Inflammatory Bowel Disease (IBD)
Ohio GI is an acknowledged local, regional, and national leader in treatment of patients with inflammatory bowel diseases (IBD). Annually we see hundreds of patients with Crohn’s Disease, Ulcerative Colitis, and Microscopic/Lymphocytic/Collagenous Colitis. The number of patients seen and the broad geographic area they come from highlights our extensive experience and why many patients are seen in consultation by us for second opinion consultation. For decades, we have been actively involved in IBD clinical research, leading to publication of innumerable journal articles and participation in many national conferences. Our patients with IBD may chose to participate in clinical trials, availing them of treatments not otherwise available. In Cincinnati, we helped found the local chapter of the Crohn’s & Colitis Foundation of America (CCFA) and have remained very active in its organization, research, fund raising, and educational activities.
We strive to provide IBD patients the most effective and safe therapies available (either by prescription, over-the-counter, dietary, or as part of clinical research trials). We have had great success in reducing the use of steroids which have many short and long-term side effects. We had a full-time IBD nursing staff who are responsible for administering and monitoring biologic medications such as Remicade (infliximab). We utilize additional tools such as disease activity indices to follow many patients to track their progress and provide objective information on each patient’s status. We have developed IBD specific flow sheets to follow and track many aspects of an individual patient’s treatment.
Crohn’s disease is a lifelong and serious condition that has significant medical, economic and social impact. The use of expensive biologic therapies thus needs to be carefully evaluated in terms of providing substantial benefits for our patients. In addition to our clinical research work in developing new medical therapies, we also delve into areas such as the effectiveness of currently available therapies we recommend. For example, we performed a study to examine and document the response of patients with Crohn’s disease to biologic therapy with Remicade (Infliximab). A previously standardized inflammatory bowel disease questionnaire (IBDQ) was used as the tool to measure the patient’s clinical status. Patients entering this study were patients with moderate to severe Crohn’s disease, most of whom who had active disease in spite of treatment with other available modalities typically steroids and immunomodulatory therapies such as azathioprine or 6-mercaptopurine. After treatment with Remicade, the IBDQ score improved in 72% of our patients, was unchanged in 8% and worsened in 20%. This study did document improvement in a very significant percentage of our patients undergoing biologic treatment.
IBD – ULCERATIVE COLITIS AND CROHN’S DISEASE INTRODUCTION
Inflammation can occur anywhere in the body. On the skin, it can cause redness or a sore, in the joints it leads to arthritis. In the digestive tract, inflammation can be an acute process, such as from an intestinal infection/flu or even a stomach ulcer caused by aspirin. Chronic intestinal inflammation is usually due to Crohn’s Disease or Ulcerative Colitis (UC), the two major Inflammatory Bowel Diseases (IBD).
Crohn’s Disease is an inflammatory process within the gastrointestinal tract that can occur anywhere from the mouth to the anus, but more typically affects 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. It can be patchy in its distribution, leaving normal areas in between inflamed ones.
In Ulcerative Colitis (UC), inflammation develops in the inner more superficial lining of only the colon (the colon is the same thing as the large intestine). Ulcerative colitis always involves the lower portions of the colon (the rectum) and from there can spread to involve other higher segments of the colon in a continuous fashion. If the rectum is the only area that is inflamed, the condition is referred to as ulcerative proctitis.
HOW COMMON IS IBD?
It is estimated that there are nearly 1,500,000 Americans with either ulcerative colitis or Crohn’s disease, roughly half of that number for each disease. These diseases are often diagnosed before age 30, although they can occur at any age. There is a greater incidence in Caucasians and in Jews.
WHAT IS THE CAUSE OF IBD?
The ultimate cause of IBD is unknown, but there seem to be several factors that play a role.
- Genetics: Up to 25% of patients with IBD have family members who also have been diagnosed with inflammatory bowel disease. The pattern of inheritance is indirect; rather than a parent, there may be a cousin, aunt, or uncle who have been diagnosed. There are many genes that have been shown to be assiciated with IBD, highlighting exciting ongoing genetic research. The overall risk for a child of a patient with IBD developing the disease is approximately 2-6%.
- Altered Immune Function: There are a number of abnormalities in the immune system that have been identified in the inflammatory process. There is extensive ongoing worldwide research in this area which has led to effective new medications targeted at the altered areas of the immune pathways.
- Infection/Environment: A specific bacterial or viral infection or environmental exposure is probably not the specific cause of IBD but may act as a triggering event to initiate the inflammation or a propagating factor stimulating ongoing inflammation. Possible offending agents could include infecting organisms or some of the myriad of bacteria that normall inhabit the GI tract.
- Stress, anxiety, and diet are often quieried by patients with IBD but these factors do not cause IBD but may play an indirect role in accentuating flares of the disease.
Putting this all together, in a genetically susceptible person, a triggering event (infection or other) stimulates the body’s immune system to inappropriately cause inflammation in the digestive tract. Bacteria and possibly food in the gut probably also have a role in continued inflammation. The inflammation causes damage to the intestines which responsible for the symptoms of the disease.
SYMPTOMS OF IBD
Crohn’s Disease. The location of inflammation, the amount of intestine affected, and other complications such as scarring or narrowing of the bowel (strictures) and the presence of abnormal communication between two areas (fistula) determine the type of problems that a patient will experience. Active inflammation usually causes diarrhea, abdominal pain, bloody stools, low-grade fever, and weight loss. Areas of scarring or narrowing (stricture) usually lead to abdominal pain often with bloating, distention and sometimes 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. A fistula 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. A fistula can occur between two loops of bowel or between the bowel and the bladder, the vagina, or the skin. Fistulas around the anal area are fairly common. These fistulas can lead to infection, bleeding, pain, and drainage.
Ulcerative Colitis. The type and degree of symptoms depend on the amount of colon that is inflamed and the severity of the inflammation. Most patients experience bleeding with bowel movements. Bloody diarrhea is seen if the inflammation involves more that just the lower few inches of the colon/rectum. 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 if just the rectum is involved (proctitis). In these patients, constipation with straining and blood on the stools mimics hemorrhoidal bleeding. Loss of appetite, weight loss and low-grade fever often indicate active inflammation.
Manifestations Outside the Digestive Tract. Symptoms due to the underlying inflammatory disorder can include weight loss, fever, and loss of appetite. In children, poor weight gain or a delayed growth pattern may be the initial manifestation of IBD. Effects of IBD outside of the gastrointestinal tract can occur causing certain skin rashes (pyoderma gangrenosum and erythema nodosum) and pink eye (conjunctivitis, uveitis), joint aches, back pain, arthritis, and certain liver conditions (sclerosing cholangitis). Anemia is common due to bleeding, malabsorption, and dietary factors. Patients with IBD are at risk for osteoporosis due to the affect of inflammation and of steroids on the bones.
TESTING FOR IBD
To evaluate the lower intestine, colonoscopy is usually the test of choice Colonoscopy allows for comfortable direct inspection of the colon and the last portion of the small intestine (terminal ileum) using a fiberoptic scope in a sedated patient. Crohn’s Disease appears as redness, bleeding, ulcers or sores in a spotty distribution. Ulcerative colitis appears as confluent redness and bleeding. An x-ray examination of the small bowel (small bowel follow through or enteroclysis) evaluates the small intestine for active Crohn’s Disease or stricture (narrowing) or fistula. This is performed by drinking barium while taking abdominal x-rays as the barium flows down the intestinal tract. A CT Scan is an x-ray technique allowing for cross-sectional imaging of the abdominal structures. This can help to identify areas of bowel wall thickening/inflammation and also look for pockets of infection (abscess). MRI uses magnetic forces to image the body and does not involve radiation. Both CT and MRI can evaluate the small bowel (CT-enterography and MR- enterography). Endoscopic ultrasound utilizes an ultrasound probe placed under endoscopic control to carefully evaluate the area around the rectum for infection and inflammation, especially in Crohn’s disease. Blood work can evaluate for anemia (low blood count) and evaluate the liver and other parameters. Blood levels of inflammatory markers including the white blood cell count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR or sed rate) can signify inflammation or infection. Blood testing for certain IBD-related markers can sometimes support a diagnosis in some patients.
COURSE OF IBD
Crohn’s and ulcerative colitis often follow a pattern of flares (when the condition worsens) and remissions (when it improves). The pattern can be quite variable, ranging from rapid and continued remission to recurrent periods of symptoms to disabling symptoms. The goal of medical therapy is to drive active disease into remission and then maintain remission.
MEDICATIONS TO TREAT IBD
Many different drugs are used to treat IBD. The choice of medications depends upon the severity of disease and the area of the digestive tract affected.
Symptomatic treatment – In addition to using medications aimed at reducing inflammation (see below), treatments to address certain symptoms can also be beneficial. These include anti-diarrheals (immodium, lomotil), antispasmodics (hyoscyamine, dicyclomine), anti-nausea (zofran, phenergan), and nutritional supplements.
Sulfasalazine (Azulfidine) – Sulfasalazine was one of the first drugs used to treat IBD and developed when the theory was to combine an anti-inflammatory with an antibiotic. This medication contains the bowel anti-inflammatory 5-ASA (see below) and sulfapyridine (which basically serves to carry the 5-ASA down into the lower gut) and has been used sucessfully for decades. The sulfapyridine component can cause side effects in some patients.
5-aminosalicylates (5-ASA or mesalamine) – 5-aminosalicylate (5-ASA) drugs are available in oral forms (such as Asacol, Pentasa, Lialda, Apriso, Colazol) and medicated enemas (Rowasa) and suppositories (Canasa). In ulcerative colitis, these drugs are helpful in achieving and then maintaining remission. They seem to be less potent in Crohn’s disease.
Antibiotics – Antibiotics can reduce the number of bacteria in the intestine, and in some patients reduce inflammation. They are primarily used to treat infections associated with Crohn’s disease (abscess) and treating Crohn’s disease involving the perianal region. Ciprofloxacin (cipro) and flagyl (metronidazole) are commonly used.
Probiotics – There are normally tremendous quantities of bacteria that are peacefully and healthfully cohabitating in our colon. There can develop an inbalance of “good and bad” bacteria causing symptoms and inflammation. Probiotics are potentially “good” bacteria given orally to restore the bacterial balance in a more favorable distribution. Extensive ongoing research may help find “the best” probiotic. There are a wide variety of commercially available probiotics most of which have not yet been tested in IBD. Probiotics can be used and can be beneficial in some patients.
Steroids – Steroids can induce remission in patients in active ulcerative colitis and Crohn’s disease. They can be given intravenously or orally (prednisone) or as a medicated suppository or enema. Budesonide (Entocort) provides a beneficial steroid effect on mainly the small bowel and is then absorbed and then most of it broken down in the liver, leaving little to get into the blood stream. Steroids do not prolong remission and there are many potential side effects of long-term steroid use.
Immunomodulatory agents – Immunomodulatory drugs decrease the inflammation associated with IBD by addressing an imbalance of different types of immune cells. The most commonly used drugs include azathioprine, 6-mercaptopurine (6-MP or purinithol), and methotrexate. These drugs are used for long-term control of IBD and can take 1-3 or more months to see a therapeutic response.
Anti –TNF (tumor necrosis factor) agents are antibody molecules that neutralize the inflammatory mediator TNF. There are currently three anti-TNF medications available. Infliximab (Remicade) was the first developed and is given by IV infusion. It is composed of a combined mouse and human antibody and is given by IV infusion usually every 2 months after an initial induction period. Adalimumab (Humira) is composed of a fully humanized antibody molecule and is given by injection usually every 2 weeks. Certolizumab pegol (Cimzia) hooks the active portion of a human anti-TNF antibody to a molecule (PEG) that can allow less frequent injections, every 2-4 weeks.
Natalizumab (Tysabri) is used for Crohn’s disease and blocks the egress of white blood cells from blood vessels into the bowel, reducing inflammation.
With the cause and the cure for IBD unknown, there are extensive research efforts underway. We have been active in IBD research for decades and have participated in clinical trials through the spectrum of IBD medications. Our research company, Consultants for Clinical Research (www.ccrstudy.com phone 513-872-4549) has several ongoing clinical trials to advance the science of IBD and allow patients to participate in research and receive medications that would otherwise not be available to then.
There have not been any specific foods or dietary factors shown to cause or flare IBD. Generally, if a food causes symptoms in an individual, it can be avoided. It is important to maintain good overall nutrition. If malnuorished, there can exist reduced fuction of the metabolic machinery needed to heal the IBD and restore health. In Crohn’s disease with strictures (narrowing of the bowel) avoiding high residue and chunky foods (corn etc) is advised to reduce the chance of food particles obstructing the bowel at the narrowed area.
WHAT CAUSES IBD FLARES?
Factors may include stopping or reducing medications, smoking (makes Crohn’s disease more refractory), use of antibiotics, use of NSAIDs (ibuprofen, naproxen and others), and gut infections. Please see our brochure “Staying Healthy with IBD” on our website at www.ohiogi.com under Disease Management then under Symptoms and Solutions.
Ulcerative Colitis– Surgery for UC involves removal of the entire colon. A permanent ileostomy can be placed or a pouch reservior created from small bowel can be formed and sewn to the anus (ileoanal pull through) without a permanent ileostomy. Surgery for UC is considered when the disease is refractory to medical therapy, for colon cancer or precancer (dysplasia) developing in the setting of chronic UC, and rarely emergently for toxic colitis. The patient is considered cured of UC, but postoperative complications and long term effects of having no colon are concerns.
Crohn’s Disease – There is no cure (medical or surgical) for Crohn’s disease. Therefor, surgery for Crohn’s disease is usually used only when considered “necessary”. Indications for surgery can include obstruction of the bowel, refractory disease, cancer, complications of Crohn’s such as fistuala or abscess or perforation. Statastically, about 80 percent of patients with Crohn’s disease will require an operation at some time but newer more potent medications now used may be reducing the rate of surgery and the postoperative recurrence of Crohn’s (historically 90% with time).
CANCER RISK IN IBD
There is an increased incidence of colon cancer in patients with ulcerative colitis and Crohn’s disease when it significantly affects the colon . 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. The longer a person has had IBD, 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 IBD will undergo periodic colonoscopy to obtain biopsies. The biopsies are evaluated for dysplasia (pre-cancerous changes) and cancer.
As with any chronic illness, IBD can affect ones’ activities, lifestyle, emotions, relationships and more. Attention to the impact of IBD on the psychosocial situation and vissa versa is an important part of comprehensive care.
CROHN’S AND COLITIS FOUNDATION OF AMERICA (CCFA)
The 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 that offers educational brochures, seminars, support groups, and fund raising events that are planned with an eye toward fun and sociability. The CCFA phone number is 513-772-3550. The CCFA website is www.ccfa.org.