-
Effectiveness of infliximab
-
Duration of benefits of infliximab
-
Side effects of infliximab
-
Precautions with infliximab
-
Identifying patients
who will respond to infliximab
What Is Crohn's Disease?
Crohn's disease is a chronic inflammatory disease of the intestines. It
primarily causes ulcerations of the small and large intestines, but can
affect the digestive system anywhere from the mouth to the anus. It is named
after the physician who described the disease in 1932. It also is called
granulomatous enteritis or colitis, regional enteritis, ileitis, or terminal
ileitis.
Crohn's disease is related closely to another chronic inflammatory condition
that involves only the colon called ulcerative colitis. Together, Crohn's
disease and ulcerative colitis are frequently referred to as inflammatory bowel
disease (IBD). Ulcerative colitis and Crohn's disease have no medical cure.
Once the diseases begin, they tend to fluctuate between periods of inactivity
(remission) and activity (relapse). Men and women are equally affected.
IBD most commonly begins during adolescence and early adulthood, but it also
can begin during childhood and later in life.
Crohn's disease tends to be more common in relatives of patients with Crohn's
disease. It also is more common among relatives of patients with ulcerative
colitis.
Causes Of Crohn's
Disease
The cause of Crohn's disease is unknown. Some scientists suspect that infection
by certain bacteria, such as strains of mycobacterium, may be the cause of
Crohn's disease. To date, however, there has been no convincing evidence that
the disease is caused by infection. Crohn's disease is not contagious. Although
diet may affect the symptoms in patients with Crohn's disease, it is unlikely
that diet is responsible for the disease.
Activation of the immune system in the intestines appears to be important in
IBD. The immune system is composed of immune cells and the proteins that these
immune cells produce. Normally, these cells and proteins defend the body
against harmful bacteria, viruses, fungi, and other foreign invaders.
Activation of the immune system causes inflammation within the tissues where
the activation occurs. (Inflammation is an important mechanism of defense used
by the immune system.)
Normally, the immune system is activated only when the body is exposed to
harmful invaders. In patients with IBD, however, the immune system is
abnormally and chronically activated in the absence of any known invader. The
continued abnormal activation of the immune system results in chronic
inflammation and ulceration. The susceptibility to abnormal activation of the
immune system is genetically inherited. Thus, first degree relatives (brothers,
sisters, children, and parents) of patients with IBD are more likely to develop
these diseases. Recently a gene called NOD2 has been identified as being
associated with Crohn's disease. This gene is important in determining how the
body responds to some bacterial products. Individuals with mutations in this
gene are more susceptible to developing Crohn's disease.
How
does Crohn's disease affect the intestines?
In the early stages, Crohn's disease causes small, scattered, shallow,
crater-like areas (erosions) on the inner surface of the bowel. These erosions
are called aphthous ulcers. With time, the erosions become deeper and larger,
ultimately becoming true ulcers (which are deeper than erosions) and causing
scarring and stiffness of the bowel. As the disease progresses, the bowel
becomes increasingly narrowed, and ultimately can become obstructed. Deep
ulcers can puncture holes in the wall of the bowel, and bacteria from within
the bowel can spread to infect adjacent organs and the surrounding abdominal
cavity.
When Crohn's disease narrows the small intestine to the point of obstruction,
the flow of the contents through the intestine ceases. Sometimes, the
obstruction can be caused suddenly by poorly-digestible fruit or vegetables
that plug the already-narrowed segment of the intestine. When the intestine is
obstructed, digesting food, fluid and gas from the stomach and the small
intestine cannot pass into the colon. The symptoms of small intestinal
obstruction then appear, including severe abdominal cramps, nausea, vomiting,
and abdominal distention. Obstruction of the small intestine is much more
likely since the small intestine is much narrower than the colon to begin with.
Deep ulcers can puncture holes in the walls of the small intestine and the
colon, and create a tunnel between the intestine and adjacent organs. If the
ulcer tunnel reaches an adjacent empty space inside the abdominal cavity, a
collection of infected pus (an abdominal abscess) is formed. Patients with
abdominal abscesses can develop tender abdominal masses, high fevers, and
abdominal pain.
When the ulcer tunnels into an adjacent organ, a channel (fistula) is formed.
The formation of a fistula between the intestine and the bladder
(enteric-vesicular fistula) can cause frequent urinary tract infections and the
passage of gas and feces during urination. When a fistula develops between the
intestine and the skin (enteric-cutaneous fistula), pus and mucous emerge from
a small painful opening on the skin of the abdomen. The development of a
fistula between the colon and the vagina (colonic-vaginal fistula) causes gas
and feces to emerge through the vagina. The
presence of a fistula from the intestines to the anus (anal fistula) leads to a
discharge of mucous and pus from the fistula's opening around the anus.
How is Crohn's disease different from ulcerative colitis?
While ulcerative colitis causes inflammation only in the colon (colitis) and/or
the rectum (proctitis), Crohn's disease may cause inflammation in the colon,
rectum, small intestine (jejunum and ileum), and, occasionally, even the
stomach, mouth, and esophagus.
The patterns of inflammation in Crohn's disease are different from ulcerative
colitis. Except in the most severe cases, the inflammation of ulcerative
colitis tends to involve the superficial layers of the inner lining of the
bowel. The inflammation also tends to be diffuse and uniform. (All of the
lining in the affected segment of the intestine is inflamed.) Unlike ulcerative
colitis, the inflammation of Crohn's disease is concentrated in some areas more
than others and involves layers of the bowel that are deeper than the
superficial inner layers. Therefore, the affected segment(s) of bowel in
Crohn's disease often is studded with deeper ulcers with normal lining between
these ulcers.
The
symptoms of Crohn's disease:
Common symptoms of Crohn's disease include abdominal pain, diarrhea, and weight
loss. Less common symptoms include poor appetite, fever, night sweats, rectal
pain, and rectal bleeding. The symptoms of Crohn's disease are dependent on the
location, the extent, and the severity of the inflammation. The different
subtypes of Crohn's disease and their symptoms are:
-
Crohn's colitis is inflammation that is confined to the colon. Abdominal pain
and bloody diarrhea are the common symptoms. Anal fistulae and peri-rectal
abscesses also can occur.
-
Crohn's enteritis refers to inflammation confined to the small intestine (the
first part, called the jejunum or the second part, called the ileum).
Involvement of the ileum alone is referred to as Crohn's ileitis. Abdominal
pain and diarrhea are the common symptoms. Obstruction of the small intestine
also can occur.
-
Crohn's terminal ileitis is inflammation that affects only the very end of the
small intestine (terminal ileum), the part of the small intestine closest to
the colon. Abdominal pain and diarrhea are the common symptoms. Small
intestinal obstruction also can occur.
-
Crohn's entero-colitis and ileo-colitis are terms to describe inflammation that
involve both the small intestine and the colon. Bloody diarrhea and abdominal
pain are the common symptoms. Small intestinal obstruction also can occur.
Crohn's terminal ileitis and ileo-colitis are the most common types of Crohn's
disease. (Ulcerative colitis frequently involves only the rectum or rectum and
sigmoid colon at the distal end of the colon. These are called ulcerative
proctitis and procto-sigmoiditis, respectively.)
Up to one third of patients with Crohn's disease may have one or more of the
following conditions involving the anal area:
-
Swelling of the tissue of the anal sphincter, the muscle at the end of the
colon that controls defecation.
-
Development of ulcers and fissures (long ulcers) within the anal sphincter.
These ulcers and fissures can cause bleeding and pain with defecation.
-
Development of anal fistulae (abnormal tunnels) between the anus or rectum and
the skin surrounding the anus). Mucous and pus may drain from the openings of
the fistulae on the skin.
-
Development of peri-rectal abscesses (collections of pus in the anal and rectal
area). Peri-rectal abscesses can cause fever, pain and tenderness around the
anus.
The
Complications Of Crohn's Disease:
Complications of Crohn's disease may be related or unrelated to the inflammation
within the intestine (i.e., intestinal or extra-intestinal). Intestinal
complications of Crohn's disease include obstruction and perforation of the
small intestine, abscesses (collections of pus), fistulae, and intestinal
bleeding. Massive distention or dilatation of the colon (megacolon), and
rupture (perforation) of the intestine are potentially life-threatening
complications. Both generally require surgery, but, fortunately, these two
complications are rare. Recent data suggest that there is an increased risk of
cancer of the small intestine and colon in patients with long-standing Crohn's
disease.
Extra-intestinal complications involve the skin, joints, spine, eyes, liver,
and bile ducts. Skin involvement includes painful red raised spots on the legs
(erythema nodosum) and an ulcerating skin condition generally found around the
ankles called pyoderma gangrenosum. Painful eye conditions (uveitis,
episcleritis) can cause visual difficulties. Arthritis can cause pain,
swelling, and stiffness of the joints of the extremities. Inflammation of the
low back (sacroiliac joint arthritis) and of the spine (ankylosing spondylitis)
can cause pain and stiffness of the spine. Inflammation of the liver
(hepatitis) or bile ducts (primary sclerosing cholangitis) also can occur.
Sclerosing cholangitis causes narrowing and obstruction of the ducts draining
the liver and can lead to yellow skin (jaundice), recurrent bacterial
infections, and liver cirrhosis with liver failure. Sclerosing cholangitis with
liver failure is one of the reasons for performing liver transplantation.
Sclerosing cholangitis frequently is complicated by the development of cancer
of the bile ducts.
Diagnosis Of Crohn's Disease:
The diagnosis of Crohn's disease is suspected in patients with fever, abdominal
pain and tenderness, diarrhea with or without bleeding, and anal diseases.
Laboratory blood tests may show elevated white cell counts and sedimentation
rates, both of which suggest infection or inflammation. Other blood tests may
show low red blood cell counts (anemia), low blood proteins, and low body
minerals, reflecting loss of these elements due to chronic diarrhea.
Barium x-ray studies can be used to define the distribution, nature, and
severity of the disease. Barium is a chalky material that is visible by x-ray
and appears white on x-ray films. When barium is ingested orally (Upper GI
Series)it fills the intestine and pictures (x-rays) can be taken of the stomach
and the small intestines. When barium is administered through the rectum
(Barium Enema), pictures of the colon and the terminal ileum can be obtained.
Barium x-rays can show ulcerations, narrowing, and, sometimes, fistulae of the
bowel.
Direct visualization of the rectum and the large intestine can be accomplished
with flexible viewing tubes (colonoscopes). Colonoscopy is more accurate than
barium x-rays in detecting small ulcers or small areas of inflammation of the
colon and terminal ileum. Colonoscopy also allows for small tissue samples
(biopsies) to be taken and sent for examination under the microscope to confirm
the diagnosis of Crohn's disease. Colonoscopy also is more accurate than barium
x-rays in assessing the degree (activity) of inflammation.
Computerized Axial Tomography (CAT or CT) scanning is a computerized x-ray
technique that allows imaging of the entire abdomen and pelvis. It can be
especially helpful in detecting abscesses.
Most recently, video capsule endoscopy has been added to the list of diagnostic
tests for diagnosing Crohn's disease. For video capsule endoscopy, a capsule
containing a minature video camera is swallowed. As the capsule travels through
the small intestine, it sends video images of the lining of the small intestine
to a receiver carried on a belt at the waist. The images are downloaded and
then reviewed on a computer. The value of video capsule endoscopy is that it
can identify the early, mild abnormalities of Crohn's disease. Video capsule
endoscopy may be particularly useful when there is a strong suspicion of
Crohn's disease but the barium x-rays are normal. (Barium x-rays are not as
good at identifying early, mild Crohn's disease.)
Video capsule endoscopy should not be performed in patients who have
obstruction of the small intestine. The capsule may get stuck behind the
obstruction and make the obstruction worse. Doctors usually also are reluctant
to perform video-capsule endoscopy for the same reason in patients who they
suspect of having small intestinal strictures (narrowed segments of small
intestine that can result from prior surgery, prior radiation, or chronic
ulceration, for example, from Crohn's disease).There is also a theoretical
concern for electrical interference between the capsule and implanted cardiac
pacemakers and defibrillators; however, so far in a small number of patients
with pacemakers or defibrillators who have undergone video capsule endoscopy
there have been no problems.
Treatments Of
Crohn's Disease:
The symptoms and severity of Crohn's disease vary among patients. Patients with
mild or no symptoms may not need treatment. Patients whose disease is in
remission (where symptoms are absent) also may not need treatment.
There is no medication that can cure Crohn's disease. Patients with Crohn's
disease typically will experience periods of relapse (worsening of
inflammation) followed by periods of remission (reduced inflammation) lasting
months to years. During relapses, symptoms of abdominal pain, diarrhea, and
rectal bleeding worsen. During remissions, these symptoms improve. Remissions
usually occur because of treatment with medications or surgery, but
occasionally they occur spontaneously, that is, without any treatment.
Since there is no cure for Crohn's disease, the goals of treatment are to 1)
induce remissions, 2) maintain remissions, 3) minimize side effects of
treatment, and 4) improve the quality of life. Treatment of Crohn's disease and
ulcerative colitis with medications is similar though not always identical.
Medications for treating Crohn's disease include 1) anti-inflammatory agents
such as 5-ASA compounds, corticosteroids, topical antibiotics, 2)
immuno-modulators, 3)other medications.
Anti-inflammatory medications
Anti-inflammatory medications that decrease intestinal inflammation are
analogous to arthritis medications that decrease joint inflammation. Different
types of anti-inflammatory medications used in the treatment of Crohn's disease
are:
-
5-ASA compounds such as sulfasalazine (Azulfidine) and mesalamine (Pentasa,
Asacol, Dipentum, Colazal, Rowasa enema, Canasa suppository) that act via
direct contact (topically) with the inflamed tissue in order to be effective.
-
Corticosteroids that act systemically (without the need for direct contact with
the inflamed tissue) to decrease inflammation throughout the body. Systemic
corticosteroids have important and predictable side effects if used long-term.
-
A new class of topical corticosteroid (e.g., budesonide) that acts via direct
contact (topically) with the inflamed tissue. This class of corticosteroids has
fewer side effects than systemic corticosteroids which are absorbed into the
body.
-
Antibiotics such as metronidazole (Flagyl) and ciprofloxacin (Cipro) that
decrease inflammation by an unknown mechanism.
5-ASA
(mesalamine) oral medications
5-aminosalicylic acid (5-ASA)), also called mesalamine, is similar chemically to
aspirin. Aspirin has been used for many years for treating arthritis, bursitis,
and tendonitis (conditions of tissue inflammation). Aspirin, however, is not
effective in treating Crohn's disease and ulcerative colitis, and even may
worsen the inflammation. On the other hand, 5-ASA can be effective in treating
Crohn's disease and ulcerative colitis if the drug can be delivered topically
onto the inflamed intestinal lining. For example, Rowasa is an enema containing
5-ASA that is effective in treating inflammation in the rectum. However, the
enema solution cannot reach high enough to treat inflammation in the upper
colon and the small intestine. Therefore, for most patients with Crohn's
disease involving both the ileum (distal small intestine) and colon, 5-ASA must
be taken orally.
If pure 5-ASA is taken orally, however, most of the 5-ASA would be absorbed in
the stomach and the upper small intestine, and very little 5-ASA would reach
the ileum and colon. To be effective as an oral agent in treating Crohn's
disease, 5-ASA has to be modified chemically to escape absorption by the
stomach and the upper intestines.
Azulfidine
(sulfasalazine)
Azulfidine (sulfasalazine) was the first modified 5-ASA compound used in the
treatment of Crohn's colitis and ulcerative colitis. It has been used
successfully for many years to induce remissions among patients with mild to
moderate ulcerative colitis. Azulfidine also has been used for prolonged
periods for maintaining remissions.
Sulfasalazine consists of a 5-ASA molecule linked chemically to a sulfapyridine
molecule. (Sulfapyridine is a sulfa antibiotic). Connecting the two molecules
together prevents absorption by the stomach and the upper intestines. When
Azulfidine reaches the ileum and the colon, the bacteria that normally are
present break the link between the two molecules. After breaking away from
5-ASA, sulfapyridine is absorbed into the body and later eliminated in the
urine. Most of the active 5-ASA, however, is available within the terminal
ileum and colon to treat the colitis.
Most of the side effects of Azulfidine are due to the sulfapyridine molecule.
These side effects include nausea, heartburn, headache, anemia, skin rashes,
and, in rare instances, hepatitis and kidney inflammation. In men, Azulfidine
can reduce the sperm count. The reduction in sperm count is reversible, and the
count usually becomes normal after the Azulfidine is discontinued or changed to
a different 5- ASA compound.
Because the newer 5-ASA compounds (e.g., Asacol and Pentasa) do not have the
sulfapyridine component and have fewer side effects than Azulfidine, they are
being used more frequently in treating Crohn's disease and ulcerative colitis.
Asacol
Asacol is a tablet consisting of the 5-ASA compound surrounded by an acrylic
resin coating. (Asacol is sulfa-free). The resin coating prevents the 5-ASA
from being absorbed as it passes through the stomach and the small intestine.
When the tablet reaches the terminal ileum and the colon, the resin coating
dissolves, and the active 5-ASA drug is released.
Asacol is effective in inducing remissions in patients with mild to moderate
ulcerative colitis. It also is effective when used in the longer term to
maintain remissions. Some studies have shown that Asacol also is effective in
treating Crohn's ileitis and ileo-colitis, as well as in maintaining remission
in patients with Crohn's disease.
The recommended dose of Asacol for inducing remissions is two 400 mg tablets
three times daily (a total of 2.4 grams a day). At least two tablets of Asacol
twice daily (1.6 grams a day) is recommended for maintaining remission.
Occasionally, the maintenance dose is higher.
As with Azulfidine, the benefits of Asacol are dose-related. If patients do not
respond to 2.4 grams a day of Asacol, the dose frequently is increased to 3.6 -
4.8 grams a day to induce remission. If patients fail to respond to the higher
doses of Asacol, then other alternatives such as corticosteroids are
considered.
Pentasa
Pentasa is a capsule consisting of small spheres containing 5-ASA. It is
sulfa-free. As
the capsule travels down the intestines, the 5-ASA inside the spheres is
released slowly into the intestine. Unlike Asacol, the active drug 5-ASA in
Pentasa is released into the small intestine as well as the colon. Therefore,
Pentasa can be effective in treating inflammation in the small intestine and is
currently the most commonly used 5-ASA compound for treating mild to moderate
Crohn's disease in the small intestine.
Patients with Crohn's disease occasionally undergo surgery to relieve small
intestinal obstruction, drain abscesses, or remove fistulae. Usually, the
diseased portions of the intestines are removed during surgery. After
successful surgery, patients can be free of disease and symptoms (in remission)
for a while. In many patients, however, Crohn's disease eventually returns.
Pentasa helps maintain remissions and reduces the chances of the recurrence of
Crohn's disease after surgery.
In the treatment of Crohn's ileitis or ileocolitis, the
dose of Pentasa usually is four 250 mg capsules four times daily (a total of 4
grams a day). For maintenance of remission in patients after surgery, the dose
of Pentasa is between 3-4 grams daily.
Dipentum
Dipentum (olsalazine) is a capsule in which two molecules of 5-ASA are joined
together by a chemical bond. In this form, the 5-ASA cannot be absorbed from
the stomach and intestine. Intestinal bacteria are able to break apart the two
molecules, releasing the active, individual 5-ASA molecules into the intestine.
Since intestinal bacteria are more abundant in the ileum and colon, most of the
active 5-ASA is released in these areas. Therefore, Dipentum is most effective
for disease that is limited to the ileum or colon. Although clinical studies
have shown that Dipentum is effective for maintenance of remission in
ulcerative colitis, up to 11% of patients experience diarrhea when taking
Dipentum. Because of this, Dipentum is not often used. The recommended dose of
Dipentum is 500 mg twice a day.
Colazal
Colazal (balsalazide) is a capsule in which the 5-ASA is linked by a chemical
bond to another molecule that is inert (without effect on the intestine) and
prevents the 5-ASA from being absorbed. This drug is able to travel through the
intestine unchanged until it reaches the end of the small bowel (terminal
ileum) and colon. There, intestinal bacteria break apart the 5-ASA and the
inert molecule, releasing the 5-ASA. Because intestinal bacteria are most
abundant in the terminal ileum and colon, Colazal is used to treat inflammatory
bowel disease predominantly localized to the colon. Colazal recently has been
approved by the FDA for use in the United States.
Side effects
of oral 5-ASA compounds
The 5-ASA compounds have fewer side effects than Azulfidine and also do not
reduce sperm counts. They are safe medications for long-term use and are
well-tolerated.
Patients allergic to aspirin should avoid 5-ASA compounds because they are
similar chemically to aspirin.
Rare kidney and lung inflammation has been reported with the use of 5-ASA
compounds. Therefore, 5-ASA should be used with caution in patients with kidney
disease. It also is recommended that blood tests of kidney function be done
before starting and periodically during treatment.
Rare instances of worsening of diarrhea, cramps, and abdominal pain, at times
accompanied by fever, rash, and malaise, may occur. This reaction is believed
to represent an allergy to the 5-ASA compound.
5-ASA
rectal medications (Rowasa Canasa)
Rowasa is 5-ASA in enema form. 5-ASA by enema is most useful for treating
ulcerative colitis involving only the distal colon since the enema easily can
reach the
inflamed tissues of the distal colon. Rowasa also is used in treating Crohn's
disease in which there is inflammation in and near the rectum. Each Rowasa
enema contains 4 grams of 5-ASA. The enema usually is administered at bedtime,
and patients are encouraged to retain the enema through the night. The enema
contains sulfite and should not be used by patients with sulfite allergy.
Otherwise, Rowasa enemas are safe and well-tolerated.
Canasa is 5-ASA in suppository form. It is used for treating ulcerative
proctitis. Each suppository contains 500 mg of 5-ASA and usually is
administered twice daily.
Both enemas and suppositories have been shown to be effective in maintaining
remission in patients with ulcerative colitis limited to the distal colon and
rectum.
Corticosteroids
Corticosteroids (e.g., prednisone, prednisolone, hydrocortisone, etc.) have
been used for many years to treat patients with moderate to severe Crohn's
disease and ulcerative colitis and to treat patients who fail to respond to
5-ASA. Unlike 5-ASA, corticosteroids do not require direct contact with the
inflamed intestinal tissues to be effective.
Oral corticosteroids are potent anti-inflammatory medications. After
absorption, corticosteroids exert prompt anti-inflammatory actions throughout
the body, including the intestines. Consequently, they are used in treating
Crohn's disease anywhere in the small intestine, as well as ulcerative and
Crohn's colitis. In critically ill patients, intravenous corticosteroids (such
as hydrocortisone) can be given in the hospital. For patients with proctitis,
hydrocortisone enemas (Cortenema) can be used to deliver the corticosteroid
directly to the inflamed tissue. By using the corticosteroid topically, less of
it is absorbed into the body and the frequency and severity of side effects are
lessened (but not eliminated) as compared with systemic corticosteroids.
Corticosteroids are faster-acting than 5-ASA, and patients frequently
experience improvement in their symptoms within days of beginning them.
Corticosteroids, however, do not appear to be useful in maintaining remission
in Crohn's disease and ulcerative colitis or in preventing the return of
Crohn's disease after surgery.
Side effects of
corticosteroids
The frequency and severity of side effects of corticosteroids depend on the
dose and duration of their use. Short courses of corticosteroids, for example,
usually are well-tolerated with few and mild side effects. Long-term use of
high doses of corticosteroids usually produces predictable and potentially
serious side effects. Common side effects include rounding of the face (moon
face), acne, increased body hair, diabetes, weight gain, high blood pressure,
cataracts, glaucoma, increased susceptibility to infections, muscle weakness,
depression, insomnia, mood swings, personality changes, irritability, and
thinning of the bones (osteoporosis) with fractures of the spine. Children
receiving corticosteroids experience stunted growth.
The most serious complication from long term corticosteroid use is aseptic
necrosis of the hip joints. Aseptic necrosis is a condition in which there is
death and degeneration of the hip bone. It is a painful condition that can
ultimately lead to the need for surgical replacement of the hip. Aseptic
necrosis also has been reported in the knee joints. It is not known how
corticosteroids cause aseptic necrosis. The estimated incidence of aseptic
necrosis among corticosteroid users is 3-4%. Patients on corticosteroids who
develop pain in the hips or knees should report the pain to their doctors
promptly. Early diagnosis of aseptic necrosis with cessation of corticosteroids
might decrease the severity of the aseptic necrosis and the need for hip
replacement surgery.
Prolonged use of corticosteroids can depress the ability of the body's adrenal
glands to produce cortisol (a natural corticosteroid necessary for proper
functioning of the body). Therefore, abruptly discontinuing corticosteroids can
cause symptoms due to a lack of natural cortisol (a condition called adrenal
insufficiency). Symptoms of adrenal insufficiency include nausea, vomiting, and
even shock. Withdrawing corticosteroids too quickly also can produce symptoms
of joint pain, fever, and malaise. Therefore, when corticosteroids are
discontinued, the dose usually is tapered gradually rather than stopped
abruptly.
Even after corticosteroids are discontinued, the adrenal glands' ability to
produce cortisol can remain depressed from months up to two years. The
depressed adrenal glands may not be able to produce increased amounts of
cortisol to help the body handle the stress of accidents, surgery, and
infections. Therefore, patients need additional corticosteroids during
stressful situations to avoid developing adrenal insufficiency. Because
corticosteroids are not useful in maintaining remission in ulcerative colitis
and Crohn's disease, and because they have predictable and potentially serious
side effects, they should be used for the shortest possible length of time.
Proper use of
corticosteroids
Once the decision is made to use systemic corticosteroids, treatment usually is
initiated with prednisone, 40-60 mg daily. The majority of patients with
Crohn's disease respond with an improvement in symptoms within a few weeks.
Once symptoms have improved, prednisone is reduced by 5-10 mg per week until a
dose of 20 mg per day is reached. The dose then is reduced at a slower rate
until the corticosteroid is discontinued. Gradually reducing corticosteroids
not only minimizes the symptoms of adrenal insufficiency, it also reduces the
chances of an abrupt
recurrence of inflammation.
Many doctors use 5-ASA compounds and corticosteroids together. In patients who
achieve remission with corticosteroids, 5-ASA compounds often are continued
alone to maintain remission.
In patients whose symptoms return corticosteroids are slowly being reduced, the
dose of corticosteroids is increased slightly to control the symptoms. Once the
symptoms are under control, the reduction of corticosteroids can resume at a
slower pace. Unfortunately, many patients who require corticosteroids to induce
remissions become corticosteroid dependent. These patients consistently develop
symptoms whenever the corticosteroid dose falls below a certain level. In such
patients who are corticosteroid dependent as well as in patients who are
unresponsive to corticosteroids and other anti-inflammatory medications,
immuno-modulator medications or surgery must be considered. The management of
patients who are corticosteroid dependent or patients with severe disease that
responds poorly to medications is complex. Doctors who are experienced in
treating ulcerative colitis and Crohn's disease and in using immuno-modulators
should evaluate these patients.
Prevention of
osteoporosis
Long-term use of corticosteroids can cause osteoporosis. Calcium is very
important in the formation and maintenance of healthy bones. Corticosteroids
decrease the absorption of calcium from the intestine and increase the loss of
calcium from the kidneys. Increasing dietary calcium intake is important but
alone cannot halt corticosteroid-induced osteoporosis. To prevent or minimize
osteoporosis, management of patients on long-term corticosteroids should
include:
-
Adequate intake of calcium (1000 mg daily in premenopausal women, 1500 mg daily
in postmenopausal women) and vitamin D (800 units daily).
-
Periodic review with the doctor of the need for continued corticosteroid
treatment and use of the lowest effective dose if continued treatment is
necessary.
-
For patients taking corticosteroids for more than 3 months, a bone density
study may be helpful in determining the extent of bone loss and the need for
more aggressive treatment.
-
Regular weight-bearing exercise and stopping smoking (cigarettes).
-
Discussion with the doctor regarding the use of alendronate (Fosamax),
risedronate (Actonel), or etidronate (Didronel) to prevent or treat
corticosteroid-induced osteoporosis.
Budesonide (Entocort EC)
Budesonide (Entocort EC) is a new type of corticosteroid for treating Crohn's
disease. Like other corticosteroids, budesonide is a potent anti-inflammatory
medication. Unlike other corticosteroids, however, budesonide acts only via
direct contact with the inflamed tissues (topically) and not systemically. As
soon as budesonide is absorbed into the body, the liver converts it into
inactive chemicals. Therefore, for effective treatment of Crohn's disease,
budesonide, like topical 5-ASA, must be brought into direct contact with the
inflamed intestinal tissue.
Budesonide capsules contain granules that allow a slow release of the drug into
the ileum and the colon. In a double-blind multicenter study (published in
1998), 182 patients with Crohn's ileitis and/or Crohn's disease of the right
colon were treated with either budesonide (9 mg daily) or Pentasa (2 grams
twice daily). Budesonide was more effective than Pentasa in inducing remissions
while the side effects were similar to Pentasa. In another study comparing the
effectiveness of budesonide with corticosteroids, budesonide was not better
than corticosteroids in treating Crohn's disease but had fewer side effects.
Because budesonide is broken down by the liver into inactive chemicals, it has
fewer side effects than systemic corticosteroids. It also suppresses the
adrenal glands less than systemic corticosteroids. Budesonide will be available
as an enema for the treatment of proctitis.
Budesonide has not been shown to be effective in maintaining remission in
patients with Crohn's disease. If used long-term, budesonide also may cause
some of the same side effects as corticosteroids. Because of this, the use of
budesonide should be limited to short-term treatment for inducing remission.
Most budesonide is released in the terminal ileum, it will have its best
results in Crohn's disease limited to the terminal ileum.
It is not known whether budesonide is effective in treating patients with
ulcerative colitis, and it is currently not recommended for the treatment of
ulcerative colitis.
Antibiotics for Crohn's disease
Antibiotics such as metronidazole (Flagyl) and ciprofloxacin (Cipro) have been
used for treating Crohn's colitis. Flagyl also has been useful in treating anal
fistulae in patients with Crohn's disease. The mechanism of action of these
antibiotics in Crohn's disease is not well understood.
Metronidazole (Flagyl)
Metronidazole (Flagyl) is an antibiotic that is used for treating several
infections caused by parasites (e.g., giardia) and bacteria (e.g., infections
caused by anaerobic bacteria, and vaginal infections). It is effective in
treating Crohn's colitis and is particularly useful in treating patients with
anal fistulae. Chronic use of metronidazole in doses higher than 1 gram daily
can be associated with permanent nerve damage (peripheral neuropathy). The
early symptoms of peripheral neuropathy are numbness and tingling in the
fingertips, toes, and other parts of the extremities. Metronidazole should be
stopped promptly if these symptoms appear. Metronidazole and alcohol together
can cause severe nausea, vomiting, cramps, flushing, and headache. Patients
taking metronidazole should avoid alcohol. Other side effects of metronidazole
include nausea, headaches, loss of appetite, a metallic taste, and, rarely, a
rash.
Ciprofloxacin (Cipro)
Ciprofloxacin (Cipro) is another antibiotic used in the treatment of Crohn's
disease. It can be used in combination with metronidazole.
Summary of
anti-inflammatory medications
-
Azulfidine, Asacol, Pentasa, Dipentum, Colazal and Rowasa all contain 5-ASA
which is the active topical anti-inflammatory ingredient. Azulfidine was the
first 5-ASA medication used in treating ulcerative colitis and Crohn's disease,
but the newer 5-ASA medications have fewer side effects.
-
Pentasa and Asacol have been found to be effective in treating patients with
Crohn's ileitis and ileo-colitis. Rowasa enemas and Canasa suppositories are
safe and effective for treating patients with proctitis. For mild to moderate
Crohn's ileitis or ileo-colitis, doctors usually start with Pentasa or
Asacol.If Pentasa or Asacol is ineffective, doctors may try antibiotics such as
Cipro or Flagyl for prolonged periods (often months).
-
In patients with moderate to severe disease and in patients who fail to respond
to 5-ASA compounds and/or antibiotics, systemic corticosteroids can be used.
Systemic corticosteroids are potent and fast-acting anti-inflammatory agents
for treating Crohn's enteritis and colitis as well as ulcerative colitis.
-
Systemic corticosteroids are not effective in maintaining remission in patients
with Crohn's disease. Serious side effects can result from prolonged
corticosteroid treatment.
-
To minimize side effects, corticosteroids should be gradually tapered as soon
as a remission is achieved. In patients who become corticosteroid dependent or
are unresponsive to corticosteroid treatment, surgery or immuno-modulator
treatment are considered.
-
A new class of topical corticosteroids (budesonide) may have fewer side effects
than systemic corticosteroids.
Immuno-modulator
medications
Immuno-modulators are medications that affect the body's immune system. The
immune system is composed of immune cells and the proteins that they produce.
These cells and proteins serve to protect the body against harmful bacteria,
viruses, fungi, and other foreign invaders. Activation of the immune system
causes inflammation within the tissues where the activation occurs.
(Inflammation is, in fact, an important mechanism used by the immune system to
defend the body.) Normally, the immune system is activated only when the body
is exposed to foreign invaders. In patients with Crohn's disease and ulcerative
colitis, however, the immune system is abnormally and chronically activated in
the absence of any known invader.
Immuno-modulators decrease tissue inflammation by reducing the population of
immune cells and/or by interfering with their production of proteins.
Decreasing the activity of the immune system with immuno-modulators increases
the risk of infections; however, the benefits of controlling moderate to severe
Crohn's disease usually outweigh the risks of infection due to weakened
immunity. Examples of immuno-modulators are 6-mercaptopurine (6-MP),
azathioprine, methotrexate, and
infliximab.
Azathioprine (Imuran) and 6-mercaptopurine (6-MP, Purinethol)
Azathioprine (Imuran) and 6-mercaptopurine (6-MP, Purinethol) are medications
that weaken the body's immune system by reducing the population of a class of
immune cells called lymphocytes. Azathioprine and 6-MP are related chemically.
(Actually, azathioprine is converted into 6-MP within the body.) In high doses,
these two drugs have been useful in preventing rejection of transplanted organs
and in treating leukemia. In low doses, they have been used for many years to
treat patients with moderate to severe Crohn's disease and ulcerative colitis.
Azathioprine and 6-MP are increasingly recognized by doctors as valuable drugs
in treating Crohn's disease and ulcerative colitis. Some 70% of patients with
moderate to severe disease will benefit from these drugs. Azathioprine and 6-MP
are used primarily in the following situations:
-
Severe Crohn's disease and ulcerative colitis not responding to
corticosteroids.
-
The presence of undesirable corticosteroid-related side effects.
-
Corticosteroid dependency, a condition in which patients are unable to
discontinue corticosteroids without developing relapses of their disease.
-
Maintenance of remission.
When azathioprine and 6-MP are added to corticosteroids in the treatment of
Crohn's disease not responding to corticosteroids alone, there may be an
improved response. Also, smaller doses and shorter courses of corticosteroids
may be able to be used. Some patients can discontinue corticosteroids
altogether without experiencing relapses of their disease. This
corticosteroid-lowering effect has earned azathioprine and 6-MP their
reputation as "steroid-sparing" medications.
In Crohn's disease patients with severe disease who suffer frequent relapses,
5-ASA may not be sufficient, and the more potent azathioprine and 6-MP will be
necessary to maintain remissions. In the lower doses used to treat Crohn's
disease, the long-term side effects of azathioprine or 6- MP are less serious
than those of long-term corticosteroids or repeated courses of corticosteroids.
Patients with Crohn's disease may undergo surgery to remove a segment of the
intestine that is obstructed or contains a fistula. After surgical removal of
the diseased segments, the patients often will be free of disease and symptoms
for a while, but many eventually will have their disease recur. During these
recurrences, previously healthy intestine can become inflamed. Long-term 5-ASA
(such as Pentasa) and 6-MP both are effective in reducing the chances of
recurrence after surgery.
Anal fistulae can develop in some patients with Crohn's disease. Anal fistulae
are abnormal tracts (tunnels) that form between the small intestine or colon
and the skin around the anus. Drainage of fluid and mucous from the opening of
the fistula is a troublesome problem. These fistulae are difficult to treat and
do not heal readily. Metronidazole (Flagyl) has been used with some success in
promoting healing of these fistulae. In difficult cases, azathioprine and 6-MP
may be successful in promoting healing.
Side effects
of azathioprine and 6-MP
Side effects of azathioprine and 6-MP include increased vulnerability to
infections, inflammation of the liver (hepatitis) and the pancreas
(pancreatitis), and bone marrow toxicity (interference with the formation of
cells that circulate in the blood).
The goal of treatment with azathioprine and 6-MP is to lower the body's
production of certain types of white blood cells (lymphocytes) in order to
decrease the inflammation in the intestines; however, lowering the number of
lymphocytes may increase vulnerability to infections. For example, in a group
of patients with severe Crohn's disease unresponsive to standard doses of
azathioprine, raising the dose of azathioprine helped to control the disease,
but two patients developed cytomegalovirus (CMV) infection. (CMV typically
infects individuals with weakened immune systems such as patients with AIDS and
cancer patients receiving chemotherapy).
Azathioprine and 6-MP can induce inflammation of the liver (hepatitis) and
pancreas (pancreatitis). Pancreatitis typically causes severe abdominal pain
and sometimes vomiting. Pancreatitis due to azathioprine or 6-MP occurs in
3%-5% of patients, usually during the first several weeks of treatment.
Patients who develop pancreatitis should not receive either of these two
medications again.
Azathioprine and 6-MP also suppress the bone marrow. The bone marrow is where
the red blood cells, white blood cells, and platelets are made. Actually, a
slight reduction in the white cell count during treatment is desirable since it
suggests that the dose of azathioprine or 6-MP is high enough to have an
effect; however, excessively low red or white blood cell counts indicates bone
marrow toxicity. Therefore, patients on azathioprine or 6-MP should have
periodic blood counts (usually every two weeks initially and then every 3
months during maintenance) to monitor the effect of the drugs on the bone
marrow.
Patients on long-term, high dose azathioprine to prevent rejection of the
kidney after kidney transplantation have an increased risk of developing
lymphoma, a malignant disease of lymph cells. There is no evidence at present
that long term use of azathioprine or 6-MP, in the lower doses used in Crohn's
disease, increases the risk of lymphoma, leukemia or other malignancies.
The use of azathioprine and 6-MP in pregnant women must be carefully
considered. There are reports suggesting that the use of
azathioprine or 6-MP in pregnancy is safer than once thought. The risk of
continuing azathioprine or 6-MP during conception and pregnancy must be weighed
against the risk of worsening disease if they are stopped. On the other hand,
worsening disease has been shown clearly to be a significant risk to the fetus.
Other
issues with azathioprine and 6-MP
One problem with 6-MP and azathioprine is their slow onset of action. Typically,
full benefit of these drugs is not realized for 3 months or longer. During this
time, corticosteroids frequently have to be maintained at high levels to
control inflammation.
The reason for this slow onset of action is partly due to the way doctors
prescribe these drugs. For example, 6-MP is typically started at a dose of 50
mg daily. The blood count is then checked two weeks later. If the lymphocytes
are not reduced, the dose of 6-MP is increased. This cautious, stepwise
approach helps reduce bone marrow and liver toxicity but also delays benefit
from the drug.
Studies have shown that giving higher doses of 6-MP early can hasten the
benefit of 6-MP without increasing the toxicity in most patients, but some
patients do develop severe bone marrow toxicity. Scientists now believe that an
individual's vulnerability to 6-MP toxicity is genetically inherited. Blood
tests can be performed to identify those individuals with increased
vulnerability to 6-MP toxicity. Blood tests also can be performed to measure
the levels of certain by-products of 6-MP. The levels of these by-products in
the blood help doctors more quickly determine whether the dose of 6-MP is right
for the patient.
TPMT genetics and safety of azathioprine and 6-MP
Azathioprine is converted into 6-MP in the body and 6-MP then is partially
converted in the body into inactive and non-toxic chemicals by an enzyme called
TPMT. These chemicals then are eliminated from the body. The activity of TPMT
enzyme (i.e. the ability of the enzyme to convert 6-MP into inactive and
non-toxic chemicals) is genetically determined, and approximately 10% of the
population in the Untied States has a reduced or absent TPMT activity. In this
10% of patients, 6-MP accumulates and is converted into chemicals that are
toxic to the bone marrow where blood cells are produced. Thus, when given
normal doses of azathioprine or 6-MP, these patients with reduced or absent
TPMT activities can develop seriously low white blood cell counts for prolonged
periods of time, exposing them to serious life-threatening infections.
Doctors now can perform genetic testing for TPMT before starting azathioprine
or 6-MP. Patients found to have genes associated with reduced or absent TPMT
activity are treated with alternative medications or are prescribed
substantially lower than normal doses of 6-MP or Azathioprine.
A word of caution is in order, however. Having normal TPMT genes is no
guarantee against azathioprine or 6-MP toxicity. Rarely, a patient with normal
TPMT genes can develop severe toxicity in the bone marrow and a low white blood
cell count even with normal doses of 6-MP or azathioprine. Therefore, all
patients taking 6-MP or azathioprine (regardless of TPMT genetics) have to be
closely monitored by a doctor who will order periodic blood counts for as long
as the medication is taken.
Another cautionary note; allopurinol (Zyloprim), used in treating high blood
uric acids levels, can induce bone marrow toxicity when used together with
azathioprine or 6 MP. Zyloprim used together with azathiprine or 6-MP has
similar effect as having reduced TPMT activity, causing increased accumulation
of the 6-MP metabolite that is toxic to the bone marrow.
6-MP metabolite levels
In addition to monitoring blood cell counts and liver tests, doctors also may
measure blood levels of the chemicals that are formed from 6-MP (6-MP
metabolites), which can be helpful in several situations such as:
-
If a patient's disease is not responding to standard doses of 6-MP or
azathioprine and his/her 6-MP blood metabolite levels are low, doctors may
increase the 6-MP or azathioprine dose.
-
If a patient's disease is not responding to treatment and his/her 6-MP blood
metabolite levels are zero, he/she is not taking his/her medication. The lack
of response in this case is due to patient non-compliance.
Duration
of treatment with azathioprine and 6-MP
Patients have been maintained on 6-MP or azathioprine for years without
important long-term side effects. Patients on long-term azathioprine or 6-MP,
however, should be closely monitored by their doctors. There are data
suggesting that patients on long-term maintenance fare better than those who
stop these medications. Thus, those who stop azathioprine or 6-MP are more
likely to experience recurrence of their disease and are more likely to need
corticosteroids or undergo surgery.
Infliximab (Remicade)
Infliximab (Remicade) is an antibody that attaches to a protein called tumor
necrosis factor-alpha (TNF-alpha). TNF-alpha is one of the proteins produced by
immune cells during activation of the immune system. TNF-alpha, in turn,
stimulates other cells of the immune system to produce and release other
proteins that promote inflammation. In Crohn's disease, there is continued
production of TNF-alpha as part of the immune activation. Infliximab, by
attaching to TNF-alpha, blocks its activity and in so doing decreases the
inflammation.
Infliximab, an antibody to TNF-alpha, is produced by the immune system of mice
after the mice are injected with human TNF-alpha. The mouse antibody then is
modified to make it look more like a human antibody, and this modified antibody
is infliximab. Such modifications are necessary to decrease the likelihood of
allergic reactions when the antibody is administered to humans. Infliximab is
given by intravenous infusion over two hours. Patients are monitored throughout
the infusion for adverse reactions.
In August, 1998 the United States Food and Drug Administration approved the use
of infliximab for the short-term treatment of moderate to severe Crohn's
disease patients who respond inadequately to corticosteroids, azathioprine, or
6-MP.
Effectiveness of
infliximab
Infliximab is an effective and fast-acting drug for the treatment of active
Crohn's disease. In a study involving patients with moderate to severe Crohn's
disease who were not responding to corticosteroids or immuno-modulators, 65%
experienced improvement in their disease after one infusion of infliximab. Some
patients noticed improvement in symptoms within days of the infusion. Most
patients experienced improvement within 2 weeks.
In patients who respond to infliximab, the improvements in symptoms can be
dramatic. Moreover, there can be impressively rapid healing of the ulcers and
the inflammation in the intestines after just one infusion.
The anal fistulae of Crohn's disease are troublesome and often difficult to
treat. Infliximab has been found to be effective for treating fistulae.
Duration of
benefits with infliximab
The majority of the patients who responded to a first infusion of infliximab
developed recurrence of their disease within 3 months. However, studies have
shown that repeated infusions of Infliximab every 8 weeks are safe and
effective in maintaining remission in many patients over a 1-2 year period.
Response to infliximab after repeated infusions sometimes is lost if the
patient starts to develop antibodies to the infliximab (which attach to the
infliximab and prevent it from working). Studies are now
being done to determine the long-term safety and effectiveness of repeated
infusions of infliximab.
One potential use of infliximab is to quickly control active and severe
disease. The use of infliximab then may be followed by maintenance treatment
with azathioprine, 6-MP or 5-ASA compounds. Azathioprine or 6-MP also may be
helpful in preventing the development of antibodies against infliximab.
Side effects of
infliximab
Infliximab generally is well-tolerated. There have been rare reports of side
effects during infusions, including chest pain, shortness of breath, and
nausea. These effects usually resolve spontaneously within minutes if the
infusion is stopped. Other commonly-reported side effects include headache and
upper respiratory tract infection.
TNF-alpha is an important protein for defending the body
against infections. Infliximab, like immuno-modulators, increases the risk for
infection. One case of salmonella colitis and several cases of pneumonia have
been reported with the use of infliximab.
Because infliximab is partly a mouse protein, it may induce an immune reaction
when given to humans, especially with repeated infusions. In addition to the
side effects that occur while the infusion is being given, patients also may
develop a "delayed allergic reaction" that occurs 7-10 days after receiving the
infliximab. This type of reaction may cause flu-like symptoms with fever, joint
pain and swelling, and a worsening of Crohn's disease symptoms. It can be
serious, and if it occurs, a physician should be contacted. Paradoxically,
those patients who have more frequent infusions of Remicade are less likely to
develop this type of delayed reaction compared to those patients who receive
infusions separated by long intervals (6-12 months). Although Remicade is only
FDA approved at this time for a single infusion, patients should be aware that
they are likely to require repeated infusions once Remicade therapy has been
initiated.
Precautions with
infliximab
Infliximab can aggravate and cause the spread of an existing infection.
Therefore, it should not be given to patients with pneumonia, urinary tract
infection or abscess (localized collection of pus).
There also have been cases of tuberculosis (TB) reported after the use of
infliximab. The majority of these cases occurred in Europe and in individuals
who had tuberculosis in the past. It now is recommended that patients be tested
for TB prior to receiving infliximab. Patients who previously had TB should
inform their physician of this before they receive infliximab
Infliximab can cause the spread of cancer cells. Therefore, it should not be
given to patients with cancer or a history of cancer.
Infliximab can promote intestinal scarring (part of the process of healing)
and, therefore, can worsen strictures (narrowed areas of the intestine caused
by inflammation and subsequent scaring) and lead to intestinal obstruction. It
also can cause partial healing (partial closure) of anal fistulae. Partial
closure of fistulae impedes drainage of fluid through the fistulae and may
result in collections of fluid in which bacteria multiply. This can result in
abscesses.
Infliximab also should be avoided in pregnancy since its effects on the fetus
are not known.
Because infliximab is partly a mouse protein, some patients can develop
antibodies against infliximab with repeated infusions. Such
antibodies occur in approximately 13% of patients.
There are some reports of worsening heart disease in patients who have received
Remicade. The precise mechanism and role of infliximab in the development of
this side effect is unclear. As a precaution, individuals with heart disease
should inform their physician of this condition before receiving infliximab.
While infliximab represents an exciting new class of medications in the fight
against Crohn's disease, caution is warranted in its use. The long-term safety
and effectiveness is not yet known.
Identifying patients who will respond to infliximab
There is insufficient data regarding infliximab in ulcerative colitis.
Infliximab most likely is not effective in treating ulcerative colitis.
PANCA and ASCA are serologic tests performed on blood that frequently are
abnormal in patients with ulcerative colitis and Crohn's disease. These
serologic tests can be helpful in establishing a diagnosis of ulcerative
colitis and Crohn's disease and in distinguishing Crohn's disease from
ulcerative colitis. Studies are now being done to see whether these antibodies
are useful in predicting which patients will respond to infliximab.
Methotrexate
Methotrexate is both an immuno-modulator and anti-inflammatory medication.
Methotrexate has been used for many years in the treatment of severe rheumatoid
arthritis and psoriasis. It has been helpful in treating patients with moderate
to severe Crohn's disease who are either not responding to azathioprine and 6-
MP or are intolerant of them. Methotrexate also may be effective in patients
with moderate to severe ulcerative colitis who are not responding to
corticosteroids, azathioprine, or 6-MP. It can be given orally or by weekly
injections under the skin or into the muscles, but it is more reliably absorbed
with the injections.
One major complication of methotrexate is the development of liver cirrhosis
when the medication is given over a prolonged period of time (years). The risk
of liver damage is higher in patients who also abuse alcohol or are severely
obese. Although it has
been recommended that a liver biopsy should be obtained in patients who have
received a cumulative (total) methotrexate dose of 1.5 grams or higher, the
need for such biopsies is controversial.
Other side effects of methotrexate include low white blood cell counts and
inflammation of the lungs.
Methotrexate should not be used in pregnant women because of toxic effects on
the fetus.
Surgery in Crohn's
disease
There is no surgical cure for Crohn's disease. Even when all of the diseased
parts of the intestines are removed, inflammation frequently recurs in
previously healthy intestines months to years after the surgery. Therefore,
surgery in Crohn's disease is used primarily for:
-
Removal of a diseased segment of the small intestine that is causing
obstruction.
-
Drainage of pus from abdominal and peri-rectal abscesses.
-
Treatment of severe anal fistulae that do not respond to drugs.
-
Resection of internal fistulae (such as a fistula between the colon and
bladder) that are causing infections.
Usually, after the diseased portions of the intestines are removed surgically,
patients can be free of disease and symptoms for some time, often years.
Surgery, when successfully performed, can lead to a marked improvement in a
patient's quality of life. In many patients, however, Crohn's disease
eventually returns, affecting previously healthy intestines. The recurrent
disease usually is located at or near the previous site of surgery. In fact,
50% of patients can expect to have a recurrence of symptoms within four years
of surgery. Drugs such as Pentasa or 6-MP have been useful in some patients to
reduce the chances of relapse of Crohn's disease after surgery.
General measures
General measures which may help control Crohn's disease include dietary changes
and supplementation. Since fiber is poorly digestible, it can worsen the
symptoms of intestinal obstruction. Hence, a low fiber diet may be recommended,
especially in those patients with small intestinal disease. A liquid diet may
be of benefit when symptoms are more severe. Intravenous nutrition or TPN
(total peripheral nutrition) may be utilized when it is felt that the intestine
needs to "rest." Supplementation of calcium, folate and vitamin B12 is helpful
when malabsorption of these nutrients is apparent. The use of anti-diarrheal
agents (Lomotil, Imodium) and anti-spasmotics also can help relieve symptoms of
cramps and diarrhea.
Conclusions
Crohn's disease is a chronic inflammatory disease involving predominantly the
small intestine and colon. The symptoms and the activity of the disease can
come and go. Even though many effective medications are available to control
the activity of the disease, there is as yet no cure for Crohn's disease.
Surgery can significantly improve the quality of life in selected individuals,
but recurrence of the disease after surgery is common. The disease can have
complications, both within and outside of the intestine. Newer treatments are
actively being evaluated. A better understanding of the role of genetics and
environmental factors in the cause of Crohn's disease may lead to improved
treatments and prevention of the disease.
Crohn's Disease At A
Glance
-
Crohn's disease is a chronic inflammatory disease of the intestines.
-
The cause of Crohn's disease is unknown.
-
Crohn's disease can cause ulcers in the small intestine, colon, or both.
-
Abdominal pain, diarrhea, vomiting, fever, and weight loss are symptoms of
Crohn's disease.
-
Crohn's disease of the small intestine may cause obstruction of the intestine.
-
Crohn's disease can be associated with reddish, tender skin nodules, and
inflammation of the joints, spine, eyes, and liver.
-
The diagnosis of Crohn's disease is made by barium enema, barium x-ray of the
small bowel, and colonoscopy.
-
The choice of treatment for Crohn's disease depends on the location and
severity of the disease.
-
Treatment of Crohn's disease includes drugs for suppressing inflammation or the
immune system, antibiotics, and surgery.
|
