Welcome to the Walter Reed Army Medical Center

Common Questions about Crohn's Disease ( Part II )

by James C, Roll, MD., MAJ
Staff Gastroenterologist
Walter Reed Army Medical Center

"Doctor's Corner"

Are life styles and dietary changes important?

Cessation of smokingis an important addition to any therapeutic regimen. Smoking has been identified as a risk factor for the occurrence of Crohn's disease.

Avoidance of Non-steroidal inflammatory agents (NSAIDs) may be helpful. These medications are often cited as "triggers" for disease flares or recurrences.

Psychosocial stress does not cause the development of Crohn's disease. However, effective management of Crohn's needs to address the patient's psychological well-being to optimize their ability to cope with the disease and to comply with therapy.

Dietary influences may be important in the development of the Crohn's disease. However, despite extensive research in this area, no specific dietary factors have yet been clearly identified. In fact, for most patients with mild to moderate disease, no dietary restrictions are necessary. Even so, some patients have reported a notable decrease in their symptoms on a low fiber, low residue diet. Others have identified specific food groups, such as milk and dairy products, that seem to worsen their food intake and symptoms (e,g. abdominal cramping or diarrhea). In such cases, it would be reasonable to avoid these foods. Patients are encouraged to keep a diary of their food intake and symptom response, at least initially in their disease.

Fish oil productsas dietary supplements appear to have an antiinflammatory properties. Studies have shown a remarkable response in some patients with Crohn's disease. Unfortunately, such positive results have not been a consistent finding, and patient tolerance of the fish oil has been a concern. Further studies are ongoing.

Elemental diets have been shown to be beneficial in some with Crohn's disease that is difficult to control. Such diets are severely restricted in content to the very basic constituents which are easily processed and absorbed by the proximal (early) small intestine. Because they are so well absorbed, the patient's nutritional status should improve, and the inflammation of the bowel wall should decrease. Unfortunately, these diets are expensive, poorly tolerated (not palatable), and often must be given by a nasogastric feeding tube. Thus, their use is limited to special circumstances.

Total parenteral nutrition (TPN) is occasionally given intravenously to patients with severe inflammatory disease and unable to tolerate oral feedings. Its benefit as a preoperative measure to improve nutrition in someone who appears malnourished has yet to be proven.

How will Crohn's disease effect pregnancy? (and visa versa)

Patients with Crohn's disease may have a slightly decreased fertility. In certain patients, this may be related to the medications. Sulfasalazine, for instance, causes a reduction in the sperm count in males. This is reversible after discontinuation of the medication. In other patients, the cause is not clear.

The effect of Crohn's disease on the course of pregnancy is minimal. The rate of birth defects is not notably different than that of the general population. There is a mild increased risk of spontaneous abortion and premature delivery, especially if the disease was active at the time of conception. The best time to conceive (become pregnant) is during a time of remission, when the Crohn's disease appears inactive. In the absence of active disease, the likelihood of a normal birth is about 80%.

Pregnancy has no consistent effect on the course of Crohn's disease. Of those who are in remission when they become pregnant, most will remain free of disease activity throughout the pregnancy.

Sulfasalazine and mesalamine are considered relatively safe for use in pregnancy, and their continued use is recommended. As well, in patients who require corticosteriods for control of their disease, it is generally accepted that the benefit of these medications outweigh any small risk of adverse effects. Although the immunosuppressants (6-MP and azathioprine) have not as yet been shown to have any adverse fetal outcomes in humans, they are to be used with caution and only if absolutely necessary. Methotrexate and cyclosporine are best avoided during pregnancy.

What medical treatments are available for Crohn's disease?

Crohn's disease is not curable by either medical or surgical treatment. The disorder is lifelong, with a tendency for recurrences. The primary goals of treatment, therefore, are to minimize the extent of disease activity, prolong periods of remission (quiescence of clinical disease), and to avoid, or minimize, complications.

Aminosalycilates are the primary choice of treatment for patients with mild to moderate Crohn's disease. Aminosalycilates are used because of inherent antiinflammatory properties. The precise mechanism of action is not clear. Most of the benefit from such drugs appears to be topical in nature, meaning it is due to the direct exposure of the medication to the lining of the wall of the gastrointestinal tract. There may be a time lag of several weeks before the maximal therapeutic effect is realized. The aminosalycilates have been shown to be effective in decreasing the inflammation of acute Crohn's disease, achieving remission of the disease, and helping to maintain remission for extended periods.

Sulfasalazine (azulfidine) is the prototype of this class of medications. Initially developed for patients with inflammatory arthritis, it was fortuitously found to improve the gastrointestinal symptoms of patients who also had inflammatory bowel disease. The medication is a combination of an antibacterial agent (sulfapyridine) combined with an antiinflammatory (5-aminosalicylic acid, 5-ASA). To become active, the medication needs to be 'split' to separate its two components. This process takes place predominantly in the large bowel (colon). As a result, sulfasalazine has shown less consistent results when used for disease of the small intestine. Another limitation is that as many as one fourth or more of the patients will develop side effects related to the use of this medication. Most of these side effects are due to the absorption of the sulfapyridine component of sulfasalazine.

Mesalamine (5-aminosalicylic acid, 5-ASA) is the active component of sulfasalazine. As an alternative to sulfasalazine, oral 5-ASA has been packaged into several different delivery forms, without the need for sulfapyridine. These newer agents avoid the side effects related to sulfapyridine and significantly improve the effectiveness of the medication in patients with Crohn's disease of the small intestine. One drawback to these alternatives has been the increase costs of the medications.

Enema and rectal suppository forms of mesalamine are available as well. Such preparations appear to be as effective as oral medications in active disease of the distal colon and rectum. Further trials are ongoing. Their use in more proximal disease is obviously limited.

Corticosteroids are very effective in active Crohn's disease and are among the most rapidly acting agents. They act to suppress the cells of the immune system, and the chemicals that can cause inflammation. Corticosteroids are used most often in mild to moderate disease that does not respond to aminosalycilates, and in cases of severe disease, where rapid, effective control is necessary. They are available in oral form, the most common being prednisone, and in liquid for intravenous (injection into the vein) use. The intravenous formulations are most helpful in patients who can not tolerate oral intake, or whose disease is so severe that effective delivery of an oral preparation may be in doubt. Long term use of cortcosteroids is discouraged due to an association with significant side effects related to the absorption of the mediation from the intestine tract. These side effects include osteoporosis (bone mineral loss), high blood pressure, weight gain, glucose(sugar) intolerance, acne, cataracts, and suppression of the adrenal glands. Most of these effects are dose dependent, meaning they can be minimized by using the least possible dose if long term use in necessary, Although effective for active disease, corticosteroids have not been shown to be helpful in maintaining remission.

Enema, suppository, and foam rectal delivery systems are also available for cortcosteroids. Again, their application is limited to disease of the distal colon and rectum. Although, theoretically, the absorption may be less than the oral pill versions of cortcosteroids, it is not insignificant. At sufficient dose and with prolonged use, these topical forms of corticosteroids may predispose a patient to similar long term complications as described above.

Budesonide is one of several relatively new cortcosteroids that may soon be available for wide-spread use in the United States. Its oral form appears to be nearly as effective as prednisone in controlling active Crohn's disease, but with less of the long term side effects. This low side effect profile is due to significant "first pass metabolism" of the medication by the liver. After absorption by the cells lining the gut lumen, where the medication has its predominant effect, most of the medication is then transported to the liver where it is rendered inactive. Therefore, only a minimal amount of active drug actually reaches the main blood circulation. Currently, availability and cost limit its use.

Immunosuppressive agents have been shown to be effective for active Crohn's disease, and for maintaining the state of remission. The two most used and studied are 6-mercaptopurine (6-MP) and azathioprine (imuran), whose active by-product is 6-MP. These medications interfere with nucleic acid metabolism which is essential for the growth and activity of the cells of the immune system, and thus, they decrease inflammation. There is typically a delay of 2-3 months to realize the maximum therapeutic benefit. Thus, their usefulness in the setting of acute disease is less helpful. As such, these agents are used in patients who have frequent recurrences, or disease that requires long term corticosteroids for adequate control. The goal in such cases is to minimize, or eliminate, the need for corticosteriods, and thus avoid the steroid -associated complications. 6-MP and Emirian also have potential for side effects and their use must be monitored closely.

Methotrexateis another immunosuppressive agent found to be effective in some patients with difficult Crohn's disease who have not responded completely to 6-MP or Emirian. The medication is administered as an intramuscular injection once weekly. Although side effects are minimal, a patient must be monitored for liver and lung toxicity.

Cyclosporine is a highly effective agent that is used by some institutions. Currently, it is most often indicated only for short term use in seriously ill patients who need rapid control of their disease, and as a "bridge" to other forms of long term therapy. Although very effective, it possesses considerable potential for toxicity. Cyclosporine should be limited to institutions with significant experience with its use.

Antibiotics have been shown to be effective as primary therapy is some studies. Aside from the known antibacterial activity of these drugs, the specific mechanism(s) of action in Crohn's disease is not known. Metronidazole (flagyl) is the antibiotic most often used and studied. It appears most effective in disease limited to the colon, especially for perianal disease. Unfortunately, a number of patients do . not tolerate long term use due to side effects such as a metallic taste, 'furry' tongue, indigestion, and peripheral neuropathy (an abnormal sensation in the hands and feet) which is reversible after stopping the medicine. Other antibiotics (ciprofloxacin, clarithromycin, ..) appear promising and are currently under investigation.

On the horizonare a number of medications being developed to act specifically at certain steps of the inflammatory process in Crohn's disease. Some of these are designed to block specific chemicals found to be important in the progression of inflammation (e.g. anti-tumor necrosis factor). Others are medications that behave like 'protective' chemicals that occur naturally in the human body to fight against inflammatory(e.g. interleukin10). The primary goal in all these new medications under study is to improve effectiveness while minimizing the drug side effects

When Medical Management Is Exhausted

Written by Sharon R. May, RN, CETN

When medical management for Crohn's disease is no longer effective, surgical intervention is warranted. Other indications necessitating surgery are: relief of chronic symptoms, complications do to obstruction, toxic megacolon, bowel perforation, hemorrhaging, strictures, and perianal disease, to include fistulas, and abscesses.

The specific surgical procedure is dependent upon the clinical picture. If Crohn's is limited to a section of the colon, a segmental resection with anastomosis will be done. However, if the disease is extensive involving the entire colon and rectum a protocolectomy with a permanent ileostomy will be required. The surgery is not cure, but only palliative.

Once the decision has been made for surgery, the doctor will explain the surgical options to the patient. If the doctor feels that a stoma is warranted,, the Enterostomal Therapist will be contacted. The E.T. nurse is a specialist trained in teaching patients how to care for their stoma. The E.T. will make a pre-op marking for placement of the stoma and provide information that will be needed to prepare the patient for surgery. Also, before the surgery, the E.T. will contact the United Ostomy Association, in order, to arrange for a visitor to see the patient providing emotional support. The visitor also provides encouragement to the patients during this stressful time.

Post operative care commences two days after surgery. The E.T. begins teaching the patient how to care for his stoma, the importance of diet and adequate fluid intake. On the fourth post op day, the patient will demonstrate how to remove the appliance, clean the stoma and the peristomal skin, how to measure, cut and fit the appliance. The patient will also be told when to return to the General Surgery Clinic for follow up care.

The patient will be given printed information on the care of his stoma and who he should contact in case of a problem. A final point to be made is to assure the patient that his doctor and E.T. nurse will still continue to be their resource long after recovery.