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Crohn's Disease and Ulcerative Colitis

Inflammatory bowel disease is a term that encompasses both ulcerative colitis and Crohn's disease - diseases that affect millions of Americans. These disorders of unknown cause result in inflammation of the large or small intestines. In ulcerative colitis, ulcers form in the inner lining, or mucosa, of the colon or rectum. This often results in diarrhea, blood, and purulent material mixed with the stool. In Crohn's disease, inflammation  is most often found in the ileum and the first part of the large intestine (cecum). This area is known as the ileocecal area.  In Crohn's disease the inflammation extends deeper into the intestine wall, where small specialized "pockets" of inflammed tissue called granulomas are often found. Crohn's disease differs from ulcerative colitis in that inflammation and active disease can develop in any part of the gastrointestinal tract, including the anus, stomach, esophagus, and even the mouth. It may affect the entire colon, or form a string of ulcers in one part of the colon, or develop as scattered clusters of ulcers. This scattered distribution of affected areas in Crohn's disease leads to the formation of "skip lesions" in the colon where normal areas intersperse diseased segments.

Both ulcerative colitis and Crohn's disease tend to run in families in up to 25% of cases. The chance of inherited disease is highest if a mother has the same diagnosis, followed by a sibling.  A father with Crohn's or ulcerative colitis poses the least chance of having inherited disease in his children.  Many have theorized that either a virus, bacteria, or other immunogenic agent acts as a "trigger" in susceptible individuals.   Because inflammatory bowel disease is much more common in Western countries, experts believe environmental factors such as diet must play some role, although studies have not been conclusive. One study found that high animal fat intake was linked with subsequent diagnosis of inflammatory bowel disease.  A high level of processed sugar intake was related in studies to both ulcerative colitis and Crohn's disease.

Symptoms of inflammatory bowel disease can include chronic bleeding, diarrhea, and anemia.  The most common symptom of both ulcerative colitis and Crohn's disease is diarrhea.  Constipation, cramps, and abdominal pain can also be found in different presentations of both diseases.  Crohn's disease sometimes results in strictures (localized narrowing from scar tissue) of the small intestine leading to increasing crampy abdominal pain and the development of  "pus pockets" (abscesses) in or around the wall of the intestine.  Crohn's disease is also associated with the development of fistulas.  These are abnormal "connecting tunnels" between the bowel and other organs, other portions of the bowel, or the skin.  When fistulas develop between the loops of the small and large intestines, they can interfere with absorption of nutrients. This is a likely scenario for abscesses to form. Crohn's disease and ulcerative colitis may cause persistent diarrhea and fever and bleeding, and uncontrolled disease or active "flares" can become life threatening without treatment.

Inflammatory bowel disease may have effects outside the gastrointestinal tract, most commonly in the joints.  This can lead to stiffness and arthritis-like symptoms. Inflammation in other sites can also cause skin ulcers, mouth sores, problems in the eyes, hepatitis, and complications in the kidneys.  Disorders of the gallbladder, biliary system (such as sclerosing cholangitis, a specialized disease of the small bile vessels in the liver),  and gallstones are common complications of inflammatory bowel disease.  Silent blood loss from ulcers into the intestine can cause anemia, leading to weakness and fatigue. Patients with Crohn's disease or ulcerative colitis are at higher risk for forming blood clots (thromboembolism). Women with inflammatory bowel disease have a higher risk for menstrual abnormalities, with 25% reporting problems in fertility.  About fifty percent of women with Crohn's disease report pain during sexual intercourse.  Crohn's disease is also associated with psoriasis.  Recent reports suggest a genetic link between Crohn's disease and psoriasis.

Diagnosis of inflammatory bowel disease is not always straightforward.  Often the early symptoms, especially if mild, are confused with irritable bowel syndrome.  The usual tests helpful in making a diagnosis are sigmoidoscopy or colonoscopy - tests where a thin tube with a fiberoptic light source is used to inspect the lining of the lower bowel, often with the collection of tiny tissue samples whose microscopic inspection aids in diagnosis.  This is often supplemented by Barium X-ray inspection of the upper and lower bowel (small bowel series/barium enema) and computed tomography (CT scan or CAT scan).  In difficult cases of Crohn's disease small bowel endoscopy, where a long lighted tube is passed through the mouth to the intestines with the help of sedation, is sometimes needed for diagnosis.  Cultures and other studies of the stool are also helpful to rule out other identifiable causes of inflammatory bowel-type symptoms.

Treatment of inflammatory bowel disease centers around control of the inflammation.  At present there is no cure for inflammatory bowel disease.  The most common first line agents used are derivatives of sulfasalazine, which act as topical anti-inflammatories in the GI tract.  These agents' active ingredients are 5-ASA type molecules, and are generally well tolerated. While sulfasalazine has such side effects as heartburn, headache, loss of appetite, abdominal discomfort, dizziness, anemia, fever, and rashes. The drug may temporarily lower sperm count in men and can turn urine a bright orange-yellow color. Most of these side effects are due to the sulfa part of sulfasalazine.  Sulfasalazine can also cause folic acid deficiency, requiring oral folic acid supplementation.  The newer 5-ASA compounds are free of many of these effects but are more expensive.  These agents are often packed in special pill coatings or formulations to aid in getting active drug to the distal bowel before it is absorbed by the gut.  Rectal enema formulations are also available.

For those with active flares of whose disease does not respond to the above approaches, corticosteroids are useful, potent antiinflammatory drugs.  They can be given orally (Prednisone) or intravenously in seriously ill patients.  ACTH, which is a hormone that stimulates the adrenal gland to produce extra natural steroids, is also used.  While these drugs can be very effective in inducing a remission from symptoms, they have serious side effects. These include susceptibility to infection, weight gain (particularly increased fatty tissue on the face and upper trunk and back), acne, excess hair growth, hypertension, osteoporosis, cataracts, glaucoma, diabetes, wasting of the muscles, and irregular menses.  Personality changes can occur, including irritability, insomnia, psychosis, and depression.  These drugs are not useful in maintenance therapy due to the above limitations.  Antibiotic therapy can also be effective against many of the symptoms of inflammatory bowel disease.

If response is not adequate to these agents, drugs which suppress the body's ability to make antibodies against the disease (known as anti-immune therapy) are used. Azathioprine and 6-mercaptopurine (6-MP) are the two most commonly used drugs for anti-immune therapy.  These too have serious side effects.  A newer agent, infliximab (Remicade), is a genetically engineered antibody to an active substance causing inflammation in Crohn's disease.  It blocks the activity of tumor necrosis factor (TNF). It too can have major side effects, mostly associated with its infusion, but it can be effective against Crohn's disease that has been unsuccessfully treated with other drugs.

Researchers continue to look for more effective treatments. Examples of investigational treatments include the following:

Anti-TNF. Research has shown that cells affected by Crohn's disease contain a cytokine, a protein produced by the immune system, called tumor necrosis factor (TNF). TNF may be responsible for the inflammation of Crohn's disease. Anti-TNF is a substance that finds TNF in the bloodstream, binds to it, and removes it before it can reach the intestines and cause inflammation. In studies, anti-TNF seems particularly helpful in closing fistulas. Interleukin 10 (IL-10) is a cytokine that suppresses inflammation. Researchers are now studying the effectiveness of synthetic IL-10 in treating Crohn's disease.  Researchers recently identified a new corticosteroid called budesonide that appears to be as effective as other corticosteroids but causes fewer side effects. Free radicals--molecules produced during fat metabolism, stress, and infection, among other things--may contribute to inflammation in Crohn's disease. Free radicals sometimes cause cell damage when they interact with other molecules in the body. The mineral zinc removes free radicals from the bloodstream. Studies are under way to determine whether zinc supplementation might reduce inflammation.