Treatment of Crohn's disease depends on its severity and the extent of gastrointestinal tract involvement. The aims of treatment are to achieve remission of symptoms, to suppress active inflammatory disease, to conserve the bowels, and to maintain remission. Surgery is generally reserved for managing serious complications, such as fistulas, abscesses, or bowel obstructions that may occur as the walls of the intestines narrow from scar tissue after years of inflammation, or Crohn's disease that doesn't get better with non-surgical therapy.
Generally, with proper medications, symptoms resolve in the first few days or weeks. If symptoms persist, physicians often suspect bowel obstruction, abscess, or an error in diagnosis.
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There are a variety of medications available for treating Crohn's. They generally fall into these categories:
The most common anti-inflammatory drugs used to treat mild Crohn's disease are 5-aminosalicylate-containing agents, or 5-ASAs. Compounds of 5-aminosalicyclic acid are chemical cousins to aspirin (acetylsalicylic acid). (Aspirin and the common non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen are associated with ulceration of the gastrointestinal tract and with increased risk of Crohn's disease flares. The 5-aminosalicyclic acid compounds are associated with a decreased risk of Crohn's flares and are not associated with Crohn's disease ulcerations.) Aminosalicylates have anti-inflammatory effects on the mucosa lining the organs of the GI tract. They also inhibit the function and production of immune system cells.
Several aminosalicylates are available for the treatment of Crohn's disease. Oral 5-ASAs include balsalazide (Colazal), olsalazine (DiPentum), mesalamine (Asacol and Pentasa), and sulfasalazine (Azulfidine). Rectal 5-ASA treatments include mesalamine enemas (Rowasa) and suppositories (Canasa).
These compounds can be targeted to sites along the gastrointestinal tract. Asacol, for example, is coated with a pH-sensitive acrylic polymer to release the 5-ASA in the distal ileum and colon. Sulfasalazine contains a sulfa group chemically bound to the 5-ASA group. The 5-ASA group is released in the colon upon digestion from colonic bacteria where it may treat Crohn's colonic inflammation. There is some evidence that the entire sulfasalazine compound may also have anti-inflammatory effects and sulfasalazine has also been used to treat psoriasis and arthritis. Balsalazide uses the same principle as sulfasalazine. It has an inert compound chemically bound to the 5-ASA group; the 5-ASA group is similarly released upon digestion by colonic bacteria. Balsalazide and 5-ASA coated therapies have an advantage of generally fewer side effects compared to sulfasalazine, and the non-sulfa compounds can be used in patients with sulfa allergies. Pentasa is made up of coated granules that have greater release of 5-ASA in the ileum as well as the colon and hence is often preferred for patients with ileal Crohn's disease. Rectal and sigmoid colonic Crohn's disease can be treated with 5-ASA enema and suppository therapies.
Antibiotics have a modest effect on Crohn's disease, with greater evidence in clinical trials than the 5-ASA medications. There is evidence that antibiotics are more effective in Crohn's colitis than Crohn's ileitis. They are particularly used to treat perianal disease, including fistulas, and in all abscesses associated with Crohn's disease. The most commonly used antibiotic is metronidazole (Flagyl), an antibiotic also prescribed for treating parasites and vaginal infections. It is particularly useful for Crohn's patients who have anal fistulas. Metronidazole interacts badly with alcohol, so patients taking the drug should refrain from drinking. Chronic use at high doses has been associated with permanent nerve damage, so the drug should be stopped if patients experience numbness or tingling in their fingertips, toes, or other extremities.
Ciprofloxacin (Cipro), another antibiotic, is commonly used in treating mild to moderate Crohn's disease. It is sometimes prescribed in combination with metronidazole for Crohn's disease, particularly for abscesses and anal disease.
Corticosteroids improve symptoms in about 75 percent of patients. Corticosteroids are most effective when given intravenously. They are usually given to hospitalized patients and for severe Crohn's disease flares. Intravenous corticosteroids include methylprednisolone and hydrocortisone. Oral corticosteroids include prednisone, methylprednisolone, and hydrocortisone. Recently, a topical therapy, budesonide (EntocortEC),has been used in mild to moderate ileal Crohn's disease. It has the advantage of having fewer systemic side effects relative to the effect on the ileum. Topical therapies for disease in the rectum include rectal foams (ProctoFoam-HC), rectal enemas (Cortenema), and suppositories. Patients may experience rapid improvement in symptoms.
Short courses of systemic steroids usually have mild side effects, but the side effects increase with their dose and duration of use. Long term, high-dose corticosteroids result in potentially serious side effects. These may include increased body hair, diabetes, weight gain, high blood pressure, cataracts, glaucoma, increased susceptibility to infections, mood swings, and osteoporosis with accompanying fractures. One of the most serious side effects associated with long-term use of steroid drugs is aseptic necrosis of the hip joints, or the death of bone tissue in the hips, ultimately requiring hip replacement. Aseptic necrosis of the knee joints has also been reported.
Because osteoporosis is a common complication of Crohn's disease, all patients need to be monitored periodically for bone loss with bone density scans. This is particularly true of those patients who are taking corticosteroid drugs. If there is evidence of bone loss, therapy with a bone-building drug, such as a bisphosphonate or calcitonin, is necessary. Weight-bearing exercise, calcium supplements, and vitamin D are also recommended to protect the bones.
Budesonide is a new type of oral steroid that works by direct contact with the inflamed tissues and is considered a nonsystemic steroid. Budesonide capsules have been formulated to allow a slow release of the drug into the ileum and the right side of the colon, with most released in the terminal ileum, the tip of the small intestine. Patients tend to experience fewer systemic side effects than the more completely absorbed corticosteroids, although there is still evidence that it can cause osteoporosis.
Immunomodulators are drugs that weaken or suppress the immune system. While the immune system protects the body from harmful bacteria, viruses, and other invaders, activation of the immune system results in inflammation. Immunomodulating drugs decrease tissue inflammation by reducing the population of activated immune cells or interfering with the production of proteins that summon the immune cells to an organ. Some of these drugs used to treat Crohn's disease include 6-mercaptopurine (6-MP or Purinethol), azathioprine (Imuran or Azasan), and methotrexate. Immunomodulator therapy has been shown to be more effective than steroids in maintaining remission. Remission can be achieved in over 60 percent of patients.
The drugs 6-MP and azathioprine (Purinethol and Imuran) are related molecules given orally for Crohn's disease of the small intestine and colon. They are quite effective in treating Crohn's disease but have a slow onset of effect (two to four months). Because of this, they are often given along with a corticosteroid, with the intention of gradually decreasing the steroid dose as the 6-MP or azathioprine takes effect. Azathioprine rapidly gets metabolized in the blood to 6-MP. 6-MP in turn is metabolized in immune cells to the active compound 6-thioguanine (6-TG). It is the 6-TG that results in elimination of chronically activated immune cells. 6-TG can suppress the bone marrow, requiring close monitoring of the blood while on therapy. Some people are genetically susceptible to bone marrow suppression with only small doses of azathioprine or 6-MP. They lack the normal enzyme (called TPMT) which rapidly detoxifies 6-TG. In addition, both can adversely affect the liver and pancreas. 6-MP and azathioprine increase the risk of lymphoma and skin cancer, and with bone marrow suppression increase the risk of serious infections.
Methotrexate (Rheumatrex) is an alternative to 6-MP or azathioprine. It is typically given as an intramuscular or subcutaneous injection once a week. It is effective in about 40% of patients with Crohn's disease that doesn't respond to steroids. Methotrexate may cause interstitial pneumonitis, which often presents as a cough and difficulty breathing. Patients need to be monitored for bone marrow suppression. Methotrexate can cause liver damage, especially in patients treated long-term and in those that use alcohol or have pre-existing liver disease.
Cyclosporine (Sandimmune and Neoral), also used to suppress organ rejection after a transplant, has been used successfully in patients whose illness did not respond to steroid drugs. It may be especially helpful in fistulizing Crohn's disease. However, cyclosporine has a number of side effects, including fever, rash, nausea, low white cell count, kidney failure, and hepatitis. Inflammation of the pancreas, or pancreatitis, may occur in 3 to 15 percent of patients on the drug. It is generally used as a last resort when other immunomodulators or anti-Tumor Necrosis Factor Alpha medications are not effective.
Anti-Tumor Necrosis Factor Alpha medications Biologic therapies are genetically engineered medicines that have been made to treat human diseases. The major biological agents used to treat Crohn's disease are anti-Tumor Necrosis Factor Alpha antibodies (anti-TNF-alpha antibodies). The first FDA-approved biologic therapy was infliximab (Remicade), approved in 1998. It is currently approved for the treatment of Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, and psoriasis. TNF-alpha is a molecule that is found at higher levels in active Crohn's disease. It is important for producing inflammation. More recent modifications of infliximab include adalimumab (Humira) and certolizumab-pegol (Cimzia), which is retained in the body for longer periods. Infliximab is given by intravenous (IV) infusions initially three times over 6 weeks and then every 8 weeks. Adalimumab and certolizumab-pegol are given by subcutaneous injection every two weeks and monthly, respectively.
Studies show some 60 percent of Crohn's patients with moderate to severe disease show improvement on anti-TNF-alpha medications, with 35% to 50% achieving remission. The anti-TNF-alpha medications seem particularly helpful for patients with perianal fistulizing Crohn's disease. Inflliximab has also been found to prevent recurrence after surgical resection of bowel segments involved with Crohn's disease.
Anti-TNF-alpha medications increase the risk of serious and potentially life-threatening infections, including tuberculosis and histoplasmosis. All patients receiving these medications should be tested for tuberculosis exposure (and treated if exposed) before they start taking these medications. Like 6-MP and azathioprine, these medications increase the risk of lymphoma and may increase the risk of solid tumors. They should not be used in people with significant congestive heart failure or demyelinating disorders.
Natalizumab (Tysabri) is an antibody against the cellular adhesion molecule α4-integrin. α4-integrin is required for immune cells (white blood cells) to cross blood vessels and into tissues. Natalizumab was approved in 2008 for use in Crohn's disease and multiple sclerosis. It is meant for moderate to severe Crohn's disease that hasn't responded to other medical therapies, including anti-TNF-alpha or immunomodulator medications. Because of a small risk of a potentially fatal brain disorder, progressive multifocal leukoencephalopathy (PML), natalizumab has a restricted approval by the FDA. That means it can only be used through a monitored program. As with 6-MP and azathioprine, patients taking Natalizumab have to be monitored for liver injury.
It is estimated that 60 percent of patients with Crohn's disease will need surgery to remove a section of the small or large intestine within 10 years of their first symptoms. This is more common in patients with disease involving the small intestine (as opposed to those whose disease is restricted to the colon). Surgery is often required for complications of obstruction, abscesses, fistulas, and disease that doesn't respond to medications. Surgery is not a cure for Crohn's disease, so 60 percent of patients who undergo an operation experience clinical recurrence of the illness. When surgery removes portions of the ileum, the ability to absorb vitamin B12 may be reduced or lost and B12 injections are required to avoid serious consequences of vitamin deficiencies.
The most likely complications of Crohn's disease are abscesses, fistulas, and obstructions. These are usually managed with medications and surgery.
Abscesses: Abscesses occur in 15 to 20 percent of patients with Crohn's disease. The symptoms of an abscess are fever and pain in the region affected including the abdomen, pelvis, perineum, ano-rectal region and back. A high white cell count may be found in a blood test. Abscesses are often first treated with antibiotics and drainage. Occasionally patients are put on total intravenous nutrition so that less material passes through the bowel. Abscesses frequently require surgical removal of the area involved. Sometimes the rectum and other parts of the large intestine have to be removed.
Fistulas and Perianal disease: Fistulas occur in about 40 percent of patients with Crohn's disease. Generally, these abnormal passages are formed when a deep abscess penetrates into an adjacent organ or the skin. Fistulas are most common around the anus. The terminal ileum of the small intestine is another site that is frequently involved.
Symptoms of fistulas depend on the site and where the fistulas drain. Fistulas that go from the small intestine to the skin are particularly problematic. These usually require surgery. Fistulas that go from one segment of the bowel to another can cause diarrhea, weight loss, and nutritional deficiencies. These fistulas often do not require treatment. If they have symptoms, they can be treated with anti-TNF-alpha therapy or immunomodulators.
Perianal and perineal fistulas may involve the skin around the anus, the groin, vulva, vagina, and scrotum. Painful abscesses (exacerbated by defecation, sitting, or walking) and fever may accompany this complication.
For perianal fistulas, treatment is aimed at relief of symptoms and preservation of the anal sphincter. Fistulas that are not causing symptoms need no treatment. Sitz baths and antibiotics may be the first form of treatment. Antibiotics and anti-TNF-alpha medications are often given. Perianal fistulas and fistulas often requjre surgical placement of a suture or other material through the fistulas (called a "seton") and then to the opening of the anus on one side and the rectum on the other side to help the fistulas drain properly rather than cause an abscess. In severe cases permanent fecal incontinence occurs, and you may need the bowel to be diverted or removed.
Obstructions: Obstruction of the small intestine is a common complication of Crohn's disease and a major indication for surgery. As a result of acute inflammation, the wall of the small bowel thickens and scarring may occur, obstructing the flow of intestinal contents. The symptoms of a bowel obstruction are abdominal pain, rumbling sounds in the stomach, feeling full sooner than usual when you eat, and occasionally diarrhea. Nausea and vomiting may accompany episodes of obstruction. These symptoms may disappear with fasting. Depending on the location of the obstruction, barium studies, CT scans, and colonoscopy may be useful in evaluating the location of the obstruction and areas of narrowing in the intestines.
The initial treatment for an obstruction is to give nothing by mouth, suction out the stomach through a nasogastric tube, and provide intravenous fluids. Steroid drugs and occasionally anti-TNF-alpha biologics may help reduce inflammation. Patients are required to go on diets that minimize poorly digested fruits and vegetables. If the obstruction does not clear with this treatment, surgery to remove the obstruction or the bowel segment may become necessary.
Colon cancer: The risk of colon cancer is increased in patients with Crohn's disease involving the colon. Those who have had Crohn's disease for eight to 10 years should undergo colonoscopy screening at twoyear intervals. Crohn's patients battling the illness for 20 years or more should be screened for colon cancer yearly. During such a screening colonoscopy in the Crohn's patient, taking at least 30 biopsy samples of the colon lining is recommended so a pathologist can look for microscopic evidence of pre-cancerous lesions known as "dysplasia."
Last reviewed on 6/4/09
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