title: The presence of fistulas and NOD2 homozygosity strongly predict intestinal stenosis in Crohn's disease independent of the IL23R genotype.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Fistulizing CD is strongly associated with concomitant intestinal stenosis, particularly in homozygous carriers of NOD2 mutations.
authors.affiliation: Department of Medicine II, Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Jürgens
authors.forename: Stephan
authors.initials: S
authors.lastname: Brand
authors.forename: Rüdiger P
authors.initials: RP
authors.lastname: Laubender
authors.forename: Julia
authors.initials: J
authors.lastname: Seiderer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Glas
authors.forename: Martin
authors.initials: M
authors.lastname: Wetzke
authors.forename: Johanna
authors.initials: J
authors.lastname: Wagner
authors.forename: Simone
authors.initials: S
authors.lastname: Pfennig
authors.forename: Cornelia
authors.initials: C
authors.lastname: Tillack
authors.forename: Florian
authors.initials: F
authors.lastname: Beigel
authors.forename: Maria
authors.initials: M
authors.lastname: Weidinger
authors.forename: Fabian
authors.initials: F
authors.lastname: Schnitzler
authors.forename: Martin E
authors.initials: ME
authors.lastname: Kreis
authors.forename: Burkhard
authors.initials: B
authors.lastname: Göke
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Karin
authors.initials: K
authors.lastname: Herrmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Ochsenkühn
mesh_terms: D003251:Constriction, Pathologic / Q000209:etiology / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics / Q000503:physiopathology*; D005838:Genotype; D006801:Humans; D007412:Intestinal Fistula / Q000209:etiology* / Q000235:genetics; D007415:Intestinal Obstruction / Q000209:etiology / Q000235:genetics; D016015:Logistic Models; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018123:Receptors, Interleukin / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: C515500:IL23R protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin