CD25 deficiency: A new conformational mutation prevents the receptor expression on cell surface.

CD25 deficiency is a very rare autosomal recessive disorder that shows a clinical phenotype highly overlapping IPEX syndrome with an increased susceptibility to viral, bacterial, and fungal infections. It is due to mutations in the IL2Rα gene that codes for the α subunit of the IL2 receptor complex. Here we report the characterization of a novel IL2Rα gene mutation leading to a severe protein conformational alteration that abrogates its cell surface expression in a child presenting with early-onset IPEX-like disorder.

Efficacy of adalimumab as second-line therapy in a pediatric cohort of Crohn's disease patients who failed infliximab therapy: the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition experience.

Background: Adalimumab (Ada) treatment is an available option for pediatric Crohn's disease (CD) and the published experience as rescue therapy is limited.

Objectives: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months.

Methods: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up.

Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study.

Background And Aims: An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment.

Methods: A total of 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD [n = 185] or an anamnesis suggestive of a monogenic disorder [n = 22].

Treating children with inflammatory bowel disease: Current and new perspectives.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gut characterised by alternating periods of remission and relapse. Whilst the mechanism underlying this disease is yet to be fully understood, old and newer generation treatments can only target selected pathways of this complex inflammatory process. This narrative review aims to provide an update on the most recent advances in treatment of paediatric IBD.

Assessing pediatric ileocolonic Crohn's disease activity based on global MR enterography scores.

Objectives: This study was aimed at correlating a magnetic resonance index of activity (MaRIA) and a magnetic resonance enterography global score (MEGS) with activity indexes in a paediatric population with Crohn's disease (CD).

Methods: This retrospective study included 32 paediatric patients (median age 14.5 years, 18 male) with proven CD who underwent magnetic resonance enterography (MRE).

Clinical course and outcomes of diagnosing Inflammatory Bowel Disease in children 10 years and under: retrospective cohort study from two tertiary centres in the United Kingdom and in Italy.

Background: Most children with Inflammatory Bowel Disease (IBD) are diagnosed between 11 and 16 years of age, commonly presenting with features of typical IBD. Children with onset of gut inflammation under 5 years of age often have a different underlying pathophysiology, one that is genetically and phenotypically distinct from other children with IBD. We therefore set out to assess whether children diagnosed after the age of 5 years, but before the age of 11, have a different clinical presentation and outcome when compared to those presenting later.

Italian survey on non-steroidal anti-inflammatory drugs and gastrointestinal bleeding in children.

Aim: To investigate gastrointestinal complications associated with non-steroidal anti-inflammatory drug (NSAIDs) use in children.

Methods: A retrospective, multicenter study was conducted between January 2005 and January 2013, with the participation of 8 Italian pediatric gastroenterology centers. We collected all the cases of patients who refer to emergency room for suspected gastrointestinal bleeding following NSAIDs consumption, and underwent endoscopic evaluation.

Transition of gastroenterological patients from paediatric to adult care: A position statement by the Italian Societies of Gastroenterology.

In 2013, four Italian Gastroenterological Societies (the Italian Society of Paediatric Gastroenterology, Hepatology and Nutrition, the Italian Society of Hospital Gastroenterologists and Endoscopists, the Italian Society of Endoscopy, and the Italian Society of Gastroenterology) formed a joint panel of experts with the aim of preparing an official statement on transition medicine in Gastroenterology. The transition of adolescents from paediatric to adult care is a crucial moment in managing chronic diseases such as celiac disease, inflammatory bowel disease, liver disease and liver transplantation. Improved medical treatment and availability of new drugs and surgical techniques have improved the prognosis of many paediatric disorders, prolonging survival, thus making the transition to adulthood possible and necessary.

TNFA Haplotype Genetic Testing Improves HLA in Estimating the Risk of Celiac Disease in Children.

Background: TNF-α and IFN-γ play a role in the development of mucosal damage in celiac disease (CD). Polymorphisms of TNFA and IFNG genes, as well as of the TNFRSF1A gene, encoding the TNF-α receptor 1, might underlie different inter-individual disease susceptibility over a common HLA risk background. The aims of this study were to ascertain whether five SNPs in the TNFA promoter (-1031T>C,-857C>T,-376G>A,-308G>A,-238G>A), sequence variants of the TNFRSF1A gene and IFNG +874A>T polymorphism are associated with CD in a HLA independent manner.

The multidisciplinary health care team in the management of stenosis in Crohn's disease.

Background: Stricture formation is a common complication of Crohn's disease (CD), occurring in approximately one-third of all patients with this condition. Our aim was to summarize the available epidemiology data on strictures in patients with CD, to outline the principal evidence on diagnostic imaging, and to provide an overview of the current knowledge on treatment strategies, including surgical and endoscopic options. Overall, the unifying theme of this narrative review is the multidisciplinary approach in the clinical management of patients with stricturing CD.

Natural history of pancreatic involvement in paediatric inflammatory bowel disease.

Background: Few case reports describe the clinical features of pancreatic involvement in inflammatory bowel disease.

Aim: To investigate prevalence and disease course of inflammatory bowel disease children with pancreatitis and with exclusive hyperamylasemia and hyperlipasemia.

Methods: We used a web-registry to retrospectively identify paediatric inflammatory bowel disease patients with hyperamylasemia and hyperlipasemia.

Crohn's disease and growth deficiency in children and adolescents.

Nutritional concerns, linear growth deficiency, and delayed puberty are currently detected in up to 85% of patients with Crohn's disease (CD) diagnosed at childhood. To provide advice on how to assess and manage nutritional concerns in these patients, a Medline search was conducted using "pediatric inflammatory bowel disease", "pediatric Crohn's disease", "linear growth", "pubertal growth", "bone health", and "vitamin D" as key words. Clinical trials, systematic reviews, and meta-analyses published between 2008 and 2013 were selected to produce this narrative review.

Introduction of gluten, HLA status, and the risk of celiac disease in children.

Background: The relationship between the risk of celiac disease and both the age at which gluten is introduced to a child's diet and a child's early dietary pattern is unclear.

Methods: We randomly assigned 832 newborns who had a first-degree relative with celiac disease to the introduction of dietary gluten at 6 months (group A) or 12 months (group B). The HLA genotype was determined at 15 months of age, and serologic screening for celiac disease was evaluated at 15, 24, and 36 months and at 5, 8, and 10 years.

Phenotype and disease course of early-onset pediatric inflammatory bowel disease.

Background: Early-onset (EO) pediatric inflammatory bowel diseases (IBD) seem to be more extensive than those with a later onset. To test this hypothesis, we examined the phenotype and disease course of patients with IBD diagnosis at 0 to 5 years, compared with the ranges 6 to 11 and 12 to 18 years.

Methods: Anatomic locations and behaviors were assessed according to Paris classification in 506 consecutive patients: 224 Crohn's disease, 245 ulcerative colitis, and 37 IBD-unclassified.

Highlights in IBD Epidemiology and Its Natural History in the Paediatric Age.

Background. The number of patients of all age brackets diagnosed with Inflammatory Bowel Disease (IBD) has risen dramatically worldwide over the past 50 years. IBD's changing epidemiology suggests that environmental factors play a major role in modifying disease expression.

Phenotypic characterization of very early-onset IBD due to mutations in the IL10, IL10 receptor alpha or beta gene: a survey of the Genius Working Group.

Objective: Early-onset inflammatory bowel disease starting within the first months of life could be due to a particular genetic defect. We set up the GENetically determined ImmUne-mediated enteropathieS (GENIUS) network and collected infants with a proven defect of the IL10 axis for accurate phenotyping of disease presentation and evolution.

Design: Ten patients with early-onset inflammatory bowel disease with confirmed mutations in IL10, IL10RA, or IL10RB genes were characterized on clinical, endoscopic-histological, immunobiological, and radiological findings.

Early-life factors associated with pediatric functional constipation.

Objective: This multicenter prospective study aimed to establish possible risk factors for functional constipation (FC) in the first year of life.

Methods: At the infant's age of 3, 6, and 12 months, parents of all included infants completed 2 questionnaires: one about the presence of FC and the other screened the possible risk factors for FC. Parents of 465 infants completed the questionnaires at 3 and 6 months and of 402 infants at 12 months of life.

Chemiluminescence and ELISA-based serum assays for diagnosing and monitoring celiac disease in children: a comparative study.

Background: Anti-transglutaminase (tTG) or anti-deamidated gliadin peptides (DGP) serum determination is the first step in diagnosing celiac disease (CD). Our aims were to: compare the performance of novel chemiluminescent tool in the detection of tTG and DGP (Q-Flash®, Inova) with that of the established ELISA (Q-Lite®, Inova) methods; identify the more reliable index for making a sound diagnosis and monitoring therapy.

Methods: Using Q-Flash® and Q-Lite®, IgA and IgG class tTG and DGP were measured in the sera of 155 CD pediatric patients and 166 healthy age-matched controls.

Conservative treatment for cystic duct stenosis in a child.

Introduction. Few cases of common bile duct stenosis have been reported in the literature, and observations of strictures in the cystic duct are even more rare. Surgical cholecystectomy is the treatment needed in most cases of gallbladder hydrops.

Colonic perforation in a child with Crohn's disease: successful medical treatment rescues from colectomy.

Background. The challenging treatment of penetrating paediatric Crohn's disease (CD) involves pharmacological and surgical approaches. Despite a proved efficacy of anti-TNF agents for treatment of complex fistula, a large number of patients cannot achieve a complete healing and relapse during the followup.

Infliximab and pediatric stricturing Crohn's disease: a possible alternative to surgery? Experience of seven cases.

Introduction: Infliximab (IFX) is one of the treatments of choice for the different phenotypes of pediatric Crohn's disease (CD). Although it was initially feared that anti-TNFα treatment might cause bowel stenosis, recent studies have validated the efficacy of IFX as an anti-stricturing agent.

Aim: To assess the efficacy of IFX treatment for pediatric stricturing CD.

Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy.

Background & Aims: Homozygous loss of function mutations in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) cause severe infantile (very early onset) inflammatory bowel disease (IBD). Allogeneic hematopoietic stem cell transplantation (HSCT) was reported to induce sustained remission in 1 patient with IL-10R deficiency. We investigated heterogeneity among patients with very early onset IBD, its mechanisms, and the use of allogeneic HSCT to treat this disorder.