Inflammatory Bowel Disease (IBD)

Picture of Crohn's disease and ulcerative colitis.

• 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 ulcerative colitis (UC) and Crohn's disease (CD).
• Ulcerative colitis is limited to the colon (large intestine).
• 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.
• Signs and symptoms of IBD include abdominal cramps and pain, bloody diarrhea, severe urgent need to have a bowel movement, fever, loss of appetite, weight loss, and anemia (due to blood loss).
• Intestinal complications of IBD include bleeding ulcers, perforation of the bowel, obstruction of the bowel from scarring, fistulae (abnormal passage), perianal disease, toxic megacolon, and a higher risk of colon and small intestinal cancers. Other complications of IBD include arthritis, skin conditions, eye inflammation, liver and kidney disorders, and bone loss.
• Tests used to diagnose IBD include stool examination, complete blood count, barium X-ray of the upper and/or lower GI tract, sigmoidoscopy, colonoscopy, and upper endoscopy.
• Diet changes that may help with IBD include decreasing the amount of fiber or dairy products.
• Diet has little or no influence on the inflammatory activity in ulcerative colitis but it may influence symptoms, and low-residue diets may decrease the frequency of bowel movements.
• Diet can influence inflammatory activity in Crohn's disease. Nothing by mouth, a liquid diet, or a predigested formula may reduce inflammation.
• Stress management and quitting smoking are also important in treating and managing IBD.
• Medical treatment for IBD depends upon whether it is Crohn's disease or ulcerative colitis. Medications may be prescribed. Ulcerative colitis can be cured with surgery but Crohn's disease cannot.
• Medications used to treat IBD include amino-salicylates, antibiotics, corticosteroids, immune modifying agents, and biologic agents (anti-tumor necrosis factor (TNF) agents).
• The prognosis for IBD varies. Most patients will have periods of remission interspersed with occasional flare-ups. A person with ulcerative colitis has a 50% probability of having another flare-up during the next 2 years. The course of Crohn's disease is much more variable than that of ulcerative colitis.

• Inflammatory bowel disease (IBD) is a group of chronic diseases that cause inflammation of the intestines and are believed to be a result of a disordered immune system attacking itself. However, the cause for this immune reaction remains unknown.
• The two main types of IBD are ulcerative colitis (UC), which affects only the colon and rectum, and Crohn's disease (CD), which can affect any part of the gastrointestinal tract from the mouth to the anus.
• IBD has a genetic component and tends to run in families. About 1.6 million Americans are affected, both males and females equally. Patients with IBD also have a higher risk of developing colon or rectal cancers.

Inflammatory bowel disease is a chronic disease (lasting a long time), and a person has periods of time 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. Signs and symptoms of IBD include:

1. Abdominal cramps and pain
2. Bloody diarrhea
3. Severe urgency to have a bowel movement
4. Fever
5. Loss of appetite
6. Weight loss
7. Anemia (due to blood loss)

If a person has the previously mentioned symptoms and signs, a visit to a doctor is warranted. Although those symptoms can suggest that the person may have inflammatory bowel disease, tests must first be performed to see if they do have IBD. The same symptoms are seen in several other disorders as well, and so the symptoms alone do not necessarily mean a person has IBD. Irritable bowel syndrome (IBS) is a different disorder that may have symptoms similar to those of IBD.

The two common types of inflammatory bowel disease, Crohn's Diseased and ulcerative colitis or UC. Both Crohn's diseases are similar, but they affect different parts of the digestive system. 

Ulcerative Colitis

• Ulcerative colitis affects the large intestine and rectum, and causes swelling and tiny open sores, or ulcers, on the surface of the lining of the large intestine or rectum.
• The ulcers can bleed and produce pus.
• In ulcerative colitis, there is a continuous area of damage along the large intestine and rectum, rather than patches of damage.

Crohn's Disease

• In Crohn's disease, it affects any part of the digestive system, from the mouth to the anus.
• Inflammation affects the entire digestive tract in Crohn’s disease while ulcerative colitis only affects the large intestine (also called the colon).

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.

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.

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

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.

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.

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

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).

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 associated with influencing the development of IBD.

There is a genetic predisposition (or perhaps susceptibility) to the development of IBD, but the triggering factor for the 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 (for example, 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 the normal immune responses.

Both inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) may have similar symptoms including abdominal pain, diarrhea, and urgent bowel movements, but IBD is not the same as IBS.

• IBD is a group of separate diseases that includes Crohn's disease and ulcerative colitis, and is a more severe condition. Inflammatory bowel disease can result in permanent damage to the intestines, intestinal bleeding, rectal bleeding, ulcers, or serious complications.
• IBS is considered a functional gastrointestinal disorder because there is abnormal bowel function. In general, IBS has few associated complications other than the symptoms of the disorder itself.

Intestinal complications of inflammatory bowel disease include:

• Profuse bleeding from the ulcers
• Perforation (rupture) of the bowel
• Strictures and obstruction: In persons with Crohn's disease, narrowing of the intestines due to inflammation occurs, and frequently resolves 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 mega-colon (acute without obstructive dilation of the colon): Although rare, toxic mega colon is a life-threatening complication of ulcerative colitis and requires urgent surgical intervention.
• Malignancy: The risk of colon cancer in ulcerative colitis begins to rise significantly above that of the general population after approximately 8 to 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
  • Bone loss
• Of all the extraintestinal complications, arthritis is the most common. Joint, eye, and skin complications often occur together.

A healthcare professional makes the diagnosis of inflammatory bowel disease based on the patient's symptoms and various diagnostic procedures 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 infection in the body.
• If a person has severe bleeding, the red blood cell count may decrease and hemoglobin levels 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 swallow barium (a chalky white substance), which coats the inside of the intestinal tract, and can be documented on X-rays. If a person has Crohn's disease, abnormalities will be seen on barium X-rays.
• Lower gastrointestinal (GI) tract: In this exam, barium is given as 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, a doctor 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, the doctor 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% to 10% of persons with Crohn's disease.

Diet changes may be necessary for both diseases. It is important to eat a healthy diet.

• Depending on the person's symptoms, a health care professional may ask them to decrease the amount of fiber or dairy products in their 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 the reduction of inflammation, as might the use of a liquid diet or a predigested formula.
• When a person becomes extremely stressed, IBD symptoms may get worse. Therefore, it is important that patients learn to manage the stress in their lives.

Medical treatment for IBD depends upon whether it is Crohn's disease or ulcerative colitis. There are a variety of medications prescribed to treat the disease and symptoms of the disease. While ulcerative colitis can be resolved with surgery, Crohn's disease cannot, and the patient may continue to suffer from the disease.

The goal of medical treatment is to suppress the abnormal inflammatory response. This allows the intestinal tissue to heal, 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 that are less benign are used.

• The amino-salicylates work on the lining of the intestine and are step I drugs under this scheme. Antibiotics are step IA drugs; they are particularly used in persons with Crohn's disease who have perianal disease or an inflammatory mass where infection is a concern.
• 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 it may take up to 2 to 3 months for these drugs to work. Examples of immune modifying agents are azathioprine (Azasan, Imuran) and 6 mercaptopurine (Purinethol).
• Biologic agents are anti TNF and non anti TNF agents. These are step IIIA drugs to be used in persons with Crohn's disease and ulcerative colitis. The biologic agents which are now approved by the FDA for treatment of Crohn's disease are infliximab (Remicade), adalimumab (Humira), certolizumab (Cimzia). Anti-TNF agents approved for ulcerative colitis are: infliximab (Remicade), adalimumab (Humira) and golimumab (Simponi). Non anti-TNF biologic agents that have been approved are: vedolizumab (Entyvio), ustekinumab (Stelera) and natalizumab (Tysabri).
• The experimental agents are step IV drugs to be used only after failure of the previous steps and only by health care professionals familiar with their use.

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

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

• Amino-salicylates are aspirin-like anti-inflammatory drugs. The oral amino salicylate preparations available for use in the US: sulfasalazine (Azulfidine), mesalamine (Asacol, Pentasa, Apriso, Lialda), olsalazine (Dipentum), balsalazide (Colazal). The topical rectal formulation of mesalamine is Rowasa and Canasa.
• These drugs can be given either orally or rectally (enema, suppository formulations). They are useful both for treating flare-ups of IBD and maintenance of remission.

Corticosteroids

• Corticosteroids are rapid-acting anti-inflammatory drugs. 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 [Medrol, Medrol Dosepak], hydrocortisone [Cortef, Hydrocortone]) in the hospital, orally (prednisone, prednisolone, budesonide [Entocort EC), dexamethasone [AK-Dex, Ocu-Dex]), 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 to 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 amino-salicylates.
• If a patient is taking immune modifiers, their blood cell count is monitored on a regular basis because the immune modifiers can cause a significant reduction in the number of white blood cells, predisposing the patient to serious infections.
• Folic acid supplements are recommended when taking immune modifiers.

Anti-TNF Agents

Examples of anti-TNF agents include infliximab (Remicade), adalimumab (Humira), and certolizumab (Cimzia). Another anti-TNF agent, golimumab (Simponi), has been approved only for ulcerative colitis.

• Infliximab (Remicade) is an anti-TNF agent. TNF (tumor necrosis factor) is produced by white blood cells and is believed to be responsible for promoting the tissue damage noted in persons with Crohn's disease and ulcerative colitis. 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 (Flagyl, Flagyl 375, Flagyl ER) and ciprofloxacin (Cipro, Cipro XR, Proquin XR) 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) where infection is a concern.
• It is generally recommended that the use of metronidazole and ciprofloxacin be limited to short durations and be used intermittently as much as possible. Long term continuous use of metronidazole can lead to peripheral neuropathy - tingling and numbness in feet. Ciprofloxacin in long term continuous use can increase the chance of rupturing the Achilles tendon.

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

Experimental Agents

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

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 to possibly allow for healing of the disease away from the site where surgery is done.

Ulcerative Colitis Surgery

• In about 25% to 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 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 Surgery

• 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 re-anastomosed (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 of the distal colon and the rectum is halted to allow healing, and then the ileostomy/colostomy is reversed.

• 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 to 10 years of the onset of the disease. For cancer prevention, surveillance colonoscopy every 1 to 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.
• Patients taking steroids should undergo a yearly ophthalmologic examination because of the risk of development of cataracts.
• Persons with IBD may 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.

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 one flare-up over 25 years (as many as 10%); others may have almost constant flare-ups (much less common).
• Persons with ulcerative colitis involving 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) alone continue to have disease limited to the rectum over 20 years. Most of the patients 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 surgical interventions are 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) of the disease 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 will 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 patients should be aware that it is not curative and that disease recurrence after surgery is the rule.

• 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 an increase in the number and severity of flare-ups of Crohn's disease. Quitting smoking occasionally is sufficient to make a person with refractory (not responding to treatment) Crohn's disease go into remission.