What Causes Crohn's Disease?

Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract. Though the terminal ileum and colon are most commonly involved, this disease may affect any region of the alimentary canal. Approximately 50 percent of patients with Crohn's disease will have involvement of both the terminal ileum and colon, 30 percent the terminal ileum alone, and 20 percent will have disease restricted to the colon. The disease may be either acute or subacute.

Though Crohn's disease is worldwide in its distribution, the incidence, prevalence, and severity vary greatly. Incidence is increasing in the United States and is currently five to 10 cases per 100,000. It is 20 to 50 percent more common in whites than in blacks, up to 30 percent more common in women than in men, and three to eight times more common in Jews compared with non-Jews. The risk for first-degree relatives of patients with Crohn's disease is 8.9 percent for offspring, 8.8 percent for siblings, and 3.5 percent for parents. The peak age of onset is between 15 and 25 years, and there may be a second, lesser peak that occurs at age 55 to 65. Crohn's disease may occur in childhood, though its incidence is much lower prior to adolescence.

The precise etiology and pathogenesis of Crohn's disease continue to elude investigators. Genetic, environmental, microbial, and immunologic processes must be considered in any theory of pathogenesis. Substantial evidence supporting a genetic role in pathogene-sis includes population and family studies, twin studies, genetic marker studies, the association of rare genetic syndromes with Crohn's disease, and the increased frequency of certain other diseases in Crohn's disease patients. Cigarette smoking has been examined as an environmental factor. In one study, cigarette smoking was associated with a significantly increased risk of Crohn's disease. Cigarette smokers have also been shown to have an increased incidence of recurrence following surgical resection compared with non-smokers. Several studies have demonstrated that oral contraceptives double the risk of Crohn's disease, though one case-controlled study failed to show such an association.

Since the beginning of this century, investigators have searched for a microbial agent responsible for development and/or activation of the immune response. A variety of microbial agents, including bacteria, viruses, chlamydia, and mycobacteria, have been implicated, but none could be directly implicated in a conventional microbial etiology. Currently, various mycobacteria are being investigated as possible pathogens involved in the development of Crohn's disease.

An abundance of evidence supports activation of the immune response as playing a central role in pathogenesis. Unfortunately, the identification of an antigenic stimulus remains elusive. In view of this, one must give serious consideration to a defect in immunoregulation of the mucosal immune system. In the last decade, much attention has been given to the study of various soluble mediators of the immune system, including prostaglandins, leukotrienes, interleukins, interferon, platelet activating factor, histamine, kinins, and neuropeptides. Further review of the immunologic basis of Crohn's disease is beyond the scope of this article.

Last updated Jan 4/07