The presence of fistulas and NOD2 homozygosity strongly predict intestinal stenosis in Crohn’s disease independent of the IL23R genotype
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Background and aims
We analyzed the prevalence of concomitant intestinal stenosis in patients with fistulizing Crohn’s disease (CD), including the NOD2/CARD15 and IL23R genotype status.
Medical records of n = 1,110 patients with inflammatory bowel diseases were screened for patients with fistulizing and stricturing CD. Study inclusion required diagnosis of stenosis made within 6 months of diagnosing fistulas. CD-associated NOD2 and IL23R variants were genotyped. Similarly, we prospectively investigated 42 patients presenting with fistulizing CD.
In the retrospective study (n = 333 CD patients), fistulas were found in 145 (43.5%) patients and stenoses in 223 (67.0%) patients. Concomitant stenosis was diagnosed in 125 patients with fistulas resulting in a positive predictive value (PPV) of 86.2% for fistulas predicting intestinal stenosis (p = 5.53 × 10−11; OR 5.74, 95% CI 3.22–10.50). In logistic regression analysis, presence of fistulas (OR 4.51; 95% CI 2.54–8.01, p = 2.68 × 10−7) and disease duration (OR 1.09; 95% CI 1.05–1.13; p = 3.19 × 10−6) were strongly associated with intestinal stenosis. NOD2 genotype information, but not IL23R status, increased the PPV for the correct diagnosis of stenosis (PPV = 89.9%). All homozygous carriers (100%) of NOD2 variants with fistulizing CD were diagnosed with stenosis; 1007fs homozygotes were found more often among patients with fistulas and stenoses than in patients without stenoses and fistulas (p = 0.00037). Similar results were found in the prospective analysis, in which 83.3% of the patients with fistulizing CD had concomitant stenosis.
Fistulizing CD is strongly associated with concomitant intestinal stenosis, particularly in homozygous carriers of NOD2 mutations.
KeywordsCrohn’s disease Inflammatory bowel disease Fistula Stenosis NOD2/CARD15 IL23R
Caspase-activation recruitment domain
Inflammatory bowel disease
Interleukin 23 receptor (gene)
Multivariable fractional polynomials
Magnetic resonance imaging
Nucleotide-binding oligomerization domain
Negative predictive value
Polymerase chain reaction
Positive predictive value
Single nucleotide polymorphism
This manuscript contains parts of the unpublished degree thesis of J. Wagner. S. Brand was supported by grants from Deutsche Forschungsgemeinschaft (DFG; BR 1912/5-1), the Else Kröner-Fresenius-Stiftung (Else Kröner Fresenius Memorial Stipendium 2005; P50/05/EKMS05/62), the Ludwig-Demling Grant 2007 from DCCV e.V. and by grants from the Ludwig-Maximilians-University Munich (Excellence Initiative, Investment Funds 2008 and FöFoLe program). M. Jürgens and T. Ochsenkühn were supported by a grant from Centocor, Inc. J. Seiderer was supported by grants from the Ludwig-Maximilians-University (FöFoLe 422), Robert-Bosch-Stiftung and Else Kröner-Fresenius-Stiftung (Else Kröner-Fresenius Memorial Grant 2008; P81/08//EKMS08/01).
Conflict of interest statement
None of the authors and co-authors have a conflict of interest related to this manuscript.
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