Ulcerative colitis is a non-specific inflammatory disease of the large bowel, usually starting in the rectum and eventually progressing to involve the colon. It is part of a spectrum of diseases that fall under the umbrella label of 'inflammatory bowel disease'. It is similar to Crohn's disease in that it is a chronically remitting inflammatory disorder of the digestive system. The difference is that Crohn's disease involves all layers of the entire length of the alimentary tract, while ulcerative colitis is confined to the mucosal surface of the large intestine, with occasional involvement of the terminal ileum of the small intestine in severe cases. The mucosa of the anal canal is spared. It is the commonest cause of persistent diarrhoea associated with the passage of blood, mucus and pus in temperate climates, and can be very distressing for those who are affected.
Epidemiology and Aetiology
The disease has a worldwide distribution, but is commonest in Europe and North America. In the UK, there is an incidence of 6-15 per 100,000 per year, with a prevalence of 40-50 per 100,000. Rates are much lower for underdeveloped countries with warmer climates, though the reason for this is unknown. It is slightly more common in males than females (M : F = 1.2 : 1) with the mean age of diagnosis being 34yrs (Kumar, Clark, 2002). However, patients can present as children and young adults, and all ages are affected. It is more common in Caucasians than other races, and is also more frequently seen in those of Jewish descent, especially Ashkenazi Jews.
The aetiology is currently unknown, but current opinion favours a genetic predisposition to the disease in addition to environmental triggers. The evidence for an underlying genetic factor comes from documented familial clusterings of the disease, twin studies and the increased prevalence in certain ethnic groups.
In a direct contrast to Crohn's Disease, where about 50% (some studies show up to 72%) of patients are smokers, ulcerative colitis appears to be a disease of non-smokers (Birrenbach, Böcker, 2004). This trait was first observed by Samuelsson in 1976, and then later confirmed by Harries et al in 1982. Harries et al were conducting a survey into the nutritional aspects of inflammatory bowel disease when they noted that, in comparison to the 44% of the control group who were regular smokers, only 8% of those with ulcerative colitis smoked.
Pathogenesis
Ulcerative colitis has an association with the HLA-DR2 gene. HLA stands for 'human leukocyte antigen', and it is these genes that produce the proteins that identify 'self' to an individual's immune system so that it doesn't attack normal body cells. Some diseases are associated with HLA antigens, and this results in the patient experiencing a chronic inflammatory disease because their immune system has been tricked into attacking the normal cells of the body. In the case of ulcerative colitis, this leads to inflammation of the mucosal lining of the colon. T-lymphocytes normally resident in the gut are inappropriately activated, leading to a cascade of cytokine-induced immune reactions by the mucosal cells. This inflammation attracts other inflammatory cells to the area, such as neutrophils, which release destructive proteases, nitric oxide and superoxide radicals. It is the action of these inflammatory cells that causes the mucosal injury, resulting in ulceration of the lining of the gut.
Ulcerative colitis is a progressive disease that begins in the rectum and extends back along the course of the colon. The percentage breakdown for the distribution of the disease in adults is:
- 55% - proctitis (rectum only)
- 30% - left sided colitis (rectum plus descending and sigmoid colon)
- 15% - pancolitis (rectum plus ascending, transverse, descending and sigmoid colon)(Ghosh et al, 2000)
Some patients who have a pancolitis may experience irritation of the terminal ileum due to 'backwash' out of the large intestine into the small intestine. Whilst the disease does not involve the mucosa of the anal canal, a small number of patients may have anal tags and fissures.
The ulcers themselves are irregular in outline and orientation, and eventually enlarge and become confluent. Pathological specimens show the colon as having small, discrete islands of normal mucosal surface surrounded by ulcerated tissue. The ulcers are haemorrhagic, and the patient often has an accompanying iron deficiency anaemia due to continuous loss of blood into the bowel.
Signs and Symptoms
The most characteristic symptom is the frequent passage of diarrhoea. Often, blood is seen mixed in with the stool; in more severe cases, there may be mucus and pus present. The severity of the disease is variable, from complete remission to a fulminating attack that requires in-patient hospital care. Some patients may only ever have a single attack of ulcerative colitis; unfortunately, 10% experience chronic symptoms. Most patients fall somewhere in between, running a course of remissions and exacerbations.
Mild
In mild cases, ulceration is confined to the rectum. There may be blood mixed in with the loose stool, and the patient may experience urgency (the need to open their bowels) and tenesmus (a feeling of incomplete evacuation). The patient may experience very few constitutional symptoms, but are usually greatly inconvenienced by the frequency of defecation; sometimes feeling the need to pass stools up to five times a day.
Moderate
In moderate cases, more of the bowel is affected. The patient may need to open their bowels up to 10 times a day, and blood is mixed in the loose / liquid stool. They may also experience lower abdominal discomfort, lethargy, anorexia, weight loss and a feeling of general malaise.
Severe
In severe attacks, most or the entirety of the bowel is affected. The patient, in addition to being in pain and constitutionally unwell, will also be tachycardic and running a fever. They will be opening their bowels up to 20 times a day, and will have pus and blood mixed in with the liquid stool. There is urgency, and there may be incontinence.
There are few physical signs to find on general examination of the patients. There may be distension of the abdomen, with guarding if the patient is in pain. Rectal examination will show the presence of blood.
Investigations
Blood tests - Simple blood tests are useful but limited in what they can tell you. In moderate / severe disease there will be iron deficiency anaemia and raised white cell count. The CRP and ESR will be raised because of inflammatory status, and liver biochemistry may be altered, with low albumin levels seen in severe disease. It is worth testing for pANCA (autoantibodies against neutrophils - perinuclear type), as it sometimes comes up positive in ulcerative colitis. pANCA is always negative in Crohn's, and so is helpful in distinguishing between the two diseases.
Stool culture - A stool culture should always be performed to rule out infective causes of diarrhoea.
Abdominal X-ray - It is vital to take an abdominal x-ray in moderate / severe attacks in order to judge the extent of the disease and to pick-up possible complications.
Sigmoidoscopy - A sigmoidoscopy will show an inflamed, bleeding and friable mucosa.
Colonoscopy - A colonoscopy should not be performed during severe attacks as there is a significant danger of perforation of the bowel. In more long-standing and chronic disease, it is a useful way of defining the extent and activity of disease, and to check for any signs of colon cancer.
Biopsy - A biopsy is required to confirm the diagnosis of ulcerative colitis. The patient will also need to have regular biopsies performed to pick up any dysplasia or colon cancer.
Barium enema - Barium enemas are another good investigation to show the extent of disease, and show a tubular, featureless colon in ulcerative colitis.
Management
Medical
There are three main classes of drugs that are currently used to treat ulcerative colitis.
Aminosalicylates - balsalazide, mesalazine, olsalazine, sulfsalazine
The active compound of the group of drugs called aminosalicylates is 5-aminosalicylic acid. The original aminosalicylate was sulfasalazine. This was made up of 5-aminosalicylic acid combined with sulfapyridine (a sulfonamide), which acts as a carrier to the colonic site of action. Whilst an effective treatment for ulcerative colitis, it had a variety of unwelcome side-effects caused by the sulfapyridine. Newer aminosalicylates avoid this by just using the dimer and prodrug of 5-aminosalicylic acid, and 5-aminosalicylic acid itself.
Its mechanism of action is unknown, but is thought that it might act by scavenging free radicals, inhibiting prostaglandin and leukotriene production and/or by decreasing neutrophil chemotaxis and superoxide generation (Rang et al, 2003) .
Glucocorticoids - hydrocortisone, budesonide, prednisolone
Glucocorticoids (corticosteroids) are anti-inflammatory and immunosuppressive agents that are used in a variety of autoimmune diseases. They work in a variety of ways, but the main mode of action seems to be inhibition of transcription of the genes for cyclooxygenase-2, cytokines, cell adhesion molecules and the inducible form of nitric oxide synthase.
Immunosupressants - cyclosporin
In severe cases of ulcerative colitis, patients may benefit from a short course of cyclosporin, an immunosupressant that inhibits the production and action of interleukin-2 (IL-2).
Mild to moderate disease is treated by local application of either a corticosteroid or an aminosalicylate. This is usually in the form of an enema, but special foam preparations are available if the patient has difficulty retaining liquid enemas. If there is little or no response to local therapy, then oral treatment with aminosalicylates alone is begun. The use of oral steroids is to be avoided if possible, but occasional flair-ups may require a 4-8 week course of prednisolone.
Severe disease requires hospital admission and immediate treatment with intravenous corticosteroid. There should also be supportive therapy, including water and electrolyte replacement, blood transfusion, and parenteral nutrition and antibiotics.
Remission is maintained using aminosalicylates. Patients also need to be given appropriate dietary advice; while no special diet needs to be adopted, patients should know that they should increase their fibre intake and be sure to eat nutritionally balanced meals. Some patients find that cutting milk and other dairy products out of their diet is beneficial, but this is by no means the rule. They should also be advised to take iron supplementation to counteract their anaemia.
Surgical
While the treatment of ulcerative colitis is mainly medical, surgery plays an important role in treating the disease. Emergency surgery may be needed in acute severe disease if medical therapy to treat the severe attack fails, the patient begins to haemorrhage into the bowel, or to prevent perforation of the bowel. The surgery of choice in this instance is a total colectomy with end ileostomy and preservation of the rectum using a Hartmann's pouch. This is life-saving treatment, with the removal of the colon being vital in helping the patient to recover their health. When the patient's condition has improved satisfactorily, further surgery can be performed to convert the emergency ileostomy into a more permanent solution. This means either a total proctocolectomy with ileal pouch-anal anastomosis (IPAA), where the rectum is removed and a replacement fashioned out of the patient's ileum, or a total proctocolectomy with end ileostomy, where the rectum is removed, anal canal sealed and the patient left with a permanent ileostomy.
Elective surgery is also performed. This is often out of patient choice due to chronic disease that is difficult to control. Surgical removal of the colon allows a 'cure' to be made, and most patients, while unwilling to have a stoma, find that life is greatly improved after surgery. Other reasons for elective surgery include the discovery of a dysplasia or carcinoma on biopsy, or because of growth retardation in children with ulcerative colitis. Again, the choice for surgery is either an IPAA or permanent end ileostomy.
Complications
Carcinoma - Patients with ulcerative colitis are at an increased risk of developing bowel cancer as a result of dysplastic change caused by long-standing disease. The risk is small in those who've had the disease less than 10yrs, but after this time, these patients are given regular colonoscopies and biopsies in the hope of detecting any changes. The risk is greatest for those who have had a pancolitis, with their risk of developing bowel cancer within 20yrs approaching 20%, compared to 5% for those who haven't had a pancolitis.
Toxic Megacolon - Toxic megacolon is a complication of severe disease where the colon dilates to the point of perforation, resulting in faecal peritonitis.
Massive haemorrhage into the bowel - Very rare.
Systemic complications - These are uncommon, and of a number of different types. They are part of the spectrum of autoimmune disease, and are an indication of the severity of the colitis. Examples include erythema nodosum, glomerulonephritis and ankylosing spondylitis. Usually resolve on successful treatment of the ulcerative colitis.
Prognosis
- A third of patients with mild disease will go on to develop moderate symptoms due to progression of the ulcerative colitis. Of these, 5-10% will develop a pancolitis.
- A third of patients with ulcerative colitis will have a single attack; the rest will have a relapsing-remitting course.
- A third of patients with ulcerative colitis will undergo a total colectomy within 20yrs of diagnosis. (Kumar, Clark, 2002)
Patient Support Sites
UK - The National Association for Colitis and Crohn's Disease, http://www.nacc.org.uk/content/home.asp
US - Crohn's & Colitis Foundation of America, http://www.ccfa.org/
References
- Birrenbach T, Böcker U, 2004,
Inflammatory Bowel Disease and Smoking: A Review of Epidemiology, Pathophysiology, and Therapeutic Implications , Inflamm Bowel Dis 2004; 10(6):848-59
- Cima R R, Pemberton J H, 2005,
Medical and Surgical Management of Chronic Ulcerative Colitis , Arch Surg 2005; 140:300-310
- Ghosh S, Shand A, Ferguson A, 2000,
Ulcerative Colitis , BMJ 2000; 320:1119-1123
- Harries A D, Baird A, Rhodes J, 1982,
Non-smoking: a feature of ulcerative colitis , BMJ 1982; 706:284
- Hanauer S B, 1996,
Inflammatory Bowel Disease , N Engl J Med 1996; 334:841-848
- Kumar P, Clark M, 2002,
Clinical Medicine , 5th edition, WB Saunders, 300-309
- Rang H P, Dale M M, Ritter J M, Moore P K, 2003,
Pharmacology , 5th edition, Churchill Livingstone, 377-378
- Samuelsson S, 1976,
Ulceros Colit och Proktit [dissertation] . Uppsala, Sweden: Department of Social Medicine, University of Uppsala
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