Relationship between clinical features of Crohn's disease and the risk of developing extraintestinal manifestations

Eur J Gastroenterol Hepatol. 2007 Jan;19(1):73-8. doi: 10.1097/01.meg.0000243883.47938.aa.


Objectives: Crohn's disease is frequently associated with extraintestinal manifestations. The aim of this study was to evaluate the degree of association between the development of extraintestinal manifestations, the clinical forms of Crohn's disease according to the Vienna Classification and to the presence of several potential risk factors of the disease.

Methods: One hundred and seventy-three consecutive Crohn's disease patients were studied. Sex, smoking habits, previous Crohn's disease-related surgery, family history of Crohn's disease, steroid dependency, steroid resistance and the presence of at least one mutant allele in any of the three considered variants of CARD15 gene were considered as potential risk factors. The Vienna Classification was applied, and the presence of extraintestinal manifestations was evaluated.

Results: A total of 61 (35.3%) patients developed extraintestinal manifestations. They were more frequently seen in women than in men (41.1 vs. 26.7%), (odds ratio 1.92, 95% confidence interval: 0.99-3.70; P=0.05) and in steroid-dependent patients than in steroid responders (61.1 vs. 28.5%), (odds ratio 3.94, 95% confidence interval: 1.83-8.49; P<0.01). No relationship was found in general between the extraintestinal manifestations of Crohn's disease and smoking habits, previous Crohn's disease-related surgery, a family history of Crohn's disease, steroid resistance and CARD15 mutations. Such relationships were, however, detected for some individual extraintestinal manifestations as between both smoking habits (odds ratio 9.09, 95% confidence interval: 1.15-71.66; P<0.05) and the G908R CARD15 mutation (odds ratio 4.76, 95% confidence interval: 1.11-20.43; P<0.05), respectively, and erythema nodosum. Patients with any colonic involvement of Crohn's disease (L2+L3) suffered from extraintestinal manifestations of the disease more frequently than patients without colonic involvement (42.7 vs. 25.9%, respectively; odds ratio 2.12, 95% confidence interval: 1.10-4.07; P<0.05).

Conclusions: Female gender, steroid-dependency and colonic involvement are associated with the risk of developing extraintestinal manifestations of Crohn's disease.

MeSH terms

  • Adult
  • Aged
  • Arthritis / etiology
  • Cholelithiasis / etiology
  • Colitis / complications
  • Colitis / drug therapy
  • Colitis / genetics
  • Crohn Disease / complications*
  • Crohn Disease / drug therapy
  • Crohn Disease / genetics
  • Crohn Disease / pathology
  • Erythema Nodosum / etiology
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Nod2 Signaling Adaptor Protein / genetics
  • Risk Factors
  • Sex Factors


  • Glucocorticoids
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein