Ulcerative Colitis Blog

Extraintestinal Manifestations of Ulcerative Colitis Part I
Ulcerative colitis and Crohns disease are chronic inflammatory conditions primarily involving the intestine. The systemic nature of these diseases, however, may result in pathological processes involving other organ systems. The constellation of disease associated, non-gastrointestinal symptoms experienced by patients are referred to as extraintestinal manifestations (EMs) of IBD. The reason why some IBD patients develop EMs and others do not is not known. It is suspected that both genetics and autoimmunity play a role in the development of symptoms outside the gastrointestinal tract.

Estimates suggest that 20-40% of IBD patients have EMs, with a slightly greater prevalence among individuals with Crohns disease than UC. The most common EMs of UC involve the musculoskeletal system, skin, eyes, and liver. While the vast majority of EMs develop after the diagnosis of UC, 10% of patients may experience non-gastrointestinal symptoms as the first sign of their UC.

Musculoskeletal Manifestations
Arthritis - The arthritis associated with UC is typically described as an aching or stiffness in the knees, hips, ankles, wrists, or elbows. Unlike other forms of arthritis (ie; rheumatoid arthritis/osteoarthritis) the joints tend not to swell or become deformed. It has been suggested that the severity of arthritis correlates with disease extent and activity in the bowel.
Sacroiliitis - Inflammation of the joints of the tailbone is a common cause of low back pain among patients with UC.
Ankylosing spondylitis - Ankylosing spondylitis is a rheumatologic condition of the spine which can exist by itself or in association with UC. Inflammation and fusion of spinal joints results in back pain and stiffness. For further information click on the link below.– http://www.wheelessonline.com/ortho/ankylosing_spondylitis

Skin Manifestations
Erythema nodosum – Erythema nodosum presents with red, painful, warm, raised nodules symmetrically distributed on the legs, and sometimes arms. The appearance of the nodules is often associated with underlying bowel activity and arthritis. For photos and further information - http://www.aafp.org/afp/20070301/695.html
Pyoderma gangrenosum – Pyoderma gangrenosum begins as a pustular or nodular lesion which subsequently ulcerates and erodes surrounding tissue. These lesions are often seen on the front of the legs, at sites of prior trauma, and around ostomies. Their evolution tends to be independent of bowel activity. For photos and further information click on the link below.– http://postgradmed.com/.../12_02/puzzles_answer.htn

Colorectal cancer (CRC) affects about 3% of the general population, but it is the most significant cause of increased death in patient's with UC. Early studies began following patients in the 1950's, concluding that the risk of CRC was not increased during the first decade of disease, but after 10 years the annual risk was 0.5-1.0%. Whether these estimates apply to today's, more recently diagnosed, patients is unclear, since early studies may have had design flaws which exaggerated the risk of cancer.

A recent study of patients with extensive UC, found a rate of dysplasia (pre-cancer) and cancer which was 8% at 20 years after diagnosis and 16% after 30 years; slightly lower than the rate of cancer alone reported in older studies. The cancer risk was 8% at 30 years and 11% at 40 years, <0.5% per year.

In addition to duration of disease, the following factors have been found to increase cancer risk:

1) Greater extent of colonic involvement (pancolonic proctitis)
2) Greater disease activity
3) Young age at onset
4) Primary sclerosing cholangitis (stricturing disease of the bile ducts)
5) Family history of colon cancer

Other than disease activity, the other risk factors are fixed, so what can we do to prevent cancer in UC? ...Next time, next time.

Please feel free to send a comment, ask a question, or suggest a topic.

Eye Manifestations
Episcleritis - Episcleritis is a condition in which the sclera (white part of the eye) becomes red. It may be painless or associated with some mild discomfort and tearing. Vision is not affected. Therapy consists of treating the underlying disorder (ie; UC) or steroid eye drops. For more information and photos -http://www.revoptom.com/handbook/sect2f.htm
Uveitis and Iritis - Uveitis and iritis refer to inflammation of deeper structures of the eye. Symptoms are more severe than episcleritis and consist of eye pain, blurred vision, sensitivity to light, and headache. The onset of eye symptoms associated with visual changes warrants immediate referral to an ophthalmologist. Treatment includes topical or systemic steroid therapy. For more information and photos - http://www.revoptom.com/handbook/oct02_sec4_6.htm

Liver (Hepatobiliary) Manifestations
Primary sclerosing cholangitis (PSC) – PSC is chronic liver disease in which the ducts of the liver become scarred and fibrotic. Over time, the liver itself becomes scarred and eventually results in liver failure. There is a well-recognized association between PSC and IBD. It is estimated that 4-5% of patients with IBD have PSC; it is more commonly seen in individuals with UC than Crohn’s disease. Patients typically present with weight loss, fatigue, jaundice and itching. At present, there are no medications that can cure PSC. Ultimately, patients who develop severe complications of chronic liver disease require liver transplantation.

Hematologic Manifestations
Thrombophilia - Patients with IBD have a predilection to the development of blood clots known as thrombophilia. The thrombophilia associated with IBD is believed to be due to abnormal levels of circulating factors enhancing clot formation, elevated numbers of platelets, and/or underlying genetic mutations. Most commonly, blood clots occur in the legs, however, they can also form in the brain, lung, liver and upper extremities.

The first line of colon cancer prevention is surveillance colonoscopy performed every 1-3 years beginning 10 years after the diagnosis of UC. These colonoscopies are performed by taking approximately 32 random tissue biopsies throughout the colon, in addition to samples of any abnormal appearing tissue. Dysplasia, a pre-cancerous lesion, can often be identified before it progresses into cancer. Once dysplasia is identified, options include more frequent colonoscopy or colectomy.

While no randomized trials have been performed to assess the efficacy of surveillance colonoscopy, several observational studies have been performed throughout the US and Europe. These studies suggest that there is a lower risk of cancer in patients with UC who have had at least one surveillance colonoscopy and that colonoscopy is an effective method of identifying dysplasia and cancer.

Several new colonoscopic technologies and techniques are being studied in order to improve the ability of colonoscopy to identify dysplasia and cancer.

High definition endoscopy - Scopes today offer high definition video, which increases visibility of small lesions.

Chromoendoscopy – Use of indigo-carmine dye sprayed into the colon helps to highlight abnormal colonic tissue for biopsy.

Narrow Band Imaging (NBI)– Similar to chromoendoscopy, NBI uses light filters, instead of dye, to aid identification of abnormal tissue.

Endomicroscopy- A microscope mounted on the colonoscope enables the evaluation of suspicious lesions in real time for more directed examination and biopsy.

Which, if any, of these methods will become standard of care is yet to be seen.

Next week:
Are there medications that prevent colon cancer?...Is there any way to guarantee that colon cancer will not occur?

Making a diagnosis of inflammatory bowel disease is like putting together a puzzle. A patient’s symptoms, laboratory tests, endoscopic findings, and radiographic tests serve as the pieces physicians fit together to determine a diagnosis. A brief overview of the diagnostic approach to UC includes the following:

1) Patient History and Symptoms: The evaluation of UC always begins with thorough history taking and physical examination of the patient. The most common symptoms experienced by patients with UC are rectal bleeding, a sense of urgency to have a bowel movement, and the passage of mucus from the rectum. Among patients in whom the disease spreads along the length of the colon, diarrhea and abdominal pain may become predominant symptoms. As noted in previous blog entries, UC is a systemic disease and can also be associated manifestations outside the GI tract such as arthritis, skin rashes, and eye changes.

2) Laboratory Tests: If a patient’s symptoms are suspicious for UC, the next step in the diagnosis involves performing laboratory tests. Some of the most common tests are:

Complete blood count (CBC) This blood test examines the types of cells in the blood. In UC and infectious colitis, infection fighting cells known as white blood cells and clotting factors known as platelets may be elevated. By contrast, the red blood cell count which measures the cells in the blood that carry oxygen may be decreased from blood lost by the inflamed colon.

Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) You may hear your doctor talk about the ESR or CRP rate. These are chemicals in the blood that become elevated when inflammation or infection is present in the body. The level of inflammation typically correlates with the degree of inflammation. Therefore, the levels of these factors can be followed as markers of disease activity.

Stool Cultures Infectious colitis can present with the same symptoms as UC. Therefore, it is important that a patient’s stool is examined for bacteria and parasites. It is common for several stool samples to be collected, as infectious organisms can be missed if only one specimen is examined.

Serologic Markers In recent years, research has suggested that there are particular antibodies in the blood of some patients with IBD. The antibody known as pANCA (Peripheral anti-neutrophil cytoplasmic antibody) is present in up to 70% of patients with UC and 20% of patients with Crohn’s colitis. Because these antibodies are not present in everyone with IBD, a person with a negative serologic test may still have disease.

3) Endoscopic studies: The most important test for making a diagnosis of UC is a colonoscopy. If a patient’s history, symptoms, and laboratory tests suggest a diagnosis of UC, then the next step is to evaluate the lining of the intestine and take tissue samples to examine under the microscope. The colonoscopy is performed under sedation and involves insertion of a long, flexible tube with a camera into the anus through the length of the colon. The colonoscopy is useful not only for making the diagnosis, but also to define the extent and severity of disease. If there is a question of UC vs. Crohn’s disease, some physicians may perform a video capsule endoscopy, which involves the patient swallowing a small pill containing a camera to examine the small intestine.

4) Radiographic tests: Sometimes x-ray tests are needed to help make a diagnosis of IBD or to differentiate UC from Crohn’s disease. The most common tests performed are:

Small bowel follow-through This test involves drinking barium material and serial x-rays are performed to examine how the intestine looks as the material travels through the gut. In patients with UC, changes to the lining of the intestine are seen in the large intestine and not the small intestine. In 15-20% of UC patients who have colitis affecting the entire length of the colon, x-ray changes may be seen in the very last portion of the small intestine called the terminal ileum. In this case, further evaluation is done to differentiate these changes from Crohn’s disease.

CT enterography A CT enterography is a cat scan test that involves drinking a contrast material that lines the intestine. A cat scan is then performed to examine the bowel wall for thickening and other changes suggestive of Crohn’s disease or UC.

From this overview, you can see that there are several important pieces of information that need to fit together to make a diagnosis of UC. This process can be both challenging and frustrating at times for patients when the pieces of the puzzle don’t fit together easily. With patience and a methodical stepwise approach, however, a confident diagnosis can usually be reached.

The ability of a medication to decrease the risk of a disease development is known as chemoprevention. In the setting of UC, investigators are looking for a safe drug that would decrease the risk of dysplasia and cancer.

5-aminosalicylate (5-ASA) compounds are the most promising chemopreventive agents. This class of drugs includes mesalamine, sulfasalazine, and balsalazide. They are used as first line therapy for mild-moderate UC. A recent analysis, summarizing the data of 9 case-control studies, included almost 2000 patients with 334 cancers and 140 cases of dysplasia. Those who used 5-ASA medications decreased their rate of cancer by about 50%, although the rate of dysplasia was unchanged.

These studies are retrospective so that even though they corrected for differences in certain patient characteristics, we have to be aware that there could be unmeasured or unadjusted factors which correlate with the use of 5-ASA. The gold standard is to perform a prospective randomized controlled trial, but such study is unlikely to be performed due to prohibitive cost and duration. As a result, the use of these medications for cancer preventions remains controversial.

Use of other UC medications, such as the immunosuppressant azathioprine, have failed to correlate with a decreased risk of colon cancer.

There is only one way to guarantee that colon cancer does not occur- take out the colon. Colectomy is often performed for patients who do not respond to UC medications or who have pre-cancerous or cancerous colonic lesions. It is rarely performed purely for prevention of colon cancer, especially since the lifetime risk of colon cancer in UC may be less than was once thought. (see previous postings)

In the future, I will examine surgical options and approaches.