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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Allergen-Specific Immunotherapy for Respiratory Allergy in Children: Unmet Needs and Future Goals.

Allergen-specific immunotherapy for the treatment of respiratory allergy is currently supported, at least for selected products, by evidence of efficacy and effectiveness in the pediatric age. However, unmet needs remain in terms of administration regimens, duration of treatment, biomarkers, and preventive effects. These knowledge gaps need to be urgently addressed to provide pediatricians and pediatric allergists with more definite recommendations for the use of this treatment in children. This article critically appraises the most relevant debated issues on allergen-specific immunotherapy in children, focusing on allergen standardization procedures, heterogeneity of clinical studies, and regulatory and pharmacoeconomic aspects.

Vitamin D status and body mass index in children with atopic dermatitis: A pilot study in Italian children.

BACKGROUND: Vitamin D (vitD) is involved in important regulatory functions of the innate and adaptive immune system. So, it has been hypothesized that vitD might influence the course of atopic dermatitis (AD). Also obesity may have impact on immune system. The aim of our study was to investigate vitamin D status and body mass index (BMI) in urban children with AD. METHODS: 52 children with AD and 43 healthy children were enrolled. SCORAD, BMI and serum vitD levels were evaluated. RESULTS: There was an association between vitamin D and the AD occurrence but neither between vitamin D and the AD severity, nor between vitamin D and BMI. A positive correlation was observed between BMI and the AD severity in males. CONCLUSIONS: This study highlights the complex inter-relationships among atopic dermatitis severity, vitamin D and body mass index and suggests the need to investigate the role of genetic factors and/or gender-related differences to possibly identify new prevention strategies.

Prevention of food and airway allergy: consensus of the Italian Society of Preventive and Social Paediatrics, the Italian Society of Paediatric Allergy and Immunology, and Italian Society of Pediatrics.

BACKGROUND: Allergic sensitization in children and allergic diseases arising therefrom are increasing for decades. Several interventions, functional foods, pro- and prebiotics, vitamins are proposed for the prevention of allergies and they can't be uncritically adopted. OBJECTIVE: This Consensus document was developed by the Italian Society of Preventive and Social Paediatrics and the Italian Society of Paediatric Allergy and Immunology. The aim is to provide updated recommendations regarding allergy prevention in children. METHODS: The document has been issued by a multidisciplinary expert panel and it is intended to be mainly directed to primary care paediatricians. It includes 19 questions which have been preliminarily considered relevant by the panel. Relatively to each question, a literature search has been performed, according to the Italian National Guideline Program. Methodology, and a brief summary of the available literature data, has been provided. Many topics have been analyzed including the role of mother's diet restriction, use of breast/formula/hydrolyzed milk; timing of introduction of complementary foods, role (if any) of probiotics, prebiotics, vitamins, exposure to dust mites, animals and to tobacco smoke. RESULTS: Some preventive interventions have a strong level of recommendation. (e.g., the dehumidifier to reduce exposure to mite allergens). With regard to other types of intervention, such as the use of partially and extensively hydrolyzed formulas, the document underlines the lack of evidence of effectiveness. No preventive effect of dietary supplementation with polyunsaturated fatty acids, vitamins or minerals has been demonstrated. There is no preventive effect of probiotics on asthma, rhinitis and allergic diseases. It has demonstrated a modest effect, but steady, in the prevention of atopic dermatitis. CONCLUSIONS: The recommendations of the Consensus are based on a careful analysis of the evidence available. The lack of evidence of efficacy does not necessarily imply that some interventions may not be effective, but currently they can't be recommended.

Pharmacological interventions on early functional gastrointestinal disorders.

BACKGROUND: Functional gastrointestinal disorders (FGIDs) are chronic or recurrent gastrointestinal symptoms without structural or biochemical abnormalities. FGIDs are multifactorial conditions with different pathophysiologic mechanisms including altered motility, visceral hyperalgesia, brain-gut disturbance, genetic, environmental and psychological factors. Although in most cases gastrointestinal symptoms are transient and with spontaneous resolution in infancy multiple dietary changes and pharmacological therapy are often started despite a lack of evidence-based data. Our aim was to update and critically review the current literature to assess the effects and the clinical appropriateness of drug treatment in early (occurring in infants and toddlers) FGIDs. METHODS: We systematically searched the Medline and GIMBE (Italian Group on Medicine Based on Evidence) databases, according to the methodology of the Critically Appraised Topics (CATs). We included reviews, clinical studies, and evidence-based guidelines reporting on pharmacological treatments. Systematic reviews and randomized controlled trials (RCTs) concerning pharmacologic therapies in children with early FGIDs were included, and data were extracted on participants, interventions, and outcomes. RESULTS: We found no evidence-based guidelines or systematic reviews about the utility of pharmacological therapy in functional regurgitation, infant colic and functional diarrhea. In case of regurgitation associated with marked distress, some evidences support a short trial with alginate when other non pharmacological approach failed (stepped-care approach). In constipated infants younger than 6 months of age Lactulose is recommended, whilst in older ages Polyethylene glycol (PEG) represents the first-line therapy both for fecal disimpaction and maintenance therapy of constipation. Conversely, no evidence supports the use of laxatives for dyschezia. Furthermore, we found no RCTs regarding the pharmacological treatment of cyclic vomiting syndrome, but retrospective studies showed a high percentage of clinical response using cyproheptadine, propanolol and pizotifen. CONCLUSION: There is some evidence that a pharmacological intervention is necessary for rectal disimpaction in childhood constipation and that PEG is the first line therapy. In contrast, for the other early FGIDs there is a lack of well-designed high-quality RCTs and no evidence on the use of pharmacological therapy was found.

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.

Effect of high-dose sublingual immunotherapy on respiratory infections in children allergic to house dust mite.

BACKGROUND: Allergic rhinitis is characterized by eosinophil inflammation. Allergic inflammation may induce susceptibility to respiratory infections (RI). House dust mite (HDM) sensitization is very frequent in childhood. Allergen immunotherapy may cure allergy as it restores a physiologic immune and clinical tolerance to allergen and exerts anti-inflammatory activity. OBJECTIVE: This study investigated whether six-month high-dose, such as 300 IR (index of reactivity), HDM-sublingual immunotherapy (SLIT) could affect RI in allergic children. METHODS: Globally, 40 HDM allergic children (18 males; mean age, 9.3 years) were subdivided in 2 groups: 20 treated by symptomatic drugs (group 1) and 20 by high-dose HDM-SLIT (group 2), since September 2012 to April 2013. The daily maintenance dose of HDM-SLIT was 4 pressures corresponding to 24, 4.8, and 60 µg, respectively of the major allergens Dermatophagoides pteronyssinus (Der p) 1, Der p 2, and Dermatophagoides farinae (Der f) 1. RI was diagnosed when at least 2 symptoms or signs, and fever were present for at least 48 hours. A family pediatrician provided diagnosis on a clinical ground. RESULTS: SLIT-treated children had significantly (p = 0.01) less RI episodes (3.5) than control group (5.45). About secondary outcomes, SLIT-treated children had less episodes of pharyngo-tonsillitis (p < 0.05) and bronchitis (p < 0.005), and snoring (p < 0.05) than control group. 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 control group. CONCLUSION: This preliminary study might suggest that also a short course (6 months) of high-dose SLIT, titrated in µg of major allergens, could reduce RI in allergic children.

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.