ULCERATIVE COLITIS

• ULCERATIVE COLITIS
Aetiology: The cause of UC is unknown.
Epidemiology
The disease has been rare in eastern populations but is now being reported more commonly, suggesting an environmental cause that has developed as a result of an increasing ‘westernization’ of diet and/or social habits and better diagnostic facilities.
The sex ratio is equal in the first four decades of life. From the age of 40 years, the incidence in females falls whereas it remains the same in males. Most patients are between the ages of 20 and 40 years.

Pathology
In 95% of cases, the disease starts in the rectum and spreads proximally.
It is a diffuse inflammatory disease, primarily affecting the mucosa and superficial submucosa, and only in severe disease are the deeper layers of the intestinal wall affected.
There are multiple minute ulcers. When the disease is chronic, inflammatory polyps (pseudopolyps) occur in up to 20% of cases and may be numerous.
On microscopic investigation, there is an increase in inflammatory cells in the lamina propria, the walls of crypts are infiltrated by inflammatory cells and there are crypt abscesses. There is depletion of goblet cell mucin. With time, these changes become severe, and precancerous changes can develop (= severe dysplasia or carcinoma in situ).

Symptoms
The first symptom is watery or blood diarrhoea; there may be a rectal discharge of mucus that is either blood-stained or purulent. Pain as an early symptom is unusual. In most cases, the disease is chronic and characterized by relapses and remissions.
In general, a poor prognosis is indicated by
(1) A severe initial attack,
(2) Disease involving the whole colon and
(3) Increasing age, especially after 60 years.

Disease severity can be graded as:
1. Mild – rectal bleeding or diarrhoea with four or fewer motions per day and the absence of systemic signs of disease;
2. Moderate – more than four motions per day but no systemic signs of illness;
3. Severe – more than four motions a day together with one or more signs of systemic illness:
Fever over 37.5°C,
Tachycardia more than 90 min–1,
Hypoalbuminaemia less than 30 g l–1,
Weight loss more than 3 kg.

Complications of UC
Acute
? Fulminating colitis and toxic dilatation (megacolon); the diagnosis is confirmed by the presence on a plain abdominal radiograph of the colon with a diameter of more than 6 cm.
? Perforation
? Haemorrhage
Chronic
? Cancer
? Extra-alimentary manifestations: skin lesions, eye problems, liver disease.

Investigations
A plain abdominal film can often show the severity of disease.

Barium enema
The principal signs are;
• Loss of haustration, especially in the distal colon;
• Mucosal changes caused by granularity;
• Pseudo polyps;
• Narrow contracted colon in chronic cases.
In some centres, an instant enema is used with a water-soluble medium for contrast instead of barium and no bowel preparation to avoid aggravating any underlying colitis.

Sigmoidoscopy Is essential for diagnosis of early cases and mild disease not showing up on a barium enema. The initial findings are those of proctitis: the mucosa is hyperaemic and bleeds on touch, and there may be pus-like exudates.
Where there has been remission and relapse, there may be the presence of regeneration nodules or pseudopolyps. Later, tiny ulcers may be seen that appear to coalesce.
This is different from the picture of amoebic dysentery, in which there are large, deep ulcers with intervening normal mucosa.

Colonoscopy and biopsy
This has an important place in management:
1. To establish the extent of inflammation;
2. To distinguish between UC and Crohn’s colitis;
3. To monitor response to treatment;
4. To assess longstanding cases for malignant change.
Although it may occasionally be helpful, colonoscopy is not usually used in acute cases for fear of aggravating the disease or perforation.

Bacteriology
Pathologically, it is difficult to distinguish infective colitis from UC.
A stool specimen needs to be sent for microbiology analysis when UC is suspected.

The cancer risk in colitis
The overall risk is about 3.5%. It is much less in early cases but increases with duration of disease. Carcinoma is more likely to occur if the whole colon is involved and if the disease started in early life.
The golden rule is that, when the disease has been present for 10 years or more, Annual colonoscopic checks must be carried out to check for dysplasia, even if the disease is clinically quiescent.
If on biopsy, there is severe epithelial dysplasia, which is a marker for impending or frank carcinomatous change, surgery is indicated.

Extra intestinal manifestations
Arthritis occurs in around 15% of patients and is of the large joint polyarthropathy type, affecting knees, ankles, elbows and wrists. Sacroiliitis and ankylosing spondylitis are 20 times more common in patients with UC.
Bile duct cancer is a rare complication, and colectomy does not appear to reduce the risk of subsequent bile duct cancer or sclerosing cholangitis.
Skin lesions: erythema nodosum, pyoderma gangrenosum or aphthous ulceration;
Eye problems: iritis;
Liver disease: sclerosing cholangitis has been reported in up to 70% of cases.

Medical treatment of an acute attack
Corticosteroids are the most useful drugs and can be given either locally for inflammation of the rectum or systemically when the disease is more extensive.
5-aminosalicylic acid (5- ASA) derivatives can be given both topically and systemically.
Their main function is in maintaining remission rather than treating an acute attack.
In Severe attacks; patients must be regarded as medical emergencies and require immediate admission to hospital.
It is important to monitor vital signs (pulse, temperature and blood pressure).
Weight needs to be recorded at admission and twice a week while in hospital.
A stool chart should be kept.
Increasing abdominal girth is a potential sign of megacolon developing.
A plain abdominal radiograph is taken daily and inspected for dilatation of the transverse colon of more than 5.5 cm. The presence of mucosal islands or intramural gas on plain radiographs, increasing colonic diameter or a sudden increase in pulse and temperature may indicate a colonic perforation.
Fluid and electrolyte balance is maintained, anaemia is corrected and adequate nutrition is provided, sometimes intravenously in severe cases.
The patient is treated with intravenous hydrocortisone 100–200 mg four times daily.
This can be supplemented with a rectal infusion of prednisolone.
Some patients are treated with azathioprine or ciclosporin A to induce remission.
If there is failure to gain an improvement within 3–5 days, then surgery must be seriously considered.

Indications for surgery
The need for surgery is highest in the first year after the disease onset, for:
1. Severe or fulminating disease failing to respond to medical therapy.
2. Chronic disease with anaemia, frequent stools, urgency and tenesmus.
3. Steroid-dependent disease – here, the disease is not severe but remission cannot be maintained without substantial doses of steroids.
4. The risk of neoplastic change: patients who have severe dysplasia on review colonoscopy.
5. Extraintestinal manifestations.
6. Rarely, severe haemorrhage .
7. Stenosis causing obstruction.

In the emergency situation, the ‘first aid procedure’ is a total abdominal colectomy and ileostomy. The rectum can either be brought out at the lower end of the wound as a mucous fistula or closed just beneath the skin.
Proctocolectomy and ileostomy; It is indicated in patients who are not candidates for restoration.The patient is left with a permanent ileostomy.
Restorative proctocolectomy with an ileoanal pouch (Parks); in this operation, a pouch is made out of ileum as a substitute for the rectum and sewn or stapled to the anal canal.
This avoids a permanent stoma.
Colectomy and ileorectal anastomosis; If there is minimal rectal inflammation.


CROHN’S DISEASE (REGIONAL ENTERITIS)
CD can affect any part of the gastrointestinal tract from the lips to the anal margin, but ileocolonic disease is the most common presentation. It is slightly more common in women than in men, but is most commonly diagnosed in young patients between the ages of 25 and 40 years.

Aetiology
Although CD has some features suggesting chronic infection, no causative organism has ever been found.
Focal ischaemia has also been postulated as a causative factor, possibly originating from a vasculitis arising through an immunological process.
A wide variety of foods has now been implicated, but none conclusively.
Smoking increases the risk threefold.
Genetic factors are thought to play a part.
There is an association with ankylosing spondylitis.
CD can predispose to cancer, although the incidence of malignant change is not nearly as high as in UC and is most manifest in the ileum.

Pathogenesis
As in UC, there is thought to be an increased permeability of the mucous membrane.
This leads to increased passage of antigens, which are thought to induce a cell-mediated inflammatory response. This results in the release of cytokines, such as interleukin-2 and tumour necrosis factor, which coordinate local and systemic responses.
In CD, there is thought to be a defect in suppressor T cells, which usually act to prevent escalation of the inflammatory process.

Pathology
Ileal disease is the most common, accounting for 60% of cases.
Anal lesions are common.
Resection specimens show a fibrotic thickening of the intestinal wall with a narrow lumen. There is usually dilated gut just proximal to the stricture and, in the strictured area; there are deep mucosal ulcerations with linear or snake-like patterns.
Oedema in the mucosa between the ulcers gives rise to a cobblestone appearance.
The transmural inflammation leads to adhesions, inflammatory masses with mesenteric abscesses and fistulae into adjacent organs.
The condition is discontinuous, with inflamed areas separated from normal intestine, so called skip lesions.
Under the microscope, there are focal areas of chronic inflammation involving all layers of the intestinal wall. There are non-caseating giant cell granulomas, but these are only found in 60% of patients.

Clinical features
Presentation depends upon the area of involvement.
Acute Crohn’s disease; occurs in only 5% of cases.
Symptoms and signs resemble those of acute appendicitis, but there is usually diarrhoea preceding the attack. Rarely, there could be a free perforation of the small intestine, resulting in a local or diffuse peritonitis. Acute colitis with or without toxic megacolon can occur in CD but is less common than in UC.
Chronic Crohn’s disease; There is often a history of mild diarrhoea extending over many months, occurring in bouts accompanied by intestinal colic.Intestine begins to narrow with fibrosis, causing obstructive symptoms.
A perianal abscess or fissure may be the first presenting feature of CD.
With progression of the disease, adhesions and transmural fissuring, intra-abdominal abscesses and fistula tracts can develop.
1. Enteroenteric fistulae can occur into adjacent small bowel loops or the pelvic colon, and enterovesical fistulae may cause repeated urinary tract infections and pneumaturia.
2. Enterocutaneous fistulae rarely occur spontaneously and usually follow previous surgery.

Investigation
Laboratory
A full blood count needs to be performed to exclude anaemia.
Protein levels that correspond to disease activity include C-reactive protein and orosomucoid.

Endoscopy
Sigmoidoscopic examination may be normal or show minimal involvement.
However, ulceration in the anal canal will be readily seen.
As a result of the discontinuous nature of CD, there will be areas of normal colon or rectum.
In between these, there are areas of inflamed mucosa that are irregular and ulcerated, with mucopurulent exudates.
Upper gastrointestinal symptoms may have to be investigated by way of upper gastrointestinal endoscopy, which may reveal deep longitudinal ulcers and cobblestone mucosa.
Capsule endoscopy may also have a useful role in those with chronic gastrointestinal bleeding.

Barium enema will show similar features to those of colonoscopy in the colon.
Small bowel enema is the best investigation of the small intestine. The involved areas tend to be narrowed, irregular and, sometimes, when a length of terminal ileum is involved, there may be the string sign of Kantor.
Sinograms are useful in patients with enterocutaneous fistulae.
CT scans are used in patients with fistulae and those with intra-abdominal abscesses and complex involvement.
Magnetic resonance imaging (MRI) has been shown to be useful in assessing perianal disease.

Medical therapy
Steroids are the mainstay of treatment. These are effective in inducing remission in moderate to severe disease in 70–80% of cases. Steroids can also be used as topical agents in the rectum with reduced systemic bioavailability, but long-term use causes adrenal suppression.
5-ASA compounds can be used after remission to reduce the absolute risk of recurrence in those patients with colonic involvement.
Azathioprine is used for its additive and steroid-sparing effect and is now standard maintenance therapy. Ciclosporin acts by inhibiting cell-mediated immunity.
Nutritional support is essential. Severely malnourished people may require intravenous feeding or nasoenteric feeding regimens.
Anaemia, hypoproteinaemia and electrolyte, vitamin and metabolic bone problems must all be addressed.

Indications for surgery
Surgical resection will not cure CD. Surgery is therefore focused on the complications of the disease.
These complications include:
• Recurrent intestinal obstruction;
• Bleeding;
• Perforation;
• Failure of medical therapy;
• Intestinal fistula;
• Fulminant colitis;
• Malignant change;
• Perianal disease

The main surgical principle is to Preserve functional gut length and maintain gut function. Resection is kept to a minimum so as to deal with the local problem. The course of the disease after surgery is unpredictable, but recurrence is common.
1. Ileocaecal resection is the usual procedure for ileocaecal disease with a primary anastomosis between the ileum and the ascending or transverse colon depending on the extent of the disease.
2. Segmental resection. Short segments of small or large bowel involvement can be treated by segmental resection.
3. Colectomy and ileorectal anastomosis. In patients with widespread colonic disease with rectal sparing and a normal anus.
4. Emergency colectomy; the indications are similar to those for UC.
5. Laparoscopic surgery. Resections and diversion are safe in uncomplicated CD.
6. Temporary loop ileostomy. This can be used either in patients with acute distal CD, allowing remission and later restoration of continuity, or in patients with severe perianal or rectal disease.
7. Proctocolectomy. Patients with colonic and anal disease failing to respond to medical treatment or defunction will eventually require a permanent ileostomy.
8. Strictureplasty. Multiple strictured areas of CD can be treated by a local widening procedure, strictureplasty, to avoid excessive small bowel resection.
9. Anal diseases is usually treated conservatively by simple drainage of abscesses, placing setons around any fistulae and, occasionally in patients with inactive disease, primary repair of a rectovaginal or high fistula-in-ano could be attempted.

Differences between UC and CD
? UC affects the colon; CD can affect any part of the gastrointestinal tract, but particularly the small and large bowel
? UC is a mucosal disease whereas CD affects the full thickness of the bowel wall
? UC produces confluent disease in the colon and rectum whereas CD is characterized by skip lesions
? CD more commonly causes stricturing and fistulation
? Granulomas may be found on histology in CD but not in UC
? CD is often associated with perianal disease whereas this is unusual in UC
? CD affecting the terminal ileum may produce symptoms mimicking appendicitis, but this does not occur in UC
? Resection of the colon and rectum cures the patient with UC, whereas recurrence is common after resection in CD