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Jean-Paul Achkar, M.D., Cleveland Clinic Foundation,
Cleveland, Ohio
1. What is inflammatory bowel disease?
Inflammatory bowel disease (IBD) refers to two related but
different diseases: ulcerative colitis and Crohn's disease.
These diseases cause chronic inflammation of the intestinal
tract, which leads to a variety of symptoms. The inflammation
can also lead to involvement of organs other than the intestines.
IBD is a lifelong disease with periods of active disease alternating
with periods of disease control (remission). IBD is sometimes
confused with but is different than irritable bowel syndrome.
There are more than 1 million people with IBD in the United
States with new cases diagnosed at a rate of 10 cases per
100,000 people. These diseases account for 700,000 physician
visits per year and 100,000 hospitalizations per year in the
United States. Ulcerative colitis can be cured with surgery
but Crohn's disease cannot be cured. There are good medical
therapies available for both diseases.
2. Who gets IBD?
IBD is generally a disease of young people because it most
commonly develops between the ages of 10 and 30. However,
a second smaller peak of developing IBD is seen between ages
of 50 and 60.
There are racial and ethnic differences in the risk for developing
IBD. Whites have a higher risk of developing IBD than non-whites.
Similarly persons of Jewish ethnic background have a higher
risk of developing IBD than those of non-Jewish background.
In addition, among persons of Jewish ethnic background, the
risk of IBD is higher for those of Ashkenazi Jewish descent
compared to those of Sephardic Jewish descent.
3. What causes IBD?
The exact cause of IBD is not known but is related to protective
immune cells that are present in the lining of the intestines.
This immune system normally turns on and off to fight harmful
substances like bacteria and viruses that pass through intestines.
In IBD it appears that there is an initial trigger such as
an infection or something taken in from the diet or the surrounding
environmental that activates the immune system. However, the
difference in those who develop IBD is that the immune system
does not turn off once this initial trigger is eliminated.
This leads to uncontrolled inflammation and attack on normal
intestinal cells. The exact contributions of such factors
are poorly understood and are difficult to define.
The best-documented environmental factor associated with
IBD is cigarette smoking. Smokers are more likely to develop
Crohn's disease than non-smokers. In addition, among those
with Crohn's disease, smokers tend to have a more aggressive
form of disease than non-smokers. Interestingly, the opposite
is true for ulcerative colitis, that is, smokers are less
likely to develop ulcerative colitis and tend to have a less
severe course than non-smokers. The exact effects of cigarette
smoking on the intestinal tract and risk for IBD are not well
understood.
Finally, there is a genetic (hereditary) risk of developing
IBD: 10-20% of IBD patients have one or more other family
members affected with IBD. The occurrence of Crohn's disease
is increased among relatives of Crohn's disease patients while
the occurrence of ulcerative colitis is increased among relatives
of ulcerative colitis patients. Both diseases can also exist
in the same family with one family member having ulcerative
colitis and another family member having Crohn's disease.
4. What are the differences between ulcerative
colitis and Crohn's disease?
In ulcerative colitis, inflammation occurs only in the large
intestine (colon) and is limited to the inner lining of the
intestinal wall. The inflammation nearly always starts in
the lowest part of the colon (the rectum) and extends upwards
in continuous pattern. The length of colon that is involved
varies between patients. In some patients, the inflammation
is confined to the rectum only, in others it extends part
of the way up the colon, and in others it involves the entire
colon. Because the inflammation is confined to the colon,
ulcerative colitis is curable by surgical removal of the colon.
Crohn's disease, on the other hand, can involve any part of
the intestinal tract from the mouth to the anal area. The
most commonly involved areas are the lower part of the small
intestine (the ileum) and the colon. Unlike ulcerative colitis,
"skip" lesions can be found in Crohn's disease- this means
that there can be normal areas in between areas that are inflamed.
In addition all layers of the intestinal wall can be involved
which may lead to particular complications that are seen only
in Crohn's disease including: 1. fistula- an abnormal connection
between the intestine and other organs, 2. abscess- collection
of pus, 3. stricture- an area of narrowing that can lead to
intestinal blockage. Because Crohn's disease usually comes
back after surgery, it is generally not curable.
5. What are the symptoms of IBD?
The most common symptoms seen in both ulcerative colitis
and Crohn's disease are diarrhea, rectal bleeding, urgency
to have bowel movements, abdominal cramps and pain, fever,
and weight loss. In Crohn's disease, symptoms can result from
complications of the disease. Fistulas can lead to openings
in the skin and around the anal region that drain stool and
infected material. An abscess can lead to symptoms of severe
pain and fever. A stricture can lead to intestinal blockage
with symptoms of filling up quickly after meals, nausea and
vomiting.
In addition, organs other than the intestinal tract can be
involved by the underlying inflammation of IBD. These organs
include the eyes (symptoms of red eye or blurred vision),
the mouth (symptoms of sores in the mouth), joints (symptoms
of joint pain with or without joint swelling and redness),
and skin (symptoms of rashes or skin ulcers most commonly
involving the lower legs).
6. How is the diagnosis of IBD made?
The initial part of the evaluation of a patient with the
above symptoms includes a full medical history and physical
examination. Doctors collect information such as the details
and duration of symptoms, whether there is a family history
of IBD, and cigarette smoking history. Blood tests can help
detect changes such as low red blood cell counts (anemia),
high white blood cell counts (indicate inflammation or infection),
and low nutrient levels. Stool samples are sometimes checked
to rule out intestinal infections, which can lead to similar
symptoms as those of IBD.
The most direct way to make a firm diagnosis of IBD involves
the use of endoscopy (putting a tube with a light at the end
into the intestines), biopsies, or special X-rays. With endoscopy,
the lining of the intestinal tract can be directly seen by
the doctor performing the procedure and biopsies can be obtained.
Typical changes of IBD can be detected by endoscopy and by
examining biopsies under a microscope. Picture 1 shows
the appearance of a normal colon at endoscopy while Picture
2 shows an inflamed colon that is typical for the appearance
of ulcerative colitis at endoscopy. Picture 3 shows
ulcers in the intestine that are typical for Crohn's disease.
Barium X-rays known as small bowel series are also commonly
used to diagnose IBD. Patients drink barium (a white fluid),
which allows doctors to take X-ray pictures of the small intestine
and to look for changes typical of IBD. This test is particularly
helpful in evaluating the small intestine, which is the part
of the intestinal tract that cannot be fully examined with
endoscopes. Another type of X-ray that is sometimes done in
patients with IBD is a CAT scan, which is used to look for
the presence of an abscess in the abdomen of patients with
Crohn's disease. Capsule endoscopy is a newer test in which
a pill is swallowed and then travels through the small intestine
taking pictures that are transmitted to a recorder and later
viewed on a computer. Recent studies indicate that capsule
endoscopy is more sensitive for Crohn's in the small intestine
than x-rays, but the role of capsule endoscopy in Crohn's
disease is not yet identified.
7. What medications can be used to treat
IBD?
Because ulcerative colitis and Crohn's disease are chronic
illnesses, they often require long-term treatment with medications.
In general there are two main goals of medical therapy for
IBD: 1. Bring active disease under control (into remission),
and 2. Keep the disease in remission. Fortunately, there are
several good medical therapies available to treat IBD and
the most commonly used drugs will be reviewed below.
Aminosalicylates:
These types of medications are among the most commonly used
to treat IBD and include agents such as sulfasalazine (Azulfidine®)
and mesalamine (Asacol®, Pentasa®, Colazal®).
The active component of these medications is a compound named
5-aminosalicylic acid, which works to reduce inflammation
in the intestinal wall. These compounds are prepared differently
and based on this release 5-aminosalicylic acid in different
parts of the intestinal tract. All the above preparations
come as pills taken by mouth but there are also suppository
and enema forms of mesalamine that are applied directly into
the rectum and used to treat patients with inflammation in
the bottom part of the colon.
These medications work well for mild to moderate ulcerative
colitis and Crohn's disease affecting the colon. They are
not as effective for Crohn's inflammation of the small intestine
or for more severe IBD. When effective, they work both to
bring active disease under control and to maintain disease
in remission. They are generally well tolerated with minimal
side effects.
Steroids:
Steroids such as prednisone and methylprednisolone are commonly
used to treat patients with both ulcerative colitis and Crohn's
disease. These particular types of steroids are called glucocorticoids
and work as anti-inflammatory agents. They are different from
anabolic steroids, which are known for their use by body builders
and athletes.
The main role of these medications in IBD is to bring the
disease into remission. For patients whose disease seems to
require repeated or chronic steroid courses, other medical
treatment options described below are available and should
be pursued (see discussion of side effects below). Most commonly
these medications are given orally. However, in moderate to
severe cases of IBD, patients are brought into the hospital
and intravenous steroids are used to bring the disease under
control. There are also enema and suppository preparations
of steroids available.
There are multiple possible side effects from steroids most
of which are more likely to develop with higher doses and
longer duration of therapy. Early side effects can
include mood changes, irritability, difficulty sleeping, increased
appetite, and increased blood sugar levels. Side effects associated
with long-term use include osteoporosis (weakening
of the bones), cataracts, acne, development of a fatty hump
at the base of the neck, and a rounded/swollen appearance
to the face (moon facies). Although there are possible side
effects from these types of steroids, they remain an important
part of the medical management of inflammatory bowel disease.
With appropriate dosing and tapering regimens, most patients
tolerate steroids well.
More recently a new steroid preparation named budesonide
(Entocort®) has been made available in the United States
for treatment of Crohn's disease. This steroid is specifically
designed to release in the intestines with very little of
it reaching the bloodstream. Because of this, budesonide has
less in terms of side effects when compared to conventional
steroids. In its current formulation, this agent works mostly
in treating inflammation in the bottom part of the small intestine
(the ileum) and the right part of the colon.
6-Mercaptopurine and Azathioprine:
6-mercaptopurine (Purinethol®) and azathioprine (Imuran®)
work to decrease the activity of the immune system, which
then leads to reduced inflammation in the intestines. They
are used both in ulcerative colitis and Crohn's disease to
bring active disease under control and to maintain disease
in remission. They are given orally as pills.
These agents may take a few weeks to months to take their
full effect, so other medications such as steroids are sometimes
needed on a short-term basis to keep disease under control
when starting 6-mercaptopurine or azathioprine. These medications
have less long-term side effects than steroids. Approximately
5-10% of patients cannot tolerate these medications due to
side effects such as allergic reactions, pancreatitis (inflammation
of the pancreas), and abnormal liver tests. Because these
medications affect the immune system, patients have a higher
risk of developing infections. Therefore, it is recommended
that blood counts be monitored on a frequent and regular basis
when on these medications.
Methotrexate:
Methotrexate is another medication that works to decrease
the activity of the immune system. It is used in Crohn's disease
both to bring disease into remission and to maintain remission.
There have been some reports of methotrexate for treatment
of ulcerative colitis but there are no controlled studies
that have shown a benefit. Methotrexate can be given either
as pills or as an injection under the skin or into the muscle,
but the studies that have shown that it works in IBD have
used the injection approach. A vitamin named folate (or folic
acid) should be given with methotrexate to decrease some of
the side effects. Potential side effects and risks include
nausea, vomiting, infections, bone marrow suppression, liver
inflammation, and rarely scarring in the lungs. Methotrexate
is also known to cause birth defects and therefore should
not be used in either males or females who are trying to have
a baby.
Infliximab:
Infliximab (Remicade®) may be used in moderate to severe
Crohn's disease. It is a medication that is given intravenously
and works on reducing intestinal inflammation by blocking
a part of the immune system know as TNF (tumor necrosis factor).
A single infusion or a short series of three infusions have
been shown to bring inflammation into remission and to allow
closure of fistulas. The benefit may last approximately two
months. However, recent studies have shown that repeated infusions
of infliximab over a one-year period are generally well tolerated
and can maintain remission. Side effects of this agent include
infusion reactions, which are usually mild, and infections.
Occasionally the infections are quite serious.
8. When is surgery indicated for IBD?
For ulcerative colitis, there are two main indications for
surgery: 1. Lack of response or intolerance to medications,
and 2. Precancerous or cancerous changes in the colon. Patients
with ulcerative colitis have a higher risk of developing colon
cancer so careful monitoring of the colon by colonoscopy is
recommended in those who have had the disease for many years.
As previously discussed, surgery allows for a cure in ulcerative
colitis. However, removal of the colon used to mean that patients
would have to have a permanent stoma (wearing an external
bag to drain stool). Currently, a procedure known as the pouch
procedure can be done in most patients with ulcerative colitis
and this prevents the need for a permanent stoma. In this
type of surgery, the colon is removed, a reservoir is created
out of the lower part of the small intestine (the ileum),
and the reservoir is connected to the anal region.
For Crohn's disease, indications for surgery include lack
of response or intolerance to medications and complications
of Crohn's such as a fistula, an abscess, or a stricture.
Up to 70% of patients with Crohn's disease require surgery
at some point in the course of their disease. The risk of
having Crohn's disease return after surgery is approximately
70-85% within 10-15 years after surgery. There is growing
evidence that medications can be used to decrease the risk
of Crohn's returning following surgery.
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