Lissy Ridder - Academia.edu (original) (raw)
Papers by Lissy Ridder
Rotterdam Transition Test: A Valid Tool for Monitoring Disease Knowledge in Adolescents With Inflammatory Bowel Disease
Journal of Pediatric Gastroenterology & Nutrition, 2021
Objectives: Disease knowledge is important in adolescents with inflammatory bowel disease (IBD) t... more Objectives: Disease knowledge is important in adolescents with inflammatory bowel disease (IBD) transitioning to adult care. We developed an IBD-specific knowledge questionnaire, the Rotterdam Transition Test (RTT), and aimed to validate this tool. Methods: This is a prospective longitudinal validation study. The RTT has 25 open questions on IBD, medication, lifestyle, and transition to adult care. A scoring model was developed, and inter-rater agreement was assessed. Using a Rasch model, we determined the difficulty and performance of the questions. Cronbach alpha was used to demonstrate reliability. Patient factors (age, disease, education, medication use, illness acceptance, and independence) were correlated to RTT score. Results: A total of 207 RTTs were evaluated in 111 adolescent IBD patients. The scoring model showed a kappa score of >0.61 for all questions. Reliability with Cronbach alpha was good (0.81). Mean total result of the RTT was 58% (girls) and 55% (boys) of maxi...
Mucosal Immunology, 2018
Disease heterogeneity hampers achieving long-term disease remission in inflammatory bowel disease... more Disease heterogeneity hampers achieving long-term disease remission in inflammatory bowel disease (IBD). Monitoring ongoing tissue-localized regulatory and inflammatory T-cell responses in peripheral blood would empower disease classification. We determined whether regulatory and inflammatory phenotypes of circulating CD38 + effector (CD62L neg CD4 + ) T cells, a population enriched for cells with mucosal antigen specificity, classify disease course in pediatric IBD patients. In healthy individuals, circulating CD38 + effector T cells had a predominant regulatory component with lower frequencies of IFNγ-secreting T cells, higher frequencies of IL-10-secreting T cells and higher frequencies of inhibitory molecule T-cell immunoglobulin and ITIM domain + (TIGIT) cells than CD38 neg effector T cells. TIGIT expression was stable upon stimulation and marked CD38 + T cells with inhibitory properties. In IBD patients with active intestinal inflammation this predominant regulatory component was lost: circulating CD38 + effector T cells had increased activated CD25 + CD45RA neg and decreased TIGIT + cell frequencies. TIGIT percentages below 25% before treatment associated with shorter duration of clinical remission. In conclusion, phenotypic changes in circulating CD38 + effector T cells, in particular the frequency of TIGIT + cells, classify pediatric IBD patients and predict severity of disease course. These findings have relevance for IBD and can be exploited in graft-versus-host-disease and checkpoint inhibitor-induced inflammation in cancer.
Journal of Crohn's & colitis, Jan 25, 2018
There is no standardized endoscopic description of upper gastrointestinal (UGI) disease in Crohn&... more There is no standardized endoscopic description of upper gastrointestinal (UGI) disease in Crohn's disease (CD). We prospectively applied the Simple Endoscopic Score for CD (SES-CD) to the UGI tract as a planned sub-study of the multicenter prospective ImageKids study. We aimed to assess the utility of the UGI-SES-CD and its clinical significance in pediatric CD. Patients underwent an esophagogastroduodenoscopy (EGD), ileocolonoscopy and magnetic resonance enterography (MRE) with explicit clinical data recorded. SES-CD was scored at each region (esophagus, stomach body, antrum and duodenum). Half of the patients were followed for 18 months when a repeat MRE was performed. Two hundred and two children were included (56% males, mean age 11.5 ± 3.2 years, median wPCDAI 25. UGI-SES-CD score ranged from 0-17, with 95 (47%) having a UGI-SES-CD ≥1; no narrowing was detected. UGI-SES-CD ≥1 was associated with higher wPCDAI (32.5 vs 20; p=0.03), PGA of inflammation (45mmVAS vs 30mmVAS; p...
Journal of Crohn's & colitis, Jan 9, 2017
Vedolizumab, an anti-integrin antibody, has proven to be effective in adults with Inflammatory Bo... more Vedolizumab, an anti-integrin antibody, has proven to be effective in adults with Inflammatory Bowel Disease (IBD), but the data in pediatrics are limited. We describe the short-term effectiveness and safety of vedolizumab in a European multi-center pediatric IBD cohort. Retrospective review of children (2-18 years) treated with vedolizumab from 19 centers affiliated with the Paediatric IBD Porto group of ESPGHAN. Primary outcome was week 14 corticosteroid-free remission (CFR). 64 children were included [32 (50%) male, mean age 14.5 ± 2.8 years, with a median follow-up 24 weeks (IQR 14-38; range 6-116)]; 41 (64%) UC/IBDU and 23 (36%) CD. All were previously treated with anti-TNF (28% primary failure, 53% secondary failure). Week 14 CFR was 37% in UC, and 14% in CD (p=0.06). CFR by last follow-up was 39% in UC and 24% in CD (p=0.24). Ten (17%) children required surgery, 6 of whom had colectomy for UC. Concomitant immunomodulatory drugs did not affect remission rate (42% vs 35%; p=0.3...
[Infliximab therapy in children and adolescents with refractory Crohn's disease in the Netherlands; experience with 23 patients]
Nederlands tijdschrift voor geneeskunde, Jan 5, 2002
To describe the clinical experience of infliximab treatment in children and adolescents with refr... more To describe the clinical experience of infliximab treatment in children and adolescents with refractory Crohn's disease in the Netherlands. Descriptive. From November 1998 to February 2002, 23 patients (aged 7-18 years) with refractory Crohn's disease or steroid-dependent Crohn's disease (with or without severe fistulas) were treated with infliximab. Patients were treated with 1-11 infusions, with an average follow-up of 14.5 months after the start of infliximab therapy. Ten patients had refractory Crohn's disease. Four of these showed good long-term response on infliximab treatment (modified 'Paediatric Crohn's disease activity index' (PCDAI) < or = 10 points or growth acceleration after stunting). Twelve patients had Crohn's disease with severe fistulas. Five of these showed good long-term response (closure or non-productiveness of fistulas). One patient had metastatic Crohn's disease in the skin and showed good long-term response. Response r...
Dysfagie op de kinderleeftijd
Tijdschrift voor Kindergeneeskunde, 2011
Samenvatting Patiënt A, een 13-jarige jongen, werd verwezen vanwege een slokdarmperforatie, onts... more Samenvatting Patiënt A, een 13-jarige jongen, werd verwezen vanwege een slokdarmperforatie, ontstaan tijdens endoscopie vanwege voedselimpactie in de slokdarm. Bij histologisch onderzoek van de slokdarmmucosa werd een eosinofielrijk infiltraat aangetroffen; de jongen werd behandeld met elementaire sondevoeding en prednison. Bij patiënt B, een tweejarige jongen met hardnekkige klachten van hoesten en braken, werd niet, zoals verwacht, gastro-oesofageale refluxziekte vastgesteld, maar eosinofilie
Journal of Crohn's and Colitis, 2015
Background and aims: Methotrexate [MTX] is an immunomodulating drug that can be used to maintain ... more Background and aims: Methotrexate [MTX] is an immunomodulating drug that can be used to maintain remission in patients with Crohn's disease [CD], but data on efficacy and tolerability in children and teenagers are scarce. We evaluated the long-term efficacy and tolerability of MTX monotherapy after thiopurine therapy in paediatric CD patients. Methods: A multicenter cohort of paediatric MTX users who stopped thiopurines due to ineffectiveness or intolerance between 2002 and 2012 were included and followed for at least 12 months. Relapse-free use was defined as steroid and biologics-free clinical remission after the introduction of MTX, and included intentional discontinuation of successful therapy before the end of the observation period. Results: A total of 113 patients with CD in remission were followed while on MTX monotherapy, of whom 75 [66%] had failed on thiopurines and 38 [34%] had stopped thiopurines due to side effects. Median age at the introduction of MTX was 14 years [range 7 to 17], and 93% used the subcutaneous route. Kaplan-Meier analysis showed that 52% of the study cohort were still in steroid-and biologics-free remission after 12 months of MTX monotherapy, with a difference that did not reach significance between thiopurine-intolerant and thiopurine-failing patients [p = 0.21, log-rank test]. The findings of this cohort study suggest that MTX is an effective immunomodulator to maintain remission after stopping thiopurines. MTX maintenance should be considered before stepping up to anti-tumor necrosis factor alpha therapy. MTX is probably somewhat more effective in patients who stopped thiopurines due to side effects than in those who failed on thiopurines.
Journal of Crohn's and Colitis, 2014
Introduction: Contemporary data describing treatment practices and outcomes of children with Croh... more Introduction: Contemporary data describing treatment practices and outcomes of children with Crohn's disease (CD) are limited. Aim: To describe the effect of initial treatments on clinical outcomes in children with newly diagnosed CD. Methods: Data (diagnosis, 30 day, quarterly) were extracted from a multicenter North American observational registry. Four year outcomes of cohorts diagnosed 2002 4 (Grp1) and 2007 9 (Grp2) were compared. Results: Treatments and outcomes were similar in both cohorts. Among 349 children presenting with moderate severe CD, 75 80% received corticosteroids and/or immunomodulators by 30d and Q1, and 7 14% received anti-TNF. Among 126 presenting with mild CD, 60 75% received corticosteroids and/or immunomodulators by 30d or Q1. By Q1, 9% received anti-TNF. Many children presenting with either mild or moderate severe CD received 5ASA as their only induction therapy (Mild: 30d = 40%, Q1 = 30%; Moderate-severe: 30d = 15%, Q1 = 11%). Regardless of initial CD activity or treatment by 30d, only 15 20% of subjects had inactive CD in all 4 quarterly assessments through Yr1. 30% of those with initial moderate severe CD continued to have periods of moderate severe activity in Yr1, and 15 30% in Yr2 4. For those presenting with mild CD, 10 30% had periods of moderate severe activity in Yr1, and 15 25% in Yr2 4. However, <10% of all subjects had 3 4 years with periods of moderate severe activity. Hospitalizations (Grp1 = 38%, Grp2 = 45%), IBD surgery (Grp1 = 11%, Grp2 = 19%) and change in growth Z-scores were comparable between cohorts. Conclusions: Periods of moderate severe activity continue to occur in 15 25% of children with CD despite current treatments. Re-assessment of treatment utilization appears warranted. Ten years of paediatric inflammatory bowel disease incidence in the north of Scotland
Inflammatory Bowel Diseases, 2015
Sexual health is a broad term that encompasses a variety of functions including sexual thoughts, ... more Sexual health is a broad term that encompasses a variety of functions including sexual thoughts, desire, arousal, intercourse, orgasm, and the impact of body image. Sexual dysfunction in individuals with inflammatory bowel disease is multifactorial including the impact of psychosocial factors, disease activity, medical therapies, surgical interventions, body image perceptions and changes, hypogonadism, and pelvic floor disorders. Providers caring for patients with inflammatory bowel disease should be cognizant of these concerns and develop management plans and techniques for earlier diagnosis and treatment.
Percutaneous endoscopic gastrostomy (PEG) in children is not a minor procedure: risk factors for major complications
Seminars in Pediatric Surgery, 2009
Percutaneous endoscopic gastrostomy (PEG) provides for enteral nutrition in children with feeding... more Percutaneous endoscopic gastrostomy (PEG) provides for enteral nutrition in children with feeding problems. PEG, however, is not without complications. The present study has a twofold aim: (1) comparing our incidence of major complications after PEG with the incidence in other centers, and (2) identifying risk factors for major complications. All patients receiving a PEG or laparoscopic-assisted PEG (lap PEG) in the period 1992-2008 were reviewed. Primary outcome was the occurrence of major complications, defined as the need for surgery, non-prophylactic antibiotics, or blood transfusion, and procedure-related death. Potential risk factors, eg, age under 1 year, mental retardation, scoliosis, constipation, hepatomegaly, upper abdominal surgery, ventriculoperitoneal shunt, peritoneal dialysis, esophageal stenosis, and coagulopathy, were analyzed. Of the 467 patients (448 PEG, 19 lap PEG), 12.6% developed major complications. The complication rate significantly decreased (P = 0.003) over the years. A significantly higher complication rate of 32% (P = 0.02) occurred in children with a ventriculoperitoneal shunt. None of the lap PEG procedures was associated with a major complication, but the difference was not significant, perhaps because of the small numbers in the latter group. The major complication rate after PEG in children is high. Preexisting ventriculoperitoneal shunt is a significant risk factor. Laparoscopically assisted PEG procedures seem to be associated with a lesser major complication rate.
Journal of Pediatric Gastroenterology & Nutrition, 2015
Objectives: Adalimumab, a humanised anti-tumour necrosis factor antibody, is an effective treatme... more Objectives: Adalimumab, a humanised anti-tumour necrosis factor antibody, is an effective treatment in adult patients with refractory Crohn disease (CD). The available literature on its efficacy in children remains limited. We aimed to evaluate the real-world efficacy in paediatric patients with CD and compare the efficacy between infliximab (IFX) nonresponders and patients who lost response to IFX. Methods: All Dutch patients with CD receiving adalimumab before the age of 18 years after previous IFX therapy were identified. We analysed longitudinal disease activity, assessed by the mathematically weighted Pediatric Crohn's Disease Activity Index (wPCDAI) or the physician global assessment (PGA), and adverse events (AEs). Results: Fifty-three patients with CD were included. Twelve patients received monotherapy and the others received combination treatment with thiopurines (n ¼ 21), methotrexate (n ¼ 11), steroids (n ¼ 7), or exclusive enteral nutrition (n ¼ 2). Median follow-up was 12 months (interquartile range 5-23). Remission was reached in 34 patients (64%, wPCDAI < 12.5 or PGA ¼ 0) after a median of 3.3 months, and maintained by 50% for 2 years. Eleven patients (21%) reached response but not remission (decrease in wPCDAI ! 17.5 or decrease in PGA). Eighteen patients (34%) failed adalimumab treatment because of nonresponse (n ¼ 4), lost response (n ¼ 11), or AEs (n ¼ 3). More IFX nonresponders failed adalimumab treatment than patients who lost response to IFX (2/3 vs 8/34, hazard ratio 18.8, 95% confidence interval 1.1-303.6). Only 1 patient encountered a serious AE, a severe but nonfatal infection. Conclusions: In clinical practice, adalimumab induces remission in twothirds of children with IFX refractory CD.
Journal of Pediatric Gastroenterology & Nutrition, 2012
Objective: In 2005, the Inflammatory Bowel Disease (IBD) Working Group of the European Society fo... more Objective: In 2005, the Inflammatory Bowel Disease (IBD) Working Group of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition published consensus guidelines on the diagnostic workup of paediatric IBD, the Porto criteria. According to these guidelines, children suspected of having IBD should undergo an oesophagogastroduodenoscopy (OGD), ileocolonoscopy, and (except in cases of definitive ulcerative colitis) adequate imaging of the small bowel. To audit and evaluate the diagnostic workup of paediatric patients with IBD in Europe, the Working Group created EUROKIDS, a prospective, Web-based registry of newly diagnosed paediatric patients with IBD. Methods: Patients with IBD (ages 0-18 years) were registered in 44 centres in 18 countries. Data on diagnostic workup were analysed according to the year of diagnosis, type of IBD, and centre size. Diagnostic yield of OGD and ileal intubation were evaluated. Results: Between 2004 and 2009, 2087 newly diagnosed patients were correctly registered. Both OGD and ileocolonoscopy had been performed in 64% of all of the patients and increased significantly from year 1 (52 %) to 5 (71%, P < 0.001). Small-bowel follow-through use decreased during the years (year 1 n ¼ 213, year 5 n ¼ 108; P < 0.001), whereas magnetic resonance imaging use increased (year 1 n ¼ 25, year 5 n ¼ 171; P < 0.001). Patients diagnosed as having Crohn disease (CD, 59%) and ulcerative colitis (58%) were more likely to have had a complete diagnostic workup than patients diagnosed as having IBD unclassified (45%). In CD, the diagnostic yield of OGD was 7.5% and the yield of ileal intubation was 13%. The quality of diagnostic workup in paediatric patients with IBD increased steadily between 2004 and 2009. Small-bowel imaging by magnetic resonance imaging superseded the use of smallbowel follow-through. OGD and ileal intubation contributed to a definitive diagnosis of CD.
Journal of Pediatric Gastroenterology & Nutrition, 2013
Background: The diagnosis of pediatric-onset inflammatory bowel disease (PIBD) can be challenging... more Background: The diagnosis of pediatric-onset inflammatory bowel disease (PIBD) can be challenging in choosing the most informative diagnostic tests and correctly classifying PIBD into its different subtypes. Recent advances in our understanding of the natural history and phenotype of PIBD, increasing availability of serological and fecal biomarkers, and the emergence of novel endoscopic and imaging technologies taken together have made the previous Porto criteria for the diagnosis of PIBD obsolete. Methods: We aimed to revise the original Porto criteria using an evidencebased approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD. These revised criteria are based on the Paris classification of PIBD and the original Porto criteria while incorporating novel data, such as for serum and fecal biomarkers. A consensus of at least 80% of participants was achieved for all recommendations and the summary algorithm. Results: The revised criteria depart from existing criteria by defining 2 categories of ulcerative colitis (UC, typical and atypical); atypical phenotypes of UC should be treated as UC. A novel approach based on multiple criteria for diagnosing IBD-unclassified (IBD-U) is proposed. Specifically, these revised criteria recommend upper gastrointestinal endoscopy and ileocolonscopy for all suspected patients with PIBD, with small bowel imaging (unless typical UC after endoscopy and histology) by magnetic resonance enterography or wireless capsule endoscopy.
Journal of Pediatric Gastroenterology & Nutrition, 2012
Combined immunosuppression by immunomodulators and biological therapy has become standard in the ... more Combined immunosuppression by immunomodulators and biological therapy has become standard in the medical management of moderate-tosevere inflammatory bowel disease (IBD) because of clearly demonstrated efficacy. Clinical studies, registries, and case reports warn of the increased risk of infections, particularly opportunistic infections; however, already in the steroid monotherapy era, patients are at risk because it is accepted that a patient should be considered immunosuppressed when receiving a daily dose of 20 mg of prednisone for 2 weeks. Prescriptions increasingly involve azathioprine, methotrexate, and various biological agents. The TREAT registry evaluated safety in >6000 adult patients, half of them treated with infliximab (IFX) for about 1.9 years. IFX-treated patients had an increased risk of infections and this was associated with disease severity and concomitant prednisone use. The REACH study, evaluating the efficacy of IFX in children with moderate-to-severe Crohn disease, refractory to immunomodulatory treatment, reports serious infections as the major adverse events and their frequency is higher with shorter treatment intervals. The combination of immunosuppressive medications is a risk factor for opportunistic infections. Exhaustive guidelines on prophylaxis, diagnosis, and management of opportunistic infections in adult patients with IBD have been published by a European Crohn's and Colitis Organization working group, including clear evidence-based statements. We have reviewed the literature on infections in pediatric IBD as well as the European Crohn's and Colitis Organization guidelines to present a commentary on infection prophylaxis for the pediatric age group.
Journal of Pediatric Gastroenterology & Nutrition, 2012
Background and Aims: Pediatric ulcerative colitis (UC) shares many features with adult-onset dise... more Background and Aims: Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). Methods: A group of 27 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to ESPGHAN and ECCO members. A list of 23 predefined questions were addressed by working subgroups based on a SR of the literature. Results: A total of 40 formal recommendations and 68 practice points were endorsed with a consensus rate of at least 89% regarding initial evaluation, how to monitor disease activity, the role of endoscopic evaluation, medical and surgical therapy, timing and choice of each medication, the role of combined therapy, and when to stop medications. A management flowchart, based on the Pediatric Ulcerative Colitis Activity Index (PUCAI), is presented. Conclusions: These guidelines provide clinically useful points to guide the management of UC in children. Taken together, the recommendations offer a standardized protocol that allows effective, timely management and
Journal of Crohn's and Colitis, 2013
Background and aims: Successful transfer of adolescent IBD patients to an adult gastroenterologis... more Background and aims: Successful transfer of adolescent IBD patients to an adult gastroenterologist requires anticipation of a changing role for patients and their parents. Self-efficacy has been demonstrated to be important for transfer readiness. We therefore developed an IBD-specific questionnaire (the "IBD-yourself") to assess self-efficacy in adolescent IBD patients visiting a transition clinic. Our aim was to evaluate the reliability of this questionnaire, and to describe the self-efficacy level of adolescent IBD patients, and the perceived self-efficacy level according to their parents. Methods: In a cross-sectional design, 50 IBD patients (aged 14-18 years) and 40 parents completed the "IBD-yourself" questionnaire. Internal reliability was assessed by standardised Cronbach's α. Median self-efficacy scores per domain were calculated. Results: The domains of the questionnaire for adolescents showed good to excellent internal consistency, with Cronbach's α ranging from 0.64 to 0.93. The domains of the parental questionnaire had Cronbach's α ranging from 0.47 to 0.93. Median self-efficacy scores of adolescents varied from 70 to 100%. In comparison with patient's self-assessment, parents thought that their child was more Abbreviations: IBD-SES, IBD Self-efficacy Scale; IQR, Interquartile range; SD, Standard deviation; SEm, Standard error of the measurement; VAS, Visual analogue scale. ☆ Conference presentation: Poster presentation during the 4th congress of ECCO,
Inflammatory Bowel Diseases, 2006
The intestinal microbiota may play a role in the disease process of IBD. In this study we examine... more The intestinal microbiota may play a role in the disease process of IBD. In this study we examined the small and large intestinal microbiota in children at the time of diagnosis of IBD, before medical treatment had been instituted. Patients and methods: Faecal samples were obtained from children with suspected IBD before bowel cleaning and duodenal fluids at duodenalscopy. The samples were transported anaerobically and cultivated quantitatively for aerobic and anaerobic bacteria within 24h. After diagnosis was established, microbiota composition was compared between the diagnostic groups; ulcerative colitis (UC n¼20), Crohn's disease (CD, n¼10) and diseased controls i.e. children in whom the IBD diagnosis was excluded and with no histological signs of mucosal inflammation (n¼24). Faecal samples from healthy control children (n¼11) were also included for comparison. Children with indeterminate colitis (n¼1), other type of colitis (allergic, infectious, unspecific n¼8) and celiac disease (n¼2) were excluded from the analyses due to small group numbers. Results: The duodenal microbiota did not differ significantly between the diagnostic groups. In contrast children with UC had a distinctly different faecal microbiota compared with diseased and healthy controls. Thus, children with UC had a significantly lower ratio of anaerobic to facultative bacteria in faeces (respectively 30 compared with 500 in diseased and healthy controls, p¼0.0001 and p¼0.001). Further, children in the UC group had lower counts of anaerobic bacteria (average: 10 8.8 Colony Forming Unit, CFU/g faeces) compared with diseased (10 10.1 CFU/g faeces) and healthy (10 10.2 CFU/g faeces) controls (p ¼ 0.0001 for both). The low proportion of anaerobic bacteria in the UC group was unrelated to frequency of diarrhoea or to precence of blood in stools. Among the anaerobes, bifidobacteria and clostridia were both significantly reduced in children with UC compared with diseased controls (p ¼ 0.002 and p ¼ 0.03, respectively) and healthy controls (p ¼ 0.006 and p ¼ 0.02, respectively), whereas the counts of Bacteroides did not differ between the diagnostic groups. Furthermore, the children presenting with UC had significantly increased ratio of Gram-negative to Gram-positive bacteria in faeces compared with diseased (p ¼ 0.02) and healthy (p ¼ 0.03) controls. Conclusions: The results suggest that the microbiota in UC is dysbalanced with a relative lack of certain Gram-positive anaerobes and a relative increase in facultative and Gram-negative bacteria. This dysbalanced microbiota in the colon might provoke and perpetuate inflammation.
Inflammatory Bowel Diseases, 2012
Background: Fecal Calprotectin (FC) is a validated screening test for intestinal inflammation in ... more Background: Fecal Calprotectin (FC) is a validated screening test for intestinal inflammation in Crohn's disease (CD). The objective of the study was to prospectively evaluate the limitations of FC for identifying CD in newly diagnosed untreated pediatric patients and to assess the association of FC levels with disease location and serum inflammatory markers. Methods: Consecutive children with new onset untreated CD participating in the ongoing ESPGHAN GROWTH CD study were evaluated at diagnosis for disease activity, extent, C-reactive protein (CRP), and FC. Results: In all, 60 children met the inclusion criteria (mean age 12.6 6 4.6 years,), 25 (42%) with mild disease, 17 (28%) moderate disease, and 18 (30%) severe disease. Twenty-seven (45%) had small bowel disease only. Median FC levels did not differ between children with small bowel only (2198 lg/g interquartile range [IQR] 696-2400) and those with colonic involvement (with or without small bowel disease; 2400 lg/g (IQR 475-2400) (P ¼ 0.76). FC was elevated in 95% of patients, in comparison to CRP (86%) and erythrocyte sedimentation rate (ESR) (83%). Three children (5%) who had normal calprotectin levels also had low or normal CRP and/or ESR. There was no correlation between calprotectin levels and either the pediatric CD activity index (r ¼ À0.11; P ¼ 0.94) or physicians global assessment. Conclusions: FC levels in active disease confined to the small bowel were elevated in the vast majority of children and site of disease was not a confounding factor in this setting. Patients with low FC had a trend toward low levels of inflammatory markers as well. We did not find a significant correlation between FC and clinical indices of activity (Inflamm Bowel Dis 2012;000:000-000)
Infliximab dependency in pediatric Crohnʼs disease: Long-term follow-up of an unselected cohort
Inflammatory Bowel Diseases, 2008
Infliximab is effective for induction and maintenance of remission in Crohn&amp;amp;amp;a... more Infliximab is effective for induction and maintenance of remission in Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. It is unknown how long patients should be kept on infliximab therapy. The primary aim of this study was to assess duration of effective maintenance therapy and infliximab dependency in pediatric CD patients initially responding to infliximab therapy. All pediatric patients treated with infliximab by pediatric gastroenterologists in the Netherlands because of severe luminal or fistulizing CD with initial response to infliximab therapy were reviewed. Duration of therapy, clinical response and adverse events were recorded. Sixty-six CD patients (37 boys) in 10 hospitals were initially responding to infliximab therapy. Mean age at the start of infliximab therapy was 14.5 years (range, 8.1-18.5 years). Mean follow-up since infliximab was started was 41.3 months (range 12-165). In total, 991 infusions were administered. Analysis demonstrates that 15.2% of patients had prolonged response, while 56.1% were infliximab dependent and 28.8% lost response. In total, 10 patients (15.2%) developed an infection during infliximab therapy and 8 (12.1%) had an immediate allergic reaction. Good clinical response to maintenance infliximab therapy was seen in 70% of patients. Infliximab maintenance therapy seems very effective and safe in pediatric CD. However, more than half of the patients in this cohort is dependent on repeated infliximab infusions. The number of infliximab infusions received when patients lost response to infliximab was diverse. There was no statistical difference regarding response to infliximab therapy when started early as compared to later in the course of Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease.
Inflammatory Bowel Diseases, 2012
Infliximab, adalimumab, and certolizumab are monoclonal antibodies against tumor necrosis factor-... more Infliximab, adalimumab, and certolizumab are monoclonal antibodies against tumor necrosis factor-a (TNFa), a proinflammatory cytokine with an increased expression in the inflamed tissues of inflammatory bowel disease (IBD) patients. Currently, infliximab is the only anti-TNF drug that has been approved for use in refractory pediatric Crohn's disease (CD). Nevertheless, adalimumab and certolizumab have been used off-label to treat refractory pediatric IBD. Over the past 10 years, anti-TNF treatment has been of great benefit to many pediatric IBD patients, but their use is not without risks (infections, autoimmune diseases, malignancies). Despite the growing experience with these drugs in children with IBD, optimal treatment strategies still need to be determined. The purpose of this review is to summarize the current knowledge on the use of anti-TNF drugs in pediatric IBD and to discuss the yet-unsolved issues.
Rotterdam Transition Test: A Valid Tool for Monitoring Disease Knowledge in Adolescents With Inflammatory Bowel Disease
Journal of Pediatric Gastroenterology & Nutrition, 2021
Objectives: Disease knowledge is important in adolescents with inflammatory bowel disease (IBD) t... more Objectives: Disease knowledge is important in adolescents with inflammatory bowel disease (IBD) transitioning to adult care. We developed an IBD-specific knowledge questionnaire, the Rotterdam Transition Test (RTT), and aimed to validate this tool. Methods: This is a prospective longitudinal validation study. The RTT has 25 open questions on IBD, medication, lifestyle, and transition to adult care. A scoring model was developed, and inter-rater agreement was assessed. Using a Rasch model, we determined the difficulty and performance of the questions. Cronbach alpha was used to demonstrate reliability. Patient factors (age, disease, education, medication use, illness acceptance, and independence) were correlated to RTT score. Results: A total of 207 RTTs were evaluated in 111 adolescent IBD patients. The scoring model showed a kappa score of >0.61 for all questions. Reliability with Cronbach alpha was good (0.81). Mean total result of the RTT was 58% (girls) and 55% (boys) of maxi...
Mucosal Immunology, 2018
Disease heterogeneity hampers achieving long-term disease remission in inflammatory bowel disease... more Disease heterogeneity hampers achieving long-term disease remission in inflammatory bowel disease (IBD). Monitoring ongoing tissue-localized regulatory and inflammatory T-cell responses in peripheral blood would empower disease classification. We determined whether regulatory and inflammatory phenotypes of circulating CD38 + effector (CD62L neg CD4 + ) T cells, a population enriched for cells with mucosal antigen specificity, classify disease course in pediatric IBD patients. In healthy individuals, circulating CD38 + effector T cells had a predominant regulatory component with lower frequencies of IFNγ-secreting T cells, higher frequencies of IL-10-secreting T cells and higher frequencies of inhibitory molecule T-cell immunoglobulin and ITIM domain + (TIGIT) cells than CD38 neg effector T cells. TIGIT expression was stable upon stimulation and marked CD38 + T cells with inhibitory properties. In IBD patients with active intestinal inflammation this predominant regulatory component was lost: circulating CD38 + effector T cells had increased activated CD25 + CD45RA neg and decreased TIGIT + cell frequencies. TIGIT percentages below 25% before treatment associated with shorter duration of clinical remission. In conclusion, phenotypic changes in circulating CD38 + effector T cells, in particular the frequency of TIGIT + cells, classify pediatric IBD patients and predict severity of disease course. These findings have relevance for IBD and can be exploited in graft-versus-host-disease and checkpoint inhibitor-induced inflammation in cancer.
Journal of Crohn's & colitis, Jan 25, 2018
There is no standardized endoscopic description of upper gastrointestinal (UGI) disease in Crohn&... more There is no standardized endoscopic description of upper gastrointestinal (UGI) disease in Crohn's disease (CD). We prospectively applied the Simple Endoscopic Score for CD (SES-CD) to the UGI tract as a planned sub-study of the multicenter prospective ImageKids study. We aimed to assess the utility of the UGI-SES-CD and its clinical significance in pediatric CD. Patients underwent an esophagogastroduodenoscopy (EGD), ileocolonoscopy and magnetic resonance enterography (MRE) with explicit clinical data recorded. SES-CD was scored at each region (esophagus, stomach body, antrum and duodenum). Half of the patients were followed for 18 months when a repeat MRE was performed. Two hundred and two children were included (56% males, mean age 11.5 ± 3.2 years, median wPCDAI 25. UGI-SES-CD score ranged from 0-17, with 95 (47%) having a UGI-SES-CD ≥1; no narrowing was detected. UGI-SES-CD ≥1 was associated with higher wPCDAI (32.5 vs 20; p=0.03), PGA of inflammation (45mmVAS vs 30mmVAS; p...
Journal of Crohn's & colitis, Jan 9, 2017
Vedolizumab, an anti-integrin antibody, has proven to be effective in adults with Inflammatory Bo... more Vedolizumab, an anti-integrin antibody, has proven to be effective in adults with Inflammatory Bowel Disease (IBD), but the data in pediatrics are limited. We describe the short-term effectiveness and safety of vedolizumab in a European multi-center pediatric IBD cohort. Retrospective review of children (2-18 years) treated with vedolizumab from 19 centers affiliated with the Paediatric IBD Porto group of ESPGHAN. Primary outcome was week 14 corticosteroid-free remission (CFR). 64 children were included [32 (50%) male, mean age 14.5 ± 2.8 years, with a median follow-up 24 weeks (IQR 14-38; range 6-116)]; 41 (64%) UC/IBDU and 23 (36%) CD. All were previously treated with anti-TNF (28% primary failure, 53% secondary failure). Week 14 CFR was 37% in UC, and 14% in CD (p=0.06). CFR by last follow-up was 39% in UC and 24% in CD (p=0.24). Ten (17%) children required surgery, 6 of whom had colectomy for UC. Concomitant immunomodulatory drugs did not affect remission rate (42% vs 35%; p=0.3...
[Infliximab therapy in children and adolescents with refractory Crohn's disease in the Netherlands; experience with 23 patients]
Nederlands tijdschrift voor geneeskunde, Jan 5, 2002
To describe the clinical experience of infliximab treatment in children and adolescents with refr... more To describe the clinical experience of infliximab treatment in children and adolescents with refractory Crohn's disease in the Netherlands. Descriptive. From November 1998 to February 2002, 23 patients (aged 7-18 years) with refractory Crohn's disease or steroid-dependent Crohn's disease (with or without severe fistulas) were treated with infliximab. Patients were treated with 1-11 infusions, with an average follow-up of 14.5 months after the start of infliximab therapy. Ten patients had refractory Crohn's disease. Four of these showed good long-term response on infliximab treatment (modified 'Paediatric Crohn's disease activity index' (PCDAI) < or = 10 points or growth acceleration after stunting). Twelve patients had Crohn's disease with severe fistulas. Five of these showed good long-term response (closure or non-productiveness of fistulas). One patient had metastatic Crohn's disease in the skin and showed good long-term response. Response r...
Dysfagie op de kinderleeftijd
Tijdschrift voor Kindergeneeskunde, 2011
Samenvatting Patiënt A, een 13-jarige jongen, werd verwezen vanwege een slokdarmperforatie, onts... more Samenvatting Patiënt A, een 13-jarige jongen, werd verwezen vanwege een slokdarmperforatie, ontstaan tijdens endoscopie vanwege voedselimpactie in de slokdarm. Bij histologisch onderzoek van de slokdarmmucosa werd een eosinofielrijk infiltraat aangetroffen; de jongen werd behandeld met elementaire sondevoeding en prednison. Bij patiënt B, een tweejarige jongen met hardnekkige klachten van hoesten en braken, werd niet, zoals verwacht, gastro-oesofageale refluxziekte vastgesteld, maar eosinofilie
Journal of Crohn's and Colitis, 2015
Background and aims: Methotrexate [MTX] is an immunomodulating drug that can be used to maintain ... more Background and aims: Methotrexate [MTX] is an immunomodulating drug that can be used to maintain remission in patients with Crohn's disease [CD], but data on efficacy and tolerability in children and teenagers are scarce. We evaluated the long-term efficacy and tolerability of MTX monotherapy after thiopurine therapy in paediatric CD patients. Methods: A multicenter cohort of paediatric MTX users who stopped thiopurines due to ineffectiveness or intolerance between 2002 and 2012 were included and followed for at least 12 months. Relapse-free use was defined as steroid and biologics-free clinical remission after the introduction of MTX, and included intentional discontinuation of successful therapy before the end of the observation period. Results: A total of 113 patients with CD in remission were followed while on MTX monotherapy, of whom 75 [66%] had failed on thiopurines and 38 [34%] had stopped thiopurines due to side effects. Median age at the introduction of MTX was 14 years [range 7 to 17], and 93% used the subcutaneous route. Kaplan-Meier analysis showed that 52% of the study cohort were still in steroid-and biologics-free remission after 12 months of MTX monotherapy, with a difference that did not reach significance between thiopurine-intolerant and thiopurine-failing patients [p = 0.21, log-rank test]. The findings of this cohort study suggest that MTX is an effective immunomodulator to maintain remission after stopping thiopurines. MTX maintenance should be considered before stepping up to anti-tumor necrosis factor alpha therapy. MTX is probably somewhat more effective in patients who stopped thiopurines due to side effects than in those who failed on thiopurines.
Journal of Crohn's and Colitis, 2014
Introduction: Contemporary data describing treatment practices and outcomes of children with Croh... more Introduction: Contemporary data describing treatment practices and outcomes of children with Crohn's disease (CD) are limited. Aim: To describe the effect of initial treatments on clinical outcomes in children with newly diagnosed CD. Methods: Data (diagnosis, 30 day, quarterly) were extracted from a multicenter North American observational registry. Four year outcomes of cohorts diagnosed 2002 4 (Grp1) and 2007 9 (Grp2) were compared. Results: Treatments and outcomes were similar in both cohorts. Among 349 children presenting with moderate severe CD, 75 80% received corticosteroids and/or immunomodulators by 30d and Q1, and 7 14% received anti-TNF. Among 126 presenting with mild CD, 60 75% received corticosteroids and/or immunomodulators by 30d or Q1. By Q1, 9% received anti-TNF. Many children presenting with either mild or moderate severe CD received 5ASA as their only induction therapy (Mild: 30d = 40%, Q1 = 30%; Moderate-severe: 30d = 15%, Q1 = 11%). Regardless of initial CD activity or treatment by 30d, only 15 20% of subjects had inactive CD in all 4 quarterly assessments through Yr1. 30% of those with initial moderate severe CD continued to have periods of moderate severe activity in Yr1, and 15 30% in Yr2 4. For those presenting with mild CD, 10 30% had periods of moderate severe activity in Yr1, and 15 25% in Yr2 4. However, <10% of all subjects had 3 4 years with periods of moderate severe activity. Hospitalizations (Grp1 = 38%, Grp2 = 45%), IBD surgery (Grp1 = 11%, Grp2 = 19%) and change in growth Z-scores were comparable between cohorts. Conclusions: Periods of moderate severe activity continue to occur in 15 25% of children with CD despite current treatments. Re-assessment of treatment utilization appears warranted. Ten years of paediatric inflammatory bowel disease incidence in the north of Scotland
Inflammatory Bowel Diseases, 2015
Sexual health is a broad term that encompasses a variety of functions including sexual thoughts, ... more Sexual health is a broad term that encompasses a variety of functions including sexual thoughts, desire, arousal, intercourse, orgasm, and the impact of body image. Sexual dysfunction in individuals with inflammatory bowel disease is multifactorial including the impact of psychosocial factors, disease activity, medical therapies, surgical interventions, body image perceptions and changes, hypogonadism, and pelvic floor disorders. Providers caring for patients with inflammatory bowel disease should be cognizant of these concerns and develop management plans and techniques for earlier diagnosis and treatment.
Percutaneous endoscopic gastrostomy (PEG) in children is not a minor procedure: risk factors for major complications
Seminars in Pediatric Surgery, 2009
Percutaneous endoscopic gastrostomy (PEG) provides for enteral nutrition in children with feeding... more Percutaneous endoscopic gastrostomy (PEG) provides for enteral nutrition in children with feeding problems. PEG, however, is not without complications. The present study has a twofold aim: (1) comparing our incidence of major complications after PEG with the incidence in other centers, and (2) identifying risk factors for major complications. All patients receiving a PEG or laparoscopic-assisted PEG (lap PEG) in the period 1992-2008 were reviewed. Primary outcome was the occurrence of major complications, defined as the need for surgery, non-prophylactic antibiotics, or blood transfusion, and procedure-related death. Potential risk factors, eg, age under 1 year, mental retardation, scoliosis, constipation, hepatomegaly, upper abdominal surgery, ventriculoperitoneal shunt, peritoneal dialysis, esophageal stenosis, and coagulopathy, were analyzed. Of the 467 patients (448 PEG, 19 lap PEG), 12.6% developed major complications. The complication rate significantly decreased (P = 0.003) over the years. A significantly higher complication rate of 32% (P = 0.02) occurred in children with a ventriculoperitoneal shunt. None of the lap PEG procedures was associated with a major complication, but the difference was not significant, perhaps because of the small numbers in the latter group. The major complication rate after PEG in children is high. Preexisting ventriculoperitoneal shunt is a significant risk factor. Laparoscopically assisted PEG procedures seem to be associated with a lesser major complication rate.
Journal of Pediatric Gastroenterology & Nutrition, 2015
Objectives: Adalimumab, a humanised anti-tumour necrosis factor antibody, is an effective treatme... more Objectives: Adalimumab, a humanised anti-tumour necrosis factor antibody, is an effective treatment in adult patients with refractory Crohn disease (CD). The available literature on its efficacy in children remains limited. We aimed to evaluate the real-world efficacy in paediatric patients with CD and compare the efficacy between infliximab (IFX) nonresponders and patients who lost response to IFX. Methods: All Dutch patients with CD receiving adalimumab before the age of 18 years after previous IFX therapy were identified. We analysed longitudinal disease activity, assessed by the mathematically weighted Pediatric Crohn's Disease Activity Index (wPCDAI) or the physician global assessment (PGA), and adverse events (AEs). Results: Fifty-three patients with CD were included. Twelve patients received monotherapy and the others received combination treatment with thiopurines (n ¼ 21), methotrexate (n ¼ 11), steroids (n ¼ 7), or exclusive enteral nutrition (n ¼ 2). Median follow-up was 12 months (interquartile range 5-23). Remission was reached in 34 patients (64%, wPCDAI < 12.5 or PGA ¼ 0) after a median of 3.3 months, and maintained by 50% for 2 years. Eleven patients (21%) reached response but not remission (decrease in wPCDAI ! 17.5 or decrease in PGA). Eighteen patients (34%) failed adalimumab treatment because of nonresponse (n ¼ 4), lost response (n ¼ 11), or AEs (n ¼ 3). More IFX nonresponders failed adalimumab treatment than patients who lost response to IFX (2/3 vs 8/34, hazard ratio 18.8, 95% confidence interval 1.1-303.6). Only 1 patient encountered a serious AE, a severe but nonfatal infection. Conclusions: In clinical practice, adalimumab induces remission in twothirds of children with IFX refractory CD.
Journal of Pediatric Gastroenterology & Nutrition, 2012
Objective: In 2005, the Inflammatory Bowel Disease (IBD) Working Group of the European Society fo... more Objective: In 2005, the Inflammatory Bowel Disease (IBD) Working Group of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition published consensus guidelines on the diagnostic workup of paediatric IBD, the Porto criteria. According to these guidelines, children suspected of having IBD should undergo an oesophagogastroduodenoscopy (OGD), ileocolonoscopy, and (except in cases of definitive ulcerative colitis) adequate imaging of the small bowel. To audit and evaluate the diagnostic workup of paediatric patients with IBD in Europe, the Working Group created EUROKIDS, a prospective, Web-based registry of newly diagnosed paediatric patients with IBD. Methods: Patients with IBD (ages 0-18 years) were registered in 44 centres in 18 countries. Data on diagnostic workup were analysed according to the year of diagnosis, type of IBD, and centre size. Diagnostic yield of OGD and ileal intubation were evaluated. Results: Between 2004 and 2009, 2087 newly diagnosed patients were correctly registered. Both OGD and ileocolonoscopy had been performed in 64% of all of the patients and increased significantly from year 1 (52 %) to 5 (71%, P < 0.001). Small-bowel follow-through use decreased during the years (year 1 n ¼ 213, year 5 n ¼ 108; P < 0.001), whereas magnetic resonance imaging use increased (year 1 n ¼ 25, year 5 n ¼ 171; P < 0.001). Patients diagnosed as having Crohn disease (CD, 59%) and ulcerative colitis (58%) were more likely to have had a complete diagnostic workup than patients diagnosed as having IBD unclassified (45%). In CD, the diagnostic yield of OGD was 7.5% and the yield of ileal intubation was 13%. The quality of diagnostic workup in paediatric patients with IBD increased steadily between 2004 and 2009. Small-bowel imaging by magnetic resonance imaging superseded the use of smallbowel follow-through. OGD and ileal intubation contributed to a definitive diagnosis of CD.
Journal of Pediatric Gastroenterology & Nutrition, 2013
Background: The diagnosis of pediatric-onset inflammatory bowel disease (PIBD) can be challenging... more Background: The diagnosis of pediatric-onset inflammatory bowel disease (PIBD) can be challenging in choosing the most informative diagnostic tests and correctly classifying PIBD into its different subtypes. Recent advances in our understanding of the natural history and phenotype of PIBD, increasing availability of serological and fecal biomarkers, and the emergence of novel endoscopic and imaging technologies taken together have made the previous Porto criteria for the diagnosis of PIBD obsolete. Methods: We aimed to revise the original Porto criteria using an evidencebased approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD. These revised criteria are based on the Paris classification of PIBD and the original Porto criteria while incorporating novel data, such as for serum and fecal biomarkers. A consensus of at least 80% of participants was achieved for all recommendations and the summary algorithm. Results: The revised criteria depart from existing criteria by defining 2 categories of ulcerative colitis (UC, typical and atypical); atypical phenotypes of UC should be treated as UC. A novel approach based on multiple criteria for diagnosing IBD-unclassified (IBD-U) is proposed. Specifically, these revised criteria recommend upper gastrointestinal endoscopy and ileocolonscopy for all suspected patients with PIBD, with small bowel imaging (unless typical UC after endoscopy and histology) by magnetic resonance enterography or wireless capsule endoscopy.
Journal of Pediatric Gastroenterology & Nutrition, 2012
Combined immunosuppression by immunomodulators and biological therapy has become standard in the ... more Combined immunosuppression by immunomodulators and biological therapy has become standard in the medical management of moderate-tosevere inflammatory bowel disease (IBD) because of clearly demonstrated efficacy. Clinical studies, registries, and case reports warn of the increased risk of infections, particularly opportunistic infections; however, already in the steroid monotherapy era, patients are at risk because it is accepted that a patient should be considered immunosuppressed when receiving a daily dose of 20 mg of prednisone for 2 weeks. Prescriptions increasingly involve azathioprine, methotrexate, and various biological agents. The TREAT registry evaluated safety in >6000 adult patients, half of them treated with infliximab (IFX) for about 1.9 years. IFX-treated patients had an increased risk of infections and this was associated with disease severity and concomitant prednisone use. The REACH study, evaluating the efficacy of IFX in children with moderate-to-severe Crohn disease, refractory to immunomodulatory treatment, reports serious infections as the major adverse events and their frequency is higher with shorter treatment intervals. The combination of immunosuppressive medications is a risk factor for opportunistic infections. Exhaustive guidelines on prophylaxis, diagnosis, and management of opportunistic infections in adult patients with IBD have been published by a European Crohn's and Colitis Organization working group, including clear evidence-based statements. We have reviewed the literature on infections in pediatric IBD as well as the European Crohn's and Colitis Organization guidelines to present a commentary on infection prophylaxis for the pediatric age group.
Journal of Pediatric Gastroenterology & Nutrition, 2012
Background and Aims: Pediatric ulcerative colitis (UC) shares many features with adult-onset dise... more Background and Aims: Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). Methods: A group of 27 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to ESPGHAN and ECCO members. A list of 23 predefined questions were addressed by working subgroups based on a SR of the literature. Results: A total of 40 formal recommendations and 68 practice points were endorsed with a consensus rate of at least 89% regarding initial evaluation, how to monitor disease activity, the role of endoscopic evaluation, medical and surgical therapy, timing and choice of each medication, the role of combined therapy, and when to stop medications. A management flowchart, based on the Pediatric Ulcerative Colitis Activity Index (PUCAI), is presented. Conclusions: These guidelines provide clinically useful points to guide the management of UC in children. Taken together, the recommendations offer a standardized protocol that allows effective, timely management and
Journal of Crohn's and Colitis, 2013
Background and aims: Successful transfer of adolescent IBD patients to an adult gastroenterologis... more Background and aims: Successful transfer of adolescent IBD patients to an adult gastroenterologist requires anticipation of a changing role for patients and their parents. Self-efficacy has been demonstrated to be important for transfer readiness. We therefore developed an IBD-specific questionnaire (the "IBD-yourself") to assess self-efficacy in adolescent IBD patients visiting a transition clinic. Our aim was to evaluate the reliability of this questionnaire, and to describe the self-efficacy level of adolescent IBD patients, and the perceived self-efficacy level according to their parents. Methods: In a cross-sectional design, 50 IBD patients (aged 14-18 years) and 40 parents completed the "IBD-yourself" questionnaire. Internal reliability was assessed by standardised Cronbach's α. Median self-efficacy scores per domain were calculated. Results: The domains of the questionnaire for adolescents showed good to excellent internal consistency, with Cronbach's α ranging from 0.64 to 0.93. The domains of the parental questionnaire had Cronbach's α ranging from 0.47 to 0.93. Median self-efficacy scores of adolescents varied from 70 to 100%. In comparison with patient's self-assessment, parents thought that their child was more Abbreviations: IBD-SES, IBD Self-efficacy Scale; IQR, Interquartile range; SD, Standard deviation; SEm, Standard error of the measurement; VAS, Visual analogue scale. ☆ Conference presentation: Poster presentation during the 4th congress of ECCO,
Inflammatory Bowel Diseases, 2006
The intestinal microbiota may play a role in the disease process of IBD. In this study we examine... more The intestinal microbiota may play a role in the disease process of IBD. In this study we examined the small and large intestinal microbiota in children at the time of diagnosis of IBD, before medical treatment had been instituted. Patients and methods: Faecal samples were obtained from children with suspected IBD before bowel cleaning and duodenal fluids at duodenalscopy. The samples were transported anaerobically and cultivated quantitatively for aerobic and anaerobic bacteria within 24h. After diagnosis was established, microbiota composition was compared between the diagnostic groups; ulcerative colitis (UC n¼20), Crohn's disease (CD, n¼10) and diseased controls i.e. children in whom the IBD diagnosis was excluded and with no histological signs of mucosal inflammation (n¼24). Faecal samples from healthy control children (n¼11) were also included for comparison. Children with indeterminate colitis (n¼1), other type of colitis (allergic, infectious, unspecific n¼8) and celiac disease (n¼2) were excluded from the analyses due to small group numbers. Results: The duodenal microbiota did not differ significantly between the diagnostic groups. In contrast children with UC had a distinctly different faecal microbiota compared with diseased and healthy controls. Thus, children with UC had a significantly lower ratio of anaerobic to facultative bacteria in faeces (respectively 30 compared with 500 in diseased and healthy controls, p¼0.0001 and p¼0.001). Further, children in the UC group had lower counts of anaerobic bacteria (average: 10 8.8 Colony Forming Unit, CFU/g faeces) compared with diseased (10 10.1 CFU/g faeces) and healthy (10 10.2 CFU/g faeces) controls (p ¼ 0.0001 for both). The low proportion of anaerobic bacteria in the UC group was unrelated to frequency of diarrhoea or to precence of blood in stools. Among the anaerobes, bifidobacteria and clostridia were both significantly reduced in children with UC compared with diseased controls (p ¼ 0.002 and p ¼ 0.03, respectively) and healthy controls (p ¼ 0.006 and p ¼ 0.02, respectively), whereas the counts of Bacteroides did not differ between the diagnostic groups. Furthermore, the children presenting with UC had significantly increased ratio of Gram-negative to Gram-positive bacteria in faeces compared with diseased (p ¼ 0.02) and healthy (p ¼ 0.03) controls. Conclusions: The results suggest that the microbiota in UC is dysbalanced with a relative lack of certain Gram-positive anaerobes and a relative increase in facultative and Gram-negative bacteria. This dysbalanced microbiota in the colon might provoke and perpetuate inflammation.
Inflammatory Bowel Diseases, 2012
Background: Fecal Calprotectin (FC) is a validated screening test for intestinal inflammation in ... more Background: Fecal Calprotectin (FC) is a validated screening test for intestinal inflammation in Crohn's disease (CD). The objective of the study was to prospectively evaluate the limitations of FC for identifying CD in newly diagnosed untreated pediatric patients and to assess the association of FC levels with disease location and serum inflammatory markers. Methods: Consecutive children with new onset untreated CD participating in the ongoing ESPGHAN GROWTH CD study were evaluated at diagnosis for disease activity, extent, C-reactive protein (CRP), and FC. Results: In all, 60 children met the inclusion criteria (mean age 12.6 6 4.6 years,), 25 (42%) with mild disease, 17 (28%) moderate disease, and 18 (30%) severe disease. Twenty-seven (45%) had small bowel disease only. Median FC levels did not differ between children with small bowel only (2198 lg/g interquartile range [IQR] 696-2400) and those with colonic involvement (with or without small bowel disease; 2400 lg/g (IQR 475-2400) (P ¼ 0.76). FC was elevated in 95% of patients, in comparison to CRP (86%) and erythrocyte sedimentation rate (ESR) (83%). Three children (5%) who had normal calprotectin levels also had low or normal CRP and/or ESR. There was no correlation between calprotectin levels and either the pediatric CD activity index (r ¼ À0.11; P ¼ 0.94) or physicians global assessment. Conclusions: FC levels in active disease confined to the small bowel were elevated in the vast majority of children and site of disease was not a confounding factor in this setting. Patients with low FC had a trend toward low levels of inflammatory markers as well. We did not find a significant correlation between FC and clinical indices of activity (Inflamm Bowel Dis 2012;000:000-000)
Infliximab dependency in pediatric Crohnʼs disease: Long-term follow-up of an unselected cohort
Inflammatory Bowel Diseases, 2008
Infliximab is effective for induction and maintenance of remission in Crohn&amp;amp;amp;a... more Infliximab is effective for induction and maintenance of remission in Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. It is unknown how long patients should be kept on infliximab therapy. The primary aim of this study was to assess duration of effective maintenance therapy and infliximab dependency in pediatric CD patients initially responding to infliximab therapy. All pediatric patients treated with infliximab by pediatric gastroenterologists in the Netherlands because of severe luminal or fistulizing CD with initial response to infliximab therapy were reviewed. Duration of therapy, clinical response and adverse events were recorded. Sixty-six CD patients (37 boys) in 10 hospitals were initially responding to infliximab therapy. Mean age at the start of infliximab therapy was 14.5 years (range, 8.1-18.5 years). Mean follow-up since infliximab was started was 41.3 months (range 12-165). In total, 991 infusions were administered. Analysis demonstrates that 15.2% of patients had prolonged response, while 56.1% were infliximab dependent and 28.8% lost response. In total, 10 patients (15.2%) developed an infection during infliximab therapy and 8 (12.1%) had an immediate allergic reaction. Good clinical response to maintenance infliximab therapy was seen in 70% of patients. Infliximab maintenance therapy seems very effective and safe in pediatric CD. However, more than half of the patients in this cohort is dependent on repeated infliximab infusions. The number of infliximab infusions received when patients lost response to infliximab was diverse. There was no statistical difference regarding response to infliximab therapy when started early as compared to later in the course of Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease.
Inflammatory Bowel Diseases, 2012
Infliximab, adalimumab, and certolizumab are monoclonal antibodies against tumor necrosis factor-... more Infliximab, adalimumab, and certolizumab are monoclonal antibodies against tumor necrosis factor-a (TNFa), a proinflammatory cytokine with an increased expression in the inflamed tissues of inflammatory bowel disease (IBD) patients. Currently, infliximab is the only anti-TNF drug that has been approved for use in refractory pediatric Crohn's disease (CD). Nevertheless, adalimumab and certolizumab have been used off-label to treat refractory pediatric IBD. Over the past 10 years, anti-TNF treatment has been of great benefit to many pediatric IBD patients, but their use is not without risks (infections, autoimmune diseases, malignancies). Despite the growing experience with these drugs in children with IBD, optimal treatment strategies still need to be determined. The purpose of this review is to summarize the current knowledge on the use of anti-TNF drugs in pediatric IBD and to discuss the yet-unsolved issues.