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Crohn Disease ˈkrōnz-

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

Crohn disease (regional enteritis, granulomatous ileitis, or ileocolitis) is chronic inflammation of the intestinal wall that typically involves the lower part of the small intestine, the upper part of the large intestine, or both but may affect any part of the digestive tract.

  • Although the exact cause is unknown, an improperly functioning immune system may result in Crohn disease.

  • Typical symptoms include chronic diarrhea (which sometimes is bloody), crampy abdominal pain, fever, loss of appetite, and weight loss.

  • The diagnosis is based on a colonoscopy and imaging tests such as barium x-rays, computed tomography, or magnetic resonance imaging.

  • There is no cure for Crohn disease.

  • Treatment is aimed at relieving symptoms and reducing inflammation, but some people require surgery.

In the past few decades, Crohn disease has become more common worldwide. However, it is most common among people of Northern European and Anglo-Saxon descent. It occurs about equally in both sexes, often runs in families, and seems to be more common among Ashkenazi Jews. Most people develop Crohn disease before age 30, usually between the ages of 14 and 24.

Most commonly, Crohn 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 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 rectum is rarely affected, unlike in ulcerative colitis, in which the rectum is always involved. However, infections and other complications around the anus are not unusual. The disease may affect some segments of the intestinal tract while leaving normal segments (called skip areas) between the affected areas. Where Crohn disease is active, the full thickness of the bowel is usually involved.

The cause of Crohn disease is not known for certain, but many researchers believe that a dysfunction of the immune system causes the intestine to overreact to an environmental, dietary, or infectious agent. Certain people may have a hereditary predisposition to this immune system dysfunction. Cigarette smoking seems to contribute to both the development and the periodic flare-ups (bouts or attacks) of Crohn disease. Oral contraceptives may increase the risk of Crohn disease.

Symptoms

The most common early symptoms of Crohn disease are chronic diarrhea (which sometimes is bloody when the large intestine is severely affected), 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 disease almost always 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, constant pain, fever, and dehydration. Why the symptoms come and go and what triggers new flare-ups or determines their severity is not known. Recurrent inflammation tends to appear in the same area of the intestine, but it may spread to adjacent areas after a diseased segment has been removed surgically.

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

Complications

Common complications of inflammation include

  • Intestinal blockage (obstruction)

  • Abscesses (pus-filled pockets of infection) in the abdomen

  • Fistulas (abnormal connecting channels between the intestine and skin or other organs)

  • Anal fissures (tears in the skin of the anus), abscesses, and fistulas

Scarring due to chronic inflammation can cause intestinal blockage. Deep ulcers that penetrate through the bowel wall can create abscesses or open 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 holes (perforations) are rare. Fissures in the skin of the anus are common.

When the large intestine is affected extensively by Crohn 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 disease have problems around the anus, especially fistulas and fissures in the lining of the mucus membrane of the anus.

Crohn disease may lead to complications in other parts of the body. These complications include gallstones, inadequate absorption of nutrients, urinary tract infections, kidney stones, and deposits of the protein amyloid in several organs (amyloidosis).

When Crohn disease causes a flare-up of gastrointestinal symptoms, the person may also have 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). Even when Crohn disease is not causing a flare-up of gastrointestinal symptoms, the person still may have inflammation of the spine (ankylosing spondylitis), inflammation of the pelvic joints (sacroiliitis), inflammation inside the eye (uveitis), or inflammation of the bile ducts (primary sclerosing cholangitis) entirely without relation to the bowel disease.

Diagnosis

A doctor may suspect Crohn disease in a person with recurring crampy abdominal pain and diarrhea, particularly if the person has a family history of Crohn disease or a history of problems around the anus. Other clues to the diagnosis may include inflammation in the joints, eyes, or skin or, in a child, stunted growth. 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 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 such as an elevated erythrocyte sedimentation rate or level of C-reactive protein.

People who have severe abdominal pain and tenderness have a computed tomography (CT) scan of their abdomen. CT may show a blockage, abscesses or fistulas, and other possible causes of inflammation of the abdomen (such as appendicitis).

People who have less severe inflammation or who have had symptoms that recur over a period of time have CT or magnetic resonance enterography, or plain x-rays are taken after barium is swallowed or given by enema. Another way in which the small intestine can be evaluated is with wireless capsule endoscopy (see Video Capsule Endoscopy).

People who have little pain and mostly diarrhea undergo a colonoscopy (an examination of the large intestine with a flexible viewing tube) and a biopsy (removal of a tissue specimen for microscopic examination). If Crohn disease is limited to the small intestine, colonoscopy will not detect the disease unless the colonoscope is advanced all the way through the colon into the last part of the small intestine where the inflammation most often resides.

Prognosis

Crohn disease has no known cure and is characterized by intermittent flare-ups of symptoms. Flare-ups may be mild or severe, few or frequent.

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

Treatment

Many treatments help reduce inflammation and relieve symptoms.

Antidiarrheal drugs

These drugs, which may relieve cramps and diarrhea (see Agents Used to Prevent or Treat Constipation), include drugs that have anticholinergic effects (drugs that block certain pathways of the nervous system―see Anticholinergic: What Does It Mean?) such as diphenoxylate, loperamide, deodorized opium tincture, and codeine. They 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 related drugs such as mesalamine, olsalazine, and balsalazide reduce inflammation. These drugs can suppress symptoms when they occur and reduce inflammation, especially in the large intestine. Typically these drugs are taken by mouth. Mesalamine is also available as a suppository or enema. Mesalamine may be effective in preventing recurrences. These drugs do not work as 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 Corticosteroids: Uses and Side Effects). Usually, high doses are taken initially to relieve major inflammation and symptoms. The dose is then reduced and the drug is discontinued as soon as possible. Another corticosteroid called budesonide has fewer side effects than prednisone, but it may not be quite as rapidly effective and usually does not prevent relapses beyond 6 months.

As with corticosteroids taken by mouth, the dose of corticosteroids taken in enema or foam form (such as hydrocortisone) is reduced and gradually stopped.

If the disease becomes severe, the person is hospitalized and corticosteroids are given by vein (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. People who have more chronic anemia may require iron supplements by mouth or intravenously.

Immunomodulating drugs

Drugs such as azathioprine and mercaptopurine, which modify the actions of the immune system, are effective for people with Crohn disease who do not respond to other drugs and are especially effective for maintaining long periods of remission (periods of no symptoms). They significantly improve the person's overall condition, decrease the need for corticosteroids, and often heal fistulas. However, these drugs may not produce clinical benefits for 1 to 3 months and may have potentially serious side effects. Therefore, a doctor closely monitors the person for allergy, a suppression of bone marrow, inflammation of the pancreas (pancreatitis), a low white blood cell count, and sometimes liver problems. Blood tests that detect variations in one of the enzymes that metabolize azathioprine and mercaptopurine and that directly measure metabolite levels may sometimes help the doctor ensure safe and effective drug dosages.

Methotrexate, given by injection or by mouth once a week, often benefits people who do not respond to or who cannot tolerate corticosteroids, azathioprine, or mercaptopurine.

Cyclosporine is given by injection in high doses. This drug may help heal fistulas caused by Crohn disease but it cannot safely be used long term.

Infliximab, which is derived from monoclonal antibodies to tumor necrosis factor, is another modifier of the immune system's actions. Infliximab is given as a series of infusions. This drug can be given to treat moderate to severe Crohn disease that has not responded to other drugs, to treat people with fistulas, and to maintain response when the disease is difficult to control. However, because the benefits of each infusion of infliximab are short-lived, other treatments are needed between infusions. Such treatments may include other immunomodulating drugs such as azathioprine, mercaptopurine, or methotrexate. Because infliximab is a relatively new drug, its long-term benefit and all of its side effects are not yet known, but it may worsen an existing uncontrolled bacterial infection, may reactivate tuberculosis, and may increase the risk of some types of cancer. Some people have reactions such as fever, chills, nausea, headache, itching, or rash during the infusion.

Adalimumab is a drug related to infliximab and also focuses on regulating the immune system. Adalimumab is given as a series of injections. Adalimumab is particularly helpful for people who cannot tolerate or who no longer respond to infliximab. People may have pain and itching at the injection site.

Certolizumab is given as monthly injections. This drug works in a similar way as and causes side effects similar to those of infliximab and adalimumab.

Drugs That Reduce Bowel Inflammation Caused by Crohn Disease

Drug

Some Side Effects

Comments

Aminosalicylates

  • Sulfasalazine

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

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

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

Hepatitis and pancreatitis are unrelated to dose.

  • Balsalazide

  • Mesalamine

  • Olsalazine

Common: Fever and rash

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

For olsalazine: Watery diarrhea

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

Corticosteroids

Prednisone

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

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

Budesonide

Diabetes mellitus, high blood pressure, cataracts, and osteoporosis

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

Immunomodulators

  • Azathioprine

  • Mercaptopurine

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

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

Interval blood monitoring is required.

Cyclosporine

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

This drug is mainly for people with fistulas.

Side effects become more likely with long-term use.

Methotrexate

Nausea, vomiting, abdominal distress, headache, rash, soreness of the mouth, fatigue, scarring of the liver (cirrhosis), low white blood cell count, and infections

Liver toxicity is likely dose dependent.

Methotrexate also causes abortion and birth defects during pregnancy so it is not prescribed for pregnant women or women who may become pregnant.

Tacrolimus

Similar to cyclosporine

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

Infliximab

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

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

People should be screened for tuberculosis before initiating treatment.

Adalimumab

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

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

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

Certolizumab

Similar to infliximab and adalimumab

Certolizumab works in a similar way as and causes side effects similar to those of infliximab and adalimumab.

Some doctors prefer this drug over infliximab and adalimumab for pregnant and nursing women.

Broad-spectrum antibiotics and probiotics

Antibiotics that are effective against many types of bacteria are often prescribed. 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 disease, such as diarrhea and abdominal cramps. However, when used for a long time, metronidazole can damage nerves, resulting in a pins-and-needles feeling in the arms and legs. This side effect usually disappears when the drug is stopped, but relapses of Crohn 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. Rifaximin, a nonabsorbable antibiotic, is also sometimes used in treating active Crohn disease.

Some bacteria are naturally found in the body and promote the growth of good bacteria (probiotics). The daily use of probiotics, such as lactobacillus (typically present in yogurt) may be effective in preventing pouchitis (see Inflammatory Bowel Diseases (IBD):Surgery).

Dietary regimens

Defined-formula liquid 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. Nutritional therapy also may help children grow more than they might otherwise, especially when given at nighttime by tube feeding. 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 disease.

Surgery

Most people with Crohn disease require surgery at some point during their illness. Surgery is 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 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.

Because smoking increases the risk of recurrence, especially in women, doctors encourage people to quit smoking.

General management

Cramps and diarrhea may be relieved by taking loperamide or drugs that stop spasms in the abdomen (ideally before meals). Methylcellulose or psyllium preparations sometimes help prevent anal irritation by making the stool firmer.

Severity of symptoms

For people who have mild to moderate symptoms, mesalamine is typically the first drug of choice. Some doctors give antibiotics instead of mesalamine or give antibiotics to people who are not helped by mesalamine.

For people who have moderate to severe symptoms, corticosteroids (such as prednisone or budesonide) are given by mouth or vein. People who are not helped by corticosteroids are given other drugs such as azathioprine, mercaptopurine, or methotrexate. If people have an obstruction, doctors do nasogastric suction and give fluids by vein. In nasogastric suction, a tube is passed through the nose into the stomach or small intestine, and suction is applied to the tube to relieve abdominal swelling (distention).

For people whose symptoms developed suddenly or who have an abscess, fluids and antibiotics are given by vein in a hospital. Doctors drain the abscess surgically or by inserting a needle under the skin and drawing out the fluid. Doctors give corticosteroids by vein to people who have no infection or have an infection that is being controlled. Surgery is usually needed if people are not helped by corticosteroids and antibiotics within 5 to 7 days.

Fistulas

People with fistulas are given metronidazole and ciprofloxacin. If these drugs do not help people in 3 to 4 weeks, doctors may give azathioprine or mercaptopurine and possibly infliximab, adalimumab, or certolizumab. Cyclosporine is an alternative, but fistulas often recur after treatment. People typically need definitive surgery to prevent the fistulas from recurring.

Maintenance regimens

To keep symptoms from returning (that is, to maintain remission), people must continue to take a regimen of mesalamine or corticosteroids or a combination of azathioprine, mercaptopurine, methotrexate, or infliximab or adalimumab or certolizumab. To maintain remission, the doses for most people will need to be increased or the intervals between regimens will need to be shortened within a year. During remission, doctors monitor people's symptoms and do blood tests. X-rays are taken or a colonoscopy is done in people who have had Crohn disease for 7 or 8 years.

Resources In This Article

Drugs Mentioned In This Article

  • Generic Name
    Select Brand Names
  • IMODIUM
  • No US brand name
  • AZULFIDINE
  • COLAZAL
  • DIPENTUM
  • PULMICORT, RHINOCORT
  • RAYOS
  • ASACOL, ROWASA
  • CORTEF, SOLU-CORTEF
  • REMICADE
  • PROGRAF
  • OTREXUP
  • PURINETHOL
  • NEORAL, SANDIMMUNE
  • IMURAN
  • HUMIRA
  • IQUIX, LEVAQUIN, QUIXIN
  • FLAGYL
  • CILOXAN, CIPRO
  • XIFAXAN