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In This Report

•	Highlights
•	Introduction
•	Causes
•	Symptoms
•	Risk Factors
•	Complications
•	Diagnosis
•	Dietary Considerations
•	Symptom Management
•	Medications
•	Surgical Procedures
•	Resources
•	References

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•	Peptic ulcers
•	Colon and rectal cancers...
•	Crohn's disease

Encyclopedia

•	Ulcerative colitis

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Ulcerative colitis

Highlights

Drug Approval

Infliximab (Remicade) was approved in 2005 for treatment of adults with ulcerative colitis. It is the first biologic drug approved for ulcerative colitis (UC). According to results published in the New England Journal of Medicine, infliximab helped patients with moderate-to-severe UC achieve and maintain remission.

Quality of Life

UC symptoms impact many patients’ quality of life, according to a 2005 survey. Survey results indicated:

• UC symptoms can interfere with work, family, and social situations.
• 40% of patients with UC experience severe symptoms 180 days per year.
• Patients with UC feel that their condition is misunderstood and underestimated by family, friends, and co-workers.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

NSAIDS such as acetaminophen (Tylenol), naproxen (Aleve), and celecoxib (Celebrex) are as safe for patients with UC as for other people, according to several 2006 studies. The studies found that NSAIDs may provide pain relief and prevent symptom relapse. However, patients should always discuss NSAID use with their doctors.

Complications

Patients with UC have an increased risk of developing other inflammatory and autoimmune conditions such as arthritis, asthma, bronchitis, psoriasis, and multiple sclerosis.

Colorectal Cancer and Ulcerative Colitis

• Patients with UC have an increased risk of developing colorectal cancer. The longer a patient has UC, and the more severe the condition, the greater the risk for cancer.
• Regular colonoscopy exams, and some types of anti-inflammatory drugs, may help reduce cancer risk.
• Patients with UC who develop colorectal cancer have a poorer survival outlook than those without UC.

Surgery

Ileal pouch anal anastomosis (IPAA) surgery triples the risk of infertility in women who have the procedure, indicates a 2006 study. Doctors think that the surgery may scar and block the fallopian tubes, making it more difficult for women to conceive.

Introduction

Inflammatory bowel disease (IBD) is a general term that covers two disorders:

• Ulcerative colitis
• Crohn's disease

Some evidence suggests that they are part of a biologic continuum, but at this time they are considered distinct disorders with somewhat different treatment options. The basic distinctions are location and severity. As many as 10% of patients with IBD have findings and symptoms that match the criteria for both disorders, at least in the early stages (which is called indeterminate colitis).

Crohn's disease, also called regional enteritis, is a chronic inflammation of the intestines that is usually confined to the ileum, the terminal portion of the small intestine. Ulcerative colitis is a similar inflammation of the colon, or large intestine. These and other inflammatory bowel diseases have been linked with an increased risk of colorectal cancer.

Ulcerative Colitis. Ulcerative colitis occurs only in the large intestine. Ulcers form in the inner lining, or mucosa, of the colon or rectum, often resulting in diarrhea, blood, and pus. The inflammation is usually most severe in the sigmoid and rectum and usually diminishes higher in the colon. It is sometimes divided into one of four categories depending on the location of the disease:

Click the icon to see an image of the structure of the colon.

• Proctitis. Disease only in the rectum (the lowest part of the large intestine that connects with the anus). Constitutes about 30% of cases.
• Proctosigmoiditis. Disease in the rectum and sigmoid (the next portion of the intestine leading up from the rectum). Constitutes about 30% of cases.
• Left-Sided Colitis. Disease in the left side of the large intestine. Constitutes about 40% of cases.
• Pancolitis. Disease in entire colon. Very uncommon.

Click the icon to see an image of the types of ulcerative colitis.

In most patients the location of the disease does not change, but as many as 30% of patients with proctitis or proctosigmoiditis will experience some progression.

Crohn's Disease. Crohn's disease is an inflammation that extends into the deeper layers of the intestinal wall. It is found most often in the area bridging the small and large intestines, specifically in the ileum and the cecum, which is sometimes referred to as the ileocecal region. Crohn's disease less frequently occurs in other parts of the gastrointestinal tract, including the anus, stomach, esophagus, and even the mouth. It may affect the entire colon, form a string of contiguous ulcers in one part of the colon, or develop as multiple scattered clusters of ulcers skipping healthy tissue in between. [For more information, see In-Depth Report #103: Crohn's disease.]

Click the icon to see an image of the digestive system.

Click the icon to see an image of the stomach.

Click the icon to see an image of the small intestine.

Click the icon to see an image of the large intestine.

Causes

Inflammatory bowel disease is due to many causes. Often, genetic problems in the intestine enable viruses or bacteria to trigger an immune response that causes inflammation and injury in the intestines. In IBD, the defense systems appear to be impaired, because of either defects in the mucosal lining that provides a barrier in the intestine or an inability to make repairs after injury.

The Inflammatory Response

The Immune System's Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

Lymphocytes include two subtypes known as T cells and B cells. Both types of cells are designed to recognize foreign invaders (antigens) and to launch an offensive or defensive action against them:

• B cells produce antibodies, substances that can either ride along with a B cell or travel on their own to attack the antigen.
• T cells have special receptors attached to their surface that recognize the specific antigen.

T cells are further categorized as killer T cells or helper T cells.

• Killer T cells directly attack antigens that occur in any cells that contain a nucleus.
• Helper T cells also recognize antigens, but their role is two-fold. They stimulate B cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process.

Helper T-Cells and Inflammatory Bowel Disease. The actions of the helper T cells (TH cells) are of special interest in inflammatory bowel disease:

• TH cells stimulate other white blood cells called B cells to produce antibodies. In this case, however, they appear to direct the B cells to produce autoantibodies, which are directed against the body's own cells.
• TH cells also secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for healing. If overproduced, however, they can cause serious damage, including inflammation and cellular injury. Cytokines, particularly specific ones known as tumor necrosis factor, interferon-gamma, and interleukins, cause intestinal inflammation and damage, which, in a vicious cycle, attract even more helper T cells.

Helper T cells are further categorized as TH1 and TH2. An imbalance in these two types appears to occur in IBD, although each disorder has a different balance:

• Patients with ulcerative colitis favor a TH2 response, which activates the interleukins IL-5, IL-6, and IL-10. These proteins affect mostly mucosal areas in the intestine.
• Research indicates that Crohn's disease patients have increased activity in TH1 helper cells, which activates interleukin-2 (IL-2) and interferon-gamma. These substances affect intestinal cells. Tumor necrosis factor may be a particularly potent immune factor in Crohn's disease. It is important in properties that regulate inflammation and cell proliferation. If genetic or other factors increase production of this immune compound, it can lead to great harm.

Interleukin 6 appears to play a part in both IBDs. Interleukin 6 inhibits a natural mechanism called apoptosis, a process in which cells self-destruct. In such cases, cells proliferate faster than they die, causing an excessively strong immune response.

Adhesion Molecules. Increased levels of certain molecules called E-selectin and intercellular adhesion molecule-1 (ICAM-1) also appear to play a major role in the inflammatory process by causing damaging immune factors to accumulate on intestinal cells. E-selectin may be involved in the early stages of the disease (especially ulcerative colitis). ICAM-1 plays a role in either inflammatory bowel disease.

Matrix Metalloproteinase. Greater activity of enzymes called matrix metalloproteinase has been detected in the colons of patients with IBD. Such increased levels tend to break down the extracellular matrix, a barrier composed of structural proteins and elastic fibers that surrounds and supports cells, in this case in the colon. Researchers suggest that this activity may cause persistent damage once the inflammatory process has triggered IBD.

Genetic Factors

Although the causes of inflammatory bowel disease are not yet known, genetic factors certainly play some role. Between 10 - 20% of people with ulcerative colitis have family members with the disease. A number of candidate genes and chromosome locations have been identified that might prove to play a role in the development of ulcerative colitis, Crohn's disease, or both. Genetic factors appear to be more important in Crohn's disease, although there is evidence that they may have genetic defects in common. In either case, multiple genetic factors are likely to be responsible for susceptibility to these disorders.

Infections

One theory suggests that viruses or bacteria within the intestine may alter properties in the lining and intestinal tract. Over time, these changes may trigger the injurious processes that lead to inflammatory bowel disease. Some studies report that children with IBD may have had more and earlier childhood infections. The measles virus has been of particular interest. However, according to the U.S. Centers for Disease Control, and many studies, the measles virus does not cause Crohn’s or IBD. In addition, studies conclusively report that the measles, mumps, and rubella (MMR) vaccine does not cause Crohn’s disease, ulcerative colitis, or autism.

Dietary Factors

Inflammatory bowel disease is much more prevalent in industrialized nations and in higher-income groups. Experts believe that diet must play some role, although studies have been conflicting over its importance.

Symptoms

The two major inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease, share certain characteristics:

• Symptoms usually appear in young adults.
• Symptoms can develop gradually or have a sudden onset.
• Both are chronic. In either disease, symptoms may flare up (relapse) after symptom-free periods (remission) or symptoms may be continuous without treatment.
• Symptoms can be mild or very severe and disabling.
• The severity of symptoms and relapse rates of both IBDs vary with seasons, with the highest risk in the winter and autumn and lowest in summer.

The two disorders, however, have different symptom profiles. It is important to differentiate between them, since they require different treatments.

Risk Factors

An estimated 1 - 2 million Americans suffer from inflammatory bowel disease (IBD). (This wide statistical variation is due to the difficulty in diagnosing these disorders and because people in remission may not be identified.) It was thought that Crohn's disease was far less common than ulcerative colitis, but currently the incidences of each are estimated to be about equal. The incidence may vary depending on gender, age, and geography:

• Men and women have equal risk for ulcerative colitis.
• IBD is diagnosed most often in young people between the ages of 10 and 19, but it can occur at any age. A smaller peak onset occurs between ages 50 and 80. About 2% of IBD cases appear in children below age 10.
• Ulcerative colitis is most common among people of European descent. People of African descent have a lower incidence than Caucasians. Low incidence regions include Asia and South America. Ethnically, Jewish people have a higher risk.
• Ulcerative colitis may disproportionately affect people of higher socioeconomic classes, but evidence for this is inconclusive.

Factors Associated with a Higher or Lower Risk for Ulcerative Colitis

Smoking. Smokers have lower than average rates of ulcerative colitis (but higher than average rates of Crohn's disease). Some patients with ulcerative colitis, in fact, have reported that their disorder began after they quit smoking, and many studies have reinforced the association between smoking and protection against ulcerative colitis. (This information is certainly no encouragement to smoke. Rather, patients should ask their doctor about trials using nicotine replacement aids.)

Breastfeeding. Breastfeeding appears linked to lower risk for UC.

Left-Handedness. People who are left-handed have a significantly higher risk for both IBDs as well as for certain other diseases associated with immune abnormalities.

Depression. A 2001 study reported that patients with ulcerative colitis were more likely to have a history of depression or anxiety than those without IBD. Some researchers suggest that depression may alter the immune system and make people more susceptible to ulcerative colitis.

Complications

Surgical removal of the colon is the only cure for ulcerative colitis, but the disease varies greatly in severity. In one 10-year study, 87% of patients went into complete remission after a single attack, and only 8% developed a chronic persistent condition. Mortality rates were about the same as in the general population, although they were higher in patients with UC with severe initial attacks or extensive disease. Surgical and medical treatments have complications of their own that can be very severe.

Criteria for Severity of Ulcerative Colitis

Ulcerative colitis is considered mild if a patient has the following symptoms:

• Four or less bowel movements a day
• Only occasional blood in the stool
• A normal temperature and pulse rate
• Normal hemoglobin or red blood cell count
• No abnormalities observed on x-rays of the colon.

Ulcerative colitis is considered serious if the following symptoms are present:

• More than six movements a day
• Frequent to persistent blood and mucus in the stool (in serious cases, stool is liquid and looks like anchovy sauce)
• Fever
• A rapid pulse
• Anemia
• Abnormal x-rays of the colon
• Tenderness in the abdomen when pressed, with possible distention

Complications in the Intestine

Malabsorption and Malnutrition. Malabsorption is the inability of the intestines to absorb nutrients. In IBD, this occurs as a result of bleeding and diarrhea, as a side effect from some of the medications, and as a result of surgery. Malnutrition typically develops rapidly after the condition has been present for some time.

Toxic Megacolon. Toxic megacolon is a serious complication that can occur if inflammation spreads into the deeper layers of the colon. In such cases, the colon enlarges and becomes paralyzed. In severe cases, it may rupture, which is a life-threatening event and requires emergency surgery. Symptoms include weakness and abdominal pain and bloating. You may be disoriented or groggy. X-rays are needed to confirm the diagnosis, but barium enemas and colonoscopies should not be performed. Medications used for pain and diarrhea, such as opiates and drugs that reduce spasms of the colon, may increase the risk of toxic megacolon. People with UC have a higher than normal risk, although this is still an uncommon occurrence. Its incidence is decreasing with treatment advances.

Toxic megacolon is characterized by extreme inflammation and distention of the colon. Common symptoms are pain, distention of the abdomen, fever, rapid heart rate, and dehydration. This is a life-threatening complication that requires immediate medical treatment.

Bleeding. Bleeding due to ulcers in the colon is a common complication of UC. It can increase the risk for anemia. In some cases, bleeding can be massive and dangerous, requiring surgery.

Colorectal Cancers. Patients with UC have a higher than normal risk for cancers of the colon and rectum. About 5 – 8% of patients with ulcerative colitis will develop colorectal cancer within 20 years of their UC diagnosis. The risk of colorectal cancer increases with the duration and severity of the ulcerative colitis condition. The presence of inflammatory polyps (pseudopolyps) more than doubles the risk. Some research suggests that anti-inflammatory drugs, such as 5-ASA, may help reduce the risk of cancer. Doctors also advise that patients with ulcerative colitis receive regular (every 1 – 3 years) colonoscopy exams to help screen for cancer. According to a 2006 study, patients with ulcerative colitis who are diagnosed with colorectal cancer have a worse prognosis, and poorer survival, than those without ulcerative colitis. [For more information, see In-Depth Report #55: Colon and rectal cancers.]

Click the icon to see an image of the colonoscopy procedure.

Complications Outside the Intestine

People with inflammatory bowel disease have a higher risk of developing other inflammatory diseases that affect the lungs and central nervous system.

Asthma. According to a 2005 study, people with IBD are 1.5 times more likely to have asthma than people without IBD. Of all the conditions that can accompany IBD, asthma is the most common. People with IBD are also at increased risk for bronchitis and other lung inflammations.

Eyes. Inflammation in parts of the eye is a common complication. Retinal disease, including detachment can occur but is rare. People with accompanying arthritic complications may be at higher risk for eye problems.

Joints. Inflammation causes arthritis and stiffness in the joints.

Bones. Low body weight and calcium loss from corticosteroids contribute to osteoporosis (bone loss). However, ulcerative colitis itself causes less bone loss than Crohn’s disease.

Click the icon to see an image of osteoporosis.

Heart. People with IBD have more than three times the risk of developing pericarditis (inflammation of the sac enclosing the heart) than healthy people

Anemia. UC poses a higher than normal risk for anemia.

Liver and Gallbladder Disorders. People have a higher than average risk for mild but not severe liver abnormalities. There is a higher risk (although rare) for primary sclerosing cholangitis, which is persistent inflammation of the bile duct that can later cause serious obstruction.

Skin Disorders. Patients with UC have a higher risk for skin disorders and may experience ulcer eruptions called pyoderma gangrenosum that heal in the center and spread.

Thromboembolism (Blood Clots). People with UC are at higher risk for blood clots, especially in the legs and pelvic area.

Click the icon to see an image depicting a thrombus.

Kidney Disorders. People with UC have a higher than normal risk for kidney stones.

Click the icon to see an image of kidney stones.

Lung Involvement. Lung involvement may develop but it can progress for years without symptoms.

Mouth Sores. There is a slightly higher than average risk for mouth sores and infections in UC, but they are uncommon and lower than those with Crohn's disease.

Delayed Growth and Development in Children. Children with UC are at slightly higher than average risk for delayed growth, but their risk is lower than the risk is for people with Crohn's disease.

Fertility. Fertility rates in women are close to normal, but UC surgery can increase the risk for infertility. Prematurity rates are high with both types of IBD.

Hodgkin's Disease. Patients with UC are at higher risk for Hodgkin's disease, according to a 2000 Italian study. The risk of other cancers was not increased, however.

Menstrual Problems in Women. Menstrual problems are common, including premenstrual disorder, abnormal bleeding, and pain. Pain with intercourse occurs in about half of patients. Sexual function may be impaired, not only because of the emotional impact, but also by treatment of side effects and complications of the diseases, such as fistulas.

Neurologic Factors. Inflammatory bowel disease has been associated with neurologic complications, including a higher risk for dementia, movement disorder, and stroke. People with IBD have a higher risk for developing multiple sclerosis and inflammation of the optic nerve (optic neuritis).

Emotional Factors. The emotional consequences of UC cannot be overestimated. Eating becomes associated with fear of abdominal pain before the end of the meal. Frequent attacks of diarrhea can cause such a strong sense of humiliation that social isolation and low self-esteem may result. UC takes a serious toll on work, family, and social activities. According to a 2005 survey, 40% of patients report incapacitating symptoms at least 180 days per year. Adolescents with IBD may have added problems that increase emotional distress, including weight gain from steroid treatments and delayed puberty.

Diagnosis

The doctor will take your medical history and perform a thorough physical examination. The disease is particularly difficult to diagnose in children, in whom IBD may be mistaken for an infection or even depression if other characteristic symptoms, such as bloody diarrhea and weight loss, are not present. Slow growth may be a key feature in making a diagnosis, particularly of Crohn's disease, in children.

Several laboratory tests may be taken, such as the following:

• Blood tests are used for various purposes. An increased number of white blood cells may indicate the presence of inflammation. Blood tests are used to determine the presence of anemia and to measure liver enzymes. (They are abnormal in about 3% of ulcerative colitis cases.) New blood tests that measure certain antibodies may make it easier to differentiate Crohn's disease from ulcerative colitis in children.
• A stool sample is taken and examined for blood, infectious organisms, or both.

Imaging Procedures Used for Diagnosis

Endoscopic Procedures. Flexible sigmoidoscopy and colonoscopy are endoscopic procedures. They are important in the diagnosis of both ulcerative colitis and Crohn's disease. Both procedures involve snaking a fiberoptic tube called an endoscope through the rectum to view the lining of the colon. The doctor may also insert instruments through the endoscope to remove a tissue sample for a biopsy.

• Sigmoidoscopy, which is used to examine the rectum and left (sigmoid) colon, lasts about 10 minutes and is done without sedation. It may be mildly uncomfortable, but it is not painful. Ulcerative colitis almost always involves the lower left colon and rectum and is diagnosed using sigmoidoscopy. The doctor usually observes an evenly distributed inflamed surface lining the intestine, and the bowel wall bleeds easily when touched with a swab.
• Colonoscopy allows a view of the entire colon and requires a sedative, but it is still performed on an outpatient basis. It is helpful for distinguishing between Crohn's disease and ulcerative colitis and in screening for colon cancer.

Patients diagnosed with UC may also need periodic endoscopies to evaluate their condition when symptoms flare up. However, a 2005 study suggested that these routine endoscopies may not be necessary. The study found that people self-reporting symptoms provides as much information as the endoscopies.

X-rays and Barium Enema. The double-contrast barium enema, which uses an x-ray image, is less expensive than a colonoscopy for viewing the entire colon. Although not as accurate as colonoscopy, it is very valuable in diagnosing both Crohn's disease and ulcerative colitis in early stages. In patients with active ulcerative colitis, this procedure may increase the risk for toxic megacolon.

A barium enema is a valuable diagnostic tool that helps detect abnormalities in the large intestine (colon). A barium enema, along with colonoscopy, remain standards in the diagnosis of colon cancer, ulcerative colitis, and other diseases of the colon.

X-rays of the abdomen are also useful when a patient has a severe attack of ulcerative colitis. In such cases, the edges of the colon are swollen and irregular. X-rays may also reveal thickened walls and other signs of severity.

Ultrasound. Intestinal wall ultrasound may be useful for identifying the extent and severity of Crohn's disease. Although it is unclear if ultrasound is useful for an initial diagnosis, one study indicated that, when used by experienced professionals, it is effective for identifying Crohn's disease or ulcerative colitis.

Other Imaging Procedures. Magnetic resonance spectroscopy (MRS) is a variant of magnetic resonance imaging (MRI) that may prove to be useful for differentiating between Crohn's disease and ulcerative colitis.

Computed tomography (CT) scans may be useful for determining the extent of the disease on the intestine and for detecting abscesses and other complications of advanced IBD.

A promising experimental technique called virtual colonoscopy allows three-dimensional imaging of the colon without using invasive instruments. The procedure involves pumping air into the colon and scanning the intestine using computed tomography (CT) or magnetic resonance imaging (MRI). It is very safe, requires no sedation, and takes only about 10 minutes.

Ruling Out Diseases Resembling Inflammatory Bowel Disease

Irritable Bowel Syndrome. Irritable bowel syndrome (IBS), also known as spastic colon, functional bowel disease, and spastic colitis, causes many of the same symptoms as inflammatory bowel disease. Bloating, diarrhea, constipation, and abdominal cramps are all symptoms of IBS. Irritable bowel syndrome is not caused by inflammation, however, and no fever or bleeding occurs. Behavioral therapy may be helpful in treating IBS. (Psychological therapy does not improve inflammatory bowel disease.)

Microscopic Colitis. Microscopic colitis causes chronic watery diarrhea, but the colon lining shows little or no signs of inflammation. It may be genetically linked to celiac sprue. Most patients can expect to improve.

Celiac Sprue. Celiac sprue, or celiac disease, is an intolerance to gluten (found in wheat) that triggers inflammation in the small intestine and causes diarrhea, vitamin deficiencies, and stool abnormalities. It occurs in a significant number of people with IBD and is usually first noticed in children.

Click the icon to see foods to avoid when you have celiac sprue.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. Some evidence suggests that the risk for IBD in these patients is 100 times above that in the general population and that there may be some common factor to both conditions. The average age of patients with IC is 40, but 25% of cases occur in women under 30. Symptoms are very similar to urinary tract infections, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Infections. If endoscopy reveals inflammation, a doctor must always rule out possible infections before a diagnosis of inflammatory bowel disease can be confirmed.

Acute Appendicitis. Crohn's disease may cause tenderness in the right lower part of the abdomen where the appendix is located and resembles appendicitis.

Cancer. Colon or rectal cancers must always be ruled out when symptoms of IBD occur.

Intestinal Ischemia. Symptoms similar to IBS can be caused by blockage of blood flow in the intestine. This is more likely to occur in elderly people.

Dietary Considerations

Malnutrition is very common in ulcerative colitis (UC), although it tends to be more severe in Crohn's disease. Some experts recommend that children with IBD increase their calorie and protein intake by 150% of the daily recommended allowance for their specific ages and heights. Studies indicate that nutritional support in children is as important as medications for achieving remission. People whose weights are normal or no less than 90% of normal do not need to add extra calories.

Foods Important for Intestinal Protection

Fluids (Non-Caffeinated). Drinking plenty of water is extremely important. It not only benefits the intestine but also helps prevent kidney stones, which are common in IBD. Vegetable juice and sports drinks may be helpful for restoring important minerals.

Protein. Proteins are very important for growth in children and for repair of cells. Diarrhea can cause protein deficiency and so patients may need more protein than the general population. Patients might consider using soy as one of their primary protein sources. One study reported that a soy protein diet was particularly useful for people with UC who were intolerant to milk products. Dried beans and legumes also provide protein.

Complex Carbohydrates. Complex carbohydrates found in whole grains, fruits, and vegetables should make up half of your calories. Fresh fruit (such as apples, grapefruit, oranges, plums, blueberries, raspberries, and strawberries) might actually be specifically protective for IBD and may also reduce the risk for colon cancer. (Simple sugars can increase inflammation, however, so you should avoid dried fruits and high-sugar fruits, such as grapes, pineapple, and watermelon.)

Foods made up of complex carbohydrates are also often a good source of fiber. Fiber may help reduce damage in the intestinal tract caused by UC, and may even help protect against cancer. Oat bran is of particular interest. In the intestinal tract, this whole grain increases levels of a fatty acid called butyrate, which may help reduce GI symptoms due to ulcerative colitis. However, high-fiber foods can cause gas, bloating, and pain, particularly in people with IBD. Available commercial products (Beano) can reduce gas. Eating small, frequent meals can also help.

Potassium-rich Foods. Potassium rich foods not only help protect the intestine. They may ralso educe the risk for kidney stones. Such foods include bananas, oranges, pears, cantaloupes, tomatoes, dried peas and beans, nuts, potatoes, and avocados.

Fish Oil. Omega-3 fatty acids, which are found in oily fish, have been associated with protection against inflammation, including in the intestinal tract. Some studies have even reported lowered use of anti-inflammatory medications in people who consume fish oil. Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaneoic (EPA) acids. Standards for optimal amounts and forms of omega-3 fatty acids have not yet been established, however.

Omega-3 fatty acids, found plentifully in oily fish, flaxseed, and canola oils, may help people with IBD (inflammatory bowel disease).

Eliminating Foods That Might Produce Symptoms (Exclusion Diets)

According to a 2002 major analysis, the exclusion (also called the elimination) diet was the only dietary approach to be effective for patients with ulcerative colitis. Exclusion diets are those that eliminate certain allergenic foods or those that might irritate the intestine. To determine these foods, patients use a so-called elimination-and-challenge approach. First, they remove all suspect foods from their diet for 2 weeks and then reintroduce one food every 3 days. Patients then watch for any symptoms that might indicate an allergic or irritant response, including gastrointestinal problems, headaches, and flushing.

Typical foods to avoid are:

• Saturated fats, found in animal and dairy products. People with inflammatory bowel disease should limit fats. Some studies have found an association between high-fat intake and later development of ulcerative colitis. Animal (saturated) fats are often suspected in IBD.
• Milk products. Some people with IBD are lactose intolerant (unable to digest the sugar lactose, found in milk products). However, milk and with the calcium it contains have been associated with a lower risk for colon cancer. Taking lactase tablets or specially prepared dairy products may help. (Many lactose-intolerant people are still able to eat yogurt with active cultures, which could be helpful for IBD.)
• Foods associated with inflammation (alcohol, simple sugars, and caffeine). Fruits may be protective, but you should avoid dried fruits or high-sugar fruits, such as grapes, watermelon, or pineapple.
• Products containing corn or gluten (those made from wheat, oats, barley, or triticale).
• Common allergenic foods, such as soy, eggs, peanuts, tomatoes.
• Foods that may irritate the intestine, particularly so-called Brassica vegetables (cabbage, Brussels sprouts, broccoli, cauliflower, kale).
• Some experts believe, however, that elimination diets are very difficult to maintain, and it is not clear if they prevent relapse.

Dietary Considerations for Reducing Kidney Stones

Kidney stones are painful and common complications in IBD, particularly in people who have had intestinal surgery. People with IBD are at risk for the most common types of stones -- those composed of either calcium oxalate or uric acid crystals. The following are some considerations in reducing the risk for stones:

• The most important dietary recommendations for reducing the risk for kidney stones are increasing fluid and restricting sodium intake.
• Limiting protein is recommended for reducing kidney stones. Jowever, people with IBD with frequent diarrhea are protein deficient. Sufficient protein, particularly in children with IBD, is very important and should be weighed against any risk for stones.
• You should increase intake of potassium-rich foods.
• You should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine that promote stone formation.
• Many kidney stones are formed from calcium-oxalate stones. You should avoid or limit intake oxalate-rich foods, such as beets, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb quarters, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard. A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids and dietary potassium and phosphate. Importantly, calcium is associated with protection against colon cancer and osteoporosis -- two conditions that are associated with IBD.
• People who have stones associated with short-bowel syndrome should restrict their intake of fat as well oxalates. In such cases, calcium may bind to unabsorbed fat instead of to oxalates, which increase oxalate levels.

The general recommendations for avoiding kidney stones must be tailored to the dietary requirements of IBD. You should work with their doctors to develop an individualized plan.

Probiotics and Prebiotics

Researchers are currently investigating a mix of bacteria (called probiotics), specific foods (called prebiotics) that are metabolized by these bacteria, and the compounds they produce (called synbiotics). Some evidence suggests that alone or in combination, they may have significant benefits in the intestine.

• Probiotics are helpful bacterial strains that by themselves may provide a barrier against harmful bacteria, possibly through various mechanisms, such as by excreting certain acids (lactate, acetate) that inhibit harmful bacteria or competing with them for nutrients. Evidence is now suggesting that probiotics may help maintain remission in patients with IBD. They are also proving to be effective in people with pouchitis -- a common surgical complication. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which is found in yogurt and other fermented milk products. Others, such as bifidobacteria and GG lactobacilli, however, may prove to be more important in IBD. Other probiotics include lactobacilli rhamnosus, casel, plantarium, bulgaricus, salivarius, Enterococcus faecium, and Streptococcus thermophilus.
• Prebiotics are specific non-digestible molecules called fructo-oligosaccharides (FOS), which stimulate the growth of probiotics. FOS are found in many foods, including Jerusalem artichokes, onions, salsify, bananas, honey, garlic, and leeks. (However, some of these foods themselves can irritate the intestine in patients with IBD.)

Researchers are investigating probiotics, prebiotics, or both for intestinal protection, including benefits for patients with IBD. Foods and supplements containing these substances are available in the US and overseas. To date, however, no studies have determined any clear benefits on any specific organism or formulation.

Vitamins and Other Supplements

Vitamins. Deficiencies of vitamins A, C, E, B12, and folate (a B vitamin) may result from malabsorption. In general, vitamin supplements may be recommended for everyone with IBD, particularly for children to avoid growth retardation. Vitamins A, C, and E are antioxidants, which protect the body against damaging particles. Folic acid supplements are particularly important for patients who must restrict fresh fruits and vegetables and for those taking sulfasalazine. Folate deficiencies may contribute to the increased risk for colon cancer in patients with ulcerative colitis. Monthly injections of vitamin B-12 may be necessary. Vitamin D is necessary for bone protection. Because some vitamins, such as A and D, can be toxic in high doses, patients should discuss specific dosages with their doctors.

Mineral Supplements. Supplements of calcium, magnesium, zinc, selenium, and iron may be needed to offset deficiencies in patients with severe IBD. Zinc is specifically important for gastrointestinal health. Calcium and magnesium are critical for health and strong bones. Selenium is a potent antioxidant. Iron supplements may be required for anemia. A doctor should advise patients carefully on the correct dosages since minerals can be toxic in high levels.

Symptom Management

Diarrhea and Constipation

The following are some ways of managing diarrhea, constipation, or both:

• To reduce mild to moderate diarrhea, take one teaspoon of psyllium hydrophilic colloid (Metamucil) twice a day in a glass of water.
• Anti-diarrhea drugs, such as loperamide (Imodium) and atropine/diphenoxylate (Lomotil), may help. In very ill patients, large doses of some drugs, such as Lomotil, can trigger the onset of toxic megacolon.
• Opiates or drugs used to relax muscle spasms may help relieve mild to moderate diarrhea and abdominal cramps, but they should be used for very short periods and not for severe cases.
• Bulk-type laxatives can help constipation.

Treating Anemia

Iron supplements may be required for anemia. Intravenous (IV) iron with or without erythropoietin (a hormone that acts in the bone marrow to increase the production of red blood cells) is effective for severe anemia in IBD that does not respond to iron alone. Crohn's disease patients benefit from the combination. Patients with ulcerative colitis usually improve on IV iron alone.

Antidepressants

Antidepressants may help relieve emotional problems. However, inflammatory bowel disease is not a psychological disorder, and such drugs will not affect the basic illness.

Pain-Relievers

Acetaminophen (Tylenol) is the drug of choice for mild pain. Acetaminophen is not a nonsteroidal anti-inflammatory drugs (NSAIDs), which include, among dozens of others, aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), and the Cox-2 inhibitor celecoxib (Celebrex). NSAIDs have been thought to cause symptom flare-ups in patients with IBD. However, a comprehensive 2006 study concluded that these drugs are as safe for patients with IBD as for other patients, and that they can help prevent relapse as well as provide short-term pain relief. You should talk to your doctor about whether NSAIDs are right for you.

Stress Reduction

Although stress is not a cause of inflammatory bowel disease, there are reports of an association between stress and symptom flare-ups. Patients with IBD, in fact, may have a more exaggerated physical response to stressful events than people without IBD. Although no evidence exists to confirm that stress reduction techniques, such as relaxation methods, meditation, or cognitive therapy, manage the disease, they might be helpful.

Alternative Remedies

Castor Oil Pack. Some people report relief from the use of a castor oil pack for 3 consecutive days. The oil is applied directly to the skin and then covered with a clean soft cloth and plastic wrap. A hot water bottle or heating pad is then placed over the pack for 30 - 60 minutes.

Acupuncture. Acupuncture may help relieve symptoms in some patients.

Medications

Drugs cannot cure inflammatory bowel disease, but they can help reduce the inflammation and accompanying symptoms in up to 80% of patients. The primary goal of drug therapy is to reduce inflammation in the intestine.

Drugs Used. Many drugs are available in different forms and may be used at various stages of the disease.

• Aminosalicylates. The best treatments of ulcerative colitis are preparations of aspirin-like medications called aminosalicylates or 5-ASAs. They are used in all phases of the disease, including maintenance during remission. They may be administered rectally in patients who have mild-to-moderate disease that occurs only in the lower intestine. They may also be taken by mouth.
• Corticosteroids. Corticosteroids (steroids) may be added or used alone to reduce acute inflammation. (They are not recommended for maintenance therapy). Steroids may be administered rectally as an alternative to an aminosalicylate if the disease is limited to the lowest parts of the intestine. Oral forms may treat moderate to severe cases. People who do not respond to less aggressive treatments may need intravenous steroids.
• Immunosuppressants. Drugs that suppress the immune system (immunosuppressants) are useful, either alone or in combinations, for disease that does not respond to other treatments or for maintenance of remissions.
• Biologic Response Modifiers. Unlike drugs that are made from chemicals, biologic response modifiers, (also called biologics), are produced from living organisms. Biologics are designed to stimulate the immune system and interfere with specific proteins (cytokines) involved with the inflammatory response. Infliximab (Remicade) is the first biologic drug approved for ulcerative colitis. It blocks a cytokine called tumor necrosis factor (TNF).

Determining Success. The success of therapy is determined by its ability to induce and maintain remissions without causing significant side effects. The patient's condition is generally considered in remission when the intestinal lining has healed and symptoms such as diarrhea, abdominal cramps, and tenesmus (straining painfully or ineffectively to defecate or urinate) are normal or close to normal.

Aminosalicylates (Mesalamine and its Derivatives)

Mesalamine is an aminosalicylate (the common name of the compound 5-aminosalicylic acid or 5-ASA). This compound inhibits factors in the immune system, importantly, the cytokines that cause inflammation. Mesalamine preparations and formulations are very useful for treating active mild-to-moderate ulcerative colitis. Although not as effective as corticosteroids in active disease, they can be used for maintenance therapy and for preventing relapse. (Corticosteroids cannot be used for this phase.) There is also some evidence that mesalamine reduces the risk for colon cancer. Mesalamine seems to benefit women more than men. All mesalamine preparations appear to be safe for children and for women who are pregnant or nursing.

Mesalamine has few side effects, but it is absorbed so quickly in the upper gastrointestinal tract that it usually fails to reach the colon if used orally and as a single drug. Other substances, therefore, are added to mesalamine or it is formulated so that it can reach the lower intestine before it is absorbed. Sulfasalazine (Azulfidine), which contains mesalamine and sulfapyridine (a sulfa antibiotic), is the standard preparation.

Administering mesalamine topically using enemas or suppositories is also an effective method for reaching disease in the lower left intestine, which occurs in about two-thirds of patients with ulcerative colitis. A combination of oral and topical mesalamine in such people is more effective than an oral form alone.

Sulfasalazine. Sulfasalazine (Azulfidine) is the standard mesalamine preparation. Sulfasalazine is known as a prodrug because it becomes an active drug when it breaks down by intestinal bacteria. In this event, it is broken down into two components: mesalamine and sulfapyridine.

• Mesalamine, the active component, blocks the inflammatory process
• Sulfapyridine (a sulfa antibiotic) plays no role in treating the disease, but it does prevent mesalamine from being absorbed until it reaches the colon

It is useful for treating mild-to-moderate UC attacks and for maintaining remission. Long-term therapy may even help protect against colon and rectal cancers in people with UC. A syrup form of sulfasalazine is available for children.

Side effects of sulfasalazine differ depending on the specific component.

• Mesalamine Component. Mesalamine has a chemical structure similar to aspirin. Therefore, people allergic to aspirin should not take any of the 5-ASA drugs or preparations. Mesalamine itself has few side effects and is considered safe to take during pregnancy. One of the most common side effects is diarrhea, which varies depending on the preparation. For example, olsalazine poses a risk for diarrhea, which may be minimized by starting out with lower doses and taking the medication with meals. Other side effects of oral forms of mesalamine are skin disorders, nausea, cramps, itchiness, anxiety attacks, and inflammation of other organs. Oral mesalamine, particularly Asacol, may slightly increase the risk for kidney damage. (Olsalazine has a lesser effect on the kidneys.)
• Sulfapyridine, the Sulfa Component. The sulfa component is responsible for most of sulfasalazine's adverse side effects, which are experienced by up to 30% of patients. Common side effects include allergic reactions, heartburn, headache, loss of appetite, abdominal discomfort, dizziness, anemia, fever, and rashes. The sulfa component may temporarily lower sperm count in men and can turn urine a bright orange-yellow color. Rare but serious side effects include a lupus-like disorder, pancreatitis, liver damage, and blood disorders, such as hemolytic anemia. (Hemolytic anemia occurs in some cases of ulcerative colitis even without this treatment.) Blood counts should be performed regularly, particularly during the first few weeks of treatment. Sulfasalazine completely inhibits the absorption of folic acid, and people with UC should take supplements of this important B vitamin. This is critical during pregnancy. As with most major drugs for IBD, withdrawal of sulfasalazine when the disease is still active can trigger a severe relapse.

Other Mesalamine Prodrugs. Olsalazine (Dipentum) and balsalazide (Colazal) are similar to sulfasalazine, in that they are broken down by intestinal bacteria into two components, one of which is mesalamine. Unlike sulfasalazine, however, the other component in each drug is a harmless molecule that does not produce the adverse side effects of the sulfa component. (Mesalamine side effects in all three drugs are the same.) Studies suggest that these newer preparations are effective both for first-line treatment and for maintenance in mild-to-moderate UC. Major 2002 analyses suggest that although they may be more effective in inducing remission than sulfasalazine, they are not as effective for maintenance. They are also considerably more expensive. They may have greater adverse effects on the kidney than sulfasalazine, so kidney function should be monitored periodically.

Mesalamine Enemas and Suppositories. Mesalamine enemas (Rowasa) and suppositories (Canasa) are available. Rowasa is effective for ulcerative colitis in the rectum and lower colon. Canasa is useful only in the rectum. Rowasa relieves mild-to-moderately active UC and prevents relapse. According to a 2000 review, mesalamine enemas are more effective than steroid enemas and oral therapies for left-sided ulcerative colitis.

Delayed or Sustained Release Mesalamines. Formulations have been developed that allow mesalamine alone to reach the lower intestine without the need for the sulfa component. A number of oral forms of mesalamine use coatings or time-released formulations to prevent absorption in the upper intestine. Different brands affect different regions in the intestine:

• Pentasa is an oral sustained-release mesalamine that is coated in a substance called ethyl cellulose. It is slowly released from the stomach through the intestine and is the only aminosalicylate that works in both the small intestine and colon. Twelve-month remission rates of up to 64% have been reported in patients with mild-to-moderate ulcerative colitis.
• Asacol and Salofalk are coated with an acrylic, and the active drug is released in an alkaline environment. It is therefore effective from the colon through the last section of the ileum. Studies have indicated that it has resulted in symptomatic improvement, including remission, in nearly three-quarters of patients with mild-to-moderate ulcerative colitis. In low doses, Asacol does not appear to be as effective as olsalazine for maintaining remission, although higher doses or combinations may improve its effectiveness.

Corticosteroids

General Guidelines. Corticosteroids (commonly called steroids) are powerful anti-inflammatory drugs. They are used only for active ulcerative colitis. Steroids are frequently combined with other drugs to produce more rapid symptom relief and to allow quicker withdrawal, although such combinations do not improve remission time. Because they have serious long-term effects, steroids are not useful for maintenance therapy. Patients who are malnourished are less likely to respond to steroids, and those who had an initial inadequate response to steroids are also less likely to do well with repeat therapy.

Corticosteroid Types. Prednisone, prednisolone, hydrocortisone, and methylprednisolone are the most common corticosteroids. Newer steroids, such as budesonide, fluticasone, beclomethasone, dipropionate, prednisolone-21-methasulphobenzoate, and tixocortol, affect only local areas in the intestine and do not circulate throughout the body. Such drugs may avoid the widespread side effects that are a serious problem with long-term treatment using the older steroids.

Administering Corticosteroids. Steroids can be taken orally, intravenously, by injection, or rectally as a suppository, enema, or foam. The severity or location of the condition often determines the form.

• In general, oral preparations are used for moderate-to-severe ulcerative colitis. Oral steroids can have serious long-term widespread effects in the body. Delayed-release forms of corticosteroids, such as beclomethasone or budesonide, affect only local areas of the intestine and may be useful for mild-to-moderate UC without causing systemic side effects.
• Enemas, suppositories, and, in limited cases, foam preparations may be used for mild-to-moderate ulcerative colitis located in the left section of the colon, the rectum, and anus. Most of the newer drugs can be administered rectally. They affect only local areas in the intestine and do not circulate throughout the body. Such drugs may avoid the widespread side effects that are a serious problem with long-term treatment using the older steroids, but they are not without risks.
• If the patient requires hospitalization, intravenous steroid therapy (with or without rectal steroids) is administered initially. (If these drugs are not effective after a week of intravenous therapy, they are not likely to work.)
• Once bowel movements are normal and the patient can eat, oral doses replace intravenous and rectal forms, and then they are tapered gradually.

Side Effects of Corticosteroids. Standard steroids can have distressing and sometimes serious long-term side effects. Adverse effects include:

• Susceptibility to infection
• Weight gain (particularly increased fatty tissue on the face and upper trunk and back)
• Acne
• Excess hair growth
• High blood pressure (hypertension)
• Accelerated osteoporosis
• Cataracts and glaucoma
• Diabetes, wasting of the muscles
• Menstrual irregularities
• Upper gastrointestinal ulcers, especially when patients also take NSAIDs
• Personality change, including irritability, insomnia, psychosis, and depression. Such emotional changes are sometimes severe enough to produce suicidal thoughts
• Growth may be retarded in children

Treatments are available for steroid-induced diabetes, swelling, and hypertension. Vaccines are available to help prevent influenza and pneumonia. Any infection should be treated promptly. Supplemental calcium and vitamin D are important to help to preserve bone mass against osteoporosis. The newer oral steroids, such as budesonide, have far fewer and less severe side effects.

Withdrawing from Corticosteroids. Once the intestinal inflammation has subsided, steroids must be withdrawn very gradually in order to give the body time to recover its own ability to produce natural steroids. Withdrawal symptoms, including fever, malaise, and joint pain, may occur if the dosage is lowered too rapidly. If this happens, the dosage is increased slightly and maintained until symptoms are gone. More gradual withdrawal is then resumed.

Immunosuppressive Drugs

For very active inflammatory bowel disease that does not respond to standard treatments, immunosuppressant drugs are now being used for long-term therapy. Such drugs suppress actions of the immune system and therefore its inflammatory response, which causes ulcerative colitis. Immunosuppressants can prevent relapse, even when used alone, and in some studies have proved to be effective for maintaining remissions in ulcerative colitis that have lasted at least 2 years.

An immunosuppressant is often combined with a corticosteroid to speed up response during active attacks. Lower doses of the steroid are then needed, resulting in fewer side effects. Corticosteroids may also be withdrawn more quickly. Immunosuppressants, then, are sometimes referred to as steroid-sparing drugs.

Purine Analogues. Purine analogues prevent cell proliferation in ways that are not yet clear. They include 6-mercaptopurine (Purinethol) and its prodrug azathioprine (Imuran). (A prodrug is a compound that breaks down into the active drug.) They are used for maintenance treatment in chronic active ulcerative colitis to reduce dependency on steroids. These drugs can take several weeks to 6 months to achieve peak effectiveness, so they are not useful for treating an acute attack. Some evidence suggests that these drugs are safe during pregnancy.

Complications include a higher risk for infections, such as pneumonia and herpes zoster, a risk for diabetes, and liver toxicity. Other serious side effects include pancreatitis, which occurs in about 1.2% of patients taking these drugs. Symptoms of pancreatitis usually occur within the first few weeks and include nausea, vomiting, and upper abdominal pain that may radiate to the back. Both of these effects are reversible when the drugs are stopped. A small percentage of patients carry a genetic factor that poses a risk for a life-threatening side effect of the drug, which is bone-marrow suppression, causing a dangerous drop in white blood cell production. (Of note, a mild drop in white blood cells is an indicator that the drug is working.) Monitoring specific enzymes that are metabolized by these drugs may be very helpful in predicting patients genetically at risk for these effects and for determining adequate doses.

Cyclosporine. Intravenous cyclosporine in combination with corticosteroids is often used for patients with acute severe ulcerative colitis and can help many patients avoid surgery. Serious complications, some life threatening, can occur, however. They include kidney failure, hypertension, infections, seizures, and allergic reactions. An alternative approach uses low-dose intravenous cyclosporine alone without the steroids followed by azathioprine (Imuran). Some researchers report that this is as effective as the standard approach and should pose a lower risk for serious side effects.

Tacrolimus. Tacrolimus is similar to cyclosporine, but its oral form is better absorbed than oral cyclosporine. Studies have been mixed on its effects.

General Side Effects of Immunosuppressants. Although experts have been concerned about dangerous side effects based on experience with immunosuppressants used in transplant operations, the lower doses of the drugs required for IBD and other inflammatory disorders may make them safer for long-term treatments than steroids. Specific side effects occur with individual drugs.

The most common side effects of immunosuppressants include:

• Stomach and intestinal distress
• Rash
• Numbness or tingling in the hands and feet, mouth sores
• Hair loss (or excessive hair growth with cyclosporine)

The actions of immunosuppressants, however, have more serious effects:

• They inhibit certain rapidly growing immune system cells, including those that produce antibodies, causing an increased risk for infections.
• In pregnancy, the use of immunosuppressants by the mother is associated with birth defects such as cleft palate, limb deformities, and eye problems. Their use is generally not recommended for women during pregnancy or breastfeeding. Pregnant women should absolutely avoid methotrexate.
• Other serious adverse effects include hepatitis, bladder problems, and menstrual irregularity with possible sterility. (Administering pulsed doses at the time of menstruation may avert infertility in women.)

Infliximab and Anti-Tumor Necrosis Factor Drugs

Biologic response modifiers are drugs that interfere with the inflammatory response. Of special interest are drugs that are designed to target inflammatory immune factors known as cytokines, particularly a cytokine called tumor necrosis factor (TNF).

Infliximab. Infliximab (Remicade) is made from a specially developed antibody (a monoclonal antibody) called cA2, which blocks the activity of tumor necrosis factor-alpha (TNF-a), a major player in the inflammatory process that causes IBD. In 2005, infliximab was approved for treatment of moderate-to-severe ulcerative colitis in patients who have not responded well to other treatments. It is the first biologic drug approved for UC. Infliximab is also approved for Crohn’s disease.

Studies indicate that infliximab may reduce UC symptoms and help patients achieve remission. Infliximab may also help heal ulcers and inflammation of the colon’s inner lining (mucosa). Some patients who take infliximab may be able to stop taking corticosteroids or avoid surgical removal of the colon.

Infliximab is given as a 2-hour intravenous infusion in a doctor’s office. After the first dose, the patient receives a second dose 2 weeks later, and a third dose 6 weeks after that. After these three doses, the drug is given every 8 weeks.

Common side effects may include a skin reaction at the injection site, stomach pain, and coughing. Potential serious side effects include tuberculosis, pneumonia, and other respiratory infections; lymphoma (a type of cancer); liver failure; and aplastic anemia. Infliximab is not appropriate for most patients with heart failure.

Local Anesthetics

Small studies indicate that enemas or topical gels using the anesthetics lidocaine and ropivacaine may be helpful for patients with mild-to-moderate ulcerative colitis. These drugs not only block pain but may have properties that help block several steps in the inflammatory response.

Investigative Therapies

Nicotine. Studies show that nicotine patches help to induce remission and reduce symptoms in almost 40% of patients who use then for 4 weeks. A 2002 study further reported that nicotine patches improved the effectiveness of mesalamine enemas. Side effects, particularly in nonsmokers, include nausea, lightheadedness, and headache. Investigators are studying methods of applying nicotine directly into the colon. (No one should smoke for relief of ulcerative colitis symptoms. The risks from cigarettes far outweigh the potential benefits of their nicotine.)

Heparin. Intravenous heparin is an anti-blood clotting drug that also has anti-inflammatory properties. Some evidence is suggesting that specific forms of heparin, notably low-molecular weight heparin, may prove to be beneficial for patients with IBD.

Interferon. Interferons suppress important inflammatory factors in the immune system. They are now used in multiple sclerosis, and research suggests that the drug interferon (IFN) beta-1a (Avonex, Rebif) may help patients with ulcerative colitis. Side effects include flu-like symptoms and reactions at the site of injection.

Epidermal Growth Factor. Researchers are interested in specific peptide growth factors, especially epidermal growth factor (EGF), which is important in maintaining intestinal health and wound healing.

Adsorptive Granulocyte and Monocyte Apheresis (GMA). Adsorptive apheresis is a process in which the fluid part of the blood, called plasma, is removed from blood cells. The procedure involves withdrawing blood from the patient, filtering it through a device, and then infusing the filtered blood back into the patient. The process removes inflammatory antibodies and other immunologically active substances. It is used for patients with rheumatoid arthritis and may be helpful for patients with UC. Recent clinical trials have reported promising results for treatment of refractory UC.

Parasites. Inflammatory bowel disease is rare in countries where intestinal infection with parasites called helminthes is common. Small studies are reporting significant remission rates in patients with Crohn's disease or ulcerative colitis who have swallowed the eggs of a specific parasitic worm. The parasite does not invade tissue or spread other diseases. The parasite induces production of specific T cells, called TH-2, which are immune factors that may be protective against overactivity of cytokines that trigger Crohn's.

DHEA. Some research is investigating the use of dehydroepiandrosterone (DHEA), a mild male hormone with anti-inflammatory effects that is reduced in inflammatory bowel disease. Very small studies suggest it may be helpful for patient with Crohn's disease or ulcerative colitis.

RDP58. RDP58 is a drug that interferes with the production of several inflammatory factors, including tumor necrosis factors, that are involved in UC and Crohn's disease. In one early study, it achieved remission rates of over 70% in patients with UC and caused few side effects.

Alicaforsen. Antisense drugs bind to target RNA and block the production of key proteins. Alicaforsen is an antisense drug that inhibits an intercellular adhesion molecule (ICAM-1) thought to play a pivotal role in the inflammatory process. Several clinical trials of alicaforsen enemas have reported encouraging results for improvement of ulcerative colitis symptoms.

Surgical Procedures

In 20% of people with ulcerative colitis, drug therapy is not effective, and surgery to remove diseased sections is necessary. In such cases, part or all of the colon is removed, depending on the extent of the disease. Surgeries may also be required because of hemorrhage, chronic illness, perforation of the colon, or to prevent colon cancer. Studies report that surgery improves the quality of life in most patients. Some experts are urging, in fact, that many patients should consider intestinal surgery in the early stages of the disease.

Proctocolectomy

Proctocolectomy is removal of the entire colon, including the lower part of the rectum and the sphincter muscles that control bowel movements. It can achieve a complete cure, but it is a last resort. There are different variations that may be performed depending on various factors. The procedures must be performed only on patients in whom it is absolutely clear that ulcerative colitis, and not Crohn’s disease, is causing the IBD. Discovering underlying Crohn's disease or other problems during the procedure can increase the risk for complications.

Ileostomy. In some proctocolectomies, the surgeon creates an opening in the abdominal wall (called a stoma) to allow passage of waste material. This part of the procedure is referred to as an ileostomy, and the stoma is created in the lower right corner of the abdomen. The surgeon then connects cut ends of the small intestine to this opening. A bag is placed over the opening and accumulates waste matter. It requires emptying several times a day.

Ileoanal Anastomosis. Ileal pouch anal anastomosis (IPAA), also simply called ileoanal anastomosis, has now largely replaced ileostomy because it preserves part of the anus and allows for more normal bowel movements. The procedure creates a natural pouch to collect waste, rather than using an ileostomy bag. The standard procedure involves:

• The colon is removed as in proctocolectomy, but the surgeon only strips the superficial diseased inner layer of the rectum, leaving the sphincter muscles intact.
• The anus is then attached to the ileum (the final portion of the small intestine leading to the colon).
• A pouch is constructed out of the small bowel above the anus. The pouch is able to collect waste material, and the patient can pass bowel movements normally through the anus, although they are watery and more frequent than normal (five or six times a day). Closing the pouch with a staple, rather than hand-sewn stitches, achieves better continence rates.
• A temporary abdominal opening (ileostomy) is usually required, but it is typically closed up in a second operation a few months later.

Managing Daily Life After Surgery

Flatulence is the most socially distressing problem. Unfortunately many of the fiber rich vegetables and whole grains that can benefit patients with ulcerative colitis can also cause gas. (Surgical patients should avoid or chew thoroughly insoluble fiber foods, such as popcorn, olives, and vegetable skins, which can obstruct the stoma.) Some pouching systems have filters that can help limit flatulence. Typically, flatulence occurs 2 - 4 hours after eating, which may help patients time their meals to ensure privacy afterward.

Patients must increase fluid intake, and include not only water but also broth, sports drinks, and vegetable juice to maintain appropriate levels of sodium and potassium.

Patients should avoid time-released, coated, or large pills, which often are not completely absorbed and may block the stoma.

The ileostomy does not interfere with bathing or showering or most physical activity. (Patients should avoid contact sports.) As a rule, the surgeries do not impair sexual function. If it does, according to one study, taking sildenafil (Viagra) restores sexual function to near or complete improvement in 80% of men.

Outcome and Complications from Ileoanal Anastomosis

Complications are common with any intestinal operation. In about 5 - 10% of IPAA procedures, complications occur that require conversion to an ileostomy. In general, patient satisfaction is very high with this procedure. Over 80% of patients report better or much better quality of life 5 years after the procedure. According to one study, 90% of patients can expect to have a functioning pouch for at least 20 years. Most patients can postpone their bowel movements until they are convenient. Bowel movements still average about seven a day.

Pouchitis. Inflammation of the pouch (pouchitis) is the most common complication of the pouch procedures, and one study reported its occurrence in up to 60% of patients. Symptoms include rectal bleeding, cramps, and fever. It can usually be easily treated. According to one study, however, in about 10% of these patients the condition becomes chronic, and the pouch may need to be removed. Metronidazole (Flagyl) is effective in treating active flare-ups of pouchitis. Evidence also suggests that the use of a probiotic (VSL-3) helps maintain remission in chronic pouchitis.

Irritable Pouch Syndrome. Irritable pouch syndrome is a recently defined problem that includes frequent movements, an urgent need to defecate, and abdominal pain. There are no signs of inflammation, however, as there are with pouchitis. Stress and diet play a role in this condition, and it is usually relieved after a bowel movement.

Fecal Incontinence. About 70% of patients are fully continent indefinitely after the procedure. (In other words, they experience no leakage.) The other patients typically experience occasional spotting and minor leakage, which is manageable.

Infertility. IPAA triples the risk of infertility in women with ulcerative colitis. The surgery may cause scarring or blocking of fallopian tubes, which increases the risk of infertility. About 48% of women who undergo this procedure become infertile

Severe scarring at the incision occurs in more than half of patients. One study found that placing an experimental absorbable membrane made from hyaluronate (a natural lubricating substance) along the incision reduced the rate of scarring up to 15%. When the rectum is removed, there is a small danger of injury to the nerves that control erection and bladder function.

Small bowel obstruction may occur with some of the procedures. If this occurs in pouch procedures, the pouch may need to be removed.

Pelvic infection occurs in less than 10% of pouch procedures (more often after hand-sewn than stapled anastomoses), and it occurs almost four times more often in men than in women. It is also more common in patients with ulcerative colitis who also have toxic megacolon.

Valve leakage may occur or the catheter may become blocked in continent ileostomies. In at least 10% of these procedures, the valve needs to be repaired later on.

Appendectomy

Some studies have also reported that appendectomy (removal of the appendix) protects against ulcerative colitis, and one 2001 study even suggested that removing the appendix may help prevent UC recurrence. Some experts theorize that removing the appendix alters the T cell balance in the immune system that then works in favor of people with UC. A major 2001 study suggested, however, that specific inflammatory conditions leading to appendicitis were the protective factors -- and only in people under age 20. (An appendectomy may actually increase the risk for Crohn's disease.)

Click the icon to see an illustrated series detailing an appendectomy surgery.

Resources

• www.ccfa.org -- Crohn's & Colitis Foundation of America
• www.gastro.org -- American Gastroenterological Association
• www.acg.gi.org -- American College of Gastroenterology
• digestive.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse

References

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Jess T, Loftus EV Jr, Velayos FS, Harmsen WS, Zinsmeister AR, Smyrk TC, et al. Risk of intestinal cancer in inflammatory bowel disease: a population-based study from Olmsted county, Minnesota. Gastroenterology. 2006 Apr;130(4):1039-46.

Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76.

Sandborn WJ, Stenson WF, Brynskov J, Lorenz RG, Steidle GM, Robbins JL, et al. Safety of celecoxib in patients with ulcerative colitis in remission: a randomized, placebo-controlled, pilot study. Clin Gastroenterol Hepatol. 2006 Feb;4(2):203-11.

Takeuchi K, Smale S, Premchand P, Maiden L, Sherwood R, Thjodleifsson B, et al. Prevalence and mechanism of nonsteroidal anti-inflammatory drug-induced clinical relapse in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2006 Feb;4(2):196-202.

Velayos FS, Loftus EV Jr, Jess T, Harmsen WS, Bida J, Zinsmeister AR, et al. Predictive and protective factors associated with colorectal cancer in ulcerative colitis: A case-control study. Gastroenterology. 2006 Jun;130(7):1941-9.

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