Background: Appropriateness of diagnostic test prescriptions represents a critical component of quality care in pediatric allergology, directly influencing diagnostic accuracy, therapeutic decisions, healthcare resource utilization, and patient outcomes. A multidisciplinary expert panel was convened to develop evidence-based clinical recommendations addressing the appropriate use of specialist consultations and diagnostic investigations in children with asthma, allergic rhinoconjunctivitis, and vernal keratoconjunctivitis (VKC). Methods: Clinical questions were formulated using the PICO framework and prioritized through structured expert consensus. Systematic literature reviews were conducted across major databases, and the certainty of evidence was assessed using the GRADE methodology. Results: Specialist evaluation emerged as a key determinant of improved diagnostic precision, optimization of treatment strategies, and reduction of inappropriate therapies. In asthma, spirometry, FeNO measurement, and allergy testing contributed to enhanced diagnostic accuracy and better control. In allergic rhinoconjunctivitis, allergological assessment supported diagnosis and the selection of immunotherapy, with demonstrated benefits on symptoms and quality of life. For VKC, multidisciplinary specialist involvement facilitated early diagnosis, personalized management, and prevention of complications. Conclusions: Although the overall certainty of evidence ranged from moderate to low, consistent clinical benefits supported consensus-based recommendations. Implementation of these recommendations may improve care quality, promote equitable access to diagnostic resources, and reduce unnecessary healthcare utilization.
BACKGROUND:Panallergens are ubiquitously expressed molecules that may drive IgE sensitization across diverse allergen sources, thereby shaping complex clinical phenotypes such as asthma and pollen-food allergy syndrome (PFAS). Although several panallergen families have been extensively characterized, unexplained sensitization patterns are still observed in clinical practice. Cyclophilins, a conserved protein family, have recently been proposed as candidate panallergens; however, their molecular, clinical, and functional roles remain largely undefined. METHODS:Within the Panallergens in Pediatrics (PAN-PED) cohort, we investigated 100 Italian children with seasonal allergic rhinitis (SAR) for IgE sensitization to the cyclophilins Bet v 7 and Ara h 18. Functional assays were performed by sensitizing mast cells with patient sera (n = 11) and assessing activation upon stimulation with increasing concentrations of recombinant Bet v 7 (rBet v 7), using CD63 expression as readout. Additional experiments evaluated the impact of heat treatment (60°C, 80°C, or 100°C) and saliva digestion on rBet v 7 activity. RESULTS:rBet v 7 induced mast cell activation in a dose-dependent manner, with peak responses at intermediate allergen concentrations, followed by attenuation at higher doses. rBet v 7 maintained functional activity after exposure to mild heat and saliva. A strong correlation was found between specific IgE levels to Bet v 7 and Ara h 18 (r = 0.996, p < 0.0001). CONCLUSION:Bet v 7 has the functional capacity to activate mast cells and is resistant to mild heat and saliva digestion, supporting its role as a clinically relevant panallergen. In addition, Bet v 7 shows high similarity to cyclophilins from other plant sources and exhibits virtually identical IgE-binding properties to Ara h 18. These findings suggest a potential rationale for considering the inclusion of cyclophilins into molecular diagnostic panels, particularly in children with SAR.
Atopic dermatitis is a compelling challenge in daily practice. Type 2 inflammation is the most common endotype in children and adolescents with AD. As a result, anti-inflammatory drugs, mainly corticosteroids (CS) and immunomodulatory agents, represent the first-line treatment to dampen type 2 inflammation. However, biologics, particularly dupilumab, dramatically changed the natural history of AD patients. A steering committee composed by expert pediatricians and dermatologists promoted a multidisciplinary Delphi Consensus to improve the knowledge about this topic. Experts in this field participated in the Consensus of three groups of statements concerning definition, diagnosis, and management. There was agreement for all proposed statements. The outcomes of the present multidisciplinary Delphi Consensus propose shared, evidence-based recommendations that may be fruitful in clinical practice.
Severe treatment-resistant asthma (STRA) in children is often sustained by type 2 inflammation and eosinophil-dependent airway disease that persists despite optimized inhaled therapy and the mitigation of modifiable factors. This review summarizes the clinical and translational evidence on monoclonal antibodies targeting the interleukin-5 (IL-5) axis (anti-IL-5 and anti-IL-5Rα) available in pediatric severe asthma. PubMed/MEDLINE was searched up to January 2026 for English-language studies in patients aged 0-18 years addressing mepolizumab and benralizumab, including randomized trials, high-quality observational studies, meta-analyses, and international guidance. Mepolizumab has the most robust pediatric data, showing consistent reductions in exacerbations and blood eosinophils, and improvements in symptom control and quality of life, with safety broadly comparable to adults. The pediatric evidence for benralizumab is more limited but shows rapid eosinophil depletion, improved outcomes in selected children, and acceptable safety; further trials are ongoing. Overall, IL-5-directed biologics represent a key add-on option for carefully selected children with severe eosinophilic asthma, while pediatric-specific predictors of response, comparative effectiveness, and standardized long-term monitoring and stopping criteria remain priorities.
Asthma is a common chronic disease in children, contributing to significant morbidity and healthcare utilization worldwide. The integration of artificial intelligence (AI) and machine learning (ML) into pediatric asthma care is rapidly advancing, offering new opportunities for early diagnosis, risk stratification, and personalized management. AI-driven tools can analyze complex clinical, genetic, and environmental data to identify asthma phenotypes and endotypes, predict exacerbations, and support timely interventions. In pediatric populations, these technologies enable non-invasive diagnostic approaches, remote monitoring through wearable devices, and improved medication adherence via smart inhalers and digital health platforms. Despite these advances, challenges remain, including the need for pediatric-specific datasets, transparency in AI decision-making, and careful attention to data privacy and equity. The integration of AI in pediatric asthma care and into the clinical decision system can offer personalized treatment plans, reducing the burden of the disease both for patients and health professionals. This is a narrative review on the applications of AI and ML in pediatric asthma care.
Macrolides are widely prescribed antibiotics in pediatric practice and are commonly used as alternatives in children with suspected or confirmed beta-lactam allergy. Although generally considered safe and associated with low allergenic potential, hypersensitivity reactions to macrolides do occur and may lead to inappropriate drug avoidance. This review critically appraises the current evidence on macrolide-induced hypersensitivity reactions in the pediatric population, focusing on clinical manifestations, diagnostic approaches, cross-reactivity, and management strategies. Hypersensitivity reactions to macrolides are estimated to occur in 0.4–3
Background/Objectives: Evidence-based recommendations are vital in healthcare to standardize care, reduce variability, and improve patient outcomes. In children, anaphylaxis, allergy to antibiotics, and hymenoptera venom allergy are among the commonest reasons for allergological evaluation. This work was intended to optimize the prescriptions for allergological evaluation and for the related diagnostic tests with the aim of improving the management of children with allergic diseases and promoting resource efficiency. Methods: A systematic literature review of the literature was performed to formulate recommendations on the diagnostic management of children with anaphylaxis, drug allergy, and hymenoptera venom allergy. Results: Effective management of anaphylaxis involves rapid assessment and specialist follow-up to identify triggers, prevent recurrence, and ensure patients and caregivers are educated and equipped with an adrenaline auto-injector. Integrating skin testing, specific serological assays, and oral provocation tests into the diagnostic process for children with suspected beta-lactam allergy enhances diagnostic accuracy and minimizes unnecessary avoidance of first-line antibiotics. Children and adolescents with systemic reactions to hymenopteran stings should be referred to an allergy specialist for diagnosis, risk assessment, management education, and adrenaline prescription. Conclusions: These recommendations may enhance care quality, minimize inappropriate prescriptions, and support standardized methods of diagnosis of allergological diseases in children.
Background: Food allergy is a heterogeneous pediatric disease involving IgE-mediated, non-IgE-mediated, and mixed immune mechanisms, with manifestations ranging from mild symptoms to life-threatening anaphylaxis. Current diagnostic tools, including clinical history, skin prick testing, serum-specific IgE measurement, and oral food challenge, have limitations in specificity, invasiveness, prognostic value, and ability to guide personalized management. Methods: This narrative review summarizes emerging biomarkers in pediatric food allergy and evaluates their diagnostic, prognostic, predictive, and therapeutic potential. A literature search was conducted in PubMed/MEDLINE and Cochrane Central for English-language studies published between December 2015 and March 2026. Eligible studies included original clinical or translational research involving children aged 0–18 years and assessing functional cellular assays, epithelial barrier markers, intestinal permeability, gut microbiota, metabolomics, transcriptomics, proteomics, epigenetics, and immune biomarkers. Findings were synthesized qualitatively according to biomarker category and biological function. Results: Functional cellular biomarkers, particularly the basophil activation test, show the greatest translational readiness, with high diagnostic specificity, utility in reaction threshold and severity assessment, and potential value for monitoring oral immunotherapy. Biomarkers of epithelial barrier dysfunction, including zonulin, tight junction proteins, epithelial injury markers, filaggrin variants, and epithelial-derived cytokines, provide mechanistic insight into allergic sensitization and gastrointestinal phenotypes but remain insufficiently validated. Microbiota-derived, metabolomic, transcriptomic, proteomic, epigenetic, and integrated multi-omics approaches offer promising tools for risk prediction, tolerance monitoring, endotype identification, and precision medicine. Conclusions: Emerging biomarkers may improve diagnosis, risk stratification, therapeutic monitoring, and personalized care in pediatric food allergy. However, standardized assays, large longitudinal pediatric studies, and external validation are required before routine clinical implementation.
BACKGROUND:Several guidelines recommended how to manage delayed maculopapular exanthemas during antibiotic treatment. The aim of the present survey was to assess knowledge gaps of primary care pediatricians in managing children with delayed maculopapular exanthemas during a course of antibiotics. METHODS:We conducted an online survey among primary care pediatricians in Italy, focusing on the management of children with maculopapular exanthemas occurring during antibiotic administration. RESULTS:We found that 41% of pediatricians continued with the same antibiotic after the onset of mild to moderate maculopapular exanthemas. Additionally, only 25% took pictures of the skin manifestations during the acute phase, and 66% recorded the latency of the reaction. CONCLUSIONS:Primary care management of children with suspected antibiotic induced maculopapular exanthemas is heterogeneous. Primary care physicians and allergists need to share common decisions and protocols to avoid mislabelling children as allergic to antibiotics.
Cow’s milk allergy is one of the most prevalent food allergies in infancy. Exclusive breastfeeding is the recommended source of nutrition for the first six months of life, but some infants may develop cow’s milk allergy due to the transfer of milk proteins such as β-lactoglobulin through breast milk. There are still many uncertainties about cow’s milk allergy in breastfed babies. The purpose of this review is to summarize the latest findings mainly focused on immunological mechanisms and challenges in diagnosis. We pointed out which clinical signs in breastfed infants are associated with immediate IgE responses and which are linked to delayed non-IgE mechanisms or mixed IgE/non-IgE-mediated reactions. Since standard IgE tests are often useless in non-IgE cases, diagnosis typically involves dietary elimination and cow’s milk challenge. This study addresses the controversial topic of maternal elimination diets, assessing the nutritional risks to both mothers and infants in relation to their possible benefits. It has also been discussed whether the microbiota signature could be a potential factor in both tolerance development and the risk of cow’s milk allergy in early life. Overall, accurate diagnosis and personalized treatment plans are vital to prevent overdiagnosis and ensure proper growth while maintaining the practice of breastfeeding.
Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) have been classified as immediate (or acute) and delayed. Immediate reactions can be further classified into 4 clinical types: NSAID-exacerbated respiratory disease (N-ERD), NSAID-exacerbated cutaneous disease (NECD), NSAID-induced urticaria/angioedema (NIUA), and single NSAID-induced urticaria/angioedema/anaphylaxis (SNIUAA). Specifically, the NIUA type references reactions to ≥2 NSAIDs belonging to different chemical groups, involving urticaria and/or angioedema in patients with no underlying chronic spontaneous urticaria. However, there are patients meeting cross-reactive criteria for NIUA phenotype who report reactions that involve 2 organ systems (eg, cutaneous and respiratory; cutaneous and gastrointestinal) and have been termed “blended”. In pediatrics, this type of reaction is recognized and has been termed NSAID-induced urticaria/angioedema/anaphylaxis (NIUAA), an acronym we suggest be extended now to adults. There are small subgroups of N-ERD patients who also report skin symptoms and, alternatively, NECD patients who report respiratory symptoms. These 2 subgroups could be diagnosed as having mixed N-ERD and mixed NECD, respectively. In fact, they are patients suffering from N-ERD or NECD who have had reactions consistent with anaphylaxis.In the current classifications of NSAID hypersensitivity, the reactions in which NSAIDs act as aggravating factors or cofactors in subjects with sensitization to foods are not included. Recently, this type of reactions has been defined as NSAID-exacerbated food allergy (NEFA) and NSAID-induced food allergy (NIFA), respectively.This Statement of the World Allergy Organization (WAO) aims to update both the classification of hypersensitivity reactions to NSAIDs and their diagnosis, addressing the novel issues.
Background: Food allergies are a growing global health concern, particularly among children, with no widely approved curative treatment beyond strict allergen avoidance. Oral immunotherapy (OIT) has emerged as a promising strategy to induce desensitization, yet its implementation is limited due to high rates of allergic reactions and patient non-compliance. Omalizumab, a monoclonal anti-IgE antibody, has been proposed as an adjunct to OIT to enhance safety and efficacy. Objective: This systematic review and meta-analysis aim to evaluate the efficacy and safety of omalizumab in combination with OIT for IgE-mediated food allergy in children. Methods: A systematic literature search was conducted in PubMed/MEDLINE and Cochrane Central databases to identify randomized controlled trials (RCTs), controlled clinical trials (CCTs), and observational studies assessing omalizumab as an adjunct to OIT in pediatric food allergy. Studies were evaluated for desensitization rates, immunological changes, adverse events, and quality-of-life improvements. Results: OIT combined with omalizumab led to significantly higher rates of desensitization, allowing patients to tolerate higher doses of allergens in a shorter timeframe compared to OIT alone. Omalizumab was associated with a reduction in adverse reactions, including anaphylaxis, and improved treatment adherence. However, the long-term sustainability of tolerance post-omalizumab discontinuation remains uncertain. Conclusions: Omalizumab facilitates rapid and effective desensitization in pediatric food allergy, enhancing the safety of OIT. Further research is needed to determine optimal treatment duration, long-term outcomes, and cost-effectiveness before widespread clinical adoption.
BACKGROUND:The EAACI Task Force entitled "Improving Chronic Urticaria (CU) Management in Pediatrics" aimed to explore the differences in the diagnostic and management practices for CU in children (0-18 years). METHODS:An online clinical survey including 41 multiple choice questions on current practices for the management of childhood CU was disseminated among EAACI members. RESULTS:The survey was circulated to 50,472 contacts via mass email and to 2343 contacts via EAACI social media channels and answered by 161 participants from 55 countries. Most respondents were pediatric allergists (74.5%). While 68.3% of the respondents stated that they use the EAACI/GA2LEN/EuroGuiDerm/APAAACI guideline, 10.6% declared that they do not use any guideline. Full blood count (83.3%), thyroid profile (64.6%), IgE (62.7%), thyroid antibodies (62.1%), C-reactive protein (59%), and antinuclear antibodies (ANA) or other antibodies (50.9%) were the most commonly used routine tests when diagnosing CU patients. Less than 20% of the respondents said they test their patients routinely for chronic induced urticaria when clinically suspected. Reasons for not testing at all were a lack of needed equipment or not knowing how to perform the test. In patients who do not respond to second-generation antihistamine standard dose, two to four-times increased dosage was the preferred step, independently of the child's age. Many participants do not prescribe omalizumab in children aged <5 years (77.6%), 6-11 years (45%), and adolescents (24.7%). In children who do not respond to omalizumab, almost half of the prescribing clinicians stated that they prefer oral ciclosporin-A, and 20% use oral corticosteroids. CONCLUSIONS:Some challenges to the effective use of evidence-based CU guidelines persist around basic testing in the diagnostic workup and pharmacological treatment in children. This study suggests the need for broader availability of specific testing tools and for further education and research in this field.
Over the past year, there have been several developments in various fields of pediatric medicine. This review features essential publications that have been published in the Italian Journal of Pediatrics in 2024. Papers have been selected in the areas of allergy, cardiology, critical care, endocrinology, gastroenterology, immunology, infectious diseases, neonatology, nephrology, neurology, nutrition, palliative care, respiratory tract illnesses, and social media. The findings have been examined to identify opportunities for improving the management of the diseases.
Exercise-induced bronchoconstriction (EIB) is a common clinical entity in people with asthma. EIB is characterized by postexercise airway obstruction that results in symptoms such as coughing, dyspnea, wheezing, chest tightness, and increased fatigue. The underlying mechanism of EIB is not completely understood. “Osmotic theory” and “thermal or vascular theory” have been proposed. Initial assessment must include a specific work-up to exclude alternative diagnoses like exercise-induced laryngeal obstruction (EILO), cardiac disease, or physical deconditioning. Detailed medical history and clinical examination must be followed by basal spirometry and exercise challenge test. The standardized treadmill running (TR) test, a controlled and standardized method to assess bronchial response to exercise, is the most adopted exercise challenge test for children aged at least 8 years. In the TR test, the goal is to reach the target heart rate in a short period and maintain it for at least 6 min. The test is then followed by spirometry at specific time points (5, 10, 15, and 30 min after exercise). In addition, bronchoprovocation tests like dry air hyperpnea (exercise and eucapnic voluntary hyperpnea) or osmotic aerosols (inhaled mannitol) can be considered when the diagnosis is uncertain. Treatment options include both pharmacological and behavioral approaches. Considering medications, the use of short-acting beta-agonists (SABA) just before exercise is the commonest option strategy, but daily inhaled corticosteroids (ICS) can also be considered, especially when EIB is not controlled with SABA only or when the patients practice physical activity very often. Among the behavioral approaches, warm-up before exercise, breathing through the nose or face mask, and avoiding polluted environments are all recommended strategies to reduce EIB risk. This review summarizes the latest evidence published over the last 10 years on the pathogenesis, diagnosis using spirometry and indirect bronchoprovocation tests, and treatment strategies, including SABA and ICS, of EIB. A specific focus has been placed on EIB management in young athletes, since this condition can not only prevent them from practicing regular physical activity but also competitive sports.
In the last year, there have been many remarkable articles published in the Italian Journal of Pediatrics. This review highlights papers that can be potentially helpful in healthcare practice among the most cited or accessed papers on the journal website. We have chosen key articles on allergy, analgesics, cardiology, endocrinology, gastroenterology, genetics, global health, infectious diseases, neonatology, neurology and pulmonology. Advances in understanding risk factors, mechanisms, diagnosis, treatment options and prevention of pediatric diseases have been discussed and in the context of the subsequent steps. We think that progresses achieved in 2023 will have a significant impact on the management of diseases in childhood.