Crohn's Disease

Crohn’s disease is one of the two major inflammatory bowel diseases (IBD). Crohn’s disease is an inflammatory process within the gastrointestinal tract that can involve anywhere from the mouth to the anus, but more typically involves sections of the large intestine (colon) and/or lower portions of the small intestine (ileum). The inflammation forms ulcers or sores that involve the entire thickness of the affected intestine.

What Causes Crohn’s Disease?

1. Genetics: Up to 25% of patients with Crohn’s disease have family members who also have been diagnosed with Crohn’s disease or Ulcerative Colitis. The disease is not inherited in a direct fashion, for example from parent to child. The pattern of inheritance is somewhat more indirect as the family history is analyzed, often there may be a cousin, aunt, or uncle who have been diagnosed with IBD. The overall risk of a child of a patient with Crohn’s disease developing the disease is approximately 2-6%. Specific genes such as the NOD2 genes and others, have recently been discovered that are associated with Crohn's disease. They are not present in all patients and thus are not useful for testing purposes (yet).

2. Altered Immune Function: There have been a number of changes in the immune system that have been identified in the inflammatory process. There is extensive ongoing research in this area and to date, no one specific immune malfunction has yet been found responsible for the disease. This research has, however, led to targeting specific new medications at altered areas of the immune pathways.

3. Infection/Environment: A specific bacterial or viral infection has not been isolated as the cause of Crohn’s disease, however, an infection may act as a triggering event to initiate the inflammation which then continues even though the infection has cleared. Patients who have Crohn’s disease who develop an infection (flu, gastroenteritis, etc.) can sometimes notice a flare in their Crohn’s disease at those times as well. Environmental exposure or stimuli also theoretically can play a role here, but to date, no specific factor has been isolated as the cause of Crohn’s disease.

Symptoms

Crohn’s disease can manifest itself with a variety of symptoms and problems. The location of inflammation, the amount of intestine affected, the degree of scarring or narrowing of the bowel and the presence of fistulae (abnormal communication between two areas) determine the types of problems that a patient will experience. With significant active inflammation, diarrhea, pain and bleeding may result. Areas of scarring or narrowing (stricture) usually lead to abdominal pain often with bloating, distention, nausea, vomiting, and weight loss. Abdominal pain in patients with Crohn’s disease can occur anywhere in the abdomen, but is commonly located around the belly button or the right lower abdomen. As mentioned, a fistula is an abnormal communication or connection between two structures. This occurs when inflammation in a loop of bowel erodes into whatever is positioned next to it creating a hole or a tunnel between these two structures. Thus, fistula can occur between two loops of bowel or between the bowel and the bladder, the vagina, or the skin. Fistula around the anal area are fairly commonly seen. These fistulas can lead to infection, bleeding, pain, or discomfort. At other times, the fistula are more of a nuisance than a cause of severe symptoms.

Other symptoms due to the underlying inflammatory disorder can include weight loss, fever, loss of appetite and in children poor weight gain. Effects of Crohn’s disease outside of the gastrointestinal tract can occur causing certain skin rashes (pyoderma gangrenosum and erythema nodosum), pink eye (conjunctivitis), joint aches and arthritis, and certain liver conditions (sclerosing cholangitis and others).

Testing

To evaluate the large intestine, colonoscopy is usually the test of choice (please see separate article on "Colonoscopy" for further details about this procedure). Colonoscopy allows for direct inspection of the colon and often the last portion of the small intestine (terminal ileum). Crohn’s disease appears as an inflammatory process (redness, bleeding, ulcers or sores) often found in a spotty distribution. This is different than ulcerative colitis where the inflammation is confluent. An x-ray examination of the small bowel (small bowel follow through) may be performed to evaluate the small intestine for signs of active inflammatory Crohn’s disease, stricture/narrowing, or fistula. The small bowel follow through is performed by drinking barium and taking abdominal x-rays periodically as the barium flows down the intestinal tract. An x-ray examination of the colon with barium can be useful to look for stricture/narrowing or fistula. A CT Scan is an x-ray technique allowing for cross-sectional imaging of the abdominal structures. This can help to identify areas of Crohn’s disease and also look for pockets of infection (abscess) that sometimes can occur. Blood work such as a CBC to evaluate the white blood cell count as a marker of inflammation and to look at the red blood cell count to rule out anemia is useful.  Certain specialized antibodies (currently available through one company, Prometheus) that can be measured in the blood may be markers for inflammatory bowel disease can be useful in certain cases.

Treatment

1. Nonspecific Treatments

These treatments are aimed at controlling symptoms associated with Crohn’s disease. 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) 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 Crohn’s disease and 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 portion of sulfasalazine is the active anti-inflammatory component and the sulphapyradine 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 and small intestine. Lacking sulphapyridine, 5-ASA (also known as Mesalamine) 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 (usual dose two tablets of 400 mg. each, three to four times daily), Dipentum (dose two 250 mg. tablets, twice per day), Pentasa (four 250 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. 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 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) are 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. Pouchitis, inflammation of a surgically created intestinal pouch can also be successfully  treated with probiotics.

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 (Anusol and others) can be used to treat proctitis and are taken at bedtime and/or twice daily. Budesonide (Entocort) is an interesting steroid that is absorbed in the GI tract an has its beneficial effect there.  As it travels through the liver, it is broken down into inactive substances that then have little steroid effect on the rest of the body. This medicine thus does not have many of the steroid side effects mentioned above. The currently available form is useful mainly for Crohn's disease in the ileum. It has been demonstrated effective for active flares of disease but not for maintaining remission.

Immunosuppressive Medication

Medications that can suppress the immune system can be used in certain patients to control Crohn’s disease 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 to 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)

Tumor necrosis factor appears to play a central role in the inflammatory process. Therapy using an antibody against TNF (Infliximab or Remicade) has been developed and is approved for certain patients with Crohn’s disease. The medication is given over a 2 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 with symptomatic fistula that have not responded to other treatments also may benefit by this treatment.  Patients require re-infusion about every 2 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.

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. Further details regarding current medications under study and eligibility of patients to enroll in these studies may be found by calling (513) 872-4549 or via e-mail info@ccrstudy.com

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 all patients with Crohn’s disease, 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 the stools looser and more uncomfortable to pass. If there is an area of stricture or narrowing, high residue foods should be avoided. These foods (i.e. popcorn, corn, seeds, and nuts) pass through the GI tract relatively whole and can then block an area of stricturing to cause obstruction. Milk does not need to be avoided unless the person has 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 taken safely. 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.

Stress

Stress and anxiety can also be aggravating factors and deserve proper attention, but in and of themselves, are not felt to be responsible for causing the underlying Crohn’s disease.

Surgery

Surgery is needed at some time during the course of Crohn’s disease in approximately half of patients. This usually involves removing a portion of the diseased bowel where inflammation, infection, fistula, or obstruction has occurred. Surgical removal of all visible areas of Crohn’s disease is not a cure. Unfortunately, the disease does recur in almost all patients over the ensuing years following surgery.

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. The Chapter office can be contacted at (513) 772-3550 or visit the CCFA website, www.ccfa.org

Related Sites

Crohn's and Colitis Foundation of America (CCFA), www.ccfa.org

Crohn's Disease Resource Center, http://www.healingwell.com/ibd/

United Ostomy Associations of America Inc., http://www.uoa.org