Current state and advances in desensitization for peanut allergy in pediatric age.

Peanut allergy affects about 1%-3% of the pediatric population in the world, with an important increase in the last decades. Nowadays, international guidelines recommend the early introduction of peanuts in the infant diet, with poor information about the quantity and the frequency of the intake. Allergen immunotherapy may represent the only therapeutic strategy able to modify the natural history of peanut allergy. In particular, oral immunotherapy showed the most promising results in terms of efficacy, but with significant rates of adverse reactions, mostly gastrointestinal. In 2020, the Food and Drug Administration and the European Medicines Agency approved Palforzia®, an oral drug for patients aged 4-17 years. Several studies are ongoing to improve the tolerability of oral immunotherapy and standardize the desensitization protocols. Sublingual immunotherapy permits to offer much lower doses than oral immunotherapy, but fewer adverse events are shown. Subcutaneous immunotherapy is associated with the greatest systemic adverse effects. Epicutaneous immunotherapy, for which Viaskin® patch was approved, has the highest safety profile. Innovative studies are evaluating the use of biological drugs, such as omalizumab or dupilumab, and probiotics, such as Lactobacillus rhamnosus, in monotherapy or associated with oral immunotherapy. Therapy for peanut allergy is constantly evolving, and new perspectives are ongoing to develop.

Safety of allergen-specific immunotherapy in children.

Allergic respiratory diseases, such as asthma and allergic rhinitis, are global health issues and have had an increasing prevalence in the last decades. Allergen-specific immunotherapy (AIT) is the only curative treatment for allergic rhinitis and asthma, as it has a disease-modifying effect. AIT is generally administered by two routes: subcutaneous (SCIT) and sublingual immunotherapy (SLIT). Local side effects are common, but usually well-tolerated and self-limited. However, systemic side effects are rare, and associated with uncontrolled asthma and bronchial obstruction, or related to errors in administration. Physicians should constantly assess potential risk factors for not only reporting systemic reactions and fatalities but also implementing other therapies to improve AIT safety. This paper highlights recent evidence on local and systemic reactions related to SCIT and SLIT in children.

Omalizumab and allergen immunotherapy for respiratory allergies: A mini-review from the Allergen-Immunotherapy Committee of the Italian Society of Pediatric Allergy and Immunology (SIAIP).

Although currently approved to treat severe asthma and chronic spontaneous urticaria, omalizumab has also been an effective and safe add-on treatment for other allergic diseases. Namely, omalizumab has been proposed to be used as add-on therapy in patients with allergic rhinitis and asthma and undergoing specific allergen immunotherapy (AIT). AIT is the only treatment that modifies the natural history of IgE-mediated diseases. This brief review summarizes the available evidence and controversies on the efficacy and safety of omalizumab combined with specific AIT.

Eosinophilic gastrointestinal disorders and allergen immunotherapy: Lights and shadows.

Allergic diseases, such as IgE-mediated food allergy, asthma, and allergic rhinitis, are relevant health problems worldwide and show an increasing prevalence. Therapies for food allergies are food avoidance and the prompt administration of intramuscular epinephrine in anaphylaxis occurring after accidental exposure. However, allergen immunotherapy (AIT) is being investigated as a new potential tool for treating severe food allergies. Effective oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) induce desensitization and restore immune tolerance to the causal allergen. While immediate side effects are well known, the long-term effects of food AIT are still underestimated. In this regard, eosinophilic gastrointestinal disorders (EGIDs), mainly eosinophilic esophagitis, have been reported as putative complications of OIT for food allergy and sublingual immunotherapy (SLIT) for allergic asthma and rhinitis. Fortunately, these complications are usually reversible and the patient recovers after AIT discontinuation. This review summarizes current knowledge on the possible causative link between eosinophilic gastrointestinal disorders and AIT, highlighting recent evidence and controversies.

Allergen immunotherapy in atopic dermatitis: Light and shadow in children.

Atopic dermatitis (AD) is a chronic remitting-relapsing inflammatory skin disorder. Due to the multifactorial pathogenesis, there are numerous therapeutic management approaches, mainly based on symptomatic treatments. In recent years, allergen immunotherapy (AIT) has been progressively advanced as targeted disease-modifying treatment of allergic disease. The most recent guideline from the American Academy of Dermatology concludes that data available do not support its use in AD. The Joint Task Force and The European Academy of Dermatology suggest that clinicians can consider AIT treatment in selected patients characterized by aeroallergen sensitization, prevalently HDM, severe AD, and clinical exacerbation after exposure to the causative allergen. Nevertheless, its role in AD is still under debate, especially in children.

Allergen immunotherapy and respiratory infections in children: an encouraging experience.

BACKGROUND: Allergic inflammation may promote respiratory infections (RI). House dust mite (HDM) sensitization is common in childhood. Allergen immunotherapy may cure allergy as it restores a physiological immune and clinical tolerance toward the causal allergen and exerts anti-inflammatory activity. This study retrospectively investigated whether 3 year high-dose HDM-sublingual immunotherapy (SLIT) could affect respiratory infections in children with allergic rhinitis. METHODS: Globally, 33 HDM allergic children (18 males, mean age 9.3 years) were subdivided in 2 groups: 20 treated with symptomatic drugs alone (group 1) and 13 by high-dose SLIT, titrated in mcg of major allergens (group 2) for 3 years. RESULTS: SLIT-treated children had significantly (P=0.01) less RI episodes (3.6) than symptomatically-treated children (5.4). In addition, SLIT-treated children had less fever (P<0.01) and took fewer medications, such as antibiotics (P<0.05) and fever-reducers (P<0.01), than symptomatically-treated children. CONCLUSIONS: This preliminary study suggests that high-dose 3-year SLIT might lessen RI in allergic children.

Atopic dermatitis: recent insight on pathogenesis and novel therapeutic target.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. It affects infancy, but it is also highly prevalent in adults and it is one of the disease burdens for the patients and their families. Nowadays, AD is recognized as a heterogenous disease with different subtypes with variable clinical manifestations which is affected by the impairments of the skin barrier. The severity of AD dictates the level of treatment. Current AD treatment focuses on restoration of the barrier function, mainly through the use of moisturizers and corticosteroids to control the inflammation, topical calcineurin inhibitors, and immunosuppresive drugs in the most severe cases. However, targeted disease-modifying therapies are under investigation. The most recent findings on the skin microbial dysbiosis is a promising future direction for the development of new treatments. We need to improve the understanding of the complex microbiome-host interactions, the role of autoimmunity, the comparative effectiveness of therapies and the ways to appropriately implement the educational strategies.

Anaphylaxis in pediatric population: A 1-year survey on the Medical Emergency Service in Liguria, Italy.

Anaphylaxis is a severe, life-threatening, generalized, or systemic hypersensitivity reaction. The diagnosis is mainly based on a clinical ground. This study aimed to evaluate the records of both phone calls and medical visits for anaphylaxis managed by the Liguria Medical Emergency Service (MES) in a pediatric population, occurred during 2013. The phone call is managed at each center and classified according to a level of care intensity and a presumed level of criticality, according to established criteria. Criticality is then re-evaluated (detected criticality) at the end of the medical visit following the same score adding the black code for patients who died. Most of the phone calls (86) to the MES were recorded in summer (40.7%), followed by spring (26.7%), autumn (16.3%), and winter (16.3%). Forty-eight patients (55.8%) were male. Anaphylaxis was confirmed in about half of patients. In addition, almost all subjects (97.7%) were referred to the Emergency Room. In conclusion, the present study shows that anaphylaxis represents a serious and relevant medical problem in the pediatric population and should be ever carefully managed.

Omega-3 fatty acids and asthma in children.

The purpose of this study was to summarize and analyze the results of studies supporting the use of omega-3 fatty acids for their therapeutic and preventive value in childhood asthma in light of recent genetic evidence strongly suggesting a pathogenetic role in asthma and to discuss the implications of these findings for future research. Although a considerable number of observational studies have been conducted in children showing a beneficial effect of omega-3 dietary intake in asthma, a fully well-designed, rigorously conducted investigational study is still lacking. Additionally, the few interventional trials with omega-3 supplementation conducted in asthmatic children have often yielded conflicting results. The genetic polymorphism and the gene-nutritional interactions that accompany asthma can be the missing factors and may explain the inconsistent results found in these interventional trials. Therefore, the analyses of key genes variants should be included in future studies to thoroughly investigate the effects of long-chain polyunsaturated fatty acid on asthma. Although a definitive conclusion can not be made supporting a beneficial effect of dietary modification or supplementation with omega-3 for the prevention or modification of asthmatic disease in children, there is sufficient evidence to support this possibility. There is, therefore, a clear need for future research to investigate the feasibility of this dietetic approach to reduce the likely development of asthma and/or the successful treatment of asthmatic disease. From a public health perspective, if a dietetic approach is successfully documented, even if only in a cohort of susceptible individuals, it would offer a far better management tool than currently available, better tolerated, and, in the long run, more cost-effective.

Adenoids in children: Advances in immunology, diagnosis, and surgery.

Adenoids are strategically located for mediating local and regional immune functions as they are exposed to antigens from both the outside air and the alimentary tract. Recurrent or chronic respiratory infections can induce histomorphological and functional changes in the adenoidal immunological barrier, sometimes making surgical treatment necessary. Our aim in this review is to summarize the crucial points about not only the immunological histopathology of adenoidal tissue, especially in patients with adenoid hypertrophy, but also the most common and useful diagnostic techniques and surgical options.

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.

Aetiological factors associated with chronic urticaria in children: a systematic review.

Chronic urticaria is a distressing condition with high costs. The aim of this literature review was to assess the relative frequency of causes of chronic urticaria in childhood and to provide guidance on which laboratory tests should be performed. Using PubMed, EMBASE and Cochrane databases, the literature from 1966 to 2010 (week 25) was systematically reviewed. Data from studies conducted on children who had had urticaria for at least 6 weeks, and assessing at least 3 different causes of urticaria, were analysed by reviewers using independent extraction. Six studies, all of low quality, met the inclusion criteria. Idiopathic and physical urticaria were common. Infections, autoimmunity and allergy were also reported. We conclude that children with chronic urticaria not caused by physical stimuli should undergo tests for allergy or infections only when there is a history of cause-effect correlation. High-quality trials are warranted to evaluate the causes of chronic urticaria in childhood.

Does a parent-reported history of pneumonia increase the likelihood of respiratory symptoms needing therapy in asthmatic children and adolescents?

BACKGROUND: Asthmatic children and adolescents attending outpatient clinics often have a history of pneumonia. Whether respiratory symptoms, lung function, and airway inflammation differ in asthmatic patients with and without a history of pneumonia remains controversial. AIMS: To compare clinical, lung functional, and inflammatory variables in asthmatic outpatients with and without a history of pneumonia. Methods. In 190 asthmatic outpatients, aged 6-18 years, we assessed respiratory symptoms, lung function (flows, volumes, and pulmonary diffusion capacity, DLCO/VA), and atopic-airway inflammation as measured by the fractional concentration of exhaled nitric oxide (FE(NO)). A previous medical and radiological diagnosis of pneumonia was defined as "recurrent pneumonia" if subjects had at least three pneumonia episodes or two episodes within a year. RESULTS: Of the 190 outpatients studied, 38 (20%) had a history of pneumonia. These patients had more frequent upper-respiratory symptoms, nighttime awakenings in the past 4 weeks, daily use of inhaled corticosteroids, and lower FE(NO) than the 152 asthmatic children without previous pneumonia (FE(NO): 20.6 ppb, 95% CI: 15.2-28.0 vs. 31.1 ppb, 95% CI: 27.0-35.8; p < .05). Of the 38 patients with previous pneumonia, 14 had recurrent pneumonia. Despite comparable lung volumes and flows, they also had lower DLCO/VA than asthmatic children with no recurrent pneumonia and asthmatic children without previous pneumonia (DLCO/VA%: 91.2 ± 11.3 vs. 108.5 ± 14.7 vs. 97.9 ± 18.6, p < .05). CONCLUSION: Respiratory assessment in asthmatic children and adolescents with a history of pneumonia, especially recurrent pneumonia, often discloses symptoms needing corticosteroid therapy, and despite normal lung volumes and flows, mild reductions in the variables reflecting gas diffusion and atopic-airway inflammation (DLCO/VA and FE(NO)). Whether these respiratory abnormalities persist in adulthood remains an open question.

Evaluation of safety and tolerability of a rush up-dosing allergen-specific immunotherapy with grass pollen, birch, hazel, and alder allergoid in children with allergic rhinoconjunctivitis, with or without asthma.

BACKGROUND Usually, the number of injections required to achieve the maintenance dose in subcutaneous immunotherapy (SCIT) is relatively small for some of the currently used allergens, but this may still be uncomfortable for patients, thus compromising adherence and compliance. OBJECTIVE The purpose of this study was to evaluate the safety and tolerability of a dose acceleration of a conventional induction schedule using an allergoid extract of grass pollen, birch, hazel, and alder, needed to achieve the ideal maintenance dose. METHODS In this open-label study, 34 patients with allergic rhinoconjunctivitis, with or without asthma, were treated with SCIT using an allergoid for grass pollen or birch or mix trees with an increase in accelerated induction dose comprising only 3 injections, one per week, compared to a conventional induction pattern in five injections (once a week). Safety determination was assessed by evaluating local and systemic adverse events. Tolerability was evaluated by patients and physicians who performed the treatment. RESULTS No treatment-related adverse events were observed in any of the patients undergoing rush SCIT. No local reactions, no systemic reactions of any degree (WAO Grade) have been observed. Tolerability has always been rated as very good by both patients and physician. CONCLUSIONS The induction phase, needed to achieve the monthly maintenance dose for a pollen extract, can be greatly accelerated, ensuring a tolerability comparable to that of the conventional schedule.

Inter-society consensus for the use of inhaled corticosteroids in infants, children and adolescents with airway diseases.

BACKGROUND: In 2019, a multidisciplinary panel of experts from eight Italian scientific paediatric societies developed a consensus document for the use of inhaled corticosteroids in the management and prevention of the most common paediatric airways disorders. The aim is to provide healthcare providers with a multidisciplinary document including indications useful in the clinical practice. The consensus document was intended to be addressed to paediatricians who work in the Paediatric Divisions, the Primary Care Services and the Emergency Departments, as well as to Residents or PhD students, paediatric nurses and specialists or consultants in paediatric pulmonology, allergy, infectious diseases, and ear, nose, and throat medicine. METHODS: Clinical questions identifying Population, Intervention(s), Comparison and Outcome(s) were addressed by methodologists and a general agreement on the topics and the strength of the recommendations (according to the GRADE system) was obtained following the Delphi method. The literature selection included secondary sources such as evidence-based guidelines and systematic reviews and was integrated with primary studies subsequently published. RESULTS: The expert panel provided a number of recommendations on the use of inhaled corticosteroids in preschool wheezing, bronchial asthma, allergic and non-allergic rhinitis, acute and chronic rhinosinusitis, adenoid hypertrophy, laryngitis and laryngospasm. CONCLUSIONS: We provided a multidisciplinary update on the current recommendations for the management and prevention of the most common paediatric airways disorders requiring inhaled corticosteroids, in order to share useful indications, identify gaps in knowledge and drive future research.

Consensus statement of the Italian society of pediatric allergy and immunology for the pragmatic management of children and adolescents with allergic or immunological diseases during the COVID-19 pandemic.

The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic.Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases.

Prevalence of EEG paroxysmal activity in a population of children with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Sleep breathing disorders may trigger paroxysmal events during sleep such as parasomnias and may exacerbate preexisting seizures. We verified the hypothesis that the amount of EEG paroxysmal activity (PA) may be high in children with obstructive sleep apnea syndrome (OSAS). DESIGN: Prospective study. SETTINGS: Sleep unit of an academic center. PARTICIPANTS: Polysomnographic studies were performed in a population of children recruited prospectively, for suspected OSAS, from January to December 2007, with no previous history of epileptic seizures or any other medical conditions. All sleep studies included > or = 8 EEG channels, including centrotemporal leads. We collected data about clinical and respiratory parameters of children with OSAS and with primary snoring, then we performed sleep microstructure analysis in 2 OSAS subgroups, matched for age and sex, with and without paroxysmal activity. MEASUREMENTS AND RESULTS: We found 40 children who met the criteria for primary snoring, none of them showed PA, while 127 children met the criteria for OSAS and 18 of them (14.2%) showed PA. Children with PA were older, had a predominance of boys, a longer duration of OSAS, and a lower percentage of adenotonsillar hypertrophy than children without PA. Moreover, PA occurred over the centrotemporal regions in 9 cases, over temporal-occipital regions in 5, and over frontocentral regions in 4. Children with PA showed a lower percentage of REM sleep, a lower CAP rate and lower A1 index during slow wave sleep, and lower total A2 and arousal index than children without EEG abnormalities. CONCLUSIONS: We found a higher percentage of paroxysmal activity in children with OSAS, compared to children with primary snoring, who did not exhibit EEG abnormalities. The children with paroxysmal activity have peculiar clinical and sleep microstructure characteristics that may have implications in the neurocognitive outcome of OSAS.

A new protocol for specific oral tolerance induction in children with IgE-mediated cow's milk allergy.

IgE-mediated cow's milk allergy (CMA) is a heavy burden for patients, particularly for children and their families. Allergen avoidance represents the only therapeutic option, but oral desensitization protocols have been suggested. Because of the long duration and complexity of these protocols we examined the feasibility of an oral tolerance induction protocol using a weekly up-dosing schedule. Children with IgE-mediated food allergy to milk, confirmed by a double-blind placebo-controlled food challenge, were recruited. Six of them were randomized to double-blind desensitization with milk or soy formula as placebo. Seven patients underwent the protocol in open fashion. The desensitization schedule started with one drop of whole CM diluted 1:25 every week. The dose was doubled weekly until the 18th week to achieve an intake of 200 mL in approximately 4 months. Of the 13 children enrolled, 10 children received CM and 3 control children received soy formula. Full tolerance (200 mL of milk) was achieved in 7 children; in 2 children this therapeutic approach failed, because severe reactions occurred during the procedure. One patient achieved a partial tolerance (64 mL of milk). The three control children receiving placebo still showed a positive food challenge at the end of the study. A weekly up-dosing oral tolerance induction could be a viable alternative to traditional protocols for children with IgE-mediated CMA.

Pru p 3 sensitization in children with allergy to Parietaria pollens.

BACKGROUND: Pru p 3 is the major allergen of the peach and belongs to the LTP family. Pru p 3 sensitization has been associated with severe allergic symptoms after eating LTP-containing foods. However, a previous experience partially downsized the potential danger of Pru p 3 sensitization in a group of adult rhinitics. This study aimed to evaluate the real impact of Pru p 3 sensitization in children in a real-world setting. METHODS: 82 consecutive paediatric patients (55 males and 27 females, mean age 8.19±4.23 years) with allergic rhinitis due to Parietaria pollen allergy and sensitization to Pru p 3, documented by ISAC test, were evaluated. Serum IgE was measured by ImmunoCap method. Allergic symptoms occurring after ingesting LTP-containing foods were considered and scored as oral allergy syndrome, food allergy, and anaphylaxis. RESULTS: About one-quarter of Pru p 3-sensitized children reported anaphylaxis after ingesting LTP-containing foods, about half reported food allergy or oral allergy syndrome. Only » was merely sensitized. CONCLUSIONS: Pru p 3 sensitization deserves careful attention in children contrary to what might occur in adult patients. It could depend on the age and the serum IgE level. Thus, Pru p 3 sensitization should be adequately interepreted and managed in clinical practice.