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Ulcerative Colitis
What is the Cause of Ulcerative Colitis?
The ultimate cause of ulcerative colitis is unknown, but there seem to be several factors that play a role.
Symptoms
The type and degree of symptoms depend on the amount of colon that is inflamed and the severity of the inflammation. The disease is often rated as being mild, moderate, or severely active depending upon the number of bowel habits, the amount of blood, and the appearance of the colon during colonoscopy or sigmoidoscopy. Most patients experience bleeding with bowel movements. Bloody diarrhea is seen if the inflammation involves more than just the lower few inches of the colon. Passage of the bowel movements may be painful and often associated with a sensation of incomplete evacuation of feces. A sense of urgency to defecate is common. Constipation can be a symptom particularly if just the rectum is involved (proctitis). In these patients, constipation, straining and blood on the stools mimicking hemorrhoidal bleeding is observed. Loss of appetite, weight loss and low grade fever often indicate moderate or severe disease activity. In a small percentage of people, symptoms outside of the gastrointestinal tract occur, such as rash, canker sores in the mouth, liver disease, conjunctivitis (pink eye), and arthritis particularly in the knees, ankles, wrists and low back.
Testing
Colonoscopy allows for direct inspection of the colon and the ability to obtain biopsies for microscopic examination.
Flexible sigmoidoscopy inspects the lower portion of the colon. The choice between these two examinations usually depends upon the location of the disease and the amount and type of information needed at that time.
An x-ray examination of the colon (lower GI or Barium Enema), less accurately evaluates the subtle details of the inflammatory process and is usually not helpful in ulcerative colitis.
Blood work to evaluate for anemia (low blood count) and evaluate liver and thyroid tests are monitored from time to time.
Treatment
1. Nonspecific Treatments These treatments are aimed at controlling symptoms associated with ulcerative colitis. For example, anti-diarrhea medications (Imodium, Lomotil) may be recommended to control frequent bowel movements in a patient with mild disease activity. Antispasmodic medications (Bentyl, Levsin, Donnatal) may be recommended to control cramps and discomfort associated with the disease. These medications can be used at times in an attempt to avoid other prescription medications that may have potential for more significant side effects. Diet and nutrition are important considerations and are discussed in a separate section below.
2. Medications Specific for IBD
Sulfasalazine (Azulfidine) This medication has been available for many decades. It was initially synthesized by a Scandinavian physician who was treating her king who had arthritis. At that time, the prevailing theory on arthritis was that it was caused by bacterial infections. She then combined what she thought was Aspirin (5-ASA) and an antibiotic (Sulfapyridine). This improved the king’s arthritis significantly. She then began administering this medication to other patients, some of whom had arthritis symptoms secondary to ulcerative colitis and she keenly observed that the ulcerative colitis symptoms improved. Since then, Sulfasalazine has been a mainstay of therapy for ulcerative colitis. It is used for patients with mild to moderately active disease and is also continued once the patient is feeling well to "maintain" remission. Sulfasalazine can cause malabsorption of folic acid and thus folic acid supplementation (1 mg., per day ) is usually taken with this medication. A typical daily dose is two tablets (500 mg. each, four times daily). Side effects can be seen in up to 20% of patients and most commonly would include nausea, headache, rash, or abdominal discomfort.
Mesalamine/5-ASA It has been determined that the 5-ASA (also known as Mesalamine) portion of sulfasalazine is the active anti-inflammatory component and the sulfapyridine portion is responsible for most of the side effects. More recently, pharmaceutical companies have been able to package 5-ASA, such that it may be taken in a pill or capsule form and thus delivered to the inflammatory site in the colon. Lacking sulfapyridine, 5-ASA is generally better tolerated than Azulfidine (sulfasalazine). Fertility problems (reduction of sperm count) is usually not seen from 5-ASA, as has been found with sulfasalazine. Mesalamine preparations include Asacol (two to four tablets of 400 mg. each, three to four times daily), Dipentum (dose two 250 mg. tablets, twice per day), Pentasa (two 500 mg. capsules, four times daily), and Colazal (three 750mg capsules three times a day). A rectal form of administration is available as an enema or suppository for patients with proctitis. The doses of 5-ASA may be increased further in some patients. The enema (Rowasa enema) is taken at bedtime and an attempt should be made to hold the enema in throughout the night while asleep. The volume of enema is rather small ( 60 ml). 5-ASA suppositories (Rowasa suppositories) are often taken twice daily, at bedtime and in the morning after completion of "bathrooming." Side effects from 5-ASA medications are rare, but can include headache, nausea, rash, and hair loss.
Antibiotics and Probiotics
IBD develops in
an area of
high bacterial concentration in the gut and does not occur in mouse
research animals that have no bacteria in their bodies. We normally have
trillions of bacteria of many different types in our GI tract some
of which may be "good" or "bad" in terms of
contributing to gut inflammation. Treatment with antibiotics do help some IBD patients presumably by changing the balance of “good vs. bad”
bacteria and thus their ability to affect the gut immune system. Usually,
ciprofloxacin (Cipro) with or without metronidazole (Flagyl) is used.
Rifaximin
(Xifaxan) is an oral, non-absorbed antibiotic with activity against many
gut organisms and pathogens. It is useful for traveler’s diarrhea and
antibiotic-associated diarrhea. Several small studies show benefit in IBD.
Probiotics are “beneficial” live bacteria that are given to change the balance and type of bacteria in the gut. Studies in IBD have shown benefit in treating active disease and in maintenance of remission.
Steroids Steroids can be given by mouth (Prednisone) or intravenously (Hydrocortisone, Solu-Medrol and others). Usually steroids are used in moderately active or severe disease. Steroids can be quite effective bringing the inflammatory response under control very rapidly in most patients. Unfortunately, there are a number of side effects to be aware of. Steroids can cause elevation of the blood sugar (temporary diabetes or worsening of blood sugar in a patient with preexisting diabetes), change in physical appearance (swelling of the face known as moon-face, thinning of arms, and deposition of fat around the trunk), cataracts in the eyes, susceptibility to infection, and a thinning of the bones (osteoporosis) which can even lead to fractures in areas such as the knee and hip. It is for these reasons that if steroids are used, they should be used at the lowest reasonable dose and for the shortest period of time possible. The time frame is usually several months, but there is a lot of variation depending upon the patient’s individual circumstances. Prednisone is used to treat active disease, but does not have a role to maintain disease remission once the patient is feeling well. Steroid enemas (Cort enema) are used to treat disease located in the rectum and lower colon and are taken at bedtime and are held through the night while sleeping. Steroid suppositories (i.e. Anusol) can be used to treat proctitis and are taken at bedtime and/or twice daily.
Immunosuppressive Medication Medications that can suppress the immune system can be used in certain patients to control ulcerative colitis over the long term. These medications are usually used for patients who require frequent significant doses of steroids to control their symptoms. 6-MP (Purinethol) and Azathioprine (Imuran) are the two main immunosuppressive medications used in ulcerative colitis. The dose is often adjusted depending upon the patient’s body weight, typically 1-2 mg/kg per day total dose. These medications do not work in the acute phase, that is, they take an average of three months to see a therapeutic benefit. Occasional side effects are observed including pancreatitis (inflammation of the pancreas causing abdominal pain with nausea), hepatitis (inflammation of the liver), allergic reactions, rash, and slightly increased susceptibility to infections. The white blood cell count needs to be followed (medications can affect the bone marrow). Thus, a patient on these medications needs to have their blood count checked on a regular basis (every one to two months after they have reached a stable dose of medications. Patients that are unable or unwilling to have their blood counts checked frequently and regularly will not have their medications refilled. There is a potential for the development of malignancies, such as lymphoma as a result of suppressing the immune system. To date, there have been thousands of patients that have been treated worldwide with these medications and only a few cases of lymphoma have developed. It is thus not clear whether the lymphoma is due to the medications or not, but this is a potential side effect that we discuss with patients who are started on these medications. These side effects occur in less than 2% of patients.
Tumor necrosis factor (TNF) appears to play a role in the inflammatory process. Therapy using an antibody against TNF (Infliximab or Remicade) has been developed and is now approved for certain patients with Ulcerative Colitis. The medication is given over a two hour I.V. infusion. Selected patients may be considered for this treatment if they have significant ongoing disease that has not responded to more conventional therapies. Patients will likely require re-infusion about every two months to maintain the therapeutic benefit. Nausea, fever and rash can occur with infusion. On the long-term basis, there are questions regarding immunological alterations and several patients treated with Infliximab have developed cancers (i.e. lymphoma). It is not clear at this time whether the tumors are due to Infliximab or not. Not insignificant is the cost of treatment which can be several thousands of dollars per infusion.
Diet Although there is no evidence that dietary factors cause inflammatory bowel disease, dietary therapy plays a role in controlling symptoms of treating patients. There is not a special diet that is prescribed for patients with ulcerative colitis, but certain foods can stimulate more frequent bowel movements (make diarrhea worse) and should be avoided. These generally include caffeine, alcohol, and spicy, fried, or fatty foods. Some fresh fruits and vegetables can make stools looser and more uncomfortable to pass. Milk does not need to be avoided unless the person has an underlying lactase deficiency (milk intolerance). In this situation, drinking milk or eating milk products leads to diarrhea and gas due to poor absorption of milk/sugar (lactose). Vitamin supplements are not absolutely necessary, but a multivitamin can usually be safely taken. Patients on Sulfasalazine (Azulfidine) should take folic acid, 1 mg. daily as a supplement. Malnutrition needs to be prevented and treated, that is, if there has been significant weight loss then dietary therapy/advice to regain muscle mass is beneficial. It is difficult for the body to promote healing without the proper "metabolic machinery" to do so.
Surgery Most patients with ulcerative colitis respond adequately to medical therapy. Occasionally, surgery is recommended in an emergency situation or for elective (non-emergent) reasons. Fulminant (sudden, severe) ulcerative colitis and toxic mega-colon (severe dilation of the colon that can lead to perforation) may require urgent surgery. Elective indications for surgery include patients with chronic significant symptoms that are not controlled with medical therapy or in patients who develop pre-cancerous areas in the colon or even colon cancer. Surgery for ulcerative colitis involves removal of the entire colon and rectum and, as such, is a "cure" for the ulcerative colitis (after surgery the disease does not recur). To accomplish removal of the colon, the patient might have a permanent ileostomy (ostomy bag), but many patients can undergo a "pull through" procedure where the small intestine is reattached by forming a pouch and sewing this new pouch internally to the anus.
Research Studies
Basic research from around the world on inflammatory bowel disease has been able to focus upon the specific inflammatory mediators within the blood and on the immunologically active blood cells. These breakthroughs continue to lead to new exciting medications to treat inflammatory bowel diseases. In the Cincinnati area, Consultants for Clinical Research (CCR) has been involved as a site for national research studies since 1981. CCR was the first group in the Cincinnati area devoted to performing clinical studies for gastrointestinal diseases. These research studies can potentially offer patients new medications that would not otherwise be available to them. For further details regarding current medications under study and eligibility of patients to enroll in these studies, please call (513) 872-4549 or e-mail info@ccrstudy.com
Colon Cancer Risk
There is an increased incidence of colon cancer in ulcerative colitis patients. The factors increasing this risk are the length of time a person has had the disease and the amount of colon involved. If only a limited amount of colon is involved, the overall risk of colon cancer may be only slightly increased over patients without ulcerative colitis. The longer a person has had ulcerative colitis, the greater the risk. The disease is usually present for greater than eight years before any increased risk is recognized. To try to minimize the risk of colon cancer, a patient with chronic ulcerative colitis will undergo periodic colonoscopy to obtain biopsies. The biopsies are evaluated for dysplasia (pre-cancerous changes) and cancer. If these are found, surgery to remove the colon would then be recommended. After having been diagnosed with ulcerative colitis for more than eight to ten years, a colonoscopy is usually then done on a yearly basis.
Crohn’s & Colitis Foundation of America (CCFA)
The Crohn’s & Colitis Foundation of America (CCFA) is a national organization devoted to the interest of patients and significant others with ulcerative colitis and Crohn’s disease. In Cincinnati, we have an active CCFA chapter. Greater Cincinnati Gastroenterology Associates (GCGA) has taken a leadership role in founding the local chapter and continues to provide support on an ongoing basis. Dr. Michael Kreines has been the Chairman of the Chapter’s Medical Advisory Committee and Board member since inception of the local chapter. The Cincinnati Chapter in concert with the national organization has much to offer our community. Educational brochures and pamphlets are available that cover a wide range of inflammatory bowel disease related topics. Educational seminars for patients and interested others are held at a variety of locations throughout the year. Topics cover basic information regarding inflammatory bowel disease, surgery, medications, diet and nutrition, psychological support, insurance issues and a variety of other topics. Several support groups have been established covering a diverse geographic area to provide easy access to patients and their significant others. A number of fund raising events are held throughout the year which very importantly raise money for research, but also are planned with an eye toward fun and sociability. One of the primary goals of the CCFA is fund raising to support research to find the cause and eventually the cure of Crohn’s disease and ulcerative colitis. If you would like more information about the local Chapter office please call (513) 772-3550 or visit the CCFA web site, www.ccfa.org
Related Sites Crohn's and Colitis Foundation of America (CCFA), http://www.ccfa.org Crohn's Disease Resource Center, http://www.healingwell.com/ibd/
United Ostomy
Associations of America, Inc., http://www.uoa.org
Greater Cincinnati Gastroenterology Associates, Inc.
Office Phone (513) 751-6667
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Ulcerative
colitis is one of the two major inflammatory bowel diseases (IBD). In
ulcerative colitis, the lining of the colon (large intestine) becomes inflamed causing ulcers or sores which
lead to symptoms. The loss of the superficial lining of the large intestine
often results in bleeding with bowel movements. Oozing of body fluids
and reduced ability of the colon to properly reabsorb fluids can cause
diarrhea. Thus the two main symptoms of ulcerative colitis are bleeding
and diarrhea. Ulcerative colitis always involves the lower portions of
the colon and from there can spread to involve other segments of the colon
in a continuous fashion or even the entire colon can be involved. If the
rectum is the only area that is inflamed, the condition is often referred
to as ulcerative proctitis, thus, ulcerative proctitis is a limited form
of ulcerative colitis. It is estimated that 500,000 people in the United
States have ulcerative colitis. 
