L. de Ridder

Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease

Children and adolescents with Crohns 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 Crohns 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.

High intra-uterine exposure to infliximab following maternal anti-TNF treatment during pregnancy

Aliment Pharmacol Ther 2011; 33: 1053–1058

Infliximab therapy in 30 patients with refractory pediatric Crohn disease with and without fistulas in the Netherlands

Objective: The purpose of this study was to describe the clinical experience with the anti–tumor necrosis factor chimeric monoclonal antibody, infliximab, in pediatric patients with Crohn disease in The Netherlands. Design: Descriptive. Methods: Clinical response and adverse effects of infliximab were recorded for pediatric patients with Crohn disease treated from October 1992 to January 2003. Results: Thirty patients (aged 7–18 years) with refractory Crohn disease (with or without severe fistulas) were treated with infliximab. Patients were treated with up to 30 infusions. Mean follow-up was 25.3 months. A total of 212 infusions were administered. Thirteen patients had refractory Crohn disease without fistulas. Six patients showed good long-term response to infliximab treatment (defined as clinical index ≤10 points). Sixteen patients had refractory Crohn disease with draining fistulas. Nine showed good long-term response (closure or nonproductiveness of fistulas). One patient with metastatic Crohn disease in the skin had a good long-term response. Six patients developed an allergic reaction during infusion. In one patient, the allergic reaction occurred after an infliximab-free interval of 9 years. One patient died of sepsis. Conclusions: Infliximab was an effective therapy in 53% of patients with refractory pediatric Crohn disease, with or without fistulas. Approximately half of the patients become unresponsive to infliximab therapy. Randomized controlled studies are mandatory to assess long-term efficacy and safety to define the optimal therapeutic strategy of infliximab therapy in children with Crohn disease.

Rapid test for fecal calprotectin levels in children with Crohn disease.

ABSTRACT 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 &mgr;g/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.

Manifestations of Munchausen syndrome by proxy in pediatric gastroenterology.

During the past years, Munchausen syndrome by proxy has received considerable attention and has taken its place among other forms of child abuse. The critical relevance of this entity to the pediatrician emerged in 1977 when Meadow reported the first cases (1). The syndrome is described as the persistent fabrication of symptoms or actual illness in young children by parents, usually the mother. Recently, an increasing number of cases have been reported in which the father is the perpetrator (2). The underlying psychopathologic structure is difficult to identify (3). The main, if not sole benefit for the perpetrating parent lies in the leading role she or he plays during repeated hospital admissions as the medical staff puzzles over the child’s problem. The physician who is involved with these patients may unwittingly participate in this form of child abuse. In general, the child undergoes many unnecessary investigations and procedures (1,4). There are few data about the epidemiology of this syndrome. In the United Kingdom, McClure et al. (5) have reported on the incidence of Munchausen syndrome by proxy combined with nonaccidental poisoning and nonaccidental suffocation. The annual incidence in children aged under 16 years was at least 0.5/100,000 and in children aged under 1 year at least 2.8/100,000. It is the general impression that awareness of the condition is increasing and that more cases are being reported. A broad scale of manifestations has been described of which gastroenterologic manifestations are a substantial part, such as vomiting, diarrhea, and failure to thrive (6). In this report, we attempt to collect all manifestations of Munchausen syndrome by proxy that pediatric gastroenterologists have observed, to increase the awareness of the condition. METHODS

1 Functional consequences of a novel IL-10 receptor alpha mutation on innate and adaptive immunity in early-onset inflammatory bowel disease

M.A. van Leeuwen1, S. Veenbergen1, R. Kersseboom2, L.F. de Ruiter1, H. Raatgeep1, D.J. Lindenbergh-Kortleve1, Y. SimonsOosterhuis1, L. de Ridder1, G.J.A. Driessen3, J.C. Escher1, J.N. Samsom1 *. 1Erasmus Medical Centre Sophia Children’s Hospital, Dept. of Paediatric Gastroenterology, Rotterdam, 2Erasmus Medical Centre, Dept. of Clinical Genetics, Rotterdam, 3Erasmus Medical Centre, Dept. of Paediatric Infectious Disease and Immunology, Rotterdam, Netherlands

Anti-tnf-behandeling bij de ziekte van Crohn

SummaryInfliximab (ifx), a chimeric monoclonal antibody against tumour necrosis factor-α (tnf-α), is indicated in therapy resistant patients with Crohns disease, with or without fistulas. Studies pointed out that one third up to half of these patients can be treated effectively with ifx maintenance therapy. Although adverse events often occur during ifx therapy, severe adverse events are little. Infusion related reactions and infections are reported most. Autoimmune disorders hardly occur and up till now there are no indications that ifx treatment increases the risk on cancer or lymphomas. There are indications that ifx therapy started early in the course of paediatric Crohns disease is more effective. Although efficacy of ifx is proven, more information on efficacy and safety during long term ifx maintenance therapy is needed to determine the right position for ifx in the contemporary farmacotherapeutic arsenal.SamenvattingInfliximab (ifx), een chimere monoklonale antistof tegen tumornecrosefactor-α (tnf-α), is geïndiceerd bij patiënten met therapieresistente ziekte van Crohn met/zonder fistels. Onderzoek heeft uitgewezen dat ongeveer een derde tot de helft van deze groep patiënten effectief behandeld kan worden met ifx-onderhoudstherapie. Alhoewel er vaak bijwerkingen tijdens ifx-behandeling optreden, is het aantal ernstige bijwerkingen gering. Het meest voorkomend zijn infuusgerelateerde reacties en infecties. Auto-immuunaandoeningen komen nagenoeg niet voor, en er zijn momenteel geen aanwijzingen dat ifx-behandeling het risico op kanker of lymfomen verhoogt. Er zijn aanwijzingen dat ifx-behandeling bij pediatrische Crohn-patiënten effectiever is indien dit in een vroeg stadium gestart wordt. Ondanks de bewezen effectiviteit van ifx, zullen meer resultaten over effectiviteit en veiligheid bij langdurige ifx-onderhoudstherapie noodzakelijk zijn voor een juiste afweging van ifx binnen het huidige medicamenteuze arsenaal.

Genetic polymorphisms and inflammatory bowel diseases

SummaryThe ultimate goal of intensive care is to bridge critical failure of vital functions in order to achieve an acceptable perspective for further life for as many patients as possible and hence in a cost-effective way. Decisions should be based on valid data on patient outcome. These data are often lacking or are not applicable to an individual patient. The specific developmental medical and social needs and the special legal position of children and their parents or caregivers are explicit topics in pediatric intensive care. This article focuses on the difficult decision process when multiple handicapped children are proposed for admission to the intensive care unit. Decisions as to life support in these children need to be made in advance before the vital functions fail. The decision not to (re)admit a child to the intensive care unit does not imply disregarding other modes of curative care. Do-not-resuscitate orders should be specified and preferably be replaced by individually defined comfort care policies. Withdrawing treatment does not mean withdrawing care.SamenvattingHet doel van intensive care is om een periode met insufficiënte vitale functies te overbruggen, om in de daarmee verkregen tijd de patiënt te laten herstellen tot een voor hem of haar acceptabel niveau. De daartoe beschikbare technologie dient kosteneffectief te worden ingezet. Besluiten dienen op grond van valide gegevens over behandelingsresultaten genomen te worden. Deze gegevens ontbreken echter vaak of zijn niet van toepassing op een individuele patiënt. Daarnaast vereist de bijzondere sociale en juridische positie van kinderen en hun ouders of verzorgers binnen de kinder-ic specifieke aandacht. Dit artikel gaat over de problemen waarvoor de kinderarts-intensivist zich geplaatst ziet bij de besluitvorming over opname van ernstig multipel gehandicapte kinderen. Deze besluitvorming dient niet uitgesteld te worden tot de vitale functies van het kind manifest tekortschieten. In een vroege fase dienen kinderarts en andere relevante disciplines in overleg met de kinderarts-intensivist een voor kind en ouders aanvaardbaar beleid in dezen vast te stellen. Als afgesproken wordt het kind niet (meer) op de intensive care-afdeling op te nemen, betekent dit niet dat in het geheel geen curatieve behandeling meer wordt ingesteld. Niet-reanimeer opdrachten zijn als zodanig te weinig specifiek en dienen vervangen te worden door een goed omschreven behandel- en verzorgingsplan.

Malignancy and mortality in paediatric-onset inflammatory bowel disease: a 3-year prospective, multinational study from the paediatric IBD Porto group of ESPGHAN

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.

Cytomegalovirus infection in pediatric acute severe ulcerative colitis - a multicenter case-controlled study from the Pediatric IBD Porto group of ESPGHAN

Background: Data on the clinical course and outcomes of pediatric patients with cytomegalovirus (CMV) infection complicating acute severe ulcerative colitis (ASC) is very limited. The aim of our study was to compare the outcome of CMV-positive and negative pediatric ASC. Methods: This was a multicenter retrospective case-controlled study, from centers in Europe and Israel. We included CMV –positive pediatric patients hospitalized for acute severe colitis and compared their outcomes (rate of colectomy up to 1 year from hospitalization) to matched CMV-negative controls. Results: A total of 56 children from 10 centers were included. Fifteen patients were CMV-positive and 41 CMVnegative. Significantly higher proportion of CMV positive patients were resistant to intravenous corticosteroids (p=0.009). After diagnosis of CMV infection, 14/15 patients were started on gancyclovir. During hospitalization, 3 (20%) CMV positive and 3 (7.8%) CMV-negative patients required colectomy (p=0.17). By 12 months of follow-up,5 (33.3%) and 5 (12.5%) CMV positive and negative patients required colectomy, respectively (p=0.049). Previous antiTNF exposure and Pediatric Ulcerative Colitis Activity Index score on index date were significantly associated with risk of colectomy during hospitalization and by 12 months on univariate analysis, however none of the factors retained significance on multivariate analysis. Conclusions: A statisticaly significant high prevalence of CMV positivity was found in patients who required colectomy. Disease severity and history of anti-TNF treatment were the main factors associated with the risk of colectomy. Further studies are merited to clarify the impact of CMV infection on the outcome of acute severe colitis in