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Management of Severe Ulcerative Colitis

Management of Severe Ulcerative Colitis

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2/3/14, 11:55 AMManagement of severe ulcerative colitisPage 1 of 7http://www.uptodate.com.libproxy.ucl.ac.uk/contents/management-of-s…F4068&elapsedTimeMs=6&source=see_link&view=print&displayedView=full
Official reprint from UpToDate www.uptodate.com ©2014 UpToDate
Authors
Mark A Peppercorn, MDRichard J Farrell, MD
Section Editor 
Paul Rutgeerts, MD, PhD, FRCP
Deputy Editor 
Shilpa Grover, MD, MPH
Management of severe ulcerative colitisDisclosures
 All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through:
 Dec 2013. |
This topic last updated:
 Jan 9, 2013.
 — Ulcerative colitis is a chronic inflammatory condition characterized by relapsingand 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 fulminantulcerative colitis:Patients with a severe ulcerative colitis have frequent loose bloody stools (
!
6 per day) with severe cramps andevidence of systemic toxicity as demonstrated by a fever (temperature
!
37.5°C), tachycardia (heart rate [HR]
!
90beats/minute), anemia (hemoglobin <10.5 g/dL), or an elevated erythrocyte sedimentation rate (ESR) (
!
30mm/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 andanorexia. 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 moderatecolitis, steroid-refractory and steroid-dependant ulcerative colitis, and toxic megacolon are discussed separately. (See"Management of mild to moderate ulcerative colitis" 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 previouslyestablished. (See "Management of mild to moderate ulcerative colitis", section on 'Assessment of clinical severity' and"Management of mild to moderate ulcerative colitis", 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 obtainbiopsies to exclude the presence of an infection (eg, cytomegalovirus). A full colonoscopy should be avoided inhospitalized patients with severe colitis because of the potential to precipitate toxic megacolon. Because of the severityof symptoms, treatment should proceed pending the results of investigations [1]. (See "Management of mild to moderate ulcerative colitis", section on 'Pretreatment evaluation'.)
®®
 
2/3/14, 11:55 AMManagement of severe ulcerative colitisPage 2 of 7http://www.uptodate.com.libproxy.ucl.ac.uk/contents/management-of-s…F4068&elapsedTimeMs=6&source=see_link&view=print&displayedView=full
Patients with severe or fulminant ulcerative colitis should also undergo plain abdominal radiography both at presentationand at any time there is clinical deterioration to determine if there is colonic dilation (diameter
!
5.5 cm) or toxicmegacolon (diameter
!
6 cm or cecum >9 cm and systemic toxicity). The management of toxic megacolon is discussedseparately. (See "Toxic megacolon", section on 'Diagnosis' and "Toxic megacolon", section on 'Treatment'.)
TREATMENT OF SEVERE ULCERATIVE COLITIS
 — Patients with a severe ulcerative colitis have frequent loosebloody 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 elevatederythrocyte 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 combinationtherapy 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", section on 'Initialapproach'). Some patients should also receive antibiotics. Initiation of oral glucocorticoids should not be delayed until theresults 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, clinicalexperience along with their documented benefit in patients with milder symptoms suggests that oral 5-ASA medicationsmay be a helpful adjunct in the management of patients with severe colitis. However, in rare cases, some 5-ASAmedications have been found to cause exacerbations of colitis [2
 
]. If an ulcerative colitis flare coincides with a recentincrease 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 inrelieving rectal symptoms of tenesmus and urgency. (See "Management of mild to moderate ulcerative colitis", sectionon 'Ulcerative proctitis or proctosigmoiditis'.) Anticholinergic, antidiarrheal agents, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioid drugs should bediscontinued 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), andperitoneal signs or megacolon. There is no role of antibiotics in patients with severe colitis without signs of systemictoxicity [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 establishedbenefit 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 shortchain 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 dietaryinterventions 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 oral5-ASA, and topical 5-ASA or steroids medications should be hospitalized for further management that includesintravenous 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 preferredbecause they are associated with less sodium-retention and potassium-wasting. A systematic review of 32 trials and
 
2/3/14, 11:55 AMManagement of severe ulcerative colitisPage 3 of 7http://www.uptodate.com.libproxy.ucl.ac.uk/contents/management-of-s…F4068&elapsedTimeMs=6&source=see_link&view=print&displayedView=full
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 patientsrequired a colectomy. Continuous infusions of intravenous glucocorticoids are not safer or more effective than bolusinjection 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 whocontinue 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 increasedrisk of venous thromboembolism and pulmonary embolism in patients with inflammatory bowel disease in bothpopulation-based and hospital-based cohorts [14-16]. (See "Prevention of venous thromboembolic disease in medical patients", section on 'Prevention of VTE' 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 consideredsteroid refractory and should either be treated with cyclosporine or an anti-tumor necrosis factor (anti-TNF) agent. Anapproach to patients with steroid-refractory ulcerative colitis is presented separately. (See "Approach to adults withsteroid-refractory and steroid-dependent ulcerative colitis".)
Maintenance therapy
 — In patients who respond, intravenous glucocorticoids should be converted to equivalent doseof 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 everyweek until a daily dose of 20 mg is reached, and then by 2.5 mg every week [17]. Rectal 5-ASA/steroids can begradually tapered over two to four months. Oral 5-ASA medications should be continued at the same dose asmaintenance therapy.Patients are considered to have steroid dependent ulcerative colitis if glucocorticoids cannot be tapered to less than 10mg/day within three months of starting glucocorticoids without recurrent disease, or if relapse occurs within three monthsof 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 whocannot tolerate 5-ASA medications should be treated with 6-mercaptopurine (6-MP)/azathioprine (AZA) or an anti-TNFagent for maintenance of remission [18-24]. An approach to patients with steroid-dependant ulcerative colitis and theadministration, safety, and monitoring of AZA and 6-MP are discussed in detail separately. (See "Approach to adults withsteroid-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 severeulcerative 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 andbowel 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 andphysical examination every four to six hours to evaluate abdominal and rebound tenderness and more frequently if thereis 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 bechecked every 12 to 24 hours and more frequently if there is clinical deterioration. Patients should be managed bygastroenterologists and colorectal surgeons [1,25
 
].

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