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Management of severe ulcerative colitis in adults
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Management of severe ulcerative colitis in adults
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2016. | This topic last updated: Sep 06, 2016.

INTRODUCTION AND DEFINITIONS — Ulcerative colitis is a chronic inflammatory condition characterized by relapsing and remitting episodes of inflammation limited to the mucosal layer of the colon. It almost invariably involves the rectum, and may extend in a proximal and continuous fashion to involve other portions of the colon.

Patients with severe presentations of ulcerative colitis are generally categorized as having either severe or fulminant ulcerative colitis:

Patients with a severe ulcerative colitis have frequent loose bloody stools (≥6 per day) with severe cramps and evidence of systemic toxicity as demonstrated by a fever (temperature ≥37.5°C), tachycardia (heart rate [HR] ≥90 beats/minute), anemia (hemoglobin <10.5 g/dL), or an elevated erythrocyte sedimentation rate (ESR) (≥30 mm/hour). Patients may have rapid weight loss.

Fulminant colitis refers to a subgroup of patients with severe ulcerative colitis who have more than 10 stools per day, continuous bleeding, abdominal pain, distension, and acute, severe toxic symptoms including fever and anorexia. Such patients are at risk of progressing to toxic megacolon and bowel perforation.

This topic will review the management of severe and fulminant ulcerative colitis. The management of mild to moderate colitis, steroid-refractory and steroid-dependant ulcerative colitis, and toxic megacolon are discussed separately. (See "Management of mild to moderate ulcerative colitis in adults" and "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis" and "Toxic megacolon".)

PRETREATMENT EVALUATION — When a patient presents with symptoms suggestive of ulcerative colitis, an assessment of disease severity is important in guiding management. It is also important to exclude alternative and/or comorbid conditions as a cause for their symptoms even when the diagnosis of ulcerative colitis has been previously established. (See "Management of mild to moderate ulcerative colitis in adults", section on 'Assessment of clinical severity' and "Management of mild to moderate ulcerative colitis in adults", section on 'Pretreatment evaluation'.)

Evaluation should consist of laboratory studies including blood counts, liver tests, measurement of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), stool studies to rule out an infectious colitis, and a limited evaluation of the colon with flexible sigmoidoscopy to confirm the presence, severity, and extent of inflammation, and to obtain biopsies to exclude the presence of an infection (eg, cytomegalovirus). A full colonoscopy should be avoided in hospitalized patients with severe colitis because of the potential to precipitate toxic megacolon. Because of the severity of symptoms, treatment should proceed pending the results of investigations [1]. (See "Management of mild to moderate ulcerative colitis in adults", section on 'Pretreatment evaluation'.)

Patients with severe or fulminant ulcerative colitis should also undergo plain abdominal radiography both at presentation and at any time there is clinical deterioration to determine if there is colonic dilation (diameter ≥5.5 cm) or toxic megacolon (diameter ≥6 cm or cecum >9 cm and systemic toxicity). The management of toxic megacolon is discussed separately. (See "Toxic megacolon", section on 'Diagnosis' and "Toxic megacolon", section on 'Treatment'.)

A multidisciplinary approach is fundamental to the successful management of all patients with severe ulcerative colitis. When possible, patients should be managed with aggressive medical therapy, though in some surgery will be required. In addition to proper nutritional assessment and support, a colorectal surgeon should be contacted and involved early in the patient's admission. Surgery is indicated for patients who have life-threatening complications of severe ulcerative colitis, such as massive bleeding, perforation, or infection. It may also be necessary for those who have fulminant or chronic severe colitis that fails to improve with intravenous steroids and/or biologic therapy. It is important the patient be comfortable that all reasonable medical therapy has been attempted prior to considering colectomy.

TREATMENT OF SEVERE ULCERATIVE COLITIS — Patients with a severe ulcerative colitis have frequent loose bloody stools (≥6 per day) with severe cramps and evidence of systemic toxicity as demonstrated by a fever (temperature ≥37.5°C), tachycardia (heart rate [HR] ≥90 beats/minute), anemia (hemoglobin <10.5 g/dL), or an elevated erythrocyte sedimentation rate (ESR) (≥30 mm/hour). Patients may have rapid weight loss.

Initial therapy — Patients with severe ulcerative colitis should be treated with oral glucocorticoids and combination therapy with high dose oral 5-aminosalicylic acid (5-ASA) (eg, mesalamine 4.8 grams/day), 5-ASA or steroid suppository, and 5-ASA, steroid enema, or foam (see "Management of mild to moderate ulcerative colitis in adults", section on 'Initial approach'). Some patients should also receive antibiotics. Initiation of oral glucocorticoids should not be delayed until the results of stool studies and cultures are available [1]. (See 'Pretreatment evaluation' above.)

Although there are no randomized controlled trials to support the use of oral 5-ASA medications in severe colitis, clinical experience along with their documented benefit in patients with milder symptoms suggests that oral 5-ASA medications may be a helpful adjunct in the management of patients with severe colitis. However, in rare cases, some 5-ASA medications have been found to cause exacerbations of colitis [2]. If an ulcerative colitis flare coincides with a recent increase in dose or addition of an oral 5-ASA medication, oral 5-ASA medications should be discontinued.

No randomized controlled trials have demonstrated a benefit to topical therapy in patients with severe ulcerative colitis. However, we have found that steroid enemas/foam and suppositories or 5-ASA enemas twice daily may be helpful in relieving rectal symptoms of tenesmus and urgency. (See "Management of mild to moderate ulcerative colitis in adults", section on 'Ulcerative proctitis or proctosigmoiditis'.)

Anticholinergic, antidiarrheal agents, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioid drugs should be discontinued in patients with severe colitis due to the risk of precipitating toxic megacolon. (See "Toxic megacolon".)

We recommend intravenous antibiotics (eg, ciprofloxacin and metronidazole) in patients with severe colitis and high grade fever, leukocytosis with extreme numbers of immature neutrophils (band form count greater than 700/microL), and peritoneal signs or megacolon. There is no role of antibiotics in patients with severe colitis without signs of systemic toxicity [3,4].

Bowel rest is not recommended in patients with severe ulcerative colitis in the absence of fulminant disease (see 'Treatment of fulminant ulcerative colitis' below). Although bowel rest can help reduce stool volume, it has no established benefit on disease activity [5,6].

Nutritional support should be considered in patients who are malnourished. In such cases, enteral nutrition is preferred, as it is associated with significantly fewer complications than parenteral nutrition and does not deprive the colon of short chain fatty acids needed for the metabolism and repair of colon epithelial cells [7,8]. (See "Nutrition and dietary interventions in adults with inflammatory bowel disease", section on 'Nutritional assessment' and "Nutrition and dietary interventions in adults with inflammatory bowel disease", section on 'Dietary interventions'.)

Subsequent therapy — Patients who continue to have symptoms despite optimal doses of oral steroids, high dose oral 5-ASA, and topical 5-ASA or steroids medications should be hospitalized for further management that includes intravenous fluids, electrolyte repletion, and intravenous steroids.

Regimens for intravenous steroids include prednisolone (30 mg IV every 12 hours), methylprednisolone (16 to 20 mg IV every eight hours), or hydrocortisone (100 mg IV every eight hours). Prednisolone or methylprednisolone are preferred because they are associated with less sodium-retention and potassium-wasting. A systematic review of 32 trials and cohort studies of intravenous glucocorticoids included 1991 patients with acute severe colitis between 1974 and 2006 [9]. The overall response rate (both partial and complete) to glucocorticoids was 67 percent; 27 percent of patients required a colectomy. Continuous infusions of intravenous glucocorticoids are not safer or more effective than bolus injection in achieving clinical remission in patients with severe ulcerative colitis [10].

We suggest broad-spectrum antibiotics in patients who improve but do not fully respond to glucocorticoids, and who continue to run low grade fevers with evidence of band forms in their differential. We typically use a regimen of intravenous ciprofloxacin and metronidazole in this setting.

Pharmacologic venous thromboembolism prophylaxis (eg, heparin) should be administered to reduce the risk of thromboembolism in patients hospitalized with severe ulcerative colitis [11-13]. Studies have demonstrated an increased risk of venous thromboembolism and pulmonary embolism in patients with inflammatory bowel disease in both population-based and hospital-based cohorts [14-16]. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults", section on 'Our approach' and "Pulmonary complications of inflammatory bowel disease", section on 'Prophylaxis for venous thromboembolism'.)

Patients who have no meaningful clinical response to intravenous glucocorticoids within 7 to 10 days are considered steroid refractory and should either be treated with cyclosporine or an anti-tumor necrosis factor (anti-TNF) agent. An approach to patients with steroid-refractory ulcerative colitis is presented separately. (See "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis".)

Maintenance therapy — In patients who respond, intravenous glucocorticoids should be converted to equivalent dose of oral glucocorticoids in three to five days. Oral glucocorticoids should be tapered after the patient has been stable for two to four weeks. Oral glucocorticoids should be tapered over eight weeks by decreasing the dose by 5 to 10 mg every week until a daily dose of 20 mg is reached, and then by 2.5 mg every week [17]. Rectal 5-ASA/steroids can be gradually tapered over two to four months. Oral 5-ASA medications should be continued at the same dose as maintenance therapy.

Patients are considered to have steroid dependent ulcerative colitis if glucocorticoids cannot be tapered to less than 10 mg/day within three months of starting glucocorticoids without recurrent disease, or if relapse occurs within three months of stopping glucocorticoids. Patients with steroid-dependant ulcerative colitis, patients with severe ulcerative colitis with >2 relapses requiring glucocorticoids in 12 months despite optimal doses of oral 5-ASA medication, or patients who cannot tolerate 5-ASA medications should be treated with 6-mercaptopurine (6-MP)/azathioprine (AZA) or an anti-TNF agent for maintenance of remission [18-24]. An approach to patients with steroid-dependant ulcerative colitis and the administration, safety, and monitoring of AZA and 6-MP are discussed in detail separately. (See "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Steroid-dependent ulcerative colitis' and "Azathioprine and 6-mercaptopurine in inflammatory bowel disease".)

TREATMENT OF FULMINANT ULCERATIVE COLITIS — Fulminant colitis refers to a subgroup of patients with severe ulcerative colitis who have more than 10 stools per day, continuous bleeding, abdominal pain, distension, and acute, severe toxic symptoms including fever and anorexia. Such patients are at risk of progressing to toxic megacolon and bowel perforation. The treatment of fulminant colitis is the same regardless of the extent of colonic involvement [17].

Initial therapy — Patients with fulminant colitis should be admitted to a hospital and followed closely with vital signs and physical examination every four to six hours to evaluate abdominal and rebound tenderness and more frequently if there is clinical deterioration. Stool output should be recorded to chart the number and character of bowel movements, including the presence or absence of blood and liquid versus solid stool. A complete blood count, serum electrolytes, serum albumin, liver function tests, and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) should be checked every 12 to 24 hours and more frequently if there is clinical deterioration. Patients should be managed by gastroenterologists and colorectal surgeons [1,25].

Patients with fulminant ulcerative colitis should be kept NPO. Nutritional support should be considered if the patient is malnourished. (See "Nutrition and dietary interventions in adults with inflammatory bowel disease", section on 'Nutritional assessment' and "Nutrition and dietary interventions in adults with inflammatory bowel disease", section on 'Dietary interventions'.)

Intravenous fluid and electrolyte replacement are necessary to correct and prevent dehydration or electrolyte imbalance. Blood transfusions may be needed to maintain a hemoglobin ≥10 g/dL.

Patients with intestinal dilation (transverse colon diameter ≥5.5 cm) should receive decompression with a nasoenteric tube. Intermittent rolling maneuvers every two hours or the knee-elbow position should be recommended to help redistribute gas in the colon and thereby promote decompression [26,27]. Plain abdominal radiography should be repeated if there is clinical deterioration to determine if there is colonic dilation (diameter ≥5.5 cm) or toxic megacolon (diameter ≥6 cm or cecum >9 cm and systemic toxicity).

Patients with fulminant colitis should be treated with intravenous glucocorticoids. Prednisolone (30 mg IV every 12 hours) or methylprednisolone (16 to 20 mg IV every eight hours) are preferred because they produce less sodium-retention and potassium-wasting.

All patients with fulminant disease should be treated with broad-spectrum antibiotics (eg, ciprofloxacin 400 mg every 12 hours and metronidazole 500 mg every eight hours).

All patients should receive pharmacological venous thromboembolism prophylaxis (eg, heparin) to reduce the risk of thromboembolism [11-13]. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults", section on 'Pharmacologic thromboprophylaxis'.)

Subsequent therapy — Patients with fulminant ulcerative colitis who fail to improve by the third day of intensive treatment should be managed as patients with steroid-refractory ulcerative colitis with either cyclosporine or infliximab, or undergo colectomy. However, the threshold to undergo colectomy in patients who fail to respond to cyclosporine or infliximab is lower.

Cyclosporine — Intravenous cyclosporine has a role in induction of remission in patients with severe or fulminant colitis, but is not effective and/or safe for long-term use [28,29]. Cyclosporine is used as a short-term "bridge" to therapy with the slower onset, longer acting medications, including azathioprine (AZA) or 6-mercaptopurine (6-MP). The role of cyclosporine in steroid-refractory ulcerative colitis is discussed in detail separately. (See "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Cyclosporine'.)

Infliximab — Infliximab can induce remission rapidly and can be used for the maintenance of remission [30]. However, it is unclear if anti-tumor necrosis factor (anti-TNF) therapy can prevent or reduce rates of colectomy in the long term. We therefore suggest infliximab in patients with an allergy to AZA/6-MP or who have failed to AZA/6-MP. The role of infliximab in steroid-refractory ulcerative colitis is discussed in detail separately. (See "Anti-tumor necrosis factor therapy in ulcerative colitis" and "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Steroid-refractory ulcerative colitis'.)

Colectomy — Patients with fulminant colitis who fail treatment with cyclosporine or infliximab (either due to a failure to respond or due to relapse) within four to seven days and those with toxic megacolon (diameter ≥6 cm or cecum >9 cm and systemic toxicity) who do not respond to therapy within 72 hours, require colectomy. (See "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Surgery' and "Surgical management of ulcerative colitis" and "Toxic megacolon" and "Toxic megacolon", section on 'Treatment'.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Ulcerative colitis in adults (The Basics)")

Beyond the Basics topics (see "Patient education: Ulcerative colitis (Beyond the Basics)" and "Patient education: Sulfasalazine and the 5-aminosalicylates (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

When a patient presents with symptoms suggestive of severe or fulminant ulcerative colitis, it is important to exclude alternative and/or comorbid conditions as a cause for their symptoms. Evaluation should consist of laboratory studies, stool studies, flexible sigmoidoscopy, and plain abdominal radiography. (See 'Pretreatment evaluation' above.)

Severe ulcerative colitis

Patients with a severe ulcerative colitis have frequent loose bloody stools (≥6 per day) with severe cramps and evidence of systemic toxicity as demonstrated by a fever (temperature ≥37.5°C), tachycardia (heart rate [HR] ≥90 beats/minute), anemia (hemoglobin <10.5 g/dL), or an elevated erythrocyte sedimentation rate (ESR) (≥30 mm/hour). Patients may have rapid weight loss. (See 'Treatment of severe ulcerative colitis' above.)

For patients with severe ulcerative colitis, we recommend treatment with oral glucocorticoids and high dose oral 5-ASA, and topical 5-ASA or steroids (Grade 1B). Antibiotic therapy is used only in patients with signs of systemic toxicity. (See 'Initial therapy' above.)

Patients who continue to have severe symptoms despite optimal doses of oral glucocorticoids, high dose oral 5-ASA and topical 5-ASA, or steroids should be hospitalized for further management, including intravenous fluids and electrolytes. We recommend treatment with intravenous glucocorticoids in these patients (Grade 1B). (See 'Initial therapy' above.)

In patients who respond, intravenous glucocorticoids should be converted to equivalent oral dose and then gradually discontinued. We recommend oral 5-ASA medications for maintenance therapy in patients with severe ulcerative colitis (Grade 1A). (See 'Maintenance therapy' above.)

Patients with severe ulcerative colitis with >2 relapses requiring glucocorticoids in 12 months despite optimal doses of oral 5-ASA medication, patients who cannot tolerate oral 5-ASA medication, and patients with steroid-dependant ulcerative colitis should be treated with 6-mercaptopurine/azathioprine (AZA) or an anti-tumor necrosis factor (anti-TNF) agent (Grade 1B). An approach to patients with steroid-dependant ulcerative colitis and the administration, safety, and monitoring of AZA and 6-MP are discussed in detail separately. (See "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Steroid-dependent ulcerative colitis' and "Sulfasalazine and 5-aminosalicylates in the treatment of inflammatory bowel disease", section on 'Side effects'.)

Fulminant colitis

Fulminant colitis refers to a subgroup of patients with severe ulcerative colitis who have more than 10 stools per day, continuous bleeding, abdominal pain, and distension, and acute, severe toxic symptoms including fever and anorexia. (See 'Treatment of fulminant ulcerative colitis' above.)

Patients with fulminant ulcerative colitis should be admitted to a hospital, closely monitored, and kept NPO. We recommend treatment with intravenous fluids, broad spectrum antibiotics, and intravenous glucocorticoids (Grade 1B). (See 'Initial therapy' above.)

In patients who do not respond to intravenous glucocorticoids after three days, we recommend treatment with cyclosporine or infliximab (Grade 1A). (See 'Cyclosporine' above and 'Infliximab' above and "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Steroid-refractory ulcerative colitis'.)

Patients with fulminant colitis who fail treatment with cyclosporine or infliximab (either due to a failure to respond or due to relapse) within four to seven days, and those with toxic megacolon who do not respond to therapy within 72 hours, require colectomy. (See "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Surgery' and "Surgical management of ulcerative colitis".)

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