Ulcerative Colitis
Chronic Colitis

Author: edoardo piacibello
Date: 24/02/2011


Ulcerative Colitis

Edoardo Piacibello , Alessandro Borello


Ulcerative colitis, an inflammatory bowel disease (IBD) that causes chronic inflammation of the digestive tract, is characterized by abdominal pain and diarrhea. Like Crohn's disease, another common IBD, ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications.
Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum. It occurs only through continuous stretches of your colon, unlike Crohn's disease, which occurs in patches anywhere in the digestive tract and often spreads deep into the layers of affected tissues.
There's no known cure for ulcerative colitis, but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis and even bring about a long-term remission.


The incidence of ulcerative colitis in North America is 10–12 cases per 100,000 per year, with a peak incidence of ulcerative colitis occurring between the ages of 15 and 25. Prevalence is 1 per 1000. There is thought to be a bimodal distribution in age of onset, with a second peak in incidence occurring in the 6th decade of life. The disease affects females more than males.
The geographic distribution of ulcerative colitis and Crohn's disease is similar worldwide, with highest incidences in the United States, Canada, the United Kingdom, and Scandinavia. Higher incidences are seen in northern locations compared to southern locations in Europe and the United States.
As with Crohn's disease, the prevalence of ulcerative colitis is greater among Ashkenazi Jews and decreases progressively in other persons of Jewish descent, non-Jewish Caucasians, Africans, Hispanics, and Asians.Appendectomy prior to age 20 for appendicitis and tobacco use are protective against development of ulcerative colitis


Ulcerative colitis symptoms can vary, depending on the severity of inflammation and where it occurs. For these reasons, doctors often classify ulcerative colitis according to its location.
Here are the signs and symptoms that may accompany ulcerative colitis, depending on its classification:
•Abdominal pain

•Blood in your stool

•Ongoing bouts of diarrhea that don't respond to over-the-counter (OTC) medications

•An unexplained fever lasting more than a day or two

•Ulcerative proctitis. In this form of ulcerative colitis, inflammation is confined to the rectum and for some people, rectal bleeding may be the only sign of the disease. Others may have rectal pain, a feeling of urgency or an inability to move the bowels in spite of the urge to do so (tenesmus). This form of ulcerative colitis tends to be the mildest.

•Proctosigmoiditis. This form involves the rectum and the lower end of the colon, known as the sigmoid colon. Bloody diarrhea, abdominal cramps and pain and tenesmus are common problems associated with this form of the disease.

•Left-sided colitis. As the name suggests, inflammation extends from the rectum up the left side through the sigmoid and descending colon. Signs and symptoms include bloody diarrhea, abdominal cramping and pain on the left side, and unintended weight loss.

•Pancolitis. Affecting the entire colon, pancolitis causes bouts of bloody diarrhea that may be severe, abdominal cramps and pain, fatigue, and significant weight loss.

•Fulminant colitis. This rare, life-threatening form of colitis affects the entire colon and causes severe pain, profuse diarrhea and, sometimes, dehydration and shock. People with fulminant colitis are at risk of serious complications, including colon rupture and toxic megacolon, which occurs when the colon becomes severely distended.

•Extraintestinal features.As ulcerative colitis is believed to have a systemic (i.e., autoimmune) origin, patients may present with comorbidities leading to symptoms and complications outside the colon. These include the following:
•aphthous ulcers of the mouth
•Ophthalmic (involving the eyes):
o Iritis or uveitis, which is inflammation of the iris
o Episcleritis
o Seronegative arthritis, which can be a large-joint oligoarthritis (affecting one or two joints), or may affect many small joints of the hands and feet
o Ankylosing spondylitis, arthritis of the spine
o Sacroiliitis, arthritis of the lower spine
•Cutaneous (related to the skin):
o Erythema nodosum, which is a panniculitis, or inflammation of subcutaneous tissue involving the lower extremities
o Pyoderma gangrenosum, which is a painful ulcerating lesion involving the skin
•Deep venous thrombosis and pulmonary embolism
•Autoimmune hemolytic anemia
•clubbing, a deformity of the ends of the fingers
•Primary sclerosing cholangitis, a distinct disease that causes inflammation of the bile ducts

The course of ulcerative colitis varies, with periods of acute illness often alternating with periods of remission. But over time, the severity of the disease usually remains the same. Most people with a milder condition, such as ulcerative proctitis, won't go on to develop more-severe signs and symptoms.
Although ulcerative colitis usually isn't fatal, it's a serious disease that, in some cases, may cause life-threatening complications.


H&E stain of a colonic biopsy showing a crypt abscess, a classic finding in ulcerative colitis
The initial diagnostic workup for ulcerative colitis includes the following:

• A complete blood count is done to check for anemia; thrombocytosis, a high platelet count, is occasionally seen.
• p-ANCA positivity (Sostegni. Digestive and liver disease. 2001)
• Electrolyte studies and renal function tests are done, as chronic diarrhea may be associated with hypokalemia, hypomagnesemia and pre-renal failure.
• Liver function tests are performed to screen for bile duct involvement: primary sclerosing cholangitis.
• X-ray
• Urinalysis
• Stool culture, to rule out parasites and infectious causes.
• Erythrocyte sedimentation rate can be measured, with an elevated sedimentation rate indicating that an inflammatory process is present.
• C-reactive protein can be measured, with an elevated level being another indication of inflammation.

Although ulcerative colitis is a disease of unknown causation, inquiry should be made as to unusual factors believed to trigger the disease. Factors may include: recent cessation of tobacco smoking; recent administration of large doses of iron or vitamin B6; hydrogen peroxide in enemas or other procedures.


Biopsy sample (H&E stain) that demonstrates marked lymphocytic infiltration (blue/purple) of the intestinal mucosa and architectural distortion of the crypts.
The best test for diagnosis of ulcerative colitis remains endoscopy. Full colonoscopy to the cecum and entry into the terminal ileum is attempted only if diagnosis of UC is unclear. Otherwise, a flexible sigmoidoscopy is sufficient to support the diagnosis. The physician may elect to limit the extent of the exam if severe colitis is encountered to minimize the risk of perforation of the colon. Endoscopic findings in ulcerative colitis include the following:
•Loss of the vascular appearance of the colon
•Erythema (or redness of the mucosa) and friability of the mucosa
•Superficial ulceration, which may be confluent, and

Ulcerative colitis is usually continuous from the rectum, with the rectum almost universally being involved. There is rarely peri-anal disease, but cases have been reported. The degree of involvement endoscopically ranges from proctitis or inflammation of the rectum, to left sided colitis, to pancolitis, which is inflammation involving the ascending colon.


Biopsies of the mucosa are taken to definitively diagnose UC and differentiate it from Crohn's disease, which is managed differently clinically. Microbiological samples are typically taken at the time of endoscopy. The pathology in ulcerative colitis typically involves distortion of crypt architecture, inflammation of crypts (cryptitis), frank crypt abscesses, and hemorrhage or inflammatory cells in the lamina propria. In cases where the clinical picture is unclear, the histomorphologic analysis often plays a pivotal role in determining the diagnosis and thus the management. By contrast, a biopsy analysis may be indeterminate, and thus the clinical progression of the disease must inform its treatment.

Like Crohn's disease, ulcerative colitis causes inflammation and ulcers in your intestine. But unlike Crohn's, which can affect the colon in various sections, ulcerative colitis usually affects one continuous section of the inner lining of the colon beginning with the rectum.
No one is quite sure what triggers ulcerative colitis, but there's a consensus as to what doesn't. Researchers no longer believe that stress is the main culprit, although stress can often aggravate symptoms. Instead, current thinking focuses on the following possibilities:

•Immune system. Some scientists think a virus (morbillivirus and other paramixovirus) or bacterium (chlamidie and mycobacterium) may trigger ulcerative colitis. The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen). It's also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present. Some sources list ulcerative colitis as an autoimmune disease,a disease in which the immune system malfunctions, attacking some part of the body. In contrast to Crohn's disease, which can affect areas of the gastrointestinal tract outside of the colon, ulcerative colitis usually involves the rectum and is confined to the colon, with occasional involvement of the ileum. This so-called "backwash ileitis" can occur in 10–20% of patients with pancolitis and is believed to be of little clinical significance.Ulcerative colitis can also be associated with comorbidities that produce symptoms in many areas of the body outside the digestive system. Surgical removal of the large intestine often cures the disease.

•Heredity. Because you're more likely to develop ulcerative colitis if you have a parent or sibling with the disease, scientists suspect that genetic makeup may play a contributing role.


Ulcerative colitis affects about the same number of women and men. Risk factors may include:

•Age. Ulcerative colitis can occur at any age, but ulcerative colitis often affects people in their 30s. Some people may not develop the disease until their 50s or 60s.

•Genetic factors.A genetic component to the aetiology of ulcerative colitis can be hypothesized based on the following:
• Aggregation of ulcerative colitis in families.
• Identical twin concordance rate of 10% and dizygotic twin concordance rate of 3%
• Ethnic differences in incidence
• Genetic markers and linkages

There are 12 regions of the genome which may be linked to ulcerative colitis. This includes chromosomes 16, 12, 6, 14, 5, 19, 1,and 3 in the order of their discovery.However, none of these loci has been consistently shown to be at fault, suggesting that the disorder arises from the combination of multiple genes. For example, chromosome band 1p36 is one such region thought to be linked to inflammatory bowel disease.Some of the putative regions encode transporter proteins such as OCTN1 and OCTN2. Other potential regions involve cell scaffolding proteins such as the MAGUK family. There are even human leukocyte antigen associations which may be at work. In fact, this linkage on chromosome 6 may be the most convincing and consistent of the genetic candidates.
Multiple autoimmune disorders have been recorded with the neurovisceral and cutaneous genetic porphyrias including ulcerative colitis, Crohn's disease, celiac disease, dermatitis herpetiformis, diabetes, systemic and discoid lupus, rheumatoid arthritis, ankylosing spondylitis, scleroderma, Sjogren's disease and scleritis. Physicians should be on high alert for porphyrias in families with autoimmune disorders and care must be taken with potential porphyrinogenic drugs, including sulfasalazine.

•Race or ethnicity. Although whites have the highest risk of the disease, it can occur in any race. If you're of Jewish descent, your risk is even higher.

•Diet: as the colon is exposed to many dietary substances which may encourage inflammation, dietary factors have been hypothesized to play a role in the pathogenesis of both ulcerative colitis and Crohn's disease. There have been few studies to investigate such an association, but one study showed no association of refined sugar on the prevalence of ulcerative colitis.

•Diet: A diet low in fermentable dietary fiber may affect ulcerative colitis incidence.

•Isotretinoin (Accutane) use. Isotretinoin (Accutane) is a powerful medication sometimes used to treat scarring cystic acne or acne that doesn't respond to other treatments. Although cause and effect hasn't been proved, studies have reported the development of inflammatory bowel disease with isotretinoin use.

•Nonsteroidal anti-inflammatory medication(NSAID). Although these medications — ibuprofen (Advil, Motrin, others), naproxen (Aleve), diclofenac (Cataflam, Voltaren), piroxicam (Feldene) and others — haven't been shown to cause ulcerative colitis, they can cause similar signs and symptoms.

Additionally, these medications can make existing ulcerative colitis worse, and may make your initial diagnosis more difficult.
• Other theories. Levels of sulfate-reducing bacteria tend to be higher in persons with ulcerative colitis. This could mean that there are higher levels of hydrogen sulfide in the intestine. An alternative theory suggests that the symptoms of the disease may be caused by toxic effects of the hydrogen sulfide on the cells lining the intestine.It may be caused by occlusions in the capillaries of the subepithelial linings, degenerated fibers beneath the mucosa and infiltration of the lamina propria with plasma cells


Possible complications of ulcerative colitis include:
• Severe bleeding
• Perforated colon
• Severe dehydration
Liver disease
• Prmary sclerosin cholangitis
• Inflammation of your skin, joints and eyes
• An increased risk of colon cancer (20 X normal population)
• Toxic megacolon

Treatments and drugs

The goal of medical treatment is to reduce the inflammation that triggers your signs and symptoms. In the best cases, this may lead not only to symptom relief but also to long-term remission. Ulcerative colitis treatment usually involves either drug therapy or surgery.
Doctors use several categories of drugs that control inflammation in different ways. But drugs that work well for some people may not work for others, so it may take time to find a medication that helps you. In addition, because some drugs have serious side effects, you'll need to weigh the benefits and risks of any treatment.

Anti-inflammatory drugs

Anti-inflammatory drugs are often the first step in the treatment of inflammatory bowel disease. They include:
• Sulfasalazine (Azulfidine). Sulfasalazine can be effective in reducing symptoms of ulcerative colitis, but it has a number of side effects, including nausea, vomiting, diarrhea, heartburn and headache. Don't take this medication if you're allergic to sulfa medications.
• Mesalamine (Asacol, Rowasa, others), balsalazide (Colazal) and olsalazine (Dipentum). These medications tend to have fewer side effects than sulfasalazine has. You take them in tablet form or use them rectally in the form of enemas or suppositories, depending on the area of your colon affected by ulcerative colitis. You may prescribe a combination of two different forms, such as oral and an enema or suppository. Mesalamine can relieve signs and symptoms in more than 90 percent of people with mild ulcerative colitis. People with proctitis tend to respond better to combination therapy with oral mesalamine and suppositories. For left-sided colitis, a combination of oral mesalamine and mesalamine enemas seems to work better than either agent alone if symptoms are mild to moderate.
Corticosteroids. Corticosteroids can help reduce inflammation, but they have numerous side effects, including weight gain, excessive facial hair, high blood pressure, type 2 diabetes, osteoporosis and an increased susceptibility to infections. Doctors generally use corticosteroids only if you have moderate to severe inflammatory bowel disease that doesn't respond to other treatments. Corticosteroids aren't for long-term use and are generally prescribed for a period of three to four months.
They may also be used in conjunction with other medications as a means to induce remission. For example, corticosteroids may be used with an immune system suppressor — the corticosteroids can induce remission, while the immune system suppressors can help maintain remission. Occasionally, you may also prescribe short-term use of steroid enemas to treat disease in your lower colon or rectum.
Immune system suppressors
These drugs also reduce inflammation, but they target your immune system rather than treating inflammation itself. Because immune suppressors can be effective in treating ulcerative colitis, scientists theorize that damage to digestive tissues is caused by your body's immune response to an invading virus or bacterium or even to your own tissue. By suppressing this response, inflammation is also reduced. Immunosuppressant drugs include:
• Azathioprine (Azasan, Imuran) and mercaptopurine (Purinethol). Because azathioprine and mercaptopurine act slowly — taking three months or longer to start working — they're sometimes initially combined with a corticosteroid, but in time, they seem to produce benefits on their own.
Side effects can include allergic reactions, bone marrow suppression, infections, and inflammation of the liver and pancreas. There also is a small risk of development of cancer with these medications. If you're taking either of these medications, you'll need to follow up closely with your doctor and have your blood checked regularly to look for side effects. If you've had cancer, discuss this with your doctor before starting these medications.
Cyclosporine (Gengraf, Neoral, Sandimmune). This potent drug is normally reserved for people who don't respond well to other medications or who face surgery because of severe ulcerative colitis. In some cases, cyclosporine may be used to delay surgery until you're strong enough to undergo the procedure; in others, it's used to control signs and symptoms until less toxic drugs start working. Cyclosporine begins working in one to two weeks, but because it has the potential for severe side effects, including kidney damage and fatal infections, talk to your doctor about the risks and benefits of treatment. There's also a small risk of cancer with these medications, so let your doctor know if you've previously had cancer.
• Infliximab (Remicade). This drug is specifically for those with moderate to severe ulcerative colitis who don't respond to or can't tolerate other treatments. It works by neutralizing a protein produced by your immune system known as tumor necrosis factor (TNF). Infliximab finds TNF in your bloodstream and removes it before it causes inflammation in your intestinal tract.
Some people with heart failure, people with multiple sclerosis, and people with cancer or a history of cancer can't take infliximab. The drug has been linked to an increased risk of infection, especially tuberculosis and reactivation of viral hepatitis, and may increase your risk of blood problems and cancer. You'll need to have a skin test for tuberculosis before taking infliximab.
Also, because infliximab contains mouse protein, it can cause serious allergic reactions in some people — reactions that may be delayed for days to weeks after starting treatment. Once started, infliximab is often continued as long-term therapy, although its effectiveness may wear off over time.

Nicotine patches
These skin patches — the same kind used to quit smoking — seem to provide short-term relief from flare-ups of mild ulcerative colitis for some people. How nicotine patches work isn't exactly clear, and the evidence that they provide relief that's better than other therapies is contested among researchers. Talk to your doctor before trying this treatment. One thing that is clear, however, is that the overall health risks from smoking far outweigh any potential benefit that nicotine might provide, so don't begin smoking to treat ulcerative colitis.

Other medications

In addition to controlling inflammation, some medications may help relieve your signs and symptoms. Depending on the severity of your ulcerative colitis, your doctor may recommend one or more of the following:
• Antibiotics. People with ulcerative colitis who run fevers will likely be given antibiotics to help prevent or control infection.
• Anti-diarrheals. A fiber supplement such as psyllium powder (Metamucil) or methylcellulose (Citrucel) can help relieve signs and symptoms of mild to moderate diarrhea by adding bulk to your stool. For more severe diarrhea, loperamide (Imodium) may be effective. Use anti-diarrheal medications with great caution, however, because they increase the risk of toxic megacolon.
• Pain relievers. For mild pain, your doctor may recommend acetaminophen (Tylenol, others). Don't use nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen (Advil, Motrin, others) or naproxen (Aleve). These are likely to make your symptoms worse.
• Iron supplements. If you have chronic intestinal bleeding, you may develop iron deficiency anemia. Taking iron supplements may help restore your iron levels to normal and reduce this type of anemia once your bleeding has stopped or diminished.

If diet and lifestyle changes, drug therapy or other treatments don't relieve your signs and symptoms, your doctor may recommend surgery. Surgery can often eliminate ulcerative colitis. But that usually means removing your entire colon and rectum (proctocolectomy). In the past, after this surgery you would wear a small bag over an opening in your abdomen (ileostomy) to collect stool. But a procedure called ileoanal anastomosis eliminates the need to wear a bag. Instead, your surgeon constructs a pouch from the end of your small intestine. The pouch is then attached directly to your anus. This allows you to expel waste more normally, although you may have more-frequent bowel movements that are soft or watery because you no longer have your colon to absorb water.
Between 25 and 40 percent of people with ulcerative colitis eventually need surgery.


Women with ulcerative colitis can usually have successful pregnancies, especially if they can keep the disease in remission during pregnancy. There is a slight increase in the risk of premature delivery and babies with low birth weights. Ideally, you'll become pregnant when your disease is in remission. Some medications may not be indicated for use in pregnancy, especially during the first trimester, and the effects of certain medications may linger after you stop them. Talk with your doctor about the best way to manage your illness before you conceive. If you stop certain medications, their effects may linger. It's estimated that the risk of passing ulcerative colitis to your offspring if your partner doesn't have ulcerative colitis is less than 5 percent.

Comparison to Crohn's disease
The most common disease that mimics the symptoms of ulcerative colitis is Crohn's disease, as both are inflammatory bowel diseases that can affect the colon with similar symptoms. It is important to differentiate these diseases, since the course of the diseases and treatments may be different. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as indeterminate colitis.

Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis. C D Gillen, R S Walmsley, P Prior, H A Andrews, and R N Allan. 1994 November

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