Ulcerative colitis

Ulcerative colitis
Classification and external resources
Endoscopic image of a bowel section known as the sigmoid colon afflicted with ulcerative colitis. The internal surface of the colon is blotchy and broken in places.
ICD-10	K51
ICD-9	556
OMIM	191390
DiseasesDB	13495
MedlinePlus	000250
eMedicine	med/2336
MeSH	D003093

Ulcerative colitis (Colitis ulcerosa, UC) is a form of inflammatory bowel disease (IBD). Ulcerative colitis is a form of colitis, a disease of the colon (large intestine), that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset. IBD is often confused with irritable bowel syndrome (IBS).

Ulcerative colitis has similarities to Crohn's disease, another form of IBD. Ulcerative colitis is an intermittent disease, with periods of exacerbated symptoms, and periods that are relatively symptom-free. Although the symptoms of ulcerative colitis can sometimes diminish on their own, the disease usually requires treatment to go into remission. Ulcerative colitis has an incidence of 1 to 20 cases per 100,000 individuals per year, and a prevalence of 8 to 246 per 100,000 individuals.^[1]

The disease is more prevalent in northern countries of the world, as well as in northern areas of individual countries or other regions. Rates tend to be higher in more affluent countries, which may indicate the increased prevalence is due to increased rates of diagnosis. It may also indicate that an industrial or Western diet and lifestyle increases the prevalence of this disease, including symptoms which may or may not be related to "UC." 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.

Ulcerative colitis is treated as an autoimmune disease. Treatment is with anti-inflammatory drugs, immunosuppression, and biological therapy targeting specific components of the immune response. Colectomy (partial or total removal of the large bowel through surgery) is occasionally necessary if the disease is severe, doesn't respond to treatment, or if significant complications develop. A total proctocolectomy (removal of the entirety of the large bowel) can be "curative" (extraintestinal symptoms will remain), but it may be associated with complications.^[2]

Signs and symptoms

Signs and symptoms

[ v t e ]	Crohn's disease	Ulcerative colitis
Defecation	Often porridge-like[3], sometimes steatorrhea	Often mucus-like and with blood[3]
Tenesmus	Less common[3]	More common[3]
Fever	Common[3]	Indicates severe disease[3]
Fistulae	Common[4]	Seldom
Weight loss	Often	More seldom

Gastrointestinal

The clinical presentation^[5] of ulcerative colitis depends on the extent of the disease process. Patients usually present with diarrhea mixed with blood and mucus, of gradual onset that persists for an extended period (weeks). They may also have weight loss and blood on rectal examination. The inflammation caused by the disease along with chronic loss of blood from the GI tract leads to increased rates of anaemia. The disease may be accompanied with different degrees of abdominal pain, from mild discomfort to painful bowel movements or painful abdominal cramping with bowel movements.

Ulcerative colitis is associated with a general inflammatory process that affects many parts of the body. Sometimes these associated extra-intestinal symptoms are the initial signs of the disease, such as painful arthritic knees in a teenager and may be seen in adults also. The presence of the disease may not be confirmed immediately, however, until the onset of intestinal manifestations.

Extent of involvement

Ulcerative colitis is normally continuous from the rectum up the colon. The disease is classified by the extent of involvement, depending on how far up the colon the disease extends:

• Distal colitis, potentially treatable with enemas:^[6]
  • Proctitis: Involvement limited to the rectum.
  • Proctosigmoiditis: Involvement of the rectosigmoid colon, the portion of the colon adjacent to the rectum.
  • Left-sided colitis: Involvement of the descending colon, which runs along the patient's left side, up to the splenic flexure and the beginning of the transverse colon.
• Extensive colitis, inflammation extending beyond the reach of enemas:
  • Pancolitis: Involvement of the entire colon, extending from the rectum to the cecum, beyond which the small intestine begins.

Severity of disease

In addition to the extent of involvement, people may also be characterized by the severity of their disease.^[6]

• Mild disease correlates with fewer than four stools daily, with or without blood, no systemic signs of toxicity, and a normal erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). There may be mild abdominal pain or cramping. Patients may believe they are constipated when in fact they are experiencing tenesmus, which is a constant feeling of the need to empty the bowel accompanied by involuntary straining efforts, pain, and cramping with little or no fecal output. Rectal pain is uncommon.
• Moderate disease correlates with more than four stools daily, but with minimal signs of toxicity. Patients may display anemia (not requiring transfusions), moderate abdominal pain, and low grade fever, 38 to 39 °C (100 to 102 °F).
• Severe disease, correlates with more than six bloody stools a day or observable massive and significant bloody bowel movement, and evidence of toxicity as demonstrated by fever, tachycardia, anemia or an elevated ESR or CRP.
• Fulminant disease correlates with more than ten bowel movements daily, continuous bleeding, toxicity, abdominal tenderness and distension, blood transfusion requirement and colonic dilation (expansion). Patients in this category may have inflammation extending beyond just the mucosal layer, causing impaired colonic motility and leading to toxic megacolon. If the serous membrane is involved, colonic perforation may ensue. Unless treated, fulminant disease will soon lead to death.

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. The frequency of such extraintestinal manifestations has been reported as anywhere between 6 and 47 percent.^[7] These include the following:

• Aphthous ulcer of the mouth
• Ophthalmic (involving the eyes):
  • Iritis or uveitis, which is inflammation of the iris
  • Episcleritis
• Musculoskeletal:
  • 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
  • Ankylosing spondylitis, arthritis of the spine
  • Sacroiliitis, arthritis of the lower spine
• Cutaneous (related to the skin):
  • Erythema nodosum, which is a panniculitis, or inflammation of subcutaneous tissue involving the lower extremities
  • 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

Causes

There are no direct known causes for ulcerative colitis, but there are many possible factors such as genetics and stress.

Genetic factors

A genetic component to the etiology of ulcerative colitis can be hypothesized based on the following:^[8]

• Aggregation of ulcerative colitis in families.
• Identical twin concordance rate of 10% and dizygotic twin concordance rate of 3%^[9]
• Ethnic differences in incidence
• Genetic markers and linkages

There are 12 regions of the genome that may be linked to ulcerative colitis, including, in the order of their discovery, chromosomes 16, 12, 6, 14, 5, 19, 1, and 3,^[10] but 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.^[11]

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 may even be human leukocyte antigen associations at work. In fact, this linkage on chromosome 6 may be the most convincing and consistent of the genetic candidates.^[10]

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.

Environmental factors

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 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.^[12] High intake of unsaturated fat and vitamin B6 may enhance the risk of developing ulcerative colitis.^[13] Other identified dietary factors that may influence the development and/or relapse of the disease include meat protein and alcoholic beverages.^[14][15] Specifically, sulfur has been investigated as being involved in the etiology of ulcerative colitis, but this is controversial.^[16] Sulfur restricted diets have been investigated in patients with UC and animal models of the disease. The theory of sulfur as an etiological factor is related to the gut microbiota and mucosal sulfide detoxification in addition to the diet.^[17][18][19]

• 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.^[20]

• Several scientific studies have posted that Accutane is a possible trigger of Crohn's disease and ulcerative colitis in some individuals. Three cases in the United States have gone to trial thus far, with all three resulting in multi-million dollar judgements against the makers of isotretinoin. There were an additional 425 cases pending as of.^{[21][22][23][24][25]}

Autoimmune disease

Ulcerative colitis is an autoimmune disease characterized by T-cells infiltrating the colon.^[26] 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.^[27] 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.^[6]

Alternative theories

Risk factors

[ v t e ]	Crohn's disease	Ulcerative colitis
Smoking	Higher risk for smokers	Lower risk for smokers[28]
Age	Usual onset between 15 and 30 years[29]	Peak incidence between 15 and 25 years

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.^[30]

Comparison to Crohn's disease

Ulcerative colitis and Crohn's disease are the main types of inflammatory bowel disease, and may mimic each other to great extent, but differ somewhat in etiology and pathophysiology:

Pathophysiology

Pathophysiology

[ v t e ]	Crohn's disease	Ulcerative colitis
Cytokine response	Associated with Th17[31]	Vaguely associated with Th2

An increased amount of colonic sulfate-reducing bacteria has been observed in some patients with ulcerative colitis, resulting in higher concentrations of the toxic gas hydrogen sulfide. Human colonic mucosa is maintained by the colonic epithelial barrier and immune cells in the lamina propria. N-butyrate, a short-chain fatty acid, gets oxidized through the beta oxidation pathway into carbon dioxide and ketone bodies. It has been shown that N-butyrate helps supply nutrients to this epithelial barrier. Studies have proposed that hydrogen sulfide plays a role in impairing this beta oxidation pathway by interrupting the short chain acetyl CoA dehydrogenase, an enzyme within the pathway. Furthermore, it has been suggested that the protective benefit of smoking in ulcerative colitis is due to the hydrogen cyanide from cigarette smoke reacting with hydrogen sulfide to produce the nontoxic isothiocyanate, thereby inhibiting sulfides from interrupting the pathway.^[32] An unrelated study suggested that the sulphur contained in red meats and alcohol may lead to an increased risk of relapse for patients in remission.^[30]

Diagnosis

The initial diagnostic workup for ulcerative colitis includes the following:^[6][33]

• A complete blood count is done to check for anemia; thrombocytosis, a high platelet count, is occasionally seen
• 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.^[6] 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.^{[citation needed]}

Endoscopic

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
• Pseudopolyps.

Ulcerative colitis is usually continuous from the rectum, with the rectum almost universally being involved. There is rarely perianal 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.

Histologic

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.

Differential diagnosis

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 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.

Diagnostic findings

Sign [ v t e ]	Crohn's disease	Ulcerative colitis
Terminal ileum involvement	Commonly	Seldom
Colon involvement	Usually	Always
Rectum involvement	Seldom	Usually[28]
Involvement around the anus	Common[4]	Seldom
Bile duct involvement	No increase in rate of primary sclerosing cholangitis	Higher rate[34]
Distribution of Disease	Patchy areas of inflammation (Skip lesions)	Continuous area of inflammation[28]
Endoscopy	Deep geographic and serpiginous (snake-like) ulcers	Continuous ulcer
Depth of inflammation	May be transmural, deep into tissues[10][4]	Shallow, mucosal
Stenosis	Common	Seldom
Granulomas on biopsy	May have non-necrotizing non-peri-intestinal crypt granulomas[4][35][36]	Non-peri-intestinal crypt granulomas not seen[28]

Management

Standard treatment for ulcerative colitis depends on extent of involvement and disease severity. The goal is to induce remission initially with medications, followed by the administration of maintenance medications to prevent a relapse of the disease. The concept of induction of remission and maintenance of remission is very important. The medications used to induce and maintain a remission somewhat overlap, but the treatments are different. Physicians first direct treatment to inducing a remission which involves relief of symptoms and mucosal healing of the lining of the colon and then longer term treatment to maintain the remission and prevent complications.

Medication

Ulcerative colitis can be treated with a number of medications including 5-ASA drugs such as Sulfasalazine and Mesalazine. Corticosteroids such as prednisone can also be used due to their immunosuppressing and short term healing properties, but due to the risks outweighing the benefits, they are not used long term in treatment. Immunosuppressive medications such as azathioprine, and biological agents such as infliximab and adalimumab are given lastly, only if patients cannot achieve remission with 5-ASA and Corticosteroids, due to their possible risk factors, including, but not limited to increased risk of cancers in teenagers and adults, TB and new or worsening heart failure (these side effects are rare). A formulation of budesonide was approved by the FDA for treatment of active ulcerative colitis in January 2013.^[37]

Aminosalicylates

Sulfasalazine has been a major agent in the therapy of mild to moderate UC for over 50 years. In 1977, Mastan S. Kalsi et al. determined that 5-aminosalicylic acid (5-ASA and mesalazine) was the therapeutically active in sulfasalazine.^{[citation needed]} Since then many 5-ASA compounds have been developed with the aim of maintaining efficacy but reducing the common side effects associated with the sulfapyridine moiety in sulfasalazine.^[38]

Biologics

Biologic treatments such as TNF inhibitors Infliximab (trade name Remicade), adalimumab (trade name Humira) and Golimumab (trade name Simponi) are commonly used to treat patients with Ulcerative Colitis who are no longer responding to corticosteroids. Usually these medications are only used after other options have been exhausted (i.e. patient has received high dose corticosteroids, immunomodulators such as Azathioprine and Mesalazine) but in certain cases, patients may skip these steps and start biologic treatments under doctor orders.

Unlike Aminosalicylates, Biologics can cause harsh side effects such as mild heart failure or worsening of heart failure, skin cancer (excluding melanoma), weakening of the immune system leading to possible fatal infections and Tuberculosis. For this reason patients on these treatments are closely monitored and must be given tests for Hepatitis and Tuberculosis at least once a year. Blood tests must also be taken every 4–8 weeks.

Nicotine

Unlike Crohn's disease, ulcerative colitis has a lesser prevalence in smokers than non-smokers. Patients who choose to use smoking as a treatment should keep a record regarding smoking cessation and the onset or relapse of ulcerative colitis to verify associations.^[39][40] Studies using a transdermal nicotine patch have shown clinical and histological improvement.^[41]

In one double-blind, placebo controlled, study conducted in the United Kingdom 48.6% of patients who used the nicotine patch, in conjunction with their standard treatment, showed complete resolution of symptoms. Another randomized, double-blind, placebo-controlled, single-center clinical trial conducted in the United States showed that 39% of participants showed significant improvement vs. 9% of placebo.^[42] Use of a transdermal nicotine patch without the addition of other standard treatments such as mesalazine has relapse occurrence rates similar to standard treatment without the use of nicotine.

Iron supplementation

The gradual loss of blood from the gastrointestinal tract, as well as chronic inflammation, often leads to anemia, and professional guidelines suggest routinely monitoring for this with blood tests repeated 3 monthly in active disease and annually in quiescent disease.^[43] Adequate disease control usually improves anemia of chronic disease, but iron deficiency anaemia should be treated with iron supplements. The form in which treatment is administered depends both on the severity of the anaemia as well as the guidelines that are followed. Some advise parenteral iron to be used first line as patients respond quicker, is associated with fewer gastrointestinal side effects and is not associated with compliance issues^[44] Others require oral iron to be used as first line, as patients eventually respond and many will tolerate the side effects.^[43][45] All do advise than in severe anaemia (a Hemoglobin less than 10) parenteral iron is administered.

Treatments in development

Inflammation of the colon is a characteristic symptom of ulcerative colitis and a new series of drugs in development look to disrupt the inflammation process by selectively targeting an ion channel. A crucial step involved in the inflammation signaling cascade involves an intermediate conductance calcium activated potassium channel (IK channel) known as KCa3.1;^[46] a protein coded for in the human gene KCNN4.^[47] Ongoing research seeks to prevent T-cell activation and inflammation by inhibiting the KCa3.1 channel, selectively.^[48] Since there is an upregulation of IK channel activity during T cell activation,^[46] inhibition of the KCa3.1 is able to disrupt the production of Th1 cytokines IL-2 and TNF-∝. Production of these cytokines decreases because inhibition of KCa3.1 reduces the efflux of K+ which in turn diminishes the influx of Ca2+. By lowering elevated intracellular Ca2+ in patients with ulcerative colitis these novel drug candidates can inhibit the signaling cascade involved in the inflammation process^[48] and help relieve many of the symptoms associated with ulcerative colitis.

Preclinical study results in 2012 indicated that these selective inhibitors decreased colon inflammation in mice and rats cloned with the human KCa3.1 protein as effectively as the standard inflammatory bowel disease treatment of sulfasalazine. However, these novel selective IK channel blockers are significantly more potent and theoretically would be able to taken at a much more manageable dosage.^[48]

Benzothiazinone, NS6180, is a novel class KCa3.1 channel inhibitor in development.Through a number of in vitro experiments, NS6180 was qualified for KCa3.1 channel inhibition. In vivo experiment of DNBS (2,4 - dinitrobenzene sulfonic acid) induced rat colitis, a frequently used animal model for inflammatory bowel disease, showed comparable efficacy and greater potency than sulfasalazine.^[48]

Surgery

Management

[ v t e ]	Crohn's disease	Ulcerative colitis
Mesalazine	Less useful[49]	More useful[49]
Antibiotics	Effective in long-term[50]	Generally not useful[51]
Surgery	Often returns following removal of affected part	Usually cured by removal of colon

Unlike Crohn's disease, the gastrointestinal aspect ulcerative colitis can generally be cured by surgical removal of the large intestine, also known as a colectomy. This procedure is necessary in the event of: exsanguinating hemorrhage, frank perforation or documented or strongly suspected carcinoma. Surgery is also indicated for patients with severe colitis or toxic megacolon. Patients with symptoms that are disabling and do not respond to drugs may wish to consider whether surgery would improve the quality of life.

Ulcerative colitis (UC) is a disease that affects many parts of the body outside the intestinal tract. In rare cases the extra-intestinal manifestations of the disease may require removal of the colon.^[6]

Another surgical option for ulcerative colitis that is affecting most of the large bowel is called the ileo-anal pouch procedure. This procedure is a two- to three-step procedure in which the large bowel is removed, except for the rectal stump and anus, and a temporary ileostomy is made. The next part of the surgery can be done in one or two steps and is usually done at six to twelve month intervals from each prior surgery.

In the next step of the surgery an internal pouch is made of the patients' own small bowel and this pouch is then hooked back up internally to the rectal stump so that patient can once again have a reasonably functioning bowel system, all internal. The temporary ileostomy can be reversed at this time so that the patient is now internalized for bowel functions, or in another step to the procedure, the pouch and rectal stump anastamosis can be left inside the patient to heal for some time, while the patient still uses the ileostomy for bowel function. Then on a subsequent surgery the ileostomy is reversed and the patient has internalized bowel function again.

Bacterial recolonization

• In a number of randomized clinical trials, probiotics have demonstrated the potential to be helpful in the treatment of ulcerative colitis. Specific types of probiotics such as Escherichia coli Nissle have been shown to induce remission in some patients for up to a year.^[52] Another type of probiotic that is said to have a similar effect is Lactobacillus acidophilus.The probiotics are said to work by calming some of the ongoing inflammation that causes the disease, which in turn allows the body to mobilize dendritic cells, otherwise known as messenger immune cells. These cells then are able to produce other T-cells that further aid in restoring balance in the intestines by rebalancing systematic inflammation.^[53]

• Fecal bacteriotherapy involves the infusion of human probiotics through fecal enemas.^[54] It suggests that the cause of ulcerative colitis may be a previous infection by a still unknown pathogen. This initial infection resolves itself naturally, but somehow causes an imbalance in the colonic bacterial flora, leading to a cycle of inflammation which can be broken by "recolonizing" the colon with bacteria from a healthy bowel. There have been several reported cases of patients who have remained in remission for up to 13 years.^[55] In the United States it can be difficult to find doctors who perform this procedure so some patients have performed the procedure at home using a protocol outlined in a published study.^[56]

Alternative medicine

About 21% of inflammatory bowel disease patients use alternative treatments.^[57] A variety of dietary treatments show promise, but they require further research before they can be recommended.^[58]

In vitro research, animal evidence, and limited human study suggest that melatonin may be beneficial.^[59]

Dietary fiber, meaning indigestible plant matter, has been recommended for decades in the maintenance of bowel function. Of peculiar note is fiber from brassica, which seems to contain soluble constituents capable of reversing ulcers along the entire human digestive tract before it is cooked.^[60] Oatmeal is also commonly prescribed.^{[citation needed]}

• Fish oil, and eicosapentaenoic acid (EPA) derived from fish oil, inhibits leukotriene activity, the latter which may be a key factor of inflammation. As an IBD therapy, there are no conclusive studies in support and no recommended dosage. But dosages of EPA between 180 to 1500 mg/day are recommended for other conditions, most commonly cardiac.^[61]

• Short chain fatty acid (butyrate) enema. The colon utilizes butyrate from the contents of the intestine as an energy source. The amount of butyrate available decreases toward the rectum. Inadequate butyrate levels in the lower intestine have been suggested as a contributing factor for the disease. This might be addressed through butyrate enemas.^[62] The results however are not conclusive.^{[citation needed]}

• Herbal medications are used by patients with ulcerative colitis. Compounds that contain sulfhydryl may have an effect in ulcerative colitis (under a similar hypothesis that the sulfa moiety of sulfasalazine may have activity in addition to the active 5-ASA component).^[63] One randomized control trial evaluated the over-the-counter medication S-methylmethionine and found a significant decreased rate of relapse when the medication was used in conjunction with oral sulfasalazine.^[64]

• Boswellia is an Ayurvedic (Indian traditional medicine) herb, used as a natural alternative to drugs. One study has found its effectiveness similar to sulfasalazine.^[65]

• cannabis is a natural anti-inflammatory and recreational drug, prescribed by many doctors in the United States, in states where Medical Cannabis is legal, and there is much anecdotal evidence to support its use as an effective form of treatment.
• Many people have seen symptoms lessen or disappear after simply moving away from their (typically) western countries (changing lifestyle, diet, etc).

Prognosis

Complications

[ v t e ]		Crohn's disease	Ulcerative colitis
Nutrient deficiency		Higher risk
Colon cancer risk		Slight	Considerable
Prevalence of extraintestinal complications[66]
Iritis/uveitis	Females	2.2%	3.2%
	Males	1.3%	0.9%
Primary sclerosing cholangitis	Females	0.3%	1%
	Males	0.4%	3%
Ankylosing spondylitis	Females	0.7%	0.8%
	Males	2.7%	1.5%
Pyoderma gangrenosum	Females	1.2%	0.8%
	Males	1.3%	0.7%
Erythema nodosum	Females	1.9%	2%
	Males	0.6%	0.7%

Progression or remission

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.

Ulcerative colitis and colorectal cancer

There is a significantly increased risk of colorectal cancer in patients with ulcerative colitis after ten years if involvement is beyond the splenic flexure. Those with only proctitis or rectosigmoiditis usually have no increased risk.^[6] It is recommended that patients have screening colonoscopies with random biopsies to look for dysplasia after eight years of disease activity, at one to two year intervals.^[67]

Primary sclerosing cholangitis

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.^[68]

Mortality

Research has not revealed any difference in overall risk of dying in patients with Ulcerative colitis from that of the background population. The cause-of-death distribution may be different from that of the background population.^[69] It is thought that the disease primarily affects quality of life, and not lifespan.

Other long-term features

Changes that can be seen in chronic ulcerative colitis include granularity, loss of the vascular pattern of the mucosa, loss of haustra, effacement of the ileocecal valve, mucosal bridging, strictures and pseudopolyps.^[70]

Epidemiology

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.^[5]

The geographic distribution of ulcerative colitis and Crohn's disease is similar worldwide,^[71] 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^[72] and the United States.^[73]

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.^[27] Appendectomy prior to age 20 for appendicitis^[74] and current tobacco use^[75] are protective against development of ulcerative colitis (although former tobacco use is associated with a higher risk of developing ulcerative colitis.^[75])

Research

Helminthic therapy using the whipworm Trichuris suis has been shown in a randomized control trial from Iowa to show benefit in patients with ulcerative colitis.^[76] The therapy tests the hygiene hypothesis which argues that the absence of helminths in the colons of patients in the developed world may lead to inflammation. Both helminthic therapy and fecal bacteriotherapy induce a characteristic Th2 white cell response in the diseased areas, which was unexpected given that ulcerative colitis was thought to involve Th2 overproduction.^[77]

Alicaforsen is a first generation antisense oligodeoxynucleotide designed to bind specifically to the human ICAM-1 messenger RNA through Watson-Crick base pair interactions in order to subdue expression of ICAM-1.^[78] ICAM-1 propagates an inflammatory response promoting the extravasation and activation of leukocytes (white blood cells) into inflamed tissue.^[78] Increased expression of ICAM-1 has been observed within the inflamed intestinal mucosa of ulcerative colitis sufferers, where ICAM-1 over production correlated with disease activity.^[79] This suggests that ICAM-1 is a potential therapeutic target in the treatment of ulcerative colitis.^[80]

Notable cases

References

External links

• Ulcerative colitis at MedlinePlus
• Ulcerative colitis on the Open Directory Project
• Torpy, JM; Lynm, C; Golub, RM (2012). "Ulcerative Colitis". JAMA: the Journal of the American Medical Association 307 (1): 104. doi:10.1001/jama.2011.1889. 
• Crohn's and Colitis Foundation of America (CCFA)

v t e Digestive system, Digestive disease, Gastroenterology (primarily K20–K93, 530–579) Upper GI tract Esophagus Esophagitis Candidal Herpetiform Rupture Boerhaave syndrome Mallory-Weiss syndrome UES Zenker's diverticulum LES Barrett's esophagus Esophageal motility disorder Nutcracker esophagus Achalasia Diffuse esophageal spasm Gastroesophageal reflux disease (GERD) Laryngopharyngeal reflux (LPR) Esophageal stricture Megaesophagus Stomach Gastritis Atrophic Ménétrier's disease Gastroenteritis Peptic (gastric) ulcer Cushing ulcer Dieulafoy's lesion Dyspepsia Pyloric stenosis Achlorhydria Gastroparesis Gastroptosis Portal hypertensive gastropathy Gastric antral vascular ectasia Gastric dumping syndrome Gastric volvulus Lower GI tract: Intestinal/ Enteropathy Small intestine (Duodenum/Jejunum/Ileum) Enteritis Duodenitis Jejunitis Ileitis Peptic (duodenal) ulcer Curling's ulcer Malabsorption: Coeliac Tropical sprue Blind loop syndrome Small bowel bacterial overgrowth syndrome Whipple's Short bowel syndrome Steatorrhea Milroy disease bile acid malabsorption Large intestine (Appendix/Colon) Appendicitis Colitis Pseudomembranous Ulcerative Ischemic Microscopic Collagenous Lymphocytic Functional colonic disease IBS Intestinal pseudoobstruction / Ogilvie syndrome Megacolon / Toxic megacolon Diverticulitis/Diverticulosis Large and/or small Enterocolitis Necrotizing IBD Crohn's disease Vascular: Abdominal angina Mesenteric ischemia Angiodysplasia Bowel obstruction: Ileus Intussusception Volvulus Fecal impaction Constipation Diarrhea Infectious Intestinal adhesions Rectum Proctitis Radiation proctitis Proctalgia fugax Rectal prolapse Anismus Anal canal Anal fissure/Anal fistula Anal abscess Anal dysplasia Pruritus ani GI bleeding/BIS Upper Hematemesis Melena Lower Hematochezia Accessory Liver Hepatitis Viral hepatitis Autoimmune hepatitis Alcoholic hepatitis Cirrhosis PBC Fatty liver NASH Vascular Budd-Chiari syndrome Hepatic veno-occlusive disease Portal hypertension Nutmeg liver Alcoholic liver disease Liver failure Hepatic encephalopathy Acute liver failure Liver abscess Pyogenic Amoebic Hepatorenal syndrome Peliosis hepatis Metabolic Disorders Wilson's Disease Hemochromatosis Gallbladder Cholecystitis Gallstones/Cholecystolithiasis Cholesterolosis Rokitansky-Aschoff sinuses Postcholecystectomy syndrome Porcelain gallbladder Bile duct/ Other biliary tree Cholangitis PSC Secondary sclerosing cholangitis Ascending Cholestasis/Mirizzi's syndrome Biliary fistula Haemobilia Gallstones/Cholelithiasis Common bile duct Choledocholithiasis Biliary dyskinesia Sphincter of Oddi dysfunction Pancreatic Pancreatitis Acute Chronic Hereditary Pancreatic abscess Pancreatic pseudocyst Exocrine pancreatic insufficiency Pancreatic fistula Abdominopelvic Hernia Diaphragmatic Congenital Hiatus Inguinal Indirect Direct Umbilical Femoral Obturator Spigelian Lumbar Petit's Grynfeltt-Lesshaft Undefined location Incisional Internal hernia Peritoneal Peritonitis Spontaneous bacterial peritonitis Hemoperitoneum Pneumoperitoneum M: DIG anat (t, g, p)/phys/devp/enzy noco/cong/tumr, sysi/epon proc, drug (A2A/2B/3/4/5/6/7/14/16), blte

v t e Inflammatory bowel disease: Crohn's disease and ulcerative colitis Main Biological therapy for inflammatory bowel disease Management of Crohn's disease Crohn's Disease Activity Index Anatomical terms Abdominal pain Anal abscess Erythema nodosum Fistula Granuloma Ileum Ileitis Malabsorption Proctitis Protein losing enteropathy Pyoderma gangrenosum Sacroiliitis Short bowel syndrome Small bowel obstruction Stenosis History Giovanni Battista Morgagni Burrill Bernard Crohn Organizations Crohn's and Colitis Foundation of America National Society for Colitis and Crohn's Disease The Crohn's and Colitis Foundation of Canada People List of people diagnosed with Crohn's disease List of people diagnosed with ulcerative colitis Deaths from Crohn's disease M: DIG anat (t, g, p)/phys/devp/enzy noco/cong/tumr, sysi/epon proc, drug (A2A/2B/3/4/5/6/7/14/16), blte