US Gastroenterology & Hepatology Review, 2008;4(2):44-46
Crohn’s disease is a chronic inflammatory disorder of the gastrointestinal tract affecting approximately 0.001% of the US population, totalling an estimated 700,000 cases.1 The disease usually presents in teenagers or early adulthood with a smaller incidence peak later in life.2 The precise etiology of Crohn’s disease remains elusive. The current hypothesis is that affected individuals have a genetic predisposition that when combined with environmental factors triggers an imbalance in the immune system, possibly related to defects in innate immunity, and results in an inability to control mucosal inflammation. One environmental factor—smoking— has been associated with more severe Crohn’s disease that requires more aggressive therapy.3 Furthermore, recurrence following surgery is more frequent and more rapid in patients who smoke.4
Disease severity can be classified into mild, moderate, or severe based on clinical signs and symptoms, including the amount of abdominal pain, the frequency of bowel movements, the presence of transmural complications, such as strictures and fistulae, and extra-intestinal systemic symptoms. Classification according to the disease location and intestinal complications is important for treatment selection. Refractory disease is defined as those patients with persistent or progressive symptoms despite any level of therapy, and mostly applies to patients who require recurrent courses of prolonged steroids, repeated surgery, or immunomodulators or biologic agents.5,6
Treatment Regimen Options
Therapeutic recommendations for patients with a new presentation or relapse of Crohn’s disease depend on the disease location, severity, and complications. Treatment is then individualized according to symptomatic response and tolerance to medical intervention, and once symptoms and signs of disease are controlled (induction of a response or remission), treatment is administered to ‘maintain response or remission.’ Surgery is appropriate for obstructing stenoses, suppurative complications, or medically refractory disease.
In 2001, Hanauer et al. published guidelines on the management of Crohn’s disease in adults;5 updates to these guidelines are expected in February 2009. Mild to moderate symptomatic ileal, ileocolonic, or colonic disease can be treated with an oral aminosalicylate (mesalamine or sulfasalazine— first used in the 1970s) or metronidazole, which is effective in a proportion of patients not responding to sulfasalazine. Ciprofloxacin is equally effective as mesalamine, but budesonide delivered to the ileum and right colon is more effective for the short-term induction of remission. Patients with moderate to severe disease are treated with prednisone, frequently in high doses, until resolution of symptoms. Infection or abscesses require antibiotic therapy or drainage. However, over 40% of patients treated acutely with corticosteroids will become steroid-dependent or -resistant,7 particularly smokers or those with colonic disease.8 Azathioprine and mercaptopurine, two antimetabolite agents, are beneficial to maintain remissions following steroid-induction therapy but may require a period of up to four to six months to become effective.9 Severe or fulminant Crohn’s disease requires hospitalization, treatment with intravenous hydrocortisone and intensive support, including nutritional supplementation.
Biologic agents in the form of chimeric antibodies to tumor necrosis factor (TNF)-a were first introduced to clinical practice a decade ago. Infliximab was the first approved by the US Food and Drug Administration (FDA) for treatment of Crohn’s disease. It is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult and pediatric patients with moderately to severely active disease who have had an inadequate response to conventional therapy. It is also indicated for treating enterocutaneous (primarily peri-anal) and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn’s disease.10 Infusions of infliximab are an effective adjunct and may be an alternative to steroid therapy in selected patients in whom corticosteroids are contraindicated or ineffective.
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