Asthma is one of the most common chronic respiratory diseases worldwide. It affects all ages but frequently begins in childhood. Initiation and exacerbations may depend on individual susceptibility, ...viral infections, allergen exposure, tobacco smoke exposure, and outdoor air pollution. The aim of this review was to analyze the role of the gut⁻lung axis in asthma development, considering all asthma phenotypes, and to evaluate whether microbe-based therapies may be used for asthma prevention. Several studies have confirmed the role of microbiota in the regulation of immune function and the development of atopy and asthma. These clinical conditions have apparent roots in an insufficiency of early life exposure to the diverse environmental microbiota necessary to ensure colonization of the gastrointestinal and/or respiratory tracts. Commensal microbes are necessary for the induction of a balanced, tolerogenic immune system. The identification of commensal bacteria in both the gastroenteric and respiratory tracts could be an innovative and important issue. In conclusion, the function of microbiota in healthy immune response is generally acknowledged, and gut dysbacteriosis might result in chronic inflammatory respiratory disorders, particularly asthma. Further investigations are needed to improve our understanding of the role of the microbiome in inflammation and its influence on important risk factors for asthma, including tobacco smoke and host genetic features.
Most focal seizures originate in the temporal lobe and are commonly divided into mesial and lateral temporal epilepsy, depending upon the neuronal circuitry involved. The hallmark features of the ...mesial temporal epilepsy are aura, unconsciousness, and automatisms. Symptoms often overlap with the lateral temporal epilepsy. However, the latter present a less evident psychomotor arrest, frequent clones and dystonic postures, and common focal to bilateral tonic-clonic seizures. Sclerosis of the hippocampus is the most frequent cause of temporal lobe epilepsy (TLE). TLE is among all epilepsies the most frequently associated with psychiatric comorbidity. Anxiety, depression, and interictal dysphoria are recurrent psychiatric disorders in pediatric patients with TLE. In addition, these alterations are often combined with cognitive, learning, and behavioral impairment. These comorbidities occur more frequently in TLE with hippocampal sclerosis and with pharmacoresistance. According to the bidirectional hypothesis, the close relationship between TLE and psychiatric features should lead to considering common pathophysiology underlying these disorders. Psychiatric comorbidities considerably reduce the quality of life of these children and their families. Thus, early detection and appropriate management and therapeutic strategies could improve the prognosis of these patients. The aim of this review is to analyze TLE correlation with psychiatric disorders and its underlying conditions.
The emergence of Multisystem Inflammatory Syndrome (MIS-C) following SARS-CoV-2 infection in children and adolescents provided a new diagnostic and management challenge as there is limited knowledge ...about this condition and its natural history. In existing literature on MIS-C, there are currently no data about long-term outcomes. We report the case of a 14-year-old boy, with no significant past medical history, who presented a condition of multiorgan dysfunction due to MIS-C, after a SARS CoV-2 infection, and subsequent clinical-laboratory signs of hepatic steatosis at short-term follow-up. The case suggests how hepatic steatosis may be a possible sequela following SARS-CoV-2 infection, MIS-C and its medical treatment. Therefore, a close and long-term follow-up is needed to establish the pathophysiology and the evolution of this condition in patients following MIS-C.
: The use of temporary henna tattoos has increased dramatically in recent years, especially in children and adolescents. To obtain a darker colour and prolong the life of the tattoo, red henna, a ...plant-derived substance, is typically added to
-phenylenediamine (PPD). The mixture is called temporary black henna tattoo (TBHT). Because of its molecular characteristics, PPD can induce skin sensitization that may cause various clinical manifestations with successive exposures, among which the most common is allergic contact dermatitis (ACD). This report describes two paediatric cases of PPD sensitization and ACD after the exposure to TBHT and summarizes the literature on this emerging clinical problem.
: We describe two cases of childhood-onset ACD that occurred 2 and 10 days, respectively, after the application of a TBHT during the summer holidays. Patch tests showed an evident positive response to 1% PPD in both cases. Sensitization to PPD occurred in the first case because a previous henna tattoo did not result in overt symptoms; in the second case, the reaction occurred after the same tattoo was retouched. In both cases, hypopigmentation persisted and both the patients and their families were advised to avoid further contact with PPD-containing materials and substances that could lead to cross-reactions.
: Sensitization to PPD is a growing phenomenon in children. The most common cause appears to be exposure to TBHT in which PPD might be present at unknown or high concentrations. Once sensitization occurs, patients may experience severe clinical symptoms which can present with a persistent hypopigmentation when they are re-exposed to substances that contain or cross-react with PPD. Given the widespread use of PPD, TBHT could adversely affect the daily life of paediatric patients; thus, for this reason, this practice as a fashion accessory must be discouraged. In addition, it is extremely important to provide scientific information on the risks of TBHT to consumers, especially to adolescents and to the parents of younger children to prevent PPD sensitization.
Despite the introduction of new anti-seizure medications in recent years, approximately one-third of the epileptic population continues to experience seizures. Recently, the anti-obesity medication ...fenfluramine (FFA) has been successfully repur-posed, and it has received approval from various regulatory agencies for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome. The potential antiseizure effects of FFA were initially observed in patients with photosensitive epilepsy in the 1980s but it was not rigorously explored as a treatment option until 30 years later. This narrative review aims to provide an overview of the historical progression of FFA's use, starting from initial clinical observations to preclinical studies and, ultimately, successful clinical trials in the field of epilepsy. Keywords: fenfluramine, seizures, Dravet syndrome, drug-resistant epilepsy, serotonin
Rett Syndrome (RTT) is a rare and severe X-linked developmental brain disorder that occurs primarily in females, with a ratio of 1:10.000.
mutations in the Methyl-CpG Binding protein 2 (MECP2) gene ...on the long arm of X chromosome are responsible for more than 95% cases of classical Rett. In the remaining cases (atypical Rett), other genes are involved such as the cyclin-dependent kinase-like 5 (CDKL5) and the forkhead box G1 (FOXG1). Duplications of the MECP2 locus cause MECP2 duplication syndrome (MDS) which concerns about 1% of male patients with intellectual disability. Sleep disorders are common in individuals with intellectual disability, while the prevalence in children is between 16 and 42%. Over 80% of individuals affected by RTT show sleep problems, with a higher prevalence in the first 7 years of life and some degree of variability in correlation to age and genotype. Abnormalities in circadian rhythm and loss of glutamate homeostasis play a key role in the development of these disorders. Sleep disorders, epilepsy, gastrointestinal problems characterize CDKL5 Deficiency Disorder (CDD). Sleep impairment is an area of overlap between RTT and MECP2 duplication syndrome along with epilepsy, regression and others. Sleep dysfunction and epilepsy are deeply linked. Sleep deprivation could be an aggravating factor of epilepsy and anti-comitial therapy could interfere in sleep structure. Epilepsy prevalence in atypical Rett syndrome with severe clinical phenotype is higher than in classical Rett syndrome. However, RTT present a significant lifetime risk of epilepsy too. Sleep disturbances impact on child's development and patients' families and the evidence for its management is still limited. The aim of this review is to analyze pathophysiology, clinical features, the impact on other comorbidities and the management of sleep disorders in Rett syndrome and Rett-related syndrome.
Strategies for diagnosing celiac disease (CD) include case-finding and population-screening programs. Case finding consists of testing individuals at increased risk for the disease due to symptoms or ...associated conditions. Screening programs are widespread campaigns, which definitely perform better in terms of unveiling CD diagnoses but nowadays are still debatable. The global prevalence of CD is around 1% but it almost doubles when considering screening programs among school children. Within this framework, we aimed to estimate the prevalence of CD among hospitalized children in the Pediatric Department of a Southern Italy University Hospital in the period from January 2018 through December 2021. In addition, we attempted to explore, at the time of diagnosis, the prevalence of leading clinical alerts due to malabsorption/malnutrition such as anemia or failure to thrive or due to systemic inflammation/immune dysfunction as hypertransaminasemia and thyroid dysfunction.
Data records of pediatric patients admitted as inpatients and tested by anti-transglutaminase IgA antibodies (TGA-IgA) were retrospectively analyzed. CD was diagnosed according to either 2012 or 2020 ESPGHAN guidelines, depending on the year of diagnosis. CD autoimmunity (CDA) was a wider group defined within our protocol if patients had elevated TGA-IgA on at least one occasion, regardless of anti-endomysial antibodies (EMA-IgA) and without biopsy confirmation.
During the observation period, 3608 pediatric patients were admitted and 1320 were screened for CD (median age 5 years, IQR 2-9 years; CD test rate: 36.6% out of all admissions). The available prevalence of newly diagnosed CD was 1.59% (21 patients diagnosed) and the available prevalence of CDA was 3.86% (51 subjects). Among CD patients, underweight/malnourished children accounted for 28.6% (6 out of 21).
The estimated prevalence of CD diagnoses within our setting was comparable to the most recent population-screening programs. The estimated prevalence of CDA was even higher. A hospital-admission CD testing during routine blood draws might be a non-invasive, cost-effective and valuable approach to reduce discrepancy of prevalence between case-finding and population-screening programs.
Dietary supplements are products that are ingested in addition to the regular diet to provide additional health-promoting nutrients. Dietary supplements are defined and regulated differently in the ...European Union (EU) and the United States (US). A fundamental aspect, besides the one related to the composition of the various products on the market, is linked to their quality, both from a nutritional and a pharmacological point of view. Concerning the knowledge of the metabolic aspects, the analysis of the interference, as an inductive or an inhibitory effect, of the p450 enzyme on individual preparations of supplements, is crucial. In this study, we present the results of the interference analysis of a new nutraceutical product based on 38% Bergamot Polyphenolic Fraction BPF® (Citrus bergamia Risso et Poit.), Pomegranate (Punica granatum) and Citrus fruits (Citrus aurantium var. dulcis, Citrus maxima Burm. Merr, Citrus paradisi Macfad) extract with cytochrome p450, showing that the product has limited activity on the cytochromes involved in most of human drug metabolism. This nutraceutical product is to be considered safe and potentially useful in the context of multiple treatments, not interfering with the traditional chronic therapies of patients. These findings open the door to modern "pharma-grade" nutraceuticals, expanding the safety and quality profiles of these new products.
Aim
Asthma and allergic rhinitis share common pathophysiological mechanisms. However, while asthma phenotypes and endotypes are defined basing on both clinical and immunological features, rhinitis ...classification is still based on severity and frequency of symptoms. Recently, fractional exhaled nitric oxide (FeNO) has been suggested as a possible biomarker of rhinitis to asthma development. The aim of our study was to define the prevalence of a high FeNO allergic rhinitis endotype in a paediatric population of children with allergic rhinitis in order to quantify the impact of such patients in general practice.
Methods
A total of 159 children (aged 7–16 years) with allergic rhinitis and no asthmatic symptoms were enrolled in our study. Severity assessment of rhinitis and asthma was evaluated in accordance with ARIA and GINA guidelines. All patients performed the following assessments: skin prick test (SPT), spirometry and FeNO measurement.
Results
FeNO was increased in 54 (33.9%) of 159 patients. No significant correlation with age, severity and frequency of rhinitis was evidenced. Positive SPT for house dust mites was related with a higher prevalence of high FeNO (P = 0.04), with no significant correlation with other sensitisations. All patients showed normal spirometric values.
Conclusion
A possible new endotype of allergic rhinitis and lower airways inflammation showed to be significantly present in our population. The lack of correlation with allergic rhinitis severity assessment suggests that FeNO could be considered as an independent variable, possibly linked to a higher risk of asthma development in children with no lower airways symptoms and normal spirometry.
The 22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder in humans and is the result of a recurrent 1.5 to 2.5 Mb deletion, encompassing approximately 20–40 genes, respectively. ...The clinical presentation of the typical deletion includes: Velocardiofacial, Di George, Opitz G/BBB and Conotruncalanomaly face syndromes. Atypical deletions (proximal, distal or nested) are rare and characterized mainly by normal phenotype or mild intellectual disability and variable clinical features. The pathogenetic mechanisms underlying this disorder are not completely understood. Because the 22q11.2 region harbours genes coding for transcriptional factors and chromatin remodelers, in this study, we performed analysis of genome-wide DNA methylation of peripheral blood from 49 patients with 22q11.2DS using the Illumina Infinium Methylation EPIC bead chip arrays. This cohort comprises 43 typical, 2 proximal and 4 distal deletions. We demonstrated the evidence of a unique and highly specific episignature in all typical and proximal 22q11.2DS. The sensitivity and specificity of this signature was further confirmed by comparing it to over 1500 patients with other neurodevelopmental disorders with known episignatures. Mapping the 22q11.2DS DNA methylation episignature provides both novel insights into the molecular pathogenesis of this disorder and an effective tool in the molecular diagnosis of 22q11.2DS.
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