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Ulcerative Colitis

By Aaron E. Walfish, MD, Beth Israel Medical Center;Mount Sinai Medical Center ; Rafael Antonio Ching Companioni, MD, Icahn School of Medicine, Elmhurst Hospital Center

Ulcerative colitis is a chronic inflammatory bowel 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.

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 occasionally 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 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

The main complications of ulcerative colitis include

  • Bleeding

  • Fulminant colitis

  • Colon cancer

Bleeding, the most common complication, often causes iron deficiency anemia.

Fulminant colitis is a particularly severe complication. In nearly 10% of people who have ulcerative colitis, a rapidly progressing first attack becomes very severe, with massive bleeding, rupture (perforation) of the colon, or widespread infection. 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 fulminant colitis worsens, the large intestine loses muscle tone and within days—or even hours—it starts to expand (a condition sometimes referred to as toxic megacolon). 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 cancerstarts 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 20 years of disease, about 7 to 10% of people will have developed cancer, and after 35 years of disease, as high as 30% of people will have developed cancer. Cancer is found each year thereafter in about 1 in 100 to 200 people after 8 to 10 years of disease in people who have extensive ulcerative colitis. However, people who have both inflammatory bowel disease and inflammation of the bile ducts ( primary sclerosing cholangitis) are at a higher risk of colon cancer starting from the time when the colitis is diagnosed.

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 or who have primary sclerosing cholangitis. During colonoscopy, tissue samples are taken from areas throughout the large intestine for examination under a microscope to detect the early warning signs of cancer (dysplasia). This removal and examination of tissue is called a biopsy. In a newer type of colonoscopy called chromoendoscopy, dyes are inserted into the colon during colonoscopy to highlight cancerous (malignant) and precancerous areas and may better help doctors identify areas for biopsy.

Other complications can occur, as in Crohn disease. When ulcerative colitis causes a flare-up of gastrointestinal symptoms, the person also may have the following:

When ulcerative colitis is not causing a flare-up of gastrointestinal symptoms, the person still may have pyoderma gangrenosum, 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.

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

  • Stool tests

  • Sigmoidoscopy

  • Blood tests

  • Imaging tests

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.

Sigmoidoscopy (an examination of the sigmoid colon using a flexible viewing tube) confirms the diagnosis of ulcerative colitis. This procedure 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 for examination under a microscope (called a biopsy). Even during symptom-free intervals, the intestine rarely appears entirely normal, and tissue samples removed for examination under a microscope 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 (occurs with inflammation), a low level of the protein albumin, and an elevated erythrocyte sedimentation rate (ESR) or C-reactive protein level, which also indicate active inflammation. A doctor may also do tests to determine how the liver is functioning.

X-rays of the abdomen taken after barium is given by enema (called a barium enema) may indicate the severity and extent of the disease but are not done when the disease is active, such as during a flare-up, because of the risk of causing a perforation. Other x-rays of the abdomen may also be taken.

Recurring or severe symptoms of ulcerative colitis

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. Doctors may do other tests to look for infection or parasites.

When symptoms are severe, people are hospitalized. Doctors 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% of people recover completely after a single attack. The remaining people have some degree of recurring disease.

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

  • Dietary management and loperamide

  • Aminosalicylates

  • Corticosteroids

  • Immunomodulating drugs

  • Biologic agents

  • Sometimes surgery

Ulcerative colitis treatment aims to control the inflammation, reduce symptoms, and replace any lost fluids and nutrients.

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

General management of ulcerative colitis

Iron supplements may offset anemia caused by ongoing blood loss in the stool.

Usually, if the large intestine is swollen, people should avoid foods such as nuts, corn hulls, raw fruits, and vegetables 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 does not need to be continued if no benefit is noted.

All people who have ulcerative colitis should take calcium and vitamin D supplements.

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 because of the risk of fulminant colitis.

Aminosalicylates

Aminosalicylates are drugs used to treat inflammation caused by inflammatory bowel disease. Drugs such as sulfasalazine, olsalazine, mesalamine, and balsalazide are types of aminosalicylates and 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 preventing symptoms from reappearing (maintaining remission).

Corticosteroids

People with moderately severe disease who are not hospitalized 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, an immunomodulating drug or a biologic agent is often is given to maintain the improvement. Gradually, the prednisone dosage is decreased, and ultimately the prednisone is discontinued.

Budesonide is another corticosteroid that may be used. It has fewer side effects than prednisone but does not work as quickly and is typically given to people whose disease is less severe.

Long-term corticosteroid treatment almost always causes side effects (see Corticosteroids: Uses and 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. Corticosteroid treatment is reduced and gradually stopped over several weeks.

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

Immunomodulating drugs

Immunomodulating drugs modify the action of the body's immune system, decreasing its activity. Drugs such as azathioprine and mercaptopurine have been used to maintain remissions in people with ulcerative colitis who would otherwise need long-term corticosteroid treatment. 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 corticosteroids. Most of these people respond initially to the cyclosporine, but some may still ultimately require surgery.

Tacrolimus is given by mouth. This drug has been given as short-term treatment to people whose ulcerative colitis is difficult to manage while they begin treatment with azathioprine and mercaptopurine. Tacrolimus may help maintain remission.

Biologic agents

Infliximab, which is derived from monoclonal antibodies to tumor necrosis factor (called a tumor necrosis factor inhibitor or TNF inhibitor) 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, adalimumab, and golimumab are beneficial for people whose ulcerative colitis is difficult to treat or for people who depend on corticosteroids.

Side effects that may occur with infliximab include worsening of an existing uncontrolled bacterial infection, reactivation of tuberculosis or hepatitis B, and an increase in the risk of some types of cancer. Some people have reactions such as fever, chills, nausea, headache, itching, or rash during the infusion (called infusion reactions). Before starting treatment with infliximab or other TNF inhibitors such as adalimumab and golimumab, people must be tested for tuberculosis and hepatitis B infections.

Vedolizumab is a drug for people who have moderate to severe ulcerative colitis that has not responded to TNF inhibitors or other immunomodulating drugs or who are unable to tolerate these drugs. The most serious side effect it causes is increased susceptibility to infection. Vedolizumab has a theoretical risk of a serious brain infection called progressive multifocal leukoencephalopathy (PML) because this infection has been reported with the use of a related drug called natalizumab.

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, general feeling of illness, 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.

Tacrolimus

Similar to cyclosporine

This drug is closely related to cyclosporine and shares a number of its side effects.

Biologic agents

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 and hepatitis B 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 is given under the skin (subcutaneously) and so does not cause infusion reactions.

Hypersensitivity reactions that occur at the injection site include pain, rash, itching, and hives. More severe hypersensitivity reactions are possible.

Golimumab

When given subcutaneously, pain or itching at the injection site; infections; and cancer

Side effects are similar to infliximab. When given subcutaneously, this drug does not cause infusion reactions. Hypersensitivity reactions that occur at the injection site include pain, rash, itching, and hives. More severe hypersensitivity reactions are possible.

Vedolizumab

Infections, hypersensitivity reactions, common colds

This drug has a theoretical risk of progressive multifocal leukoencephalopathy (PML).

Severity of symptoms

People with proctitis, or colitis 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 an immunomodulating drug (azathioprine or mercaptopurine). Additionally, some people benefit from infliximab, adalimumab, or golimumab. Doctors may give these drugs to some people whose symptoms cannot be controlled with azathioprine or mercaptopurine or corticosteroids and to people who are corticosteroid-dependent.

People with severe colitis are 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.

Fulminant colitis

People whose disease occurs suddenly, rapidly, and with great pain or who may have toxic megacolon are hospitalized. All antidiarrheal drugs are stopped, no food or drugs are given by mouth, and doctors pass a tube through the nose and into the stomach or small intestine to remove contents from the stomach or small intestine. 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 infection or a perforation. People whose condition does not improve in 24 to 48 hours need immediate surgery to remove all or most of the large intestine.

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 (called relapse). Studies suggest that a combination of oral and rectal mesalamine treatment is significantly more effective than either treatment alone.

People who cannot stop taking corticosteroids are given immunomodulating drugs (azathioprine or mercaptopurine), TNF inhibitors (infliximab, adalimumab, or golimumab), or a combination. People whose disease is difficult to manage may be given vedolizumab.

Surgery

About 30% of people with extensive ulcerative colitis require surgery. Emergency surgery may be necessary for sudden life-threatening attacks with massive bleeding, perforation, or fulminant colitis.

Sometimes surgery is needed even when there is no emergency reason for surgery. These situations include chronic colitis that is disabling or that constantly requires high doses of corticosteroids, cancer, and narrowing of the large intestine or growth retardation in children.

Complete removal of the large intestine, rectum, and anus (total proctocolectomy) permanently cures ulcerative colitis, restores life expectancy to normal, and eliminates the risk of colon cancer. However, because the rectum and anus are removed, people must have a permanent ileostomy. In an ileostomy, a surgeon brings the end of the lowest portion of the small intestine (ileum) out through an opening in the abdominal wall (stoma). People who have an ileostomy must always wear a plastic bag (ileostomy bag) over the opening to collect the stool that comes out. An ileostomy used to be the traditional price of this cure.

However, various alternative procedures are now available, and the most common one is a procedure called proctocolectomy with ileal pouch-anal anastomosis (IPAA). 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. Because the muscles of the anus (anal sphincter) are not removed, this procedure allows people to remain in control of their bowels (continence). However, because a small amount of tissue of the rectum can remain, the risk of cancer is significantly decreased but not eliminated. A common complication of IPAA is inflammation of the reservoir (called pouchitis). To treat pouchitis, doctors give antibiotics. Most cases of pouchitis can be controlled with drugs, but a small percentage cannot. For these cases, doctors create an ileostomy to correct the problem.

For people with ulcerative proctitis, surgery is rarely needed, and life expectancy is normal. In some people, though, the symptoms may be very difficult to treat.

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