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The fast diffusion of the SARS-CoV-2 pandemic have called for an equally rapid evolution of the therapeutic options.The Human recombinant monoclonal antibodies (mAbs) have recently been approved by the Food and Drug Administration (FDA) and by the Italian Medicines Agency (AIFA) in subjects aged ≥12 with SARS-CoV-2 infection and specific risk factors.Currently the indications are specific for the use of two different mAbs combination: Bamlanivimab+Etesevimab (produced by Eli Lilly) and Casirivimab+Imdevimab (produced by Regeneron).These drugs have shown favorable effects in adult patients in the initial phase of infection, whereas to date few data are available on their use in children.AIFA criteria derived from the existing literature which reports an increased risk of severe COVID-19 in children with comorbidities. However, the studies analyzing the determinants for progression to severe disease are mainly monocentric, with limited numbers and reporting mostly generic risk categories.Thus, the Italian Society of Pediatrics invited its affiliated Scientific Societies to produce a Consensus document based on the revision of the criteria proposed by AIFA in light of the most recent literature and experts’ agreement.This Consensus tries to detail which patients actually have the risk to develop severe disease, analyzing the most common comorbidities in children, in order to detail the indications for mAbs administration and to guide the clinicians in identifying eligible patients.

Chronic spontaneous urticaria (CSU) is a condition defined by the presence of recurrent urticaria, angioedema, or both, which persist for more than six weeks in duration and occurs in the absence of an identifiable trigger. Both children and adults can develop CSU, although it is more common in adults and in women than in men, with a peak occurrence in the third to fifth decades of life. It imposes a significant burden on patients, families and healthcare systems. The goal of therapy in patients with CSU is to achieve a level of symptom control and improvement in quality of life that is acceptable to the patient, while minimizing therapy-related side effects. The recent introduction of biologic drugs has changed the management of the disease. This work aims to provide a narrative review of the current state of biological therapy and the promising drugs under development for CSU.

In recent years there has been an important implementation in the medical field of both Mobile Health, such as the use of mobile communication devices, and of other telemedicine tools in general, with the aim of supporting the supervision of diseases from the moment of the first diagnosis to the therapeutic follow-up. In fact, Digital Health can also have a very positive impact on the management of allergic patients, who are known to have the greatest need for regular monitoring, simplifying contact between doctor and patient, but there is still a need to improve implementation regulations, define certification programs and adequate reimbursement systems, as well as to guarantee a high level of attention to the protection of sensitive data. The hope is that one positive outcome of the Covid-19 pandemic will be an acceleration, by all stake-holders involved, of the process of the modernization of health care. (www.actabiomedica.it).

Hypersensitivity reactions to polyethylene glycol (PEG) is an emerging challenge and the interest about this disease is growing since PEG is considered one of the possible causes of coronavirus disease 2019 (COVID 19) vaccine-associated anaphylaxis. PEG is used in a wide variety of pharmaceutical, medical, in-dustrial, cosmetic, and food products and can be an active ingredient or used as an excipient. PEG is present in several medications, and it may or may not be present in different formulations and dosages of the same drug. Lack of standardization nomenclature, inadequate labelling of products and lack of knowledge about PEG involvement in hypersensitivity reactions expose patients at risk of presenting multiple reactions before a diagnosis could be made. In this review we describe the main cases published in literature and propose an allergy work-up and management. (www.actabiomedica.it).

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy (FA) characterized by delayed and severe gastrointestinal symptoms that typically occurs within the first year of life. Many aspects of this pathology are currently unclear. FPIES is classified as a non-IgE immune-mediated FA in which the immune response is thought to act mainly through cell-mediated mechanisms. In patients with FPIES, the symptom pattern is determined by the frequency and dose of food allergen in the diet. Diagnosis of FPIES may be difficult, mainly due to the lack of specific biomarkers to confirm or exclude the diagnosis. FPIES is a clinical diagnosis, mainly based on clinical features which, although not specific, are reproducible every time the patient takes the food. Different diagnostic criteria of FPIES were published over time in the literature. The present narrative review aims to analyze the current clinical evidence in epidemiology, pathophysiology, diagnosis, and management of this condition.

In the last few years much attention has been focused on research on severe asthma and the role of biologicals in its treatment, also in children. However, mild asthma is way more common in childhood and still causes as many as 30-40% of asthma exacerbations requiring emergency consultation. The management of "intermittent" and "mild persistent" asthma phenotypes is still a matter of debate, even if the role of inhaled corticosteroids, both continuous and intermittent, is a cornerstone in this field. Nevertheless, updates on the strategies to manage these patients are coming, since evidence emerged on the role of inflammation also in these asthma phenotypes as well as on the potential side effect and risks of short-acting beta 2 agonists overuse, which is common in patients for which they have been prescribed as the only as-needed treatment. Unsurprisingly, international guidelines, including GINA, are starting to recommend associating a corticosteroid when using a reliver. In this paper we overview the (r)evolution regarding the management of intermittent and mild persistent asthma. We also focus on the importance of knowing the chemical and physical characteristics of drugs and inhaler devices in order to optimize the treatment and reach the distal airways, as well as of trying to achieve a good compliance to treatments, especially in adolescents, for which it is currently possible to rely also on new digital health technologies.

Histaminergic urticaria-angiodema is a common complaint in children. According to clinical criteria, it is classified as acute and chronic urticaria. A further clinical classification relies on triggering factors. We focus on diagnosis and therapeutic strategies. We report the main progresses in the field and issues that remain to be understood. (www.actabiomedica.it)

Primary immunodeficiencies (PIDs) are inherited disorders classically characterized by increased susceptibility to infections. Nevertheless, in the last two decades, genomic analysis (such as NGS) coupled with biochemical and cellular studies led to a more accurate definition for a growing number of novel genetic disorders associated with PIDs. This revealed new aspects of the immune system and its function and regulation within these diseases. In particular, it has been clarified that the clinical features of PIDs are much broader that originally thought and extend beyond an increased susceptibility to infections. More specifically, immune dysregulation is very often described in novel characterized PIDs and can lead to multiple autoimmune diseases, lymphoproliferation and malignancies. If not promptly diagnosed, these could negatively impact patient’s prognosis. The aim of this review is to increase the awareness of recently discovered PIDs, characterized predominantly by immune dysregulation phenotypes. Findings highlighted in this review suggest screening for immunodeficiency in patients with lymphoproliferation or early onset/multiple autoimmune diseases. Prompt diagnosis would potentially allow most successful treatment and clinical outcome for patients with PIDs. (www.actabiomedica.it)

Allergic rhinoconjunctivitis (AR) treatment is usually pharmacological in children, but medications are merely symptomatic, may not be completely effective, and may have relevant side effects. Thus, doctors and parents look at complementary medicine, including nutraceuticals. Lertal®, an oral nutraceutical, contains extract of Perilla, quercetin, and Vitamin D3 It has been reported that adults with AR diminished allergic symptoms and medication use during Lertal® therapy. Therefore, the current polycentric, randomized, double blind, parallel-group, placebo-controlled study aimed to evaluate the efficacy and safety of Lertal® as an add-on treatment in children with AR. In this study, 146 children (94 males and 52 females, mean age 9.1±1.88) were randomly assigned to Lertal® + standard treatment or Placebo + standard treatment and were visited at baseline (W0), and after 2 (W2) and 4 weeks (W4). Standard treatment consisted of continuous antihistaminic schedule. The primary endpoint was the Total Symptom Score (TSS - last 12 hours) change from the baseline to the end of the 4-week treatment. Both groups significantly (p less 0.0001 for both) reduced TSS (last 12 hours) after 4 weeks (% change: - 63.6% in Lertal®-group and - 60.7% in Placebo-group; p= n.s. intergroup analysis). Notably, 24 children had symptom worsening between W2 and W4: 8 in the Lertal®-group and 16 in the Placebo-group, with significant intergroup difference (p less than 0.05). All of them were poly-allergic subjects exposed to multiple allergens. There was no relevant adverse event. The present study documented that Lertal®, as add-on treatment, was able to significantly prevent the occurrence of clinical worsening and was safe in AR poly-allergic children.

Questo documento è stato sviluppato a seguito della riunione del Gruppo di Lavoro Italiano sull’Immunoterapia allergene specifica (AIT) promosso dalla Società Italiana di Allergologia e Immunologia Pediatrica (SIAIP). L’obiettivo è implementare e ottimizzare la pratica clinica dell’AIT per i pazienti in età pediatrica con malattie allergiche. Questo documento costituisce una guida per un efficace e sicuro utilizzo dell’AIT nei bambini allergici, allo scopo di supportare lo specialista, per quanto possibile, nella pratica clinica . Per la preparazione di questo documento, il Gruppo di Lavoro ha eseguito un’approfondita ricerca nella letteratura medica, con l’ausilio di Pub-Med. Gli studi clinici pubblicati sono stati valutati per categorie di evidenza e utilizzati per stabilire la forza della raccomandazione.

Allergic immunotherapy (AIT) today represents a therapeutic practice for the treatment of allergic diseases such as rhinitis or asthma and is recognized as the only treatment able to modify the natural history of the disease. Administering gradually increasing doses of the causative allergen, AIT, has the objective of achieving immune tolerance against allergens. One of the administration routes most used in clinical practice is represented by the sublingual route. Current research on sublingual immunotherapy (SLIT) is focused on confirming the efficacy for all the different relevant allergens, on a better definition of allergen extracts and the improvement of their immunological properties and safety, on the identification of best treatment regimens, and on the possibility of extending the clinical indications. The aim of this review is to describe the most recent step in the field of SLIT development.

The increasing prevalence of allergy and its impact on individual quality of life underline the need of an improvement of the treatment options in order to modify the natural course of allergic diseases. In this context, specific sublingual immunotherapy (SLIT) represents an approach currently available to redirect inappropriate immune response in atopic patients. The immunological mechanism that underlies SLIT has only started to be investigated. Oral mucosal tissue displays high permeability for allergens. It is conceivable that the sublingual administration route might induce immunological tolerance towards allergens involving cells and mediators specific of oral and intestinal mucosa. Recent literature data stated the presence in oral mucosa of dendritic cells (DCs) which express the high-affinity receptor for immunoglobulin (Ig)E (FcERI). Moreover some studies indicated that the mechanism of immunotherapy might be based on the increase of number and activity of regulatory T cells. Accumulating evidences suggest that the generation of T regulatory cells in periphery is orchestrated by a particular subset of DCs. It seems that repeated stimulation of naive CD4 T cells with allogenic immature DCs induce Tr1 cells maturation. Nevertheless other cells are involved in this process, such as TLR, MHC of I and II class and costimolatory molecules such as CD40, CD 80/B7.1 and CD 86/B7.2. An increase of serum IgG4 and IgA, a reduced number of inflammatory cells infiltrating target organs, as well as a reduction of eosinophilic cationic protein and a very heterogenous influence on T cells in the peripheral blood in terms of T cell suppression also occur with SLIT. All these molecules orchestrate the immune response within the regional immune system, recreating a favourite environment for the induction of tolerance operated by SLIT.

Recently, there has been considerable interest in the relationship between allergic and autoimmune diseases. We evaluated the prevalence of thyroid autoimmunity in 566 children affected by atopic dermatitis (AD), urticaria, rhinitis, chronic cough, and asthma. Our results suggest that allergy and autoimmunity can be two potential outcomes of dysregulated immunity. It is tempting to speculate that NK Th2 cells can favour asthma onset and at the same time improve thyroid autoimmunity.

Approximately 50 percent of the world population is infected with Helicobacter pylori (H. pylori), with the highest prevalence rates in developing countries. The current guidelines suggest the use of triple therapy as first choice treatment of Helicobacter pylori infection, although the eradication failure rate is more than 30 percent. Current interest in probiotics as therapeutic agents against Helicobacter pylori is stimulated by the increasing resistance of pathogenic bacteria to antibiotics, thus the interest for alternative therapies is a real actual topic. Available data in children indicate that probiotics seem to be efficacious for the prevention of antibiotic associated side-effects, and might be of help for the prevention of Helicobacter pylori complications by decreasing Helicobacter pylori density and gastritis, and for the prevention of Helicobacter pylori colonization or re-infection by inhibiting adhesion to gastric epithelial cells. There is no clear evidence that probiotics may increase the Helicobacter pylori eradication rate.

Background: No study has compared allergic sensitization patterns in infants with atopic eczema from different countries. The aim of this study was to investigate the patterns of allergic sensitization in a cohort of infants with atopic eczema participating in a multicentre, international study. Methods: Two thousand one hundred and eighty-four infants (mean age 17.6 months) with atopic eczema from allergic families were screened in 94 centres in 12 countries to participate in a randomized trial for the early prevention of asthma. Clinical history, Severity Scoring of Atopic Dermatitis Index, measurements for total serum IgE and specific IgE antibodies to eight food and inhalant allergens were entered into a database before randomization to treatment. A history of type of feeding in the first weeks of life and exposure to animals was recorded. Results: A total of 52.9% of the infants had raised total IgE, and 55.5% were sensitized to at least one allergen. There was a wide difference in the total IgE values and in the sensitization rates to foods and aeroallergens among infants from different countries. The highest prevalence rates of allergen-sensitized infants were found in Australia (83%), the UK (79%) and Italy (76%). Infants from Belgium and Poland consistently had the lowest sensitization rates. In each country, a characteristic pattern of sensitization was found for aeroallergens (house dust mite > cat > grass pollen > Alternaria), but not for food allergens. Conclusions: In infants with atopic eczema, there is a wide variation in the pattern of allergic sensitization between countries, and data from one country are not necessarily generalizable to other countries.