Ulcerative Colitis Blog

What is ulcerative colitis and how is it different from other types of colitis?

Colitis is a general term referring to inflammation of the colon. It is derived from col = colon, and itis = inflammation. There are several types of colitis, such as infectious, ulcerative, and microscopic. While all involve inflammation of the colon, they each have a different underlying cause. By analogy, you can liken this to arthritis (arth = joint and itis = inflammation) which is an umbrella term describing inflammation of the joints. Similar to colitis, there are many different forms of arthritis, such as osteoarthritis and rheumatoid arthritis. Therefore, you can think of colitis as an all-encompassing word that describes any type of inflammation of the colon.

UC is a specific form of colitis in which the body’s immune system becomes overactive and does not respond to normal signals to turn off inflammatory responses. The continued cascade of immune factors released in the body primarily targets the colon resulting in inflammation of that particular organ. It is for this reason you may hear people describe UC as an autoimmune disorder, or as the immune system attacking the colon. The cornerstone of UC treatment is medication which suppresses the overactive immune system, dampening it to a normal level of regulation.

UC is differentiated from other types of colitis such as infectious and microscopic colitis based upon patient history, laboratory tests, colonoscopy results, and pathology studies. Prior to making a diagnosis of UC, your doctor may perform blood tests, stool examinations, and endoscopies with tissue biopsies to help him or her sort out what type of colitis you have. It is important to distinguish the various types of colitis from one another as their treatments and prognoses are very different.

One of the first issues when a patient presents with symptoms suggestive of inflammatory bowel disease is to determine whether there is UC or Crohn disease (CD). There are many similarities and differences between UC and CD. There are also times when they cannot even be distinguished.

We are still learning about the underlying genetics and disease process of UC and CD, but the clinical signs, symptoms, and histopathology are well described.

Here are some of the key differences between UC and CD:

1. UC only affects the colon, while CD can involve any part of the gastrointestinal tract from the mouth to the anus. Most commonly, CD affects the terminal ileum (distal small intestine) and/or colon, less often proximal small bowel (5%), and <5% of patients have upper GI involvement (stomach/esophagus).

2. UC typically involves, and is most severe in, the rectum. There is circumferential and continuous involvement moving proximally. The severity of inflammation decreases more proximally until there is a transition to normal tissue. CD tends to spare the rectum and often has patchy involvement throughout the colon and small intestine with normal intervening mucosa.

3. The ulcers of UC are typically superficial, while those of CD, though usually superficial, are more likely to extend deeper and can even erode through the entire bowel wall.

4. Many patients with CD will develop strictures, fistulas, and abscesses in the abdomen or the anorectum. Since UC is not a transmural disease these complications are quite rare.

5. UC is strongly associated with primary sclerosing cholangitis (PSC), a disease causing strictures of the bile ducts in the liver. While only 5% of patients with UC have PSC, 50% of patients with PSC have UC. CD tends to cause kidney stones due to altered intestinal handling of oxalate.

Despite these differences, UC and CD are both autoimmune diseases, overactive immune responses against self. About 10% of the time CD can be difficult, or even impossible, to distinguish from UC, but does that even matter?

What is severe ulcerative colitis?
The course of UC is variable among patients ranging from mild, limited colitis to severe, fulminant colitis. While the vast majority of UC patients are able to control their disease with currently available medications, approximately 15% will experience an attack of severe colitis requiring hospitalization and intensive therapy. Criteria that defines severe colitis includes the passage of > 6 bloody bowel movements per day, fever, accelerated heart rate, anemia (low blood count), elevated inflammatory markers in the blood, and electrolyte disturbances.

Patients manifesting symptoms of severe UC are typically admitted to the hospital for close monitoring and intravenous fluids and steroids. Examination of stool specimens for bacterial, viral, and parastitic organisms is performed in an attempt to identify potentially treatable causes of the disease flare. Careful attention to a patient’s vital signs, blood counts/chemistries, and abdominal exam is imperative. Potential serious complications of severe colitis may include toxic megacolon, gastrointestinal hemorrhage, perforation, and multi-organ system dysfunction requiring intensive care unit management.

Steroid treatment of severe ulcerative colitis
It is standard to initiate therapy with intravenous methylprednisolone at a dose of 40-60mg/day. Previous studies suggest that 75% of patients with severe colitis will respond to this form of treatment. Patients who respond to intravenous steroids will generally note an improvement in symptoms within 3-5 days. Failure of symptoms to improve within 7 days indicates steroid-refractory disease which may require alternative medical management or surgery.

Treatment options for steroid-refractory, severe ulcerative colitis
1) Cyclosporine - Cyclosporine is an immune suppressant administered intravenously at a dose of 2mg/kg/day. Response rates to cyclosporine range from 50-80%. As cyclosporine can be associated with serious side effects (hypertension, kidney failure, seizures, infection), drug administration must be carefully monitored and long-term use is not recommended. Patients who respond to intravenous cyclosporine in the hospital are subsequently placed on an oral formulation for a period of months, and then transitioned to azathioprine or 6-mercaptopurine.

2) Tacrolimus – Tacrolimus is an alternative therapy for steroid-refractory UC which has been administered both orally and intravenously in previous trials. Response rates to therapy are estimated to be about 50%. In one long-term follow-up study, 50% of patients with steroid-refractory colitis (UC and indeterminate colitis) still required surgery within 2 years.

3) Infliximab - Another alternative is infliximab, which is also a potent intravenous immune suppressant. Although there has been limited data regarding the use of infliximab in the setting of severe colitis, mounting evidence suggests it could be of at least short-term benefit. Infliximab is usually administered at a dose of 5mg/kg at 0, 2, and 6 weeks to induce remission. Current registry data regarding the safety of infliximab, indicates no greater mortality or infection risk with infliximab than other therapies. Whether infliximab can help stave off colectomy in the long-term is not known.

4) Visilizumab – A recent study reported encouraging results pertaining to the use of a new drug, visilizumab, in the treatment of steroid-refractory ulcerative colitis. Thirty-two patients with severe ulcerative colitis unresponsive to intravenous steroids were treated with visilizumab at doses of 10-15mcg/kg. After one month, 84% demonstrated a clinical response and 40-45% achieved disease remission. Forty-five percent did not require surgery or other salvage therapies within one year of receiving the medication. Further studies regarding the use of vislizumab are ongoing.

5) Surgery
Of the 15% of UC patients who develop severe colitis, 30% will ultimately require colectomy. The timing of surgery is dependent on the severity of the patient’s colitis, age, co-morbid medical conditions, response to medical therapy, and presence of complications of colitis noted above. Discussion regarding surgery in UC will be presented in future blogs.

One of my patients recently diagnosed with UC became quite tearful during her last office visit. When I inquired what had upset her, she replied that she had been seeking information about UC on the internet and was frightened by some of the stories she read. She encountered uncensored websites with postings that did not contain medically accurate information, as well as patient stories that seemed to indicate to her that a surgery was inevitable so she should start planning now. We had a long discussion about the wide spectrum of disease severity in UC and how "you should not believe everything you read," particularly on the internet. While the World Wide Web has opened new avenues to obtaining information about almost everything you could want to know at any given time, it is important to review medical information from the internet with your doctor to verify its validity. Below are a few internet sites that contain reliable information and resources for patients regarding UC and Crohn's:

General Resources

The Crohn's and Colitis Foundation of America
http://www.ccfa.org/

The American Gastroenterology Association
http://www.gastro.org

The American College of Gastroenterology
http://www.acg.gi.org

National Institutes of Health
http://www.nlm.nih.gov/medlineplus/ulcerativecolitis.html#cat10

Living with UC
http://www.livingwithuc.com/livingwithuc/home.html

Pediatric IBD Resources

Boston Children's Hospital
http://www.experiencejournal.com/ibd/

American Pediatric Surgical Association
http://www.eapsa.org/parents/resources/ulcer_coli.cfm

Ostomy Resources

United Ostomy Associations of America
http://www.uoaa.org/

A common question from patients is: "Why is it recommended that non-steroidal anti-inflammatory medications (NSAIDS), such as ibuprofen, be avoided in IBD?"

While NSAIDs can serve as potent anti-inflammatory medications to treat things such as joint pains and backaches, they can have a paradoxical pro-inflammatory effect on the GI tract. The reason this happens is that the GI tract needs multiple lines of defense to protect its inner lining (think of all things the GI tract must be able to withstand - food, stomach acid, bile, medications, alcohol). One of the defense mechanisms our body uses to protect the GI tract is the secretion of hormone-like chemicals called prostaglandins. Prostaglandins help protect the intestinal lining against ulcer formation and aid in healing the GI tract when the protective barrier is broken. NSAID medications inhibit the production of prostaglandins throughout the body, and therefore leave the lining of the GI tract vulnerable to various insults. Furthermore, studies have demonstrated an association between NSAID use and increased risk of IBD flares. It is thought that a reduction in prostaglandin levels in the GI tract may account for this observation.

As such, IBD patients are counseled to avoid products pain relievers and cold medicines that contain ibuprofen. Alternative pain medications that are safe for most IBD patients include acetaminophen and tramadol. Patients with questions about which pain medication is best for them should consult with their physician

The inflammation in ulcerative colitis (UC) and ulcerative proctitis (UP) is dynamic and the extent of the colon involved can change over time. UC and UP uniformly affect the rectum (the lowest part of the colon) and the inflammation extends for a variable length upwards through the colon. Studies of UP patients suggest that the disease moves further up to involve more of the colon in about 25% of patients after diagnosis. The probability of disease extension appears to increase over time, with cumulative probabilities of extension estimated to be 20% and 55% at 5 and 10 years, respectively. Why the amount of colon involved remains stable in some patients and extends over time in others is not known. Risk factors for extension of disease include severe, and poorly controlled UP and UC. It is noteworthy that extension of disease can occur even in patients who are asymptomatic. Understanding the anatomic location of inflammation in the colon is important because we know that segments that have been inflamed are at greater risk of developing cancer than uninflammed segments. As such, taking medications as prescribed and staying on schedule for colon cancer screening are important for UP and UC patients.