MANAGEMENT OF SEVERE COLITIS

The patient with severe colitis refractory to maximal oral treatment with prednisone, oral aminosalicylate drugs, and topical medications, or the patient who presents with toxicity, should be treated for 7-10 days with intravenous steroids. Failure to demonstrate significant improvement within 7-10 days is an indication for either colectomy or treatment with intravenous cyclosporine in specialized centers.

The patient who continues to have severe symptoms despite optimal doses of oral steroids (40-60 mg daily of prednisone), oral aminosalicylates (4-6 g of sulfasalazine or 4.8 g of mesalamine), and topical medications, should be hospitalized for further treatment [78] [79] [80] [81] [82] . The mainstay of therapy at this point is intravenous steroids in a daily dose equivalent to 300 mg of hydrocortisone or 48 mg of methylprednisolone if the patient has received steroids in the prior month, or perhaps intravenous adrenocorticotropic hormone if the patient has not recently received steroids [82] [83] [84] . There is no benefit to treatment with a much higher daily dose of steroids [85] . The clinical impression that continuous infusion is preferable to bolus therapy has not been subjected to a controlled trial. Controlled trials of antibiotics, however, have demonstrated no therapeutic benefit from the use of either oral vancomycin [86] , or intravenous metronidazole [81] when added to intravenous steroids.

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MILD-MODERATE EXTENSIVE COLITIS: MAINTENANCE OF REMISSION

When the acute attack is controlled, a maintenance regimen is usually required, especially in patients with severe, extensive, or relapsing disease. Sulfasalazine, olsalazine, or mesalamine are all effective in reducing relapses. As a rule, patients should not be treated chronically with steroids. Azathioprine or 6-MP may be useful as steroid-sparing agents for steroid-dependent patients, and for maintenance of remission not adequately sustained by aminosalicylates, and occasionally for patients who are steroid-refractory but not acutely ill.

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MANAGEMENT OF MILD-MODERATE EXTENSIVE COLITIS: ACTIVE DISEASE

Patients with mild to moderate extensive colitis should begin therapy with oral sulfasalazine in daily doses titrated up to 4-6 g/day, or an alternate aminosalicylate in doses up to 4.8 g/day. Oral steroids are generally reserved for patients who are refractory to oral aminosalicylates with or without topical therapy, or for patients whose symptoms are so troubling as to demand a “quick fix.” 6-Mercaptopurine (6-MP) or azathioprine are effective for patients who do not respond to oral prednisone but are not so acutely ill as to require intravenous therapy.

When inflammation extends proximal to the reach of topical therapy (i.e., middescending colon-splenic flexure) oral therapy is required, either solely or in combination with topical therapy (though this latter option has not been studied in randomized controlled trials). For clinically mild to moderate, but anatomically extensive disease, the first-line therapy traditionally has been sulfasalazine. Responses are dose related with up to 80% of patients who receive daily doses of 4-6 g manifesting complete clinical remission or significant clinical improvement within 4 weeks [11] [12] and approximately half achieving sigmoidoscopic remission [11] . However, the benefits of greater efficacy with the higher dose are offset by the increase in side effects. The advantages of sulfasalazine compared with the newer aminosalicylates are its longer track record and considerably lower cost. If it happens or is anticipated that these higher doses of sulfasalazine will not be well tolerated, then a 5-aminosalicylate should be used at doses of at least 2 g/day, titrating up to 4.8 g/day [14] .

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MAINTENANCE OF REMISSION IN DISTAL DISEASE

Mesalamine suppositories in a dose of 500 mg twice daily are effective in the maintenance of remission, in patients with proctitis, whereas mesalamine enemas (2-4 grams) are effective in patients with distal colitis. Sulfasalazine (2-4 g/day) and mesalamine (1.5-4 g/day) are also effective in maintaining remission, whereas topical corticosteroids, on the other hand, have not proven effective for maintaining remission in distal colitis.

MANAGEMENT OF MILD-MODERATE DISTAL COLITIS

Patients with mild to moderate distal colitis may be treated with either oral aminosalicylates, topical mesalamine, or topical steroids. In patients refractory to oral aminosalicylates or topical corticosteroids, mesalamine enemas may still be effective. The unusual patient who is refractory to all of the above agents in maximal doses may require treatment with oral prednisone in doses up to 40-60 mg/day.

The therapeutic plan here is largely determined by the patient’s preference because either oral or topical therapy is effective. Oral therapy with aminosalicylates, either sulfasalazine, olsalazine, or mesalamine, is beneficial in achieving and maintaining remission [1] [9] [10] . Effective doses of sulfasalazine range between 4 and 6 g/day in four divided doses [11] [12] ; for mesalamine, at least 2-4 g/day in divided doses [13] [14] , and for olsalazine 1.5-3 g/day in divided doses [15] [16] [17] [18] , although efficacy of olsalazine in active UC is not conclusively established, perhaps in part because of a confounding dose-related diarrhea. These drugs generally are efficacious within 2-4 weeks [11] [12] [13] [14] [15] [16] [17] [18] and are effective in 40-80% of patients. Intolerance to the sulfapyridine moiety is not uncommon and may result in nausea, vomiting, dyspepsia, anorexia, and headache. More severe, but less common, adverse effects include allergic reactions, pancreatitis, hepatotoxicity, drug-induced connective tissue disease, bone marrow suppression, interstitial nephritis, nephrotoxicity, hemolytic anemia, or megaloblastic anemia. Abnormal sperm counts, motility, and morphology are related to the sulfapyridine moiety and are not seen with the mesalamine preparations. Approximately 80% of patients intolerant to sulfasalazine are able to tolerate olsalazine and mesalamine [9] [18] [19] [20] . However, several of the allergic reactions previously thought to be due to the sulfa moiety have been seen with newer aminosalicylates as well [9] .

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APPROACH TO MANAGEMENT

Goals of treatment are directed at inducing and then maintaining remission of symptoms and mucosal inflammation. Once the diagnosis of UC is confirmed, the anatomic extent is assessed endoscopically. The key question to be addressed at this point is whether the inflammation is “distal” (i.e., limited to below the splenic flexure and thus within reach of topical therapy) or “extensive” (i.e., extending proximal to the splenic flexure, requiring systemic medication). Therefore, a delineation of the proximal margin of inflammation, if not achieved on initial evaluation, is desirable at some point in the management of the case once the patient’s condition permits. Read the rest of this entry »

RECOMMENDATIONS FOR DIAGNOSIS AND ASSESSMENT

In a patient presenting with persistent bloody diarrhea, rectal urgency, or tenesmus, stool examinations and sigmoidoscopy and biopsy should be performed to confirm the presence of a colitis and to rule out infectious causes. Characteristic endoscopic and histologic findings with negative evaluation for infectious causes will suggest the diagnosis of ulcerative colitis.

The diagnosis of UC is suspected on clinical grounds and supported by the appropriate findings on proctosigmoidoscopy or colonoscopy, biopsy, and by negative stool examination for infectious causes. Infectious etiologies of colitis can produce clinical findings indistinguishable from idiopathic UC, so microbiologic studies for bacterial and parasitic infection, as well as serologic testing for ameoba when clinical suspicion is high, should be performed in each new patient and in patients with stable symptoms who develop a severe exacerbation. Similarly, patients who have had recent antibiotics, or have recently been hospitalized, should have stools examined for Clostridium difficile.

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