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Definition
Crohn’s disease is a disease of unknown cause, which is characterized by recurring episodes of inflammation, which can occur anywhere in the intestinal tract. In contrast to ulcerative colitis, the inflammation involves the full thickness of the wall of the intestine (transmural). The transmural inflammation can result in areas of narrowing in the small intestine as well as sinus tracts or fistulas (an abnormal passage from one loop of intestine to another structure, such as to another loop of intestine, skin, or bladder). Crohn’s disease is also often characterized by "skip" areas of normal intestine between areas of involvement. Unlike ulcerative colitis, which involves just the colon, Crohn’s disease can involve any portion of the intestinal tract.
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Causes and Risk Factors
The cause of Crohn’s disease remains unknown. There may be several factors at play. The current thinking is that there may be genetic and environmental factors that provoke an alteration in the way the body’s immune system works.
Genetics: A number of observations suggest that genetically determined factors may contribute to Crohn’s disease. Ten to twenty-five percent of affected individuals have a relative with either Crohn’s disease or ulcerative colitis. Studies of twins also suggest an inherited factor.
Cigarette Smoking: Crohn’s disease is twice as common among smokers as nonsmokers. There is additional evidence that the risk of recurrence of Crohn’s symptoms is increased among smokers.
Immune System: In the process of carrying out the absorption of nutrients, the intestine must discriminate between innocuous food substances and potentially harmful infectious or toxic agents. The immune system serves as a protective barrier to harmful agents. Many studies suggest that Crohn’s disease may be associated with an abnormal immune system. The relationship between immune defects and the development of Crohn’s disease is not certain. It is clear, however, that there is an alteration of regulation of immune responses to various bacteria and other substances. Drugs which suppress the immune system have benefit in treatment of Crohn’s disease.
Diet: No studies have directly identified a specific dietary factor that is either absent, or present in excess, in patients with Crohn’s disease.
Psychosocial Factors: There is no evidence that emotional disturbances cause Crohn’s disease. However, any chronic illness can be stressful and cause anxiety. Furthermore, anxiety and stress in ones personal life can make coping with illness that much more difficult, and may even cause symptoms to worsen.
Oral Contraceptives: Some studies have suggested a correlation between oral contraceptive use and Crohn’s disease. Other studies have contradicted this finding.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs): There is some evidence that some arthritis drugs such as aspirin, ibuprofen (Motrin, Advil), indomethecin (Indocin), and naproxen (Aleve, Naprosyn) may exacerbate Crohn’s disease. The newer cox-2 inhibitors (Celebrex, Vioxx), while safer for the stomach, may still provoke a flare of Crohn’s disease.
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Symptoms
Patients usually present between ages 15 and 40. Because of the variability of extent and location of disease, symptoms can vary greatly from one patient to the next. Approximately 80% of patients have involvement of the small intestine, usually the distal ileum, (ileitis). Approximately 50% have involvement of both the ileum and colon (ileocolitis), and 20% have disease limited to the colon (colitis). About 30% have involvement of the anus and a small number have involvement of the mouth, esophagus, stomach, or duodenum.
Diarrhea, weight loss, abdominal pain, and fever are the most common symptoms. Some patients may have problems with bleeding, and others may have troublesome perianal disease such as hemorrhoids.
In addition, there may be symptoms indirectly related to small bowel disease. Malabsorption of certain nutrients may cause problems such as anemia and kidney stones.
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Diagnosis
A typical history should alert the clinician to the possibility of Crohn’s disease. Prolonged diarrhea with abdominal pain, weight loss and fever are the hallmarks of Crohn’s disease. Physical examination may be normal or there may be a tender mass in the right lower portion of the abdomen, perianal skin tags, or sinus tracts. The intestinal tract is evaluated with endoscopic (colonoscopy or gastroscopy) or radiagraphic studies (small bowel x-ray, CT scan, or barium enema). The choice of procedure depends in part upon the suspected site of involvement.
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Cancer of the Intestinal Tract and Crohn’s Disease
Some persons with Crohn’s may be at increased risk for the development of cancer. The risk is related to the length of time that has elapsed since initial diagnosis, and the extent of involvement. It is not related to the severity of symptoms. The incidence of small bowel cancer in patients with Crohn’s disease is higher than in the normal population. However, because of the rarity of these tumors, the risk to an individual is quite small. Patients with extensive involvement of the colon should have periodic screening with colonoscopy. With proper surveillance, early diagnosis with cure can often be achieved.
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Extraintestinal Manifestations
Crohn’s disease can be associated with a number of non-intestinal problems, some of which are listed below. It is important that your gastroenterologist be notified if you develop any other medical problem, and any other physicians you see should be aware that you have ulcerative colitis. With the exceptions of ankylosing spondylitis and sclerosing cholangitis, which usually run their own course, aggressive treatment of the colitis often results in improvement of the extraintestinal manifestations.
Erythema Nodosum: tender red bumps that often occur over the shins or ankles.
Pyoderma Gangrenosa: chronic ulcers that occur on the shins or ankles.
Apthous Stomatitis: canker sores that occur in the mouth.
Arthritis: small joints of the hands and feet can be involved.
Ankylosing Spondylitis: arthritis of the spine.
Uveitis: a painful inflammation of the eye.
Sclerosing Cholangitis: inflammation in the bile ducts, which can result in jaundice.
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Medical Treatment
There are several types of treatment available, and most patients respond well and go about their lives with few interruptions. Occasionally, some attacks may be more severe requiring periods of bowel rest, intravenous treatment, and hospitalization and surgery.
Corticosteroids: Corticosteroids are a class of medications that are similar to chemicals made by the one’s own adrenal gland. They can be given topically in enema form (Cortenema), orally (prednisone), or intravenously (hydrocortisone or prednisolone). These are highly effective drugs, which often bring symptoms under control within a couple of weeks. Unfortunately, they have many side effects, which include (but are not limited to) water retention and weight gain, bone thinning, acne, mood alterations, sleep disturbance, muscle weakness, cataracts, and increased susceptibility to certain types of infections. Side effects are usually related to the dose and the length of time on the drug, and can usually be managed by reducing the dose. A high dose (40 to 60 mg. of prednisone) is often used initially to bring the symptoms under control. The dose is then reduced at a rate, which is determined by the presence of side effects and any persistent symptoms.
Budesonide: Budesonide (Entocort EC) is a new synthetic corticosteroid that became available in the United States in November, 2001. The formulation contains granules that are coated and released in the small intestine where it has a topical effect (much like the topical effect that the Cortenema has on the lining of the rectum). When the active ingredient is absorbed, it is immediately eliminated from the blood stream by the liver and so it has fewer side effects than other corticosteroids taken by mouth. It is effective for treating Crohn’s disease involving the small intestine and the beginning of the colon. Grapefruit juice can inactivate the granules and should not be taken with budesonide.
5 ASA products: Mesalamine (Pentasa and Asacol) can be very effective in treating mild symptoms and is used as an adjunct to therapy with prednisone in patients with more severe symptoms. These drugs can be very important to take when feeling well since they have been shown to prolong periods of remission and reduce recurrence rates after surgery. They have very few side effects and are also safe to take during pregnancy. Occasionally, at high doses, they can cause headaches or upset stomach. They should be avoided by patients who have allergy to aspirin. Other 5 ASA products such as sulfasalazine (Azulfidine) and olsalazine (Dipentum) have a more limited role in Crohn’s disease since they have benefit in the colon but not the small intestine.
Azothioprine (Imuran) and 6- Mercaptopurine (Purinethol): For those whose symptoms remain troublesome despite intensive therapy with prednisone and mesalamine, these immune suppressing drugs may be helpful. After 3 to 4 months of therapy, they may allow a reduction in the dose of prednisone.
Antibiotics: Antibiotics may be helpful for some patients. Metronidazole is the most widely studied. Antibiotics are widely used for the treatment of abscesses, which may occur in the perianal region or associated with inflammation in the terminal ileum. There is some limited evidence that they may be helpful postoperatively to prevent relapse.
Infliximab (Remicade): Infliximab is an antibody directed against a substance called "tumor necrosis factor, alpha" (TNFa). TNFa is elevated in the stools of patients with Crohn’s disease and correlates with disease activity. It has several biologic functions, which may play a role in the development of inflammatory bowel disease. Infliximab neutralizes some of the activity of TNFa and has been shown to be useful in the treatment of Crohn’s disease. Early studies suggest that it may be particularly useful for patients with fistulas, and that the benefit of a single dose may last several months. The long term benefits and risks are not yet known. The manufacturer provides a summary of clinical trials at its web site http://www.centacor.com/remicade.htm
Cyclosporine: Cyclosporine suppresses the immune system and may be of some benefit in treating patients with refractory fistulas. Therapy is usually initiated in the hospital.
Fish Oil: One study showed benefit from a four month course of eicoapentaenoic acid (EPA) derived from fish oil. However, this study was flawed by the lack of a good control group. This therapy requires about 18 capsules per day and causes a fishy odor in the breath.
Nutritional Considerations: Although dietary factors have not been implicated in the cause of Crohn’s, food intolerances may occur. More importantly, chronic illness, poor appetite, chronic blood loss, and intestinal dysfunction can lead to malnutrition. Therefore it is very important to discuss with your doctor the best way to balance nutritional needs with specific food intolerances, which may occur. Specific vitamin and mineral supplementation may be warranted. In patients with abdominal pain it may be advisable to avoid raw fruits and vegetables, caffeine, carbonated drinks, and sorbitol containing diet foods. If there is a lactose intolerance, milk should be avoided and a calcium supplement taken. If there is frequent bleeding, iron supplementation may be needed.
Psychosocial Considerations: Coping with chronic illness can be very stressful. For some patients, support groups organized by the Crohn’s & Colitis Foundation of America (CCFA) can be helpful. Generally, medications are not needed for psychological distress associated with a flare of Crohn’s. However, some individuals may experience greater difficulties with anxiety or depression and benefit from medication.
Constipating agents: Medications such as loperimide (Imodium) and lomotil may be helpful. If the cause of diarrhea is thought to be malabsorption of bile salts from the terminal ileum, then bile salt binding resins such as cholestyramine (Questran) may be helpful.
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Surgery
Surgery is often needed at some time during the course of Crohn’s disease. Occasionally an abscess may need to be drained or a fistula excised (removed). Surgical removal of the diseased portion of the bowel may result in a symptom free period that may last years. However, surgery does not cure Crohn’s disease and therefore should be used as an adjunct to medical therapy to control specific problems that may occur. For most patients, it is important to use drugs such as mesalamine after surgery to delay relapse.
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Pregnancy and Crohn’s Disease
Women with Crohn’s disease have normal deliveries and healthy babies in roughly the same proportions as healthy women in the general population. However, any women contemplating pregnancy should consider the state of her health before conceiving. It is generally a good idea for a woman to have her disease in remission before pregnancy. Women with active Crohn’s disease have a slightly higher risk of premature delivery, stillbirth, or spontaneous abortion. Prednisone, sulfasalazine, and 5-ASA compounds (Dipentum, Asacol, Pentasa) are safe during pregnancy. In fact, drugs such as the 5-ASA compounds, which can prevent relapse, should generally be continued during pregnancy since a flare of the disease is more hazardous than the medications. On the other hand, immunosuppressive drugs such as cyclosporine, azothioprine, and 6-mercaptopurine may cause genetic damage and should be avoided if pregnancy is anticipated.
It is probably safe to nurse while taking 5 ASA products or small doses of prednisone. Small amounts of these drugs may pass into breast milk. Five ASA products have not been shown to be harmful to the newborn. Large doses of prednisone could the affect the baby.
For more information on Crohn’s disease, contact Crohn’s & Colitis Foundation of America (CCFA).
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