Section 9. Digestive Disorders

Chapter 126. Inflammatory Bowel Diseases

Topics: Introduction | Crohn's Disease | Ulcerative Colitis | Collagenous Colitis and Lymphocytic Colitis | Diversion Colitis

Crohn's Disease

Crohn's disease (regional enteritis, granulomatous ileitis, ileocolitis) is a chronic inflammation of the intestinal wall that may affect any part of the digestive tract.

The cause of Crohn's disease is not known. Researchers believe that a dysfunction of the immune system results in the intestine overreacting to an environmental, dietary, or infectious agent. Certain people may have a hereditary predisposition to this immune system dysfunction. Cigarette smoking appears to contribute to both the development and the periodic flare-ups (bouts or attacks) of Crohn's disease.

In the past few decades, Crohn's disease has become more common worldwide. It occurs about equally in both sexes, is more common among Jews, and tends to run in families. Most people develop Crohn's disease before age 35, usually between the ages of 15 and 25.

Most commonly, Crohn's disease occurs in the last portion of the small intestine (ileum) and in the large intestine, but it can occur in any part of the digestive tract, from the mouth to the anus and even in the skin around the anus. Crohn's disease affects the small intestine alone (35% of people), the large intestine alone (20% of people), or both the last portion of the small intestine and the large intestine (45% of people). The disease may affect some segments of the intestinal tract while leaving normal segments (skip areas) between the affected areas. Where Crohn's disease is active, the full thickness of the bowel is involved.

Symptoms and Complications

The most common early symptoms of Crohn's disease are chronic diarrhea (which sometimes is bloody), crampy abdominal pain, fever, loss of appetite, and weight loss. Symptoms may continue for days or weeks and may resolve without treatment. Complete and permanent recovery after a single attack is extremely rare. Crohn's disease almost invariably flares up at irregular intervals throughout a person's life. Flare-ups can be mild or severe, brief or prolonged. Severe flare-ups can lead to intense pain, dehydration, and blood loss. Why the symptoms come and go and what triggers new flare-ups or determines their severity are not known. The inflammation tends to recur in the same area of the intestine, but it may spread to other areas after a diseased area has been removed surgically.

Common complications of inflammation include the development of an intestinal obstruction, pus-filled pockets of infection (abscesses), and abnormal connecting channels (fistulas). Fistulas may connect two different parts of the intestine. Fistulas also may connect the intestine and bladder or the intestine and the skin surface, especially around the anus. Although fistulas from the small intestine are common, wide-open perforations are rare.

When the large intestine is affected extensively by Crohn's disease, rectal bleeding commonly occurs; after many years, the risk of colon cancer (cancer of the large intestine) is greatly increased. About one third of people who develop Crohn's disease have problems around the anus, especially fistulas and cracks (fissures) in the lining of the mucus membrane of the anus. Crohn's disease may be complicated by certain disorders affecting other parts of the body--such as gallstones, inadequate absorption of nutrients, urinary tract infections, kidney stones, and deposits of the protein amyloid in several organs (amyloidosis).

When Crohn's disease causes a flare-up of gastrointestinal symptoms, the person may also experience inflammation of the joints (arthritis), inflammation of the whites of the eyes (episcleritis), mouth sores (aphthous stomatitis), inflamed skin nodules on the arms and legs (erythema nodosum), and blue-red skin sores containing pus (pyoderma gangrenosum). When Crohn's disease is not causing a flare-up of gastrointestinal symptoms, the person still may experience inflammation of the spine (ankylosing spondylitis), inflammation of the pelvic joints (sacroiliitis), inflammation inside the eye (uveitis), and inflammation of the bile ducts (primary sclerosing cholangitis).

In children, gastrointestinal symptoms such as abdominal pain and diarrhea often are not the main symptoms and may not appear at all. Instead, the main symptom may be slow growth, joint inflammation, fever, or weakness and fatigue resulting from anemia.

Diagnosis

A doctor may suspect Crohn's disease in a person with recurring crampy abdominal pain and diarrhea, particularly if the person has a family history of Crohn's disease or a history of problems around the anus. Other clues to the diagnosis may include inflammation in the joints, eyes, or skin. The doctor may feel a lump or fullness in the lower part of the abdomen, most often on the right side.

No laboratory test specifically identifies Crohn's disease, but blood tests may show anemia, abnormally high numbers of white blood cells, low levels of the protein albumin, and other indications of inflammation.

A colonoscopy (an examination of the large intestine with a flexible viewing tube) and a biopsy (removal of a tissue specimen for microscopic examination) are usually the first tests performed after a physical examination and blood tests have been completed.

If Crohn's disease is limited to the small intestine, a colonoscopy will not detect the disease. However, Crohn's disease can almost always be detected on x-rays after barium is swallowed. X-rays taken after barium is given by enema can reveal the characteristic appearance of Crohn's disease in the large intestine. Computed tomography (CT) can show changes that are helpful in distinguishing between Crohn's disease and ulcerative colitis and is the best way to identify complications that occur outside the walls of the intestinal tract, such as abscesses or fistulas.

Treatment and Prognosis

Although Crohn's disease has no known cure, many treatments help reduce inflammation and relieve symptoms.

Antidiarrheal Drugs: These drugs may relieve cramps and diarrhea (see Section 9, Chapter 129). These drugs, which include anticholinergic drugs (drugs that block the normal action of part of the nervous system) (see Section 2, Chapter 14), diphenoxylate, loperamide, deodorized opium tincture, and codeine, are taken by mouth--preferably before meals. Taking methylcellulose or psyllium preparations sometimes helps prevent anal irritation by making the stool firmer.

Anti-inflammatory Drugs: Sulfasalazine and mesalamine, olsalazine, and balsalazide (drugs chemically related to sulfasalazine) reduce inflammation. These drugs can suppress symptoms when they occur and reduce inflammation, especially in the large intestine. Mesalamine is marginally effective in preventing recurrences. However, all of these drugs work less well for relieving severe flare-ups.

Corticosteroids such as prednisone, which is given by mouth, may dramatically reduce fever and diarrhea, relieve abdominal pain and tenderness, and improve appetite and sense of well-being. However, long-term corticosteroid therapy invariably results in side effects (see Section 5, Chapter 67). Generally, high doses are taken to relieve major inflammation and symptoms; then the dose is reduced, and the drug is discontinued as soon as possible. A new corticosteroid called budesonide has fewer side effects than prednisone, although it is not as effective and generally does not prevent relapses beyond 6 to 9 months.

If the disease becomes severe, the person is hospitalized, and corticosteroids are given intravenously. Initially, the person is given nothing by mouth, and intravenous fluids are given to restore and maintain body fluids (hydration). People with heavy rectal bleeding may require blood transfusions; those people with mild anemia require iron supplements by mouth.

Immunomodulating Drugs: Drugs such as azathioprine and mercaptopurine, which modify the actions of the immune system, are effective for people with Crohn's disease who do not respond to other drugs and are especially effective for maintaining long periods of remission. They significantly improve the person's overall condition, decrease the need for corticosteroids, and often heal fistulas. However, these drugs often do not produce benefits for 2 to 4 months and may have potentially serious side effects. Therefore, a doctor closely monitors the person for allergy, inflammation of the pancreas (pancreatitis), and a low white blood cell count. Newly available blood tests may help the doctor ensure safe and effective drug dosages.

Methotrexate, given by injection once a week, benefits some people who do not respond to or who cannot tolerate corticosteroids, azathioprine, or mercaptopurine. High-dose cyclosporine may help reduce inflammation and heal fistulas, but it cannot safely be used long-term.

Infliximab, derived from monoclonal antibodies, is another modifier of the immune system's actions. Infliximab can be given intravenously for moderate to severe Crohn's disease that has not responded to other drugs. However, because the benefits of each infusion are short-lived, other treatments are needed between infusions of infliximab. Because infliximab is a relatively new drug, its long-term benefit and all of its side effects are not yet known. Many other drugs that focus on regulating the immune system are being developed.

See the drug table Drugs That Reduce Bowel Inflammation.

Broad-spectrum Antibiotics: Antibiotics that are effective against many types of bacteria are often prescribed to treat infectious complications. The antibiotic metronidazole is the most common choice for the treatment of abscesses and fistulas around the anus. Metronidazole may also help relieve the noninfectious symptoms of Crohn's disease, such as diarrhea and abdominal cramps. However, when used for a long time, metronidazole can damage nerves, resulting in a pins-and-needles sensation in the arms and legs. This side effect usually disappears when the drug is stopped, but relapses of Crohn's disease after discontinuing metronidazole are common. Some other antibiotics, such as ciprofloxacin or levofloxacin, may be used in place of or in combination with metronidazole.

Dietary Regimens: Defined-formula diets, in which each nutritional component is precisely measured, may improve the condition of an intestinal obstruction or fistula at least for a short time and also may help children grow more than they might otherwise. These diets may be tried before or in addition to surgery. Occasionally, concentrated nutrients are given intravenously to compensate for the poor absorption of nutrients that is typical of Crohn's disease.

Surgery: Surgery may be needed when the intestine is obstructed or when abscesses or fistulas do not heal. An operation to remove diseased sections of the intestine may relieve symptoms indefinitely, but it does not cure the disease. Crohn's disease tends to recur where the remaining intestine is rejoined, although several drug therapies initiated after surgery reduce this tendency. A second operation is ultimately needed in nearly half of the people. Consequently, surgery is performed only if specific complications or the failure of drug therapy makes it necessary. Still, most people who have undergone surgery consider their quality of life to be better than it was before the operation.

Crohn's disease usually does not shorten a person's life. However, some people die of cancer of the digestive tract, which may develop in long-standing Crohn's disease.