A challenge for pediatrician: non allergic urticaria

In general population about 15-20% of subjects have suffered from one episode of urticaria-angioedema syndrome in their life. The etiology of his condition is various and multifactorial. In children the principal cause of acute urticaria is infection, while physical factors are the main agents of chronic urticaria. All those conditions which lack an etiology are named chronic idiopathic urticaria, but in reality a considerable number of these patients is affected by a chronic autoimmune urticaria. For this reason, screening out the most frequent causes of chronic urticaria, it's useful to know when it's possible to apply specific diagnostic tests for this condition and which therapies are employable

Macro- And Microvascular Functions In Cystic Fibrosis Adults Without Cardiovascular Risk Factors: A Case-Control Study.

Increasing survival from cystic fibrosis show untypical systems involvement, such as cardiocirculatory. In particular, the presence of CFTR in smooth muscle and endothelial cells, systemic inflammation and oxidative stress could explain vascular alterations in these patients. We aimed at noninvasely evaluating macro- and microvascular dysfunction in cystic fibrosis adults without cardiovascular risk factors. Twenty-twoadults affected by cystic fibrosis and 24 healthy volunteers matched for age and sex were enrolled. None had known cardiovascular risk factors. All people underwent blood pressure measurement, microvascular function assessment by EndoPAT-2000 device (calculating RH-PAT index) and macrovascular evaluation by pulse wave velocity (PWV). RH-PAT index was significantly lower in patients than in controls (1.74±0.59 vs 2.33±0.34; p<0.001). Thirteen patients of 22 had a value inferior to the threshold of 1.67 (59.1%), while no controls had (p<0.001). Carotid-femoral PWV did not differ between the two groups (5.2±1.5 m/s vs 5.4±1.1; p=0.9), while brachial-ankle one did (11.0±2.2 m/s vs 10.1±0.8 m/s; p=0.04).Adults patients affected by cystic fibrosis show peripheral endothelial dysfunction, which is the first alteration in atherosclerotic phenomenon. Moreover, arterial stiffness measured by PWV unclearly seems to differ respect of healthy people, perhaps because PWV alterations are typical of above 50 years old people. It is unclear what prognostic role of future developing of atherosclerotic disease these findings could be, but it seems evident that cystic fibrosis directly affects cardiovascular system itself

Plasmacytoid Dendritic Cells Depletion and Elevation of IFN-γ Dependent Chemokines CXCL9 and CXCL10 in Children With Multisystem Inflammatory Syndrome

BackgroundSARS-CoV-2 occurs in the majority of children as COVID-19, without symptoms or with a paucisymptomatic respiratory syndrome, but a small proportion of children develop the systemic Multi Inflammatory Syndrome (MIS-C), characterized by persistent fever and systemic hyperinflammation, with some clinical features resembling Kawasaki Disease (KD).ObjectiveWith this study we aimed to shed new light on the pathogenesis of these two SARS-CoV-2-related clinical manifestations.MethodsWe investigated lymphocyte and dendritic cells subsets, chemokine/cytokine profiles and evaluated the neutrophil activity mediators, myeloperoxidase (MPO), and reactive oxygen species (ROS), in 10 children with COVID-19 and 9 with MIS-C at the time of hospital admission.ResultsPatients with MIS-C showed higher plasma levels of C reactive protein (CRP), MPO, IL-6, and of the pro-inflammatory chemokines CXCL8 and CCL2 than COVID-19 children. In addition, they displayed higher levels of the chemokines CXCL9 and CXCL10, mainly induced by IFN-gamma. By contrast, we detected IFN-alpha in plasma of children with COVID-19, but not in patients with MIS-C. This observation was consistent with the increase of ISG15 and IFIT1 mRNAs in cells of COVID-19 patients, while ISG15 and IFIT1 mRNA were detected in MIS-C at levels comparable to healthy controls. Moreover, quantification of the number of plasmacytoid dendritic cells (pDCs), which constitute the main source of IFN-alpha, showed profound depletion of this subset in MIS-C, but not in COVID-19.ConclusionsOur results show a pattern of immune response which is suggestive of type I interferon activation in COVID-19 children, probably related to a recent interaction with the virus, while in MIS-C the immune response is characterized by elevation of the inflammatory cytokines/chemokines IL-6, CCL2, and CXCL8 and of the chemokines CXCL9 and CXL10, which are markers of an active Th1 type immune response. We believe that these immunological events, together with neutrophil activation, might be crucial in inducing the multisystem and cardiovascular damage observed in MIS-C

Transitory pancreatic insufficiency in cystic fibrosis children

n/

Paranasal mucoceles in children with cystic fibrosis: Management of a not so rare clinical condition

Paranasal mucocele (PM) is reported as a complication in children with cystic fibrosis (CF) in up to 4% of patients. The objective of this study was to identify PMs in the personal large series of children with CF and to assess their diagnosis and treatment

Plasmacytoid Dendritic Cells Depletion and Elevation of IFN-\u3b3 Dependent Chemokines CXCL9 and CXCL10 in Children With Multisystem Inflammatory Syndrome

SARS-CoV-2 occurs in the majority of children as COVID-19, without symptoms or with a paucisymptomatic respiratory syndrome, but a small proportion of children develop the systemic Multi Inflammatory Syndrome (MIS-C), characterized by persistent fever and systemic hyperinflammation, with some clinical features resembling Kawasaki Disease (KD)

Abstracts from the 23rd Italian congress of Cystic Fibrosis and the 13th National congress of Cystic Fibrosis Italian Society

Cystic Fibrosis (CF) occurs most frequently in caucasian populations. Although less common, this disorder have been reported in all the ethnicities. Currently, there are more than 2000 described sequence variations in CFTR gene, uniformly distributed and including variants pathogenic and benign (CFTR1:www.genet.sickkids.on.ca/). To date,only a subset have been firmily established as variants annotated as disease-causing (CFTR2: www.cftr2.org). The spectrum and the frequency of individual CFTR variants, however, vary among specific ethnic groups and geographic areas. Genetic screening for CF with standard panels of CFTR mutations is widely used for the diagnosis of CF in newborns and symptomatic patients, and to diagnose CF carrier status. These screening panels have an high diagnostic sensitivity (around 85%) for CFTR mutations in caucasians populations but very low for non caucasians. Developed in the last decade, Next-Generation Sequencing (NGS) has been the last breakthrough technology in genetic studies with a substantial reduction in cost per sequenced base and a considerable enhancement of the sequence generation capabilities. Extended CFTR gene sequencing in NGS includes all the coding regions, the splicing sites and their flankig intronic regions, deep intronic regions where are localized known mutations,the promoter and the 5'-3' UTR regions. NGS allows the analysis of many samples concurrently in a shorter period of time compared to Sanger method . Moreover, NGS platforms are able to identify CFTR copy number variation (CNVs), not detected by Sanger sequencing. This technology has provided new and reliable approaches to molecular diagnosis of CF and CFTR-Related Disorders. It also allows to improve the diagnostic sensitivity of newborn and carrier screeningmolecular tests. In fact, bioinformatics tools suitable for all the NGS platforms can filter data generated from the gene sequencing, and analyze only mutations with well-established disease liability. This approach allows the development of targeted mutations panels with a higher number of frequent CF mutations for the target populationcompared to the standard panels and a consequent enhancement of the diagnostic sensitivity. Moreover, in the emerging challenge of diagnosing CF in non caucasians patients, the possibility of customize a NGS targeted mutations panel should increase the diagnostic sensitivity when the target population has different ethnicities

Impact of COVID-19 infection on lung function and nutritional status amongst individuals with cystic fibrosis: A global cohort study

International audienceBackground: Factors associated with severe COVID-19 infection have been identified; however, the impact of infection on longer-term outcomes is unclear. The objective of this study was to examine the impact of COVID-19 infection on the trajectory of lung function and nutritional status in people with cystic fibrosis (pwCF).Methods: This is a retrospective global cohort study of pwCF who had confirmed COVID-19 infection diagnosed between January 1, 2020 and December 31, 2021. Forced expiratory volume in one second percent predicted (ppFEV 1 ) and body mass index (BMI) twelve months prior to and following a diagnosis of COVID-19 were recorded. Change in mean ppFEV 1 and BMI were compared using a t-test. A linear mixed-effects model was used to estimate change over time and to compare the rate of change before and after infection.Results: A total of 6,500 cases of COVID-19 in pwCF from 33 countries were included for analysis. The mean difference in ppFEV 1 pre-and post-infection was 1.4 %, (95 % CI 1.1, 1.7). In those not on modulators, the difference in rate of change pre-and post-infection was 1.34 %, (95 % CI -0.88, 3.56) per year (p = 0.24) and -0.74 % (-1.89, 0.41) per year (p = 0.21) for those on elexacaftor/tezacaftor/ivacaftor. No clinically significant change was noted in BMI or BMI percentile before and after COVID-19 infection.Conclusions: No clinically meaningful impact on lung function and BMI trajectory in the year following infection with COVID-19 was identified. This work highlights the ability of the global CF community to unify and address critical issues facing pwCF