Ulcerative Colitis

Diagram of the Human Intestine

Ulcerative colitis is an inflammatory disease of the bowel that usually affects the distal end of the large intestine and rectum. It has no known cause, although there is a genetic component to susceptibility.

Features

• Chronic diarrhoea (sometimes bloody). Other symptoms may include abdominal pain and discomfort, bloating, and nausea.
• No infective cause of diarrhea found.
• Inflammatory changes are most often confined to the left side and distal parts of the large intestine, however, any part of the colon can be affected. Inflammatory changes can expand over time and affect larger areas of the colon. Long periods of inflammaton lead to fibrotic changes and can cause colon de-haustration, which results in the characteristic narrowing of the bowel.
• Disease variable in severity from patient to patient and time to time. This makes long-term prognosis very difficult, since a specific patient may remain in clinical remission for years between exacerbations.
• Significant risk of carcinoma after 10 years, which may in some cases require frequent surveillance biopsies or even prophylactic bowel removal.
• Patients may have other auto-immune features and extra-bowel complications including but not limited to iritis, uveitis, episcleritis, migratory polyarthritis, sacroiliitis, erythema nodosum, fingertip clubbing, ankylosing spondylitis and primary sclerosing cholangitis.
• Fistula formation is rare but does occur. However, unlike Crohn's disease, the probability of recurrence is low. Anal fissures are unfortunately much more common, and are in fact the very mechanism through which fistulas can be formed (although rarely) in ulcerative colitis patients - deep fissures can reach glands in the anal walls which then become infected and form abscesses which, in turn, lead directly to fistula formation.
• Often found in former smokers. Stopping smoking can cause a reduction in the protective mucus lining the colon. When this protective mucus is reduced, the bacteria in the colon can attack the colon lining causing the immune system to become active and fight the bacteria. For unknown reasons, this causes damage to the lining (ulcers) of the colon walls in one or more places. Resumption of nicotine either through patches or smoking can extend remission time although the benefits versus the other health risks of smoking are questionable.

Comparison to Crohn's disease

Ulcerative colitis is similar to Crohn's disease, but there are characteristic differences. Ulcerative colitis affects only the colon and cannot "migrate" to the small intestine, while Crohn's disease can affect the entire digestive tract. Complete colon removal can thus be considered a "cure" for ulcerative colitis. Ulcerative colitis is usually confined to the mucosal and submucosal lining of the colon, and affects whole areas of intestine. Crohn's disease, on the other hand tends to be patchy, and affect more layers of intestine, being transmural in nature. Due to the nature of the inflammation, ulcerative colitis rarely requires resection surgery in contrast to Crohn's disease where such surgery is often needed due to dangerous bowel obstructions and other complications. However, the risk of colorectal cancer development in ulcerative colitis patients is significantly greater (up to 5 times) than general population after 10 years following the diagnosis.

Cause

The cause of ulcerative colitis is unknown, although infective agents have been suspected, and there is a genetic component to susceptibility. Immune system over-activity has also been suspected as a cause.

There is much research currently being conducted in this area, and some new theories and medications show promising results. While a definitive cause of ulcerative colitis may never be discovered (since it is highly possible that it is a result of a combination of environmental, genetical, bacterial and other factors), an effective treatment or even a cure may not be very far away.

Diagnosis

A long-standing history of bloody diarrhea, with no sign of infection, is consistent with ulcerative colitis. A diagnosis is usually achieved through colonoscopy with biopsy of pathological lesions. Ulcerative colitis most often affects the rectum and the distal left side of the colon, but can occur anywhere in the large intestine. Pan-colitis is a full-blown inflammation of the entire colon (including the appendix), and is especially hard to treat.

Course

People with ulcerative colitis may initially have bloody diarrhea (the severity of which is variable from time to time). Because of destruction of the nerves in the bowel, movement may be impaired, and the intestine may dilate. This may, in some cases, result in an extreme diarrheal disease - toxic megacolon, however the probability of occurrence is very low, and is further reduced by regular routine surveillance by colonoscopy. Eventually the inflamed mucosa may develop a risk of malignancy, requiring biopsy every few months. Sometimes the risk of malignancy is such that bowel resection is offered. Many secondary complications are due to the nature of some medication prescribed for treatment of the symptoms, notably corticosteroids and immunosupresive agents, and long-term use of these drugs should be avoided if at all possible.

However, in most ulcerative colitis cases prognosis is relatively good, as remission can often be maintained through relatively harmless anti-inflammatory medication and most patients may never require any kind of surgery for their condition. While quality of life can often be impaired by unpleasant symptoms such as pain, vomiting and chronic diarrhea, the disease is very rarely fatal on its own, and most patients enjoy normal symptom-free lives while in remission.

Treatment

Although much progress has been made in the last 20 years, in understanding and treating the disease, a definitive treatment or cure for Ulcerative colitis still eludes modern medicine. Therefore, treatment for Ulcerative colitis actually aims at inducing remission, preventing relapse, improving nutritional deficiency, and ensuring normal growth and development in child patients. This is achieved primarily through medication, and sometimes surgery.

• Anti-inflammatory drugs (such as sulfasalazine or mesalamine) are often used, and in severe cases corticosteroids may be given.
• Immunosuppressive agents such as azathioprine, 6-mercaptopurine (6-MP), and more recently, cyclosporine are also used as effective preventive medications.
• Anti-diarrheal drugs (such as loperamide) should be avoided unless under specific doctors orders, as they can worsen the disease.

Surgery is rarely recommended, except in cases where drug treatment has proven completely ineffective. Since ulcerative colitis affects only the colon, a complete large intestine removal can be considered a cure. A more aesthetically and functionaly pleasing resolution may be a j-pouch surgery, where a part of the terminal ileum is used to create a "pouch" which is then connected to the anus. This preserves the appearance of normal bowel function, although bowel movements are somewhat more frequent.

There is no proven connection between dietary habits and the onset of the disease. Although opinions are somewhat divided on this issue it is safe to say that no particular diet can influence length of remission or cause inflammation if none is present. The usual recommendation for patients is to simply avoid foods that have caused them discomfort in the past, and try to eat as healthy as possible. This does not apply to acute onsets of the disease when a patient should try and maintain a low-fat and generally bland diet to facilitate faster and easier healing.

Current research and treatment alternatives

Kampo medicine is used in Japan as complementary or alternative medication to sulfasalazine. Oren-gedoku-to is one such traditional herbal medicine being used both in Japan and China since the Han Dynasty (Traditional Chinese Medicine name is Huang-Liang-Jie-Du-Tang and english name Coptis Detoxifying Formula). Another herbal supplement said to help with the bleeding hemorrhoids associated with ulcerative colitis is rutin, sold in most vitamin and supplement stores.

A significantly elevated number of sulfate-reducing bacteria in the colon has been observed in some ulcerative colitis patients, resulting in higher concentrations of the toxic gas hydrogen sulfide. It is has been suggested that this may be a major contributor to the disease, however, it is not completely clear whether this may be considered a cause or a mere side-effect of the disease itself. Further research is underway. [Roedinger 1997, Levine 1998]

Interestingly enough, another unrelated study suggested sulphur contained in red meats and alcohol may lead to an increased risk of relapse for patients in remission.[1]

One controversial theory claims that Mycobacterium paratuberculosis which is responsible for Johne's disease in cows, sheep and goats has many similarities to Crohn's and a lesser extent ulcerative colitis. The M. paratuberculosis bacteria are extremely hardy and may survive normal pasteurization method of milk which is 72 degrees celsius for 15 seconds. The theory is further that the M. paratuberculosis bacteria are only indirectly responsible, since it is the immune system of the person that overreacts in an allergic fashion to this intestinal bacteria. M. paratuberculosis is also probably underreported as the suspect variant grows very slowly in ordinary cultivation tests and recent research indicates only DNA testing will show if it is present in low numbers.[2]

Recently, probiotics have become a powerful alternative treatment for ulcerative colitis. While they do not cure the disease, they have been found to significantly reduce symptons. One probiotic formula known as VSL #3 has shown promise for people with ulcerative colitis. [3]

Another controversial area of probiotic research called Fecal bacteriotherapy involves the infusion of human probiotics through fecal enemas. It suggests that the cause of ulcerative colitis may be a previous infection by a still unknown pathogen (possibly even Mycobacterium paratuberculosis), which resolves itself naturally but somehow damages the bacterial flora of the colon, causing an imbalance, which then proceeds to reinfect and damage the colon in an endless cycle which can be broken by "recolonizing" the colon with bacteria from a healthy bowel. While there are still many questions that remain to be answered, there have been several clinicaly researched cases where people with ulcerative colitis have been "cured" or remain in remission - some of them for more than 13 years to date - without drugs. While the process itself has been used in hospitals to cure pseudomembranous colitis caused by C. difficile infection (which exhibits symptoms remarkably similar to ulcerative colitis), it has yet to be given serious consideration by the scientific community. [4]

Helminthic therapy is another promising new treatment for Ulcerative Colitis and Crohn's disease which has shown great results in clinical trials. It argues that the absence of intestinal worms (due primarily to higher hygiene standards) from the human intestinal tract may cause the immune system, which is not evolutionary adapted to this condition, to over-react causing inflammation and other negative effects, and that reintroducing helminths through ingesting eggs of a certain species (which is not dangerous to humans) can help downregulate and normalize immune responses.

It is interesting to note that both the helminthic therapy and the fecal bacteriotherapy induce a characteristic TH2 white cell response in the diseased areas which seems to be the key in achieving and maintaining remission, and may prove to be of key significance in further research. If the theories behind these new treatments prove correct, they could also very elegantly explain the similarities, differences and reasons behind Crohn's disease and ulcerative colitis (one being induced by lack of certain helminth parasites in the bowel, the other by lack of certain bacteria).

See also

• Aphthous stomatitis
• Cholangiocarcinoma
• Crohn's disease
• Ileostomy
• Inflammatory bowel disease
• Primary sclerosing cholangitis

External links

• National Association for Colitis and Crohn's disease (UK)
• Crohn's and Colitis Foundation of America
• Crohn's Zone - Support for Crohn's and Colitis
• IBD Directory - Listings for Crohn's and colitis resources
• Teen IBD - Support for teens with Colitis & Crohn's
• IBD Sucks - an online forum for people with Colitis, Crohn's, and IBS
• United Ostomy Associations of America - a national network for bowel and urinary diversion support groups.

References

• Roediger et al. "Colonic sulfide in pathogenesis and treatment of ulcerative colitis.", Dig Dis Sci. 1997 Aug;42(8):1571-9. PMID 9286219
• Levine et al. "Fecal hydrogen sulfide production in ulcerative colitis.", Am J Gastroenterol. 1998 Jan;93(1):83-7. PMID 9448181
• Borody TJ, Warren EF, Leis SM, Surace R, Ashman O, Siarakas S., "Bacteriotherapy Using Fecal Flora: Toying With Human Motions", J Clin Gastroenterol. 2004 Jul;38(6):475-483.
• Borody TJ, Warren EF, Leis S, Surace R, Ashman O., "Treatment of ulcerative colitis using fecal bacteriotherapy.", J Clin Gastroenterol. 2003 Jul;37(1):42-7.