INTRODUCTION
Ulcerative colitis (UC) is a disease in which the lining of the colon (the large intestine) becomes inflamed. The immune system inappropriately targets the lining of the colon, causing inflammation, ulceration, bleeding and diarrhea. The inflammation almost always affects the rectum and lower part of the colon, but it can also effect the entire colon (
show figure 1
).
Although ulcerative colitis is a chronic condition and has no cure, it can usually be well controlled. Most people are able to live active and productive lives. Control of the disease includes long-term medical treatment and regular monitoring for complications.
This topic review discusses the causes, symptoms, diagnosis and treatment of ulcerative colitis. Surgical treatments for UC are discussed separately. (
See "Patient information: Surgical treatment of ulcerative colitis"
). Topic reviews about another inflammatory bowel disease, Crohn's disease, are also available. (
See "Patient information: Crohn's disease"
and
see "Patient information: Surgical treatment of Crohn's disease"
).
CAUSES
The development of ulcerative colitis appears to be influenced by two factors: genetic susceptibility and environmental triggers. These two factors eventually cause the immune system to damage the lining of the colon. The mechanisms underlying this abnormal immune system response are being intensively studied.
Genetics
Ulcerative colitis tends to run in families, suggesting that genetics have a role in this disease. About 10 to 25 percent of affected people have a first-degree relative (either a sibling or parent) with inflammatory bowel disease (either ulcerative colitis or Crohn's disease).
Environment
Several environmental factors, such as infections, are suspected of triggering UC in people who have a genetic susceptibility. However, no single factor has been consistently proven to be the primary trigger. The bacteria that normally live in the colon also have an important role in the development of the disease, since animals at risk for UC do not develop it when raised in a bacteria-free environment.
For unknown reasons, ulcerative colitis is more common in people who live in northern climates and in developed countries, such as North America, Great Britain, and Scandinavia, compared to those who live in southern climates or developing countries. In two areas (Minnesota and northern Norway), approximately 13 to 15 people out of every 100,000 have UC. UC affects men and women equally. The peak incidence of UC occurs between the ages of 15 and 30.
COMMON VOCABULARY
Clinicians often use specific terms to discuss how much of the colon is affected by UC. This often related to the severity of symptoms and the course of the disease over time. Treatment varies depending upon which parts of the colon are involved. The following summarizes commonly used terms, which are also illustrated in this figure (
show figure 2
).
- Ulcerative proctitis refers to disease limited to the rectum.
- Distal colitis or proctosigmoiditis is used when the inflammatory process extends into the mid-sigmoid colon
- Left sided colitis refers to disease that extends to but not beyond the splenic flexure (the sharp bend in the intestines where the transverse colon joins the descending colon, located under the spleen)
- Extensive colitis is defined as disease that extends beyond the splenic flexure but not as far as the cecum (the beginning of the colon).
- Pancolitis is used when the inflammatory process extends to the cecum.
Patients who have large amounts of colon involved tend to be sicker. However, even those with only left-sided disease can be ill. In about 15 percent of people with limited forms of ulcerative colitis (left sided or below), the disease begins to involve more of the colon within five years of diagnosis.
SYMPTOMS
The symptoms of ulcerative colitis can be mild, moderate, or severe and can fluctuate over time. The term "flare" is used to describe periods in which the disease becomes more active. The term "remission" is used to describe periods of quiescence, or inactivity.
Mild disease
Symptoms of mild ulcerative colitis include intermittent rectal bleeding, mucus discharge, and mild diarrhea (defined as fewer than four stools per day). Symptoms may also include mild, crampy abdominal pain; painful straining with bowel movements; and bouts of constipation.
Moderate disease
Symptoms of moderate ulcerative colitis include frequent, loose bloody stools (up to 10 per day), mild anemia, mild to moderate abdominal pain, and a low-grade fever.
Severe disease
Patients with severe ulcerative colitis usually have a large region of the colon involved, often the entire colon. Symptoms of severe ulcerative colitis include frequent loose stools (more than 10 per day), severe abdominal cramps, fever, dehydration, and significant bleeding, frequently leading to anemia. Severe ulcerative colitis can lead to rapid weight loss.
Fulminant disease
Fulminant ulcerative colitis is a worsening of severe ulcerative colitis that causes a high white blood cell count, loss of appetite, and severe abdominal pain.
Extraintestinal disease
For poorly understood reasons, patients with UC can develop inflammation outside of the colon. Inflammation often affects the large joints (arthritis, and sacroiliitis), the eye (episcleritis and anterior uveitis), the skin (pyoderma gangrenosum and erythema nodosum), and, less commonly, the lung (
show picture 1-4
).
These events usually occur in patients who are having a flare of the disease. Other types of inflammation can occur in patients with UC even when the colonic disease appears to be in remission. One of these is a type of arthritis of the spine (ankylosing spondylitis), which can cause low back pain. Another, occurring in about 5 percent of people, is inflammation of the bile ducts, which can lead to a liver disease called primary sclerosing cholangitis (PSC). PSC is usually detected with blood tests of liver function. People with UC are also at increased risk for blood clots and certain types of anemia.
DIAGNOSIS
Ulcerative colitis is usually diagnosed based upon the signs and symptoms noted during a thorough medical history and physical examination. In addition, the results of certain diagnostic tests, including blood and stool tests and a sigmoidoscopy or colonoscopy are important to consider. These tests are also helpful for ruling out other causes of colitis, including Crohn's disease, and certain infections.
TREATMENT
Treatment of UC is tailored to the region of the colon that is involved, the severity of inflammation and symptoms, and other individual factors. For most patients ulcerative colitis is characterized by a frustrating pattern of flares and remissions. As a result, the two main goals of treatment are to achieve and maintain remission, which usually requires long-term medications. On the other hand, about 15 percent of people who have an initial attack will remain in remission without medications, possibly for the rest of their lives. However, it is possible that these patients actually had an undiagnosed infection and not UC.
Proctitis and proctosigmoiditis
Proctitis or proctosigmoiditis are usually treated with one or more medications that are given as an enema (for proctitis or proctosigmoiditis) or a suppository or foam for proctitis. Suppositories and foam only reach the rectum or lower sigmoid colon, while enemas can reach as high as the splenic flexure (
show figure 2
).
Some patients also require treatment with oral medications such as sulfasalazine (Azulfidine) and an 5-aminosalicylate (5-ASA) or related drugs (eg, Pentasa, Asacol, Colazal, Lialda, and Dipentum). In some cases, a steroid treatment (eg, Cortenema) is required.
These treatments usually produce improvement after three weeks, lead to remission in up to 90 percent of people, and provide prolonged remission in up to 70 percent of people. Continuous treatment with a 5-ASA-containing drug is usually recommended to maintain remission, although it is often possible to taper the dose of medication. Patients with mild symptoms may benefit from additional treatments such as antidiarrheal medications.
Extensive and pancolitis
Most patients require an oral medication if their inflammation extends above the sigmoid colon. Some patients may also benefit from combined treatment with oral and topical preparations. Patients with moderate to severe symptoms may require temporary treatment with a steroid drug (usually prednisone), either as an outpatient or given intravenously in the hospital. Remission can be achieved in most patients. Once remission is achieved, patients usually continue to take one of the oral 5-ASA drugs.
Sulfasalazine
Sulfasalazine is one of the oldest drugs used to treat UC. Common side effects associated with its use include headaches (which are dose-dependent), skin rash, nausea, and reversible infertility in men; these side effects occur in over 10 percent of patients. Much less common side-effects include hives, itching, pancreatitis (inflammation of the pancreas), hepatitis (inflammation of the liver), and a low white or red blood cell count. Rare side effects include severe allergic reactions, thyroid problems, severe liver problems, and kidney problems (
show table 1
). People who take sulfasalazine should take folic acid supplements since the drug may interfere with its absorption in foods. A full discussion of this medication is available separately. (
See "Patient information: Sulfasalazine and the 5-aminosalicylates"
).
5-Aminosalicylates
5-aminosalicylate medications are generally tolerated better than sulfasalazine. As a result, they can be given in higher doses, which is often more effective. The most common side effects are headache, malaise, gas, and cramps. Hair loss and skin rash are less common. Rare side-effects include pericarditis (inflammation of the lining surrounding the heart), myocarditis (inflammation of the heart), hypersensitivity pneumonitis (inflammation of the lungs), allergic reactions, pancreatitis, kidney problems, decreased blood counts, and hepatitis. A full discussion of this medication is available separately. (
See "Patient information: Sulfasalazine and the 5-aminosalicylates"
).
Glucocorticoids (steroids)
Steroids may be the most difficult medication to tolerate since there are many side-effects. Increased appetite, weight gain, acne, fluid retention, trembling, mood swings, and difficulty sleeping are common. Other side effects occur in patients who take steroids for long periods of time, particularly if high doses are used. These include diabetes, thinning of the skin, easy bruising, a "cushingoid" appearance (widening of the face and a hump in the back), thinning of the bones, body hair growth, cataracts, high blood pressure, stomach ulcers, avascular necrosis (a serious joint problem), and infections. Because of the risk of these side effects, most patients are tapered off of steroids as soon as possible.
TREATMENT OF REFRACTORY DISEASE
Refractory ulcerative colitis occurs when a person's disease does not respond or responds poorly to the medical treatments used to treat the disease. Patients who depend upon steroids to control their symptoms are usually referred to as having refractory disease.
Most patients are treated with drugs that suppress the immune system. The most commonly used drugs are 6-mercaptopurine and azathioprine, and more recently infliximab. Colectomy (surgical removal of the colon) may be required if medical treatments are unsuccessful or if complications develop. Patients who cannot tolerate the constant battle with their disease sometimes prefer to have their colon removed. (
See "Patient information: Surgical treatment of ulcerative colitis"
).
6-mercaptopurine and azathioprine
Azathioprine and its metabolite (6-mercaptopurine) have been used to treat refractory ulcerative colitis for many years. These drugs lessen symptoms in 60 to 70 percent of people and help to maintain remission and decrease the need for steroids. These treatments may require three to six months to produce their maximal effect. Patients taking these drugs need to be closely monitored for side effects, which can include a decrease in the white blood cell count, inflammation of the pancreas, and, less commonly, hepatitis (inflammation of the liver). Long-term use of these drugs has been associated with an increased risk of infections and possibly certain types of tumors.
Cyclosporine
Cyclosporine is a powerful immunosuppressive drug usually used after organ transplantation. It can be very effective when given into a vein (intravenously) to patients who are hospitalized with refractory fulminant colitis (
see "Fulminant disease" above
). However, it is not usually used for long-term maintenance treatment of UC.
Infliximab
Infliximab (Remicadeÿ) is a powerful medication that has been used to treat Crohn's disease and rheumatoid arthritis, and is now used to treat refractory ulcerative colitis. Infliximab works differently than other treatments for UC. It is in a class of medications known as biologic response modifiers, which work by interfering with pathways involved in inflammation. Infliximab must be given into a vein in a doctor's office or clinic, which takes one to three hours to complete.
Infliximab may be used alone or in combination with other treatments. Because of their cost (generally more than $15,000 per year in the United States) and the potential risk of side effects, biologic response agents are generally reserved for patients with severe ulcerative colitis who have not responded to steroids, who prefer to avoid surgical removal of the colon, and who cannot take cyclosporine.
Other drugs
A number of other drugs have been used in patients with refractory ulcerative colitis, including fish oil, nicotine, ciprofloxacin, probiotics (beneficial bacteria) and a variety of experimental agents. The benefit of these drugs is much less well established than for azathioprine and 6-mercaptopurine cyclosporine and infliximab.
NUTRITIONAL CONSIDERATIONS
People with advanced forms of ulcerative colitis often lose weight and develop nutritional deficiencies. A well balanced, nutritious diet can help maintain health and a normal body weight. There are no specific foods that cause ulcerative colitis or help to maintain remission. The only foods that should be avoided are those that are known to worsen symptoms (
show table 2
). People who restrict their diet for any reason should take a daily multivitamin.
Vitamins and medications
It is reasonable to take a multivitamin daily. As mentioned above, patients taking sulfasalazine should take folic acid supplements.
Pain medications containing nonsteroidal antiinflammatory drugs (NSAIDS), such as ibuprofen and naproxen, should usually be avoided since they can worsen symptoms or cause a flare. Acetaminophen (Tylenol) should not cause a problem, although you should check with your doctor or pharmacist before taking any pain medication.
Lactose intolerance
Lactose intolerance occurs when a person is not able to digest the sugar lactose, which is the main sugar contained in milk products. Symptoms of lactose intolerance occur after eating or drinking something that contains lactose, and may include diarrhea, cramps, or gas. Lactose intolerance is very common in the general population and is common in people with ulcerative colitis. The symptoms of lactose intolerance can be minimized by avoiding dairy products. If dairy products are avoided, a calcium supplement with vitamin D should be taken to prevent thinning of the bones. (
See "Patient information: Calcium and vitamin D for bone health"
).
Reduce cramps and diarrhea
Patients with abdominal cramps and diarrhea may notice relief when they reduce their intake of fresh fruit and vegetables, caffeine, carbonated drinks, and sorbitol-containing products (sorbitol is an artificial sugar commonly used in sugar-free candies and gum).
Maintain remission
For unknown reasons, certain types of dietary fiber may actually help maintain remission. One study showed that eating Plantago ovata seeds, a source of fiber, was as effective as the drug mesalamine for maintaining remission. However, more data are needed before this treatment is widely recommended.
Enteral and parenteral feeding
Enteral feeding (feeding through a tube from the nose into the stomach) and parenteral feeding (intravenous feeding) are seldom used for the long-term treatment of ulcerative colitis. However, these feeding options may be used temporarily to improve nutritional status in people who are severely ill and unable to eat for a week or longer.
Herbal therapies
Several herbal therapies given by mouth or by enema have been suggested, but these are of unproven benefit and should probably be avoided. Consuming healthy bacteria (probiotics) is also being studied, but its role remains unclear.
PSYCHOSOCIAL THERAPIES
Stress can worsen ulcerative colitis. Counseling or psychotherapy can be helpful in dealing with the frustration, depression, or anxiety that some people with UC experience. Several types of healthcare providers provide counseling, including social workers, psychologists, nurses, or psychiatrists. Some people prefer to meet one-on-one with a counselor while others prefer to meet in a group setting with other people who have a similar diagnosis. Resources to find a support group are listed below (
see "
Where to get more information" below
).
- One-on-one counseling usually includes a discussion of emotional responses to the disease, coping methods, and ways to maintain or develop personal relationships.
- Group psychotherapy allows people to compare their experiences, overcome their tendency to withdraw and become isolated, and support one another's attempts at coping and recovering.
- Relaxation techniques can help to relieve feelings of anxiety or fear, and may include meditation, progressive muscle relaxation, self-hypnosis, or biofeedback.
Antidepressant or anti-anxiety medication may be recommended for some people with depression or anxiety that interferes with day-to-day functioning.
COMPLICATIONS
Long-standing and/or severe ulcerative colitis can be associated with serious and sometimes life-threatening complications.
Stricture
A stricture is a narrowing of the colon or rectum. This occurs in a small percentage of people with ulcerative colitis. Strictures can cause a blockage of the colon.
Bleeding
Some degree of bleeding occurs in most patients with ulcerative colitis. In some patients, the colitis is severe enough that it affects a small artery in the colon, leading to heavy bleeding. Such patients may require a blood transfusion or surgery.
Toxic megacolon
Toxic megacolon is one of the most serious complications of patients with severe colitis. It occurs when inflammation in the colon causes it to dilate, causing the walls to become thin and fragile. This can eventually lead to rupture (called a perforation). Surgery is usually advised if this condition does not respond to medical treatment within about 72 hours.
COLORECTAL CANCER AND UC
Overall, people with ulcerative colitis have an increased risk of colorectal cancer, although the degree of risk varies from one person to another. The risk of colorectal cancer is related to the duration and extent of ulcerative colitis.
-
Pancolitis The risk of colorectal cancer is greatest in people with pancolitis, when the inflammatory process extends to the cecum (
show figure 1
). The risk begins to increase about 8 to 10 years after the symptoms of ulcerative colitis first appear. There is a 5 to 10 percent risk of cancer after 20 years and a 12 to 20 percent risk after 30 years of ulcerative colitis.
- Left-sided colitis In people with left-sided colitis, the risk of colorectal cancer begins to increase about 15 to 20 years after the symptoms of ulcerative colitis first appear.
- Proctitis and proctosigmoiditis The risk of colorectal cancer is not significantly increased in people with proctitis and proctosigmoiditis.
The risk of colon cancer is also increased in patients with coexisting primary sclerosing cholangitis (PSC). PSC is a chronic progressive disorder that causes inflammation, hardening, and narrowing of ducts in the liver and gall bladder. Most people with PSC have ulcerative colitis. The cause of PSC is not known.
Surveillance recommendations
Colorectal cancer usually develops from precancerous changes (dysplasia) of the colonic lining, which can be detected with regular screening tests such as colonoscopy. Although some of these changes do not progress to cancer, there is no way to know which changes will become cancerous. (
See "Patient information: Screening for colon cancer"
).
The best schedule for colonoscopy is unclear. The American Gastroenterological Association (AGA), American College of Gastroenterology (ACG), and American Society for Gastrointestinal Endoscopy (ASGE) each has its own surveillance guidelines. These guidelines should be discussed with a doctor to determine the surveillance plan that is best for you. The guidelines are discussed in detail in a separate topic review. (
See "Colorectal cancer surveillance in inflammatory bowel disease"
).
In general, colonoscopy is recommended 8 to 10 years after symptoms appear in people with pancolitis, and starting 15 years after symptoms appear in people with left-sided colitis. Thereafter, colonoscopy should be repeated every one to three years. If advanced precancerous changes or cancer are discovered, surgical removal of the colon (colectomy) is usually recommended. (
See "Patient information: Surgical treatment of ulcerative colitis"
).