ULCERATIVE COLITIS Introduction Ulcerative colitis is one of two main forms of inflammatory bowel disease, the other being Crohn’s disease. Crohn’s disease can affect any part of the gastrointestinal system from mouth to anus. Whereas ulcerative colitis affects the large bowel only. Ulcerative colitis is a relapsing and remitting inflammatory disorder of the colonic mucosa. It may affect just the rectum (proctitis) or extend proximally to affect part or the entire colon (pancolitis). Aetiology The cause of ulcerative colitis is broadly speaking undnown, however it is likely that environmental factors operative in an individual with a genetic predisposition. Many papers have postulated that some insult to the intestinal epithelial integrity permits bacteria and luminal antigens to trigger an aberrant immune response. The response is thought to be Th-2 dominant with increased production of interleukin-5. Betis (Infect Immun 71 1774) has proposed that ulcerative colitis may involve adhesin-expressing strains of E.coli capable of inducing interleukin-8 production and transepithelial migration of leukocytes. Pathogenesis Can be broadly divided into macroscopically and histologically. Affecting only the large bowel it begins in the rectum and extends proximally in varying degrees with continuous involvement. Mucosal inflammation causes a red mucosa which bleeds easily, as well as ulcers and pseudopolyps (regenerating mucosa) in severe disease. Ulcerative colitis is characterised by an absence of granulomata, however there goblet cell depletion and crypt absecesses. The inflammatory response is predominantly Th- 2 mediated. Hyperaemic/haemorrhagic granular colonic mucosa +/- “pseudopolyps” formed by inflammation. Punctate ulcers may extend deep into the lamina propria. Investigations The purpose of investigations is to define the nature of the disease and the extent and severity of bowel involvement. Bloods FBC; anaemia is common in ulcerative colitis and is usually the normochromic, normocytic anaemia of chronic disease, however iron deficiency anaemia may occur. Platelet count, ESR and CRP are often raised in severe disease. U&ES and LFTs should also be conducted as in severe disease the serum albumun may be low. Blood cultures should also be taken to investigate infective agents. Stool Microscopy Culture and Sensitivity (MC+S) and Clostridium Difficile Toxin (CDT) These tests should also be conducted to exclude infectious diarrhoea (Clostridium difficile, Salmonella, Shigella, Campylobacter, E coli, amoebae). Radiology A plain abdominal x-ray should be conducted during a severe attack of colitis to look for toxic dilatation of the colon (>6cm) which can lead to perforation. In cases of ulcerative colitis you would also expect to see mucosal thickening/islands and no faecal shadowing. Endoscopy Rigid or flexible sigmoidoscopy can establish a diagnosis of ulcerative colitis, during this procedure a rectal biopsy can be conducted to examine the histology. A histology showing inflammatory infiltrate, goblet cell depletion, glandular distortion, mucosal ulcers crypt ulcers is highly suggestive of ulcerative colitis. Colonoscopy permits the exact extent and severity of colonic and terminal ileal inflammation to be determined, and biopsies to be taken. A barium enema is useful as an investigation showing loss of haustra, granular mucosa and a shortened colon. It is important to note that a barium enema should never be conducted following an acute attack of ulcerative colitis. Management Management of ulcerative colitis is can be divided up according to whether the intervention is medical or surgical and also depending upon the severity of the ulcerative colitis. Medical Interventions Oral corticosteroids such as prednisolone are used to treat acute attacks and the dose is tailed off as the symptoms improve. In severe attacks intravenous steroids are necessary typically hydrocortisone 100mg/6h. Proctosigmoiditis can be treated locally with steroid enemas and suppositories (mesalazine 250mg/8hr PR). Budesonide is a topically acting steroid which is poorly absorbed from the gastrointestinal tract and therefore had fewer systemic effects than other steroids. In severe cases blood transfusions are considered (if Hb <10g/dL) as is the use of parenteral nutrition in severe malnourishment. Intramuscular vitamins are also given. The 5-Aminosalicyclic acid (5-ASA) tablets (mesalazine, olsalazine, balsalazine) are bowel-specific aminosalicylate drugs that are metabolized in the gut having its predominant actions there, thereby having fewer systemic side effects. 5- ASA exerts an anti-inflammatory action which induces remission in mild attacks of ulcerative colitis. In lower doses they are useful as a maintenance treatment to reduce the number of relapses, reducing the relapse rate from 80% to 20% at 1 year. 5-ASA preparations can also be administered as an enema or suppository to treat proctosigmoiditis. Azathioprine is an immunomodulatory drug that suppresses the immune system. It is a pro-drug, converted in the body to the active metabolites 6- mercaptopurine and 6-thioinosinic acid. It is used in those patients who continue to have frequent relapse despite taking an adequate dose of 5-ASAs. It is also indicated as a steroid-sparing agent in those with steroid side-effects or those who relapse quickly when steroids are reduced. Treatment is continued for several months at a time during which FBC is monitored every 4-6 weeks. The novel therapy ciclosporin (=cyclosporin) can benefit patients with steroid refractory ulcerative colitis, although there are reservations about its long-term efficacy. Surgical Interventions Indications for surgery typically include perforation or massive haemorrhage – or “toxic” dilatation of the colon. The other main indication is failure to respond to medical interventions. The surgical procedures performed in ulcerative colitis are: Ileoanal anastomosis, in which the terminal ileum is used to form a reservoir, and the patient is continent with a few bowel motions per day. The pouch may become inflamed (“pouchitis”), leading to bloody diarrhoea which is treated initially withmetronidazole. Panproctocolectomy with ileostomy (the whole colon and rectum is removed and the ileum is brought out the abdominal wall as a stome). Colectomy with an ileorectal anastomosis (diseased rectum left in situ and diarrhoea may still occur). Course and Prognosis Ulcerative colitis presents with bloody diarrhoea, often containing blood and mucus. The clinical course may be one of persistent diarrhoea, relapses and remissions, or severe fulminating colitis. Progression of ulcerative colitis is highly variable. Only 10% of patients with procitits develop more extensive disease, but with severe fulminant disease there is a risk of colonic perforation and death. Patients with extensive ulcerative colitis of more than 10 years’ duration are at an increased risk of colorectal cancer (cumulative risk 12% after 25 years). These patients are usually offered surveillance colonoscopy at intervals of 1-2 years. Colectomy is recommended if high-grade dysplasia is discovered.
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