Ulcerative colitis (UC)
Discuss UC?
- The incidence of UC is approximately 10–20 per 100 000 per year with a reported prevalence of 100–200 per 100 000.
- UC has a slight excess of mortality in the first two years after diagnosis, but little subsequent difference from the normal population. However, a severe attack of UC is still a potentially life threatening illness.
- Distal colitis- confined to the rectum (proctitis) or rectum & sigmoid
- Left sided colitis-up to the splenic flexure
- Extensive colitis-up to the hepatic flexure
- Pancolitis -affecting the whole colon.
- For UC the extent is defined as the proximal margin of macroscopic disease, because this is most clearly related to the risk of complications, including dilatation and cancer. The implications of limited macroscopic disease with extensive microscopic inflammation remain unclear.
- The clinical course of UC is marked by exacerbation and remission. About 50% of patients with UC have a relapse in any year. About 20–30% of patients with pancolitis come to colectomy.
- After the first year approximately 90% of patients are fully capable of work (defined by <1 month off work per year), although UC causes significant employment problems for a minority.
- UC- 6% rectal sparing and 7% will have backwash ileilitis. In PSC-UC group 52% rectal sparing and 51% will have backwash ileilitis
Discuss the management of UC?
Left sided or extensive UC:
- Mesalazine 2–4 g daily is an effective first line therapy for mild to moderately active disease. Mesalazine is more than twice as effective as placebo (OR 0.39; CI 0.29 to 0.52), but not significantly better than sulphasalazine 2-4gm/day (OR 0.87; CI 0.63 to 1.20).
- Olsalazine (1.5–3 g daily) may be used with left sided disease as it has a higher incidence of diarrhoea.
- Sulphasalazine has a higher incidence of side effects compared with newer 5-ASA drugs. However, it can usefully be used in patients with arthritis.
- These agents often require 3-6 weeks to exert their maximal effect.
- Prednisolone (40 mg daily) may be needed where mesalazine has been unsuccessful or a prompt response is needed. The dose can be tapered gradually, usually by 5 mg per week. More rapid reduction is associated with early relapse.
- Topical agents (either steroids or mesalazine) may be added for troublesome rectal symptoms.
Distal colitis or proctitis
- Topical mesalazine 1 g daily (500mg BD or 1 gm OD -in appropriate form for extent of disease) combined with oral mesalazine are effective first line therapy. Combination therapy is more effective than topical or systemic therapy alone.
- Choice of topical formulation is determined by the proximal extent of the inflammation (suppositories for disease to the rectosigmoid junction, foam or liquid enemas for more proximal disease).
- Liquid enemas are difficult to retain, requiring patients remain in a horizontal position for at least 30 minutes. Foam enemas may be more comfortable and easier to retain.
- Topical mesalazine is more effective and hence preferred over topical steroids.
- Systemic steroids may be needed if the patient failed to respond to combination therapy.
- Proximal constipation should be treated with stool bulking agents or laxatives. It is important to treat constipation to ensure delivery of mesalazine to the inflamed colon.
Severe UC
Severe acute ulcerative colitis (UC) is usually defined by the original classification put forward by Truelove and Witts. They defined severe UC as presence of six or more bowel motions per day associated with one or more of the following:
- temperature >37.8
- Large amounts of rectal bleeding
- Heart rate >90/minute
- Haemoglobin of <10.5 g/dl
- ESR >30 mm/h
Management of severe UC
- Daily examination to evaluate abdominal tenderness and rebound tenderness. Regular monitoring of vital signs. A stool chart to record number and character of bowel movements, including the presence or absence of blood and liquid versus solid stool.
- Measurement of FBC, ESR, or CRP, serum electrolytes, serum albumin, and liver function tests every 24–48 hours.
- Daily AXR if colonic dilatation (transverse colon diameter >5.5 cm) is detected at presentation. If not dilated, there should be a low threshold for further radiological assessment if there is clinical deterioration.
- Subcutaneous low molecular weight heparin to reduce the risk of thromboembolism.
- Nutritional support if the patient is malnourished. Fluid and electrolyte replacement as needed.
- Intravenous corticosteroids (hydrocortisone 400 mg/day or methylprednisolone 60 mg/day).
- Withdraw anticholinergic, antidiarrhoeal agents, NSAID and opioid drugs, which risk precipitating colonic dilatation. Where non-specific pain relief is needed, an opioid that has less effect on motility such as tramadol may help.
- Continue of aminosalicylates once oral intake resumes, although these have not been studied in severe disease. Topical therapy (corticosteroids or mesalazine) if tolerated and retained, although there have been limited studies in acute severe disease.
- Objective re-evaluation on the third day of intensive treatment. A stool frequency of >8/day or CRP>45 mg/l at 3 days appears to predict the need for surgery in 85% of cases. Surgical review and input from specialist colorectal nurse or stoma therapist is appropriate at this stage. There is no benefit from intravenous steroids beyond 7–10 days.
- Consideration of colectomy or intravenous ciclosporin 2 mg/kg/day if there is no improvement during the first 3 days. See the guidelines for Ciclosporin use in UC.
Discuss Toxic megacolon?
- Toxic megacolon is a severe complication of IBD that is characterized by non obstructive colonic dilatation (total or segmental) plus systemic toxicity.
- Clinical features
- Signs and symptoms of colitis poorly responsive to therapy are often present prior to the development of toxic colon. Diarrhoea may improve with the onset of toxic colon.
- Physical examination reveals a toxic patient with abdominal distension and tenderness, with or without signs of peritonitis. It is important to remember that steroids may mask the signs.
- Investigations
- AXR- the transverse or right colon is usually the most dilated. A maximum colonic diameter of more than 6 cm is consistent with the diagnosis of megacolon.
- CT scan may be needed if complication of megacolon (e.g. perforation) is suspected.
- Limited endoscopy without bowel preparation and minimal air insufflation may be done with extreme caution in suspected IBD patients presenting for the first time.
- Treatment
- Management should be jointly with the surgical team. Medical treatment is successful in almost half the patients with toxic megacolon
- NPO
- NG tube to decompress the GIT
- Broad spectrum antibiotics to reduce septic complications. A third generation cephalosporin with metronidazole can be used
- Stop all anti motility drugs (Imodium, codeine etc)
- Stress ulcer and DVT prophylaxis
- IV steroids
- Close monitoring
- Failure to improve within 48 to 72 hours, or any signs of deterioration will require immediate colectomy.
Discuss maintenance therapy in UC?
- Lifelong maintenance therapy is recommended for all patients. Discontinuation of medication may be considered for those with distal disease in prolonged remission.
- Benefits of maintenance treatment;
- Maintenance therapy with all 5-ASA drugs may reduce the risk of colorectal cancer by up to 75% (OR 0.25, CI 0.13 to 0.48).
- Reduces the risk of relapse. If you take ASA 1 in 4 chance of relapse at 1 year. If placebo- 3 in 4 chance of relapse at 1 year. Number needed to treat (NNT) is 6 to prevent one relapse of the disease.
- Drugs used for maintenance:
- Oral mesalazine 1–2 g daily or balsalazide 2.5 g daily should be considered as first line therapy. Topical mesalazine may be used in patients with distal disease with/without oral mesalazine.
- Azathioprine 1.5–2.5 mg/kg/day or mercaptopurine 0.75–1.5 mg/kg/day is effective at maintaining remission in UC. Immunomodulators are used in patients who frequently relapse despite adequate dose of mesalazine.
- No published evidence exists to support the use of methotrexate to induce or maintain remission in UC.
Discuss refractory UC?
Some patients remain symptomatic despite intensive medical treatment. Options are:
- Surgery
- Infliximab
Discuss infliximab in UC?
- The role of anti-TNF therapy in active UC, steroid-dependent UC, refractory pouchitis, and in maintenance of disease remission is unclear. It must be remembered that ulcerative colitis can be cured by colectomy. The role of infliximab in preventing colectomy is uncertain.
- The efficacy of infliximab in inducing remission in UC is not brilliant. ACT 1 trial showed that approximately four patients would need to be treated to achieve one response. A similar magnitude of benefit was observed in ACT 2.
- Response rates with infliximab in corticosteroid-refractory UC patients are inferior to those reported with intravenous ciclosporin, although the two drugs have not been compared in a head to head trial. Infliximab can be considered in patients with acute steroid-refractory disease who are reluctant to undergo colectomy and in whom Ciclosporin is contraindicated.
- Dosing- The recommended dosing regimen (based on ACT trials) for induction of remission is three IV infusions of infliximab (5mg/kg) at zero, two and six weeks. For severe steroid refractory UC, the initial dose of infliximab is an IV infusion (5mg/kg) at week 0. For responding patients the dose can be repeated at week 2 and 6.
- Maintenance dosing- No RCT has yet attempted to determine the optimal dosing of infliximab for maintaining remission in UC. The ACT 1 and ACT 2 trials used maintenance dosing of 5mg/kg on scheduled basis every 8 weeks to maintain remission following completion of an induction regime for 30 and 52 weeks respectively. While outcomes at 30 and 52 weeks continued to favour active therapy, further studies are needed to establish the therapeutic gain of long term maintenance therapy beyond one year.
Discuss acute severe colitis?
