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Crohn's disease is an inflammatory bowel disease characterized by severe, chronic inflammation of the intestinal wall or any portion of the gastrointestinal tract. The lower portion of the small intestine (ileum) and the rectum are most commonly affected by this disorder. Symptoms may include watery diarrhea, abdominal pain, fever, and weight loss. The symptoms of Crohn's disease can be difficult to manage and proper diagnosis is often delayed. The exact cause of Crohn's disease is unknown.
Crohn's disease typically affects the lower portion of the small intestine (ileum) and/or the colon, especially the right colon. Occasionally, inflammation may occur in the middle and lower portions of the small intestine (jeunoileitis). In some cases, there is inflammation of the membranes that line the mouth (mucous), the esophagus, and/or stomach.
The symptoms of Crohn's disease may begin abruptly or appear slowly over a long period of time. Symptoms that may develop over time include nausea, vomiting, fever, night sweats, loss of appetite, a general feeling of weakness (malaise), waves of abdominal pain and discomfort, diarrhea and/or bleeding from the rectum. Weight loss is common in people with Crohn's disease.
Acute attacks of Crohn's disease may cause fever, elevated white blood cell counts, and/or severe pain in the lower right abdomen. These symptoms are frequently confused with appendicitis.
Crohn's disease may cause lesions (pathological changes) in the intestinal wall and the surrounding lymph nodes. Abscesses in the anorectal area may occur before the appearance of other symptoms. Grooves on the inner surface of the intestines (fissures) may also occur. These may feel like a solid mass in the abdomen and when the mucosal lining of the intestines becomes thickened, it may feel like cobblestones. Deep open abscesses (fistulas), scarring, and some degree of intestinal obstruction may occur as a result of chronic inflammation of the intestine. In some cases, fistulas and abscesses may create an opening through the intestinal wall and result in infection by the bacteria that occur naturally in the intestines (septicemia). Massive, abnormal enlargement of the colon (toxic megacolon) is a serious complication of Crohn's disease and may result in intestinal bleeding into the abdomen and septicemia.
When Crohn's disease causes intestinal obstruction, the symptoms may include pain, constipation, swelling of the abdomen, and/or vomiting. This may be due to the accumulation of fluid (edema) in the intestines or thickening of the muscosal layers of the intestinal walls. Inflammation and obstruction may occur together and can impair digestion and the absorption of food and may lead to malnutrition.
Crohn's disease rarely occurs in children, and is characterized by failure to thrive, fever, and/or abnormally low levels of circulating red blood cells (anemia). Children may also experience joint pain and stiffness (arthritis). Growth and sexual development are often delayed. Initially, children with Crohn's disease may not experience diarrhea or abdominal pain.
People with Crohn's disease may have anemia, abnormally low levels of albumin in the blood (hypoalbuminism), abnormally high white blood cell counts, and/or a deficiency of vitamin B-12. Other laboratory findings may include abnormally low blood levels of sodium, potassium, calcium, and/or magnesium.
Individuals with Crohn's disease may also have symptoms that are not related to intestinal dysfunction. These may include joint pain, or skin and eye problems. A fatty like substance (amyloid) may accumulate in various parts of the body. Blood circulation may be impaired by abnormally thick blood, dehydration, and/or lack of movement or exercise. In some cases, arthritis may occur resulting in swollen and painful joints.
In rare cases of Crohn's disease, liver function may be impaired. These complications may include a fatty liver, inflammation of the liver and the bile ducts, chronic hepatitis, and/or cirrhosis. Kidney stones may also occur. In some cases, affected individuals may experience diminished bone mass resulting in thinning and weakness of the bones (osteoporosis).
The exact cause of Crohn's disease is unknown. The clustering of this disease within some families may suggest a genetic or environmental influence.
Scientists believe 10 to 30 percent of Crohn's disease patients may have inherited the disorder, but its genetic inheritance pattern is still unknown.
A study on Crohn's disease and ulcerative colitis (Denmark, 1991) suggested that relatives of people with either of these diseases are at an increased risk for developing the disease. The risk factor may be as great as a ten fold increase. The study also suggested that Crohn's disease and ulcerative colitis may be inherited.
Researchers believe that a susceptibility gene for Crohn's disease may be located on chromosome 16 from band p12-q13. Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as "p" and a long arm identified by the letter "q." Every chromosome also has a narrowed region at which the two arms are joined (centromere). Chromosomes are further subdivided into bands that are numbered. For example, "chromosome 16p12-q13" refers to band 12 on the short arm of chromosome 16 through band 13 on the long arm of chromosome 16 (including the centromere).
Some of the complications of Crohn's disease suggest that immunological agents may be responsible in part for the disease. Other research suggests that infectious agents may play a role in causing Crohn's disease. Emotional conditions do not cause this disease, although the psychological effects of the disease are recognized.
Crohn's disease affects males and females in equal numbers. The disorder is most common among Caucasians. Individuals of Jewish ancestry are affected approximately three to six times more frequently than others. Approximately one in 800 children in the United States have Crohn's disease, and a total of approximately 400,000 individuals in the United States have the disorder. Approximately 25 percent of individuals with Crohn's disease are likely to have a relative with either Crohn's disease or ulcerative colitis.
Crohn's disease typically affects individuals between the ages of 15 to 55 years. Most cases are diagnosed before 30 years of age. However, the disorder may also occur in young children and the elderly.
Symptoms of the following disorders can be similar to those of Crohn's disease. Comparisons may be useful for a differential diagnosis:
Ulcerative colitis is an acute inflammatory bowel disease characterized by diarrhea and blood in the stools because of multiple, irregular ulcerations of the bowel. The initial symptoms of this disorder may include a general feeling of weakness (malaise) and fatigue. There may be abdominal discomfort, along with a change in the frequency and consistency of stools. Other symptoms may include abdominal pain, cramping, and urgency (tenesmus). Weight loss and a decrease in appetite are also associated with ulcerative colitis. (For more information on this disorder, choose "Ulcerative Colitis" as your search term in the Rare Disease Database.)
Primary sclerosing cholangitis is a rare collagen disorder involving inflammation and blockage of the bile duct, liver ducts, and gallbladder. Symptoms of this disorder include abdominal pain, loss of appetite, nausea, vomiting, and/or weight loss. Later symptoms may include a yellow discoloration to the skin (jaundice), fever, chills, and/or itching of the skin. Bacterial infections resulting from ulcerative colitis, Crohn's disease, and/or vasculitis may be associated with bile duct blockages of primary sclerosing cholangitis. (For more information on this disorder, choose "Primary Sclerosing Cholangitis" as your search term in the Rare Disease Database.)
Chronic erosive gastritis is an inflammatory disorder characterized by multiple lesions in the mucosal lining of the stomach. Symptoms of this disorder may include a burning or heavy feeling in the stomach, mild nausea, vomiting, loss of appetite and general weakness. In severe cases of chronic erosive gastritis there may be bleeding from the stomach that can result in anemia. (For more information on this disorder, choose "Chronic Erosive Gastritis" as your search term in the Rare Disease Database.)
Glucose-galactose malabsorption (carbohydrate intolerance) is a rare inherited disorder characterized by the inability of the small intestine to transport and absorb glucose and galactose. The symptoms of this disorder in children may include diarrhea, dehydration, and failure to gain weight. In adults, symptoms of this disorder may include bloating, nausea, diarrhea, abdominal cramps, rumbling sounds caused by gas in the intestine (borborygmi), and/or excessive urination. (For more information on this disorder, choose "Glucose-Galactose Malabsorption" as your search term in the Rare Disease Database.)
Irritable bowel syndrome, also known as spastic colon, is a common digestive disorder that involves both the small intestine and the large bowel. This disorder is characterized by abdominal pain, constipation, bloating, nausea, headache, and/or diarrhea. The spastic colon type of this syndrome is characterized by variable bowel movements and abdominal pain that is associated with periodic constipation or diarrhea. Those patients with irritable bowel syndrome who have painless diarrhea may experience an urgent need to defecate upon arising. (For more information on this disorder, choose "Irritable Bowel Syndrome" as your search term in the Rare Disease Database.)
Other digestive diseases with similar symptoms include infectious diseases such as yersinia enterocolitica infection, amebiasis, chronic fungal bowel infections, intestinal tuberculosis, pseudomembranous colitis that is caused by excessive use of antibiotics, and certain venereal diseases. Ischemic colitis and certain cancers such as abdominal lymphoma may also have symptoms that are similar to those of Crohn's disease.
The treatment of Crohn's disease is aimed at relieving the symptoms and halting or slowing the inflammation and destruction of affected tissues. Sulfasalazine is a drug often used in the extended treatment of low grade intestinal inflammation.
People with Crohn's disease may also be treated with diphenoxylate, loperamide, opium tincture, or codeine to help relieve abdominal cramps and diarrhea. Hydrophilic mucilloids (methylcellulose or phyllium preparations) may help prevent anal irritation by increasing stool firmness. Broad spectrum antibiotics that are effective against certain bacteria may be helpful in reducing the symptoms of active Crohn's disease but may be more beneficial for those individuals who have intestinal abscesses or fistulas.
Metronidazole is a drug that has been shown to be beneficial in the treatment of Crohn's disease. This drug may reduce fever and diarrhea and relieve abdominal pain and tenderness. Metronidazole is used primarily in affected individuals who do not respond to sulfasalazine.
During acute inflammatory episodes, corticosteroids (e.g., prednisone and hydrocortisone) may help to alleviate certain symptoms, such as fever or diarrhea. However, such therapy may provoke many side effects if used over long periods of time. In addition, corticosteroids should be avoided when obvious infections are present because they impair the function of the immune system.
Nutrition is an important consideration for people with Crohn's disease, especially in children and when obstructions and fistulas are present. Vitamins, particularly B12, and minerals must be added to the daily diet. In cases of Crohn's disease where there is impairment in the ability to digest fats, affected individuals should follow a low-fat diet. A medically prescribed liquid diet (elemental supplementation) may be useful when eating is difficult. The ingestion of greater than average amounts of nutrients (hyperalimentation) may help to prepare affected individuals for surgery and to supplement their diets after surgery. In addition, in general, a low-fiber diet is advised for people with Crohn's disease.
The drug infliximab (Remicade) has been approved by the Food and Drug Administration (FDA) for the treatment of individuals with Crohn's disease. The antibody, cA2, is believed to assist in resetting the body's "immuostat," a kind of thermostat that helps to keep the immune system from overreacting. This drug is manufactured by:
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The FDA has approved a labeling supplement to cyanocobalamin (Nascobal) that allows the drug to be used to treat individuals with Crohn's disease who have vitamin B12 deficiency. The drug effectively maintains appropriate levels of vitamin B12. Nascobal is marketed is the United States by Schwarz Pharma. Nascobal is manufactured by Nastech Pharmaceutical Company, Inc.
The FDA has approved the drug budesonide (Entocort EC) for the treatment of mild to moderate active Crohn's disease affecting certain sections of the small and large intestines. Clinical studies demonstrated that oral controlled-release budesonide was effective in treating Crohn's disease that affects the ileum and ascending colon. Budesonide is a glucocorticoid that is easily absorbed and causes fewer systemic side effects than other corticosteroids. The drug is developed by AstraZeneca LP of Wilmington, DE.
Certain people with Crohn's disease may be considered for surgery when they have not received any relief for their symptoms (intractable disease) through the use of pharmaceuticals or in cases of intestinal obstruction such as fistula and/or abscess. The disease tends to recur in approximately 50% of patients after five years and further surgery may eventually be required.
Certain medications that suppress or reduce the activities of the immune system (immunosuppressive agents), such as 6-mercaptopurine or azathioprine, may also be used to treat Crohn's disease, such as for those who have not adequately responded to other therapies, to help end corticosteroid use, and to maintain periods in which there is a lessening or cessation of symptoms (remission). In many cases, the use of such medications may not produce noticeable improvement of symptoms for about three to six months following initiation of therapy. In addition, such treatment may result in potentially severe adverse effects, such as suppressing bone marrow activity (myelosuppression), resulting in low levels of certain white blood cells (leukopenia), red blood cells (anemia), and/or platelets (thrombocytopenia). Close monitoring is essential for those who receive such therapy, including tests to regularly evaluate blood cell counts and liver (hepatic) status.
On January 14th 2008, The U.S. Food and Drug Administration approved Tysabri (natalizumab) for the treatment of moderate-to-severe Crohn's disease in patients with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional Crohn's disease therapies. Crohn's disease patients using the drug must be enrolled in a special restricted distribution program called the Crohn's Disease"Tysabri Outreach Unified Commitment to Health (CD TOUCH) Prescribing Program.
The approval is consistent with an agency advisory committee recommendation to approve Tysabri for use in Crohn's patients. Tysabri was approved by the FDA in June 2006 to treat relapsing forms of multiple sclerosis.
Because of these risks, patients, prescribers, pharmacies, and infusion centers must all be enrolled in CD-TOUCH and agree to comply with the company's strict monitoring guidelines. Additionally, they must participate in an extensive educational program designed to inform people about the risks of Tysabri treatment. Tysabri is administered intravenously by trained professionals at infusion centers.
Under CD-TOUCH, health care providers evaluate Crohn's disease patients after three months of treatment to determine if they have improved on Tysabri. If not, patients should discontinue treatment. People who are taking steroids for Crohn's disease should begin tapering steroid doses while on Tysabri. Treatment should be discontinued if steroids cannot be fully tapered within six months.
Tysabri is manufactured by Biogen Idec of Cambridge, Massachusetts and Elan of Dublin, Ireland. Both companies have agreed to conduct long-term surveillance for safety, including monitoring and expedited reporting of PML infections, other serious opportunistic infections, malignancies, and deaths in people treated with Tysabri.
In April 2008 Cimzia (certolizumab pegol) received approval for adults with moderate to severe Crohn's disease who have not responded to conventional therapies. This product was approved with a Medication Guide. Patients treated with Cimzia will receive an injection every two weeks for the first three injections. Once benefit has been established, Cimzia should be given once every four weeks.
The most common side effects of Cimzia are headache, upper respiratory infections, abdominal pain, injection site reactions and nausea.
Patients taking Cimzia are at increased risk for serious adverse effects, including serious infections that can lead to hospitalization or death. Because Cimzia affects the immune system, it can lower the body's ability to fight infections, such as tuberculosis and other opportunistic infections. Cimzia is a blocker of TNF (tumor necrosis factor) and may cause lymphomas (a form of cancer) and other malignancies. Although an increased risk of tumors was not seen in studies of Cimzia, the modest size and relatively short duration of the controlled studies prevents any firm conclusion. Post-marketing studies and clinical trials will be required to obtain long-term safety data.
Patients taking Cimzia should be educated about how to identify an infection and be instructed to contact their health care professional at the first sign of infection while on Cimzia. In cases of serious infections, the drug should be discontinued immediately.
Cimzia is manufactured by UCB, Inc., Smyrna, GA.
Other treatment for Crohn's disease is symptomatic and supportive.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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In 2006, NPS Pharmaceuticals announced that it would continue advanced clinical testing of teduglutide, the company's product in development for treating moderate-to-severe Crohn's disease and other gastrointestinal diseases. For information, contact the company:
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The New England Journal of Medicine reported (Nov. 11, 2004) that an initial clinical trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) found that up to 75 percent of Crohn's disease patients responded favorably to a new treatment, and that up to 50 percent of those patients had long-term remission of symptoms. The new treatment is an antibody designed to disable interleukin-12 (IL-12), an immune system protein involved in inflammation. People with Crohn's disease produce excess IL-12. Additional studies will be conducted to test this treatment approach in a larger group of volunteers. The trial was conducted in 15 centers throughout the United States, Germany, and the Netherlands.
Infliximab (Remicade) is a medication that has been approved for the treatment of individuals with Crohn's disease. (For more information, please see the Standard Therapies section above.) A multicenter, randomized, double-blind trial was conducted to study the effectiveness of intravenous infliximab therapy in those who develop draining channels (fistulas) between certain regions of the intestine and the surface of the skin (enterocutaneous fistulas). The study included 94 adults who had draining fistulas as a complication of Crohn's disease for at least three months. In the majority of the study's participants who received infliximab therapy, there was a 50 percent or more decrease in the number of draining fistulas. In addition, some participants demonstrated closure of all fistulas. The fistulas remained closed an average of three months. The study's researchers conclude that infliximab therapy is effective for the treatment of fistulas in individuals with Crohn's disease. However, they indicate that further research is necessary to determine the overall appropriate use and long-term safety and effectiveness of infliximab as a therapy for fistulas in individuals with the disease.
Studies conducted by the Medical College of Wisconsin demonstrated that children with active, severe Crohn's disease who did not respond to conventional therapy during four months and had become dependent on steroid therapy (steroid-dependent children) showed dramatic improvement after treatment with infliximab. These children were able to decrease steroid usage four weeks after infusion with infliximab. Children with early forms of Crohn's disease (up to two years from diagnosis) displayed a significantly longer response to the drug than those who had been diagnosed with Crohn's disease more than two years earlier.
Studies are being conducted in the use of gammaglobulin as a treatment for Crohn's disease. Further investigation is needed to determine the long-term safety and effectiveness of this treatment.
Researchers have used high doses of the drug metronidazole to treat affected individuals who have just had surgery to remove affected areas of the small intestine (ileal resection). Individuals who received such therapy had lower rates of recurrence. However, in some individuals, it was necessary to discontinue therapy due to side effects.
Cyclosporine and methotrexate are immune-suppressing drugs that are also being investigated for use in the treatment of Crohn's disease, especially in those people who do not respond to other therapies. These drugs are used by organ transplant patients. Further study is required to determine the long-term safety and effectiveness of these treatments.
The drugs CDP571 and TAK-603 have received orphan drug designations for use in the treatment of Crohn's disease.
The drug thalidomide (Thalomid) has received an orphan drug designation for its use in the treatment of individuals with Crohn's disease. Thalidomide can have severe effects on a develping fetus and must be administered with extreme caution. More studies are needed to determine the long term safety and effectiveness of this drug for the treatment of Crohn's disease. For more information, please contact:
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Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 266600; 4/19/99. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?266600.
Report last updated: 2008/04/23 00:00:00 GMT+0