Sa1262 Long Diagnostic Delay in Crohn's Disease is Associated With Complicated Disease Course and Increased Operation Rate

Abstract Background Genetic variations within the regulatory region of the gene encoding NOD-like receptor pyrin domain containing 3 (NLRP3) have been associated with Crohn’s Disease (CD). NLRP3 is part of the NLRP3-inflammasome that mediates the maturation of IL-1β and IL-18. Carrying the major allele of the single nucleotide polymorphisms (SNPs) rs10733113, rs4353135 and rs55646866 is associated with an increased risk for CD. We here studied the impact of these polymorphisms on clinical characteristics in patients of the Swiss IBD Cohort Study (SIBDCS). Methods We included 981 Crohn’s disease (CD) patients and 690 ulcerative colitis (UC) patients of the SIBDCS. We analyzed whether three CD-associated NLRP3 polymorphisms have an impact on the clinical disease course in these patients. Results In CD patients presence of the major allele (G) of rs10733113 was associated with less surgeries and lower maximal CDAI and a similar trend was observed for rs55646866 and rs4353135. Presence of the major allele of all three SNPs was negatively correlated to maximal CDAI. In UC patients homozygous genotype for the major allele (CC) for rs55646866 was associated with a higher age at diagnosis and a higher MTWAI index. Homozygous genotype for the major allele of all three polymorphisms was associated with a higher number of ambulatory visits and longer hospital stays. Conclusions In CD patients presence of the major allele of all three polymorphisms was associated with markers of a less severe disease course, while in UC the homozygous genotype for all major alleles suggested a more severe disease activity.

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Systematic Analysis of the Impact of Diagnostic Delay on Bowel Damage in Paediatric Versus Adult Onset Crohn’s Disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz065 ◽

2019 ◽

Vol 13 (10) ◽

pp. 1334-1342 ◽

Cited By ~ 10

Author(s):

Alain Schoepfer ◽

Jessica Santos ◽

Nicolas Fournier ◽

Susanne Schibli ◽

Johannes Spalinger ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Diagnostic Delay ◽

Perianal Fistula ◽

Adult Patients ◽

Adult Onset ◽

Systematic Analysis ◽

Internal Fistula ◽

The Impact

Abstract Background and Aims Length of diagnostic delay is associated with bowel strictures and intestinal surgery in adult patients with Crohn’s disease [CD]. Here we assessed whether diagnostic delay similarly impacts on the natural history of paediatric CD patients. Methods Data from the Swiss IBD Cohort Study were analysed. Frequency of CD-related complications [bowel stenosis, perianal fistula, internal fistula, any fistula, resection surgery, fistula/abscess surgery, any complication] at diagnosis and in the long term [up to 30 years after CD diagnosis] was compared between paediatric patients [diagnosed <18 years] and adult patients [diagnosed ≥18 years] using multivariate Cox proportional hazard regression modelling. Results From 2006 to 2016, 387 paediatric and 1163 adult CD patients were included. Median [interquartile range: IQR] diagnostic delay was 3 [1–9] for the paediatric and 6 [1–24] months for the adult group, respectively. Adult onset CD patients presented at diagnosis more frequently with bowel stenosis [p <0.001] and bowel surgery [p <0.001] compared with paediatric CD patients. In the long term, length of diagnostic delay was significantly associated with bowel stenosis [p = 0.001], internal fistula [p = 0.038], and any complication [p = 0.024] in the adult onset CD population. No significant association between length of diagnostic delay and CD-related outcomes in the long term was observed in the paediatric population. Conclusions Adult CD patients have longer diagnostic delay compared with paediatric CD patients and present at diagnosis more often with bowel stenosis and surgery. Length of diagnostic delay was found to be predictive for CD-related complications only in the adult but not in the paediatric CD population.

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OP12 The incidence and disease course of perianal Crohn’s disease: A Danish nationwide cohort study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.011 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S012-S012

Author(s):

M D Wewer ◽

M Zhao ◽

A Nordholm-Carstensen ◽

J B Seidelin ◽

J Burisch

Keyword(s):

Rectal Cancer ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Incidence Rate ◽

Anal Cancer ◽

Perianal Fistula ◽

Disease Course ◽

Perianal Crohn’S Disease ◽

Increased Risk ◽

Perianal Crohn's Disease

Abstract Background Perianal Crohn’s disease (pCD) has a major negative impact on patients’ quality of life and is complex to treat. Despite its putative high frequency and burden for patients, only a few studies have investigated the incidence, disease course and associated cancer-risk in a population-based setting. The aim was to assess the incidence and course of pCD in adult patients with CD within a 19-year period. Specifically, describing changes in medical and surgical management as well as rates of cancer. Methods The cohort comprised all individuals >18 years diagnosed with CD in Denmark between 1 January 1997 and 31 December 2015. Patients were identified in the National Patient Registry. Chi-square test, Mann–Whitney–Wilcoxon test and multivariate Cox regression analysis were used. Results A total of 1,697/9,739 (17%) patients with CD were found to have pCD. Perianal fistulas were the most common manifestation accounting for 943 (56%) cases. The onset of pCD before CD diagnosis occurred in 32%. The overall incidence of pCD was 20/1,000 patient-years. The incidence of pCD remained stable over time. More patients with pCD were treated with immunomodulators (70%) and biologics (35%) than those without pCD (51%, p < 0.001 and 15%, p < 0.001, respectively). Defunctioning stoma was performed in 157/943 (17%) of perianal fistula patients. Stoma formation in relation to resection was performed in 112/943 (12%) of perianal fistula patients. Patients with pCD were found to have a significantly increased risk of undergoing major abdominal surgery compared with patients without pCD (hazard ratio: 1.52, 95% CI: 1.40 to 1.65, p < 0.001). The incidence rate ratios of anal and rectal cancer in pCD patients were 12.46 (95% CI: 5.07 to 30.59, p < 0.001) and 2.41 (95% CI: 1.31 to 4.42, p = 0.003) respectively, when compared with non-IBD matched controls. The incidence rate ratio of anal and rectal cancer in pCD patients was 2.36 (95% CI: 0.86 to 6.50, p = 0.09) and 1.35 (95% CI: 0.68 to 2.68, p = 0.38) respectively, when compared with CD patients without pCD. Conclusion In this nationwide study, 17% of the CD patients developed pCD. The continuing high incidence of pCD suggests a limited disease-modifying effect of biologics. Patients with pCD were at increased risk of undergoing major surgery compared with non-pCD patients. The risk of rectal or anal cancer was increased in patients with pCD compared with non-IBD matched controls. These findings encourage surveillance of rectal and anal cancer.

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The Incidence and Disease Course of Perianal Crohn’s Disease: A Danish Nationwide Cohort Study, 1997–2015

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa118 ◽

2020 ◽

Author(s):

M D Wewer ◽

M Zhao ◽

A Nordholm-Carstensen ◽

P Weimers ◽

J B Seidelin ◽

...

Keyword(s):

Rectal Cancer ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Cox Regression ◽

Major Surgery ◽

Disease Course ◽

Cox Regression Analysis ◽

Perianal Crohn’S Disease ◽

Increased Risk ◽

Perianal Crohn's Disease

Abstract Background and Aims Perianal Crohn’s disease [CD] places a considerable burden on patients’ quality of life and is complex to treat. Despite its impact and high frequency, few studies have investigated the incidence and disease course of perianal CD. The aim of this study was to assess the incidence and disease course of perianal CD in adult patients throughout a 19-year period. Methods The cohort comprised all individuals aged 18 years or older who were diagnosed with CD in Denmark between January 1, 1997, and December 31, 2015, according to the National Patient Registry [NPR]. Results A total of 1812 [19%] out of 9739 patients with CD were found to have perianal CD. Perianal fistulas were the most common manifestation, accounting for 943 [52%] cases. The incidence of perianal CD remained stable over time. Patients with perianal CD were found to have an increased risk of undergoing major abdominal surgery compared with patients without perianal CD (hazard ratio: 1.51, 95% confidence interval [CI]: 1.40 to 1.64, p <0.001) in a multivariate Cox regression analysis. The incidence rate ratios of anal and rectal cancer in perianal CD patients were 11.45 [95% CI: 4.70 to 27.91, p <0.001] and 2.29 [95% CI: 1.25 to 4.20, p = 0.006], respectively, as compared with non-IBD matched controls. Conclusions In this nationwide study, 19% of CD patients developed perianal disease. Patients with perianal CD were at increased risk of undergoing major surgery compared with non-perianal CD patients. The risk of anal and rectal cancer was increased in patients with perianal CD compared with non-IBD matched controls. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

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