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Ulcerative colitis affects about 500,000 persons in the United States and accounts for more than 30,000 hospitalizations and 1 million workdays lost each year. The exacerbations and remissions that characterize the clinical course of the disease can make its management particularly challenging. What is the optimal approach to treatment? And which agents are most effective for maintenance therapy?
Ulcerative colitis affects about 500,000 persons in the United States and accounts for more than 30,000 hospitalizations and 1 million workdays lost each year.1 The exacerbations and remissions that characterize the clinical course of the disease can make its management particularly challenging. What is the optimal approach to treatment? And which agents are most effective for maintenance therapy?
Recently published practice guidelines for the management of ulcerative colitis in adults provide answers to these and other key questions. The highlights of these guidelines, which were developed under the auspices of the American College of Gastroenterology, are summarized here.1
Stool examination, sigmoidoscopy or colonoscopy, and biopsy are indicated to confirm the presence of colitis and to rule out infectious causes in patients who have bloody diarrhea, rectal urgency, or tenesmus. Order microbiologic studies for bacteria, parasites, and amebas; include assays for Escherichia coli 0157:H7 and Clostridium difficile, particularly in patients who have recently been hospitalized or treated with antibiotics. Characteristic endoscopic and histological findings in the absence of evidence of an infectious cause suggest ulcerative colitis. The mucosal changes characteristic of ulcerative colitis, as detected by proctosigmoidoscopy or colonoscopy, include loss of the typical vascular pattern, granularity, friability, and ulceration.
Once the diagnosis of ulcerative colitis is confirmed, determine whether the inflammation is distal or extensive. Distal disease-that limited to below the splenic flexure-can be treated with topical agents. In contrast, extensive disease, which extends proximal to the splenic flexure, generally requires systemic medication. Clinical and endoscopic findings are also used to define the severity of the disease (Table).
MEDICAL TREATMENTMild to moderate distal colitis. Oral aminosalicylates, topical mesalamine, and topical corticosteroids are appropriate for patients with mild to moderate distal colitis. Mesalamine enemas or suppositories may be effective in patients with colitis that is refractory to treatment with oral aminosalicylates or topical corticosteroids. If a patient does not respond adequately to maximal doses of all 3 agents, it may be necessary to give prednisone, up to 40 to 60 mg/d, or infliximab, with an induction regimen of 5 mg/kg at weeks 0, 2, and 6.
In patients with proctitis, remission can be maintained by mesalamine suppositories, whereas mesalamine enemas are appropriate for maintaining remission in those with distal colitis. Sulfasalazine, mesalamine compounds, and balsalazide can also be used to maintain remission.
Mild to moderate extensive colitis. Give oral sulfasalazine in daily doses titrated up to 4 to 6 g/d or an alternate aminosalicylate in doses up to 4.8 g/d. Reserve oral corticosteroids for patients whose disease is refractory to oral aminosalicylates (with or without topical therapy) or for those whose symptoms are particularly troublesome. 6-Mercaptopurine or azathioprine is effective in patients who do not respond to oral prednisone, provided they are not so acutely ill that they require intravenous therapy. Infliximab is an option for patients who do not respond to corticosteroids or are dependent on these agents despite adequate doses of a thiopurine or who are unable to tolerate corticosteroids.
A maintenance regimen is usually required for patients with mild to moderate extensive colitis, particularly those who have severe or relapsing disease. Sulfasalazine, olsalazine, mesalamine, and balsalazide are all effective in this setting. Long-term corticosteroid therapy is not recommended. 6-Mercaptopurine or azathioprine may be beneficial in corticosteroid-dependent patients and for those whose remission is not sufficiently maintained by aminosalicylates; these agents are occasionally useful in patients who are refractory to corticosteroid therapy but who are not acutely ill. Infliximab can be used to maintain remission in patients who respond to the induction regimen.
Severe colitis. Patients who do not respond to maximal therapy with oral prednisone, oral aminosalicylates, and topical agents may be given infliximab, 5 mg/kg, if urgent hospitalization is not needed. However, patients who exhibit toxicity require hospitalization, and intravenous corticosteroids are the cornerstone of therapy for these patients. If significant improvement is not observed within 3 to 5 days, colectomy or intravenous cyclosporine is indicated.
In patients with severe colitis, long-term remission may be achieved with maintenance doses of 6-mercaptopurine. Infliximab may be an alternative to colectomy for patients who fail to respond to intravenous corticosteroids; however, its long-term effectiveness in this setting is unknown.
Antibiotics are of no benefit in patients with severe colitis who do not have infection. Similarly, there is no support for the routine administration of total parenteral nutrition, although it may be appropriate for patients who have severe nutritional depletion.
In adults with ulcerative colitis, the absolute indications for surgery are exsanguinating hemorrhage, perforation, and documented or strongly suspected carcinoma. Surgery is also indicated in patients with severe colitis (with or without toxic megacolon) that is unresponsive to maximal conventional medical therapy and in patients with less severe but medically intractable symptoms or intolerable medication adverse effects.
Patients with ulcerative colitis are at increased risk for colorectal cancer, and the degree of risk is associated with the duration and extent of the disease.2 The cancers that typically occur in this setting are multiple, broadly infiltrative, anaplastic, and uniformly distributed throughout the colon; they appear to arise from flat mucosa.
Annual or biannual surveillance colonoscopy with multiple biopsies at regular intervals is warranted in patients who have had colitis for 8 to 10 years. Confirmed “high-grade” dysplasia in flat mucosa is an indication for colectomy; surgery may be warranted for “low-grade” dysplasia to forestall progression to a higher grade of neoplasia.
Fewer than 4 stools daily, with or without blood; no systemic signs of toxicity; normal erythrocyte sedimentation rate
More than 4 stools daily but with minimal signs of toxicity
More than 6 bloody stools daily and systemic toxicity, as evidenced by fever, tachycardia, anemia, or an elevated erythrocyte sedimentation rate
More than 10 bowel movements daily, continuous bleeding, toxicity, and abdominal tenderness and distention; patients may also require blood transfusion; abdominal radiographs may show colonic dilation
1. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105:501-523.
2. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48:526-535.