The American College of Gastroenterology's Practice Parameters Committee has issued updated practice guidelines for the treatment of ulcerative colitis in adults. The guidelines were generated by an expert panel's review of published evidence and outline the preferred approaches to the treatment of patients with ulcerative colitis, a chronic disease characterized by diffuse mucosal inflammation of the colon and marked by bloody diarrhea, rectal urgency, and tenesmus. Ulcerative colitis affects 250,000 to 500,000 people in the United States each year resulting in steep hospital and drug costs as well as lost work. The full text of the updated practice guidelines, which originally appeared in the July 2004 issue of the American Journal of Gastroenterology, is available at http://www.acg.gi.org/physicians/guidelines/UlcerativeColitisUpdate.pdf.
The quality of evidence on which a recommendation is based is as follows:
Grade A: Homogenous evidence from multiple well-designed randomized (therapeutic) or cohort (descriptive) controlled trials, each involving a number of participants to be of sufficient statistical power.
Grade B: Evidence from at least one large well-designed clinical trial with or without randomization, from cohort or case-control analytic studies, or well-designed meta analyses.
Grade C: Evidence based on clinical experience, descriptive studies, or reports of expert committees.
Diagnosis and Management
In patients with persistently bloody diarrhea, rectal urgency, or tenesmus, stool examinations, sigmoidoscopy, and biopsy should be performed to confirm the presence of colitis and to exclude the presence of infectious etiologies. When obtaining the patient's history, the clinician should inquire about factors known to exacerbate symptoms of ulcerative colitis, such as recent or past smoking cessation or use of nonsteroidal anti-inflammatory drugs.
Because infectious agents can produce symptoms indistinguishable from ulcerative colitis, microbiologic analyses for bacteria, parasites, and amoebas should be performed. In particular, infection with Escherichia coli O157:H7 and Clostridium difficile (in patients who have been recently hospitalized or who have received antibiotics) should be excluded.
Proctosigmoidoscopy or colonoscopy will reveal the mucosal changes characteristic of ulcerative colitis: loss of the typical vascular pattern, granularity, friability, and ulceration. These changes usually appear in the distant rectum and proceed proximally to involve part or all of the colon, although isolated cecal inflammation may be seen.
If a diagnosis of Crohn's disease is being considered, radiographs of the small bowel will help distinguish it from ulcerative colitis. The diagnosis may be Crohn's disease if histology finds noncaseating granulomas or microscopic focality. In patients with acute onset of bloody diarrhea, mucosal biopsy may help distinguish ulcerative colitis from infectious colitis. In patients who have ulcerative colitis, the following occur: the mucosa more commonly demonstrates separation, distortion, and atrophy of crypts; inflammatory cells in the lamina propria; neutrophils in the crypt epithelium; elevated plasma cells near the crypt bases; and basilar lymphoid aggregates.
Treatment for ulcerative colitis seeks to improve quality of life by inducing and maintaining remission of symptoms and inflammation. The extent of the proximal margin of inflammation, assessed by endoscopy, is either distal (limited to below the splenic flexure and within reach of topical therapy) or extensive (extending proximal to the splenic flexure, requiring systemic medication). Because an important criterion for treatment of ulcerative colitis is quality of life, patients' quality-of-life concerns should be elicited, particularly as they relate to function in school, at work, or in personal relationships. Management should be tailored to meet these concerns.
Clinical and endoscopic findings will allow the clinician to assess the disorder's severity, which is characterized as mild (fewer than four stools daily, with or without blood, no systemic signs of toxicity, normal erythrocyte sedimentation rate [ESR]); moderate (more than four stools daily, minimal signs of toxicity); severe (more than six bloody stools daily, evidence of toxicity [fever, tachycardia, anemia, elevated ESR]); or fulminant (more than 10 stools daily, continuous bleeding, toxicity, abdominal tenderness and distension, blood transfusion requirement, colonic dilation on abdominal plain films).
Patients with mild or moderate distal colitis may be treated with: oral aminosalicylate (ASA) (4 to 6 g per day of sulfasalazine in four divided doses; 2 to 4.8 g per day of mesala-mine in three divided doses [Evidence A]; 6.75 g per day of balsalazide in three divided doses); topical mesalamine (suppositories, 500 mg twice a day, or enemas, in doses of 1 to 4 g); or topical steroids (100-mg hydrocortisone enema or 10 percent hydrocortisone foam). The combination of oral and topical ASAs is more effective than either alone (oral mesalamine, 2.4 g per day and 4 g per day mesalamine enema) (Evidence A). If patients do not respond to mesalamine enemas or suppositories, oral prednisone (up to 40 to 60 mg per day) should be administered.
Patients with mild or moderate extensive colitis should begin therapy with oral sulfasalazine in daily doses titrated up to 4 to 6 g per day, or an alternative ASA in doses up to 4.8 g per day of the active 5-ASA moiety. Oral steroids should be reserved for patients whose disease does not respond to other therapies or for patients with troubling symptoms that demand immediate improvement, and patients who receive steroids should be observed for signs of toxicity. When the inflammation extends beyond the reach of topical therapy, oral therapy should be used, with sulfasalazine at 4 to 6 g per day being the first line of treatment. At this dosage, 80 percent of patients will experience clinical remission or improvement within four weeks.
Treatment with transdermal nicotine patches (15 to 25 mg per day) has resulted in improvement and remission in patients with mild or moderate ulcerative colitis, but the success rate of this treatment is lower than that of traditional ASA therapy. Unsurprisingly, this treatment provides more benefit to ex-smokers and is better tolerated by them. Nicotine (15 mg per day) was not effective in maintaining remission.
Maintenance of Remission
Maintenance regimens are required after the acute attack is controlled. Patients with extensive or relapsing disease will need maintenance therapy.
Mesalamine suppositories (500 g twice a day) are effective in maintaining remission in patients with proctitis. Mesalamine enemas (2 to 4 g) are effective in patients with distal colitis, even if they receive the drug as infrequently as every third night. The following drug regimens were all found to be effective in maintaining remission in distal disease: sulfasalazine, 2 g per day; olsalazine, 1 g per day, Eudragit-S–coated mesalamine, 3.2 g per day, balsalazide, 3 to 6 g per day. The combination of oral mesalamine (1.6 g per day) and mesalamine enema (4 g twice a week) is more effective than oral mesalamine alone. Topical corticosteroids have not been proved effective for maintaining remission.
In patients with mild to moderate extensive colitis, remission is maintained by treatment with sulfasalazine (2 to 4 g per day, with the highest dose most effective but the least well tolerated), olsalazine, mesalamine, or balsalazide. If patients do not respond to this first-line therapy, steroids may be administered. Azathioprine (1.5 to 2.5 mg per kg per day) or 6-Mercaptopurine may be useful as steroid-sparing agents for steroid-dependent patients and for maintenance of remission not adequately sustained by ASA, and occasionally for patients who are refractory to steroids but not acutely ill.
In general, patients should not be chronically treated with steroids because of their toxic adverse effects, but if they are, post-menopausal women should receive calcium supplements (1,000 to 1,500 mg per day) and vitamin D (800 units per day) to stave off osteoporosis. All patients receiving steroids should stop smoking, limit alcohol intake, and increase their activity levels.
Management of Severe Colitis
Severe colitis refractory to drug treatment should be treated medically with intravenous cyclosporine (Evidence A) or surgically with colectomy (Evidence C); the latter treatment involves hospitalization and is beyond the scope of primary care practice.
Patients with ulcerative colitis are at increased risk for colorectal cancer, with the degree of risk related to the duration of disease and its anatomic extent. Patients with ulcerative colitis with a family history of colorectal cancer have a fivefold higher risk of cancer compared with matched controls, although data suggest that cancer risk is reduced in patients who take at least 2 g per day of ASA. Patients who have colitis for eight to 10 years should receive annual or biannual surveillance colonoscopy with regular biopsies (Evidence B). The finding of high-grade dysplasia in flat mucosa is an indication for colectomy; the finding of low-grade dysplasia in flat mucosa may be an indication for colectomy to prevent progression to a higher grade of neoplasia (Evidence B).
Compared with non–colitis-associated colorectal cancer, colitis-associated cancers are more often multiple, broadly infiltrating, anaplastic, and uniformly distributed throughout the colon, and they seem to arise from flat mucosa. Colitis-related tumors also occur in younger patients. High- and low-grade dysplasia standards should be used to diagnose dysplasia. Colonoscopic biopsy diagnosis of dysplasia in flat mucosa often indicates concurrent or future cancer. Patients with high-grade dysplasia should undergo colectomy; patients with low-grade dysplasia should consider it, because the five-year predictive value of the presence of low-grade dysplasia for either cancer or high-grade dysplasia is as high as 54 percent.