Inflammatory Bowel Disease

 Overview

The term inflammatory bowel disease (IBD) covers a group of disorders in which the intestines become inflamed (red and swollen), probably as a result of an immune reaction of the body against its own intestinal tissue.

Two major types of IBD are described: ulcerative colitis (UC) and Crohn's disease (CD). As the name suggests, ulcerative colitis is limited to the colon (large intestine). Although Crohn's disease can involve any part of the gastrointestinal tract from the mouth to the anus, it most commonly affects the small intestine and/or the colon.

Both ulcerative colitis and Crohn's disease usually run a waxing and waning course in the intensity and severity of illness. When there is severe inflammation, the disease is considered to be in an active stage, and the person experiences a flare-up of the condition. When the degree of inflammation is less (or absent), the person usually is without symptoms, and the disease is considered to be in remission.

Causes

Researchers do not yet know what causes inflammatory bowel disease. Therefore, IBD is called an idiopathic disease (disease with an unknown cause).
An unknown factor/agent (or a combination of factors) triggers the body’s immune system to produce an inflammatory reaction in the intestinal tract that continues without control. As a result of the inflammatory reaction, the intestinal wall is damaged leading to bloody diarrhea and abdominal pain.
Genetic, infectious, immunologic, and psychological factors have all been implicated in influencing the development of IBD.
There is a genetic predisposition (or perhaps susceptibility) to the development of IBD. However, the triggering factor for activation of the body’s immune system has yet to be identified. Factors that can turn on the body’s immune system include an infectious agent (as yet unidentified), an immune response to an antigen (eg, protein from cow milk), or an autoimmune process. As the intestines are always exposed to things that can cause immune reactions, more recent thinking is that there is a failure of the body to turn off normal immune responses.

Symptoms

Because inflammatory bowel disease is a chronic disease (lasting a long time), you will go through periods in which the disease flares up and causes symptoms. These periods are followed by remission, in which symptoms disappear or decrease and good health returns.

Symptoms may range from mild to severe and generally depend upon the part of the intestinal tract involved. They include the following:

• Abdominal cramps and pain
• Bloody diarrhea
• Severe urgency to have a bowel movement
• Fever
• Loss of appetite
• Weight loss
• Anemia (due to blood loss)

Intestinal complications of inflammatory bowel disease include the following:

• Profuse bleeding from the ulcers
• Perforation (rupture) of the bowel
• Strictures and obstruction: In persons with Crohn's disease, strictures often are inflammatory and frequently resolve with medical treatment. Fixed or fibrotic (scarring) strictures may require endoscopic or surgical intervention to relieve the obstruction. In ulcerative colitis, colonic strictures should be presumed to be malignant (cancerous).
• Fistulae (abnormal passage) and perianal disease: These are more common in persons with Crohn's disease. They may not respond to vigorous medical treatment. Surgical intervention often is required, and there is a high risk of recurrence.
• Toxic megacolon (acute nonobstructive dilation of the colon): This is a life-threatening complication of ulcerative colitis and requires urgent surgical intervention. It is fortunately relatively rare.
• Malignancy: The risk of colon cancer in ulcerative colitis begins to rise significantly above that of the general population after approximately 8-10 years of diagnosis. The risk of cancer in Crohn's disease may equal that of ulcerative colitis if the entire colon is involved. The risk of small intestine malignancy is increased in Crohn's disease.

Extraintestinal complications

• Extraintestinal involvement of IBD refers to complications involving organs other than the intestines. These affect only a small percentage of people with IBD.
• Persons with IBD may have arthritis, skin conditions, inflammation of the eye, liver and kidney disorders, and bone loss. Of all the extraintestinal complications, arthritis is the most common. Joint, eye, and skin complications often occur together.

Exams and Tests

Your health care provider makes the diagnosis of inflammatory bowel disease based on your symptoms and various exams and tests.
 
Stool examination

• A stool examination is done to eliminate the possibility of bacterial, viral, or parasitic causes of diarrhea.

• A fecal occult blood test is used to examine stool for traces of blood that cannot be seen with the naked eye.

Complete blood count

• An increase in the white blood cell count suggests the presence of inflammation in the body. 
• If you have severe bleeding, the red blood cell count may decrease and hemoglobin level may fall (anemia).

Both the above tests are not diagnostic of IBD, as they may be abnormal in many other diseases.
 
Barium x-ray

• Upper gastrointestinal (GI) tract: This exam uses x-rays to find abnormalities in the upper GI tract (esophagus, stomach, duodenum, sometimes the small intestine). For this test, you are required to swallow barium (a chalky white substance). When barium is swallowed, it coats the inside of the intestinal tract, which can be documented on x-rays. If you have Crohn's disease, abnormalities will be seen on barium x-rays.
• Lower gastrointestinal (GI) tract: In this exam, barium is given in an enema that is retained in the colon while x-rays are taken. Abnormalities will be noted in the rectum and colon in persons with Crohn's disease and ulcerative colitis.

Sigmoidoscopy: In this procedure, your health care provider uses a sigmoidoscope (a narrow, flexible tube with a lens and a light source) to visualize the last one-third of the large intestine, which includes the rectum and the sigmoid colon. The sigmoidoscope is inserted through the anus and the intestinal wall is examined for ulcers, inflammation, and bleeding. During this procedure, your health care provider may take samples (biopsies) of the lining of the intestine.

Colonoscopy: A colonoscopy is an examination similar to a sigmoidoscopy, but with this procedure, the entire colon can be examined.

Upper endoscopy: If you have upper GI symptoms (nausea, vomiting), an endoscope (narrow, flexible tube with a light source) is used to examine the esophagus, stomach, and the duodenum. The endoscope is inserted through the mouth, and the stomach and duodenum are examined for ulceration. Ulceration occurs in the stomach and duodenum in 5-10% of persons with Crohn's disease.

Treatment

Self-Care at Home

It is important to eat a healthy diet. Depending on your symptoms, your health care provider may ask you to decrease the amount of fiber or dairy products in your diet.

Diet has little or no influence on the inflammatory activity in ulcerative colitis. However, diet may influence symptoms. For this reason, people with inflammatory bowel disease often are placed on a variety of diet interventions, especially low-residue diets. Evidence does not support a low-residue diet as beneficial in treating the inflammation of ulcerative colitis, though it might decrease the frequency of bowel movements.

Unlike ulcerative colitis, diet can influence inflammatory activity in Crohn's disease. Nothing by mouth (NPO status) can hasten reduction of inflammation, as might the use of a liquid diet or a predigested formula.

When you become extremely upset, your symptoms may get worse. Therefore, it is important that you learn to manage the stress in your life.

Medical Treatment

The goal of medical treatment is to suppress the abnormal inflammatory response. This allows the intestinal tissue to heal, thereby relieving the symptoms of diarrhea and abdominal pain. Once the symptoms are under control, medical treatment is used to decrease the frequency of flare-ups and to maintain remission.

A stepwise approach to the use of medications for inflammatory bowel disease may be taken. With this approach, the most benign (least harmful) drugs or drugs taken for a short period of time are used first. If they fail to provide relief, drugs from a higher step are used.

The aminosalicylates and symptomatic agents are step I drugs under this scheme. Antibiotics are a step IA; they are particularly used in persons with Crohn's disease who have perianal disease or an inflammatory mass.

Corticosteroids constitute step II drugs to be used if the step I drugs fail to provide adequate control of the IBD. They tend to provide rapid relief of symptoms as well as a significant decrease in inflammation.

The immune modifying agents are step III drugs to be used if corticosteroids fail or are required for prolonged periods. These agents are not used in acute flare-ups because the time from initiation of treatment to the onset of significant action may be as long as 2-3 months. Infliximab is a step IIIA drug to be used in persons with Crohn's disease. As of this writing, the medications approved by the US FDA for the treatment of Crohn's disease are prednisone, budesonide, and infliximab.

The experimental agents are step IV drugs to be used only after failure of the previous steps and only by health care providers familiar with their use.

Note that drugs from all steps may be used additively; in general, the goal is to wean off the corticosteroids as soon as possible to prevent long-term side effects. There may be different opinions regarding the use of certain agents in this stepwise approach.

Medications

Different groups of drugs are used for the treatment of persons with inflammatory bowel disease. These include aminosalicylates, corticosteroids, immune modifiers, anti-tumor necrosis factor (TNF) agents, and antibiotics.

Aminosalicylates

• Aminosalicylates are aspirinlike anti-inflammatory drugs. There are 5 aminosalicylate preparations available for use in the US: sulfasalazine (Azulfidine), mesalamine (Asacol, Pentasa), olsalazine (Dipentum), and balsalazide (Colazal).
• These drugs can be given either orally or rectally (enema, suppository formulations). They are useful both for treating flare-ups of the IBD and the maintenance of remission.

Corticosteroids

• Corticosteroids are rapid-acting anti-inflammatory agents. The indication for use in IBD is for acute flare-ups of the disease only. There is no role for corticosteroids in the maintenance of remission.
• Corticosteroids may be administered by a variety of routes, depending upon the location and severity of disease; they may be administered intravenously (methylprednisolone, hydrocortisone) in the hospital, orally (prednisone, prednisolone, budesonide, dexamethasone), or rectally (enema, suppository, foam preparations).
• Corticosteroids tend to provide rapid relief of symptoms as well as a significant decrease in inflammation, but their side effects limit their use (particularly longer-term use). The consensus for treatment with corticosteroids is that they should be tapered as soon as possible.

Immune modifiers

• Immune modifiers include 6-mercaptopurine (6-MP, Purinethol) and azathioprine (Imuran). Immune modifiers may work by causing a reduction in the lymphocyte count (a type of white blood cell). Their onset of action is relatively slow (typically 2-3 months).
• They are used in selected persons with IBD when aminosalicylates and corticosteroids are either ineffective or only partially effective. They are useful in reducing or eliminating some persons' dependence on corticosteroids.
• Immune modifiers may also be helpful in maintaining remission in some persons with refractory ulcerative colitis (persons who do not respond to standard medications).
• They are also used as primary treatment of fistulae and the maintenance of remission in persons who cannot tolerate aminosalicylates.
• If you are taking immune modifiers, your blood cell count will be monitored on a regular basis because the immune modifiers can cause a significant reduction in the number of white blood cells, predisposing you to serious infections.

Anti-TNF agent

• Infliximab (Remicade) is an anti-TNF agent. TNF is produced by white blood cells and is believed to be responsible for promoting the tissue damage noted in persons with Crohn's disease. Infliximab acts by binding to TNF, thereby inhibiting its effects on the tissues. 
• It is approved by the FDA for the treatment of persons with moderate-to-severe Crohn's disease who have had an inadequate response to standard medications. In such persons, a response rate of 80% and a remission rate of 50% have been reported.
• Infliximab is also used for the treatment of fistulae, a complication of Crohn's disease. Closure of fistulae has been reported in 68% of persons treated with infliximab.
• Infliximab must be given intravenously. It is very expensive, so insurance coverage may play a factor in the decision to use this drug.

Antibiotics

• Metronidazole and ciprofloxacin are the most commonly used antibiotics in persons with IBD.
• Antibiotics are used sparingly in persons with ulcerative colitis because they have an increased risk of developing antibiotic-associated pseudomembranous colitis (a type of infectious diarrhea).
• In persons with Crohn's disease, antibiotics are used for the treatment of complications (perianal disease, fistulae, inflammatory mass).

Symptomatic treatments: You may be given antidiarrheal agents, antispasmodics, and acid suppressants for symptomatic relief.

Experimental agents

• Drugs used in Crohn's disease include methotrexate, thalidomide, and interleukin-11.
• Drugs used in ulcerative colitis include cyclosporine A, nicotine patch, butyrate enema, and heparin.

Surgery

Surgical treatment in persons with inflammatory bowel disease varies, depending upon the disease. Ulcerative colitis is a surgically curable disease because the disease is limited to the colon. However, surgical resection is not curative in persons with Crohn's disease. On the contrary, excessive surgical intervention in persons with Crohn's disease can lead to more problems. Situations arise in Crohn's disease in which surgery without resection can be used. This is done to halt function of the colon in order possibly to allow for healing of the disease distal to the site where surgery is done.

Ulcerative colitis

• In about 25-30% of persons with ulcerative colitis, medical treatment is not completely successful. In such persons and in persons with dysplasia (changes in the cells that are considered a precursor to cancer), surgery may be considered. Unlike Crohn's disease, which can recur after surgery, ulcerative colitis is cured after colectomy (surgical removal of the colon).
• The surgical options for persons with ulcerative colitis depend on a number of factors: the extent of the disease, the person's age, and his overall health. The first option involves the removal of the entire colon and rectum (proctocolectomy) with the creation of an opening on the abdomen through which feces is emptied into a pouch (ileostomy). This pouch is attached to the skin with an adhesive.
• The other most commonly used option is a technically demanding surgery and is generally a multistage procedure. The surgeon removes the colon, creates an internal ileal pouch from the small intestine, attaches it to the anal sphincter muscle (ileoanal anastomosis), and creates a temporary ileostomy. After the ileoanal anastomosis heals, the ileostomy is closed and the passage of the feces through the anus is reestablished.

Crohn's disease 

• Even though surgery is not curative in persons with Crohn's disease, approximately 75% of persons will require surgery at some point of time (especially for complications). The most simple surgery for Crohn's disease is the segmental resection, in which a segment of intestine with active disease or a stricture (narrowing) is removed and the remaining bowel is reanastomosed (two ends of healthy bowel are joined together).
• In persons with a very short stricture, instead of removal of that part of the intestine, a bowel-sparing stricturoplasty (repair) can be performed.
• Ileorectal or ileocolonic anastomosis is an option is some persons who have lower small intestine or upper colon disease.
• In persons with severe perianal fistulae, diverting ileostomy/colostomy is a surgical option. In this procedure, the function is halted for the distal colon and a temporary ileostomy or colostomy is created. The rectum, for which function is halted, is allowed to heal, and the ileostomy/colostomy is then reversed.

Next Steps

Follow-up

Persons with inflammatory bowel disease are prone to the development of malignancy (cancer). In Crohn's disease, there is a higher rate of small intestinal malignancy. Persons with involvement of the whole colon, particularly ulcerative colitis, are at a higher risk of developing colonic malignancy after 8-10 years of the onset of the disease. For cancer prevention, surveillance colonoscopy every 1-2 years after 8 years of disease is recommended.
Use of corticosteroids may lead to debilitating illness, particularly after long-term use. You should consider trying more aggressive therapies rather than remaining on corticosteroids because of the potential for side effects with these drugs.
If you are taking steroids, you should undergo a yearly ophthalmologic examination because of the risk of development of cataract.
Persons with IBD have a reduction in bone density, either from decreased calcium absorption (because of the underlying disease process) or because of corticosteroid use. Crippling osteoporosis can be a very serious complication. If you have significantly low bone density, you will be administered bisphosphonates and calcium supplements.

Prevention

No known dietary or lifestyle change prevents the development of inflammatory bowel disease.
Dietary manipulation may help symptoms in persons with ulcerative colitis, and it actually may help reduce inflammation in Crohn's disease. However, there is no evidence that consuming or avoiding any particular food item causes or avoids flare-ups of IBD.
Smoking cessation is the only lifestyle change that may benefit persons with Crohn's disease. Smoking has been linked to increases in the number and severity of flare-ups of Crohn's disease. Smoking cessation occasionally is sufficient to make a person with refractory (not responding to treatment) Crohn's disease go into remission.

Outlook

The typical course of the inflammatory bowel diseases (for the vast majority of persons) includes periods of remission interspersed with occasional flare-ups.

Ulcerative colitis

• A person with ulcerative colitis has a 50% probability of having another flare-up during the next 2 years. However, a very broad range of experiences exists; some persons may only have 1 flare-up over 25 years (as many as 10%); others may have almost constant flare-ups (much less common).
• Persons with ulcerative colitis limited to the rectum and sigmoid at the time of diagnosis have a greater than 50% chance of progressing to more extensive disease and a 12% rate of colectomy over 25 years.
• More than 70% of persons presenting with proctitis (inflammation of the rectum) alone continue to have disease limited to the rectum over 20 years. Most who develop more extensive disease do so within 5 years of diagnosis.
• Among persons with ulcerative colitis involving the entire colon, 60% eventually require colectomy, whereas very few persons with proctitis do.
• Most of the surgical intervention is required in the first year of disease; the annual colectomy rate after the first year is 1% for all persons with ulcerative colitis. Surgical resection for persons with ulcerative colitis is considered curative for the disease.

Crohn's disease

• The course of Crohn's disease is much more variable than that of ulcerative colitis. The clinical activity of Crohn's disease is independent of the anatomic location and extent of the disease.
• A person in remission has a 42% likelihood of being free of relapse for 2 years and only a 12% likelihood of being free of relapse for 10 years.
• Over a 4-year period, approximately 25% of persons remain in remission, 25% have frequent flare-ups, and 50% have a course that fluctuates between periods of flare-ups and remissions.
• Surgery for Crohn's disease generally is performed for the complications (stricture, stenosis, obstruction, fistula, bleeding) rather than for the inflammatory disease itself.
• After operation, there is a high frequency of recurrence of Crohn's disease, generally in a pattern mimicking the original disease pattern, often on one or both sides of the surgical anastomosis.
• Approximately 33% of persons with Crohn's disease who require surgery, require surgery again within 5 years, and 66% require surgery again within 15 years.
• Endoscopic evidence for recurrent inflammation is present in 93% of persons 1 year after surgery for Crohn's disease.
• Surgery is an important treatment option for Crohn's disease, but you should be aware that it is not curative and that disease recurrence after surgery is the rule.

·         Multimedia

·         Media file 1: Stricture, terminal ileum - colonoscopy. Narrowed segment visible upon intubation of the lower small intestine with colonoscope. Relatively little active inflammation is present, indicating this is a cicatrix (scar) stricture.

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Media file 2: Enteroenteric (bowel-to-bowel) fistula - small bowel series x-ray films. The narrow-appearing segments filled out relatively normally on subsequent films. Note that barium is just starting to enter the cecum in the right lower quadrant (reader's left), but that barium has also started to enter the sigmoid colon toward the bottom of the picture, thus indicating the presence of a fistula (hole) from small bowel to sigmoid colon.

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Media file 3: Severe advanced pyoderma gangrenosum (a rare skin complication of inflammatory bowel disease) is present on the left ankle.

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Media file 4: Severe colitis - colonoscopy. The mucosa is grossly denuded, with active bleeding noted. This patient had her colon resected very shortly after this view was obtained.

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Media file 5: Toxic megacolon, a rare complication of ulcerative colitis that almost always requires surgical removal of the colon. Courtesy of Dr Pauline Chu.

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Media file 6: Episcleritis, inflammation of a portion of the eye in conjunction with inflammatory bowel disease. Courtesy of Dr. David Sevel.

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Media file 7: Double-contrast barium enema examination in Crohn's colitis demonstrates numerous aphthous ulcers (the tiny spots on the lining of the intestine).

Media type:  X-RAY