Food Allergy Risk: A Comprehensive Review of Maternal Interventions for Food Allergy Prevention.

Food allergy represents a global health problem impacting patients' and caregivers' quality of life and contributing to increased healthcare costs. Efforts to identify preventive measures starting from pregnancy have recently intensified. This review aims to provide an overview of the role of maternal factors in food allergy prevention. Several studies indicate that avoiding food allergens during pregnancy does not reduce the risk of developing food allergies. International guidelines unanimously discourage avoidance diets due to potential adverse effects on essential nutrient intake and overall health for both women and children. Research on probiotics and prebiotics during pregnancy as preventive measures is promising, though evidence remains limited. Consequently, guidelines lack specific recommendations for their use in preventing food allergies. Similarly, given the absence of conclusive evidence, it is not possible to formulate definitive conclusions on the supplementation of vitamins, omega-3 fatty acids (n-3 PUFAs), and other antioxidant substances. A combination of maternal interventions, breastfeeding, and early introduction of foods to infants can reduce the risk of food allergies in the child. Further studies are needed to clarify the interaction between genetics, immunological pathways, and environmental factors.

Mini-Review on Vitamin D in Pediatric Population and its Role in Respiratory and Atopic Disorders.

In recent years, our comprehension of the function of vitamin D has significantly evolved. The ubiquitous presence of the vitamin D receptor (Vitamin D Receptor- VDR) in the body has led to its redefinition from a steroidal hormone primarily involved in skeletal functions to a hormone with pleiotropic effects, exerting its influence on the circulatory, nervous, and immune systems. This has prompted investigations into its potential use in preventing and treating chronic metabolic disorders, cardiovascular diseases, infections, and allergic and autoimmune diseases. This comprehensive review explores the various aspects of vitamin D, including its sources, synthesis, functions, and its impact on different physiological systems. It delves into the epidemiology of vitamin D deficiency, highlighting its occurrence among various age demographics and geographic regions. The impact of vitamin D on the immune system is also explored, elucidating its immunomodulatory and anti-inflammatory properties, particularly in the context of respiratory infections. The review discusses emerging evidence concerning the potential advantages of vitamin D in respiratory diseases, pediatric asthma and atopic dermatitis. It also addresses vitamin D supplementation recommendations for various pediatric populations, including term and preterm infants. The growing concern regarding the global health impacts of insufficient vitamin D levels necessitates further research to bridge gaps in knowledge, particularly in enhancing screening, prevention, and approaches to address vitamin D deficiency from birth onwards. In summary, this comprehensive overview underscores the vital role of vitamin D, highlighting the significance of understanding its multifaceted functions and the need for tailored supplementation strategies, especially in vulnerable populations.

Record of strep throat infections in Italy: what is needed to know about penicillin allergy? The point of view from the Italian Society of Pediatric Allergy and Immunology (SIAIP).

Notifications of invasive group A streptococcal (iGAS) infections have significantly increased in many European Countries compared to the previous season. In Italy, there has been an increase in streptococcal pharyngitis and scarlet fever cases since January 2023, which sparked concerns about a GAS epidemic in the pediatric population. This rise may be ascribed to the GAS infection season that began earlier than usual (off-season outbreak) and the increase in the spread of respiratory viruses and viral coinfections that raised the risk of iGAS disease. Moreover, this phenomenon was also facilitated by increased travel after reduced GAS circulation during the COVID-19 pandemic.The increase in cases of GAS disease has raised some critical issues regarding the potential reactions to administering amoxicillin, the first-line antibiotic therapy, many of which have been erroneously labeled as "allergy."For these reasons, the Italian Society of Pediatric Allergy and Immunology (SIAIP) intends to provide simple clinical indications to help pediatricians manage GAS pharyngitis, discerning the allergic from non-allergic drug hypersensitivity.

What's new in pediatric asthma and rhinitis phenotypes and endotypes?

PURPOSE OF REVIEW: This review explores the evolving landscape of pediatric asthma and rhinitis, focusing on identifying and characterizing different subtypes. RECENT FINDINGS: Childhood asthma and rhinitis are prevalent respiratory conditions frequently occurring together. To address the need for a precise definition of these diseases, an unbiased and comprehensive phenotyping approach has been undertaken with hypothesis-free analysis of extensive datasets to uncover new relationships among clinical, environmental, and biological characteristics. On the other hand, the concept of endotype is elaborate and multifaceted, representing distinct pathophysiological mechanisms underlying the clinical presentation and requires the identification of reliable biomarkers. The recognition of multiple inflammatory endotypes underscores the need for in-depth characterization, which could revolutionize the treatment landscape. SUMMARY: Comprehending phenotypes and endotypes is crucial for customizing effective and personalized management approaches for children with asthma and rhinitis. More precise and efficient care can be administered through recognition and detailed characterization, ultimately enhancing patients' quality of life.

Biological Therapies for Pediatric Atopic Dermatitis - A Review.

Atopic dermatitis (AD) is the most frequent chronic-recurrent inflammatory skin disease in the pediatric age. It has a complex and multifactorial pathogenesis: the two key actors are impaired skin barrier function and immune system dysregulation, which represent the main targets of AD therapy. Monoclonal antibodies have revolutionized the management of moderate-to-severe AD, by selective inhibition of key cytokines in the pathogenetic process. For this reason, there is great interest in exploring AD pathogenetic mechanisms to develop new therapeutic strategies. This review aims to summarize the most recent scientific evidence on available and future biological therapies for the treatment of pediatric AD, emphasizing the molecular mechanisms underlying their action.

Oral findings in pediatric patients with allergic rhinitis and asthma: a cohort study of an Italian setting.

Allergic rhinitis and asthma are two frequent respiratory clinical entities commonly encountered in pediatric clinical settings. Previous studies have evaluated the influence of these two conditions on oral health, but conflicting results have been obtained. The present cohort study aimed to record oral findings (i.e., caries, plaque, gingival inflammation and mouth breathing) in 50 pediatric patients diagnosed with allergic rhinitis and/or asthma in an Italian pediatric setting and to compare them to a control group of 50 healthy children. The following oral indexes were calculated: Periodontal Screening and Recording (PSR), Plaque Control Record (PCR), and Decayed Missing Filled Teeth (DMFT) Index. The absence or presence of mouth breathing was also recorded. Descriptive and inferential statistics were conducted. Statistically significant differences were found between cases and controls for PSR (p = 0.0051) and PCR scores (p < 0.0001), whereas no significant differences were detected for DMFT. Mouth breathing was found among 20 (40.00%) patients of the Case Group, while in the Control group only in 11 (22.00%) patients, and no significant differences were found between allergic rhinitis and asthma gradings for mouth breathers (p > 0.05). Finally, linear regressions showed a significant influence of PSR (p = 0.0051) and PCR (p < 0.0001) on the Case group. Mouth breathing also significantly influenced PCR scores of the Case group (p = 0.0206). Accordingly, allergic rhinitis and asthma can promote mouth breathing, plaque accumulation, and periodontal inflammation. Based on these considerations, pediatric dentists and physicians are expected to know the influence of respiratory conditions on oral health and consider this aspect when taking care of children.

The knowledge of orthodontic and craniofacial growth amongst Italian Pediatric Medical Residents for early diagnosis in growing patients: a cross-sectional study.

Paediatric residents usually visit children since the first years of life and can potentially diagnose craniofacial anomalies and malocclusions. Therefore, the aim of this study was to assess the ability of paediatric medical residents to diagnose malocclusions in growing subjects at an early stage. Eighty-three paediatric medical residents from the University of Pavia, Italy, who were enrolled in the Paediatric Residency program, participated in an online questionnaire. The questionnaire covered demographic variables, oral examination practices, dental and orthodontic knowledge, and sources of information. Following this, the residents were presented with a photographic analysis and asked to determine the treatment priority for 10 patients with malocclusions using the Index of Orthodontic Treatment Need (IOTN). On average, it was recommended that the first orthodontic visit should occur at around 4.92 years of age. The results showed that 75.9% of the residents always performed oral examinations on their patients, and 48.1% assigned a priority score of 8 or higher. The scores obtained by the paediatric residents did not significantly differ based on the year of study, frequency of oral examinations, or sources of information reported. Notably, there was a particular underestimation of treatment priority for malocclusions characterized by a significant increase in overjet. The findings suggest a potential lack of improvement in orthodontic knowledge during the medical residency program. It is recommended to increase the availability of orthodontic information sources for paediatric residents to enhance their understanding in this area.

A Practical Update on Pediatric Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an emerging atopic disease of unknown etiology limited to the esophagus. The pathogenesis is still understood and is likely characterized by type 2 inflammation. Food allergens are the primary triggers of EoE that stimulate inflammatory cells through an impaired esophageal barrier. In children and adolescents, clinical presentation varies with age and mainly includes food refusal, recurrent vomiting, failure to thrive, abdominal/epigastric pain, dysphagia, and food impaction. Upper-gastrointestinal endoscopy is the gold standard for diagnosing and monitoring EoE. EoE therapy aims to achieve clinical, endoscopic, and histological ("deep") remission; prevent esophageal fibrosis; and improve quality of life. In pediatrics, the cornerstones of therapy are proton pump inhibitors, topical steroids (swallowed fluticasone and viscous budesonide), and food elimination diets. In recent years, much progress has been made in understanding EoE pathogenesis, characterizing the clinical and molecular heterogeneity, and identifying new therapeutic approaches. Notably, clinical, molecular, endoscopic, and histological features reflect and influence the evolution of inflammation over time and the response to currently available treatments. Therefore, different EoE phenotypes and endotypes have recently been recognized. Dupilumab recently was approved by FDA and EMA as the first biological therapy for adolescents (≥12 years) and adults with active EoE, but other biologics are still under consideration. Due to its chronic course, EoE management requires long-term therapy, a multidisciplinary approach, and regular follow-ups.

Cold Anaphylaxis in Children: Italian Case Series and Review of the Literature.

Chronic urticaria (CU) is one of the most common skin disorders worldwide. Among the inducible subgroup of CU, cold urticaria (ColdU) can affect both children and adults and is the only type associated with the risk of anaphylaxis without cofactors. In the scientific literature, data about cold anaphylaxis (ColdA) are poor, especially at pediatric age, and little is known about risk factors associated with the onset of systemic reactions and about the criteria for prescribing adrenaline auto-injectors (AAIs) in these patients. We describe the clinical characteristics and management of a case series of 21 patients with a history of ColdA, and we compare them with the pediatric case reports and case series published so far. On the basis of the scientific literature and of our case series of patients, we suggest that AAI should be prescribed to all high-risk patients: those with urticaria caused by cold-water immersion, oropharyngeal reactions, and with a previous history of systemic symptoms or anaphylaxis.

Selective IgM Deficiency: Evidence, Controversies, and Gaps.

Selective Immunoglobulin M deficiency (SIgMD) has been recently included in the inborn errors of immunity (IEI) classification by the International Union of Immunological Societies Expert Committee. The understanding of SIgMD is still extremely limited, especially so in cases of SIgMD in the pediatric population. The epidemiology of SIgMD in the pediatric population is still unknown. The pathogenesis of SIgMD remains elusive, and thus far no genetic nor molecular basis has been clearly established as a definitive cause of this primary immunodeficiency. Recurrent respiratory infections represent the main clinical manifestations in children, followed by allergic and autoimmune diseases. No conclusive data on the correct therapeutic management of SIgMD are available. Although, for most SIgMD patients, Ig replacement therapy is not required, it may be recommended for patients with significantly associated antibody deficiency and recurrent or severe infections. Prophylactic antibiotics and the prompt treatment of febrile illness are crucial. There is insufficient evidence on the prognosis of this condition. Therefore, further studies are required to define the disease trajectories and to increase our understanding of the molecular mechanisms underlying SIgMD in order to facilitate a better clinical, immunological, and prognostic characterization of the condition and develop tailored therapeutic management strategies.

Clinical and immunological phenotypes of selective IgM deficiency in children: Results from a multicenter study.

BACKGROUND: A few studies assessed the clinical and immunological features of selective IgM deficiency (SIgMD), especially in the pediatric age. We aimed to characterize the clinical and immunological phenotypes of a cohort of pediatric patients with SIgMD according to the different diagnostic criteria available. METHODS: In this multicenter study, we evaluated pediatric SIgMD patients diagnosed at the Pediatric Clinic in Pavia, Italy, or through the Italian Primary Immunodeficiency NETwork (IPINET) and monitored changes in their diagnosis over a time frame that ranges from several months to several years. RESULTS: Forty-eight patients with SIgMD were included (mean serum IgM: 33 mg/dL). The most common clinical manifestations were recurrent infections (67%) and allergies (48%). Subgroup analysis according to SIgMD definition criteria of the European Society for Immunodeficiencies (ESID) showed no significant difference in clinical manifestations, also considering the group with additional immunological abnormalities. Sixteen patients had long-term follow-up, during which 87% preserved their SIgMD diagnosis, while two patients showed a reduction in IgA in addition to low IgM. CONCLUSIONS: Our data suggest that the identification of a reduction in serum IgM in children should lead to a complete immunological work-up to obtain a comprehensive clinical and immunological characterization of the patient. The follow-up of these patients is fundamental to define the disease evolution and appropriate management.

The Primary Prevention of Atopy: Does Early Exposure to Cats and Dogs Prevent the Development of Allergy and Asthma in Children? A Comprehensive Analysis of the Literature.

The current literature shows mixed results relating to the significance of environmental exposure, such as owning a pet, and the development of atopy in children. Our review aimed to collect the most recent evidence on the association between early-life cat and dog ownership and the development of allergy and asthma. A comprehensive literature review was performed using PubMed and Scopus. The search included the main keywords of our PICO: (((early exposure) AND (children) AND (allergy)) OR (asthma)) AND (dog) OR (cat). Randomized controlled trials (RCTs), case-control studies, clinical trials, meta-analyses, and systematic reviews of children within the last five years (2018-2023) were searched and included. During the search process, 52 articles from PubMed and 43 from Scopus were found. A total of 17 articles were deemed to be suitable and included. Fairly consistent results regarding early exposure to pets, in particular dogs, and the prevention of food allergies have been described. Furthermore, there seems to be a protective effect against allergy and asthma in relation to the number of pets owned. The likelihood of a child developing allergy and asthma seems to be influenced by various factors, including the child's genetic background and early exposure to different environmental factors, including allergens that may interact with the gut microbiota and immune system.

The role of basophil activation test and component-resolved diagnostics in the workup of egg allergy in children at low risk for severe allergic reactions: A real-life study.

BACKGROUND: The gold standard for diagnosing egg allergy in children is the oral food challenge (OFC). However, OFCs are time-consuming and risky procedures. Our study aimed to evaluate the utility of the basophil activation test (BAT) and component-resolved diagnostic in the diagnostic workup of children with egg allergy. METHODS: Overall, 86 children aged 6 months to 17 years, suspected of egg allergy, underwent OFC with boiled egg according to international standardized protocols. BAT and specific immunoglobulin E (sIgE) testing to component egg proteins (Gal d 1-4) were also performed. RESULTS: Of the 22 children who reacted to boiled egg, only one experienced anaphylaxis during the challenge. BAT was performed in samples obtained by 75 of the 86 patients of our cohort. Egg white and yolk protein extracts induced CD63 upregulation in the egg-allergic (EA) children compared with sensitized children that tolerated boiled egg (we registered an overall mean of CD63 expression in the EA population of 44.4% [SD 34.1] for egg white and 34.7% [SD 31.3] for egg yolk vs. 12.5% [SD 19.1] and 10.0% [SD 16.0] in sensitized children). BAT could discriminate between true egg allergy and egg sensitization in our population. As a second-line diagnostic step, the positivity of BAT for egg white or Gal d 1-sIgE resulted in a 40.9% OFC reduction, especially for those with a positive outcome. CONCLUSION: The BAT may be implemented in the diagnostic workup of egg allergy in children and, in a stepwise approach, separately or combined with Gal d 1-sIgE, may predict the allergic status and reduce the number of positive OFCs in children with egg allergy at low risk for severe reactions.

Role of luteinizing hormone urinary levels in the diagnostic and therapeutic management of female central precocious puberty.

BACKGROUND: Diagnosing central precocious puberty (CPP) requires an integrated approach based on clinical, biochemical and instrumental data. The diagnostic gold standard is represented by GnRH (gonadotropin-releasing hormone) stimulation test. Some undoubted limitations of this procedure led the international scientific community to look for cheaper and less invasive alternative diagnostic methods, such as luteinizing hormone urinary levels (uLH) measurement. This study aims to define the reliability of urinary LH levels as a biomarker of pubertal development, both concerning the initial diagnostic management and the monitoring of patients with central precocious puberty undergoing therapy with GnRH analogues. Furthermore, the study plans to detect the potential association between LH peak serum (pLH) and urinary LH in patients undergoing diagnostic tests with GnRH and to identify a possible cut-off of uLH that may be suggestive of ensued successful hormonal stimulation. METHODS: The study includes 130 female patients with suspected precocious puberty or in follow-up during suppressive therapy. After the collection of the informed consent, the patients underwent clinical evaluation, auxological assessment, and hormone assays (basal levels of LH, FSH, and oestradiol; GnRH stimulating test in patients with suspected precocious puberty; urinary LH assay on the first-morning urine sample, collected after waking up). RESULTS: Two uLH cut-off values have been identified: the first of 0.25 UI/L [C.I. 95% 0.23-0.27], able to distinguish between pubertal and pre-pubertal patients, the second of 0.45 UI/L [C.I. 95% 0,20 - 0,70] suggestive of occurred hormonal stimulation in patients with diagnosis of CPP at GnRH test. All 30 patients with CPP in follow-up during suppressive therapy presented uLH values ≤ 0.45 IU/L (pU < 0.05), and uLH collected in prepubertal group control. CONCLUSIONS: uLH assays on the first morning urine specimen could be considered a low-cost and minimally invasive tool for precocious puberty diagnosing and monitoring, making possible to be easily performed even by a general pediatrician. Thus, this could help referring only selected patients to pediatric endocrinologists. After an appropriate validation, this approach could reasonably reduce hospital attendance and costs of performing more invasive procedures, with a more significant emotional impact on the pediatric patient.

A 52-week multicenter retrospective real-world study on effectiveness and safety of dupilumab in children with atopic dermatitis aged from 6 to 11 years.

Background: Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years.Methods: All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled.Results: Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52.Conclusions: Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time.

Severe pediatric asthma endotypes: current limits and future perspectives.

INTRODUCTION: Although rare, pediatric severe therapy-resistant asthma (STRA) is a highly heterogeneous, resource-demanding disease that differs significantly from severe adult asthma and whose pathogenesis is still poorly understood. AREAS COVERED: This review summarizes the latest 10 years of English-written studies defining pediatric STRA endotypes using lung-specific techniques such as bronchoalveolar lavage and endobronchial biopsy. Results of the studies and limits on the field are discussed, together with some future perspectives. EXPERT OPINION: Over the years, it has become increasingly clear that 'one size does not fit all" in asthma. However, "Does an extremely tailored size fit more than one?'. Only using multicentric, longitudinal pediatric studies, will we be able to answer. Three issues could be particularly critical for future research. First, to provide, if existing, a distinction between prepuberal STRA and puberal STRA endotypes to understand the transition from pediatric to adult STRA and to design effective, tailored therapies in adolescents, usually suffering from poorer asthma control. Second, design early treatments for pediatric airway remodeling to preserve lifelong good lung function. Finally, to better characterize inflammation before and during biological therapies, to provide clues on whether to stop or change treatments.

Food allergy: cause or consequence of pediatric eosinophilic esophagitis? Potential implications of ultraprocessed foods in prevention and management.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by eosinophilic infiltration, leading to esophageal dysfunction, inflammation, and fibrotic remodeling. In the last few decades, there has been an increased prevalence of EoE at an alarming rate in the pediatric age. The pathogenesis of EoE is still largely undefined, and this limits the definition of effective strategies for the prevention and management of this condition. EoE is considered a multifactorial disease arising from a negative interaction between environmental factors and genetic background, causing an impaired esophageal epithelial barrier with subsequent abnormal allergen exposure activating type 2 (Th2) inflammation. Food antigens have been suggested as key players in Th2 inflammation in pediatric patients with EoE, but emerging evidence suggests a potential role of other dietary factors, including ultraprocessed foods, as possible triggers for the occurrence of EoE. In this paper, we discuss the potential role of these dietary factors in the development of the disease, and we propose a new approach for the management of pediatric patients with EoE.

New approaches in childhood asthma treatment.

PURPOSE OF REVIEW: This review aims to summarize the most recent advances in asthma management, focusing on novel approaches to pediatric asthma. RECENT FINDINGS: In recent years, the therapeutic tools for pediatric asthma have expanded significantly for both the nonsevere and severe forms. The use of anti-inflammatory treatment, even for the mildest cases, and the withdrawal of symptomatic bronchodilation as monotherapy have been included in the most recent guidelines. Also, different biological therapies have revolutionized the therapeutical approach for severe uncontrolled asthma in children and adolescents. SUMMARY: With the expanding landscape of novel therapeutic approaches for pediatric asthma, further evidence is needed to help clinicians choose the best option for patients, particularly those with severe asthma. The identification of novel predictive biomarkers may also help pediatricians in selecting children and adolescents for innovative therapies.