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Background Asthma control is the goal of the management, but some patients do not achieve adequate control. Adherence to prescriptions is a relevant factor in this issue. As very few studies addressed this problem in adolescents, we investigated this aspect in this setting. Methods This cross-sectional study consecutively enrolled 87 adolescents (60 males, 27 females, median age 14.2 years) with asthma visited at a third-level pediatric clinic. We used two questionnaires: Morisky Medication Adherence Scale (MMAS-8) and TAI. Results As regards MMAS-8, 23 (26.6%) adolescents had low adherence, 34 (39%) medium, and 30 (34.4%) high. Concerning TAI, 34 (39%) had low adherence, 43 (49.5%) medium, and 10 (11.5%) high. After stratification per asthma control grade, adolescents with partly-controlled asthma had the highest scores for medium adherence (p=0.0017 and 0.049, respectively for MMAS-8 and TAI). Conclusions Adolescents with asthma have poor adherence independently to the asthma control grade. This failure implicates that more attention should be paid to this issue in clinical practice.

Eosinophilic esophagitis (EoE) is an emerging antigen-mediated, inflammatory disease of unknown etiology. EoE affects about 1/2,000 patients in the United States (US), with a higher prevalence rate in adults (43.4/100,000) than in children (29.5/100,000), prevailing in Caucasians and male sex. EoE is a multifactorial disease typically characterized by type 2 inflammation. Pathogenesis is not entirely understood and is likely non-IgE mediated. Food allergens trigger EoE, stimulating the dysregulated immune cells through an impaired esophageal epithelial barrier. Clinical presentation of EoE depends on age and mainly includes food refusal, vomiting, abdominal or chest pain, dysphagia, and food impaction. Endoscopy is the gold standard to diagnose EoE. The goal of EoE therapy is to achieve clinical and histological remission to prevent esophageal fibrosis and improve patients' quality of life (QoL). Cornerstones of therapy are PPIs, topical steroids, and elimination diets. Over recent decades, research progress has been made in terms of a greater understanding of the EoE pathogenesis and new therapeutic approaches. However, there are still several unmet needs, such as non-invasive tools and biomarkers for monitoring the disease.

Obesity is a multifactorial disease, and its prevalence in children has been increased over the last 30 years in Italy and many other European Countries. Obesity significantly impacts the quality of life of affected patients and health care systems. Obesity is related to several clinical comorbidities, especially metabolic syndrome and diabetes. The standard of care in this patient is still considered lifestyle changes and a healthy diet with regular physical activity to prevent associated metabolic complications (impaired glucose tolerance and type 2 diabetes) and reduce cardiovascular risk.Therefore, pediatricians should recognize potential risk factors (sedentary lifestyle, sugar, and fats-rich diet, genetic syndromes) and early signs of overweight and obesity to promptly address the child to a pediatric endocrinologist and a specialized reference Center.

Background and aim  It is still unclear whether patients with severe asthma are at greater risk of developing severe COVID-19, particularly pediatric allergic patients under biologic therapy. Studies targeting pediatric patients are currently limited; thus, this study aims to assess the clinical characteristics of young patients with severe asthma under biological therapies during the COVID-19 pandemic. Methods We collected data from February 2020 to April 2021. Patients with severe asthma treated with biological therapies (omalizumab and mepolizumab) have been enrolled. We described demographic data, clinical features, therapies, comorbidities, and laboratory findings for each patient. For patients who got COVID-19, we also described the severity of the disease, the need for hospitalization, and specific therapy. Results A total of 14 patients were included in the study, 11 (78.6%) of them under treatment with omalizumab and 3 (21.6%) with mepolizumab. We identified four patients (28.6%) who tested positive for SARS-CoV-2. Two patients treated with mepolizumab had an asymptomatic disease, and two patients treated with omalizumab had mild disease. Only one patient with mild COVID-19 required hospitalization and specific therapy because of severe obesity. Conclusions No differences regarding the SARS-CoV-2 infection have been found between the two treatments groups. Furthermore, any poor outcome has been observed, confirming the safety of biological therapies. The limited number of patients enrolled and the lack of a control group did not establish a significant risk for infections for these patients.

Background: Coronavirus disease 2019 (COVID-19) affects people of any age with high mortality and morbidity in adults older than 65 years. Reports on pediatric cases highlighted those children generally develop milder symptoms than adults or are asymptomatic. We aimed to assess the epidemiological and clinical data of children and adolescents with SARS-CoV-2 infection to improve pediatric COVID-19., Methods: We retrospectively analyzed clinical and epidemiological features of patients with SARS-CoV-2 infection hospitalized at the Pediatric Hospital of Pavia, Italy, between February 1, 2020, to April 30, 2021., Results: 71 patients aged 0-16 years were included; 33 (46%) females and 38 (54 %) males. Thirty-three (46%) patients had comorbidities, such as obesity and hematological diseases. Thirty-one children (44%) were exposed to COVID-19-positive household members. Nine (12.7 %) patients were asymptomatic, whereas 57 (80.3%) had a mild-moderate disease. Only five (7%) showed a severe or critical disease, and two patients required ICU admission. The most frequent symptoms were fever (76%), loss of appetite (26%), gastrointestinal symptoms (19%), and cough (19%). Chest X-ray was performed in 42 patients showing lung abnormalities in more than half of symptomatic patients. The most common laboratory features were lymphopenia and eosinopenia associated with high levels of inflammation markers., Conclusions: This study confirmed that COVID-19 has a mild course in children compared to adults. Most of the enrolled children were asymptomatic or had a mild-moderate disease. Patients with comorbidities were more prone to develop clinical complications.

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Background and aim Recurrent wheezing is often triggered by viral respiratory infections. The aims of our study were: i) to evaluate whether the addition of a nutraceutical (Leucodif®), could improve the efficacy of montelukast or inhaled steroids (ICS) compared to the single treatment; ii) to verify whether a treatment is more effective than another. Our study was biased by the COVID-19 pandemic, which resulted in a lockdown of almost two months in Italy. Methods The multicenter, open-label study enrolled 84 children aged 2-6 years diagnosed with recurrent wheezing and randomized them into four treatment arms for three months: ICS treatment; ii) montelukast; iii) montelukast + Leucodif; iv) ICS + Leucodif. Children were assessed at baseline and after one, two, and three months of treatment using the TRACK score for both the caregiver and the physician. Results Out of the 84 patients, 18 patients received ICS therapy, 22 patients ICS + Leucodif, 24 patients montelukast, and 20 patients montelukast + Leucodif. All four treatments resulted in a significant reduction in symptoms with no differences among the various groups. Conclusions Our study demonstrates that montelukast therapy appears to be equally effective as ICS therapy and that the addition of the nutraceutical Leucodif does not appear to improve the treatment outcome. However, in our opinion our study was strongly influenced and biased by the lockdown due to the COVID-19 pandemic, which inherently resulted in reduced exposure to the viruses that commonly cause respiratory infections in children.

Background: Primary HHV7 infection is almost ubiquitous, and it can present as exanthema subitem. Little is known on the clinical relevance of HHV7 neuroinvasion in immunocompetent children., Methods: We describe 12 patients (median age 9.45 years, 50% males) with acute encephalopathy and active HHV7 infection. In all patients, HHV7-DNA was detected on cerebrospinal fluid (CSF) by RT-PCR., Results: 7/12 patients had meningoencephalitis (two with ADEM and one with MOG antibody-associated CIS); 5/12 showed acute neuropsychiatric symptoms. EEG showed anomalies exclusively in patients with meningoencephalitis. Six patients had RMN anomalies. CSF HHV7 copies ranged between 20 and 3,500 copies/mL (median 66 copies/mL) and mean HHV7 CSF/blood ratio was 0.75. Outcome was favorable in all children, although 3/12 had minor neurobehavioral sequelae. Mean follow-up period of 5.2 months., Conclusions: HHV7 can determine neuroinvasion in immunocompetent children, leading to acute encephalopathy. Blood-brain barrier damage and high CSF/blood viral copies ratio correlated with a more severe presentation. We speculate on the importance of immune-mediated mechanisms in provoking clinical features.

The complex association between neuroinflammation and seizures has been widely investigated in recent years. As mediators of inflammatory response, cytokines like tumor necrosis factor- a (TNF-a) are potential therapeutic targets for epileptic disorders. TNF-a is a pleiotropic cytokine with a controversial role in epileptogenesis, seemingly capable to both favor the genesis of seizures and elicit neuromodulatory responses. Anti-TNF agents are a group of monoclonal antibodies engineered to inhibit the response to this cytokine for antinflammatory purposes. The clinical experience of the use of these drugs in neurological conditions like multiple sclerosis showed controversial results. Evidence in favor of the employment of anti-TNF agents for the treatment of epilepsy are still limited to certain forms of disorders, notably Rasmussen encephalitis, and in carefully selected patients.

Background: Anxiety and depression may affect asthma control. Previously, it has been reported that the hospital anxiety depression scale (HADS) questionnaire was fruitful in the management of adolescents with asthma. This study compared the scores of two different questionnaires, namely the Childhood Anxiety Sensitivity Index (CASI) and Children's Depression Inventory (CDI), with asthma control level and lung function in asthmatic adolescents, evaluated in a real-life setting., Methods: A group of adolescents with asthma was consecutively enrolled. Asthma was diagnosed according to the GINA document, and consistently the symptom control grade was assessed. The adolescents completed the CASI, CDI, and Asthma Control Test (ACT) questionnaires. Visual Analogue Scale (VAS) for asthma symptoms perception and doctor's asthma control evaluation were considered. Lung function and clinical characteristics were also assessed., Results: Totally, 87 asthmatic adolescents (60 males, 27 females, median age 14.2 years) were evaluated. 16.1% of asthmatic adolescents had anxious symptoms detected by CASI, and 11.5% depressive symptoms revealed by CDI. High scores of both CASI and CDI were significantly associated with uncontrolled asthma (p= 0.013 and 0.043, respectively)., Conclusions: This study showed that anxiety and depression affected asthma control. Thus, in clinical practice, the psychological assessment could be included in asthmatic adolescents' asthma work-up.

SARS-CoV-2 infection has a severe course in a small percentage of children. Remdesivir has shown promising results in reducing hospitalisation time in adults, but data on mortality rate are conflicting and few studies are available on its use use in antivirals in children. We performed a quick narrative review of the available literature data regarding the usage of remdesivir in children and neonates. In children, remdesivir showed good safety profile, however bradicardia events have been reported in children. Remdesivir is currently recommended by several guidelines in some subgroups of children with severe COVID-19, and should also be considered in critically ill patients, always in the context of the overall clinical picture and drug availability.

Eosinophilic esophagitis (EoE) is an emerging allergen-mediated disease characterized by symptoms of esophageal dysfunction and eosinophilic inflammation. EoE diagnosis requires 15 eosinophils per high power field (eos/HPF) in tissue biopsies endoscopically obtained. The need for several endoscopies to monitoring the disease and the absence of validated non-invasive biomarkers or tools are the main reasons for the significant burden on affected patients and the healthcare system. There is a critical need for non-invasive or minimally invasive biomarkers. In the last years, several efforts have been made to identify potential biomarkers for diagnosing and monitoring the disease that we summarized in this review. The future of EoE is exciting from both a diagnostic and therapeutic standpoint. Further research is required to confirm phenotypes and histological or serological biomarkers to provide a novel endotype classification based on different cytokine or genetic signatures relevant to precision medicine.

Prevalence of food allergy has been increasing over the last decades. It may appear as an immediate or a delayed reaction. The disease has a major impact on the quality of life of patients and their families, and it is associated to elevated costs. Primary care physicians are the first healthcare providers who assist children with food allergy, especially in mild to moderate forms. Through the present review, we examine the steps that should be followed in primary care to manage food allergy, and to promptly prescribe an elimination diet and an emergency kit in case of accidental exposure to the allergen. We also focus on the special management of IgE and non-IgE mediated cow's milk allergy, and on management and prevention of egg and peanuts allergy.

Primary immunodeficiency disorders (PIDs) are rare inherited monogenic disorders of the immune system, characterized by an increased risk of infection, immune dysregulation and malignancies. To date, more than 420 PIDs have been identified. The recent introduction of high throughput sequencing technologies has led to identifying the molecular basis of the underlying aberrant immune pathway, and candidate targets to develop precision treatment, aimed at modifying the clinical course of the disease. In PID, targeted therapies are especially effective to manage immune dysregulation and autoimmunity, also reducing the incidence of side effects compared to conventional treatments, sparing the use of steroids and immunosuppressive drugs. Moreover, in the last years, the approach of conventional treatments such as immunoglobulin replacement therapies has evolved and the indication has expanded to new diseases, leading to individualized strategies to both improve infection control and quality of life.  Similarly, the new advent of gene therapy in selected PIDs has introduced the benefit to correct the immunological defect, reducing at the same time the complications related to the hematopoietic stem cell transplantation. Here, we illustrate the most recent findings on tailored treatments for PIDs.

The first cases of as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported in Wuhan, China in December 2019. The World Health Organization declared the global pandemic in March 2020. Coronavirus disease 2019 (COVID-19) showed high rates of mortality in the adult population, whereas a mild course was observed in childhood. Allergic diseases, characterized by a type-2 polarization of the immune system, were considered one of the major risk factor of severe COVID-19. Large amounts of clinical data and expert opinions have been collected since the pandemic outbreak. This review summarizes the latest insights on COVID-19 and allergy.

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 stakeholders involved, of the process of the modernization of health care.

Introduction Vascular complications of posterior fossa surgery are often deadly although widely preventable through in-depth knowledge of the microsurgical neurovascular anatomy of the infratentorial region and careful surgical planning.   The target of this study is to provide a synoptic overview of the normal anatomy and anatomic variants of the infratentorial neurovascular system, critical to safely operate tumors and neurovascular pathologies of the posterior fossa. Methods Two fresh-frozen and five formalin-fixed cadaveric heads were used. Cervical arteries and internal jugular veins were injected with red and blue latex, respectively. The heads were dissected under a surgical microscope, with magnifications ranging between 3× to 40×, focusing on the infratentorial region. The infratentorial arteries, their collaterals and perforating branches, the brainstem and cerebellar veins, the tentorial venous sinuses, and the relative vascular territories were summarized according to a synoptic approach.    Results The vertebral artery, basilar artery (BA), and posterior cerebral artery (PCA) are the main sources of the arterial supply of the brainstem and cerebellum through the posterior inferior cerebellar artery (PICA), the anterior inferior cerebellar artery (AICA), the superior cerebellar artery (SCA), and the perforating arteries. The perforating arteries of the vertebrobasilar system derive from the PICA, BA, AICA, SCA, and PCA, and provide for a key contribution to the vascularization of the midbrain, pons, medulla oblongata, fourth ventricle, cerebellar and cerebral peduncles, thalamus, hypothalamus, subthalamus, posterior part of the internal capsule, and optic tract. The distal segments and branches of the PCA also add a significant arterial supply to the temporal, occipital, and parietal lobes. The venous outflow of the posterior fossa is a prerogative of the internal jugular veins via the tentorial venous sinuses. Conclusion A perfect mastery of the arterial, venous, and cisternal anatomy of the infratentorial region is vital for the planning and execution of the whole range of posterior fossa approaches.

Introduction A thorough understanding of skull base anatomy is imperative to perform safely and effectively any skull base approach. In this article, we examine the microsurgical anatomy of the skull base by proposing a modular topographic organization in the median, paramedian, and lateral surgical corridors in relation to transcranial and endoscopic approaches. Methods Five dry skulls were studied focusing on the intracranial and exocranial skull base. Two lines were drawn parallel to the lateral border of the cribriform plate of the ethmoid bone and foramen lacerum, respectively. Lines 1 and 2 delimited the median, paramedian and lateral corridors of the skull base. The bony structures that formed each corridor were carefully reviewed in relation to the planning and execution of the skull base transcranial and endoscopic approaches. Results The midline corridor involves the crista galli, cribriform plate, planum and jugum sphenoidale, chiasmatic sulcus, tuberculum sellae, sellar region, dorsum sellae, clivus, and foramen magnum. The paramedian corridor includes the fovea ethmoidalis, the root of the lesser and greater sphenoid wing, anterior clinoid process, foramen lacerum, the upper half of the petro-occipital suture, and jugular tubercle. The lateral corridors include the orbital plates, sphenoid wings, squamosal and petrous parts of the temporal bone, caudal aspect of the petro-occipital suture, internal auditory canal, jugular foramen, the sulcus of the sigmoid sinus. Conclusion In-depth three-dimensional knowledge of skull base anatomy based on the modular concept of the surgical corridors is critical for the planning and execution of the transcranial and endoscopic approaches.

Introduction Treatment of cranial neurovascular pathology requires a detailed understanding of the brain, head, and neck vasculature. This study aims at a comprehensive overview of the microsurgical anatomy of the anterior cerebral circulation. Methods Five formalin-fixed adult cadaveric heads were used. Common carotid arteries, vertebral arteries, and internal jugular veins were injected with colored latex (red for arteries and blue for veins). The heads were dissected under a surgical microscope with magnifications ranging between 3× to 40× focusing on the anterior circulation. A synoptic approach was used to describe in detail the segments, branches, perforating arteries, veins, and vascular territories of the cerebral arteries and veins. Results The anterior arterial circulation of the brain is provided by the internal carotid artery (ICA), anterior cerebral artery (ACA), middle cerebral artery (MCA), anterior communicating artery (ACoA), and perforating arteries. Perforating arteries of the anterior circulation arise from the ICA, ACA, MCA, ACoA, and posterior communicating artery (PCoA). The distal segments and collateral branches of the ICA, ACA, and MCA give the arterial supply to the largest part of the forebrain, whereas perforating arteries of the anterior circulation are related to the striatum, thalamus, and basal ganglia. The ACoA is the core functional anastomosis between the left and right ICA systems. The external carotid artery provides the vascular supply to the region of the face, head, and neck, and most of the meninges. The internal jugular venous system is composed of the internal and external jugular veins, which constitutes the outflow of the cerebral and facial venous system, respectively. Conclusion Thorough knowledge of the topographic, cisternal, and functional anatomy of the anterior circulation of the brain is critical for surgery of the supratentorial lesions.

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.

Allergic rhinitis (AR) is induced by an IgE-mediated immune reaction after allergen exposure. The typical symptoms are itching, nasal discharge, sneezing and nasal obstruction. The diagnosis is based on the concordance between allergic symptoms and diagnostic tests. The skin prick test (SPT) is recommended as the "gold standard" method. First generation H1-antihistamines are widely used for treatment of AR. Intranasal glucocorticosteroids are well tolerated and can be used also in paediatric age. Allergic rhinitis cannot be considered as an isolated pathology. Other atopic diseases (allergic conjunctivitis, atopic eczema, asthma) are commonly associated.

n December 2019, in Wuhan (Hubei, China), the first COVID-19 cases due to SARS-COV-2 had been reported. On July 1st 2020, more than 10.268.839 million people had developed the disease, with at least 506.064 deaths. At present, Italy is the third country considering the number of cases (n=240.760), after Spain, and the second for the cumulative number of deaths (n=249.271), after the United States. As regard pediatric COVID-19 cases, more than 4000 cases (have been reported; however, these figures are likely to be underestimated since they are influenced by the number of diagnostic tests carried out. Three pediatric deaths have been reported in Italy to date. We aimed to review the peculiar aspects of SARS-COV-2 infection in the pediatric population.

To date, the only disease-modifying treatment strategy for allergic rhinitis and asthma is allergen immunotherapy (AIT). There is evidence that AIT improves allergic rhinitis and asthma, such as reducing symptom severity and medication use and improving of quality of life, with a long-lasting effect after the end of the course. The recent clinical trials evidenced AIT effectiveness and safety in allergic asthma. Consequently, the current version of the GINA (Global Initiative for Asthma) guidelines recommend AIT as an add-on therapy for asthma. There is also evidence that AIT may exert preventive activity on the possible progression from allergic rhinitis to asthma in children and the onset of new sensitizations.

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 specifi- cally, 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.

Food allergy (FA) is an adverse immunologic response triggered by normally innocuous food protein antigens.  FA can be broadly classified into those that are IgE mediated, those that are mediated by both IgE-dependent and IgE-independent pathways (mixed), and those that are not IgE mediated  Immunoglobulin E. (IgE)-mediated reaction is characterized by rapid onset of symptoms involving respiratory, gastrointestinal, dermatologic and cardiovascular systems; mixed and non-IgE-mediated has a longer onset and manifests primary in the gastrointestinal tract and skin. The diagnosis of food allergy is based on clinical history, diagnostic testing (skin prick test and allergen-specific IgE levels in the serum), elimination diet and, oral food challenge. In recent years the diagnosis and treatment of pediatric FA have notably improved. In the diagnostic pathway of FA an important recent innovation is the CRD introduction.  This resulted in the possibility of improving diagnostic accuracy through FA prediction severity and prognosis and thereby decreasing the OCF necessity. Recent studies emphasize the possibility of preventing FA through early introduction of food (peanuts and egg) to high-risk infants. FA management is based on avoidance of offending food and prompt treatment of allergic reaction. Currently under study are recently developed treatment approaches for FA management including specific OIT.

The control of asthma is the objective of asthma management. However, it is difficult to obtain in clinical practice. The Italian Society of Allergy and Clinical Immunology promoted the nationwide project "ControL'Asma" to investigate the real situation in a group of children and adolescents with asthma. The preliminary outcomes demonstrated that many asthmatic subjects do not achieve adequate asthma control. Moreover, asthma in Italian children and adolescents was usually more frequent in males, had an early onset and allergic phenotype with very frequent rhinitis comorbidity, uncontrolled and partly controlled asthma affected about the half of subjects. However, this project suggested that the assessment of asthma symptom perception by VAS could be a reliable tool in the asthma management.

Atopic dermatitis (AD) is a common inflammatory skin disease, clinically characterized by recurrent eczematous lesions and intense itching, leading to excoriations and susceptibility to cutaneous infections. Although it is considered a pediatric disorder, mainly starting in infancy, it is also very common in adults. Etiology of AD is complex and multifactorial: interaction between genetic susceptibility and environment, but also cutaneous barrier impairment, change in microbiome composition and innate and adaptive immune dysregulation are the main factors involved in the pathogenesis of the disease. Originally, the disorder was considered mediated by an imbalance towards a T-helper 2 response and excessive IgE production to allergens, but now it is recognized as a lifelong disposition with variable clinical expressivity, where dysfunctions of the epidermal barrier, immune system and microbiome play a central role. AD leads to a substantial psycho-social burden on patients and their relatives and increases the risk of other allergic and non allergic disorders. The real economic impact of AD is difficult to measure due to the broad spectrum of disease severity and the multiple direct and indirect costs, but the overall medical expenses seem to be very high and similar to those of other diseases such as diabetes. Currently, a multiple therapeutic approach is aimed only at improving the skin state, reducing itching and keeping a stable condition. New safety and curative treatments may be developed only after enhancing our understanding on the pathogenesis of AD and the heterogeneity of its clinical manifestations.

Drug hypersensitivity reactions (DHRs) are adverse reactions to a drug. In children, most common drugs inducing such reactions include beta-lactams (BLs) and non-steroidal anti-inflammatory drugs (NSAIDs). The aim of the present work was to provide current knowledge on the management of DHRs in the pediatric population, focusing on BLs and NSAIDs hypersensitivity. The clinical feature of DHRs include immediate and non-immediate (delayed and accelerated) reactions, that may be severe or non-severe. A systematic approach to the patient based on the reported clinical history is essential to organize a safe and adapted allergy work-up. Skin tests are the first step to assess a possible DHRs, especially in immediate reactions to BLs. Drugs concentrations for these tests are standardized and validated. The drug provocation test remains the gold standard to reach a firm diagnosis. In selected cases, a therapeutic desensitization protocol may be proposed in children with a confirmed diagnosis of drug hypersensitivity. Clinicians should be aware of the diagnostic and therapeutic options, to provide the best management in children having experienced a history of DHR.

Italy is one of the most exposed countries worldwide to COVID-19, and Lombardy is the most affected region in Italy. In this context, Fondazione IRCCS Policlinico San Matteo in Pavia, one of the largest University hospitals in the region, has been involved in the management of the outbreak since its inception. Immediately after the communication of the first Italian COVID-19+ patient, the Pediatric Unit has been completely reorganized to face the approaching outbreak. The optimization of the Pediatric Unit resources for COVID-19 emergency is reported as an example to safely preserve health activity during the pandemic.

Since the introduction of biologic response modifiers (BRMs) in the management of children affected by the immune-mediated inflammatory disease, these patients substantially improved their quality of life. BRMs are generally well tolerated and effective in most children and adolescents refractory to conventional immunosuppressive therapy. On the other hand, patients receiving BRMs, especially TNF-α inhibitors, display an increased risk of primary infections or reactivations, i.e. due to Mycobacterium tuberculosis. M. tuberculosis can cause severe disease with consequent short- and long-term morbidity in children on anti-TNF-α treatment. The present paper analyses the increased risk of reactivation of latent tuberculosis infection (LTBI) or de novo TB infection in children treated with TNF-α inhibitors, with the purpose to provide recommendations for screening strategies and safety monitoring of paediatric patients. Special attention is also given to the currently available TB screening tools (IGRAs and TST) and their utility in the diagnosis of LTBI before starting the biologic therapy and during the treatment. Finally, the paper analyses the suggested TB-preventing therapies to adopt in these children and the correct timing to overlap anti-TB and anti-TNF-a treatment.

The management of chronic diseases are paramount in health care in these days. Among them, there has been an expansion of allergic and immunologic diseases, especially in children. Thanks to the action of the Italian Society of Pediatric Allergy and Immunology (SIAIP), the quality level of care has progressively grown. SIAIP developed a task force with the purpose of proposing updated models  for  assessing,  and  prescribing  treatment in the allergy and immunology field that have been issued in this supplement. In a very difficult time for everyone, current developments covering a broad range of topics in the field are presented. All Authors have to be thanked, since they have participated with passion and have taken valuable time away from their professional and private interests. We hope that the readership will enjoy these papers.

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.

Available information suggests that anaphylaxis must be promptly recognized keeping in mind the airway patency, breathing (ventilation and respiration), circulation and mental status and treated. The first treatment is adrenaline. After successful treatment of an anaphylactic episode, attention must be paid to the prevention of early recurrences (biphasic anaphylaxis) and assessment of causes. Children should not be discharged before prescribing self-injectable adrenaline and explain how and under what circumstances it must be injected, An action plan must be communicated to their communities. Inform the school about potential reactions, how to prevent them and avoidance measures.

Allergen avoidance, allergen immunotherapy, IgE antagonists, biological medications, prevention and treatment of respiratory infections, probiotics, adapted formula, vitamins, and oligo-elements have been investigated as strategies in the prevention of allergic diseases. Promising findings were obtained. To prevent allergic diseases could be a dream that will be soon realized in clinical practice.

Neurofibromatosis Type 1 (NF1) is an autosomal dominant tumor-predisposition disorder that is caused by a heterozygous loss of function variant in the NF1 gene, which encodes a protein called neurofibromin. The absence of neurofibromin causes increased activity in the Rat sarcoma protein (RAS) signalling pathway, which results in an increased growth and cell proliferation. As a result, both oncological and non-oncological comorbidities contribute to a high morbidity and mortality in these patients. Optic pathways gliomas, plexiform neurofibromas and malignant peripheral nerve sheath tumor (MPNST) are the most frequent NF1-associated tumors. The treatment of these complications is often challenging, since surgery may not be feasible due to the location, size, and infiltrative nature of these tumors, and standard chemotherapy or radiotherapy are burdened by significant toxicity and risk for secondary malignancies. For these reasons, following the novel discoveries of the pathophysiological mechanisms that lead to cell proliferation and tumorigenesis in NF1 patients, emerging drugs targeting specific signalling pathways (i.e. the MEK/ERK cascade), have been developed with promising results.

Background and aim Seasonal allergic rhinitis (SAR) is a common disease in childhood that is characterized by bothersome symptoms and impaired quality of life (QoL). As histamine is the pivotal pathogenic mediator in SAR, antihistamines are the first-line option in the treatment. Cetirizine is a well-known effective antihistamine. This real-life pilot study aimed to investigate the effectiveness of a 4-week continuous cetirizine treatment in a group of Italian children with SAR. Methods Total symptom score (TSS) and the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) were assessed at baseline and the end of the treatment. Results Cetirizine significantly improved QoL (in all domains) and symptom severity (p<0.001 for both). Conclusions The present preliminary study showed that a 4-week cetirizine treatment was able to improve QoL significantly. Cetirizine treatment also significantly reduced symptom severity in Italian children with SAR and was safe.

In children with food allergy the visits should be limited to those that are unequivocally needed on clinical basis. Food challenge can be performed in selected situations, taking a more detailed history to make sure that patients provide whatever information we need. The maintenance of a safe diet can be hampered by several factors. Nutritional supplementation may be necessary.

Drug allergy is an increasing problem worldwide, affecting all populations and races, children and adults, and for which diagnosis and treatment are not well standardized yet. Besides classical treatments, new drugs have been developed, especially for patients suffering from malignancies and chronic inflammatory diseases, that specifically target the cause of the disease. For those patients requiring such molecules, it is sometimes difficult to find an alternative drug when hypersensitivity reactions occur. Desensitization is therefore the best option whenever no alternative therapy is available but also when alternative treatments are considered therapeutically inferior and or more toxic. Despite its clinical success, little is known about the mechanisms and molecular targets of drug desensitization. Desensitization protocols use a gradual dose escalation to allow the safe administration of a treatment to which a patient previously presented a hypersensitivity reaction. The procedure requires special training and coordination of an allergy team, including physicians, nurses, and pharmacists, working together to safely and successfully implement desensitization protocols when appropriate. There is no difference in desensitization protocol between adults and children, except for the final cumulative dose of the administered drug.