Medical Management of Ulcerative colitis

MEDICAL MANAGEMENT OF SEVERE ULCERATIVE COLITIS • • • • • UC is a chronic disease, characterized by mucosal inflammation limited to the colon. It involves the rectum in about 95% of cases and may extend proximally to involve parts or all of the large intestine. The hallmark clinical symptom is bloody diarrhea often with prominent symptoms of rectal urgency and tenesmus. The clinical course is marked by exacerbations and remissions, which may occur spontaneously or in response to treatment or intercurrent illnesses. The incidence in the US is 2-7/100,000 population per year. Diagnosis and assessment • In patients presenting with persistent bloody diarrhea, rectal urgency or tenesmus, stool cultures and sigmoidoscopy should be performed to confirm the diagnosis of colitis and to exclude the presence of infectious etiologies. • Microbiologic studies for bacterial and parasitic infection • C Diff toxin and serologic testing for amoeba are required. • Proctosigmoidoscopy or colonoscopy will reveal the mucosal changes typical of UC o loss of the typical vascular pattern o granularity, friability and ulceration. o These changes typically involve the distal rectum and proceed proximally in a continuous, circumferential pattern to involve all or part of the colon. • Histologic findings obtained with biopsies and upper GI series may be helpful in distinguishing UC from Crohn's disease. Approach to management • Goals of treatment are directed at inducing and then maintaining remission of symptoms and mucosal inflammation. • The anatomic extent and clinical severity of an acute attack will determine the approach to therapy. • The anatomic extent is assessed endoscopically. o The key question to be asked at this point is whether the inflammation is distal (below the splenic flexure and thus within reach of topical therapy) or extensive (requiring systemic medication). • Severity is defined as mild, moderate, severe or fulminant, determined by clinical and endoscopic criteria. Table 1. Modified Truelove and Witts' Criteria Truelove SC, Witts LJ. Cortisone in ulcerative colitis: final report on a therapeutic trial. BMJ 1955;2:1041–8; Sign or symptom Mild Moderate Severe Bowel movements <4/d 4–6/d >6/d (mostly bloody) Temperature (°F) Normal 90–100 >100 Weight loss (%) None 1–10 >10 Pulse (beats/min) <90 90–100 >100 Hematocrit (%) Normal 30–40 <30 Sedimentation rate (mm/h) <20 20–30 >30 Albumin (g/dL) Normal 3–3.5 <3 137 Severe UC • The presenting attack of UC may be severe in 3-14% of the patients. o For a severe attack, the mortality rate has fallen from 37% in the 1950s to less than 1%, including mortality associated with emergency surgery. o This impressive fall in the death rate is the result of the introduction of steroids, better management of fluids and electrolytes and improved surgical technique. Evaluation • • • • • Patients with UC refractory to maximal oral treatment with prednisone, oral ASA drugs and topical medications or patients who present with toxicity, need inpatient management. Superimposed infections with enteric pathogens, CDiff and CMV should be ruled out. Initial assessment should include CBC with diff, coags, LFTs, serum cholesterol and Mg. Plain abdominal films should be obtained on admission and should be repeated serially if abnormal or the patient deteriorates. Endoscopic evaluation may be helpful in assessing for active disease and ruling out infectious etiologies, but should be limited to a gentle flexible sigmoidoscopy to a distance only necessary to confirm severe colitis and to allow for biopsy specimens. Management • • • • • Supportive treatment with fluid and electrolyte replacement, transfusion if necessary. In patients with toxic signs or megacolon narcotics and anticholinergic agents should be avoided. Low residue diet if does not worsen symptoms. o NPO in the presence of toxic megacolon. TPN may be useful as a nutritional adjunct in patients with severe nutritional depletion. However, it shows no benefit as a primary therapy. Antibiotics o The role of antibiotics in the treatment of UC has not been clearly defined. o Patients with severe colitis with evidence of toxicity are often empirically treated with antibiotics . o Controlled trials failed to demonstrate therapeutic benefit from the use of oral vancomycin, IV cipro, or IV flagyl. o Patients receiving tobramycin as an adjunct to IV steroids showed higher remission rates (74% vs 43%) than those receiving adjuvant placebo. 138 • • • Glucocorticoids o Systemic glucocorticoids were first shown to be effective in treating active UC in 1956. o Glucocorticoids are also effective for active distal disease when used as topical treatment in the form of retention enemas, foams, or suppositories. o Both oral cortisone and prednisone have been shown to be ineffective in maintaining remission. o Thus, glucocorticoids should be used to treat active disease, and prolonged therapy is contraindicated not only because of long-term adverse effects, but also because it is ineffective as maintenance therapy in the vast majority of patients. o The mainstay of therapy for a patient admitted with severe colitis is IV steroids, either by divided doses or continuous infusion. ACTH may be used if the patient has not recently received steroids. Aminosalicylates o A major milestone in the management of ulcerative colitis was the introduction of sulfasalazine in 1942. o For active disease, sulfasalazine is less effective than glucocorticoids; its principal use is to maintain remission once active inflammation has subsided. o Topical treatment with ASA can be used and is effective both for active distal disease and for maintenance therapy. o There are no data to support the use of either oral or topical ASA in the setting of severe UC, but they may be used if tolerated. Immunosuppressive agents o Cyclosporine is being used increasingly in severe ulcerative colitis for patients with severe colitis who do not improve significantly after 5-10 days of maximal medical therapy. Controlled trials showed that the use of CSA can induce remission in approx 80% of patients, and avoid colectomy in the acute stage. CSA toxicity include nephrotoxicity, infection and seizures (particularly in patients with associated low cholesterol or magnesium). One of the most controversial issues is how to continue management in patients who respond well to cyclosporine. Oral cyclosporine may be continued, with or without the addition of azathioprine/6MP, or be replaced by azathioprine/6MP. o Azathioprine and 6-mercaptopurine (6-MP) have been the most widely used immunosuppressive agents. The major use of these drugs in ulcerative colitis is for the management of chronic active disease (for a glucocorticoid-sparing effect) and for the maintenance of remission. o Infliximab ( monoclonal antibody to TNF alpha)- few small studies showing mixed results. Some showing response in steroid dependent/steroid resistant patients and some fail. o Visilizumab IgG antibody that binds to the CD3 antigen, which results in apoptosis of activated T lymphocytes. A recent abstract reported preliminary five patients with severe UC despite 5 days of intravenous corticosteroids who subsequently received visilizumab. All five patients achieved clinical and endoscopic remission at day 30, and all three patients with at least 90 days of follow-up have successfully tapered off of steroids. 139 • From 20% to 40% of patients with a severe attack of ulcerative colitis will require urgent colectomy. References Feldman: Sleisenger & Fordtran's Gastrointestinal and liver disease, 7th ed 2002 Ulcerative colitis practice guidelines in adults (update): American college of gastroenterology, practice parameters committee Am J Gastroenterology 2004 Medical management of severe ulcerative colitis Gastroenterol Clin N Am 2004 Medical therapy for ulcerative colitis 2004 Gastroenterology Einat Carmon, MD 140