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Ulcerative Colitis

by Aaron E. Walfish, MD, David B. Sachar, MD

Ulcerative colitis is a chronic disease in which the large intestine (colon) becomes inflamed and ulcerated (pitted or eroded), leading to flare-ups (bouts or attacks) of bloody diarrhea, abdominal cramps, and fever. The long-term risk of colon cancer is increased.

  • The exact cause of this disease is not known.

  • Typical symptoms during flare-ups include abdominal cramps, an urge to move the bowels, and diarrhea (typically bloody).

  • The diagnosis is based on a sigmoidoscopy or sometimes a colonoscopy.

  • People who have had ulcerative colitis for a long time may develop colon cancer.

  • Treatment is aimed at controlling the inflammation, reducing symptoms, and replacing any lost fluids and nutrients.

Ulcerative colitis may start at any age but usually begins before age 30, usually between the ages of 14 and 24. A small group of people have their first attack between the ages of 50 and 70.

Ulcerative colitis usually starts in the rectum (ulcerative proctitis). It may stay confined to the rectum or over time extend to involve the entire colon. In some people, most of the large intestine is affected at once.

Ulcerative colitis usually does not affect the full thickness of the wall of the large intestine and hardly ever affects the small intestine. The affected parts of the intestine have shallow ulcers (sores). Unlike Crohn disease, ulcerative colitis does not cause fistulas or abscesses.

The cause of ulcerative colitis is not known for certain, but heredity and an overactive immune response in the intestine seem to be contributing factors. Cigarette smoking, which seems to contribute to the development and periodic flare-ups of Crohn disease, seems to decrease the risk of ulcerative colitis. However, smoking in order to reduce the risk of ulcerative colitis is ill-advised in light of the many health problems that smoking can cause. Some evidence suggests that isotretinoin, which is a drug used to treat acne, can increase the risk of ulcerative colitis.

Symptoms

The symptoms of ulcerative colitis occur in flare-ups. A flare-up may be sudden and severe, causing violent diarrhea that typically contains mucus and blood, high fever, abdominal pain, and peritonitis (inflammation of the lining of the abdominal cavity). During such flare-ups, the person is profoundly ill. More often, a flare-up begins gradually, and the person has an urgency to have a bowel movement (defecate), mild cramps in the lower abdomen, and visible blood and mucus in the stool. A flare-up can last days or weeks and can recur at any time.

When the disease is limited to the rectum and the sigmoid colon, the stool may be normal or hard and dry. However, mucus containing large numbers of red and white blood cells is discharged from the rectum during or between bowel movements. People may or may not have mild general symptoms of illness, such as fever.

If the disease extends farther up the large intestine, the stool is looser, and the person may have more than 10 bowel movements a day. Often, the person has severe abdominal cramps and distressing, painful spasms that accompany the urge to defecate. There is no relief at night. The stool may be watery or contain pus, blood, and mucus. Frequently, the stool consists almost entirely of blood and pus. The person also may have a fever and a poor appetite and may lose weight.

Complications

Bleeding, the most common complication, often causes iron deficiency anemia. In nearly 10% of people with ulcerative colitis, a rapidly progressive first attack becomes very severe, with massive bleeding, perforation, or widespread infection.

Toxic colitis, a particularly severe complication, involves damage to the entire thickness of the intestinal wall. The damage to the nerves and muscles of the bowel wall causes ileus—a condition in which the normal contractile movements of the intestinal wall temporarily stop—and thus the intestinal contents are not propelled along their way. Abdominal expansion (distention) develops. As toxic colitis worsens, the large intestine loses muscle tone and within days—or even hours—it starts to expand. This complication may cause a high fever and abdominal pain. Sometimes there is a perforation of the large intestine and the person develops peritonitis. X-rays of the abdomen may show expansion of the bowel and the presence of gas inside the wall of the paralyzed sections of intestine.

Colon cancer starts to become more common about 7 years from when the illness started in people with extensive colitis. The risk of colon cancer is highest when the entire large intestine is affected and increases the longer the person has had ulcerative colitis. After 25 years of disease, about 9% of people will have developed cancer, and cancer is found each year thereafter in about 1 of 100 to 200 people. Colonoscopy (examination of the large intestine using a flexible viewing tube) every 1 to 2 years is advised for people who have had ulcerative colitis for more than 8 to 10 years. During colonoscopy, tissue samples (biopsies) are obtained from areas throughout the large intestine for microscopic examination to detect the early warning signs of cancer (dysplasia).

Other complications can occur, as in Crohn disease. When ulcerative colitis causes a flare-up of gastrointestinal symptoms, the person also may have inflammation of the joints (arthritis), inflammation of the whites of the eyes (episcleritis), inflamed skin nodules (erythema nodosum), and blue-red skin sores containing pus (pyoderma gangrenosum). When ulcerative colitis is not causing a flare-up of gastrointestinal symptoms, the person still may have pyoderma gangrenosum about half of the time, whereas inflammation of the spine (ankylosing spondylitis), inflammation of the pelvic joints (sacroiliitis), and inflammation of the inside of the eye (uveitis) are liable to occur entirely without relation to the bowel disease. Rarely, blood clots develop in the veins.

Although people with ulcerative colitis commonly have minor liver dysfunction, only about 1 to 3% have symptoms of mild to severe liver disease. Severe liver disease can include inflammation of the liver (chronic active hepatitis); inflammation of the bile ducts (primary sclerosing cholangitis), which narrow and eventually close; and replacement of functional liver tissue with scar tissue (cirrhosis). Inflammation of the bile ducts may appear many years before any intestinal symptoms of ulcerative colitis. The inflammation greatly increases the risk of cancer of the bile ducts and also seems to be associated with a sharp increase in the risk of colon cancer.

Diagnosis

Doctors suspect ulcerative colitis in a person with recurring bloody diarrhea accompanied by cramps and a strong urge to defecate, particularly if the person has other complications, such as arthritis or liver problems, and a history of similar attacks.

Doctors examine the stool to look for parasites and rule out bacterial infections.

A sigmoidoscopy (an examination of the sigmoid colon using a flexible viewing tube) confirms the diagnosis and permits a doctor to directly observe the severity of the inflammation, take samples of mucus or stool for culture, and remove tissue samples of affected areas. Even during symptom-free intervals, the intestine rarely appears entirely normal, and tissue samples removed for microscopic examination usually show chronic inflammation. A colonoscopy is usually not necessary, but doctors may need to do a colonoscopy if the inflammation extends beyond the reach of the sigmoidoscope.

Blood tests do not confirm the diagnosis but may reveal that the person has anemia, increased numbers of white blood cells, a low level of the protein albumin, and an elevated erythrocyte sedimentation rate (ESR) or C-reactive protein level, which indicate active inflammation.

Barium enema x-rays of the abdomen may indicate the severity and extent of the disease but are not done when the disease is active, such as during a flare-up.

Recurring or severe symptoms

Doctors examine people when their typical symptoms return but they do not always do tests. If symptoms have been more frequent or longer-lasting than usual, doctors may do sigmoidoscopy or colonoscopy and a blood count. When symptoms are severe, doctors may take x-rays to look for a dilated or perforated intestine.

Prognosis

Ulcerative colitis is usually chronic, with repeated flare-ups and remissions (periods of no symptoms). In about 10% of people, an initial attack progresses rapidly and results in serious complications. Another 10% recover completely after a single attack. The remaining people have some degree of recurring disease.

Complete removal of the large intestine and rectum (proctocolectomy) cures ulcerative colitis. The risk of colon cancer is eliminated, life expectancy is restored to normal, and quality of life improves.

People who have ulcerative proctitis have the best prognosis. Severe complications are unlikely. However, in about 20 to 30% of people, the disease eventually spreads to the large intestine (thus evolving into ulcerative colitis). In people who have proctitis that has not spread, surgery is rarely required, cancer rates are not increased, and life expectancy is normal.

Colon cancer

The long-term survival rate for people with colon cancer caused by ulcerative colitis is about 50%. Most people survive if the diagnosis is made during the early stages and the colon is removed in time.

Treatment

Treatment aims to control the inflammation, reduce symptoms, and replace any lost fluids and nutrients.

Iron supplements may offset anemia caused by ongoing blood loss in the stool. Raw fruits and vegetables should be avoided to reduce injury to the inflamed lining of the large intestine. A diet free of dairy products may decrease symptoms and is worth trying but need not be continued if no benefit is noted. Doctors give calcium and vitamin D supplements if people maintain a dairy-free diet.

Small doses of loperamide are taken for relatively mild diarrhea. For more intense diarrhea, higher doses of loperamide may be needed. In severe cases, however, a doctor must closely monitor the person taking these antidiarrheal drugs to avoid suddenly causing toxic colitis.

Specific treatment depends on the severity of people's symptoms.

Anti-inflammatory drugs

Drugs such as sulfasalazine, olsalazine, mesalamine, and balsalazide are used to reduce the inflammation of ulcerative colitis and to prevent flare-ups of symptoms. These drugs usually are taken by mouth (orally), but mesalamine can also be given as an enema or a suppository (rectally). Whether given orally or rectally, these drugs are at best moderately effective for treating mild or moderately active disease, but they are more effective for maintaining remission and possibly even reducing the long-term risk of colorectal cancer.

People with moderately severe disease who are not confined to bed usually take oral corticosteroids such as prednisone. Prednisone in fairly high doses frequently induces a dramatic remission. After prednisone controls the inflammation of ulcerative colitis, sulfasalazine, olsalazine, or mesalamine often is given to maintain the improvement. Gradually, the prednisone dosage is decreased, and ultimately the prednisone is discontinued. Prolonged corticosteroid treatment almost always causes side effects. When mild or moderate ulcerative colitis is limited to the left side of the large intestine (descending colon) and the rectum, enemas or suppositories with a corticosteroid or mesalamine may be helpful.

If the disease becomes severe, the person is hospitalized, and corticosteroids and fluids are given by vein (intravenously). People with heavy rectal bleeding may require blood transfusions.

Immunomodulating drugs

Drugs such as azathioprine and mercaptopurine have been used to maintain remissions in people with ulcerative colitis who would otherwise need long-term corticosteroid therapy. These drugs inhibit the function of T cells, which are an important component of the immune system. However, these drugs are slow to act, and a benefit may not be seen for 1 to 3 months. They also have potentially serious side effects that require close monitoring by the doctor.

Cyclosporine has been given to some people who have severe flare-ups and have not responded to corticosteroid therapy. Most of these people respond initially to the cyclosporine, but some may still ultimately require surgery.

Infliximab, which is derived from monoclonal antibodies and given intravenously, is beneficial for some people with ulcerative colitis. This drug may be given to people who do not respond to corticosteroids or who develop symptoms whenever corticosteroid doses are lowered, despite the optimal use of other immunomodulating drugs. Infliximab and possibly adalimumab are beneficial for people whose ulcerative colitis is difficult to treat or for people who depend on corticosteroids.

Drugs That Reduce Bowel Inflammation Caused by Ulcerative Colitis

Drug

Some Side Effects

Comments

Aminosalicylates

  • Sulfasalazine

Common: Nausea, headache, dizziness, fatigue, fever, rash, and, in men, reversible infertility

Uncommon: Inflammation of the liver (hepatitis), pancreas (pancreatitis), or lung (pneumonitis) and hemolytic anemia

Abdominal pain, dizziness, and fatigue are related to dose.

Hepatitis and pancreatitis are unrelated to dose.

  • Balsalazide

  • Mesalamine

  • Olsalazine

Common: Fever and rash

Uncommon: Pancreatitis, inflammation of the pericardium (pericarditis), and pneumonitis

For olsalazine: Watery diarrhea

Most side effects seen with sulfasalazine may occur with any of the other aminosalicylates but much less frequently.

Corticosteroids

Prednisone

Diabetes mellitus, high blood pressure, cataracts, osteoporosis (decreased bone density), thinning of skin, mental problems, acute psychosis, mood swings, infections, acne, excessive body hair (hirsutism), menstrual irregularities, gastritis, and peptic ulcer disease

Diabetes and high blood pressure are more likely to occur in people who have other risk factors.

Budesonide

Diabetes mellitus, high blood pressure, cataracts, and osteoporosis

Budesonide causes the same side effects as prednisone but to a lesser degree.

Hydrocortisone (enema or foam)

Some of the drug is absorbed by the body, but even with long-term use, few people have serious side effects (unlike with corticosteroids such as prednisone).

Hydrocortisone enema or foam is mainly for ulcerative colitis affecting the rectum or large intestine near the rectum.

Immunomodulators

  • Azathioprine

  • Mercaptopurine

Anorexia, nausea, vomiting, infection, cancer, allergic reactions, pancreatitis, low white blood cell count, bone marrow suppression, and liver dysfunction

Side effects that are usually dose dependent include bone marrow suppression and liver dysfunction.

Interval blood monitoring is required.

Cyclosporine

High blood pressure, nausea, vomiting, diarrhea, kidney failure, tremors, infections, seizures, neuropathy, and development of lymphomas (cancers of the lymphatic system)

Side effects become more likely with long-term use.

Infliximab

Infusion reactions, infections, cancer, abdominal pain, liver dysfunction, and low white blood cell count

Infusion reactions are potentially immediate side effects that occur during the infusion (such as fever, chills, nausea, headache, itching, rash, hives, decreased blood pressure, or difficulty breathing).

People should be screened for tuberculosis before initiating treatment.

Adalimumab

Pain or itching at the injection site, headache, infections, cancer, and hypersensitivity reactions

Side effects are similar to infliximab except adalimumab does not cause infusion reactions.

Hypersensitivity reactions are side effects that occur at the injection site and include pain, rash, itching, and hives.

Surgery

About 30% of people with extensive ulcerative colitis require surgery. Emergency surgery may be necessary for acute life-threatening attacks with massive bleeding, perforations, toxic megacolon, or blood clotting. Nonemergency reasons for surgery include unremitting chronic disease that is disabling or that constantly requires high doses of corticosteroids.

Surgery is also performed on a nonemergency basis when cancer is diagnosed or dysplasia is identified in the large intestine, and sometimes when there is narrowing of the large intestine or growth retardation in children.

Complete removal of the large intestine and rectum (proctocolectomy) permanently cures ulcerative colitis and eliminates the risk of colon cancer. Living with a permanent ileostomy (a surgically created connection between the lowest portion of the small intestine and an opening in the abdominal wall) and an ileostomy bag used to be the traditional price of this cure. However, various alternative procedures are now available, the most common one being a procedure called proctocolectomy with ileal pouch-anal anastomosis. In this procedure, the large intestine and most of the rectum are removed, and a small reservoir (pouch) is created out of the small intestine and attached to the remaining rectum just above the anus. This procedure maintains continence, although some complications, such as inflammation of the reservoir (pouchitis), often occur.

For people with ulcerative proctitis, surgery is rarely needed, and life expectancy is normal. In some people, though, the symptoms may prove exceptionally resistant to treatment.

Toxic megacolon is an emergency that may require surgery. As soon as a doctor detects it or suspects impending toxic megacolon, the person is hospitalized, all antidiarrheal drugs are discontinued, the person is given nothing to eat, a tube is inserted through the nose and into the stomach or small intestine and attached to intermittent suction, and all fluids, nutrition, and drugs are given intravenously. People are given high-dose corticosteroids or cyclosporine. Doctors also give antibiotics. The person is monitored closely for signs of peritonitis or a perforation. People whose condition does not improve in 24 to 48 hours need immediate surgery. All or most of the large intestine is removed.

Severity of symptoms

People with proctitis or disease that affects only the part of the colon near the rectum are given mesalamine enemas. Corticosteroid and budesonide enemas are given to people who are not helped by or cannot tolerate mesalamine.

People with moderate or extensive disease are given mesalamine by mouth in addition to mesalamine enemas. People with severe symptoms and those who still have symptoms while using mesalamine usually take oral corticosteroids such as prednisone. Prednisone in fairly high doses frequently induces a dramatic remission. After prednisone controls the inflammation of ulcerative colitis, sulfasalazine, olsalazine, or mesalamine often is given to maintain the improvement. Gradually, the prednisone dosage is decreased, and ultimately the prednisone is discontinued because prolonged corticosteroid treatment almost always causes side effects. People whose symptoms return when prednisone is decreased are sometimes given azathioprine or mercaptopurine. Additionally, some people benefit from infliximab and adalimumab. Doctors may give these drugs to people whose symptoms cannot be controlled with azathioprine or mercaptopurine or corticosteroids and to people who are corticosteroid dependent.

If the disease becomes severe, the person is hospitalized, and high-dose corticosteroids and fluids are given intravenously. Doctors may continue to give mesalamine. People with heavy rectal bleeding may require blood transfusions. People who do not respond to these treatments within 3 to 7 days may be given intravenous cyclosporine or infliximab or may need surgery.

People whose disease occurs suddenly, rapidly, and with great pain or who may have toxic megacolon are hospitalized. No food or drugs are given by mouth, and doctors pass a tube through the nose and into the stomach or small intestine that is attached to intermittent suction. People are given intravenous fluids and electrolytes and high-dose intravenous corticosteroids or cyclosporine. Doctors also give antibiotics. People are monitored closely for signs of peritonitis or a perforation. People whose condition does not improve in 24 to 48 hours need immediate surgery. All or most of the large intestine is removed.

Maintenance regimens

To prevent symptoms from reappearing (that is, to maintain remission), people continue to take mesalamine by mouth or as an enema indefinitely because stopping this maintenance regimen often allows the disease to return (relapse). Studies suggest that a combination of oral and rectal mesalamine therapy is significantly more effective than either therapy alone.

People who cannot stop taking corticosteroids are given azathioprine or mercaptopurine. Also, infliximab or adalimumab are becoming more widely accepted as maintenance therapy for ulcerative colitis as well as for Crohn disease.

Resources In This Article

Drugs Mentioned In This Article

  • Generic Name
    Select Brand Names
  • SOTRET
  • IMODIUM
  • AZULFIDINE
  • COLAZAL
  • DIPENTUM
  • RAYOS
  • ASACOL, ROWASA
  • REMICADE
  • PULMICORT, RHINOCORT
  • PURINETHOL
  • NEORAL, SANDIMMUNE
  • IMURAN
  • CORTEF, SOLU-CORTEF
  • HUMIRA