Crohn's Disease

What is Crohn's disease?


Crohn's disease is a chronic inflammatory disease of the intestines. It primarily causes ulcerations (breaks in the lining) of the small and large intestines, but can affect the digestive system anywhere from the mouth to the anus. It is named after the physician who described the disease in 1932. It also is called granulomatous enteritis or colitis, regional enteritis, ileitis, or terminal ileitis.

Crohn's disease is related closely to another chronic inflammatory condition that involves only the colon called ulcerative colitis. Together, Crohn's disease and ulcerative colitis are frequently referred to as inflammatory bowel disease (IBD). Ulcerative colitisand Crohn's disease have no medical cure. Once the diseases begin, they tend to fluctuate between periods of inactivity (remission) and activity (relapse). They affect approximately 500,000 to two million people in the United States. Men and women are equally affected. IBD most commonly begins during adolescence and early adulthood, but it also can begin during childhood and later in life.

Crohn's disease tends to be more common in relatives of patients with Crohn's disease. It also is more common among relatives of patients with ulcerative colitis.

What causes Crohn's disease?


The cause of Crohn's disease is unknown. Some scientists suspect that infection by certain bacteria, such as strains of mycobacterium, may be the cause of Crohn's disease. To date, however, there has been no convincing evidence that the disease is caused by infection. Crohn's disease is not contagious. Although diet may affect the symptoms in patients with Crohn's disease, it is unlikely that diet is responsible for the disease.

Activation of the immune system in the intestines appears to be important in IBD. The immune system is composed of immune cells and the proteins that these immune cells produce. Normally, these cells and proteins defend the body against harmful bacteria, viruses, fungi, and other foreign invaders. Activation of the immune system causes inflammation within the tissues where the activation occurs. (Inflammation is an important mechanism of defense used by the immune system.)

Normally, the immune system is activated only when the body is exposed to harmful invaders. In patients with IBD, however, the immune system is abnormally and chronically activated in the absence of any known invader. The continued abnormal activation of the immune system results in chronic inflammation and ulceration. The susceptibility to abnormal activation of the immune system is genetically inherited. Thus, first degree relatives (brothers, sisters, children, and parents) of patients with IBD are more likely to develop these diseases. Recently a gene called NOD2 has been identified as being associated with Crohn's disease. This gene is important in determining how the body responds to some bacterial products. Individuals with mutations in this gene are more susceptible to developing Crohn's disease.


How does Crohn's disease affect the intestines?


In the early stages, Crohn's disease causes small, scattered, shallow, crater-like areas (erosions) on the inner surface of the bowel. These erosions are called aphthous ulcers. With time, the erosions become deeper and larger, ultimately becoming true ulcers (which are deeper than erosions) and causing scarring and stiffness of the bowel. As the disease progresses, the bowel becomes increasingly narrowed, and ultimately can become obstructed. Deep ulcers can puncture holes in the wall of the bowel, and bacteria from within the bowel can spread to infect adjacent organs and the surrounding abdominal cavity.

When Crohn's disease narrows the small intestine to the point of obstruction, the flow of the contents through the intestine ceases. Sometimes, the obstruction can be caused suddenly by poorly-digestible fruit or vegetables that plug the already-narrowed segment of the intestine. When the intestine is obstructed, digesting food, fluid and gas from the stomach and the small intestine cannot pass into the colon. The symptoms of small intestinal obstruction then appear, including severe abdominal cramps,nauseavomiting, and abdominal distention. Obstruction of the small intestine is much more likely since the small intestine is much narrower than the colon to begin with.

Deep ulcers can puncture holes in the walls of the small intestine and the colon, and create a tunnel between the intestine and adjacent organs. If the ulcer tunnel reaches an adjacent empty space inside the abdominal cavity, a collection of infected pus (an abdominal abscess) is formed. Patients with abdominal abscesses can develop tender abdominal masses, high fevers, andabdominal pain.

When the ulcer tunnels into an adjacent organ, a channel (fistula) is formed. The formation of a fistula between the intestine and the bladder (enteric-vesicular fistula) can cause frequent urinary tract infections and the passage of gas and feces during urination. When a fistula develops between the intestine and the skin (enteric-cutaneous fistula), pus and mucous emerge from a small painful opening on the skin of the abdomen. The development of a fistula between the colon and the vagina (colonic-vaginal fistula) causes gas and feces to emerge through the vagina. The presence of a fistula from the intestines to the anus (anal fistula) leads to a discharge of mucous and pus from the fistula's opening around the anus.

How is Crohn's disease different from ulcerative colitis?


While ulcerative colitis causes inflammation only in the colon (colitis) and/or the rectum (proctitis), Crohn's disease may cause inflammation in the colon, rectum, small intestine (jejunum and ileum), and, occasionally, even the stomach, mouth, and esophagus.

The patterns of inflammation in Crohn's disease are different from ulcerative colitis. Except in the most severe cases, the inflammation of ulcerative colitis tends to involve the superficial layers of the inner lining of the bowel. The inflammation also tends to be diffuse and uniform. (All of the lining in the affected segment of the intestine is inflamed.) Unlike ulcerative colitis, the inflammation of Crohn's disease is concentrated in some areas more than others and involves layers of the bowel that are deeper than the superficial inner layers. Therefore, the affected segment(s) of bowel in Crohn's disease often is studded with deeper ulcers with normal lining between these ulcers.


What are the symptoms of Crohn's disease?


Common symptoms of Crohn's disease include abdominal pain, diarrhea, and weight loss. Less common symptoms include poor appetite, fever, night sweats, rectal pain, andrectal bleeding. The symptoms of Crohn's disease are dependent on the location, the extent, and the severity of the inflammation. The different subtypes of Crohn's disease and their symptoms are:

  1. Crohn's colitis is inflammation that is confined to the colon. Abdominal pain and bloody diarrhea are the common symptoms. Anal fistulae and peri-rectal abscesses also can occur.
  2. Crohn's enteritis refers to inflammation confined to the small intestine (the first part, called the jejunum or the second part, called the ileum). Involvement of the ileum alone is referred to as Crohn's ileitis. Abdominal pain and diarrhea are the common symptoms. Obstruction of the small intestine also can occur.
  3. Crohn's terminal ileitis is inflammation that affects only the very end of the small intestine (terminal ileum), the part of the small intestine closest to the colon. Abdominal pain and diarrhea are the common symptoms. Small intestinal obstruction also can occur.
  4. Crohn's entero-colitis and ileo-colitisare terms to describe inflammation that involve both the small intestine and the colon. Bloody diarrhea and abdominal pain are the common symptoms. Small intestinal obstruction also can occur.

Crohn's terminal ileitis and ileo-colitis are the most common types of Crohn's disease. (Ulcerative colitis frequently involves only the rectum or rectum and sigmoid colon at the distal end of the colon. These are called ulcerative proctitis and procto-sigmoiditis, respectively.)

Up to one third of patients with Crohn's disease may have one or more of the following conditions involving the anal area:

  1. Swelling of the tissue of the anal sphincter, the muscle at the end of the colon that controls defecation.
  2. Development of ulcers and fissures (long ulcers) within the anal sphincter. These ulcers and fissures can cause bleeding and pain with defecation.
  3. Development of anal fistulae (abnormal tunnels) between the anus or rectum and the skin surrounding the anus). Mucous and pus may drain from the openings of the fistulae on the skin.
  4. Development of peri-rectal abscesses (collections of pus in the anal and rectal area). Peri-rectal abscesses can cause fever, pain and tenderness around the anus.


What are the complications of Crohn's disease?


Complications of Crohn's disease may be related or unrelated to the inflammation within the intestine (such as intestinal or extra-intestinal). Intestinal complications of Crohn's disease include obstruction and perforation of the small intestine, abscesses (collections of pus), fistulae, and intestinal bleeding. Massive distention or dilatation of the colon (megacolon), and rupture (perforation) of the intestine are potentially life-threatening complications. Both generally require surgery, but, fortunately, these two complications are rare. Recent data suggest that there is an increased risk of cancer of the small intestine and colon in patients with long-standing Crohn's disease.

Extra-intestinal complications involve the skin, joints, spine, eyes, liver, and bile ducts. Skin involvement includes painful red raised spots on the legs (erythema nodosum) and an ulcerating skin condition generally found around the ankles called pyoderma gangrenosum. Painful eye conditions (uveitis, episcleritis) can cause visual difficulties. Arthritis can cause pain, swelling, and stiffness of the joints of the extremities. Inflammation of the low back (sacroiliac joint arthritis) and of the spine (ankylosing spondylitis) can cause pain and stiffness of the spine. Inflammation of the liver (hepatitis) or bile ducts (primary sclerosing cholangitis) also can occur. Sclerosing cholangitis causes narrowing and obstruction of the ducts draining the liver and can lead to yellow skin (jaundice), recurrent bacterial infections, and liver cirrhosis with liver failure. Sclerosing cholangitis with liver failure is one of the reasons for performing liver transplantation. Sclerosing cholangitis frequently is complicated by the development of cancer of the bile ducts.



How is Crohn's disease diagnosed?


The diagnosis of Crohn's disease is suspected in patients with fever, abdominal pain and tenderness, diarrhea with or without bleeding, and anal diseases. Laboratory blood tests may show elevated white cell counts and sedimentation rates, both of which suggest infection or inflammation. Other blood tests may show low red blood cell counts (anemia), low blood proteins, and low body minerals, reflecting loss of these elements due to chronic diarrhea.

Barium x-ray studies can be used to define the distribution, nature, and severity of the disease. Barium is a chalky material that is visible by x-ray and appears white on x-ray films. When barium is ingested orally (upper GI series) it fills the intestine and pictures (x-rays) can be taken of the stomach and the small intestines. When barium is administered through the rectum (barium enema), pictures of the colon and the terminal ileum can be obtained. Barium x-rays can show ulcerations, narrowing, and, sometimes, fistulae of the bowel.

Direct visualization of the rectum and the large intestine can be accomplished with flexible viewing tubes (colonoscopes).Colonoscopy is more accurate than barium x-rays in detecting small ulcers or small areas of inflammation of the colon and terminal ileum. Colonoscopy also allows for small tissue samples (biopsies) to be taken and sent for examination under the microscope to confirm the diagnosis of Crohn's disease. Colonoscopy also is more accurate than barium x-rays in assessing the degree (activity) of inflammation.

Computerized axial tomography (CAT or CT) scanning is a computerized x-ray technique that allows imaging of the entire abdomen and pelvis. It can be especially helpful in detecting abscesses.

Most recently, video capsule endoscopy has been added to the list of diagnostic tests for diagnosing Crohn's disease. For video capsule endoscopy, a capsule containing a miniature video camera is swallowed. As the capsule travels through the small intestine, it sends video images of the lining of the small intestine to a receiver carried on a belt at the waist. The images are downloaded and then reviewed on a computer. The value of video capsule endoscopy is that it can identify the early, mild abnormalities of Crohn's disease. Video capsule endoscopy may be particularly useful when there is a strong suspicion of Crohn's disease but the barium x-rays are normal. (Barium x-rays are not as good at identifying early, mild Crohn's disease.)

Video capsule endoscopy should not be performed in patients who have obstruction of the small intestine. The capsule may get stuck behind the obstruction and make the obstruction worse. Doctors usually also are reluctant to perform video-capsule endoscopy for the same reason in patients who they suspect of having small intestinal strictures (narrowed segments of small intestine that can result from prior surgery, prior radiation, or chronic ulceration, for example, from Crohn's disease). There is also a theoretical concern for electrical interference between the capsule and implanted cardiac pacemakers and defibrillators; however, so far in a small number of patients with pacemakers or defibrillators who have undergone video capsule endoscopy there have been no problems.


How is Crohn's disease treated?


The symptoms and severity of Crohn's disease vary among patients. Patients with mild or no symptoms may not need treatment. Patients whose disease is in remission (where symptoms are absent) also may not need treatment.

There is no medication that can cure Crohn's disease. Patients with Crohn's disease typically will experience periods of relapse (worsening of inflammation) followed by periods of remission (reduced inflammation) lasting months to years. During relapses, symptoms of abdominal pain, diarrhea, andrectal bleeding worsen. During remissions, these symptoms improve. Remissions usually occur because of treatment with medications or surgery, but occasionally they occur spontaneously without any treatment.

Since there is no cure for Crohn's disease, the goals of treatment are to 1) induce remissions, 2) maintain remissions, 3) minimize side effects of treatment, and 4) improve the quality of life. Treatment of Crohn's disease and ulcerative colitis with medications is similar though not always identical.

Medications for treating Crohn's disease include 1) antiinflammatory agents such as 5-ASA compounds, corticosteroids, topical antibiotics, 2) immuno-modulators, 3) other medications.

Antiinflammatory medications


Antiinflammatory medications that decrease intestinal inflammation are analogous toarthritis medications that decrease joint inflammation. Different types of antiinflammatory medications used in the treatment of Crohn's disease are:


  • 5-ASA compounds such assulfasalazine (Azulfidine) andmesalamine (Pentasa, Asacol, Dipentum, Colazal, Rowasa enema, Canasa suppository) that act via direct contact (topically) with the inflamed tissue in order to be effective.
  • Corticosteroids that act systemically (without the need for direct contact with the inflamed tissue) to decrease inflammation throughout the body. Systemic corticosteroids have important and predictable side effects if used long-term.
  • A new class of topical corticosteroid (for example, budesonide) that acts via direct contact (topically) with the inflamed tissue. This class of corticosteroids has fewer side effects than systemic corticosteroids which are absorbed into the body.
  • Antibiotics such as metronidazole (Flagyl) and ciprofloxacin (Cipro) that decrease inflammation by an unknown mechanism


5-ASA (mesalamine) oral medications


5-aminosalicylic acid (5-ASA), also calledmesalamine, is similar chemically to aspirin. Aspirin has been used for many years for treating arthritis, bursitis, and tendonitis (conditions of tissue inflammation). Aspirin, however, is not effective in treating Crohn's disease and ulcerative colitis, and even may worsen the inflammation. On the other hand, 5-ASA can be effective in treating Crohn's disease and ulcerative colitis if the drug can be delivered topically onto the inflamed intestinal lining. For example, mesalamine (Rowasa) is an enema containing 5-ASA that is effective in treating inflammation in the rectum. However, the enema solution cannot reach high enough to treat inflammation in the upper colon and the small intestine. Therefore, for most patients with Crohn's disease involving both the ileum (distal small intestine) and colon, 5-ASA must be taken orally.

If pure 5-ASA is taken orally, however, most of the 5-ASA would be absorbed in the stomach and the upper small intestine, and very little 5-ASA would reach the ileum and colon. To be effective as an oral agent in treating Crohn's disease, 5-ASA has to be modified chemically to escape absorption by the stomach and the upper intestines.

Sulfasalazine (Azulfidine)

Sulfasalazine (Azulfidine) was the first modified 5-ASA compound used in the treatment of Crohn's colitis and ulcerative colitis. It has been used successfully for many years to induce remissions among patients with mild to moderate ulcerative colitis. Sulfasalazine also has been used for prolonged periods for maintaining remissions.

Sulfasalazine consists of a 5-ASA molecule linked chemically to a sulfapyridine molecule. (Sulfapyridine is a sulfa antibiotic.) Connecting the two molecules together prevents absorption by the stomach and the upper intestines. When sulfasalazine reaches the ileum and the colon, the bacteria that normally are present break the link between the two molecules. After breaking away from 5-ASA, sulfapyridine is absorbed into the body and later eliminated in the urine. Most of the active 5-ASA, however, is available within the terminal ileum and colon to treat the colitis.

Most of the side effects of sulfasalazine are due to the sulfapyridine molecule. These side effects include nausea, heartburn, headache, anemia, skin rashes, and, in rare instances, hepatitis and kidney inflammation. In men, sulfasalazine can reduce the sperm count. The reduction in sperm count is reversible, and the count usually becomes normal after the sulfasalazine is discontinued or changed to a different 5- ASA compound.

Because the newer 5-ASA compounds [for example, mesalamine (Asacol and Pentasa)] do not have the sulfapyridine component and have fewer side effects than sulfasalazine, they are being used more frequently in treating Crohn's disease and ulcerative colitis.


Asacol is a tablet consisting of the 5-ASA compound surrounded by an acrylic resin coating. Asacol is sulfa-free. The resin coating prevents the 5-ASA from being absorbed as it passes through the stomach and the small intestine. When the tablet reaches the terminal ileum and the colon, the resin coating dissolves, and the active 5-ASA drug is released.

Asacol is effective in inducing remissions in patients with mild to moderate ulcerative colitis. It also is effective when used in the longer term to maintain remissions. Some studies have shown that Asacol also is effective in treating Crohn's ileitis and ileo-colitis, as well as in maintaining remission in patients with Crohn's disease.

The recommended dose of Asacol for inducing remissions is two 400 mg tablets three times daily (a total of 2.4 grams a day). At least two tablets of Asacol twice daily (1.6 grams a day) is recommended for maintaining remission. Occasionally, the maintenance dose is higher.

As with Azulfidine, the benefits of Asacol are dose-related. If patients do not respond to 2.4 grams a day of Asacol, the dose frequently is increased to 3.6 - 4.8 grams a day to induce remission. If patients fail to respond to the higher doses of Asacol, then other alternatives such as corticosteroids are considered.


Pentasa is a capsule consisting of small spheres containing 5-ASA. Pentasa is sulfa-free. As the capsule travels down the intestines, the 5-ASA inside the spheres is released slowly into the intestine. Unlike Asacol, the active drug 5-ASA in Pentasa is released into the small intestine as well as the colon. Therefore, Pentasa can be effective in treating inflammation in the small intestine and is currently the most commonly used 5-ASA compound for treating mild to moderate Crohn's disease in the small intestine.

Patients with Crohn's disease occasionally undergo surgery to relieve small intestinal obstruction, drain abscesses, or remove fistulae. Usually, the diseased portions of the intestines are removed during surgery. After successful surgery, patients can be free of disease and symptoms (in remission) for a while. In many patients, however, Crohn's disease eventually returns. Pentasa helps maintain remissions and reduces the chances of the recurrence of Crohn's disease after surgery.

In the treatment of Crohn's ileitis or ileocolitis, the dose of Pentasa usually is four 250 mg capsules four times daily (a total of 4 grams a day). For maintenance of remission in patients after surgery, the dose of Pentasa is between 3-4 grams daily.

Olsalazine (Dipentum)

Olsalazine (Dipentum) is a capsule in which two molecules of 5-ASA are joined together by a chemical bond. In this form, the 5-ASA cannot be absorbed from the stomach and intestine. Intestinal bacteria are able to break apart the two molecules releasing the active individual 5-ASA molecules into the intestine. Since intestinal bacteria are more abundant in the ileum and colon, most of the active 5-ASA is released in these areas. Therefore, olsalazine is most effective for disease that is limited to the ileum or colon. Although clinical studies have shown that olsalazine is effective for maintenance of remission in ulcerative colitis, up to 11% of patients experience diarrhea when taking olsalazine. Because of this, olsalazine is not often used. The recommended dose of olsalazine is 500 mg twice a day.

Balsalazide (Colazal)

Balsalazide (Colazal) is a capsule in which the 5-ASA is linked by a chemical bond to another molecule that is inert (without effect on the intestine) and prevents the 5-ASA from being absorbed. This drug is able to travel through the intestine unchanged until it reaches the end of the small bowel (terminal ileum) and colon. There, intestinal bacteria break apart the 5-ASA and the inert molecule releasing the 5-ASA. Because intestinal bacteria are most abundant in the terminal ileum and colon, balsalazide is used to treat inflammatory bowel disease predominantly localized to the colon.

Side effects of oral 5-ASA compounds

The 5-ASA compounds have fewer side effects than Azulfidine and also do not reduce sperm counts. They are safe medications for long-term use and are well-tolerated.

Patients allergic to aspirin should avoid 5-ASA compounds because they are similar chemically to aspirin.

Rare kidney and lung inflammation has been reported with the use of 5-ASA compounds. Therefore, 5-ASA should be used with caution in patients with kidney disease. It also is recommended that blood tests of kidney function be done before starting and periodically during treatment.

Rare instances of worsening of diarrhea, cramps, and abdominal pain, at times accompanied by fever, rash, and malaise, may occur. This reaction is believed to represent an allergy to the 5-ASA compound.


5-ASA rectal medications (Rowasa Canasa)


Rowasa is 5-ASA in enema form. 5-ASA by enema is most useful for treating ulcerative colitis involving only the distal colon since the enema easily can reach the inflamed tissues of the distal colon. Rowasa also is used in treating Crohn's disease in which there is inflammation in and near the rectum. Each Rowasa enema contains 4 grams of 5-ASA. The enema usually is administered at bedtime, and patients are encouraged to retain the enema through the night. The enema contains sulfite and should not be used by patients with sulfite allergy. Otherwise, Rowasa enemas are safe and well-tolerated.

Canasa is 5-ASA in suppository form. It is used for treating ulcerative proctitis. Each suppository contains 500 mg of 5-ASA and usually is administered twice daily.

Both enemas and suppositories have been shown to be effective in maintaining remission in patients with ulcerative colitis limited to the distal colon and rectum.



Corticosteroids (for example, prednisone,prednisolone, hydrocortisone, etc.) have been used for many years to treat patients with moderate to severe Crohn's disease and ulcerative colitis and to treat patients who fail to respond to 5-ASA. Unlike 5-ASA, corticosteroids do not require direct contact with the inflamed intestinal tissues to be effective.

Oral corticosteroids are potent antiinflammatory medications. After absorption, corticosteroids exert prompt antiinflammatory actions throughout the body, including the intestines. Consequently, they are used in treating Crohn's disease anywhere in the small intestine, as well as ulcerative and Crohn's colitis. In critically ill patients, intravenous corticosteroids (such as hydrocortisone) can be given in the hospital. For patients with proctitis, hydrocortisone enemas (Cortenema) can be used to deliver the corticosteroid directly to the inflamed tissue. By using the corticosteroid topically, less of it is absorbed into the body and the frequency and severity of side effects are lessened (but not eliminated) as compared with systemic corticosteroids.

Corticosteroids are faster-acting than 5-ASA, and patients frequently experience improvement in their symptoms within days of beginning them. Corticoster

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