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.
Summary
Background
Risk benefit strategies in managing inflammatory bowel diseases (IBD) are dependent upon understanding the risks of uncontrolled inflammation vs those of treatments. Malignancy and ...mortality in IBD have been associated with disease‐related inflammation and immune suppression, but data are limited due to their rare occurrence.
Aim
To identify and describe the most common causes of mortality, types of cancer and previous or current therapy among children and young adults with paediatric‐onset IBD.
Methods
Information on paediatric‐onset IBD patients diagnosed with malignancy or mortality was prospectively collected via a survey in 25 countries over a 42‐month period. Patients were included if death or malignancy occurred after IBD diagnosis but before the age of 26 years.
Results
In total, 60 patients were identified including 43 malignancies and 26 fatal cases (9 due to cancer). Main causes of fatality were malignancies (n = 9), IBD or IBD‐therapy related nonmalignant causes (n = 10; including 5 infections), and suicides (n = 3). Three cases, all fatal, of hepatosplenic T‐cell lymphoma were identified, all were biologic‐naïve but thiopurine‐exposed. No other haematological malignancies were fatal. The 6 other fatal cancer cases included 3 colorectal adenocarcinomas and 3 cholangiocarcinomas (CCAs). Primary sclerosing cholangitis (PSC) was present in 5 (56%) fatal cancers (1 colorectal carcinoma, 3 CCAs and 1 hepatosplenic T‐cell lymphoma).
Conclusions
We report the largest number of paediatric‐onset IBD patients with cancer and/or fatal outcomes to date. Malignancies followed by infections were the major causes of mortality. We identified PSC as a significant risk factor for cancer‐associated mortality. Disease‐related adenocarcinomas were a commoner cause of death than lymphomas.
Assessment of fecal calprotectin, a surrogate marker of mucosal inflammation, is a promising means to monitor therapeutic response in pediatric inflammatory bowel disease, especially if the result is ...readily available. We tested the performance of a novel calprotectin rapid test, Quantum Blue, versus the conventional enzyme-linked immunosorbent assay in 134 stool samples from 56 pediatric patients with Crohn disease. The intraclass correlation coefficient analysis reflected good agreement (intraclass correlation coefficient 0.97 95% confidence interval 0.95-0.98) but agreement was better in lower values, where dilutions were not required. Using a cutoff of 100 μg/g for normal values, the percentage agreement between the 2 tests was 87%. The optimal cutoff values to guide clinical decisions in the therapy of inflammatory bowel disease have yet to be determined.
There are no current recommendations for bowel cleansing before colonoscopy in children. The Israeli Society of Pediatric Gastroenterology and Nutrition (ISPGAN) established an iterative working ...group to formulate evidence-based guidelines for bowel cleansing in children prior to colonoscopy.
Data were collected by systematic review of the literature and via a national-based survey of all endoscopy units in Israel. Based on the strength of evidence, the Committee reached consensus on six recommended protocols in children. Guidelines were finalized after an open audit of ISPGAN members.
Data on 900 colonoscopies per year were accrued, which represents all annual pediatric colonoscopies performed in Israel. Based on the literature review, the national survey, and the open audit, several age-stratified pediatric cleansing protocols were proposed: two PEG-ELS protocols (polyethylene-glycol with electrolyte solution); Picolax-based protocol (sodium picosulphate with magnesium citrate); sodium phosphate protocol (only in children over the age of 12 years who are at low risk for renal damage); stimulant laxative-based protocol (e. g. bisacodyl); and a PEG 3350-based protocol. A population-based analysis estimated that the acute toxicity rate of oral sodium phosphate is at most 3/7320 colonoscopies (0.041 %). Recommendations on diet and enema use are provided in relation to each proposed protocol.
There is no ideal bowel cleansing regimen and, thus, various protocols are in use. We propose several evidence-based protocols to optimize bowel cleansing in children prior to colonoscopy and minimize adverse events.
Delayed growth is a well-established feature of pediatric Crohn's disease. Several factors have been shown to affect growth, including disease location, severity, and treatment. The recently ...discovered NOD2 gene has been correlated to ileal location of Crohn's disease and subsequently could affect growth through the resulting phenotype or as an independent risk factor. The aim of our study was to determine if growth retardation is affected by genotype independently of disease location or severity.
Genotyping for 3 NOD2 single-nucleotide polymorphisms was performed in 93 patients with detailed growth records. Parameters including disease location, disease severity, and NOD 2 genotype and their effect on z scores for height and weight at disease onset and during follow-up were analyzed.
NOD2 mutations were correlated with ileal location but not with disease severity or growth retardation. Ileal involvement was significantly associated with height retardation at disease onset and the lowest z score during follow-up. Use of steroids affected weight but not height. Regression models for growth variables revealed that the strongest association with impaired growth is with disease severity (weight- and height-failure odds ratios: 6.17 and 4.52, respectively).
Severity of disease is correlated with growth failure for both height and weight. Location of disease is a weaker predictor of disordered growth and is correlated with growth retardation but not growth failure. The NOD2 genotype was not correlated with growth retardation or growth failure.
Delayed growth is common in pediatric Crohn's disease (CD). Multiple factors have been shown to affect growth in this situation, the most prominent being the presence and severity of inflammation and ...inadequate nutritional intake. Inflammation, anorexia, and weight loss are all manifestations of circulating TNF-alpha, which is elevated in CD. The ability to secrete TNF-alpha may be affected by polymorphisms in the TNF-alpha promoter. The aim of our study was to determine whether growth retardation and disease severity in pediatric onset CD are affected by TNF promoter genotype.
Genotyping for TNF-alpha and NOD2/CARD15 single nucleotide polymorphisms was performed in 87 patients with detailed growth records. Parameters including disease location and disease severity were recorded, and the effect of these polymorphisms on Z-scores for height and weight at disease onset and during follow-up were analyzed.
Lower age of onset was linked to more height retardation, while the presence of colonic disease and the absence of ileal disease were more likely to predict the absence of growth retardation. The presence of two polymorphisms thought to decrease circulating TNF-alpha was associated with higher mean Z-scores for height and a trend toward less growth retardation. Two other polymorphisms were modestly associated with disease severity.
Polymorphisms in the TNF-alpha promoter may independently modulate growth and disease severity in pediatric onset CD. The effect of these polymorphisms does not appear to be mediated via weight loss, and is relatively modest.
Purpose
Factors influencing response to medications in Crohn’s disease (CD) patients are not fully understood. We aimed to evaluate the relationships between NOD2/CARD15 mutations, disease phenotype ...and age of CD diagnosis and response to medical treatment with systemic steroids, azathioprine (AZA) or 6-mercaptopurine (6-MP), and infliximab.
Methods
A retrospective medical records analysis was made of patients previously tested for the CD-associated NOD2/CARD15 mutations. Harvey- Bradshaw score was used to assess remission or response to therapy.
Results
CD-associated NOD2/CARD15 mutations were not related to the rate of steroids dependency or clinical response to AZA/6-MP and infliximab. Steroid dependency was associated with colonic involvement. Thirty-three of 127 (26%) patients with colonic disease were steroid dependent, compared with 7/72 (9.7%) patients with isolated small bowel disease (ISBD), (
p
= 0.009). ISBD was mildly associated with a better remission/response to AZA/6-MP treatment. Disease behavior and age of diagnosis were not related to response to therapy.
Conclusions
Response to treatment with systemic steroids, AZA/6-MP and infliximab are not related to NOD2/CARD15 mutations, age of diagnosis and disease behavior. Patients with colonic disease have higher rates of steroid dependency.
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