Ulcerative Colitis

What is Ulcerative Colitis?

Ulcerative colitis is a chronic disease with recurrent, uncontrolled inflammation of the large intestine (or colon). Sharing many characteristics with Crohn's disease, both syndromes are considered forms of inflammatory bowel disease (IBD). Patients affected by ulcerative colitis present open sores (ulcers) in the colonic mucosa. The rectum is always affected in adults, and the inflammation usually spreads from the distal to the proximal segments of the colon. The main symptom is bloody or mucous diarrhea. Ulcerative colitis is an intermittent disease, alternating asymptomatic periods with other periods in which the symptoms appear exacerbated. If left untreated, chronic ulcerative colitis may result  in complications mandating surgical intervention, including toxic megacolon, significant bleeding and gastrointestinal perforation.

The prevalence of ulcerative colitis in North America has been estimated to be between 37.5 and 238 patients per 100,000 inhabitants, and between 21 and 294 in Europe. Most deaths associated with ulcerative colitis are observed in patients with severe disease during the perioperative period. Ulcerative colitis occurs slightly more frequently in males (60%) and has a tendency to increase its incidence as a country becomes Westernized.

What Causes Ulcerative Colitis?

There is no general agreement on the causes of ulcerative colitis, but the inflammation is believed to result from an aberrant immune response in individuals that are genetically predisposed to it. This immune response may be the consequence of a multifaceted interaction among some environmental factor, the endogenous flora of the gut and the colonic immune system.

The strongest evidence that genetic factors are important comes from concordance studies in twins, although they seem to play an even more important role in Crohn's disease. Twelve different regions of the genome have been associated with susceptibility to ulcerative colitis. These are located in nine different chromosomes and have been named IBD1-9.

Environmental factors also seem to play an important role in the manifestation of the disease, suggested by the increased incidence rates among immigrants from low-incidence regions moving to developed countries. In Hong Kong and mainland China, the symptoms of ulcerative colitis and Crohn's disease are strongly correlated with the degree of industrialization of the area. Inflammation triggered by substances present in the diet has been hypothesized as a cause for ulcerative colitis. Such an explanation would contribute to explain the observed geographical variation on the incidence of the disease. However, most dietary studies have weak methods and poor patient compliance, making the interpretation of their findings difficult. The evidence for seasonal variability is equally controversial.

It is widely accepted that an inappropriate response of a defective mucosal immune system to the endogenous flora of the gut and other agents present in the intestinal lumen during ulcerative colitis, leads some people to classify it as an immune disease. The reasons why microbial antigens induce this aberrant response in certain individuals remain to be elucidated.

Symptoms of Ulcerative Colitis

The main symptoms of ulcerative colitis, both as new onset and in recurring cases, include:

• Bloody and/or Mucous Diarrhea
• Rectal Urgency
• Abdominal Pain/ Abdominal Cramps
• Weight Loss
• Anemia
• Bowel Distension
• Tachycardia
• Fever

Since none of these symptoms is specific for ulcerative colitis, it is important to consider a variety of differential diagnoses before moving on to treatment, particularly in the elderly population.

Diagnosis of Ulcerative Colitis

The most conclusive single test for the diagnosis of ulcerative colitis is endoscopy (either full colonoscopy or a single sigmoidoscopy). This should be combined with biopsy of the inflamed tissue and stool examination to rule out the presence of parasites and other infectious organisms. Characteristic mucosal changes that may be observed during endoscopy, and would indicate a diagnosis of ulcerative colitis, include loss of the typical vascular pattern, granularity, friability and ulceration.

Additional tests that could be ordered by the physician to confirm a diagnosis of ulcerative colitis include a complete blood count to check for anemia, and measurements of C-reactive protein and erythrocyte sedimentation rate to confirm the presence of an inflammatory process in the patient’s gut. If there is any doubt about the diagnosis at the acute stage, endoscopic and histological confirmation should be repeated after a period of time has passed.

Treatment of Ulcerative Colitis

The choice of treatment for ulcerative colitis depends on a variety of factors, including degree of activity, distribution, course of disease, frequency of relapses, extraintestinal manifestations, previous medication and the patient’s own choice. The main goal is to induce remission of the symptoms to provide improved quality of life and minimize the risk of cancer. Cases that are limited to the rectum and show mild or moderate activity are treated with the drug mesalazine or corticosteroids such as prednisone, either topically, orally or in combination.  Nicotine treatment has also been proposed for patients of ulcerative colitis, since the incidence is lower in smokers and it has been shown to be more effective than a placebo.

When ulcerative colitis is severe and does not respond to this treatment, the patient should be hospitalized and monitored closely because of the risk of life-threatening complications. In this case, the standard treatment is intravenous steroids.

Surgery is an option in those cases of chronic continuous colitis that have been under steroid therapy for a long time, incurring a high risk of septic complications. Because of the compromised healing, a staged procedure consisting of colectomy and ileostomy is preferred, leaving the rectum intact in order to consider the option of reconstruction at a later stage.

A diagnosis of perforation or cancer of the colon or rectum is an absolute indication for surgery. The patients should always be informed of the availability of the surgical option and made aware of the risks that each procedure entails.

Prognosis of Ulcerative Colitis

Determining the prognosis of ulcerative colitis is difficult because the course of the disease is so variable and shows periods of inactivity alternated with acute bouts. Surgery cannot be regarded as a definitive treatment, since patients have a risk of developing pouchitis during the postoperative period. It has been estimated that as many as 50% of these patients would experience an episode within five years after surgery, and in up to 10% of these patients pouchitis exhibits a chronic course that does not respond well to antibiotics.

The patients also have an increased risk of developing colorectal cancer. Patients that have experienced an episode of ulcerative colitis are encouraged to undergo screening colonoscopies accompanied of biopsies to check for dysplasia.

The overall mortality of ulcerative colitis patients is not greater than that of the general population, but it is increased in patients with severe disease, with most of the deaths observed during the perioperative period.

Preventing Ulcerative Colitis

Because the cause of ulcerative colitis remains unknown, and it may have an important genetic component, there are currently no guidelines for reducing the risk of developing the disease. Incorporating vegetable fiber and oatmeal to the diet is usually mentioned as a preventive measure, since they are thought to be effective in controlling gastrointestinal ulcers. The use of non-steroidal anti-inflammatory drugs for pain relief is also discouraged in favor of acetaminophen (paracetamol) or other over-the-counter analgesics that are less aggressive with the gastrointestinal tract.

As mentioned above, once ulcerative colitis develops, the risk of developing colorectal cancer is significantly increased for the patient. Therefore, chemoprevention with agents such as 5-aminosalicylates in combination with colonoscopy surveillance programs and multiple biopsies are critical for the health status of the patient once ulcerative colitis has been declared and treated.

Living with Ulcerative Colitis

Living with a chronic illness like ulcerative colitis can be difficult for the patient, in particular because there is no clear method to predict when acute episodes or "flares" are going to occur. This carries a considerable psychological burden. Results from surveys in patients with chronic inflammatory bowel disease showed that fatigue, loss of energy, fear of losing control, fear of producing unpleasant odors, and a negative body image are very common, and this has an important impact in the ability to function normally in a social context.

A more integrated management program that takes these additional aspects of the disease into consideration is gradually being adopted. Recommendations include keeping a symptoms diary to understand which factors are more likely to trigger an acute episode, eating a balanced diet, managing stress, doing regular exercise, opening up to family members, friends or work colleagues about the condition, and seeking psychological help if necessary.

Current Research of Ulcerative Colitis

Therapy for ulcerative colitis has become more intensive in recent years, with more patients receiving immunomodulators at an early stage of their disease. New medications with enhanced effectiveness have been tested and released to the market, such as LIALDA™. Otherwise known as MMX mesalamine, this is a novel, high-strength formulation of the standard therapeutic agents used to treat ulcerative colitis that uses a multi matrix system technology to deliver the active drug throughout the colon.

Endoscopic imaging for diagnosis and post-treatment surveillance of ulcerative colitis has also benefited from the development of novel techniques such as endoscopic tri-modal imaging (ETMI), which incorporates white light endoscopy, autofluorescence imaging and narrow-band imaging.