Article

The Role of CARD15 Mutations and Smoking in the Course of Crohn's Disease in a Mediterranean Area

Ematologia II Ospedale V. Cervello, Palermo, Italy.
The American Journal of Gastroenterology (Impact Factor: 9.21). 04/2008; 103(3):649-55. DOI: 10.1111/j.1572-0241.2007.01589.x
Source: PubMed

ABSTRACT To evaluate the role of CARD15 mutations and smoking in the main events of Crohn's disease (CD).
A total of 182 patients with CD were included in a prospective study in order to evaluate the role of CARD15 mutations and smoking in the main outcomes of disease course: first operation and surgical recurrence. The following variables were evaluated in a univariable and multivariable analysis: age, sex, site of disease, pattern, smoking habit, extraintestinal manifestations, duration of disease, and CARD15 mutation. The Kaplan-Meier method for survival curves and Cox model for multivariable analysis were, respectively, used.
A total of 110 patients were operated on and 32 were reoperated on. The 7-yr cumulative free rate of surgery was 42% (95% CI 34-51%). At multivariate analysis only stricturing and penetrating pattern were predictors of surgery (HR 1.7, 95% CI 1-2.8; HR 3.2, CI 1.8-5.5, respectively). The 7-yr cumulative free rate of reoperation was 75% (95% CI 0.52-0.88). At multivariable analysis in the model with any CARD15 mutation, only smoking habit at diagnosis (HR 3.6, 95% CI 1.4-9.1) was predictive of surgical recurrence. When single mutations were considered in the model smoking (HR 4.2, 95% CI 1.8-10.1) and L1007fs mutation (HR 2.9, 95% CI 1.1-7.3) were predictive of reoperation.
In CD, smoking predicts recurrence after surgery. The role of CARD15 mutations in the clinical course of CD remains undefined.

0 Followers
 · 
148 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The majority of patients with Crohn’s disease require surgery for disease-related complications. Postoperative Crohn’s disease recurrence is common after intestinal resection. The optimal management strategy for postoperative recurrence of Crohn’s disease is controversial. In the absence of universally adopted guidelines, clinicians and patients must discuss and weigh the risks and benefits of postoperative pharmacotherapy. Those patients at low risk of disease recurrence may not require treatment. On the other hand, patients with more aggressive disease and high risk of recurrence may be best treated early in the postoperative period with an immunomodulator or antitumor necrosis factor agents. Ideally, postoperative treatment decisions would be made using predictable, reliable, and reproducible clinical prediction criteria that would guide treatment. This article reviews the data on postoperative Crohn’s disease, including predictors of early recurrence, available options for postoperative monitoring, timing of initiation, and choice of postoperative therapy for prevention and management.
  • Source
    Inflammatory Bowel Diseases 01/2008; 14(9):1313. DOI:10.1002/ibd.20424 · 5.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Crohn's disease is a chronic inflammatory condition that may involve any segment of the gastrointestinal tract. Although several drugs have proven efficacy in inducing and maintaining disease in remission, resectional surgery remains as a cornerstone in the management of the disease, mainly for the treatment of its stenosing and penetrating complications. However, the occurrence of new mucosal (endoscopic) lesions in the neoterminal ileum early after surgery is almost constant, it is followed in the mid-term by clinical symptoms and, in a proportion of patients, repeated intestinal resections are required. Pathogenesis of postoperative recurrence (POR) is not fully understood, but luminal factors (commensal microbes, dietary antigens) seem to play an important role, and environmental and genetic factors may also have a relevant influence. Many studies tried to identify clinical predictors for POR with heterogeneous results, and only smoking has repeatedly been associated with a higher risk of POR. Ileocolonoscopy remains as the gold standard for the assessment of appearance and severity of POR, although the real usefulness of the available endoscopic score needs to be revisited and alternative techniques are emerging. Several drugs have been evaluated to prevent POR with limited success. Smoking cessation seems to be one of the more beneficial therapeutic measures. Aminosalicylates have only proved to be of marginal benefit, and they are only used in low-