Cold Anaphylaxis in Children: Italian Case Series and Review of the Literature.

Chronic urticaria (CU) is one of the most common skin disorders worldwide. Among the inducible subgroup of CU, cold urticaria (ColdU) can affect both children and adults and is the only type associated with the risk of anaphylaxis without cofactors. In the scientific literature, data about cold anaphylaxis (ColdA) are poor, especially at pediatric age, and little is known about risk factors associated with the onset of systemic reactions and about the criteria for prescribing adrenaline auto-injectors (AAIs) in these patients. We describe the clinical characteristics and management of a case series of 21 patients with a history of ColdA, and we compare them with the pediatric case reports and case series published so far. On the basis of the scientific literature and of our case series of patients, we suggest that AAI should be prescribed to all high-risk patients: those with urticaria caused by cold-water immersion, oropharyngeal reactions, and with a previous history of systemic symptoms or anaphylaxis.

Maintenance Therapy for Children and Adolescents with Asthma: Guidelines and Recommendations from the Emilia-Romagna Asthma (ERA) Study Group.

Asthma is the most frequent chronic disease of childhood, affecting up to 20% of children worldwide. The main guidelines on asthma maintenance therapy in pediatrics suggest different approaches and describe different stages of asthma to determine the most appropriate treatment. This project aims to summarize the most recent evidence regarding maintenance therapy for asthma in children and adolescents. A multidisciplinary panel of experts was asked clinical questions regarding the treatment of children and adolescents with asthma. Overall, 10 clinical questions were addressed, and the search strategy included accessing electronic databases and a manual search of gray literature published in the last 25 years. After data extraction and narrative synthesis of results, recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Results showed that the choice of medication depends on the severity of the child's asthma, phenotype, age, preference, and individual factors. In addition to medications, the identification of comorbidities and modifiable factors is crucial to obtaining good control. Asthma in children is heterogeneous, and its evolution varies over time. Since most recommendations for asthma management in childhood are extrapolated from clinical studies performed in adults, more clinical trials specifically designed for young children should be conducted.

Risk Factors Affecting Development and Persistence of Preschool Wheezing: Consensus Document of the Emilia-Romagna Asthma (ERA) Study Group.

Wheezing at preschool age (i.e., before the age of six) is common, occurring in about 30% of children before the age of three. In terms of health care burden, preschool children with wheeze show double the rate of access to the emergency department and five times the rate of hospital admissions compared with school-age asthmatics. The consensus document aims to analyse the underlying mechanisms involved in the pathogenesis of preschool wheezing and define the risk factors (i.e., allergy, atopy, infection, bronchiolitis, genetics, indoor and outdoor pollution, tobacco smoke exposure, obesity, prematurity) and the protective factors (i.e., probiotics, breastfeeding, vitamin D, influenza vaccination, non-specific immunomodulators) associated with the development of the disease in the young child. A multidisciplinary panel of experts from the Emilia-Romagna Region, Italy, addressed twelve key questions regarding managing preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes). Systematic reviews have been conducted on PubMed to answer these specific questions and formulate recommendations. The GRADE approach has been used for each selected paper to assess the quality of the evidence and the degree of recommendations. Based on a panel of experts and extensive updated literature, this consensus document provides insight into the pathogenesis, risk and protective factors associated with the development and persistence of preschool wheezing. Undoubtedly, more research is needed to improve our understanding of the disease and confirm the associations between certain factors and the risk of wheezing in early life. In addition, preventive strategies must be promoted to avoid children's exposure to risk factors that may permanently affect respiratory health.

Management of Preschool Wheezing: Guideline from the Emilia-Romagna Asthma (ERA) Study Group.

Preschool wheezing should be considered an umbrella term for distinctive diseases with different observable and measurable phenotypes. Despite many efforts, there is a large gap in knowledge regarding management of preschool wheezing. In order to fill this lack of knowledge, the aim of these guidelines was to define management of wheezing disorders in preschool children (aged up to 5 years). A multidisciplinary panel of experts of the Emilia-Romagna Region, Italy, addressed twelve different key questions regarding the management of preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes) and systematic reviews have been conducted on PubMed to answer these specific questions, with the aim of formulating recommendations. The GRADE approach has been used for each selected paper, to assess the quality of the evidence and the degree of recommendations. These guidelines represent, in our opinion, the most complete and up-to-date collection of recommendations on preschool wheezing to guide pediatricians in the management of their patients, standardizing approaches. Undoubtedly, more research is needed to find objective biomarkers and understand underlying mechanisms to assess phenotype and endotype and to personalize targeted treatment.

Management of Children with Acute Asthma Attack: A RAND/UCLA Appropriateness Approach.

Bronchial asthma is the most frequent chronic disease in children and affects up to 20% of the pediatric population, depending on the geographical area. Asthma symptoms vary over time and in intensity, and acute asthma attack can resolve spontaneously or in response to therapy. The aim of this project was to define the care pathway for pediatric patients who come to the primary care pediatrician or Emergency Room with acute asthmatic access. The project was developed in the awareness that for the management of these patients, broad coordination of interventions in the pre-hospital phase and the promotion of timely and appropriate assistance modalities with the involvement of all health professionals involved are important. Through the application of the RAND method, which obliges to discuss the statements derived from the guidelines, there was a clear increase in the concordance in the behavior on the management of acute asthma between primary care pediatricians and hospital pediatricians. The RAND method was found to be useful for the selection of good practices forming the basis of an evidence-based approach, and the results obtained form the basis for further interventions that allow optimizing the care of the child with acute asthma attack at the family and pediatric level. An important point of union between the primary care pediatrician and the specialist hospital pediatrician was the need to share spirometric data, also including the use of new technologies such as teleconsultation. Monitoring the progress of asthma through spirometry could allow the pediatrician in the area to intervene early by modifying the maintenance therapy and help the patient to achieve good control of the disease.

The Diagnosis of Ceftriaxone Hypersensitivity in a Paediatric Population.

INTRODUCTION: Penicillins and cephalosporins are the most frequent causes of hypersensitivity reactions (HRs) to drugs in children. Among cephalosporins for intravenous use, ceftriaxone (CT) is the most frequently prescribed in Italy. The aims of this study were to evaluate the diagnostic methods for CT hypersensitivity in a population of children with suspected HRs to this drug and their tolerance toward amoxi-cillin/clavulanic acid (AMX/CLV). MATERIALS AND METHODS: From 2012 to 2018, 90 children were investigated for suspected HRs to CT according to the European Academy of Allergy Asthma and Clinical Immunology (EAACI) guidelines. RESULTS: Ninety children had a history of reaction to CT. The majority (79/90; 77.8%) had a history of immediate reactions (IRs). CT hypersensitivity was confirmed in 26/90 patients (28.9%). In case of IRs, skin tests can be useful (24% of positive CT intradermal tests - IDTs) particularly in cases of anaphylaxis (81.8% of positive CT IDTs). Only 5 out of 28 drug provocation tests were positive. Serum-specific IgE (sIgE) determination for CT correlated with positivity upon skin/drug provocation tests (high specificity 95.6%) but had a low sensitivity; sIgE for AMX had a very low positive predictive value (14.3%), advocating against its use. In case of non-IRs, only 7/11 patients reached a confident diagnosis, but the low number of children does not enable proper conclusions. Only 2 children showed cross- and/or co-allergy (2.2%) between CT and AMX/CLV. CONCLUSION: IDTs seem to be useful for diagnosing CT IRs. Hypersensitivity to CT is confirmed in 28.9% of children, although a large fraction of parents refused an intravenous rechallenge (45.6%). It remains unknown whether this is due to the fact this was intravenous rather than a rechallenge with the culprit, but it reflects a clinical reality. Otherwise, cross- and/or co-allergy between CT and AMX/CLV is a rare event.

Low-Dose Oral Food Challenge with Hazelnut: Efficacy and Tolerability in Children.

BACKGROUND: Hazelnut allergy (HA) is one of the more common food allergies (FAs) in Europe with a prevalence of 0.2%. The gold standard for diagnosing FA is oral food challenge (OFC) with the culprit food. Another purpose of OFC is to identify the "threshold level" of food as the dose that elicits symptoms. In this way it is possible to avoid a strict elimination diet and to determine the minimal quantity of the culprit food tolerated by the patient. OBJECTIVE: The aim of our study was to assess the efficacy and tolerability of hazelnut low-dose OFC (H-LDOFC) in children with HA. METHODS: From January 2015 to December 2016, we retrospectively analyzed the charts of patients referred to Allergy Unit of Meyer Children's Hospital, Florence, Italy for a history of HA. Prick by prick (PbP) and specific serum IgE (s-IgE) to hazelnut were performed. We proposed conducting an H-LDOFC to parents of children with HA. The H-LDOFC was considered completed when a cumulative dose of 2.5 g of hazelnut was reached. We divided the patients who underwent the H-LDOFC into an asymptomatic and a symptomatic group. For statistics we used SPSS for Windows version 16.0 and conducted a t test for comparing the averages, considering a p value of < 0.05 significant. RESULTS: Forty-three out of 70 patients (61.4%) with HA underwent an H-LDOFC. The PbP to hazelnut (mean ± SD) was 7.2 ± 2.9 mm and the s-IgE to hazelnut 25.3 ± 32.5 kU/L. Twenty-eight out of the 43 patients (65.1%) who underwent H-LDOFC reached the cumulative dose of 2.5 g of hazelnut. During the H-LDOFC, 20/43 patients (46.5%) had no reactions and 23/43 patients had a total of 55 reactions: 34 (61.8%) oral allergy syndrome, 8 (14.5%) rash, 6 (10.9%) abdominal pain, 2 (3.6%) urticaria, 2 (3.6%) angioedema, and 3 (5.4%) dyspnea. Atopic dermatitis was found to present the only statistically significant difference (p = 0.002) in patients with symptoms compared to asymptomatic patients during H-LDOFC. CONCLUSIONS: To our knowledge, this was the first study to assess the efficacy and tolerability of H-LDOFC in a pediatric population. Our study suggests that in children with HA, H-LDOFC is well accepted and safe because adverse reactions are mild and the majority are represented by localized symptoms (oral allergy syndrome) and efficient, especially in terms of improvement of quality of life. For these reasons it could be more extensively used in the treatment of HA.

Clinical characteristics of headache in Italian adolescents aged 11-16 years: a cross-sectional questionnaire school-based study.

BACKGROUND: The purpose of this study was to determine headache characteristics, impact on daily activities and medication attitudes among a large sample of adolescents in Italy. METHODS: Secondary school classes were randomly selected from a national stratified multistage sampling. Data regarding socio-familial factors, headache characteristics, impact on daily activities and medication use were recorded with an anonymous multiple-choice questionnaire. RESULTS: The survey involved 2064 adolescents. 1950 questionnaires were considered for analysis. Study population included 944 males (48.4%) and 1006 females (51.6%), aged between 11 and 16 years (mean 13.5 ± 1.87). Headache prevalence was 65.9%. Mean age at headache onset was 8.33 years. 9.8% suffered from headache > 1/week, 14.3% > 1/month, 24.2% monthly and 17.7% less than monthly. The mean duration of a headache episode was less than 30 min in 32.9%, 1 hour in 28.1%, 2 hours in 19.3% and several hours in 19.5%. Pain intensity was moderate in 52.2% and severe in 9.5%. School represented the main trigger factor (67%). Impact on daily activities was noted in 57.5%. 69.2% of adolescents reported the use of pain relievers. Up to 5.7% declared self-medication, while only 20.6% followed a physician's prescription. Female adolescents experienced headache more frequently (70.2% vs 60%) and more intensely than male peers. Girls had a higher family history of headache, could more frequently identify a trigger factor, and were more affected into their daily activities than boys. CONCLUSIONS: Population-based studies of headache disorders are important, as they inform needs assessment and underpin service policy for a disease that is a public-health priority. Headache has a high prevalence among adolescents and carries a significant burden in terms of impact on daily activities and use of medication. Furthermore, underdiagnose is common, while trigger factors are often detectable. Special consideration should be given to female adolescents and self-medication attitudes.

Anticonvulsant drugs for generalized tonic-clonic epilepsy.

INTRODUCTION: Primary generalized tonic clonic seizures (pGTCS) are still linked to major concerns for the clinic and hazards for patients suffering from idiopathic generalized epilepsy (IGE), so a quick search of the most effective and appropriate therapy is needed to control them. The key criteria for proper treatment are syndromic diagnosis and distinction between newly diagnosed and refractory patients. Other criteria include age, gender and comorbidities. Areas covered: Treatment for pGTCS has expanded in the last two years, with new antiepileptic drugs like perampanel joining valproic acid, lamotrigine, levetiracetam, topiramate, while further evidence-based data are required for zonisamide and lacosamide. Expert opinion: Currently, valproic acid can be considered as a first choice in male or menopausal women, and in the absence of weight issue, both in adults and in children, and in the absence of side effects such as insomnia and headache. Today, valproic acid is not recommended in child-bearing age and in relation to possible cognitive problems, especially in children. Lamotrigine and levetiracetam can be a viable alternative as a first choice. Topiramate is also effective as a first choice, but concerns may arise from its potential cognitive and memory adverse side effects. Additionally, perampanel and lacosamide are promising treatments.

Maternal Stress and Coping Strategies in Developmental Dyslexia: An Italian Multicenter Study.

BACKGROUND: Studies about the impact of developmental dyslexia (DD) on parenting are scarce. Our investigation aimed to assess maternal stress levels and mothers' copying styles in a population of dyslexic children. METHODS: A total of 874 children (500 boys, 374 girls; mean age 8.32 ± 2.33 years) affected by DD was included in the study. A total of 1,421 typically developing children (789 boys, 632 girls; mean age 8.25 ± 3.19 years) were recruited from local schools of participating Italian Regions (Abruzzo, Calabria, Campania, Puglia, Umbria, Sicily) and used as control-children group. All mothers (of both DD and typically developing children) filled out an evaluation for parental stress (Parenting Stress Index-Short Form) and coping strategies [Coping Inventory for Stressful Situations (CISS)]. RESULTS: No statistical differences for mean age (p = 0.456) and gender (p = 0.577) were found between DD and control children. Mothers of children affected by DD showed an higher rate of all parental stress indexes (Parental Distress domain p < 0.001, Difficult Child p < 0.001, Parent-Child Dysfunctional Interaction p < 0.001, and Total Stress subscale score p < 0.001) than controls mothers. According to the CISS evaluation, mothers of DD children reported a significantly higher rate of emotion-oriented (p < 0.001) and avoidance-oriented (p < 0.001) coping styles than mothers of typical developing children. On the other hand, a lower representation of task-oriented coping style was found in mothers of DD children (p < 0.001) in comparison to mothers of control-children. CONCLUSION: Our study shows the clinical relevance of the burden carried by the mothers of children affected by DD and suggests the importance to assess parents, particularly mothers, to improve family compliance and clinical management of this disorder.

Cessation of epilepsy therapy in children.

In epileptic children experiencing a seizure-free period, the target is to attempt antiepileptic drugs (AEDs) withdrawal. When clinicians have to decide whether to discontinue antiepileptic therapy or not, they should consider the risk of seizure relapse. Several studies have tried to identify the main factors associated with seizure recurrence after AEDs withdrawal. Analysing these data, it is possible to identify patients with a different risk and, consequently, to decide whether or not to begin therapy withdrawal. In this review, data from literature have been examined to delineate a therapeutic approach in children. Factors at risk of relapse are abnormal EEG, age at onset before 2 years or after 10 years, defined aetiology, mental retardation and seizure free period. Although larger prospective studies are needed, a seizure free period of at least 2 years before withdrawal and a slow tapering of AEDs are recommended.