Pathogenesis and therapeutic aspects of Crohn's disease

Crohn's disease is a chronic, relapsing inflammatory condition affecting any part of the human gastrointestinal tract. It is characterised by transmural inflammation with deep ulceration, thickening of the bowel wall and fistula formation. The hallmark is the non-caseating granuloma. Clinical presentation depends upon the site of the inflammation. Pain and diarrhoea are frequent. Extraintestinal manifestations develop in up to 25% of patients and perianal disease is also frequent. The aetiology of Crohn's disease remains unknown. On the host side, genetic factors are important and the immune system is central to the development of the inflammation. Several environmental factors also play a role, in particular smoking. The presence of intestinal luminal contents appears to be essential for the development of Crohn's disease. A number of specific infectious causes have also been proposed, most recently measles virus and M. avium subsp. paratuberculosis. The latter has been considered because of the similarity between BJD and Crohn's disease, although there are also important differences. Evidence suggesting that this agent plays a role includes isolation of the organism from some patients, clustering, and identification by PCR of M.a. paratuberculosis DNA in tissue. However, many other workers have been unable to reproduce these findings.Treatment of Crohn's disease is generally with 5-aminosalicylic acid (5-ASA) compounds, corticosteroids, immunosuppressive agents and antibiotics. The majority of patients with active disease will respond to one or a combination of the therapies. Recently, broad-spectrum antibiotics have been shown to be as effective as oral corticosteroids. The challenge in Crohn's disease remains the prevention of relapse once remission has been achieved. Oral 5-ASA preparations can be beneficial, particularly after surgery. Immunosuppression, particularly with azathioprine or 6-mercaptopurine, is helpful in patients with resistant inflammation. Antibiotics may delay the time to relapse when used for active disease. The use of antimycobacterial therapy directed against M.a. paratuberculosis shows promising results but needs further evaluation.Up to 80% of patients with Crohn's disease will require surgery at some stage in the course of their illness. The challenge remains to try and prevent resection of inflamed intestine and to improve the quality of life of those affected by this disorder.