The presence of fistulas and NOD2 homozygosity strongly predict intestinal stenosis in Crohn's disease independent of the IL23R genotype

J Gastroenterol. 2010 Jul;45(7):721-31. doi: 10.1007/s00535-010-0231-7. Epub 2010 Apr 29.


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.

Methods: 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.

Results: 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 x 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 x 10(-7)) and disease duration (OR 1.09; 95% CI 1.05-1.13; p = 3.19 x 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.

Conclusion: Fistulizing CD is strongly associated with concomitant intestinal stenosis, particularly in homozygous carriers of NOD2 mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Constriction, Pathologic / etiology
  • Constriction, Pathologic / genetics
  • Crohn Disease / genetics
  • Crohn Disease / physiopathology*
  • Genotype
  • Humans
  • Intestinal Fistula / etiology*
  • Intestinal Fistula / genetics
  • Intestinal Obstruction / etiology
  • Intestinal Obstruction / genetics
  • Logistic Models
  • Mutation
  • Nod2 Signaling Adaptor Protein / genetics*
  • Predictive Value of Tests
  • Prospective Studies
  • Receptors, Interleukin / genetics*
  • Retrospective Studies


  • IL23R protein, human
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Receptors, Interleukin