Ulcerative colitis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

The first case of ulcerative colitis was reported by Sir Samuel Wilks in 1859. He even coined the term ulcerative colitis and submitted the histopathological slides for the first time in his case report. It was believed that Prince Charles, young pretender of the roman empire, suffered from ulcerative colitis and cured himself by adopting a milk-free diet. In 1885, Allchin gave a detailed description of ulcerative colitis for the first time. Based on the work by Allchin, Hale-White in 1888, differentiated ulcerative colitis from Crohn’s disease.^[1]

• In 1745, Prince Charles suffered from ulcerative colitis and cured himself by adopting a milk-free diet.^[1]
• In 1859, Sir Samuel Wilks first used the term ulcerative colitis in a case report even produced photomicrographs showing the histological appearances, an outstanding technical achievement for the time.
• In 1885, Allchin gave a detailed description of ulcerative colitis for the first time.
• In 1888, Hale-White worked on the study done by Allchin and differentiated ulcerative colitis from Crohn’s disease.
• In 1965, Evans & Acheson suggested that ulcerative colitis afflicts roughly 1 in 1000 of the general population.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]

Inflammatory bowel disease (IBD) may be classified into ulcerative colitis and Crohn’s disease. Some cases which depict overlapping features of both ulcerative colitis and Crohn’s disease can be classified as intermediate colitis. Ulcerative colitis may be classified according to anatomical location as proximal or distal. Additionally, ulcerative colitis may be classified based on the severity into mild, moderate, severe or fulminant.^[1]

The inflammatory bowel disease (IBD) is divided primarily into ulcerative colitis and Crohn’s disease. Ulcerative colitis can be classified on according to anatomical location or severity.^[1][2][3][4]

Ulcerative colitis can be classified as follows based on the location of involvement of the colon:

• Distal
  • Limited below the descending colon
  • Topical therapy can be used
• Proximal
  • Extends proximal to the descending colon
  • Systemic therapy is required

• Mild
  • < 4 loose stools per day (+/- blood)
  • No dehydration
  • Mild crampy pain
  • No fever
  • Normal hemoglobin
  • Normal ESR
• Moderate
  • > 4 loose stools per day (+/- blood)
  • Mild dehydration
  • Abdominal pain that is not severe
  • Low grade fever
  • Mild anemia not requiring blood transfusions
• Severe
  • ≥6 loose bloody stools per day
  • Moderate to severe dehydration
  • Severe abdominal cramps
  • High fever (temperature ≥37.5ºC)
  • HR ≥90 beats/minute
  • Hemoglobin <10.5 g/dL
  • Elevated ESR (≥30 mm/hour)
  • Rapid weight loss
• Fulminant
  • >10 loose stools per day
  • Continuous bleeding
  • Severe dehydration
  • Severe abdominal pain
  • Abdominal distension
  • High fever (temperature ≥37.5ºC)
  • HR ≥90 beats/minute
  • Hemoglobin <10.5 g/dL
  • Elevated ESR (≥30 mm/hour)
  • Rapid weight loss

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]

The exact cause of ulcerative colitis is still unknown. Several possible causes have been suggested including genetic, environmental and autoimmune factors.^[1][2]

While the cause of ulcerative colitis is unknown, several possibly interrelated causes have been suggested.

A genetic component to the etiology of ulcerative colitis can be hypothesized based on the following:^[3]

• 20-25 patients with IBD have relatives having IBD.^[4]
• Aggregation of ulcerative colitis in families
• Identical twin concordance rate of 10% and dizygotic twin concordance rate of 3%^[5]
• 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, 16, and 3 in the order of their discovery.^[6] 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.^[7] 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 HLA associations which may be at work. In fact, this linkage on chromosome 6 may be the most convincing and consistent of the genetic candidates.^[6]

Multiple autoimmune disorders have been recorded with the neurovisceral and cutaneous genetic porphyrias including ulcerative colitis, Crohn’s disease, celiac disease, dermatitis herpetiformis, 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.

Many hypotheses have been raised for environmental contributants to the pathogenesis of ulcerative colitis. They include the following:

• Diet: As the colon is exposed to many different 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.^[8]
• Smoking: Unlike Crohn’s disease, ulcerative colitis has a lesser prevalence in smokers than non-smokers.^[9]
• Breastfeeding: There have been conflicting reports of the protection of breastfeeding in the development of inflammatory bowel disease. One Italian study showed a potential protective effect.^[10]
• Other childhood exposures, or infections
• Use of NSAIDs
• Stress

Some sources list ulcerative colitis as an autoimmune disease, a disease in which the immune system malfunctions, attacking some part of the body. As discussed above, ulcerative colitis is a systemic disease that affects many areas of the body outside the digestive system. Surgical removal of the large intestine often cures the disease, including the manifestations outside the digestive system.^[11] This suggests that the cause of the disease is in the colon itself, and not in the immune system or some other part of the body.

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.^[12][13]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]

Ulcerative colitis should be differentiated from other causes of diarrhea. It is very important to differentiate it from Crohn’s disease as the management of both conditions is different though the initial presentation may be confused for any of these disorders.^[1][2]

The following conditions may present in a similar manner as ulcerative colitis, and should be excluded:

• Crohn’s disease
• Infectious colitis, which is typically detected on stool cultures
  • Pseudomembranous colitis, or Clostridium difficile-associated colitis, bacterial upsets often seen following administration of antibiotics
• Ischemic colitis, inadequate blood supply to the intestine, which typically affects the elderly
• Radiation colitis in patients with previous pelvic radiotherapy
• Chemical colitis resulting from introduction of harsh chemicals into the colon from an enema or other procedure.

The most common disease that mimics the symptoms of Crohn’s disease is ulcerative colitis, 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.^{[1][2][3][4][5][6]}

∞Small bowel diarrhea: watery, voluminous with less than 5 WBC/high power field

Large bowel diarrhea: Mucousy and/or bloody with less volume and more than 10 WBC/high power field
† It could be as high as 1000 based on patient’s immunity system.

The table below summarizes the findings that differentiate inflammatory causes of chronic diarrhea^{[10][11][12][13][13]}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]

United States, Canada, the United Kingdom, and Scandinavia have the highest incidence of inflammatory bowel disease i.e ulcerative colitis and Crohn’s disease.The incidence of ulcerative colitis in North America is 10-12 cases per 100,000.^[1] 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.^[2]

The geographic distribution of ulcerative colitis and Crohn’s disease is similar worldwide,^[1] 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.^[3]As with Crohn’s disease, ulcerative colitis is thought to occur more commonly among Ashkenazi Jewish people than non-Jewish people.

The incidence of ulcerative colitis in North America is 10-12 cases per 100,000, with a peak incidence of ulcerative colitis occurring between the ages of 15 and 25. 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.^[4] The disease tends to be more common in northern areas. Although ulcerative colitis has no known cause, there is a presumed genetic component to susceptibility. The disease may be triggered in a susceptible person by environmental factors. Although dietary modification may reduce the discomfort of a person with the disease, ulcerative colitis is not thought to be caused by dietary factors. Although ulcerative colitis is treated as though it were an autoimmune disease, there is no consensus that it is such. Treatment is with anti-inflammatory drugs, immunosuppression (suppressing the immune system), and biological therapy targeting specific components of the immune response. Colectomy (partial or total removal of the large bowel through surgery) is occasionally necessary, and is considered to be a cure for the disease.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Risk factors include a family history of ulcerative colitis, or Jewish ancestry. It may affect any age group, although there are peaks at ages 15 – 30 and then again at ages 50 – 70. It affects men and women equally and appears to run in families, with reports of up to 20 percent of people with ulcerative colitis having a family member or relative with ulcerative colitis or Crohn’s disease. A higher incidence of ulcerative colitis is seen in Whites and people of Jewish descent.^[1][2]

Common risk factors in the development of ulcerative colitis include:^[3][4]

• Family history of ulcerative colitis
• White race and Jewish ancestry
• Age 15-40 or 60-80 years
• Long term use of NSAIDS
• Living in an industrialized country
• Campylobacter
• Clostridium difficile infection
• Salmonella
• Shigella

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Tarek Nafee, M.D. [2]

Patients with ulcerative colitis require screening for colorectal carcinoma. In patients with a confirmed diagnosis of ulcerative colitis, the risk of colorectal carcinoma is increased. The American Cancer Society and the American College of Gastroenterology recommend having the initial screening 8 years after the patient is diagnosed with severe disease or when most of, or the entire, large intestine is involved and 12 to 15 years after diagnosis when only the left side of the large intestine is involved.

There is a significantly increased risk of colorectal cancer in patients with ulcerative colitis after 10 years if involvement is beyond the splenic flexure. Those with only proctitis or rectosigmoiditis usually have no increased risk.^[1] It is recommended that patients have screening colonoscopies with random biopsies to look for dysplasia after eight years of disease activity.^[2][3]

Due to the risk of colon cancer associated with ulcerative colitis, screening with colonoscopy is recommended. The American Cancer Society recommends the following schedule for colonoscopy:^[4]

• First colonoscopy 8 years after diagnosis with severe disease, or when most of, or the entire, large intestine is involved
• First colonoscopy 12 – 15 years after diagnosis when only the left side of the large intestine is involved
• Follow-up colonoscopy should be performed every 1 – 2 years

Have follow-up examinations every 1 – 2 years.

Inadequate evidence exists to recommend routine surveillance of the pouch for dysplasia or adenocarcinoma.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]

Patients with ulcerative colitis experience intermittent symptoms. This means that there are periods of disease inactivity alternating with “flares” of disease. Anemia, bowel perforation, toxic megacolon and colorectal carcinoma are a few known complications of ulcerative colitis. Ulcerative colitis also has a significant association with primary sclerosing cholangitis (PSC). A permanent and complete cure from ulcerative colitis is unusual. 67% patients relapse within 10 years of initial diagnosis.^[1][2][1][2]

Patients with ulcerative colitis usually have an intermittent course, with periods of disease inactivity alternating with “flares” of disease. Patients with proctitis or left-sided colitis usually have a more benign course: only 15% progress proximally with their disease, and up to 20% can have sustained remission in the absence of any therapy. Patients with more extensive disease are less likely to sustain remission, but the rate of remission is independent of the severity of disease.^[1]

A few possible complications of ulcerative colitis include:

• Anemia
• Toxic megacolon
• Bowel perforation
• Colorectal carcinoma
• Ankylosing spondylitis
• Cancer
• Colon narrowing
• Complications of corticosteroid therapy
• Impaired growth and sexual development in children
• Inflammation of the joints
• Lesions in the eye
• Liver disease
• Massive bleeding in the colon
• Mouth ulcers
• Pyoderma gangrenosum (skin ulcer)
• Tears or holes (perforation) in the colon

There is a significantly increased risk of colorectal cancer in patients with ulcerative colitis after 10 years if involvement is beyond the splenic flexure. Those with only proctitis or rectosigmoiditis usually have no increased risk.^[3] It is recommended that patients have screening colonoscopies with random biopsies to look for dysplasia after eight years of disease activity^[4]

Ulcerative colitis has a significant association with primary sclerosing cholangitis (PSC), a progressive inflammatory disorder of small and large bile ducts. As many as 5% of patients with ulcerative colitis may progress to develop primary sclerosing cholangitis.^[5]

The effect of ulcerative colitis on mortality is unclear, but it is thought that the disease primarily affects quality of life, and not lifespan.^[6] A few studies show a higher mortality in patient with ulcerative colitis as compared to general population.^[7]

The course of the disease generally varies. Ulcerative colitis may be inactive and then get worse over a period of years. Sometimes ulcerative colitis can progress quickly. A permanent and complete cure is unusual.^[1][2]

• 67% patients relapse within 10 years of the initial diagnosis.^[8]

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