What is Ulcerative Colitis?
Ulcerative colitis (UC) is a disease marked by inflammation of the lining of the
colon and rectum, together known as the large intestine. This inflammation
causes irritation in the lining of the large intestine which leads to the
symptoms of UC. Though UC always affects the lowest part of the large intestine
(the rectum), in some patients it can be present throughout the entire colon. UC
belongs to a group of diseases called inflammatory bowel diseases which also
includes Crohn's disease (CD). Though it was once thought that UC and CD were
two different diseases, as many as 10% of patients may have features of both
diseases and this is called indeterminate colitis. It is important to note that
inflammatory bowel disease (IBD) is different from irritable bowel syndrome
(IBS).
What are the symptoms of UC?
The symptoms of ulcerative colitis depend on the severity of inflammation and
the amount of the colon that is affected by the disease. In patients with mild
to moderate inflammation, symptoms can include rectal bleeding, diarrhea, mild
abdominal cramping, stool urgency, and tenesmus (discomfort and the feeling that
you have not completely emptied your rectum after a bowel movement). When more
severe inflammation is present, patients often develop fever, dehydration,
severe abdominal pain, weight loss, loss of appetite or growth retardation (in
children and adolescents with UC). Individuals with moderate or severe
inflammation may also have to wake up at night to have bowel movements and may
lose control of bowel movements. Some of the symptoms of UC may be non-specific
and could be caused by other diseases such as Crohn's disease, irritable bowel
syndrome, or infection. Your doctor can help determine the cause of your
symptoms and should be consulted should you experience a significant change in
your symptoms.
How is UC diagnosed?
Your doctor will usually suspect the diagnosis of ulcerative colitis based on
your symptoms, but confirmation of the diagnosis requires testing. Blood work is
often checked to look for markers of inflammation or anemia (low blood counts),
though these tests can be normal in patients with mild disease. Tests of your
stool to look for evidence of an intestinal infection are often obtained.
Radiologic images including x-rays and CT scans are usually not recommended but
may be performed. All patients with symptoms consistent with UC should have a
colonoscopy or flexible sigmoidoscopy to confirm the diagnosis assuming that
they are healthy enough to undergo the procedure. During this procedure, your
gastroenterologist will be able to directly examine the lining of your colon and
rectum to look for evidence of inflammation and take small biopsies to be
examined under a microscope to look for the cause of the inflammation.
What causes UC?
The way in which patients get ulcerative colitis is still poorly understood.
There seems to be an interaction between the unique genetic makeup of an
individual, environmental factors, and a patient's specific immune system that
triggers the disease. UC is not an infection that can be passed from person to
person. Men and women are equally affected by UC.
UC is more common in first degree relatives (siblings, parents, and children) of
patients affected by UC and up to 20% of patients will have an affected family
member. Despite the influence of genetics, the majority of patients with UC do
not pass the disease to their children. There is no way to predict those at
higher risk. Cases of ulcerative colitis have been identified throughout the
world though certain populations, including those living in Northern climates
and those of Jewish descent, are at higher risk of developing UC.
Individuals having their appendix removed prior to the age of 20 appear to be at
lower risk of developing UC. No specific infectious agent has been linked to UC
and diet, breast feeding, and various medications have also been examined but
none have been found to cause UC.
It has been observed that smokers have lower rates of UC than non-smokers.
Furthermore, those who smoke and have UC tend to have a milder course of UC than
those who do not smoke (note that this is the exact opposite effect that smoking
has on Crohn's disease). Despite the protective role smoking appears to have on
the development and natural history of UC, it is not recommended that patients
start smoking to prevent UC due to the fact that there are so many other
illnesses and cancers in which smoking is a definite risk factor.
UC is an immune-mediated disease in which there is loss of control of the normal
bowel immune activity and the ongoing activity results in damage to the bowel
wall.
What are the possible complications of UC?
The complications of ulcerative colitis can be divided into those affecting the
colon and those occurring outside of the colon. Within the colon, UC can rarely
lead to toxic megacolon or colon cancer.
Toxic megacolon describes a severe disease flare with a high risk of infection
and colonic perforation (holes in the colon). Patients may occasionally present
with toxic megacolon as their initial presentation of UC and this complication
requires hospitalization and may lead to surgery to remove the colon
(colectomy).
UC is known to increase the risk of colon cancer. Those patients who have had UC
for a long time and those with a longer length of the colon affected are at
higher risk of developing colon cancer. In general, patients begin to have an
increased risk of colorectal cancer 10 years after the onset of disease symptoms
and should have colonoscopy every one or two years starting at this time. Colon
cancer is a rare complication and it is thought that it may be preventable based
on control of inflammation of the colon and careful colonoscopy examinations
that look for any pre-cancerous changes called dysplasia. Overall, the risk of
colon cancer increases 0.5% yearly after 10 years of disease though patients
with inflammation throughout their colon may be at higher risk. Those patients
with primary sclerosing cholangitis (PSC) are at greatest risk for colon cancer
and need to start screening upon diagnosis.
Patients with UC are also at risk for extra-intestinal manifestations of UC
(complications outside of the colon). These complications most frequently
involve the liver, skin, eyes, mouth, and joints. Within the liver, patients
with UC may develop primary sclerosing cholangitis. This occurs in about 3% of
patients with UC. PSC can progress even if UC is not active and it is often
detected by elevations in liver blood tests and confirmed by the use of MRI
scans such as Magnetic Resonance Cholangiopancreatography (MRCP) or endoscopic
procedures such as Endoscopic Retrograde Cholangiopancreatography (ERCP).
Patients with UC can develop sores in the mouth or rashes on the skin that
generally only appear when UC colon symptoms are active. The most common rashes
that are seen in UC are erythema nodosum (EN) and pyoderma gangrenosum (PG). EN
usually presents as a red, raised, painful area most commonly on the legs and is
most often seen during flares of UC. PG also presents as raised lesions on the
skin (most frequently on the legs) that often develops after trauma to the skin
and can lead to the formation of ulcers. Unlike in EN, the appearance of skin
lesions in PG may or may not mirror the activity of bowel symptoms. The eyes can
become red and painful (uveitis) and vision problems should be reported to your
doctor.
Arthritis is commonly associated with UC and can affect either small (such as
the fingers/toes) or large joints (often the knee), though involvement of the
smaller joints may have a course that is not related to activity in the colon.
The joints of the spine can be affected as well, though this is less common than
it is in Crohn's disease.
As in other chronic medical conditions, anxiety and depression are common in
patients with UC. The unpredictability of UC and the need to take medications on
a daily basis can lead to feelings of frustration or anger. Though occasional
feelings of frustration can be normal, feelings of significant anxiety or
depression should be brought to the attention of your physician. There are many
support opportunities available for those having trouble coping with UC (see the
final section).
What is the clinical course of UC?
Ulcerative colitis can present in a variety of ways. UC is often a chronic,
life-long condition. It most often is diagnosed in the 2nd and 3rd decades of
life (ages 11-30), although it can be diagnosed at any age. The initial
presentation can be mild and is sometimes confused with other conditions such as
irritable bowel syndrome or it can be very severe and require hospitalization
and surgery. For most patients, UC tends to follow a course marked by periods of
disease activity followed by variable periods during which a patient is symptom
free. Some patients may have continuous disease activity. Rarely, a patient will
have only a single disease flare. In general, those people with a severe first
attack of UC and those who have their entire colon affected by UC tend to have a
more aggressive course with more frequent flares and shorter periods of
remission. Despite the chronic nature of UC, most patients are able to function
well and the life expectancy of a patient with UC is normal.
How is UC treated?
Medical treatment of ulcerative colitis generally focuses on two separate goals:
the induction of remission (making a sick person well) and the maintenance of
remission (keeping a well person from getting sick again). Surgery is also a
treatment option for UC and will be discussed separately. Medication choices can
be grouped into four general categories: aminosalicylates, steroids,
immunomodulators, and biologics.
Aminosalicylates are a group of anti-inflammatory medications (sulfasalazine,
mesalamine, olsalazine, and balsalazide) used for both the induction and
maintenance of remission in mild to moderate UC. These medications are available
in both oral and rectal formulations and work on the lining of the colon to
decrease inflammation. They are generally well tolerated. The most common side
effects include nausea and rash. Rectal formulations of mesalamine (enemas and
suppositories) are generally used for those patients with disease at the end of
their colon.
Steroids (prednisone) are an effective medication for the induction of remission
in moderate to severe UC and are available in oral, rectal, and intravenous (IV)
forms. Steroids are absorbed into the bloodstream and have a number of severe
side effects that make them unsuitable for chronic use to maintain remission.
These side effects include cataracts, osteoporosis, mood effects, an increased
susceptibility to infection, high blood pressure, weight gain, and an
underactive adrenal gland.
Immunomodulators include medications such as 6-mercaptopurine and azathioprine.
These are taken in pill form and absorbed into the bloodstream. They are
effective for maintenance of remission in moderate to severe ulcerative colitis,
but are slow to work and can take up to 2-3 months to reach their peak effect.
Because of this, these medications are often combined with other medications
(such as steroids) in patients who are very ill. These medications require
frequent blood work as they can cause liver test abnormalities and low white
blood cell counts, both of which are reversible when the medication is stopped.
Adverse reactions can include nausea, rash, liver and bone marrow toxicity,
pancreatitis, and rarely lymphoma.
Biologic agents are medications given by injection that are used to treat
moderate to severe UC. At the current time, infliximab (Remicade®) is the only
biologic agent approved for use in UC, but other biologics used for Crohn's
disease under evaluation for the treatment of UC include adalimumab (Humira®),
and certolizumab pegol (Cimzia®). Infliximab is effective in both the induction
and maintenance of remission in UC. The side effects of this medicine may
include an allergic reaction to the medication called an "infusion reaction" or
"hypersensitivity reaction". There are also rare risks of serious infections
with these medications. Lymphoma is a rare risk of these therapies as well.
Combination therapy with azathioprine/6-mercaptopurine and biologics increases
the risk of a particularly rare type of lymphoma called hepatosplenic T-cell
lymphoma. As with all medications, you should discuss the risks and benefits
with your doctor.
Other medications used less frequently for UC include cyclosporine and
tacrolimus. These agents are sometimes used in those rare cases of severe UC
that are not responsive to steroids. Side effects of these agents include
infections and kidney problems. These agents are offered at a limited number of
hospitals and are usually used for a short period of time as a bridge to other
maintenance therapies such as azathioprine or 6-mercaptopurine.
No matter which medical therapy you and your doctor decide upon, adherence with
the prescribed course is essential. No medical therapy can work if it is not
taken and failure to take your medications can lead to unnecessary escalation of
therapy if it is not brought to the attention of your doctor. Because many of
the complications associated with UC are related to ongoing disease activity,
good medication adherence may minimize these risks.
What is the role of surgery?
Surgery in ulcerative colitis is performed for a number of reasons and is
generally considered to be curative if the entire large intestine removed.
Patients who do not respond to medications, are concerned about or have
unacceptable side effects from medications, develop toxic megacolon, dysplasia
(precancerous lesions) or cancer, or children who are not growing because of UC
are often considered for surgery. Several different surgeries are performed for
UC and the choice of surgery is dependent on patient preference and the
experience of the surgeon. The most common surgery is total proctocolectomy with
ileal pouch anal anastomosis (total removal of the colon and rectum with
creation of a pseudo-rectum from a portion of the small intestine). This
operation usually requires two separate surgeries to complete although it may
require three stages in severely ill patients. Following this surgery, patients
can expect 5-10 stools daily as they no longer have a colon to store stool.
Patients usually feel better because their sense of stool urgency improves, they
no longer have bleeding, and their medications can often be stopped. However,
these patients are at risk for post-operative inflammation of the pouch known as
pouchitis which is usually treated with antibiotics. Women who have this surgery
may have decreased ability to get pregnant naturally.
Another common surgical procedure involves a proctocolectomy with ileostomy
(removal of the entire colon and rectum and connection of the small intestine to
the abdominal wall so that stool empties into a bag). This procedure is often
undertaken in elderly patients, obese patients or those with anal dysfunction.
Should you need a surgical procedure for UC, your surgeon can help you decide
which type of surgery best fits your needs.
Do complementary and alternative therapies work in UC?
Outside of the standard medical therapies discussed for ulcerative colitis, many
alternative therapies have been studied. No studies have suggested that diet can
either cause or treat UC and there is no specific diet that patients with UC
should follow though it is advisable to eat a balanced diet. Likewise, there is
no convincing evidence that UC results from food allergies. Though vitamin and
mineral deficiencies are more common in Crohn's disease, specific deficiencies
can occur in UC patients. For this reason, a multivitamin and a calcium
supplement are not unreasonable. Malnutrition can become a concern in severe UC.
Probiotics are species of bacteria that are thought to have beneficial
properties for the bowel. There are a number of scientific studies which have
been performed to assess the role of probiotics in UC, and most of these have
not shown benefit. There is some evidence, however, that a specific probiotic
(VSL #3) may be helpful as an additive to other therapies for maintenance of
remission.
Various other herbal remedies and alternative therapies have been studied for
use in patients with IBD such as curcumin (a derivative of the herb tumeric) and
parasitic worms (helminths). Though limited studies have shown promise for a
number of alternative therapies, these have not yet been shown to be safe and
effective and are not currently recommended. Studies of homeopathic compounds
are currently ongoing and will hopefully provide novel treatments for use in UC
in the future.
What type of follow-up is required?
As mentioned earlier, ulcerative colitis is a chronic disease and establishing a
long term relationship with a gastroenterologist experienced in the treatment of
UC is advisable. Many medications used in UC require regular blood work to
ensure that they are not causing any serious side effects. Patients with UC have
a higher risk of osteoporosis associated with both underlying disease activity
and long term or frequent steroid use. Because of this risk, your doctor may
recommend measurement of Vitamin D blood levels and a bone mineral density
screening with a DEXA scan. Colorectal cancer screening is also important
because of the higher risk of cancer in patients with UC as discussed earlier.
Where can you get more information?
Many organizations provide support and information for patients with ulcerative
colitis. The ACG website (www.acg.gi.org) has additional information. The
Crohn's and Colitis Foundation of America (www.ccfa.org) has extensive patient
information along with links to various different social, financial, and medical
support groups. Other sources of information include the individual drug company
websites, and, most importantly, your personal physician.
Author(s) and Publication Date(s)
Sean Lynch, MD and Richard Bloomfeld, MD, Wake Forest University School of
Medicine, Winston-Salem, NC
IMPORTANT REMINDER:
The preceding information is intended only to provide general information and not as a definitive basis for diagnosis or treatment in any particular case. It is very important that you consult your doctor about your specific condition.