For unknown reasons, ulcerative colitis is more common in people who live in northern climates and in well developed areas of the world, such as North America, Great Britain, and Scandinavia, compared to those who live in southern climates or in underdeveloped areas. In 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.

Although UC is a chronic condition for which there is no cure, it can usually be well controlled with most people living normal and productive lives. Control of the disease entails long-term medical treatment and regular monitoring for any complications. It is very important to learn as much as you can about this condition and to take an active role in your health-care decisions and treatment.

WHAT CAUSES ULCERATIVE COLITIS? — 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. About 10 to 25 percent of effected 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 main trigger. The bacteria that normally live in the colon also have an important role in the development of the disease, since animals prone to get UC do not develop it when raised in a bacteria-free environment.

COMMON VOCABULARY — Doctors often use specific terms referring to the extent of colonic involvement. The extent of involvement is often related to the severity of symptoms and the course of the disease over time. Furthermore, treatments vary depending upon which parts of the colon are involved. The following will summarize commonly used terms:

• 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 ulcerative colitis is defined as disease that extends to the splenic flexure.
• Pancolitis is used when the inflammatory process extends beyond the splenic flexure (the sharp bend in the intestines, located under the spleen, where the transverse colon and descending colon join), even though many of these patients do not have inflammatory bowel disease to the cecum.

Patients who have large amounts of colon involved with colitis tend to be sicker. However, even those with only left-sided disease can become very 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. Doctors use the term "flare" 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 (fewer than four stools per day). They may also include mild, crampy abdominal pain; painful straining with bowel movements; and periods 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 involvement of a large region of the colon, 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 also lead to rapid weight loss.

Fulminant disease — Fulminant ulcerative colitis is an exacerbation of severe ulcerative colitis that is characterized by a high white blood cell count, loss of appetite, and marked 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), the skin (pyoderma gangrenosum and erythema nodosum), or the lung. 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 back stiffness. 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 by the presence of abnormal liver tests. 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 and the results of certain diagnostic tests, including blood and stool tests and a sigmoidoscopy or colonoscopy. These steps 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, whether these patients actually had an undiagnosed infection and not UC is unknown.

Proctitis and proctosigmoiditis — Proctitis or proctosigmoiditis are usually treated with topical drugs (eg, Rowasa and Cortenemas), which can be 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. Some patients also require treatment with oral medications such as sulfasalazine (Azulfidine) and mesalamine (eg, Pentasa, Asacol). The most commonly used drugs include as their active ingredient either mesalamine (eg, Rowasa) or agents similar to cortisone, generically referred to as "steroids" (eg, Cortenemas).

These treatments usually produce improvement after three weeks, lead to remission in up to 90 percent of people, and prolonged remission in up to 70 percent of people. Most doctors recommend continuous treatment with mesalamine-containing drugs to maintain remission, although it is often possible to taper the dose of medications. Patients with mild symptoms may benefit from additional nonspecific treatments such as antidiarrheal medications.

Left-sided colitis and pancolitis — Most patients require oral medications once 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 with prednisone), either as an outpatient or given intravenously in the hospital. Remission can be achieved in most patients. Once remission is achieved, patients are typically maintained on one of the oral mesalamine drugs.

MAJOR SIDE-EFFECTS OF THE COMMONLY USED DRUGS — As discussed above, the most common drugs used to treat UC include:

• Sulfasalazine (Azulfidine)
• Mesalamine (such as Pentasa and Asacol)
• Corticosteroids ("steroids" for short)

All drugs can cause side-effects, and many sound frightening. However, it is important for you to remember that many people take these drugs without developing serious side-effects, and that these drugs are used only when their benefit outweighs the potential risks.

Sulfasalazine — Sulfasalazine is one of the oldest drugs used to treat UC. Common side-effects (those occurring in over 10 percent of patients) associated with its use include headaches (which are dose-dependent), skin rash, nausea, and reversible infertility in men. 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. People who take sulfasalazine should take folic acid supplements since the drug may interfere with the absorption of folate in foods.

Mesalamine — Drugs that contain mesalamine or related compounds are generally tolerated better than sulfasalazine. As a result, they can be given in higher doses, which can be 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.

Corticosteroids — Corticosteroids are usually the most problematic drugs for patients since they have many side-effects. Increased appetite, weight gain, acne, fluid retention, tremulousness, mood swings, and difficulty sleeping are very common. Many other side-effects occur in patients who take corticosteroids 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), osteoporosis, body hair growth, cataracts, high blood pressure, stomach ulcers, avascular necrosis (a serious joint problem), and infections. Because of all the side-effects, doctors try to wean patients off of steroids as quickly as possible.

TREATMENT OF REFRACTORY DISEASE — Refractory ulcerative colitis refers to disease that does not respond to or responds poorly to the many drugs used to treat the disease. Patients who depend upon steroids to control their symptoms are also usually considered to be in this category.

Most of these patients are treated with drugs that suppress the immune system. The most commonly used drugs are 6-mercaptopurine and azathioprine. Colectomy (surgical removal of the colon) may be required if medical treatments are unsuccessful or if complications have developed. Patients who can no longer tolerate the constant battle with the disease may also prefer to have their colon removed.

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 also help to maintain remission and decrease the need for steroids. Both drugs 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, pancreatitis, and, less commonly, hepatitis. Long-term use of these drugs has also been associated with an increased risk of infections and possibly certain types of tumors.

Cyclosporine — Cyclosporine is a powerful immunosuppressant drug usually used in patients who have undergone organ transplantation. It can be very effective in hospitalized patients with refractory fulminant colitis when given intravenously. However, its role for maintenance therapy is limited.

Infliximab (Remicade) — Remicade is a powerful biologic agent usually used in patients who have Crohn's disease, certain autoimmune arthritis or skin conditions. It is expensive (but covered by insurance), inconvenient (given as an intravenous infusion over several hours) and needs to be given as maintenance every 8 weeks (after the first 3 infusions given over 6 weeks).

Other drugs — A number of other drugs have been used in patients with refractory colitis, including fish oil, nicotine, ciprofloxacin, heparin, and a variety of experimental agents. The benefit of these drugs is much less well established than for azathioprine and 6-mercaptopurine.

SURGERY — The most common indication for surgery is ineffectiveness or poor effectiveness of the drugs used to treat ulcerative colitis. Specific circumstances that may require surgery include:

• The persistence of symptoms despite high doses of steroids
• Dependency upon steroids to maintain remission
• Worsening of disease or new complications despite maximal drug therapy
• The occurrence of serious drug side effects
• The occurrence of premalignant or malignant changes in the colon

Although drugs and medical therapy are central in the treatment of ulcerative colitis, surgery can also has an important role in relieving symptoms, addressing serious complications, and improving quality of life. It can even be lifesaving.

About 30 percent of people with UC eventually undergo colectomy, typically after 15 to 25 years of disease. The need for colectomy varies with the extent of disease: about 9 percent of people with distal colitis and 35 percent of people with pancolitis undergo colectomy within five years of diagnosis. The need for surgery and the timing of any operation are usually determined jointly by the patient and his or her doctor.

Several surgical procedures are available to people with ulcerative colitis. All of the procedures can improve a person's quality of life and reduce the risk of colon cancer, so other factors will determine which procedure is best for each person. In emergency situations, the number of available procedures is usually limited. It is important to discuss all of the benefits and risks of surgery with your doctor, as well as having realistic expectations of the results.

NUTRITIONAL CONSIDERATIONS — People with the more advanced forms of ulcerative colitis often develop weight loss and nutritional deficiencies. A well balanced, nutritious diet can help maintain health and a normal body weight. The only foods that should be avoided are those that clearly exacerbate symptoms. People who restrict their diet for any reason should take daily multivitamins. In addition, certain dietary modifications may improve specific symptoms.

Vitamins and medications — It is reasonable to take a multivitamin daily. As mentioned above, patients taking sulfasalazine should take folic acid supplements. Folic acid supplements may also be reasonable in patients taking mesalamine-containing drugs since folic acid may also have a possible benefit in preventing colon cancer.

Pain medications containing nonsteroidal antiinflammatory drugs (NSAIDS), such as ibuprofen and naproxen, should usually be avoided, since they can worsen ongoing symptoms or cause a flare of the disease (check with your doctor or pharmacist before taking pain medications). Acetaminophen (Tylenol) should not cause a problem.

Lactose intolerance — Lactose intolerance refers to the development of symptoms (diarrhea, cramps, and gas) after ingesting the sugar lactose, which is the main sugar contained in dairy products. Lactose intolerance is very common in the general population and is thus common in people with ulcerative colitis. The symptoms of lactose intolerance can be minimized by avoiding dairy products; however, if dairy products are excluded from the diet, calcium supplements should be taken to prevent osteoporosis.

Dietary modifications to reduce cramps and diarrhea — People with abdominal cramps and diarrhea may notice relief when they consume smaller amounts 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).

Dietary modifications to 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. More data are needed before clear recommendations can be made.

Enteral and parenteral feeding — Enteral feeding (feeding through a nasogastric tube with elemental solutions that contain basic nutrients) 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 AND NATURALISTIC THERAPIES — Several natural therapies given by mouth or by enema have been suggested, but these are of unproven benefit and safety and should probably be avoided.

PSYCHOSOCIAL THERAPIES — Stress has been linked to exacerbations of ulcerative colitis. Behavior modification therapies may help relieve stress. Ulcerative colitis support groups can also provide a forum for sharing experiences and resources. Your doctor can help you to find a support group.

In rare cases, tranquilizers such as lorazepam (Ativan) and diazepam (Valium) may be prescribed to relieve stress. Antidepressant drugs may also be recommended for some people with disabling psychological symptoms.

COMPLICATIONS OF ULCERATIVE COLITIS — Long-standing and/or severe ulcerative colitis can be associated with serious and sometimes life-threatening complications.

Stricture — A stricture, a narrowing of the colon or rectum, occurs in a small percentage of people with ulcerative colitis. Strictures can cause blockage of the colon.

Bleeding — Some degree of bleeding is typical in patients with ulcerative colitis. In some patients, the colitis is severe enough to erode into a small artery in the colon, leading to copious bleeding. Such patients may require a blood transfusion or surgery.

Toxic megacolon — Toxic megacolon is one of the most serious complications seen in patients who have developed severe colitis. It occurs when inflammation in the colon causes it to dilate so that its walls become thin and fragile, which can eventually lead to their rupture (called a perforation). Thus, surgery is usually advised if this condition does not respond to medical treatment within about 72 hours.

Colorectal cancer — Overall, people with ulcerative colitis have an increased risk of colorectal cancer, but the risk varies from person to person.

  Factors that affect cancer risk — The risk of colorectal cancer is related to the duration and anatomic extent of ulcerative colitis.

• Pancolitis — The risk of colorectal cancer is greatest in people with pancolitis. Their risk begins to increase, relative to the general risk, about 8 to 10 years after the symptoms of ulcerative colitis first appear. Their cumulative risk of cancer is 5 to 10 percent after 20 years and 12 to 20 percent after 30 years of ulcerative colitis.
• Left-sided colitis — In people with left-sided colitis, the risk of colorectal cancer begins to increase, relative to the general risk, about 15 to 20 years after the symptoms of ulcerative colitis first appear.
• Proctitis and proctosigmoiditis — Preliminary studies suggest that the risk of colorectal cancer is not significantly increased in people with proctitis and proctosigmoiditis.

  Surveillance for colorectal cancer — Colorectal cancer usually arises from premalignant changes (dysplasia) of the colonic lining, which can be detected by regular screening. Although some of these changes do not progress to cancer, there is currently no way of knowing which changes will take the more serious course.

Because of the risk of developing cancer, surveillance for cancer is recommended. Surveillance entails colonoscopy at specified time intervals. This procedure can often detect premalignant changes and early colorectal cancer, and studies suggest that this early detection has a life-saving benefit. Patients who have confirmed dysplasia detected during surveillance should undergo a colectomy.

  Colonoscopy schedule — The best schedule for colonoscopy is debated. The American Gastroenterological Association (AGA), American College of Gastroenterology (ACG), and American Society for Gastrointestinal Endoscopy (ASGE) each has its own recommended surveillance guidelines. It is important to discuss the guidelines with your doctor and to select the surveillance plan that is best for you.

In general, colonoscopy is recommended starting 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 premalignant changes or cancer are discovered, doctors usually recommend colectomy; if mild premalignant changes are discovered, your doctor may recommend more frequent surveillance.

FERTILITY, PREGNANCY, AND BREASTFEEDING — Ulcerative colitis and the treatments for this disease may affect reproductive health in some people. It is important to discuss these possible effects with your doctor if you are considering pregnancy in the future.

Fertility — In general, ulcerative colitis does not decrease fertility (the ability to become pregnant) in men and women with this disease. However, some treatments for ulcerative colitis have been associated with difficulty conceiving. In men, impotence can follow colectomy, and one of the drugs used to treat UC, sulfasalazine (Azulfidine), causes sperm abnormalities that resolve when the drug is discontinued. In women, previous surgery may be associated with menstrual abnormalities and infertility.

Ulcerative colitis activity during pregnancy — The activity of a woman's ulcerative colitis at the time of conception appears to influence the course of the disease during pregnancy. About two-thirds of women in remission will stay in remission, and women with active disease are likely to have continued active disease during pregnancy. Thus, doctors usually recommend that women try to conceive while their UC is in remission.

Effects of ulcerative colitis on fetal development — Studies disagree about the effects of ulcerative colitis on the pregnancy. Some studies suggest that women with ulcerative colitis are more likely to deliver prematurely and to have low birth weight babies, but other studies suggest that women with ulcerative colitis have healthy babies. Ulcerative colitis has not been associated with an increased chance of birth defects or stillbirth.

Most women who have had surgery for ulcerative colitis before pregnancy have normal pregnancies and deliveries. Furthermore, women who have had surgery can usually have a vaginal birth.

  Safety of tests during pregnancy — Flexible sigmoidoscopy appears to be safe during pregnancy, but colonoscopy and x-rays are usually avoided, if possible.

  Safety of drugs during pregnancy and breastfeeding — The many drugs used to treat ulcerative colitis have different effects on unborn babies and on nursing babies. It is very important to discuss the safety of these drugs with your doctor if you are considering pregnancy.

• Sulfasalazine— Sulfasalazine appears to be safe for the baby during both pregnancy and breastfeeding.
• Mesalamine— The safety of oral and topical mesalamine containing drugs during pregnancy is still being studied, but these drugs appear to be safe during pregnancy.
• Steroids — In general, steroids appear to be safe during pregnancy, but your doctor may recommend avoiding these drugs during the first trimester. Steroids can worsen some pregnancy-related conditions (pregnancy-induced hypertension and gestational diabetes) and cause premature rupture of membranes, so their use therefore requires close monitoring. The steroid prednisone appears to be safe during breastfeeding, although your doctor may recommend postponing breastfeeding for several hours after taking a dose.
• Azathioprine and 6-mercaptopurine — If necessary, azathioprine and 6-mercaptopurine can be continued during pregnancy, although this is somewhat controversial. There is much greater experience with azathioprine because it has been used for many years in patients who have undergone kidney transplantation. However, some studies have suggested that these drugs cause birth defects and spontaneous abortion, and men and women taking these drugs may be advised to stop taking them at least three months before conception. Women taking azathioprine and 6-mercaptopurine are often advised not to breast feed their babies.
• Cyclosporine— Cyclosporine is generally safe during pregnancy; however, use of this drug may slow the baby's growth and trigger premature labor.
• Infliximab— It is not known if Infliximab can interfere with reproductive capacity or cause fetal harm when given during pregnancy; it should be given to pregnant women only if clearly needed. A decision to discontinue breast feeding or Infliximab should take into account the importance of the drug to the mother.
• Antidiarrheal drugs — Antidiarrheal drugs such as diphenoxylate with atropine (Lomotil) and loperamide (Imodium) have questionable safety during pregnancy and breastfeeding. Alternate drugs, such as Kaopectate and psyllium (Metamucil), are usually recommended.