Corticosteroids ulcerative colitis

Therapeutic pyramid approach to inflammatory bowel diseases. Treatment choice is predicated on both the severity of the illness and the responsiveness to therapy. Agents at the bottom of the pyramid are less efficacious but carry a lower risk of serious adverse effects. Drugs may be used alone or in various combinations. Patients with mild disease may be treated with 5-aminosalicylates (with ulcerative colitis or Crohn s colitis), topical corticosteroids (ulcerative colitis), antibiotics (Crohn s colitis or Crohn s perianal disease), or budesonide (Crohn s ileitis). Patients with moderate disease or patients who fail initial therapy for mild disease may be treated with oral corticosteroids to promote disease remission immunomodulators (azathioprine, mercaptopurine, methotrexate) to promote or maintain disease remission or anti-TNF antibodies. Patients with moderate disease who fail other therapies or patients with severe disease may require intravenous corticosteroids, anti-TNF antibodies, or surgery. Natalizumab is reserved for patients with severe Crohn s disease who have failed immunomodulators and TNF antagonists. Cyclosporine is used primarily for patients with severe ulcerative colitis who have failed a course of intravenous corticosteroids. TNF, tumor necrosis factor. 

Maintenance of remission of ulcerative colitis may be achieved with oral or topical aminosalicylates. Immunosuppressants such as azathioprine or 6-mercaptopurine can be used for unresponsive patients or those who develop corticosteroid dependency. 

Treatment of acute episodes of ulcerative colitis is dictated by the severity and extent of disease, and first-line therapy of mild to moderate disease involves oral or topical aminosalicylate derivatives. Topical suppositories and enemas are preferred for active distal UC (left-sided disease and proctitis), as they deliver mesalamine directly to the site of inflammation. Topical mesalamine is superior to both topical corticosteroids and oral aminosalicylates for inducing remission in active mild to moderate UC.1,33,34 Enemas are appropriate for patients with... 

Maintenance of remission of ulcerative colitis may be achieved with oral or topical aminosalicylates. Mesalamine suppositories 1 g daily may prevent relapse in up to 90% of patients with proctitis.1 Mesalamine enemas are appropriate for left-sided disease and may often be dosed three times weekly. Oral mesalamine at lower doses (e.g., 1.6 g per day) may be combined with topical therapies to maintain remission. Topical or oral corticosteroids are not effective for maintaining remission of distal UC and should be avoided. 

Chapman RW, Selby WS, Jewell DP Controlled trial of intravenous metronidazole as adjunct to corticosteroids in severe ulcerative colitis. Gut 1986 27 1210-1212. 

Mantzaris GJ, Hatzis A, Kontogiannis P, Triadaphyllou G Intravenous tobramycin and metronidazole as an adjunct to corticosteroids in acute, severe ulcerative colitis. Am J Gastroenterol 1994 89 43-46. 

Guslandi M, Giollo P, Testoni PA Corticosteroid-sparing effect of rifaximin, a nonabsorbable oral antibiotic in active ulcerative colitis Preliminary clinical experience. Curr Ther Res 2004 65 292-296. 

Corticosteroids and adrenocorticotropic hormone have been widely used for the treatment of ulcerative colitis and Crohn s disease and are used in moderate to severe disease. Prednisone is most commonly used. Budesonide is an oral controlled-release formulation that minimizes systemic effects. 

Speciai risk Use with caution in the following situations Nonspecific ulcerative colitis if there is a probability of impending perforation, abscess, or other pyogenic infection diverticulitis fresh intestinal anastomoses hypertension CHF thromboembolitic tendencies thrombophlebitis osteoporosis exanthema Cushing syndrome antibiotic-resistant infections convulsive disorders metastatic carcinoma myasthenia gravis vaccinia varicella diabetes mellitus hypothyroidism, cirrhosis (enhanced effect of corticosteroids). 

Treatments are broadly the same as for ulcerative colitis being based on appropriate supportive measures, and the use of corticosteroids, the cytokine infliximab or adalimumab for severe and complicated disease and immunosuppressants, typically azathio-prine, for reducing the chances of relapse. Full thickness disease leading to flstulation, free perforation, abscess formation and stricturing usually requires surgery. Aminosalicylates appear ineffective in reducing the chances of relapse. 

Sulfasalazine treatment results in an 85% remission rate in mild to moderate ulcerative colitis. Termination of therapy leads to an 80% relapse within the next year. In Crohn s disease, sulfasalazine acts primarily on involved colonic mucosa, although remission of ileal disease also has been reported. The National Cooperative Crohn s Disease Study found sulfasalazine to be better in the treatment of colonic disease, while corticosteroids were judged better in the treatment of small bowel disease. Since sulfasalazine does not prevent relapse of Crohn s disease once remission is achieved, maintenance therapy is not characteristically used. 

Infliximab is approved for the treatment of patients with moderate to severe ulcerative colitis who have had inadequate response to mesalamine or corticosteroids. After induction therapy of 5-10 mg/wk at 0, 2, and 6 weeks, 70% of patients have a clinical response and one third achieve a clinical remission. With continued maintenance infusions every 8 weeks, approximately 50% of patients have continued clinical response. 

Dwarakanath AD, Nash J, Rhodes JM. Conversion from ulcerative colitis to Crohn s disease associated with corticosteroid treatment. Gut 1994 35(8) 1141 1. 

Leung VK, Liew CT, Sung JJ. Fatal strongyloidiasis in a patient with ulcerative colitis after corticosteroid therapy. Am J Gastroenterol 1997 92(8) 1383 1. 

Although systemic absorption of the prednisolone from the enema probably does occur, especially when the colon is particularly inflamed, corticosteroids usually have less systemic effects when given this way. Furthermore, by giving an enema, the drug is being delivered directly to its site of action - remember that in ulcerative colitis the disease is confined to the lower gastrointestinal tract. 

Several studies have been conducted, including some small randomised studies, to assess the use of ciclosporin in Crohn s disease. The evidence suggests that intravenous ciclosporin can induce disease remission in severe flares of ulcerative colitis that are unresponsive to corticosteroids. Oral ciclosporin has only been shown to be useful as a bridging treatment between intravenous ciclosporin and more long-term maintenance strategies. 

The main drugs used in the treatment of ulcerative colitis and Crohn s disease are the aminosalicylates and corticosteroids. Their mode of action is obscure. Other immunosuppressives also have a role and recent studies into the mechanisms of inflammation are leading to the introduction of novel therapies to inhibit the inflammatory process. 

Aminosalicylates maintain remission in patients with ulcerative colitis (relapses are reduced by a factor of 3), and may also be used for treatment of an acute attack (corticosteroids may also be needed). 

Systemic corticosteroid. Moderately severe attacks of ulcerative colitis should be treated with systemic corticosteroid, and oral preparations usually suffice. It is important to give enough drug to bring the inflammatory process under control (starting dose... 

Severe attacks of ulcerative colitis should be treated in hospital with intravenous corticosteroid. The main danger is toxic dilatation of the colon and perforation, which can occur insidiously. Regular measurements of abdominal girth and straight x-ray of the abdomen are useful in monitoring response, which should be seen within 72 h. If there is no improvement a trial of ciclosporin (see below) may induce response. Treatment otherwise is by emergency colectomy. 

Ciclosporin may induce remission in some patients with severe ulcerative colitis unresponsive to corticosteroid. The drug is given in a dose of 2-4 mg/kg i.v. until remission is attained. Renal function should be monitored closely as ciclosporin is nephrotoxic (see p. 620). For maintenance therapy azathioprine (see below) is often substituted. Ciclosporin use only delays surgery for many patients after 1 year 50% will have relapsed and undergone colectomy. 

Methotrexate can be helpful in controlling relapses of Crohn s disease unresponsive to corticosteroid or azathioprine. It has also been used with benefit in ulcerative colitis. Its short- and long-term use are limited by a wide profile of adverse effects including bone marrow suppression and pulmonary and hepatic fibrosis (see p. 291). 

Kroegel C, Reissig A, Hengst U, Petrovic A, Hafner D, Grahmann RP. Ulcerative colitis foUowing introduction of zafirlukast and corticosteroid withdrawal in severe atopic asthma. Eur Respir J 1999 14(1) 243. 

Corticosteroids should only be used during acute exacerbations of ulcerative colitis. The total duration of therapy should not exceed 4 to 8 weeks. Many different corticosteroids are available and differ in anti-inflammatory potency and mineralocorticoid activity (Table 38-2). Choosing a corticosteroid and route of administration depends on the clinical presentation. 

Although steroids are effective in achieving remission of ulcerative colitis through their anti-inflammatory properties, they do not change the underlying disease process. In comparison with sulfasalazine or other aminosalicylates, corticosteroids seem to have a faster onset of action and induce remission in 2 to 4 weeks. Parenteral corticosteroids are indicated for severe ulcerative colitis. Once a response is achieved, IV corticosteroids should be converted to oral therapy. However, if there is no response from IV corticosteroids within 72 hours, surgery may be indicated. 

Diarrhoea is also part of some inflammatory disorders, such as irritable bowel syndrome, ulcerative colitis and Crohn s disease. These may best be relieved by treatment with corticosteroids and aminosalicylates. Diarrhoea is commonly associated with bacterial or other pathogenic infections (e.g. food poisoning) and these may require treatment with antibiotics or other antimicrobials. 

Trade name Rectovalone (not available in USA) Indications Infections, ulcerative colitis Category Corticosteroid Half-life N/A... 

Corticosteroids are often required for acute ulcerative colitis or Crohn s disease. The duration of steroid use should be minimized and the dose tapered gradually over 3 to 4 weeks. 

Patients who are unresponsive to parenteral corticosteroids after 7 to 10 days should receive cyclosporine by intravenous infusion. Most hospitalized patients who are unresponsive to corticosteroids will respond to cyclosporine. Continuous intravenous infusion of cyclosporine (4 mg/kg per day) was rapidly effective in steroid-resistant acute severe ulcerative colitis and reduced the need for emergent colectomy. Intravenous cyclosporine has been recommended as an alternative to steroids in patients with severe attacks of ulcerative colitis (fulminant colitis). Patients who are controlled on intravenous cyclosporine can then be switched to an oral cyclosporine taper regimen. 

Marshall JK, Irvine EJ. Rectal corticosteroids versus alternative treatments in ulcerative colitis A meta-analysis. Gut 1997 40 775-781. 

D Haens G, Lemmens L, Geboes K, et al. Intravenous cyclosporine versus corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology 2001 120 1323-1329. 

A careful history should be taken when one of the differential diagnoses is ulcerative colitis because corticosteroid administration has the potential to unmask amebiasis and produce toxic megacolon. All patients diagnosed as having inflammatory bowel disease should have their stools examined carefully and serologic testing done for amebiasis to avoid the serious consequence that results from the administration of corticosteroids. 

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