Narrative review on the management of moderate-severe atopic dermatitis in pediatric age of the Italian Society of Pediatric Allergology and Immunology (SIAIP), of the Italian Society of Pediatric Dermatology (SIDerP) and of the Italian Society of Pediatrics (SIP).

Currently, there are a few detailed guidelines on the overall management of children and adolescents with moderate-severe atopic dermatitis. AD ​​is a complex disease presenting with different clinical phenotypes, which require an individualized and multidisciplinary approach. Therefore, appropriate interaction between primary care pediatricians, pediatric allergists, and pediatric dermatologists is crucial to finding the best management strategy. In this manuscript, members of the Italian Society of Pediatric Allergology and Immunology (SIAIP), the Italian Society of Pediatric Dermatology (SIDerP), and the Italian Society of Pediatrics (SIP) with expertise in the management of moderate-severe atopic dermatitis have reviewed the latest scientific evidence in the field. This narrative review aims to define a pathway to appropriately managing children and adolescents with moderate-severe atopic dermatitis.

Serum Levels of Soluble Receptor for Advanced Glycation End Products Are Reduced in Euthyroid Children with Newly Diagnosed Hashimoto's Thyroiditis: A Pilot Study.

OBJECTIVE: No data are available on advanced glycation end products (AGEs) and their soluble receptor (sRAGE) in pediatric patients with Hashimoto's thyroiditis (HT). The present study was aimed to simultaneously evaluate serum levels of sRAGE, AGEs, and advanced oxidation protein products (AOPPs) and investigate the relationships between these oxidative stress markers and clinical and biochemical parameters of thyroid function in euthyroid children with HT. DESIGN: This is a case-control study carried out in a single university hospital center. METHODS: We enrolled 19 newly diagnosed euthyroid HT pediatric patients (3 M, 16 F; median age 12.44 years, range 6.54-15.81 years) and 16 age-, sex-, and BMI-matched healthy controls (5 M, 11 F; median age 12.83 years, range 5.68-15.07 years). None was on levothyroxine treatment. The exclusion criteria were autoimmune, inflammatory, and infection comorbidities. Patients did not differ significantly from controls with regard to lipid or for anthropometric parameters. RESULTS: sRAGE levels were significantly lower in HT patients (median 414.30 pg/mL, range 307.30-850.30 pg/mL) than in controls (561.30, 273.20-1121.60 pg/mL; p = 0.034). No differences emerged between patients and controls with regard to serum AGEs (124.25 AU/g prot, 71.98-186.72 vs. 133.90, 94.06-200.78 AU/g prot, p = 0.707) and AOPPs (1.13 nmol/mL, 0.62-1.83 vs. 1.17, 0.76-1.42 nmol/mL, p = 0.545). CONCLUSIONS: sRAGE levels were decreased in euthyroid children/adolescents at the onset of HT, suggesting that autoimmunity per se seems to play an important role in such a reduction of sRAGE, irrespective of any functional alteration. Children and adolescents suffering from HT may exhibit increased susceptibility to oxidative damage, even when in euthyroid status.

Quarantine due to the COVID-19 pandemic from the perspective of adolescents: the crucial role of technology.

BACKGROUND: The year 2020 will be remembered as the "year of the COVID-19 pandemic". The world population had to familiarize themselves with words as swabs, personal protective equipment, pandemic. To curb the wave of the pandemic, almost all the countries imposed self-isolation and social distancing. We conducted a web-based survey to investigate the behavioural responses during the quarantine due to the COVID-19 pandemic. METHODS: Participants were 1860 youth aged 12-18 years attending lower secondary schools and upper secondary schools. Data were collected on demographic characteristics, lifestyle changes during the quarantine period, and the psychological impact of the lock-down on adolescents' life. RESULTS: Most adolescents experienced feelings of fear, discouragement, and anxiety which strongly affected the approach to their daily lifestyles. Most of the surveyed subjects reported having used this period to acquire new skills and to practice physical activities at home. The use of technology was predominant both for recreational activities and educational purposes. CONCLUSIONS: Despite the strong psychological impact of the quarantine, adolescents showed good levels of resilience. Technology played a crucial role during the quarantine for young subjects who have increased the daily use of technological devices to stay connected with the rest of the world.

Heterogeneity of pollen food allergy syndrome in seven Southern European countries: The @IT.2020 multicenter study.

BACKGROUND: Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. OBJECTIVES: To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. METHODS: As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. RESULTS: Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). CONCLUSIONS: PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics.

The evolution of allergen-specific immunotherapy: The near and far future.

In the era of precision medicine, allergen immunotherapy (AIT) represents a landmark for the management of IgE-mediated allergic diseases. AIT is recognized as a potentially curative therapy and is currently accepted and routinely prescribed worldwide. However, there are still unmet needs. The efforts of researchers are aimed at implementing current immunotherapeutic strategies to improve the standard care of patients suffering from IgE-mediated respiratory allergic diseases. In addition, over the horizon, the most realistic option is the active treatment of IgE-mediated food allergy with oral immunotherapy. Preclinical studies and clinical trials are increasingly conducted to identify innovative forms of AIT administration, potential biomarkers, alternative immunotherapeutic allergen candidates, and new adjuvants. Telemedicine could represent a further emerging field capable of supporting health service delivery and improving clinical outcomes of AIT.

Acute haemorrhagic oedema of infancy: a condition that is not always benign.

Acute haemorrhagic oedema of infancy (AHOI) is a rare condition and an unusual diagnosis for the paediatrician, as approximately 300 cases have been reported in literature so far. Although it was considered for years a less serious variant of Henoch-Schönlein purpura, nowadays it is thought to be a different entity, with his own characteristics and clinical outcome. In literature it is described as a benign condition, self-limiting and without any systemic involvement in most of the cases. We present an atypical case of AHOI with a severe presentation and which needed an aggressive and prolonged steroid therapy.

Foreword.

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.

Nutrition and Avoidance Diets in Children With Food Allergy.

Food allergy (FA) is a significant health issue which considerably influences the quality of life of both children and their family. The increasing prevalence of FA, documented in the last 3 decades, has led to the reassessment of FA prevention strategies and particularly to giving up the approach based on delaying the introduction of potential food allergens. Several observational and interventional studies demonstrated a potential effectiveness of the early food introduction strategy in FA prevention, although strong evidence from randomized controlled trials are lacking and, sometimes, contrasting. The current approach to FA is mainly based on avoidance diet and the use of rescue medications in case of allergic reaction, although active allergen immunotherapy has recently become an increasingly important therapeutic strategy to approach IgE-mediated FA, potentially able to induce improvement through desensitization to a specific food. This review provides an overview on the historical evolution of recommendations about FA and on evidence published in the last 15 years on nutritional intervention strategy, i.e., early introduction of allergen or avoidance diet, in the prevention and management of IgE-mediated and non-IgE-mediated FA in children.

Management of pernio-like cutaneous manifestations in children during the outbreak of COVID-19.

During the outbreak of COVID-19 many pernio-like lesions have been increasingly reported. The aim of the study is to describe our management of these skin manifestations and to evaluate a possible correlation to SARS-CoV-2 infection. All patients underwent clinical and laboratory tests to detect a possible underlying connective disease and also to specific SARS-CoV-2 investigations such as oropharyngeal swab and IgG-IgM serology. Nine patients aged between 5 and 15 years old were evaluated. Skin lesions observed were purplish, erythematous and oedematous, in some cases painful and itchy. Six out of nine had respiratory and systemic symptoms (cough, nasal congestion, chills, fever, and asthenia) that preceded cutaneous findings of approximately 2 weeks. Concerning blood exams, three out of nine had D-dimer weakly increased, four had ANA positivity: two with a title 1:160, one with 1:320, and one with 1:5120 and a speckled pattern. The latter patient had also ENA SS-A positive and RF positivity, confirmed at a second check, so as to allow us to make a diagnosis of connective tissue disease. Four out of nine had aPL positivity (IgM). Reactants acute phase were all negative. Oropharyngeal swabs and serology tests for SARS-CoV-2 was negative (borderline in one patient for IgM). No treatment was needed. Even if we do not have enough data to prove it, we hypothesize a correlation between pernio-like lesions and SARS-CoV-2 infection for an increased number of these lesions described during the pandemic and also because such manifestations appeared when temperatures were mild and patients were at home in isolation for the lockdown. Many questions remain open about interaction host-virus.

Quarantine Due to the COVID-19 Pandemic From the Perspective of Pediatric Patients With Type 1 Diabetes: A Web-Based Survey.

Background: A crucial aspect of the 2019 coronavirus disease (COVID-19) pandemic was the psychological impact on the population. Most countries issued restrictive laws to reduce community-based viral spread. Children and adolescents were forced to experience physical and social distancing. Subjects with chronic diseases, such as type 1 diabetes, were more vulnerable and at higher risk of developing psychological disorders. Methods: We conducted a web-based survey to investigate the behavioral responses during quarantine due to the COVID-19 outbreak in a cohort of pediatric patients with type 1 diabetes. Data were collected on demographic and clinical characteristics, lifestyle changes, and the impact of COVID-19 on the management of diabetes. Results: Two hundred four pediatric patients (aged 5-18 years) with type 1 diabetes completed the questionnaire. Interestingly, patients ≤12 years were significantly more influenced by the quarantine period in their approach to the disease than older patients. Conclusion: Although quarantine was a stressful psychological condition, our results showed that most children and adolescents with type 1 diabetes developed high levels of resilience and excellent coping skills by using technology in a proper way.

Kawasaki disease epidemic: pitfalls.

Recent reports have described in the pediatric population a new type of hyperinflammatory response manifested following contact with SARS-CoV-2, with some of the clinical features attributable to Kawasaki disease (KD). The purpose of this commentary is to remark on a possible recent association between SARS-CoV-2 and KD. Although today little is known about the etiology of KD, the most accepted hypothesis is that of a probable viral etiology, therefore, even the SARS-CoV-2 virus could trigger, in genetically predisposed subjects, an exaggerated inflammatory response that is clinically evident like the one described in KD.

Influence of Age on Partial Clinical Remission among Children with Newly Diagnosed Type 1 Diabetes.

Partial clinical remission (PCR) is a transitory period characterized by the residual endogenous insulin secretion following type 1 diabetes (T1D) diagnosis and introducing the insulin therapy. Scientific interest in PCR has been recently increasing, as this phase could be crucial to preserve functional beta cells after T1D onset, also taking advantage of new therapeutic opportunities. The aim of this study was to assess the frequency, duration and associated factors of PCR in children newly diagnosed with T1D. Our cohort study included 167 pediatric patients aged 13.8 ± 4.1 years. The association of clinical and laboratory factors with the occurrence and duration of PCR was evaluated via logistic regression and multivariable generalized linear model, respectively. PCR occurred in 63.5% of the examined patients. Patients who achieved the remission phase were significantly older, and they had lower daily insulin requirement compared with non-remitters. PCR was positively associated to body mass index (OR = 1.11; p = 0.032), pH value (OR 49.02; p = 0.003) and c-peptide levels (OR 12.8; p = 0.002). The average duration of PCR was 13.4 months, and older age at diagnosis was the only predictor factor. Two years after diagnosis remitter patients had lower HbA1c and daily insulin requirement.

Hurthle cell carcinoma in childhood: A retrospective analysis of five cases and review of pediatric literature.

BACKGROUND: the available studies on Hurthle cell carcinoma (HCC) in pediatric age are scarce and based on isolated case reports. Aims of the present study were to review the available pediatric literature on HCC (2000-2019), to describe the cohort of children with this cancer histotype, and to estimate its relative prevalence in pediatric age. PROCEDURE: We retrospectively reconstructed an HCC course in five patients < 19 years who were identified in our departments during the period 2000-2019, and we reviewed the available pediatric studies on this differentiated thyroid cancer (DTC) variant. RESULTS: HCC occurred with a relative prevalence of 5.8% at a median chronological age of 12.5 years. None of HCC patients exhibited, at diagnosis, thyroid dysfunction, extensive lateral neck disease, or distant metastases, and all showed a persistent remission over time. Three patients showed, at diagnosis, antecedents of other diseases (Hashimoto's thyroiditis, neurofibromatosis type 1, and osteosarcoma). CONCLUSIONS: (1) In childhood, the relative prevalence of HCC among different thyroid cancer histotypes is 5.8%, that is close to the one previously reported both in the general population and in other less numerous children's cohorts; (2) HCC may develop even early, at the age of 7; (3) in childhood, HCC does not seem to have a more aggressive behavior when compared with other DTC histotypes; (4) antecedents of other diseases are not infrequent in the history of children with HCC.

GCK-MODY in a child with cystic fibrosis: the doubt of the treatment plan.

Objectives The diagnosis of cystic fibrosis related diabetes (CFRD) is not often easy as glucose homeostasis may be influenced by various disease-related conditions such as enteral continuous drip feeding, frequent acute illness, use of systemic corticosteroids and other concomitant medications. Other forms of diabetes should be considered in the diagnostic work-up, particularly in the first decade of life. Case presentation We hereby present the case of a cystic fibrosis 6-year-old female child diagnosed with glucokinase-maturity onset of diabetes of the young (GCK-MODY). The choice of treatment plan was doubtful since GCK-MODY does not usually require insulin treatment, but hyperglycemia could pose a threat to the respiratory tract. After intensive glucose monitoring, we decided to defer pharmacological treatment based on acceptable daily glycemic control. To date, no worsening in her respiratory function has been revealed. Conclusions Recognition of non-CFRD forms of diabetes is fundamental to plan the most suitable treatment and follow-up.

EAACI Allergen Immunotherapy User's Guide.

Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well-defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy.

Bone Maturation as a Predictive Factor of Catch-Up Growth During the First Year of Life in Born Small for Gestational Age Infants: A Prospective Study.

Background: About 85-90% of children born small for gestational age (SGA) experience a catch-up growth that occurs mostly during the first year of life and results in a full stature recovery by the age of 2. Objective: To investigate the relation between bone maturation (BM) and catch-up growth during the first year of life in SGA infants. Method: Newborns whose weight and/or length was <-2 SD for gestational age were classified as SGA (group A). The study included a group of 32 SGA, 21 of which are full term [37-41 gestation weeks (GW), subgroup A1] and 11 preterm (30-36 GW, subgroup A2). Control group (B) consisted of 19 full-term and adequate-for-gestational-age (AGA) newborns. All the participants were born in the same hospital and period (January-December 2017). Chromosomal disorders, congenital defects, and maternal chronic diseases were criteria of exclusion. The study population underwent longitudinal evaluation of growth parameters and BM at 0, 3, 6, and 12 months. Assessment of BM was performed by an ultrasonographic (US) study of Béclard's nucleus (NB) (<3 mm at birth, meaning intrauterine delay of BM). Results: Significantly higher height velocity (HV) was observed in subgroup A2 vs. A1 (32.4 ± 8.0 vs. 25.6 ± 2.9 cm, p = 0.01); nevertheless, more subjects in subgroup A2 had height <-2 SD at year 1 than had subgroup A1 (27.3 vs. 0%, p = 0.01). Intrauterine delay of BM was more common in group A vs. B (59.4 vs. 21.2%, p = 0.0078) and in subgroup A2 vs. A1 (90.9 vs. 42.9%, p = 0.0086). In group A, HV over the first year of life negatively correlates with NB diameter assessed at birth (r = -0.6, p < 0.001) but positively correlates with NB growth (r = 0.52, p < 0.01). Moreover, SGA babies with intrauterine delay of BM showed higher HV and better height gain at 12 months' evaluation than did SGA with adequate BM (29.75 ± 3.1 vs. 23.8 ± 2.7 cm, p = 0.003). Conclusion: Neonatal BM should be regarded as a predictive factor of SGA height gain during the first year of life. US evaluation of NB is a useful noninvasive technique to identify intrauterine delay of BM, which positively correlates with early postnatal catch-up growth of SGA infants.

Pediatric use of omalizumab for allergic asthma.

INTRODUCTION: Severe pediatric asthma is associated with significant morbidity as well as with a high economic burden. It represents a heterogeneous disease with multiple clinical phenotypes. Currently, physicians are facing the challenge to provide a 'personalized medicine approach', which is tailored to the diverse pathomechanisms underlying clinical presentations. Three main endotypes of airway inflammation have been described in children with severe asthma. While neutrophilic and paucigranulocytic inflammatory patterns are quite uncommon in childhood, type Th2 inflammation asthma with elevated IgE is the most prevalent in pediatric asthma. Considering the pivotal role of IgE in type Th2 inflammation asthma, the blockade of IgE using anti-IgE therapy represents a potent therapeutic option for severe pediatric asthma in children. AREAS COVERED: This review aims to focus on the role of omalizumab as a treatment option in pediatric patients (aged six years and above) with severe allergic asthma. EXPERT OPINION: The clinical efficacy and safety of omalizumab for the treatment of pediatric asthma is well documented in clinical trials and observational studies. Further studies are still required to characterize the potential benefit of anti-IgE therapy in airway remodeling, identify additional biomarkers of clinical response and address current unmet needs, including the limit on omalizumab use in children younger than six years.