Publication

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

Journal Paper/Review - Apr 29, 2010

Units
PubMed
Doi

Citation
Jürgens M, Herrmann K, Lohse P, Göke B, Kreis M, Schnitzler F, Weidinger M, Beigel F, Tillack C, Pfennig S, Wagner J, Wetzke M, Glas J, Seiderer J, Laubender R, Brand S, Ochsenkühn T. The presence of fistulas and NOD2 homozygosity strongly predict intestinal stenosis in Crohn's disease independent of the IL23R genotype. J Gastroenterol 2010; 45:721-31.
Type
Journal Paper/Review (English)
Journal
J Gastroenterol 2010; 45
Publication Date
Apr 29, 2010
Issn Electronic
1435-5922
Pages
721-31
Brief description/objective

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.