An in-depth report on the causes, diagnosis, treatment, and prevention of ulcerative colitis.
Doctors do not know exactly what causes inflammatory bowel disease. IBD appears to be due to an interaction of many complex factors including genetics, impaired immune system response, and environmental triggers.
The result is an abnormal immune system reaction, which in turn causes an inflammatory response in the body's intestinal regions. Ulcerative colitis and Crohn disease, like other IBDs, are considered autoimmune disorders.
The Inflammatory Response
An inflammatory response occurs when the body tries to protect itself from what it perceives as invasion by a foreign substance (antigen). Antigens may be viruses, bacteria, or other harmful substances.
In Crohn disease and ulcerative colitis, the body mistakenly targets harmless substances (food, beneficial bacteria, or the intestinal tissue itself) as harmful. To fight infection, the body releases various chemicals and white blood cells, which in turn produce byproducts that cause chronic inflammation in the intestinal lining. Over time, the inflammation damages and permanently changes the intestinal lining.
Genetic factors are certainly involved in IBD. A significant number of people with ulcerative colitis have family members with the same disease or Crohn disease. Several identified genes and chromosome locations play a role in the development of ulcerative colitis, Crohn disease, or both.
Genetic factors appear to be more important in Crohn disease, although there is evidence that both conditions have some genetic defects in common.
Inflammatory bowel disease is much more common in industrialized nations, urban areas, and northern geographical latitudes. It is not clear how or why these factors increase the risk for IBD.
It could be that “Western” lifestyle factors (smoking, exercise, diets high in fat and sugar, stress) play some role. However, there is no strong evidence that diet or stress cause Crohn disease or ulcerative colitis, although they can aggravate the conditions.
About 1 million Americans suffer from inflammatory bowel disease (IBD). About half of these people have ulcerative colitis. There are several risk factors for ulcerative colitis.
Ulcerative colitis can occur at any age, but it is most often diagnosed in people ages 15 to 35 and, less commonly, in people ages 50 to 75.
Men and women are equally at risk for developing ulcerative colitis.
Ulcerative colitis tends to run in families. People who have a first-degree relative (father, mother, brother, sister) with ulcerative colitis have a significantly greater risk for developing the disorder.
Race and Ethnicity
Crohn disease and ulcerative colitis are more common among whites than people of other races. Jews of Eastern European (Ashkenazi) descent are at especially high risk. However, rates of inflammatory bowel disease have been increasing among other racial and ethnic groups.
Smoking appears to decrease the risk of developing ulcerative colitis. (Smoking, however, should never be used to protect against ulcerative colitis.) Conversely, smoking increases the risk of developing Crohn disease, and can worsen the course of the disease.
Removal of the appendix (appendectomy) may possibly reduce the risk for developing ulcerative colitis, but increase the risk for Crohn disease.
The two major inflammatory bowel diseases, ulcerative colitis and Crohn disease, share certain characteristics:
- Symptoms usually appear in young adults.
- Symptoms can develop gradually or have a sudden onset.
- Ulcerative colitis and Crohn disease are chronic conditions. In both diseases, people experience sporadic episodes of symptom flare ups (relapse) in between symptom-free periods (remission)
- Symptoms can be mild or very severe. Severe symptoms can lead to complications.
The symptoms of ulcerative colitis depend in part on how widespread the disease is and the severity of the inflammation. Common symptoms include:
- Rectal bleeding and bloody stool
- Difficulty or pain when passing stool
- Abdominal cramps
Other symptoms may include:
- Loss of appetite and weight loss
The inflammation associated with inflammatory bowel disease (IBD) can cause symptoms outside of the gastrointestinal tract.
Joints: Arthritis is the most common non-intestinal symptom of inflammatory bowel disease.
Skin Disorders: There are many types of skin problems associated with IBD. They often tend to appear during disease flare-ups and resolve when symptoms are controlled. Canker sores (mouth ulcers) are very common. Skin disorders that tend to be seen more with ulcerative colitis than Crohn disease include, red knot-like swellings (erythema nodosum) and pus-filled skin ulcers on the shins and ankles (pyoderma gangrenosum).
Eyes: Inflammatory bowel disease is sometimes associated with various eye problems. A common complication is inflammation in the pigmented part of the eye, a condition called uveitis.
About half of people with ulcerative colitis have mild symptoms while another half go on to develop more severe forms of the disease. People with more severe ulcerative colitis tend to respond less well to medications.
The course of ulcerative colitis is unpredictable. Some people go into remission after a single attack, while others develop a chronic condition. There is no cure for ulcerative colitis (aside from surgical removal of the colon), but medications can help suppress the inflammatory response and control symptoms.
Ulcerative colitis is a chronic condition marked by variable periods of no symptoms (remission) and active symptoms (flare-ups). Treatment can help suppress the inflammatory response and manage symptoms. A treatment plan for ulcerative colitis includes:
- Diet and nutrition
- Surgery (when necessary)
Diet and Nutrition
Malnutrition may occur in ulcerative colitis, although it tends to be less severe than with Crohn disease. People with ulcerative colitis may experience reduced appetite and weight loss.
It is important to eat a well-balanced healthy diet and focus on getting enough calories, protein, and essential nutrients from a variety of food groups. These include protein sources, such as meat, chicken, fish or soy, dairy products, such as milk, yogurt, and cheese (if the patient is not lactose-intolerant), and fruits and vegetables. Depending on your nutritional status, your health care provider may recommend that you take a vitamin or iron supplement.
Drug therapy for ulcerative colitis aims to resolve symptoms (induce remission) and prevent flare-ups (maintain remission). The main types of drugs used for treating ulcerative colitis are:
Aminosalicylates: Mild-to-moderate ulcerative colitis is usually treated with aspirin-like medications called aminosalicylates, or 5-ASAs. These drugs are also used to treat relapses.
Corticosteroids: Corticosteroids (steroids) may be used short-term for moderate-to-severe ulcerative colitis to treat flares and induce remission. Because of their significant side effects, they are not recommended for long-term use and maintenance therapy.
Immunosuppressants: Drugs that suppress the immune system (immunosuppressants) are useful, either alone or in combinations, to induce remission in milder cases of ulcerative colitis, or maintain remission in people who have been treated with steroids.
Biologic Drugs: Biologic drugs used for ulcerative colitis target and block specific proteins involved with the inflammatory response. They are used to induce or maintain remission in moderate-to-severe ulcerative colitis.
Drug therapy is considered successful if it can push the disease into remission (and keep it there) without causing significant side effects. A person's condition is generally considered in remission when the intestinal lining has healed and symptoms such as diarrhea, abdominal cramps, and tenesmus (straining painfully to defecate) are normal or close to normal.
Other types of drugs may also be used to treat specific conditions and symptoms associated with ulcerative colitis:
- Antibiotics may be used to treat bacterial overgrowth or complications like pouchitis.
- Certain probiotics are also helpful in pouchitis.
- Anti-diarrheal medications such as loperamide (Imodium, generic) may help control diarrhea but you should only use them if your health care provider says it is safe to do so
Drugs are not helpful in all cases of ulcerative colitis. As a result, some people need surgical treatment. Surgery may also be necessary because of a hemorrhage, perforation of the colon, or toxic megacolon.
Total proctocolectomy with ileal pouch anal anastomosis (IPAA), also known as restorative proctolectomy, and total proctocolectomy with ileostomy are the two definitive surgical approaches for widespread ulcerative colitis that cannot be controlled with medications. Colectomy (resection of a portion of the colon) may be performed for more limited disease.
Unlike Crohn disease, which can recur after bowel resection, ulcerative colitis does not recur after total proctocolectomy. Total proctocolectomy is considered a cure for ulcerative colitis. (See the Surgery section for more detailed information.)
Aminosalicylates contain the compound 5-aminosalicylic acid, or 5-ASA, which helps reduce inflammation. These drugs are used to prevent relapses and maintain remission in mild-to-moderate ulcerative colitis.
5-ASA Types: The standard aminosalicylate drug is sulfasalazine (Azulfidine, generic). This drug combines the 5-ASA drug mesalamine with sulfapyridine, a sulfa antibiotic. While sulfasalazine is inexpensive and effective, the sulfa component of the drug can cause unpleasant side effects, including headache, nausea, and rash.
People who cannot tolerate sulfasalazine or who are allergic to sulfa drugs have other options for aminosalicylate drugs, including mesalamine (Asacol, Pentasa, Lialda, Delzicol, generic), olsalazine (Dipentum), and balsalazide (Colazal, generic). These drugs, like sulfasalazine, are taken as pills several times a day. Lialda and Apriso are once-daily mesalamine pills for people with ulcerative colitis. Mesalamine is also available in enema (Rowasa, generic) and suppository (Canasa, generic) forms.
Side Effects of 5-ASAs: Side effects of aminosalicylate drugs may include:
- Abdominal pain and cramps
- Hair loss
Corticosteroids (commonly called steroids) are powerful anti-inflammatory drugs used to treat moderate-to-severe ulcerative colitis. Because long-term steroid use can cause significant side effects, corticosteroids are used only a short period of time with the goal of inducing remission.
Corticosteroid Types: Prednisone (Deltasone, generic), methylprednisolone (Medrol, generic), and hydrocortisone (Cortef, generic) are the most common oral corticosteroids. Budesonide (Entocort, Uceris, generic) is a newer type of steroid that is used as an alternative. Most oral steroids circulate through the body and have widespread side effects. Budesonide affects only local areas in the intestine and tends to have fewer side effects.
Administering Corticosteroids: Most corticosteroids can be taken as a pill. For people who cannot take oral forms, steroids may be given intravenously or rectally as a suppository, enema, or foam. The severity or location of the condition often determines the form.
Side Effects of Corticosteroids: Common side effects of short-term treatment with oral steroids can include acne, increased appetite, and insomnia. Long-term treatment with steroids increases the risk for many serious side effects including low bone density (osteoporosis), high blood pressure, and cataracts.
Withdrawing from Corticosteroids: Once remission is achieved and the intestinal inflammation has subsided, steroids must be withdrawn very gradually. 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. To maintain remission, people who are treated with steroids are given an immunomodulator or biologic drug.
Some people cannot stop taking steroids without having a relapse of their symptoms. They may be treated with immunomodulators or biologic drugs, or be candidates for surgery.
Immunosuppressive Drugs (Immunomodulators)
Immunosuppressant drugs, also called immunodulators, suppress or limit actions of the immune system and therefore the inflammatory response that causes ulcerative colitis. These drugs may be used in combination with a biologic drug to induce remission. They may also be used alone to maintain remission in people who were treated with steroid drugs. Immunosuppressants allow corticosteroids to be safely withdrawn. (Chronic steroid use is not desirable because of its side effects). For this reason, immunosuppressants are sometimes referred to as steroid-sparing drugs.
Immunomodulator Types: Azathioprine (Imuran, Azasan, generic) and mercaptopurine ([6-MP], Purinethol, generic) are the standard oral immunosuppressant drugs. They belong to a class of medications called thiopurines. Methotrexate (MTX, Rheumatrex) is another type of immunosuppressant that is used more often for Crohn disease but may be used in some cases for ulcerative colitis.
Other pill forms of immunosuppressants include cyclosporine A (Sandimmune, Neoral) and tracrolimus (Prograf). They may be used to treat people with very severe ulcerative colitis.
Side Effects of Immunomodulators: General side effects of immunosuppressants may include:
- Susceptibility to infections
- Liver or pancreatic inflammation
People who take these drugs should receive frequent blood tests to monitor white blood cell count and liver function. A serious concern associated with thiopurines is increased risk for lymphoma, a cancer that starts in the immune system.
Biologic drugs are genetically engineered drugs to target specific proteins involved with the body's inflammatory response. Biologics are given to help induce or maintain remission.
Four biologic drugs are approved for treatment of moderate-to-severe ulcerative colitis in people who have not responded to other drugs:
- Infliximab (Remicade), which is given by intravenous (IV) infusion in a doctor's office or hospital clinic (after the first 3 doses, the drug is administered every 8 weeks)
- Adalimumab (Humira), which you can give by injection at home (after the first 2 doses, you give yourself an injection every other week)
- Golimumab (Simponi) is given by self-injection at home once a month
- Vendolizumab (Entyvio) is given by IV infusion (after the first 3 doses, the drug is administered every 8 weeks)
Infliximab, adalimumab, and golimumab target and block an inflammatory immune factor known as tumor necrosis factor (TNF). These drugs are called anti-TNF drugs or TNF blockers. Vendolizumab is an integrin receptor antagonist that works in a different way than anti-TNF drugs. It is approved for people with ulcerative colitis who were not helped by immunomodulators or anti-TNF drugs, or who are dependent on steroids.
Side Effects of Biologics: Biologic drugs can cause pain and swelling at the injection site. Other common side effects may include:
- Upper respiratory infections
- Stomach and back pain
Some people have allergic reactions to these drugs.
These drugs may increase the risk for infections, including tuberculosis and reactivation of hepatitis B. People need to be tested for these infections before starting treatment. Your health care provider should monitor you for any signs of viral, bacterial, or fungal infection. People who take biologic drugs should also receive regular tests for signs of liver problems. You will need frequent blood tests.
The anti-TNF drugs (infliximab, adalimumab) can increase the risk for lymphomas and leukemia cancers. However, evidence suggests that the risk is relatively rare. The benefits of these drugs appear to outweigh the risks for cancer.
Vendolizumab may possibly increase the risk for a rare neurological condition called progressive multifocal leukoencephalopathy (PML), which can lead to death or severe disability. It is too early to tell. Vendolizumab was approved in 2014 and is the newest drug for ulcerative colitis.
Proctocolectomy and Ileoanal Anastomosis
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 for ulcerative colitis that has not been helped by drug therapy.
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. 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. An ostomy 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 a person can pass bowel movements normally through the anus, although they are watery and more frequent than normal (5 to 6 times a day).
- 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 (passing gas) is a common problem following surgery. People may need to avoid 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.
It is important to increase fluid intake, and include not only water but also broth, sports drinks, and vegetable juice to maintain appropriate levels of sodium and potassium.
Ileostomy and ileoanal anastomosis do not interfere with bathing or showering or most physical activity except for contact sports. As a rule, the surgeries do not impair sexual function.
Outcome and Complications from Ileoanal Anastomosis
Complications are common with any intestinal operation. In a small percentage of IPAA procedures, complications occur that require conversion to an ileostomy.
Pouchitis: Inflammation of the pouch (pouchitis) is the most common complication of the pouch procedures. Symptoms include rectal bleeding, cramps, and fever. It can usually be successfully treated with antibiotics such as metronidazole (Flagyl, generic) or ciprofloxacin (Cipro, generic).
Bowel obstruction: may occur although it is less common than pouchitis. With most people, this condition can be treated by avoiding food for several days and administering intravenous fluids. In some cases of bowel obstruction, surgery may need to be performed to remove the blockage.
Pouch failure: occurs in a small percentage of people. It requires permanent removal of the pouch and use of ileostomy.
Irritable Pouch Syndrome: Irritable pouch syndrome is a problem that includes frequent bowel 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.
Infertility: IPAA can cause infertility in women because the surgery can scar or block the fallopian tubes.
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