Natural history and long-term clinical course of Crohn's disease.

Crohn's disease is a chronic inflammatory disease process involving different sites in the gastrointestinal tract. Occasionally, so-called metastatic disease occurs in extra-intestinal sites. Granulomatous inflammation may be detected in endoscopic biopsies or resected tissues. Genetic, epigenetic and environmental factors appear to play a role. Multiple susceptibility genes have been described in both familial and non-familial forms while the disease is phenotypically heterogeneous with a female predominance. The disorder occurs over a broad age spectrum, from early childhood to late adulthood. More than 80% are diagnosed before age 40 years usually with terminal ileal and colonic involvement. Pediatric-onset disease is more severe and more extensive, usually with a higher chance of upper gastrointestinal tract disease, compared to adult-onset disease. Long-term studies have shown that the disorder may evolve with time into more complex disease with stricture formation and penetrating disease complications (i.e., fistula, abscess). Although prolonged remission may occur, discrete periods of symptomatic disease may re-appear over many decades suggesting recurrence or re-activation of this inflammatory process. Eventual development of a cure will likely depend on identification of an etiologic cause and a fundamental understanding of its pathogenesis. Until now, treatment has focused on removing risk factors, particularly cigarette smoking, and improving symptoms. In clinical trials, clinical remission is largely defined as improved numerical and endoscopic indices for "mucosal healing". "Deep remission" is a conceptual, more "extended" goal that may or may not alter the long-term natural history of the disease in selected patients, albeit at a significant risk for treatment complications, including serious and unusual opportunistic infections.