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Background & Aims: Patients with Crohn's disease or ulcerative colitis have relatively high levels of stress and psychological dysfunction. Acceptance and commitment therapy (ACT) is a psychological intervention that comprises acceptance and mindfulness procedures, along with commitment and behavior change strategies, to increase psychological flexibility and reduce stress. We performed a randomized controlled trial to investigate the effect of ACT on stress in patients with inflammatory bowel diseases (IBD)., Methods: A total of 122 patients with quiescent or stable, mildly active IBD were randomly assigned to an 8-week ACT program or treatment as usual (control group). Clinical, demographic, disease activity, and psychological data and blood and feces were collected at baseline and at 8 weeks and 3 months after the intervention (week 20). Scalp hair was collected at baseline and week 20 for measurement of steroid concentrations. The primary endpoint was change in stress symptoms, assessed with the Depression Anxiety Stress Scale. Secondary endpoints included changes in perceived stress, anxiety, depression, quality-of-life domains, disease activity, and cortisol concentration in hair., Results: Overall, 79 participants were included in the complete case intention-to-treat analysis. There were 39% and 45% reductions in stress in the treatment group from baseline to 8 and 20 weeks, respectively, compared with 8% and 11% in the control group (group × time interaction, P = .001). ACT was associated with reduced perceived stress (P = .036) and depression (P = .010), but not anxiety (P = .388), compared with control individuals. In the intention-to-treat analysis, changes in all 4 quality-of-life domains over time were similar in the ACT and control groups. In the per-protocol analysis, the overall well-being quality-of-life domain improved in the ACT group compared with the control group (P = .009). Subjective and objective disease activity measurements were similar between groups over the study period (all P values >.05). Hair cortisol concentrations correlated with stress (r s  = 0.205, P = .050) and anxiety (r s  = 0.208, P = .046) at baseline but did not change significantly in the ACT group over the study period compared with the control group (P = .831)., Conclusion: In a randomized controlled trial of patients with IBD, an 8-week ACT therapy course improved stress and other indices of psychological health.ClinicalTrials.gov Identifier: NCT02350920., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Ustekinumab (USK) is licenced for intravenous induction and subcutaneous (S/C) maintenance in Crohn's disease., Aim: To evaluate ustekinumab trough concentrations and clinical response with exclusive subcutaneous ustekinumab induction., Methods: Patients with Crohn's disease who initiated treatment with subcutaneous ustekinumab at a single academic centre were included in this pilot study. A dosage of 360 mg ustekinumab was given subcutaneously in divided doses; 180 mg at Week 0, 90 mg at Week 1 and 90 mg at Week 2, with corresponding ustekinumab trough concentrations assessed to Week 8. The primary outcome measures were trough serum ustekinumab levels and clinical remission at Week 8. Secondary outcome measures were trough serum ustekinumab levels at Week 1 & 2 and changes in C-reactive protein, albumin and faecal calprotectin at Week 8., Results: Nineteen patients were included. Median Week 8 ustekinumab trough concentrations were 6.1 μg/mL (Inter-quartile range 4-9.8 μg/mL). There was a significant improvement in Harvey Bradshaw index from Week 0 (median HBI 5; interquartile range 2-8) to Week 8 (median HBI 1; interquartile range 0-3) (P = 0.002). C-reactive protein levels did not change significantly but faecal calprotectin improved significantly; median faecal calprotectin at Week 0 was 533 μg/g; at Week 8, it was 278 μg/g (P = 0.038)., Conclusions: Ustekinumab trough concentrations are comparable whether ustekinumab induction treatment was administered subcutaneously or intravenously. A significant improvement in symptoms and faecal calprotectin was noted. These results support the use of subcutaneous induction as an alternative if there are barriers to intravenous induction., (© 2018 John Wiley & Sons Ltd.)

Background: Consensus guidelines from the European Crohns and Colitis Organisation conclude that optimizing quality of care in inflammatory bowel disease [IBD] involves information and education. However, there is no standardized patient education programme in IBD and education varies from centre to centre., Aim: To assess patients' education needs in IBD to facilitate design of a patient education programme., Methods: We created focus groups of 12 patients with IBD and used qualitative analysis to generate hypotheses. We then developed a quantitative questionnaire which was disseminated to 327 IBD patients attending three different centres. Five patients declined to participate and thus 322 patients (159 [49%] male, 180 [58%] Crohn's disease, median age 38 years and disease duration 7 years) were included., Results: Patients were most keen to receive education on medications, 'what to expect in future', living with IBD and diet. They wanted to receive this information from specialist doctors or nurses and believed it could improve their quality of life. Though the internet was the preferred source of general information [i.e. planning holidays], it was the least preferred source of IBD education. While there was a trend for females to prefer peer education, family history of IBD was the only statistically significant factor associated with information preferences., Conclusion: This is a patient-centred, mixed methodology study on patient education in IBD. Patients' preferences for education include components such as what to expect and diet and patients seem to distrust the internet as an IBD information source. International validation would be valuable to create a consensus education programme.

A 35-year old woman with ileocolonic, perianal, and vulval Crohn's disease was treated with subcutaneous ustekinuamb [USK] throughout pregnancy. Dose intervals were shortened from 6-weekly to 4-weekly to maintain clinical remission. The last dose of USK was administered at 33 weeks of gestation, and a healthy baby boy was delivered by caesarean section at 37 weeks. Maternal trough USK levels remained stable during pregnancy. Cord blood USK levels were nearly 2-fold higher than contemporaneous maternal serum levels. To our knowledge, this is the first report of maternal and cord USK levels in a patient with Crohn's disease.

Background: To evaluate whether changes in expression of CD39 by regulatory T lymphocytes (Treg) impact treatment response in inflammatory bowel disease. To then define the biological role of expression of CD39 on Treg in an animal model of colitis., Methods: A prospective study of consecutive patients commencing anti-tumor necrosis factor therapy with infliximab (IFX) or adalimumab (ADA), who were then followed for 12 months. Treatment responses were defined both symptomatically and by endoscopy showing mucosal healing. Peripheral blood Tregs were quantified by flow cytometry. Functional importance of CD39 expression by Treg was determined in an adoptive T-cell transfer model of colitis., Results: Forty-seven patients (ulcerative colitis, n = 22; Crohn's disease, n = 25) were recruited; 16 patients were complete responders and 13 nonresponders to anti-tumor necrosis factor. CD39 expression by Treg was lower in active inflammatory bowel disease and increased significantly after treatment in responders (CD39Treg/total Treg; 8% at baseline to 22.5% at late time point, P < 0.001). Responders were more likely to have therapeutic drug levels and in multivariate analysis therapeutic drug levels were associated with higher expression of CD39 by FoxP3 Treg and lower frequencies of interleukin 17A expressing cells. Tregs with genetic deletion of CD39 exhibit decrements in potential to suppress intestinal inflammation in a murine (CD45RB) T-cell transfer model of colitis in vivo, when compared with wild-type Treg., Conclusions: Increased expression of CD39 by peripheral blood Treg is observed in the setting of clinical and endoscopic remission in inflammatory bowel disease. Deficiency of CD39 expression by Treg can be linked to inability to suppress experimental colitis.

Background and Aims: Psychological stress is associated with inflammatory bowel disease [IBD], but the nature of this relationship is complex. At present, there is no simple tool to screen for stress in IBD clinical practice or assess stress repeatedly in longitudinal studies. Our aim was to design a single-question 'stressometer' to rapidly measure stress and validate this in IBD patients., Methods: In all, 304 IBD patients completed a single-question 'stressometer'. This was correlated with stress as measured by the Depression Anxiety Stress Scales [DASS-21], quality of life, and disease activity. Test-retest reliability was assessed in 31 patients who completed the stressometer and the DASS-21 on two occasions 4 weeks apart., Results: Stressometer levels correlated with the DASS-21 stress dimension in both Crohn's disease [CD] (Spearman's rank correlation coefficient [rs] 0.54; p < 0.001) and ulcerative colitis [UC] [rs 0.59; p < 0.001]. Stressometer levels were less closely associated with depression and anxiety [rs range 0.36 to 0.49; all p-values < 0.001]. Stressometer scores correlated with all four Short Health Scale quality of life dimensions in both CD and UC [rs range 0.35 to 0.48; all p-values < 0.001] and with disease activity in Crohn's disease [rs 0.46; p < 0.001] and ulcerative colitis [rs 0.20; p = 0.02]. Responsiveness was confirmed with a test-retest correlation of 0.43 [p = 0.02]., Conclusions: The stressometer is a simple, valid, and responsive measure of psychological stress in IBD patients and may be a useful patient-reported outcome measure in future IBD clinical and research assessments., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: To determine whether specific magnetic resonance enterography (MRE) findings can predict outcome following commencement of antitumor necrosis factor (aTNF) in small bowel Crohn's disease (CD) PATIENTS AND METHODS: This was a single-centre retrospective study of patients with CD who commenced aTNF (infliximab or adalimumab) between 2007 and 2013. Patients who had an MRE within 6 months before commencing aTNF were included. The primary end-point was the need for CD-related surgery. The secondary end-points were time to surgery and time to treatment failure. The relationship between these end-points, clinical variables and specific MRE findings were studied., Results: Four hundred and eighteen patients commenced aTNF for CD during the study period. Seventy-five patients had an MRE within 6 months before commencing aTNF (30 infliximab; 45 adalimumab). The median time from MRE to commencing aTNF was 43 days (IQR 19.5-87 days). Eighteen of 75 (24%) had surgery during a median follow-up of 16.7 months (IQR 9.0-30.1 months). Patients with small bowel stenosis (SBS) on MRE were at a significantly higher risk of requiring surgery: 12/18 (66.7%) versus 6/57 (10.5%) (P<0.001). Time to surgery was significantly shorter in patients with SBS on MRE (P<0.001). In a multivariate analysis, SBS (P<0.0001, hazard ratio 26.45, 95% confidence interval 5.45-128.49) and presence of penetrating complications (P=0.003, hazard ratio 36.53, 95% confidence interval 3.40-393.19) were associated independently with time to surgery., Conclusion: SBS and penetrating complications on MRE are associated independently with a need for early surgery and treatment failure in patients commencing aTNF.

Background: This study evaluated the clinicopathological features and survival rates of patients with inflammatory bowel disease who developed colorectal cancer (CRC)., Methods: A retrospective review was performed on a prospectively maintained institutional database (1981-2011) to identify patients with inflammatory bowel disease who developed CRC. Clinicopathological parameters, management and outcomes were analysed., Results: A total of 2,843 patients with inflammatory bowel disease were identified. One thousand six hundred and forty-two had ulcerative colitis (UC) and 1,201 had Crohn's disease (CD). Following exclusion criteria, there were 29 patients with biopsy-proven colorectal carcinoma, 22 of whom had UC and 7 had CD. Twenty-six patients had a preoperative diagnosis of malignancy/dysplasia; 16 of these were diagnosed at surveillance endoscopy. Nodal/distant metastasis was identified at presentation in 47 and 71 % of the UC and CD group, respectively. Operative morbidity for UC and CD was 33 and 17 %, respectively. Despite the less favourable operative outcomes following surgery management of UC-related CRC, overall 5-year survival was significantly better in the UC group compared to the CD group (41 vs. 29 %; p = 0.04) reflecting the difference in stage at presentation between the two groups., Conclusions: Patients who undergo surgery for UC-related CRC have less favourable short-term outcomes but present at a less advanced stage and have a more favourable long-term prognosis than similar patients with CRC and CD.

Objective: To examine the association between single-nucleotide polymorphisms (SNPs) in CTGF (connective tissue growth factor) and patient outcomes after terminal ileal resection for Crohn's disease., Background: The primary indication for intestinal resection in Crohn's disease is fibrostenotic terminal ileal disease. CTGF is a cytokine overexpressed in the intestine of patients with Crohn's disease that influences outcomes in other disease processes., Methods: DNA was extracted from formalin-fixed, paraffin-embedded tissue from 147 patients with Crohn's disease who had undergone terminal ileal resection between 1981 and 2009. Genotyping was performed for 4 CTGF SNPs (rs9402373, rs12526196, rs6918698, and rs9399005), which modulate nuclear factor binding and CTGF production, and a smad3 SNP (rs17293632) involved in the CTGF pathway. Patients were phenotyped using the Montreal Disease Classification., Results: Sixty-seven of 147 patients (45.6%) were male; the mean age at diagnosis was 30.3 ± 12.6 years and the mean follow-up duration was 8.3 ± 7.1 years. Genotype-phenotype analysis demonstrated that the rs6918698GG genotype was associated with an older age of disease onset [>40 years; 30.6% vs 13.2%; odds ratio (OR): 2.891; 95% confidence interval (CI): 1.170-7.147). The rs9402373CC genotype was positively associated with type B1 disease (50.7% vs 26.3%; OR: 2.876; 95% CI: 1.226-6.743) and negatively associated with B2 disease (37.0% vs 65.0%; OR: 0.317; 95% CI: 0.144-0.699). None of the 5 SNPs assessed influenced clinical or surgical recurrence of Crohn's disease after intestinal resection. On multivariate analysis, male sex odds ratio (OR): 0.235; 95% CI: 0.073-0.755; P = 0.015] and never having smoked tobacco (OR: 0.249; 95% CI: 0.070-0.894; P = 0.033) reduced the risk, whereas having a prior appendectomy increased the risk (OR: 5.048; 95% CI: 1.632-15.617; P = 0.005) of surgical recurrence., Conclusions: These data implicate the rs6918698GG genotype with an age of disease onset of greater than 40 years in Crohn's disease whereas the rs9402373CC genotype is associated with a nonstricturing, nonpenetrating disease phenotype. CTGF SNPs do not influence the rate of recurrence after terminal ileal resection for Crohn's disease.

Background: Health related quality of life in inflammatory bowel disease is influenced both by disease activity as well as by the psychosocial characteristics of the individual patient. The Short Health Scale (SHS) is a four-part visual analogue scale questionnaire using open-ended questions that are designed to assess the impact of inflammatory bowel disease on a health related quality of life. The four dimensions include bowel symptoms, activities of daily life, worry and general wellbeing. It has previously been validated in Swedish and Norwegian speaking patients., Aim: To evaluate the SHS in an English speaking inflammatory bowel disease population., Methods: Four hundred and ninety Crohn's disease and ulcerative colitis patients completed the SHS. Individual SHS items were correlated with Inflammatory Bowel Disease Questionnaire (IBDQ) dimensions and with disease activity to assess validity. Test-retest reliability was assessed in 38 patients who completed the Short Health Scale two weeks apart., Results: All four items correlated with corresponding IBDQ dimensions with correlation coefficients ranging from -0.66 to -0.74 (all p values<0.001). In addition, total SHS scores correlated with total IBDQ scores in both Crohn's disease (-0.836) and ulcerative colitis (0.797). There was a stepwise increase in Short Health Scale scores with increasing disease activity (all p values<0.001). Reliability was confirmed with test-retest correlations ranging from 0.70 to 0.89 (all p values<0.005)., Conclusions: The Short Health Scale is a valid and reliable measure of health related quality of life in English speaking inflammatory bowel disease patients., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background and Aims: There is a high rate of stricturing post-operative recurrence in Crohn's disease (CD) particularly at sites of surgical anastomosis, and over 50% of these patients will require a repeat resection. Endoscopic dilatation of anastomotic strictures is an alternative to surgical resection in selected patients. We aimed to evaluate the safety and long term efficacy of endoscopic balloon dilatation of symptomatic anastomotic strictures in CD., Methods: Retrospective analysis of a prospectively maintained inflammatory bowel disease database of patients attending a single academic centre (n=1244 patients with CD) who underwent dilatation., Results: Fifty-five dilatations were performed in 31 patients (mean age 43 ± SD 12, 47% female). Median follow-up period was 46 months (IQR 14-62). Ninety percent of patients had successful initial dilatation and no complications occurred. Six (21%) avoided further dilatations or surgery in the follow-up period. Stricture recurrence was detected in 22 patients; 15 (54%) patients had repeat dilatations and seven (25%) went straight to surgery. Eight (28%) patients were managed with repeat dilatations of the stricture (median dilatations=2 range 2-6) and seven (25%) required surgery despite repeat dilatations. Median time from first dilatation to repeat surgery was 14.5 months (IQR 3-28) and to repeat dilatation was 13.8 months (IQR 4-28). There was no difference in immunomodulator use, biologic use and smoking status between the groups requiring surgery versus dilatation only., Conclusion: Endoscopic balloon dilatation of anastomotic strictures is safe and effective in providing symptomatic relief in CD patients. Forty-five percent of patients had a sustained response to single/serial balloon dilatation with avoidance of further surgical resection for a median interval of 46 months. Post-operative medical therapy and smoking status did not predict requirement for recurrent dilatation or surgery., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Introduction: Magnetic resonance enterography (MRE) is a relatively new imaging modality that involves small bowel distension with orally administered fluid. Few studies have assessed its impact on patient management., Aim: The aim of this study was to determine whether MRE influenced the management of patients with established small bowel Crohn's disease (CD)., Materials and Methods: From a prospectively maintained database of patients with inflammatory bowel disease, we identified patients with small bowel CD who underwent MRE between January 2007 and December 2010. The results of the MRE and subsequent changes in patient management within 1 month were evaluated., Results: Thirty women and 27 men with CD were included. Seven patients (12%) had a normal MRE. Forty-two of 57 (74%) patients had a change in management, and 41/50 (82%) patients with an abnormal MRE had changes in management (P<0.0008). After MRE, 20/42 (47%) patients had surgery and 22/42 (53%) had changes in medical treatment. Patients with stricturing disease had more surgical intervention (P=0.02), and patients with active disease on MRE had more medical intervention (P=0.0001). Patients with two or more abnormalities on MRE had more surgery compared with medical therapy (P=0.02)., Conclusion: The majority of patients with small bowel CD had a change in management as a result of the MRE. Because of its high clinical impact on patient management, MRE should become one of the preferred methods of small bowel evaluation in CD. Specific MRE findings may help to stratify treatment options, however, further work is required to validate this.

Introduction: The management of Crohn's disease (CD) has changed considerably over the last 20 years. Immunomodulators and biological therapies now play a role in treating patients with CD, but little is known of their influence on surgical rates., Aim: To review the surgery rates for CD in an Irish university hospital over a 20-year period and to determine whether newer therapies had an impact on surgical rates., Method: Seven hundred twenty-two patients attending St Vincent's University Hospital, Dublin, with CD over a 20-year period (January 1986 to December 2005) were identified. The patients were divided into quartiles. Resection rates were determined in all the quartiles, at both 1 and 3 years from diagnosis., Results: A decline in surgery, 3 years from diagnosis, was noted between the first quartile (72 patients, 40%) and the second quartile (58 patients, 32%; P=0.03). No significant change in surgical rates at 3 years occurred between the other 3 quartiles (32%, 30%, and 35%, respectively; P=NS). The patients who required a resection within 3 years were diagnosed at a younger age in later years. There was a similar predominance of 60% of female patients requiring surgery in all groups. The patients requiring surgery were twice as likely to be ex-smokers or current smokers in all groups. Use of infliximab, within 3 years from diagnosis, increased from 0, 0, and 16 patients (8.8%) to 40 patients (22.1%) in the last quartile. The majority of patients were treated with infliximab on an "on demand" basis. Use of infliximab earlier within the course of the disease was seen in later quartiles (ie, within 1 y of diagnosis): 0, 0, 6, and 21 patients., Conclusion: Despite the introduction of infliximab over the past 10 years, no demonstrable difference has been seen in the rates of patients requiring resection surgery within 3 years of diagnosis. The reasons for this are unclear, but may relate to episodic treatment, rather than regular maintenance treatment. Female patients and smokers seem to be particularly at risk of resection surgery.

Background & Aims: Therapeutic strategies for patients with Crohn's disease are based on American and European guidelines. High rates of corticosteroid dependency and low remission rates are identified as weaknesses of this therapy and as justification for early introduction of biologic agents (top-down treatment) in moderate/severe Crohn's disease. We reviewed outcomes and corticosteroid-dependency rates of patients with moderate-to-severe disease who were treated according to the international guidelines., Methods: Consecutive patients (102) newly diagnosed with Crohn's disease in 2000-2002 were identified from a prospectively maintained database. Severity of disease was scored using the Harvey-Bradshaw Index (HBI). Disease was classified by Montreal classification. Five-year follow-up data were recorded., Results: Seventy-two patients had moderate/severe disease at diagnosis (HBI >8). Fifty-four (75%) had nonstricturing, nonpenetrating disease (B1). Sixty-four (89%) received corticosteroids, and 44 (61%) received immunomodulators. Twenty-one patients (29%) received infliximab. Thirty-nine patients (54%) required resection surgery. At a median of 5 years, 66 of 72 (92%) patients with moderate/severe disease were in remission (median HBI, 1). Twenty-five patients (35%) required neither surgery nor biologic therapy., Conclusions: When international treatment guidelines are strictly followed, Crohn's disease patients can achieve high rates of remission and low rates of morbidity at 5 years. Indiscriminate use of biologic agents therefore is not appropriate for all patients with moderate-to-severe disease.

Background: The efficacy of biologic agents in Crohn's disease (CD) has led to proposals that they be introduced early in the disease (top-down treatment) with the aim of reducing corticosteroid dependency and surgical resection. However, the long-term use of biologic agents in limited CD may be difficult to justify. The aims were to assess outcomes for ileocecal resection in CD and evaluate its role in the current era., Methods: The study included 139 CD patients who underwent ileocecal resection between 1980 and 2000. Data were retrieved from a prospectively maintained database. Disease recurrence was defined as symptoms in addition to endoscopic or radiological evidence of disease activity. Severe disease recurrence was defined as a need for repeat resection surgery., Results: Seventy-two (52%) patients developed disease recurrence. Median (interquartile range) time to recurrence was 7.1 (5-10.6) years. Forty-nine (35%) patients required repeat resection surgery. Median (IQ range) time to repeat surgery was 7.2 (4.9-10.8) years. The presence of granulomas was associated with disease recurrence (P = 0.03) and repeat resection surgery (P = 0.01)., Conclusions: Long-term outcomes for ileocecal resection in CD are excellent with 48% of patients remaining symptom-free and only 35% requiring repeat resection surgery at 10 years. This should be borne in mind when considering biologic therapy.

Background: Infliximab is recognized as an effective therapy in unresponsive luminal and fistulating Crohn's disease. The use of maintenance or 'on demand' therapy thereafter is controversial., Aim: To assess the need for maintenance infliximab therapy in a clinical setting where immunomodulatory agents are widely used and where episodic therapy is used in preference to maintenance therapy., Methods: Ninety-three patients with Crohn's disease receiving infliximab; 72 with unresponsive luminal disease and 21 with fistulous disease. Data collected included disease site and duration, surgical and smoking history, initial response rates, duration of response maintenance and concomitant medications., Results: Fifty-six of 72 (78%) patients with luminal disease and 11 of 21 (52%) with fistulous disease achieved an initial response. Ten of 67 responders required conversion to maintenance infliximab infusions, while 31 remain in remission. Patients with luminal disease and those who had not taken previous surgery had higher response rates to infliximab. Younger patients and those with small bowel disease had higher relapse rates following initial response. Three patients developed allergic reactions to infliximab and one patient died of progressive pulmonary disease 6 weeks after their first infusion., Conclusions: Many patients with Crohn's disease can be maintained successfully with an episodic infliximab regimen.

Linkage of IBD to the pericentromeric region of chromosome 16 has been widely confirmed by analyses of multiple populations. The NOD2 gene is located in the peak region of linkage on chromosome 16 and thought to be involved in the activation of nuclear factor (NF) kappaB in response to bacterial components. Mutations in the NOD2 gene are found to be strongly associated with susceptibility to Crohn's disease (CD). A total of 65 Irish CD families were genotyped to determine if NOD2 mutations conferred susceptibility to CD and the prevalence of these mutations in sporadic and familial forms of the disease. The Irish population is relatively homogenous and thus may provide advantages in genetic studies of complex diseases. We confirmed the IBD1 locus as a susceptibility locus for IBD within the Irish population by linkage analysis followed by linkage disequilibrium studies. No significant evidence of linkage was observed to the previously identified regions on chromosomes 1, 12 and 14. In all, 131 CD affected families were then genotyped for seven of the previously published NOD2 single-nucleotide polymorphisms (SNPs). Allelic transmission distortion was investigated using the pedigree disequilibrium test (PDT). SNP13 (3020insC) was found to be associated with CD (P=0.0186). Patients who possessed a rare allele of SNP8, 12 or 13 presented earlier when compared to patients without rare variants (mean age, 20.1 vs 24 years, P=0.011) and the rare allele of SNP13 was observed to be predominantly linked to ileal disease (P=0.02). This report confirms the importance of NOD2 as a susceptibility gene for CD within the Irish population.