Pediatric-onset Crohn Research Articles

Pronostic statural au cours du syndrome d’interruption de la tige pituitaire de l’enfant

Pediatric-onset Crohn’s disease (CD) may represent a more severe form of disease. The aim of this study was to describe long-term outcome and identify associated risk factors of complicated behavior in a large population-based pediatric-onset CD cohort.Cases included all patients recorded in the EPIMAD registry diagnosed with definite or probable CD between January 1988 and December 2004, under the age of 17 years at the time of diagnosis, with at least two years of follow-up.Five hundred and thirty-five patients were included. Median follow-up was 11.1 years [IQR, 7.3–15.0]. At the end of follow-up, 8% (n = 44) of patients had pure ileal disease (L1), 8% (n = 44) had pure colonic disease (L2), and 83% (n = 439) had ileocolonic disease (L3). L4 disease and perianal disease were observed in 42% (n = 227) and 16% (n = 85) of patients, respectively. At the end of follow-up, 58% (n = 308) of patients presented complicated disease behavior (B2, 39% and B3, 19%), and 42% (n = 163) of patients with inflammatory behavior at diagnosis had evolved to complicated behavior. During follow-up, 86% of patients (n = 466) received at least one course of corticosteroids, 67% (n = 357) of patients had been exposed to immunosuppressants and 35% (n = 187) of patients received at least one anti-TNF agent. Forty-three percent (n = 230) of patients underwent at least one intestinal resection. The overall mortality rate was 0.93% and the SMR was 1.6 [0.5–3.8] (p = 0.20). Five cancers were reported with a crude cancer incidence rate of 1.1% and an SIR of 3.3 [1.2–7.0] (p = 0.01). In a multivariate Cox model, ileal (HR, 1.87 [1.09–3.21], p = 0.022) or ileocolonic (HR, 1.54 [1.01–2.34], p = 0.042) and perianal lesions at diagnosis (HR, 1.81 [1.13- 2.89], p = 0.013) were significantly associated with complicated behavior.About 80% of patients with pediatric-onset CD presented extensive ileocolonic disease during follow-up. The majority of patients evolved to complicated behavior. Surgery, cancer and mortality were observed in 43%, 0.9% and 0.9% of patients, respectively.

Long-term Outcome After First Intestinal Resection in Pediatric-onset Crohnʼs Disease

To describe long-term postoperative evolution of pediatric-onset Crohn's disease (CD) and identify predictors of outcome we studied a population-based cohort (1988-2004) of 404 patients (0-17 years), of which 130 underwent surgery. Risks for a second resection and first need for immunosuppressors (IS) and/or biologics were estimated by survival analysis and Cox models used to determine predictors of outcome. Impact of time of first surgery on nutritional catch-up was studied using regression. In all, 130 patients (70 females) with a median age at diagnosis of 14.2 years (interquartile range: 12-16) were followed for 13 years (9.4-16.6). Probability of a second resection was 8%, 17%, and 29% at 2, 5, and 10 years, respectively. In multivariate analysis, age <14, stenosing (B2) and penetrating (B3) behaviors and upper gastrointestinal location (L4) at diagnosis were associated with an increased risk of second resection. Probability of receiving IS or biologics was 18%, 34%, and 47% at 2, 5, and 10 years, respectively. In multivariate analysis, L4 was a risk factor for requiring IS or biologics, while surgery within 3 years after CD diagnosis was protective. Catch-up in height and weight was better in patients who underwent surgery within 3 years after CD diagnosis than those operated on later. In this pediatric-onset CD study, mostly performed in a prebiologic era, a first surgery performed within 3 years after CD diagnosis was associated with a reduced need for IS and biologics and a better catch-up in height and weight compared to later surgery.

Strictureplasty and intestinal resection: different options in complicated pediatric-onset Crohn disease

Background/PurposeSurgical resection or strictureplasty (SP) are different options for intestinal Crohn disease (CD) strictures. The aim of this article is evaluation of long-term outcome of SP and resection. MethodsFrom 1996 to 2011, 39 patients (23 male, 16 female) with symptomatic ileal and ileocolonic CD strictures resistant to medical/nutritional therapy and treated with surgery in 2 different surgical units were reviewed. The mean age at diagnosis was 11.82 years (range, 4-17 years). Mean age at surgery was 15.94 years (range, 4-24 years). Mean follow-up was 6.88 years (range, 0.5-15 years). Patients underwent resection (group A) or different SP techniques (group B). ResultsTwenty patients underwent intestinal resection (ileal or ileocolonic resection), and 19 patients underwent SP (jejunal, ileal, or ileocolic). Early postsurgical complications were observed in 2 patients of group A. Follow-up of group A patients revealed that 1 patient needed emergency treatment after 8 months surgery because of adhesions and 1 patient developed recurrence treated with medical therapy. In the follow-up group B, 3 patients experienced disease recurrence, 2 of them at the site of previous surgery. ConclusionsAt long-term follow-up, no significant difference in relapsing rate was observed between the 2 groups. Strictureplasty and resection represent an effective treatment of pediatric CD strictures. Strictureplasty could represent the first option for intestinal preservation.

103 Long-Term Outcome of Paediatric-Onset Crohn's Disease: A Population-Based Study

Data on long-term outcome of paediatric-onset Crohn's disease (CD) are scarce. Methods: All patients under the age of 17 years at diagnosis of definite or probable CD between 1988 and 2004 recorded by EPIMAD Registry were included. Results: 538 patients with paediatriconset CD were identified (8.5% of all cases of CD), including 293 males. The median age at diagnosis was 14 years [IQR: 12-16] and the median duration of follow-up was 11.5 years [IQR: 7-15]. Disease location was stable over time in 75% of them, 11% of patients progressed to more extensive disease, and healing of colonic lesions during follow-up was reported in 14% of patients with ileocolonic disease (L3 according to Montreal classification). The percentage of complicated behaviour (B2 or B3 according to Montreal classification) increased from diagnosis to last news: 73% vs 42% (B1); 24% vs 39% (B2); and 4 % vs 19 % (B3); p<10-3. Cumulative probabilities of receiving immunosuppressors and anti-TNF therapy were respectively 22% et 2% at 1 year, 51% and 16% at 5 years, 66% and 29% at 10 years, and 74% and 49% at 20 years. Cumulative probabilities of first intestinal resection were 9%, 15%, 31%, 44% and 54% at 1, 2, 5, 10 and 20 years. Conclusion: In this large population-based cohort, the natural history of paediatric-onset CD was characterized by a stable disease location in 75% of patients and a complicated behaviour in 60% of them after a median follow-up of 11.5 years. Twenty years after diagnosis, three-quarters of patients would have received immunosuppressors, about half an anti-TNF therapy, and half of patients would have required an intestinal resection. (1) Chouraki et al. Aliment Pharmacol Ther 2011

104 Increased Incidence of Post-Operative Complications in Older Inflammatory Bowel Disease Patients Having Intestinal Surgery

Data on long-term outcome of paediatric-onset Crohn's disease (CD) are scarce. Methods: All patients under the age of 17 years at diagnosis of definite or probable CD between 1988 and 2004 recorded by EPIMAD Registry were included. Results: 538 patients with paediatriconset CD were identified (8.5% of all cases of CD), including 293 males. The median age at diagnosis was 14 years [IQR: 12-16] and the median duration of follow-up was 11.5 years [IQR: 7-15]. Disease location was stable over time in 75% of them, 11% of patients progressed to more extensive disease, and healing of colonic lesions during follow-up was reported in 14% of patients with ileocolonic disease (L3 according to Montreal classification). The percentage of complicated behaviour (B2 or B3 according to Montreal classification) increased from diagnosis to last news: 73% vs 42% (B1); 24% vs 39% (B2); and 4 % vs 19 % (B3); p<10-3. Cumulative probabilities of receiving immunosuppressors and anti-TNF therapy were respectively 22% et 2% at 1 year, 51% and 16% at 5 years, 66% and 29% at 10 years, and 74% and 49% at 20 years. Cumulative probabilities of first intestinal resection were 9%, 15%, 31%, 44% and 54% at 1, 2, 5, 10 and 20 years. Conclusion: In this large population-based cohort, the natural history of paediatric-onset CD was characterized by a stable disease location in 75% of patients and a complicated behaviour in 60% of them after a median follow-up of 11.5 years. Twenty years after diagnosis, three-quarters of patients would have received immunosuppressors, about half an anti-TNF therapy, and half of patients would have required an intestinal resection. (1) Chouraki et al. Aliment Pharmacol Ther 2011

OP18 Long-term outcome after first intestinal resection in paediatric-onset Crohn's disease: A population-based study

OP18 Long-term outcome after first intestinal resection in paediatric-onset Crohn's disease: A population-based study

P137 Long-term outcome of paediatric-onset Crohn's disease: A population-based study

P137 Long-term outcome of paediatric-onset Crohn's disease: A population-based study

Upper gastrointestinal involvement in paediatric onset Crohn's disease: Prevalence and clinical implications

Background and aims Our study evaluated the prevalence, the characteristics and implications of the upper gastrointestinal localisation (UGI+) in paediatric Crohn's Disease (CD) patients. Methods This prospective study evaluated 45 newly diagnosed CD patients at diagnosis and follow up with respect to CD localisation. Results All patients presented CD at the colon and/or ileum. In 24/45 patients (53.3%, 12 F and 12 M) an UGI+ involvement was also found. UGI+ patients had a younger age of onset (10.9 years versus 12.6 years; P < 0.05). PCDAI at diagnosis was significantly higher in the UGI+ (41 vs. 25 P < 0.01). UGI+ patients were overall more symptomatic. Pancolitis and extraintestinal manifestations were also more frequent (19/24 (80%) vs. 12/21 (57%) P < 0.01). Growth was more impaired at diagnosis in UGI+ patients. By the end of the follow-up (mean 3 years, range 2 to 4) no significant difference was found in PCDAI (17 in UGI+ patients vs. 11 in UGI− P = NS), or the number of relapses. Weight and growth catch-up in UGI+ patients were comparable to UGI− ones. However, UGI+ patients required a more aggressive therapeutic approach. Conclusion At least half of paediatric onset CD patients have an upper gastrointestinal localisation. UGI+ patients present an earlier onset and a more severe disease. The final outcome does not differ, but UGI+ patients require a more aggressive therapeutic approach.

Terminal ileal biopsy, small bowel imaging and upper GI endoscopy are all required for the efficient diagnosis of paediatric crohn's disease

IntroductionDifferentiating Crohn's disease from UC and IBDU is vital for children. Appreciable phenotypic differences exist between adult and paediatric-onset Crohn's disease (PCD) at diagnosis. Guidelines (JPGN 2010;50:S1–S13) for PCD diagnosis...

Terminal ileal biopsy, small bowel imaging and upper-gi endoscopy are all required for the efficient diagnosis of paediatric-onset crohn's disease

IntroductionIn contrast to adult-onset Crohn's disease (CD), presentation of paediatric-onset CD (PCD) is characterised by widespread intestinal involvement; hence guidelines for diagnosis of PCD recommend evaluation of the GI tract...

Charakterystyka obrazu klinicznego 146 nowo rozpoznanych przypadków pediatrycznych choroby Leśniowskiego-Crohna

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Sładek M, Ćmiel A. Characteristics of clinical presentation of 146 cases of newly diagnosed paediatric onset Crohn’s disease. Gastroenterology Review/Przegląd Gastroenterologiczny. 2011;6(2):102-109. doi:10.5114/pg.2011.21720. APA Sładek, M., & Ćmiel, A. (2011). Characteristics of clinical presentation of 146 cases of newly diagnosed paediatric onset Crohn’s disease. Gastroenterology Review/Przegląd Gastroenterologiczny, 6(2), 102-109. https://doi.org/10.5114/pg.2011.21720 Chicago Sładek, Małgorzata, and Adam Ćmiel. 2011. "Characteristics of clinical presentation of 146 cases of newly diagnosed paediatric onset Crohn’s disease". Gastroenterology Review/Przegląd Gastroenterologiczny 6 (2): 102-109. doi:10.5114/pg.2011.21720. Harvard Sładek, M., and Ćmiel, A. (2011). Characteristics of clinical presentation of 146 cases of newly diagnosed paediatric onset Crohn’s disease. Gastroenterology Review/Przegląd Gastroenterologiczny, 6(2), pp.102-109. https://doi.org/10.5114/pg.2011.21720 MLA Sładek, Małgorzata et al. "Characteristics of clinical presentation of 146 cases of newly diagnosed paediatric onset Crohn’s disease." Gastroenterology Review/Przegląd Gastroenterologiczny, vol. 6, no. 2, 2011, pp. 102-109. doi:10.5114/pg.2011.21720. Vancouver Sładek M, Ćmiel A. Characteristics of clinical presentation of 146 cases of newly diagnosed paediatric onset Crohn’s disease. Gastroenterology Review/Przegląd Gastroenterologiczny. 2011;6(2):102-109. doi:10.5114/pg.2011.21720.

Crohnʼs Disease in a Child

Crohn's disease is a chronic inflammatory bowel disease characterized by transmural, granulomatous inflammation. In paediatric-onset Crohn's disease, the most frequent clinical features are abdominal pain, diarrhoea, fatigue and weight loss. Delayed puberty, growth retardation and osteoporosis might, however, be the predominant signs of the disease. This paper reports the case of a 13-year-old girl with Crohn's disease diagnosed at the age of 11 years, with classic gastrointestinal symptoms in the previous few months, but with severe osteoporosis at onset. The child has been on infliximab therapy for 1 year, with complete control of the disease. Therapy with infliximab appears to influence bone metabolism, bone formation and resorption, and that improvement seems to be independent of the clinical response to the drug. Infliximab has recently been approved for paediatric use, which has been a great improvement for a group of patients lacking therapeutic options.

NOD2 mutations predict the risk for surgery in pediatric-onset Crohn's disease

Backgroud/Purpose Three common mutations of the NOD2/ CARD15 gene have been associated with Crohn disease (CD), ileal disease location, and fibrostenotic behavior. The aim of this study was to investigate the effect of these mutations on disease manifestation and the risk of surgery in a cohort of German childhood–onset CD patients. Methods Genotyping for the NOD2 mutations p.Arg702Trp, p.Gly908Arg, and p.1007fs was performed in 171 CD children (onset of disease <17 years; mean 11.8 years) and in 253 controls. NOD2 mutation status was correlated with the need for surgery during childhood. Results Seventy-eight children (45.6%) were carriers of at least 1 NOD2 mutation versus 36 (14.2%) in the control group ( P < .0001). NOD2 mutations were highly associated with CD and stricturing behavior ( P < .0001), with the p.1007fs mutation also conferring a risk for isolated ileal disease ( P = .003). Thirty-two children (18.7%) needed an intestinal resection with a significant association between the need of surgery and NOD2 carrier status. Surgery occurred at an earlier stage of disease in children with p.1007fs mutations. Conclusions In children with pediatric-onset CD, the need for surgical therapy younger than 17 years is associated with the NOD2 genotype. Genetic testing therefore may identify children with CD who are at risk.

Association between genome-wide association studies reported SNPs and pediatric-onset Crohn’s disease in Canadian children

A recent pediatric-focused genome-wide association study has implicated three novel susceptibility loci for Crohn' disease (CD).We aimed to investigate whether the three recently reported and other previously reported genes/loci were also associated with CD in Canadian children. A case-control design was implemented at three pediatric gastroenterology clinics in Canada. Children <19 years of age with a confirmed diagnosis of CD were recruited along with controls. Single nucleotide polymorphisms (SNPs) in 19 reported genes/loci were genotyped. Associations between individual SNPs and CD were examined. A total of 563 cases and 553 controls were studied. The mean (+/-SD) age of the cases was 12.3 (+/-3.2) years. Most cases were male (56.0%), had ileo-colonic disease (L3 +/- L4, 48.8%) and inflammatory behavior (B1 +/- p, 87.9%) at diagnosis. Allelic association analysis (two-tailed) showed that 8 of the 19 targeted SNPs were significantly associated with overall susceptibility for CD. Associations with one additional SNP was borderline non-significant. Significantly associated SNPs included SNPs rs1250550 (p = 0.026) and rs8049439 (p = 0.04), recently reported to be specifically associated with pediatric-onset CD.Based on the results, we confirmed associations between two of the three novel pediatric-CD loci and other regions reported for associations with either pediatric and/or adult-onset CD.

955 Associations Between Genetic Variants in the Glucocorticoid Receptor (GR) Gene and Corticosteroid Dependency in Paediatric-Onset Crohn's Disease

955 Associations Between Genetic Variants in the Glucocorticoid Receptor (GR) Gene and Corticosteroid Dependency in Paediatric-Onset Crohn's Disease

S2018a Associations Between DNA Variants in the TLR5 Gene and Pediatric-Onset Crohn's Disease

S2018a Associations Between DNA Variants in the TLR5 Gene and Pediatric-Onset Crohn's Disease

Erratum: Investigation of Reported Associations Between the 20q13 and 21q22 Loci and Pediatric-Onset Crohn's Disease in Canadian Children

Erratum: Investigation of Reported Associations Between the 20q13 and 21q22 Loci and Pediatric-Onset Crohn's Disease in Canadian Children

Investigation of Reported Associations Between the 20q13 and 21q22 Loci and Pediatric-Onset Crohn's Disease in Canadian Children

A recent pediatric-focused genome-wide association study has reported novel associations of the 20q13 and 21q22 loci with inflammatory bowel disease (IBD). We aimed to investigate these associations with Crohn's disease (CD) in Canadian children. A combined case-control and case-parent design was implemented at three pediatric gastroenterology clinics in Canada. Children less than 20 years of age with a confirmed diagnosis of CD were recruited along with controls. For a subset of the patients, biological parents were also recruited. Three single-nucleotide polymorphisms (SNPs) at the 20q13 locus and 1 SNP at the 21q22 locus were genotyped. Associations between individual SNPs and haplotypes were examined. A total of 410 cases, 415 controls, and 302 parents were studied. The mean (+/-s.d.) age for the cases was 12.3 (+/-3.2) years. Most cases were men (56.1%) who had ileocolonic disease (L3+/-L4, 52.2%) and inflammatory behavior (B1+/-B4, 87.0%) at diagnosis. Single SNP analysis showed that all 3 SNPs at the 20q13 locus were significantly associated with CD (rs2297441, P=2.24x10(-4); rs2315008, P=4.77x10(-4); rs4809330, P=6.08x10(-3)). Haplotype analysis suggested that the association signal at 20q13 resided on a common haplotype comprising the minor allele of rs2297441 (P=2.8x10(-5)). SNP rs2836878 at the 21q22 locus showed a trend for association with CD that was statistically not significant (P=0.06). Our results support an association between the 20q13 locus and CD in Canadian children. Positional cloning studies are required to further dissect the potential causative genes in the region.

S1754 Interactions Between PTPN2, CARD15 and ATG16L1 Genes Are Associated with Pediatric-Onset Crohn's Disease. Findings Based On a Gene-Wide Case-Control Study in Canadian Children

Background and Aim: RNAi is a powerful biological tool whereby any specific genes of interest can be specifically targeted. However, application of RNAi for silencing genes of the GI tract has proven difficult. We recently described a bacteria-based RNAi technology (transkingdom RNAi, tkRNAi) to simultaneously produce and deliver RNAi to the GI tract (Xiang, Nat Biotech 2006, 697). The aim of this study was to examine whether tkRNAi can be used to silence the expression of IL-10, an anti-inflammatory cytokine, and induce a pro-inflammatory state In Vivo. Methods: After selection of themost powerful siRNA sequence, tkRNAi bacteria were created producing shRNA against mouse IL-10 (TRIP-sh7) and control (TRIP-scrambled). J774.A1 cells were incubated with TRIP-bearing bacteria for 2h at various MOIs, and then stimulated with LPS for 24h. IL-10 gene silencing was analyzed by quantitative RT-PCR and ELISA. To assess In Vivo gene silencing, 12 Balb/c mice were randomized into 3 groups: untreated (n=4); TRIP-sh7 (n=4); TRIP-scrambled (n=4). Following bacteria treatment for 2 weeks, colons were harvested and analyzed by qRT-PCR and IHC staining for IL-10 and γ-IFN. Results: treatment of J774.A1 cells with TRIP-sh7 reduced IL-10 mRNA and protein levels by >80% (p 70% (p < 0.05) compared to animals treated with TRIPscrambled control bacteria. IHC staining of colon tissue demonstrated a marked reduction of IL-10 protein expression in TRIP-sh7 treated mice compared to untreated or mice treated with control bacteria. Moreover, treatment with TRIP-sh7 was associated with increased colonic production of the TH1 cytokine γ-IFN. Treatment with TRIP-sh7 for two weeks was also associated with a significant loss of body weight compared to untreated or mice treated with control bacteria (p < 0.05 for both). Summary and Conclusion: bacteria expressing shRNA against IL-10 can mediate potent gene silencing in LPS-stimulated J774.A1 cells, and in colonic epithelial cells In Vivo. Furthermore colonic levels of γ-IFN were markedly increased following bacterial RNAi against IL-10. tkRNAi approach may be useful for In Vivo functional genomics studies in the GI tract, and for developing RNAi therapies for GI diseases. Since tkRNAi can be adapted to induce silencing in multiple animal species, this approach may be suited for development of animal models in rodents or non-rodent, for diseases such as IBD.

The prevalence and clinical implications of the upper gastrointestinal localization in pediatric onset Crohn's disease

Background. According to current literature, upper gastrointestinal Crohn's disease (oesophago-gastroduodenal) is a frequent condition in paediatric patients, and appears to influence both the severity and the prognosis of the disease.