Crohn Disease: Escher JC

Oliva-Hemker M, Escher JC, Moore D, Dubinksy M, Hildebrand H, Koda YK, Murch S, Sandhu B, Seo JK, Tanzi MN, Warner B, Anonymous00097. · Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD 21287-2631, USA. · J Pediatr Gastroenterol Nutr. · Pubmed #18664886 No free full text.

This publication has no abstract.

Cucchiara S, Escher JC, Hildebrand H, Amil-Dias J, Stronati L, Ruemmele FM. · Pediatric Gastroenterology Unit, University of Rome La Sapienza, University Hospital Umberto I, Rome, Italy. · J Pediatr Gastroenterol Nutr. · Pubmed #19274777 No free full text.

Abstract: Inflammatory bowel diseases (IBDs) are lifelong inflammatory gastrointestinal diseases starting in about one third of patients during childhood. Treatment strategies aim to control this chronic inflammatory process. Owing to recent advances in the understanding of IBD, immunosuppressive agents (mainly against TNFalpha directed) as well as biological drugs are more and more often used. This therapeutic approach clearly improved the clinical condition of the majority of patients with IBD. However, with this more aggressive treatment strategy, safety concerns clearly arise. Recently, the description of a series of a particularly severe form of T cell lymphoma in pediatric and young adult patients with IBD under immunomodulator and biological combination therapy raised the question of the risks of treatment-induced side effects or complications. As reviewed in the present article, there is a slightly increased risk of not only lymphoma development in IBD patients, potentially related to the inflammatory process, but also to the use of immunosuppressive therapies. On the basis of the literature data, were analyzed current treatment strategies for children with moderate-to-severe IBD, who are candidates to receive immunomodulator and/or biological agents potentially accelerating the risk of lymphoma development. Comparative clinical studies in IBD are still missing; however, it is prudent to think about adapting immunosuppressive therapies to the inflammatory process of the underlying disorder and if possible to reduce them to monotherapy. Alternative treatment strategies for heavy immunosuppression exist (eg, enteral nutrition in Crohn disease or colectomy in patients with ulcerative colitis) and should be considered whenever appropriate. There is a major need for comparative studies before evidence-based guidelines can be established for safest and best treatment strategies of pediatric patients with IBD.

van Lierop PP, Samsom JN, Escher JC, Nieuwenhuis EE. · Department of Pediatric Gastroenterology, Erasmus MC Sophia Children's Hospital-University Medical Center, Rotterdam, The Netherlands. · J Pediatr Gastroenterol Nutr. · Pubmed #19179875 No free full text.

Abstract: Crohn disease and ulcerative colitis are chronic inflammatory diseases of the intestinal tract commonly denoted as inflammatory bowel diseases. It has been proposed that these diseases result from aberrant mucosal immune responses to nonpathogenic microbial residents of the intestines. Recently, it was established that continuous interactions between the innate and the adaptive intestinal immune cells and the microbiota are directly involved in maintaining the physiological noninflammatory state of the intestinal mucosa. In light of the complexity of this mucosal homeostasis, it is astonishing that the inflammatory bowel diseases are relatively rare. Recently, altered functions of the innate immune system have been identified. As such, both hyperresponsiveness and hyporesponsiveness of innate cells have been implicated in the pathogenesis of inflammatory bowel diseases.

Escher JC, Anonymous00305. · Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital-Academic Medical Centre, Amsterdam, The Netherlands. · Eur J Gastroenterol Hepatol. · Pubmed #15095852 No free full text.

Abstract: OBJECTIVES: Budesonide is a corticosteroid with low systemic bioavailability because of its high first-pass metabolism in the liver. In this paediatric, randomized, double-blind, double-dummy, controlled, multicentre trial, the safety and efficacy of budesonide versus prednisolone were evaluated in children with active Crohn's disease. METHODS: Forty-eight children, aged 6-16 years, with active Crohn's disease (Crohn's Disease Activity Index > 200) involving ileum and/or ascending colon were randomized to receive budesonide (9 mg/day for 8 weeks, 6 mg/day for 4 weeks) or prednisolone (1 mg/kg/day for 4 weeks, tapering for 8 weeks). RESULTS: The groups were comparable for age, sex, pubertal stage, disease activity and disease duration. Mean morning plasma cortisol concentration was significantly higher in the budesonide group (200 nmol/l) than in the prednisolone group (98 nmol/l) after 8 weeks, reflecting less adrenal suppression by budesonide (difference -102 nmol/l; 95% CI -226, -52; P = 0.0028). Glucocorticosteroid side effects such as moon face and acne occurred significantly less frequently in the budesonide group. Remission (Crohn's Disease Activity Index < or = 150) was seen at 8 weeks in 12/22 (55%) patients treated with budesonide and in 17/24 (71%) patients receiving prednisolone (difference -16%; 95% CI -45,13; P = 0.25). CONCLUSIONS: Significantly fewer side effects and less adrenal suppression were observed in the children receiving budesonide. Remission rates were not significantly different in the two groups. However, there was a trend for prednisolone to be more effective for inducing remission.

Baldassano R, Braegger CP, Escher JC, DeWoody K, Hendricks DF, Keenan GF, Winter HS. · Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104- 4399, USA. · Am J Gastroenterol. · Pubmed #12738464 No free full text.

Abstract: OBJECTIVE: The aim of this study was to assess the efficacy and safety of a single infusion of infliximab in the treatment of pediatric Crohn's disease (CD). METHODS: A total of 21 pediatric CD patients were enrolled at seven study centers and randomized to receive a single infusion of infliximab 1 mg/kg (n = 6), 5 mg/kg (n = 7), or 10 mg/kg (n = 8) over at least 2 hrs at week 0 in this multicenter, open-label, dose-blinded trial. Efficacy assessments, including the Pediatric Crohn's Disease Activity Index (PCDAI), modified CDAI, C-reactive protein concentration (CRP), and erythrocyte sedimentation rate (ESR) determinations, were made at screening and at weeks 1, 2, 4, 8, and 12. Adverse events were assessed throughout study participation. RESULTS: Improvements in the PCDAI, modified CDAI, ESR, and CRP were observed with all infliximab doses, beginning at week 1. On average, all treated patients experienced approximately 50% improvement in the PCDAI by week 2. By week 12, the PCDAI remained approximately 30% improved from baseline. During the study, all 21 patients (100%) achieved a clinical response, and 10 patients (48%) achieved clinical remission. There were no infusion reactions in any of the treatment arms. CONCLUSIONS: The results of this trial suggest that infliximab may be safe and effective as short-term therapy of medically refractory moderate to severe CD in a pediatric population.

de Ridder L, Rings EH, Damen GM, Kneepkens CM, Schweizer JJ, Kokke FT, Benninga MA, Norbruis OF, Hoekstra JH, Gijsbers CF, Escher JC. · Erasmus Medical Center/Sophia Children's Hospital, Dr. Molewaterplein 60, Rotterdam, Netherlands. · Inflamm Bowel Dis. · Pubmed #18069674 links to  free full text

Abstract: BACKGROUND: Infliximab is effective for induction and maintenance of remission in Crohn'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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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's disease.

Jaspers GJ, Verkade HJ, Escher JC, de Ridder L, Taminiau JA, Rings EH. · Pediatric Gastroenterology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. · Inflamm Bowel Dis. · Pubmed #16954801 links to  free full text

Abstract: 6-Mercaptopurine (6-MP) maintains remission in pediatric Crohn's disease (CD). Azathioprine, a prodrug of 6-MP, is used for maintenance of remission of CD in Europe. We evaluated to what extent azathioprine is used in newly diagnosed pediatric CD patients and whether maintenance of remission differed between patients using azathioprine or not. Charts of children (diagnosed 1998-2003, follow-up > or = 18 mo) were reviewed. Active disease was defined as Pediatric Crohn's Disease Activity Index (PCDAI) greater than 10 or systemic corticosteroid use. Remission was defined as PCDAI 10 or less without use of corticosteroids. Eighty-eight children (55M/33F, age 12 +/- 3 yr) were included. Seventy-two (82%) patients received azathioprine during the follow-up period (38 +/- 17 mo). Patients diagnosed after 2000 received azathioprine significantly earlier during the course of disease compared with those diagnosed earlier (median, at 233 vs. 686 days; P < 0.05). At initial presentation, moderate-severe disease activity and prescription of corticosteroids were more prevalent in patients using azathioprine compared with nonazathioprine patients (75% vs. 52%; P < 0.05; and 89% vs. 58%; P < 0.005, respectively). Duration of corticosteroid use was longer in patients receiving azathioprine (232 vs. 168 days; P < 0.005). Median maintenance of first remission in patients who initially used corticosteroids, however, was longer in patients receiving azathioprine compared with nonazathioprine patients (PCDAI, 544 vs. 254 days, P = 0.08; corticosteroid free, 575 vs. 259 days, P < 0.05, respectively). We conclude that, since 2000, azathioprine is being introduced earlier in the treatment of newly diagnosed pediatric CD patients. The use of azathioprine is associated with prolonged maintenance of the first remission.

Escher JC. · Department of Pediatric Gastroenterology, Sophia Children's Hospital-Erasmus Medical Center, Rotterdam, The Netherlands. · Dig Liver Dis. · Pubmed #16574514 No free full text.

This publication has no abstract.

Caprilli R, Gassull MA, Escher JC, Moser G, Munkholm P, Forbes A, Hommes DW, Lochs H, Angelucci E, Cocco A, Vucelic B, Hildebrand H, Kolacek S, Riis L, Lukas M, de Franchis R, Hamilton M, Jantschek G, Michetti P, O'Morain C, Anwar MM, Freitas JL, Mouzas IA, Baert F, Mitchell R, Hawkey CJ, Anonymous00006. · John Radcliffe Hospital, Oxford OX3 9DU, UK. · Gut. · Pubmed #16481630 links to  free full text

Abstract: This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease.

Damen GM, Hol J, de Ruiter L, Bouquet J, Sinaasappel M, van der Woude J, Laman JD, Hop WC, Büller HA, Escher JC, Nieuwenhuis EE. · Department of Pediatric Gastroenterology and Laboratory of Pediatrics, Erasmus MC-Sophia Children's Hospital, University Medical Center, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands. · J Pediatr Gastroenterol Nutr. · Pubmed #16456405 No free full text.

Abstract: OBJECTIVES: Inflammatory bowel diseases (IBD) represent an aberrant immune response by the mucosal immune system to luminal bacteria. Because the oral mucosa harbors the first epithelial cells that interact with microorganisms, we assessed the immunologic activity of buccal epithelium in children with IBD and adults with Crohn disease. METHODS: Buccal epithelial cells were obtained from 17 children and 14 adults with Crohn disease, 18 children with ulcerative colitis, and 40 controls. Cells were cultured with and without microbial stimulation. Chemokine levels were determined in culture supernatants by cytometric bead array and enzyme-linked immunoabsorbent assay. CXCL-8 production was studied by immunohistochemical analysis of these cells. CXCL-8 production by lipopolysaccharide stimulated monocyte-derived dendritic cells from these patients was determined. RESULTS: Compared with controls, pediatric ulcerative colitis patients, and adult Crohn disease patients, only in children with Crohn disease did buccal epithelial cells exhibit enhanced production of CXCL-8, CXCL-9, and CXCL-10. In vitro stimulation with lipopolysaccharide or zymosan resulted in a further increase of chemokine levels only in cells from pediatric Crohn disease patients. CXCL-8 production by stimulated monocyte-derived dendritic cells from children with Crohn disease was equal to that of children with ulcerative colitis. CONCLUSIONS: Buccal epithelium of children with Crohn disease is immunologically active, even in the absence of oral lesions. The enhanced chemokine production is associated with pediatric Crohn disease and appears restricted to cells derived from the epithelial barrier. Assessment of chemokine production by buccal epithelial cells may become a new, rapid, noninvasive test for screening and classification of IBD in children.

Escher JC. · No affiliation provided · Inflamm Bowel Dis. · Pubmed #15475763 No free full text.

This publication has no abstract.

de Ridder L, Escher JC, Bouquet J, Schweizer JJ, Rings EH, Tolboom JJ, Houwen RH, Norbruis OF, Derkx BH, Taminiau JA. · Emma Children's Hospital/Academic Medical Centre, Amsterdam, The Netherlands. · J Pediatr Gastroenterol Nutr. · Pubmed #15187780 No free full text.

Abstract: 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 < or =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.

van der Zaag-Loonen HJ, Casparie M, Taminiau JA, Escher JC, Pereira RR, Derkx HH. · Emma Children's Hospital, AMC, Amsterdam, the Netherlands. · J Pediatr Gastroenterol Nutr. · Pubmed #15076631 No free full text.

Abstract: BACKGROUND: The incidence of inflammatory bowel disease (IBD) seems to be rising. Incidence studies could provide more insight into geographical differences and thereby lead to the identification of etiological factors. The aim of this study was to prospectively assess the incidence of pediatric IBD in the Netherlands from 1999 to 2001, using both an active physician case-reporting registry and a nationwide pathology database. METHODS: All pediatricians in the Netherlands were sent monthly identification cards to be returned if they had diagnosed a new case of IBD in a pediatric patient. Follow-up questionnaires were sent to physicians reporting new cases of IBD. The pathology database contains reports from all cytologic and histologic diagnoses made in the Netherlands. Two independent raters searched the database for new IBD cases. Cases identified from the pathology database were labeled as "probable IBD" and "possible IBD." Cases were cross-checked across databases on the basis of gender, date of birth, date of biopsy, and place of residence. Age-specific incidence rates were calculated for the Dutch population for the year 2000. RESULTS: Five hundred forty-six probable cases of IBD were identified; 217 cases were labeled as possible. The incidence rate was 5.2 new cases per 100000 children (<18 years) per year. An increase in incidence with age was observed. Only 24% of the cases were ascertained through the clinical registry. CONCLUSION: The incidence of IBD cases in the Netherlands is comparable with that reported in other European countries. Epidemiological studies using case reporting by physicians may be underestimates of true incidence rates.

Lundin PD, Edsbäcker S, Bergstrand M, Ejderhamn J, Linander H, Högberg L, Persson T, Escher JC, Lindquist B. · Experimental Medicine, Astra-Zeneca R & D Mölndal, S-431 83 Mölndal, Sweden. · Aliment Pharmacol Ther. · Pubmed #12492736 links to  free full text

Abstract: BACKGROUND: Systemic glucocorticosteroid therapy is effective in Crohn's disease, but is associated with side-effects. Budesonide has high topical anti-inflammatory activity, but considerably lower systemic activity than other oral glucocorticosteroids. AIM: To evaluate the systemic exposure to budesonide (controlled ileal release capsules) in children and adults with active Crohn's disease, and to assess the suppression of plasma cortisol. METHODS: In an open label study, patients (eight children and six adults) with active Crohn's disease received 9 mg budesonide (Entocort capsules) orally once daily for 7 days. Plasma concentrations were determined on the seventh day of administration, and pharmacokinetic parameters were calculated. For reference, 0.5 mg budesonide was given intravenously separately. Plasma cortisol levels were compared with the pre-treatment baseline values. RESULTS: Systemic exposure to budesonide (AUC0-24 h) after 1 week of oral administration was 41 +/- 21 nmol/L x h (mean +/- s.d.) in children and 35 +/- 20 nmol/L x h in adults. The estimated systemic availability in children was 9 +/- 5% and in adults 11 +/- 7%. The mean plasma cortisol (AUC0-24 h) decreased by 64 +/- 18% in children and by 50 +/- 27% in adults. CONCLUSIONS: The systemic exposure, systemic availability and cortisol suppression after oral administration of 9 mg budesonide were similar in children and adults with active Crohn's disease. Budesonide was well tolerated and no clinically important safety-related findings were identified.

de Ridder L, Escher JC, Taminiau JA. · Academisch Medisch Centrum/Emma Kinderziekenhuis, afd. Kindergeneeskunde, Meibergdreef 9, 1100 DE Amsterdam. · Ned Tijdschr Geneeskd. · Pubmed #12395595 No free full text.

Abstract: OBJECTIVE: To describe the clinical experience of infliximab treatment in children and adolescents with refractory Crohn's disease in the Netherlands. DESIGN: Descriptive. METHOD: 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. RESULTS: 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. CONCLUSION: Response rates were lower than observed in previous studies. Specifically, a decrease of response was demonstrated after repeated infusion. The treatment frequency should be determined by the increase in complaints rather than using a fixed interval of 8 weeks.

Escher JC, Stoof TJ, van Deventer SJ, van Furth AM. · Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam, The Netherlands. · J Pediatr Gastroenterol Nutr. · Pubmed #11930102 No free full text.

This publication has no abstract.

Escher JC, Taminiau JA. · Dept. of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, The Netherlands. · Scand J Gastroenterol Suppl. · Pubmed #11768561 No free full text.

Abstract: Of all patients with Crohn disease and ulcerative colitis, the first presentation of inflammatory bowel disease (IBD) is at a paediatric or adolescent age in 20% to 30%, most children being prepubertal at diagnosis. It is essential to provide an accurate diagnosis in children suspected of IBD, as the initial treatment of Crohn disease and ulcerative colitis in children is not the same as it is in adults. While the role of enteral feeding in the treatment of Crohn disease in adults continues to be controversial, there is firm evidence to support the use of enteral feeding as primary therapy for Crohn disease in children. Nutrition is improved by enteral feeding, and growth and pubertal development are promoted, while the systemic toxicity of corticosteroid therapy is avoided. Supplementary nocturnal enteral nutrition (with daytime intake of normal diet) after primary therapy and remission induction may be associated with the prolongation of remission. Drug treatment in children with IBD is characterized by a lack of evidence from controlled trials.

Damen GM, van Lierop P, de Ruiter L, Escher JC, Donders R, Samsom JN, Nieuwenhuis EE. · No affiliation provided · Gut. · Pubmed #18791123 No free full text.

This publication has no abstract.

van Lierop PP, Damen GM, Escher JC, Samsom JN, Nieuwenhuis EE. · No affiliation provided · Lancet. · Pubmed #16905017 No free full text.

This publication has no abstract.