Omalizumab reduces anaphylactic reactions and allows food introduction in food-allergic in children with severe asthma: An observational study.

BACKGROUND: In Europe, Omalizumab (anti-IgE) is indicated for the treatment of moderate to severe asthma, but not for IgE-mediated food allergy (FA). OBJECTIVE: We assessed the impact of Omalizumab on efficacy, safety, and quality of life (FA-QoL) in patients with moderate to severe asthma and who have a history of anaphylaxis to peanut, tree nuts, fish, egg, milk, and/or wheat. METHODS: Food-allergic children (6-18 years) with moderate to severe asthma underwent oral food challenges (OFCs) to establish the threshold of reaction to the culprit food(s) at baseline (T0) and at 4-month intervals (T1, T2, and T3) during their first year of treatment with Omalizumab. We recorded the number and severity of food-allergic reactions, Asthma Control Test (ACT) scores, FA-QoL, and total IgE levels. RESULTS: In 65 patients allergic to 107 foods, the No Observed Adverse Events Level (NOAEL) at T1 increased: 243- and 488-fold for fresh and baked milk, respectively; 172- and 134-fold for raw and baked egg; 245-fold for hazelnut; 55-fold for peanut; 31-fold for wheat; and 10-fold for fish. Full tolerance was achieved in 66.4% of OFCs at T1, 58.3% at T2, and 75% at T3. Ninety-five foods were liberalized in the diet of 55 patients; the remaining 12 were introduced by 10 patients at least in traces. Throughout the study, 40 out of 65 were able to get a free diet. ACT increased from 17 (Q1-Q3: 15-17) to 23.6 (Q1-Q3: 23-25). The FA-QoL score in children ≤12 years decreased from 4.63 ± 0.74 to 2.02 ± 1.13, and in adolescents from 4.68 ± 0.92 to 1.90 ± 1.50. CONCLUSIONS: During Omalizumab therapy, a safe reintroduction of allergenic foods is feasible. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT06316414.

Update on the Role of ß2AR and TRPV1 in Respiratory Diseases.

Respiratory diseases (RDs) constitute a common public health problem both in industrialized and developing countries. The comprehension of the pathophysiological mechanisms underlying these conditions and the development of new therapeutic strategies are critical for improving the quality of life of affected patients. ß2-adrenergic receptor (ß2AR) and transient receptor potential vanilloid 1 (TRPV1) are both involved in physiological responses in the airways. ß2AR is implicated in bronchodilation, mucociliary clearance, and anti-inflammatory effects, while TRPV1 is involved in the mediation of pain and cough reflexes. In RDs, such as respiratory infections, asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, the concentration and expression of these receptors can be altered, leading to significant consequences. In this review, we provided an update on the literature about the role of ß2AR and TRPV1 in these conditions. We reported how the diminished or defective expression of ß2AR during viral infections or prolonged therapy with ß2-agonists can increase the severity of these pathologies and impact the prognosis. Conversely, the role of TRPV1 was pivotal in neuroinflammation, and its modulation could lead to innovative treatment strategies in specific patients. We indicate future perspectives and potential personalized treatments in RDs through a comprehensive analysis of the roles of these receptors in the physiological and pathological mechanisms of these pathologies.

Immune Response to Respiratory Viral Infections.

The respiratory system is constantly exposed to viral infections that are responsible for mild to severe diseases. In this narrative review, we focalized the attention on respiratory syncytial virus (RSV), influenza virus, and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections, responsible for high morbidity and mortality in the last decades. We reviewed the human innate and adaptive immune responses in the airways following infection, focusing on a particular population: newborns and pregnant women. The recent Coronavirus disease-2019 (COVID-19) pandemic has highlighted how our interest in viral pathologies must not decrease. Furthermore, we must increase our knowledge of infection mechanisms to improve our future defense strategies.

Hemophagocytic lymphohistiocytosis following gene replacement therapy in a child with type 1 spinal muscular atrophy.

WHAT IS KNOWN AND OBJECTIVE: Onasemnogene abeparvovec (OA) is the first gene replacement therapy for the treatment of paediatric patients with bi-allelic mutations in the SMN1 gene. Efficacy and safety of OA have been assessed in several studies with promising results, despite rare side effects have been described. CASE SUMMARY: A 3-year-old child with spinal muscular atrophy was treated with OA and subsequently developed fever, widespread erythematous skin lesions and hepatosplenomegaly. Laboratory tests were suggestive for Hemophagocytic lymphohistiocytosis (HLH). WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first case of HLH following gene replacement therapy with OA, described in literature.

WITHDRAWN:A Practical Approach for Management of QT Prolongation Induced by Anticancer Drugs.

Ahead of Print article withdrawn by publisher.

Pathophysiology of Congenital High Production of IgE and Its Consequences: A Narrative Review Uncovering a Neglected Setting of Disorders.

Elevated serum IgE levels serve as a critical marker for uncovering hidden immunological disorders, particularly inborn errors of immunity (IEIs), which are often misdiagnosed as common allergic conditions. IgE, while typically associated with allergic diseases, plays a significant role in immune defense, especially against parasitic infections. However, extremely high levels of IgE can indicate more severe conditions, such as Hyper-IgE syndromes (HIES) and disorders with similar features, including Omenn syndrome, Wiskott-Aldrich syndrome, and IPEX syndrome. Novel insights into the genetic mutations responsible for these conditions highlight their impact on immune regulation and the resulting clinical features, including recurrent infections, eczema, and elevated IgE. This narrative review uniquely integrates recent advances in the genetic understanding of IEIs and discusses how these findings impact both diagnosis and treatment. Additionally, emerging therapeutic strategies, such as hematopoietic stem cell transplantation (HSCT) and gene therapies, are explored, underscoring the potential for personalized treatment approaches. Emphasizing the need for precise diagnosis and tailored interventions aims to enhance patient outcomes and improve the quality of care for those with elevated IgE levels and associated immunological disorders.

Correction: Klain et al. The Prevention of House Dust Mite Allergies in Pediatric Asthma. Children2024, 11, 469.

There was an error in the original publication [...].

The Prevention of House Dust Mite Allergies in Pediatric Asthma.

This review provides a concise overview of preventive measures against dust mite allergies in pediatric populations, emphasizing the need for a comprehensive and evolving approach. Dust mites, ubiquitous microscopic arachnids, pose a significant threat to children's health, triggering allergies and asthma. Traditional preventive strategies such as regular cleaning, mattress covers, and humidity control are essential but warrant refinement. Empowering children through personalized hygiene education and exploring innovative bedding solutions showcase a forward-thinking paradigm. Collaboration with healthcare professionals and embracing technology-driven solutions ensures a holistic and adaptable approach to safeguarding pediatric health against dust mite-related ailments. This abstract underscores the importance of continually reassessing and innovating preventive measures to create resilient and health-conscious living environments for children.

Baked Egg Oral Immunotherapy: Current State in Pediatric Age.

Hen's egg allergy is one of the most common food allergies in the Western world, with an increase in recent years. It affects about 9.5% of the pediatric population, and the onset most often occurs before the first year of life. The occurrence of spontaneous oral tolerance acquisition varies among studies, but it is generally high by school age. Nowadays, allergen immunotherapy may represent the only therapeutic strategy able to modify the natural history of hen's egg allergy. Specifically, many children with hen's egg allergy may tolerate baked eggs. Food processing, specifically high temperatures, alters the allergenicity of hen's egg proteins by causing conformational changes in allergen epitopes, which makes them less allergenic. This review aims to discuss the scientific evidence in the field of baked egg oral immunotherapy in hen's egg-allergic children, with a meticulous examination of the pertinent literature surrounding the subject matter.

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.

Early Assessment of Efficacy and Safety of Biologics in Pediatric Allergic Diseases: Preliminary Results from a Prospective Real-World Study.

BACKGROUND: Despite the increasing interest in biologics for the management of allergic diseases, sparse real-world data are still available in the pediatric population. This study aimed to evaluate the early real-life efficacy and safety of omalizumab for patients with moderate-to-severe asthma and chronic spontaneous urticaria (CSU), and Dupilumab for patients with moderate-to-severe atopic dermatitis (AD). METHODS: A prospective study enrolling children aged 6-18 years was designed to assess the efficacy and safety of biologic drugs at 16 weeks of treatment (T1). The effectiveness was measured using validated questionnaires (ACQ-5 for asthma, UAS7 for CSU, and EASI score for AD). Secondary outcome measures included reductions in inhaled corticosteroid (ICS) dosages, asthma-related hospitalizations/exacerbations, and quality of life (QoL) indicators (iNRS, sNRS, DLQI/cDLQI) for CSU and AD. Safety was expressed according to the descriptions of adverse events provided by EMA and FDA. RESULTS: The study cohort consisted of eighteen children (mean age 12.9 ± 3.4 years). The omalizumab treatment significantly reduced ACQ-5 and UAS7 scores (p = 0.002 and p < 0.001, respectively). In patients with asthma, decreased ICS dosage and hospitalization/exacerbation rates were observed. QoL parameters significantly improved in CSU and AD patients. No severe adverse events were reported for either treatment. CONCLUSIONS: Our findings validate omalizumab and dupilumab as effective and safe therapeutic options for managing moderate-to-severe allergic diseases in children and adolescents.

Device-Related Skin Reactions Increase Emotional Burden in Youths With Type 1 Diabetes and Their Parents.

BACKGROUND: Skin reactions due to technological devices pose a significant concern in the management of type 1 diabetes (T1D). This multicentric, comparative cross-sectional study aimed to assess the psychological impact of device-related skin issues on youths with T1D and their parents. METHODS: Participants with skin reactions were matched in a 1:1 ratio with a control group. Diabetes-related emotional distress was evaluated using the Problem Areas in Diabetes-Teen version (PAID-T) for participants aged 11 to 19 years and the Problem Areas in Diabetes-Parent Revised version (PAID-PR) completed by parents. In addition, glucose control was assessed through glycated hemoglobin (HbA1c) values and continuous glucose monitoring (CGM) metrics. RESULTS: A total of 102 children and adolescents were consecutively recruited. Adolescents with skin issues had higher PAID-T scores compared to those without (79.6 ± 21.1 vs 62 ± 16.8; P = .004). Parents of youths with skin reactions also reported higher PAID-PR scores than the control group (34.0 ± 11.0 vs 26.9 ± 12.3; P = .015). No differences were observed in HbA1c levels (6.9 ± 0.8% vs 6.8 ± 0.8%, P = .555) or CGM glucose metrics between the two groups. Remarkably, 25.5% were forced to discontinue insulin pumps and/or glucose sensors (21.5% and 5.9%, respectively). CONCLUSIONS: Our study highlighted the increased emotional burden experienced by youths with T1D and their parents due to device-related skin reactions, emphasizing the need for further research and interventions in this crucial aspect of diabetes management.

Impact of the Allergic Therapeutic Adherence in Children with Allergic Rhinitis and ADHD: A Pilot Study.

BACKGROUND: Allergic rhinitis (AR) is the most common chronic allergic disease in children. Several studies have shown an association between attention deficit hyperactivity disorder (ADHD) and allergies, especially AR. Patients with ADHD usually have poor therapeutic adherence, and untreated AR symptoms may worsen the quality of life of patients. METHODS: The aim of our study was to analyse therapeutic adherence in patients with ADHD and AR and estimate the impact of the adherence on ADHD symptoms. Total Nasal Symptoms Score (TNSS), Paediatric or Adolescent Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ 6-12 years; ARQLQ 13-17 years), Swanson, Nolan, and Pelham version IV scale (SNAP-IV), and Medication Assessment Questionnaire (MGL MAQ) were recorded. RESULTS: In the AR-ADHD group, a positive correlation between TNSS and SNAP-IV subscales was found: worse AR symptoms were related to a negative effect on ADHD scores. AR-ADHD patients with better ADHD therapeutic adherence showed higher AR symptoms and higher oppositional defiant disorder scores in the SNAP-IV questionnaire. CONCLUSIONS: Our results suggest that better adherence to AR therapy (oral antihistamines and/or intranasal corticosteroids, INCS) is associated with a reduction in inattention symptoms in children with ADHD. This data could prove to be fundamental for the psychic outcome of these patients.

Long-Term Safety of Omalizumab in Children with Asthma and/or Chronic Spontaneous Urticaria: A 4-Year Prospective Study in Real Life.

Background: Insufficient data are available on the long-term "real-life" safety profile of omalizumab in children. This study evaluated the long-term safety of omalizumab in a pediatric cohort with severe asthma or chronic spontaneous urticaria (CSU). Methods: A monocentric, prospective study evaluated the long-term safety of omalizumab in patients aged 6-18 years. Each patient completed the standardized MedDRA questionnaire to identify adverse events (AEs). Results: In total, 23 patients, median age 15 (14-18) years, affected by severe asthma (60.8%) or CSU (39.2%), treated with omalizumab for 2 (1-4) years were enrolled. The most common AEs belong to the system organ class (SOC) of general disorders and administration-site conditions (37.17%). Skin and subcutaneous tissue problems represent the second most frequently reported AEs (24.35%). Central nervous system and musculoskeletal disorders were quite frequent (15.38% and 8.97%, respectively). Other adverse events were tachycardia (5.12%), vertigo and abdominal pain (2.60% and 3.86%, respectively), and dry eye (1.3%). Only one patient reported herpes virus infection during treatment (1.3%). No cases of anaphylaxis, hemopathies, uronephropathies, respiratory, psychiatric, hepatobiliary, or oncological pathologies were reported. Conclusions: Long-term "real-life" treatment with omalizumab in children appears well tolerated. Its safety and efficacy profile makes omalizumab an excellent alternative in severe asthma and CSU in children.

An overview of the current state of food desensitization.

PURPOSE OF REVIEW: To highlight the current evidence on food desensitization in children with food allergy. RECENT FINDINGS: Food Allergen Specific Immunotherapy (FA-AIT) is currently recognised as a treatment option for treating children with allergy at least to the main common foods (i.e. milk, egg and peanut). The oral route of administration has been proven to be the most effective in achieving desensitisation. Efforts are devoted to overcome the current unmet needs mainly related to safety issues and long-term efficacy, as well as adherence to the treatment and improvement of health-related quality of life. In this perspective, alternative routes of administration and adjunctive treatments are under investigation. SUMMARY: The future of food allergy management is a personalised approach based on a shared decision-making that takes into account the needs of patients and families. Health professionals will be able to offer multiple treatment options, including FA-AIT with adjunctive or alternative therapies. Thus, patients should be correctly identified, using validated predictive factors, in order to select appropriate candidates for these therapies.

Technologies for Type 1 Diabetes and Contact Dermatitis: Therapeutic Tools and Clinical Outcomes in a Cohort of Pediatric Patients.

The increasing use of technological devices for the management of diabetes is related to the prolonged exposure of patients' skin to chemical and mechanical agents and, consequently, to the increased risk of developing dermatological complications. Among these, contact dermatitis is the most insidious skin disorder. Despite the magnitude of the issue, no universally accepted recommendations on the management of this common complication are currently available. Our observational study aimed to describe all the solutions adopted by patients and their caregivers to treat and prevent the appearance of contact dermatitis and to describe the clinical impact of this cutaneous complication. Twenty-one pediatric patients (mean age 12.1 ± 3.7 years) with type 1 diabetes were recruited in the study. The most common treatment used to treat acute skin lesions was the application of topical corticosteroids, sometimes associated with topical antibiotics (9.5%). In order to prevent the further appearance of dermatitis, the most frequently adopted measure was the use of hydrocolloid and/or silicone-based adhesives, followed by the application of protective barrier films. One patient reported benefit from the off-label use of fluticasone propionate nasal spray. However, only 52.4% of the study participants achieved a definitive resolution of the skin issue, and 38.1% of patients were forced to discontinue insulin pump therapy and/or continuous glucose monitoring. No differences were observed in glycated hemoglobin values between the period before and after the onset of contact dermatitis. Our study confirms the severity of this dermatological complication that may hinder the spread of new technologies for the management of diabetes. Finally, our findings highlight the importance of establishing close collaboration both with pediatric allergy specialists to prescribe the most suitable treatment and with manufacturing companies to ensure that adhesives of technological devices are free of harmful well-known sensitizers.

Negative effect of lockdown on juvenile idiopathic arthritis patients.

INTRODUCTION: The aim of this study is to evaluate a possible negative action of lockdown, during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, in the follow-up of juvenile idiopathic arthritis (JIA) patients. METHODS: We compared the number of JIA reactivations in the period March-July 2020 to the same months of 2018 and 2019. RESULTS: A total of 10 JIA reactivations have been documented on 58 patients (17%) visited in the period March-July 2018; 10 reactivations on 61 patients (16%) in the period March-July 2019; and 19 reactivations on 39 patients (49%) in the period March-July 2020, with a statistically significant increase (p <0.001). The other 19 patients who should have been visited during the same period, contacted by phone, indicated remission. Therefore, we hypothesize that the effective number of reactivations in the period March-July 2020 would be 19/58 patients (33%) which remains significantly greater than in the previous 2 years (p < 0.05). Among the 19 JIA patients reactivated in 2020, 3 spontaneously stopped the basic treatment due to parents' choice for fear of serious complications in case of SARS-CoV-2 infection and 4 had poor compliance with underlying treatment. In addition, 14/19 reactivated JIA patients did not perform the scheduled check according to the follow-up. In fact, the mean time interval between two follow-up visits was significantly greater in 2020 (157 ± 53 days, p < 0.0001) vs 2018 (108 ± 68 days) and 2019 (107 ± 40 days). CONCLUSIONS: We have found a significant increase in JIA reactivations in the period March-July 2020 compared to the same interval of 2018 and 2019. This increase may have been caused by poor compliance with background treatment, as documented in 7/19 JIA patients reactivated, and by a greater interval in follow-up checks. Therefore, it is necessary, in occasion of a new pandemic and lockdown, to implement greater controls using more appropriate telemedicine tools. Key Points • COVID-19 pandemic lockdown had a negative effect on the follow-up of JIA patients. • A significant increase in JIA reactivations was found during the lockdown. • Poor therapeutic compliance and follow-up checks have been proven during the lockdown. • It is necessary to improve telemedicine tools and scientific information during a pandemic and lockdown.