Children and adolescents with Crohn's disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn's and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.

Previous genome-wide association (GWA) studies typically focus on single-locus analysis, which may not have the power to detect the majority of genuinely associated loci. Here, we applied pathway analysis using Affymetrix SNP genotype data from the Wellcome Trust Case Control Consortium (WTCCC) and uncovered significant association between Crohn Disease (CD) and the IL12/IL23 pathway, harboring 20 genes (p = 8 x 10(-5)). Interestingly, the pathway contains multiple genes (IL12B and JAK2) or homologs of genes (STAT3 and CCR6) that were recently identified as genuine susceptibility genes only through meta-analysis of several GWA studies. In addition, the pathway contains other susceptibility genes for CD, including IL18R1, JUN, IL12RB1, and TYK2, which do not reach genome-wide significance by single-marker association tests. The observed pathway-specific association signal was subsequently replicated in three additional GWA studies of European and African American ancestry generated on the Illumina HumanHap550 platform. Our study suggests that examination beyond individual SNP hits, by focusing on genetic networks and pathways, is important to unleashing the true power of GWA studies.

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Several clinical reports have demonstrated that Helicobacter pylori gastric infection has emerged as a new cause of refractory iron deficiency anemia, unresponsive to iron therapy, and not attributable to usual causes such as intestinal losses or poor intake, malabsorption or diversion of iron in the reticulo-endothelial system. Although the interaction between infection and iron metabolism is now well consolidated, our understanding of the pathogenetic mechanism underlying the anemia is still wanting. Microbiological and ferrokinetic studies seem to suggest that Helicobacter pylori infected antrum could act as a sequestering focus for serum iron by means of outer membrane receptors of the bacterium, that in vitro are able to capture and utilize for growth iron from human lactoferrin. The proposed hypothesis does not answer why this complication is such a rare disease outcome in a common human infection but it may be used as a template for further controlled studies to determine the mechanisms of this atypical, medically important putative sequelae of H. pylori infection.

BACKGROUND:\ud 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.\ud METHODS:\ud 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.\ud RESULTS:\ud Eleven percent of patients were in the range 0 to 5 years, 39% in 6 to 11 years, and 50% in 12 to 18 years. Ulcerative colitis was the most frequent diagnosis in EO-IBD and in 6- to 11-year-old group, whereas Crohn's disease was predominant in older children. A classification as IBD-unclassified was more common in the range 0 to 5 years compared with the other groups (P < 0.005). EO Crohn's disease showed a more frequent isolated colonic (P < 0.005) and upper gastrointestinal involvement than later-onset disease. Sixty-two percent of the patients in the 0 to 5 years range had pancolonic ulcerative colitis, compared with 38% of 6 to 11 years (P = 0.02) and 31% of 12-18 years (P = 0.002) range. No statistical difference for family history for IBD was found in the 3-year age groups. Therapies at the diagnosis were similar for all children. However, at latest follow-up, a significantly higher proportion of younger children were under steroids compared with older groups (P < 0.05). Surgical risk did not differ according to age.\ud CONCLUSIONS:\ud EO-IBD exhibits an extensive phenotype and benefit from aggressive treatment strategies, although surgical risk is similar to later-onset disease. A family history for IBD is not common in EO disease

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IMPORTANCE Pediatric-onset Crohn disease is more aggressive than adult-onset disease, has high rates of resistance to existing drugs, and can lead to permanent impairments. Few trials have evaluated new drugs for refractory Crohn disease in children.OBJECTIVE To determine whether thalidomide is effective in inducing remission in refractory pediatric Crohn disease. DESIGN, SETTING, AND PATIENTS Multicenter, double-blind, placebo-controlled, randomized clinical trial of 56 children with active Crohn disease despite immunosuppressive treatment, conducted August 2008-September 2012 in 6 pediatric tertiary care centers in Italy. INTERVENTIONS Thalidomide, 1.5 to 2.5 mg/kg per day, or placebo once daily for 8 weeks. In an open-label extension, nonresponders to placebo received thalidomide for an additional 8 weeks. All responders continued to receive thalidomide for an additional minimum 52 weeks. MAIN OUTCOMES AND MEASURES Primary outcomes were clinical remission at week 8, measured by Pediatric Crohn Disease Activity Index (PCDAI) score and reduction in PCDAI by Ն25% or Ն75% at weeks 4 and 8. Primary outcomes during the open-label follow-up were clinical remission and 75% response. RESULTS Twenty-eight children were randomized to thalidomide and 26 to placebo. Clinical remission was achieved by significantly more children treated with thalidomide (13/28 [46.4%] vs 3/26 [11.5%]; risk ratio [RR], 4.0 [95% CI, 1.2-12.5]; P = .01; number needed to treat [NNT], 2.86). Responses were not different at 4 weeks, but greater improvement was observed at 8 weeks in the thalidomide group (75% response, 13/28 [46.4%] vs 3/26 [11.5%]; RR, 4.0 [95% CI, 1.2-12.5]; NNT = 2.86; P = .01; and 25% response, 18/28 [64.2%] vs 8/26 [30.8%]; RR, 2.1 [95% CI,]; NNT = 2.99; P = .01). Of the nonresponders to placebo who began receiving thalidomide, 11 of 21 (52.4%) subsequently reached remission at week 8 (RR, 4.5 [95% CI, 1.4-14.1]; NNT = 2.45; P = .01). Overall, 31 of 49 children treated with thalidomide (63.3%) achieved clinical remission, and 32 of 49 (65.3%) achieved 75% response. Mean duration of clinical remission in the thalidomide group was 181.1 weeks (95% CI, 144.53-217.76) vs 6.3 weeks (95% CI, 3.51-9.15) in the placebo group (P < .001). Cumulative incidence of severe adverse events was 2.1 per 1000 patient-weeks, with peripheral neuropathy the most frequent severe adverse event.CONCLUSIONS AND RELEVANCE In children and adolescents with refractory Crohn disease, thalidomide compared with placebo resulted in improved clinical remission at 8 weeks of treatment and longer-term maintenance of remission in an open-label follow-up. These findings require replication to definitively determine clinical utility of this treatment.