzed. Data relating to age at diagnosis, pancreatic anti-beta cell autoimmunity, comorbidities with date of diagnosis and family history were retrospectively collected from medical data. A case-control study was conducted to investigate the HLA types of the patients compared to a control group of 819 Tuscan donors enrolled in the National Bone Marrow Donor Register. Typing was carried out using the Eurospital \"DIABEGEN\" kit, currently in use at the immunology laboratory of the Meyer Children’s University Hospital. Results Mean age at diagnosis was 9.3 years; most children (97%) had anti-pancreatic beta cell autoimmunity; the anti-insulin antibody (IAA) was more frequent among children with early clinical disease onset (0–5 years of age). From the case control comparison performed on HLA typing, it emerged that the greatest risk for the development of type 1 diabetes is conferred by the haplotypes DR3DQ2 and DR4DQ8, but in addition to these haplotypes, already known in other countries, we identified another haplotype, DR4DQ2 (DRB1 * 04: 05-DQA1 * 03-DQB1 * 02) which appears to predispose children to type 1 diabetes (p value 2.80E-08) and it is associated with early clinical disease onset (p-value = 0.002). Conclusions We report a new haplotype which increases susceptibility to type 1 diabetes among Italian children and which is associated with early clinical disease onset. Given the central role attributed to genetic factors in the pathogenesis of T1DM and to the II class HLA genes, this new haplotype ought to be recognized as a risk factor and included in tests routinely carried out to identify patients with a genetic predisposition to type I diabetes in Italy. These findings could have practical implications in research and prevention programs.

While spice allergies are rarely documented in children, spices are becoming an increasingly common allergen in pre-packaged foods. Current literature reports contradictory findings regarding the risk of severe reactions in pediatric patients, with some evidence suggesting that small amounts of spices usually used in home-cooked meals may be safe for children. However, allergens, such as spices, are increasingly used in the food industry, coupled with diverse culinary habits and customs, necessitates a re-evaluation of this risk. To the best of our knowledge, this is the first report of cumin anaphylaxis via inhalation in a pediatric patient. Spice allergies should be suspected in patients with allergic manifestations occurring briefly after the consumption or inhalation of multiple different and unrelated foods. Our experience indicates that prick-by-prick tests with spice powders are helpful and should be recommended as part of the diagnostic workup to investigate this peculiar type of food allergy and prevent misdiagnosis of idiopathic anaphylaxis. Limited data concerning the reliability of skin tests with native spices and extracts are available in the literature. Native spices could contain irritant agents leading to false-positive results, but standardized case-control studies are currently lacking. New techniques can be used in the diagnostic process; however, they still need to be validated and integrated into clinical practice. Further investigation is required to quantify the impact of spice allergies on the pediatric population, especially in today’s multiethnic societies.

Anaphylaxis is a life-threatening reaction characterized by the acute onset of symptoms involving different organ systems and requiring immediate medical intervention. The incidence of fatal food anaphylaxis is 0.03 to 0.3 million/people/year. Most fatal food-induced anaphylaxis occurs in the second and third decades of life. The identified risk factors include the delayed use of epinephrine, the presence of asthma, the use of recreational drugs (alcohol, nicotine, cannabis, etc.), and an upright position. In the United Kingdom (UK) and Canada, the reported leading causal foods are peanuts and tree nuts. In Italy, milk seems to be the most common cause of fatal anaphylaxis in children < 18 years. Fatal food anaphylaxis in Italian children and adolescents almost always occurs outside and is characterized by cardiorespiratory arrest; auto-injectable adrenaline intramuscular was available in few cases. Mortality from food anaphylaxis, especially in children, is a very rare event with stable incidence, but its risk deeply impacts the quality of life of patients with food allergy and their families. Prevention of fatal food anaphylaxis must involve patients and their families, as well as the general public, public authorities, and patients’ associations.