Ulcerative colitis
Overview
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
(IBD). Ulcerative colitis is a form of colitis
Colitis
In medicine, colitis refers to an inflammation of the colon and is often used to describe an inflammation of the large intestine .Colitides may be acute and self-limited or chronic, i.e...
, a disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
of the colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
(large intestine
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
), that includes characteristic ulcers
Peptic ulcer
A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
, or open sores. The main symptom of active disease is usually constant diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
mixed with blood, of gradual onset. IBD is often confused with irritable bowel syndrome
Irritable bowel syndrome
Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...
(IBS), a troublesome, but much less serious, condition. Ulcerative colitis has similarities to Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
, another form of IBD.
Discussions
Encyclopedia
Ulcerative colitis 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), a troublesome, but much less serious, condition. 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 occurs in 35–100 people for every 100,000 in the United States, or less than 0.1% of the population. The disease is more prevalent in northern countries of the world, as well as in northern areas of individual countries or other regions. 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, and is considered to be a cure for the disease.
mixed with blood and mucus
, of gradual onset that persists for an extended period (weeks). They also may have weight loss and blood on rectal examination. 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.
. The disease is classified by the extent of involvement, depending on how far up the colon the disease extends:
In addition to the extent of involvement, people may also be characterized by the severity of their disease.
As ulcerative colitis is believed to have a systemic
(i.e., autoimmune) origin, patients may present with comorbidities leading to symptom
s and complications
outside the colon. The frequency of such extraintestinal manifestations has been reported as anywhere between 6 and 47 percent. These include the following:
component to the aetiology of ulcerative colitis can be hypothesized based on the following:
There are 12 regions of the genome
which may be linked to ulcerative colitis. This includes chromosomes 16, 12, 6, 14, 5, 19, 1,and 3 in the order of their discovery. 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. 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 human leukocyte antigen
associations which may be at work. In fact, this linkage on chromosome 6 may be the most convincing and consistent of the genetic candidates.
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.
, a disease in which the immune system
malfunctions, attacking some part of the body. 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. 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.
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.
are the main types of inflammatory bowel disease
, and may mimic each other to great extent, but differ somewhat in etiology and pathophysiology:
has been observed in some patients with ulcerative colitis, resulting in higher concentrations of the toxic gas hydrogen sulfide
. The role of hydrogen sulfide in pathogenesis is unclear. It has been suggested that the protective benefit of smoking that some patients report is due to hydrogen cyanide from cigarette smoke reacting with hydrogen sulfide to produce the nontoxic isothiocyanate. Another unrelated study suggested sulphur contained in red meats and alcohol may lead to an increased risk of relapse for patients in remission.
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The initial diagnostic
workup for ulcerative colitis includes the following:
Although ulcerative colitis is a disease of unknown causation, inquiry should be made as to unusual factors believed to trigger the disease. 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.
_endoscopic_biopsy.jpg)
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:
Ulcerative colitis is usually continuous from the rectum
, with the rectum
almost universally being involved. There is rarely peri-anal 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.
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 abscess
es, 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.
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.
, immunosuppressive medications such as azathioprine
, and biological agents such as infliximab
.
) was the therapeutically active in sulfasalazine. 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.
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.
Studies using a transdermal nicotine patch have shown clinical and histological improvement. 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. 3% of placebo. 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.
, 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.
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 2 to 3 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 1 or 2 steps and is usually done at 6 - 12 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.
. A variety of dietary treatments show promise, but they require further research before they can be recommended.
In vitro research, animal evidence, and limited human study suggest that melatonin
may be beneficial.
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. Oatmeal
is also commonly prescribed.
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.
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. It is recommended that patients have screening colonoscopies with random biopsies to look for dysplasia
after eight years of disease activity.
(PSC), a progressive inflammatory disorder of small and large bile duct
s. As many as 5% of patients with ulcerative colitis may progress to develop primary sclerosing cholangitis.
is unclear, but it is thought that the disease primarily affects quality of life
, and not lifespan.
, effacement of the ileocecal valve
, mucosal bridging, stricture
s and pseudopolyps.
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.
The geographic distribution of ulcerative colitis and Crohn's disease
is similar worldwide, 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
.
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. Appendectomy prior to age 20 for appendicitis and tobacco use are protective against development of ulcerative colitis.
using the whipworm
Trichuris suis has been shown in a randomized control trial from Iowa to show benefit in patients with ulcerative colitis. 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 is somewhat paradoxical given that ulcerative colitis immunology was thought to classically involve Th2 overproduction.
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
(IBD). Ulcerative colitis is a form of colitis
Colitis
In medicine, colitis refers to an inflammation of the colon and is often used to describe an inflammation of the large intestine .Colitides may be acute and self-limited or chronic, i.e...
, a disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
of the colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
(large intestine
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
), that includes characteristic ulcers
Peptic ulcer
A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
, or open sores. The main symptom of active disease is usually constant diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
mixed with blood, of gradual onset. IBD is often confused with irritable bowel syndrome
Irritable bowel syndrome
Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...
(IBS), a troublesome, but much less serious, condition. Ulcerative colitis has similarities to Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
, 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 occurs in 35–100 people for every 100,000 in the United States, or less than 0.1% of the population. The disease is more prevalent in northern countries of the world, as well as in northern areas of individual countries or other regions. Although ulcerative colitis has no known cause, there is a presumed genetic
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
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
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
. Treatment is with anti-inflammatory drugs, immunosuppression
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
, and biological therapy
Biological therapy for inflammatory bowel disease
Biological therapy refers to the use of medication that is tailored to specifically target an immune or genetic mediator of disease. Even for diseases of unknown cause, molecules that are involved in the disease process have been identified, and can be targeted for biological therapy; many of...
targeting specific components of the immune response. Colectomy
Colectomy
Colectomy consists of the surgical resection of any extent of the large intestine .-History:Sir William Arbuthnot-Lane was one of the early proponents of the usefulness of total colectomies, although his overuse of the procedure called the wisdom of the surgery into question.-Indications:Some of...
(partial or total removal of the large bowel through surgery) is occasionally necessary, and is considered to be a cure for the disease.
Gastrointestinal
The clinical presentation of ulcerative colitis depends on the extent of the disease process. Patients usually present with diarrheaDiarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
mixed with blood and mucus
Mucus
In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...
, of gradual onset that persists for an extended period (weeks). They also may have weight loss and blood on rectal examination. 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 colonColon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
. 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:
- ProctitisProctitisProctitis is an inflammation of the anus and the lining of the rectum, affecting only the last 6 inches of the rectum.-Overview:Symptoms are ineffectual straining to empty the bowels, diarrhea, rectal bleeding and possible discharge, a feeling of not having adequately emptied the bowels,...
: Involvement limited to the rectumRectumThe rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...
. - 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.
- Proctitis
- 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
- Mild disease correlates with fewer than four stools daily, with or without blood, no systemicSystemic diseaseLife-threatening disease redirects here.A systemic disease is one that affects a number of organs and tissues, or affects the body as a whole. Although most medical conditions will eventually involve multiple organs in advanced stage Life-threatening disease redirects here.A systemic disease is one...
signs of toxicity, and a normal erythrocyte sedimentation rateErythrocyte sedimentation rateThe erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
(ESR). There may be mild abdominal pain or cramping. Patients may believe they are constipatedConstipationConstipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
when in fact they are experiencing tenesmusTenesmusRectal tenesmus is a feeling of incomplete defecation. It is experienced as an inability or difficulty to empty the bowel at defecation...
, 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 feverFeverFever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, 38 to 39 °C (100.4 to 102.2 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, tachycardiaTachycardiaTachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
, anemia or an elevated ESR. - 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 megacolonToxic megacolonToxic megacolon is an acute form of colonic distension. It is characterized by a very dilated colon , accompanied by abdominal distension , and sometimes fever, abdominal pain, or shock....
. If the serous membraneSerous membraneIn anatomy, serous membrane is a smooth membrane consisting of a thin layer of cells which secrete serous fluid. Serous membranes line and enclose several body cavities, known as serous cavities, where they secrete a lubricating fluid which reduces friction from muscle movement...
is involved, colonic perforation may ensue. Unless treated, fulminant disease will soon lead to death.
Extraintestinal features
Systemic disease
Life-threatening disease redirects here.A systemic disease is one that affects a number of organs and tissues, or affects the body as a whole. Although most medical conditions will eventually involve multiple organs in advanced stage Life-threatening disease redirects here.A systemic disease is one...
(i.e., autoimmune) origin, patients may present with comorbidities leading to symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s and complications
Complication (medicine)
Complication, in medicine, is an unfavorable evolution of a disease, a health condition or a medical treatment. The disease can become worse in its severity or show a higher number of signs, symptoms or new pathological changes, become widespread throughout the body or affect other organ systems. A...
outside the colon. The frequency of such extraintestinal manifestations has been reported as anywhere between 6 and 47 percent. These include the following:
- aphthous ulcersMouth ulcerA mouth or oral ulcer is an open sore in the mouth, or rarely a break in the mucous membrane or the epithelium on the lips or surrounding the mouth. The types of mouth ulcers are diverse, with a multitude of associated causes including: physical abrasion, acidic fruit, infection, other medical...
of the mouth - Ophthalmic (involving the eyes):
- IritisIritisIritis is a form of anterior uveitis and refers to the inflammation of the iris of the eye.-Types:There are two main types of iritis: acute and chronic. They differ in numerous ways....
or uveitisUveitisUveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
, which is inflammation of the iris - Episcleritis
- Iritis
- Musculoskeletal:
- Seronegative arthritisSeronegative arthritisA seronegative arthritis is an arthritis that is distinguished from rheumatoid arthritis due the absence of rheumatoid factor .-Contrasting with rheumatoid arthritis:...
, which can be a large-joint oligoarthritisArthritisArthritis is a form of joint disorder that involves inflammation of one or more joints....
(affecting one or two joints), or may affect many small joints of the hands and feet - Ankylosing spondylitisAnkylosing spondylitisAnkylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...
, arthritis of the spine - SacroiliitisSacroiliitisIn medicine, sacroiliitis is an inflammation of the sacroiliac joint. Sacroiliitis is a feature of spondylarthropathies .-External links:*...
, arthritis of the lower spine
- Seronegative arthritis
- Cutaneous (related to the skin):
- Erythema nodosumErythema nodosumErythema nodosum is an inflammation of the fat cells under the skin characterized by tender red nodules or lumps that are usually seen on both shins...
, which is a panniculitisPanniculitisPanniculitis is a group of diseases whose hallmark is inflammation of subcutaneous adipose tissue...
, or inflammation of subcutaneous tissue involving the lower extremities - Pyoderma gangrenosumPyoderma gangrenosumPyoderma gangrenosum is a disease that causes tissue to become necrotic, causing deep ulcers that usually occur on the legs. When they occur, they can lead to chronic wounds. Ulcers usually initially look like small bug bites or papules, and they progress to larger ulcers. Though the wounds...
, which is a painful ulcerating lesion involving the skinSkin-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
- Erythema nodosum
- Deep venous thrombosis and pulmonary embolismPulmonary embolismPulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
- Autoimmune hemolytic anemiaAutoimmune hemolytic anemiaAutoimmune hemolytic anemia occurs when antibodies directed against the person's own red blood cells cause the RBCs to burst , leading to insufficient plasma concentration. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases...
- clubbing, a deformity of the ends of the fingers.
- Primary sclerosing cholangitisPrimary sclerosing cholangitisPrimary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis, liver failure and liver cancer...
, a distinct disease that causes inflammation of the bile ducts
Causes
There are no direct causes for ulcerative colitis, but there are many possible factors such as genetics and stress.Genetic factors
A geneticGenetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
component to the aetiology of ulcerative colitis can be hypothesized based on the following:
- Aggregation of ulcerative colitis in families.
- Identical twin concordance rate of 10% and dizygotic twin concordance rate of 3%
- Ethnic differences in incidence
- Genetic markerGenetic markerA genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify cells, individuals or species. It can be described as a variation that can be observed...
s and linkagesGenetic linkageGenetic linkage is the tendency of certain loci or alleles to be inherited together. Genetic loci that are physically close to one another on the same chromosome tend to stay together during meiosis, and are thus genetically linked.-Background:...
There are 12 regions of the genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
which may be linked to ulcerative colitis. This includes chromosomes 16, 12, 6, 14, 5, 19, 1,and 3 in the order of their discovery. However, none of these loci
Locus (genetics)
In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...
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. 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 human leukocyte antigen
Human leukocyte antigen
The human leukocyte antigen system is the name of the major histocompatibility complex in humans. The super locus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and...
associations which may be at work. In fact, this linkage on chromosome 6 may be the most convincing and consistent of the genetic candidates.
Multiple autoimmune disorders have been recorded with the neurovisceral and cutaneous genetic porphyrias including ulcerative colitis, Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
, celiac disease, dermatitis herpetiformis
Dermatitis herpetiformis
Dermatitis herpetiformis , or Duhring's disease,Freedberg, et al. . Fitzpatrick's Dermatology in General Medicine. . McGraw-Hill. ISBN 0-07-138076-0. is a chronic blistering skin condition, characterised by blisters filled with a watery fluid...
, diabetes, systemic and discoid lupus
Lupus erythematosus
Lupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
, rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
, ankylosing spondylitis
Ankylosing spondylitis
Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...
, scleroderma
Scleroderma
Systemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...
, Sjogren's disease and scleritis
Scleritis
Scleritis is a serious inflammatory disease that affects the white outer coating of the eye, known as the sclera. The disease is often contracted through association with other diseases of the body, such as Wegener's granulomatosis or rheumatoid arthritis; it can also be attained through disorders...
. 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:- DietDiet (nutrition)In nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...
: as the colonColon (anatomy)The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
is exposed to many dietary substances which may encourage inflammationInflammationInflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
, dietary factors have been hypothesized to play a role in the pathogenesisPathogenesisThe pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
of both ulcerative colitis and Crohn's diseaseCrohn's diseaseCrohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
. There have been few studies to investigate such an association, but one study showed no associationAssociation (statistics)In statistics, an association is any relationship between two measured quantities that renders them statistically dependent. The term "association" refers broadly to any such relationship, whereas the narrower term "correlation" refers to a linear relationship between two quantities.There are many...
of refined sugarSugarSugar is a class of edible crystalline carbohydrates, mainly sucrose, lactose, and fructose, characterized by a sweet flavor.Sucrose in its refined form primarily comes from sugar cane and sugar beet...
on the prevalence of ulcerative colitis. - BreastfeedingBreastfeedingBreastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...
: 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. - Several scientific studies have posted that Accutane is a possible trigger of Crohn's DiseaseCrohn's diseaseCrohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
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.
Autoimmune disease
Some sources list ulcerative colitis as an autoimmune diseaseAutoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
, a disease in which the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
malfunctions, attacking some part of the body. 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
Ileum
The ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...
. This so-called "backwash ileitis" can occur in 10–20% of patients with pancolitis
Pancolitis
Pancolitis is a form of Ulcerative Colitis that is very severe. Pan refers to the fact that the disease is spread throughout the large intestine. This is from the Cecum to the Rectum of the individual. Symptoms are very similar to those of any Ulcerative Colitis patient except more severe in...
and is believed to be of little clinical significance. Ulcerative colitis can also be associated with comorbidities
Comorbidity
In medicine, comorbidity is either the presence of one or more disorders in addition to a primary disease or disorder, or the effect of such additional disorders or diseases.- In medicine :...
that produce symptoms in many areas of the body outside the digestive system. Surgical removal of the large intestine often cures the disease.
Alternative theories
Levels of sulfate-reducing bacteriaSulfate-reducing bacteria
Sulfate-reducing bacteria are those bacteria and archaea that can obtain energy by oxidizing organic compounds or molecular hydrogen while reducing sulfate to hydrogen sulfide...
tend to be higher in persons with ulcerative colitis. This could mean that there are higher levels of hydrogen sulfide
Hydrogen sulfide
Hydrogen sulfide is the chemical compound with the formula . It is a colorless, very poisonous, flammable gas with the characteristic foul odor of expired eggs perceptible at concentrations as low as 0.00047 parts per million...
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.
Comparison to Crohn's disease
Ulcerative colitis and Crohn's diseaseCrohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
are the main types of inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
, and may mimic each other to great extent, but differ somewhat in etiology and pathophysiology:
Pathophysiology
An increased amount of colonic sulfate-reducing bacteriaSulfate-reducing bacteria
Sulfate-reducing bacteria are those bacteria and archaea that can obtain energy by oxidizing organic compounds or molecular hydrogen while reducing sulfate to hydrogen sulfide...
has been observed in some patients with ulcerative colitis, resulting in higher concentrations of the toxic gas hydrogen sulfide
Hydrogen sulfide
Hydrogen sulfide is the chemical compound with the formula . It is a colorless, very poisonous, flammable gas with the characteristic foul odor of expired eggs perceptible at concentrations as low as 0.00047 parts per million...
. The role of hydrogen sulfide in pathogenesis is unclear. It has been suggested that the protective benefit of smoking that some patients report is due to hydrogen cyanide from cigarette smoke reacting with hydrogen sulfide to produce the nontoxic isothiocyanate. Another unrelated study suggested sulphur contained in red meats and alcohol may lead to an increased risk of relapse for patients in remission.
Diagnosis
Medical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
workup for ulcerative colitis includes the following:
- A complete blood countComplete blood countA complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
is done to check for anemia; thrombocytosisThrombocytosisThrombocytosis is the presence of high platelet counts in the blood, and can be either primary or reactive...
, a high plateletPlateletPlatelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
count, is occasionally seen - ElectrolyteElectrolyteIn chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
studies and renal function testsRenal functionRenal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
are done, as chronic diarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
may be associated with hypokalemiaHypokalemiaHypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
, hypomagnesemiaHypomagnesemiaHypomagnesemia is an electrolyte disturbance in which there is an abnormally low level of magnesium in the blood. Usually a serum level less than 0.7 mmol/L is used as reference. The prefix hypo- means low . The middle 'magnes' refers to magnesium...
and pre-renal failure. - Liver function testsLiver function testsLiver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...
are performed to screen for bile duct involvement: primary sclerosing cholangitisPrimary sclerosing cholangitisPrimary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis, liver failure and liver cancer...
. - X-rayX-rayX-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
- UrinalysisUrinalysisA urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
- Stool culture, to rule out parasites and infectious causes.
- Erythrocyte sedimentation rateErythrocyte sedimentation rateThe erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
can be measured, with an elevated sedimentation rate indicating that an inflammatory process is present. - C-reactive proteinC-reactive proteinC-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
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. Factors may include: recent cessation of tobacco smoking; recent administration of large doses of iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
or vitamin B6
Vitamin B6
Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...
; hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
in enemas or other procedures.
Endoscopic
Endoscopy
Endoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...
. 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
- ErythemaErythemaErythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...
(or redness of the mucosa) and friabilityFriabilityFriability is the ability of a solid substance to be reduced to smaller pieces with little effort. The opposite of friable is indurated....
of the mucosa - Superficial ulceration, which may be confluent, and
- PseudopolypsPolyp (medicine)A polyp is an abnormal growth of tissue projecting from a mucous membrane. If it is attached to the surface by a narrow elongated stalk, it is said to be pedunculated. If no stalk is present, it is said to be sessile. Polyps are commonly found in the colon, stomach, nose, sinus, urinary bladder...
.
Ulcerative colitis is usually continuous from the rectum
Rectum
The rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...
, with the rectum
Rectum
The rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...
almost universally being involved. There is rarely peri-anal disease, but cases have been reported. The degree of involvement endoscopically ranges from proctitis
Proctitis
Proctitis is an inflammation of the anus and the lining of the rectum, affecting only the last 6 inches of the rectum.-Overview:Symptoms are ineffectual straining to empty the bowels, diarrhea, rectal bleeding and possible discharge, a feeling of not having adequately emptied the bowels,...
or inflammation of the rectum, to left sided colitis, to pancolitis
Colitis
In medicine, colitis refers to an inflammation of the colon and is often used to describe an inflammation of the large intestine .Colitides may be acute and self-limited or chronic, i.e...
, which is inflammation involving the ascending colon.
Histologic
BiopsiesBiopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
of the mucosa are taken to definitively diagnose
Medical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
UC and differentiate it from Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
, which is managed differently clinically. Microbiological samples are typically taken at the time of endoscopy. The pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
in ulcerative colitis typically involves distortion of crypt architecture, inflammation of crypts (cryptitis), frank crypt abscess
Abscess
An abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials...
es, and hemorrhage or inflammatory cells in the lamina propria
Lamina propria
The lamina propria is a constituent of the moist linings known as mucous membranes or mucosa, which line various tubes in the body ....
. 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 diseaseCrohn's diseaseCrohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
- InfectiousInfectious diseaseInfectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...
colitis, which is typically detected on stool cultures- Pseudomembranous colitisPseudomembranous colitisPseudomembranous colitis, a cause of antibiotic-associated diarrhea , is an infection of the colon. It is often, but not always, caused by the bacterium Clostridium difficile. Because of this, the informal name C. difficile colitis is also commonly used. The illness is characterized by...
, or Clostridium difficileClostridium difficileClostridium difficile , also known as "CDF/cdf", or "C...
-associated colitis, bacterial upsets often seen following administration of antibiotics
- Pseudomembranous colitis
- Ischemic colitisIschemic colitisIschemic colitis is a medical condition in which inflammation and injury of the large intestine result from inadequate blood supply. Although uncommon in the general population, ischemic colitis occurs with greater frequency in the elderly, and is the most common form of bowel ischemia...
, inadequate blood supply to the intestine, which typically affects the elderly - Radiation colitis in patients with previous pelvic radiotherapy
- Chemical colitisChemical colitisChemical colitis is a type of colitis, an inflammation of the large intestine or colon, caused by the introduction of harsh chemicals to the colon by an enema or other procedure. Chemical colitis can resemble ulcerative colitis, infectious colitis and pseudomembranous colitis endoscopically.Prior...
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
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
, as both are inflammatory bowel diseases that can affect the colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
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.
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 aminosalicylates such as sulfasalazine, corticosteroids such as prednisonePrednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
, immunosuppressive medications such as azathioprine
Azathioprine
Azathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
, and biological agents such as infliximab
Infliximab
Infliximab is a monoclonal antibody against tumour necrosis factor alpha . It is used to treat autoimmune diseases. Remicade is marketed by Janssen Biotech, Inc...
.
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 mesalazineMesalazine
Mesalazine , also known as Mesalamine or 5-aminosalicylic acid , is an anti-inflammatory drug used to treat inflammation of the digestive tract ulcerative colitis and mild-to-moderate Crohn's disease...
) was the therapeutically active in sulfasalazine. 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.
Nicotine
Unlike Crohn's disease, ulcerative colitis has a lesser prevalencePrevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
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.
Studies using a transdermal nicotine patch have shown clinical and histological improvement. In one double-blind, placebo controlled, study conducted in the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
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
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
showed that 39% of participants showed significant improvement vs. 3% of placebo. Use of a transdermal nicotine patch without the addition of other standard treatments such as mesalazine
Mesalazine
Mesalazine , also known as Mesalamine or 5-aminosalicylic acid , is an anti-inflammatory drug used to treat inflammation of the digestive tract ulcerative colitis and mild-to-moderate Crohn's disease...
has relapse occurrence rates similar to standard treatment without the use of nicotine.
Surgery
Unlike Crohn's disease, ulcerative colitis can generally be cured by surgical removal of the large intestineIleostomy
An ileostomy is a surgical opening constructed by bringing the end or loop of small intestine out onto the surface of the skin. Intestinal waste passes out of the ileostomy and is collected in an external pouching system stuck to the skin...
, also known as a colectomy. This procedure is necessary in the event of: exsanguinating
Exsanguination
Exsanguination is the fatal process of hypovolemia , to a degree sufficient enough to cause death. One does not have to lose literally all of one's blood to cause death...
hemorrhage
Internal bleeding
Internal bleeding is bleeding occurring inside the body. It can be a serious medical emergency depending on where it occurs , and can potentially cause death and cardiac arrest if proper medical treatment is not received quickly....
, frank perforation or documented or strongly suspected carcinoma
Carcinoma
Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...
. Surgery is also indicated for patients with severe colitis or toxic megacolon
Toxic megacolon
Toxic megacolon is an acute form of colonic distension. It is characterized by a very dilated colon , accompanied by abdominal distension , and sometimes fever, abdominal pain, or shock....
. 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.
Another surgical option for Ulcerative Colitis that is affecting most of the large bowel, is called the ileo-anal pouch
Ileo-anal pouch
The ileal pouch-anal anastomosis , also known as an ileo-anal pouch, restorative proctocolectomy, ileal-anal pullthrough, or sometimes referred to as a j-pouch, s-pouch, w-pouch or an internal pouch, is an internal reservoir; usually situated where the rectum would normally be...
procedure. This procedure is a 2 to 3 step procedure in which the large bowel is removed, except for the rectal stump and anus
Anus
The anus is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, unwanted semi-solid matter produced during digestion, which, depending on the type of animal, may be one or more of: matter which the animal cannot digest,...
, and a temporary ileostomy
Ileostomy
An ileostomy is a surgical opening constructed by bringing the end or loop of small intestine out onto the surface of the skin. Intestinal waste passes out of the ileostomy and is collected in an external pouching system stuck to the skin...
is made. The next part of the surgery can be done in 1 or 2 steps and is usually done at 6 - 12 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
Ileostomy
An ileostomy is a surgical opening constructed by bringing the end or loop of small intestine out onto the surface of the skin. Intestinal waste passes out of the ileostomy and is collected in an external pouching system stuck to the skin...
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
Ileostomy
An ileostomy is a surgical opening constructed by bringing the end or loop of small intestine out onto the surface of the skin. Intestinal waste passes out of the ileostomy and is collected in an external pouching system stuck to the skin...
for bowel function. Then on a subsequent surgery the ileostomy
Ileostomy
An ileostomy is a surgical opening constructed by bringing the end or loop of small intestine out onto the surface of the skin. Intestinal waste passes out of the ileostomy and is collected in an external pouching system stuck to the skin...
is reversed and the patient has internalized bowel function again.
Bacterial recolonization
- Probiotics may have benefit. One study which looked at a probiotic known as VSL#3 has shown promise for people with ulcerative colitis.
- Fecal bacteriotherapyFecal bacteriotherapyFecal bacteriotherapy, also known as fecal transfusion, fecal transplant, stool transplant, or human probiotic infusion , is a medical treatment for patients with pseudomembranous colitis , or ulcerative colitis that involves restoration of colon homeostasis by reintroducing normal bacterial flora...
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. 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. 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.
Alternative medicine
About 21% of inflammatory bowel disease patients use alternative treatmentsAlternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....
. A variety of dietary treatments show promise, but they require further research before they can be recommended.
In vitro research, animal evidence, and limited human study suggest that melatonin
Melatonin
Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
may be beneficial.
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. Oatmeal
OATS
OATS - Open Source Assistive Technology Software - is a source code repository or "forge" for assistive technology software. It was launched in 2006 with the goal to provide a one-stop “shop” for end users, clinicians and open-source developers to promote and develop open source assistive...
is also commonly prescribed.
- Fish oil. Eicosapentaenoic acidEicosapentaenoic acidEicosapentaenoic acid is an omega-3 fatty acid. In physiological literature, it is given the name 20:5. It also has the trivial name timnodonic acid...
(EPA), derived from fish oil. This is an EicosanoidEicosanoidIn biochemistry, eicosanoids are signaling molecules made by oxidation of twenty-carbon essential fatty acids, ....
that inhibits leukotrieneLeukotrieneLeukotrienes are fatty signaling molecules. They were first found in leukocytes . One of their roles is to trigger contractions in the smooth muscles lining the trachea; their overproduction is a major cause of inflammation in asthma and allergic rhinitis...
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. - Short chain fatty acid (butyrate) enema. The colon utilizes butyrateButyrateButyrate is the traditional name for the conjugate base of butanoic acid . The formula of the butanoate ion is C4H7O2-. The archaic name is used as part of the name of butyrates or butanoates, or esters and salts of butyric acid, a short chain fatty acid...
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. The results however are not conclusive. - HerbalHerbalAThe use of a or an depends on whether or not herbal is pronounced with a silent h. herbal is "a collection of descriptions of plants put together for medicinal purposes." Expressed more elaborately — it is a book containing the names and descriptions of plants, usually with information on their...
medications are used by patients with ulcerative colitis. Compounds that contain sulphydryl may have an effect in ulcerative colitis (under a similar hypothesis that the sulpha moiety of sulfasalazine may have activity in addition to the active 5-ASA component). One randomized control trial evaluated the over-the-counter medication methionine-methyl sulphonium chloride (abbreviated MMSC, but more commonly referred to as Vitamin U) and found a significant decreased rate of relapse when the medication was used in conjunction with oral sulfasalazine. - BoswelliaBoswelliaBoswellia is a genus of trees known for their fragrant resin which has many pharmacological uses particularly as anti-inflammatories. The Biblical incense frankincense was probably an extract from the resin of the tree, Boswellia sacra....
is an Ayurvedic (Indian traditional medicine) herb, used as a natural alternative to drugs. One study has found its effectiveness similar to sulfasalazine.
Progression or remission
Patients with ulcerative colitis usually have an intermittent course, with periods of disease inactivity alternating with "flares" of disease. Patients with proctitisProctitis
Proctitis is an inflammation of the anus and the lining of the rectum, affecting only the last 6 inches of the rectum.-Overview:Symptoms are ineffectual straining to empty the bowels, diarrhea, rectal bleeding and possible discharge, a feeling of not having adequately emptied the bowels,...
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 cancerColorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
in patients with ulcerative colitis after 10 years if involvement is beyond the splenic flexure
Splenic flexure
The splenic flexure is a sharp bend between the transverse and the descending colon in the left upper quadrant of humans. The left colic flexure is near the spleen, and hence called the splenic flexure. There are two colic flexures in the transverse colon — the other being the hepatic...
. Those with only proctitis
Proctitis
Proctitis is an inflammation of the anus and the lining of the rectum, affecting only the last 6 inches of the rectum.-Overview:Symptoms are ineffectual straining to empty the bowels, diarrhea, rectal bleeding and possible discharge, a feeling of not having adequately emptied the bowels,...
or rectosigmoiditis usually have no increased risk. It is recommended that patients have screening colonoscopies with random biopsies to look for dysplasia
Dysplasia
Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process...
after eight years of disease activity.
Primary sclerosing cholangitis
Ulcerative colitis has a significant association with primary sclerosing cholangitisPrimary sclerosing cholangitis
Primary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis, liver failure and liver cancer...
(PSC), a progressive inflammatory disorder of small and large bile duct
Bile duct
A bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine.The...
s. As many as 5% of patients with ulcerative colitis may progress to develop primary sclerosing cholangitis.
Mortality
The effect of ulcerative colitis on mortalityDeath
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
is unclear, but it is thought that the disease primarily affects quality of life
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...
, 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 haustraHaustra
The haustra of the colon are the small pouches caused by sacculation, which give the colon its segmented appearance. The taenia coli runs the length of the large intestine...
, effacement of the ileocecal valve
Ileocecal valve
The ileocecal valve, or ileocaecal valve, is of a bilabial papilla structure with physiological sphincter muscle situated at the junction of the small intestine and the large intestine, with recent evidence indicating an anatomical sphincter may also be present in humans) Its critical function is...
, mucosal bridging, stricture
Stricture
Stricture may refer to:* esophageal stricture, in medicine* stenosis, in medicine* a feature of the Perl programming language* tenet, in religion* degree of contact, in a consonant...
s and pseudopolyps.
Epidemiology
The incidenceIncidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
of ulcerative colitis in North America
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
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
Bimodal distribution
In statistics, a bimodal distribution is a continuous probability distribution with two different modes. These appear as distinct peaks in the probability density function, as shown in Figure 1....
in age of onset
Onset
Onset may refer to:*Onset , the beginning of a musical note or sound*Interonset interval, a term in music*Syllable onset, a term in phonetics and phonology*Onset, Massachusetts, village in the United States...
, with a second peak in incidence occurring in the 6th decade of life. The disease affects females more than males.
The geographic distribution of ulcerative colitis and Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
is similar worldwide, with highest incidences in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
, the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
, and Scandinavia
Scandinavia
Scandinavia is a cultural, historical and ethno-linguistic region in northern Europe that includes the three kingdoms of Denmark, Norway and Sweden, characterized by their common ethno-cultural heritage and language. Modern Norway and Sweden proper are situated on the Scandinavian Peninsula,...
. Higher incidences are seen in northern locations compared to southern locations in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
and the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
.
As with Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
, the prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
of ulcerative colitis is greater among Ashkenazi Jews and decreases progressively in other persons of Jewish descent, non-Jewish Caucasians, Africans, Hispanics, and Asians. Appendectomy prior to age 20 for appendicitis and tobacco use are protective against development of ulcerative colitis.
Research
Helminthic therapyHelminthic therapy
Helminthic therapy, a type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the ova of a helminth. Helminths are parasitic worms such as hookworms and whipworms....
using the whipworm
Whipworm
The human tapworm is a roundworm, which causes trichuriasis when it infects a human large intestine. The name whipworm refers to the shape of the worm; they look like whips with wider "handles" at the posterior end.-Life cycle:The female T. trichiura produces 2,000–10,000 single celled eggs per day...
Trichuris suis has been shown in a randomized control trial from Iowa to show benefit in patients with ulcerative colitis. The therapy tests the hygiene hypothesis
Hygiene hypothesis
In medicine, the Hygiene Hypothesis states that a lack of early childhood exposure to infectious agents, symbiotic microorganisms , and parasites increases susceptibility to allergic diseases by suppressing natural development of the immune system...
which argues that the absence of helminths in the colons
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
of patients in the developed world may lead to inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. Both helminthic therapy
Helminthic therapy
Helminthic therapy, a type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the ova of a helminth. Helminths are parasitic worms such as hookworms and whipworms....
and fecal bacteriotherapy
Fecal bacteriotherapy
Fecal bacteriotherapy, also known as fecal transfusion, fecal transplant, stool transplant, or human probiotic infusion , is a medical treatment for patients with pseudomembranous colitis , or ulcerative colitis that involves restoration of colon homeostasis by reintroducing normal bacterial flora...
induce a characteristic Th2 white cell response in the diseased areas, which is somewhat paradoxical given that ulcerative colitis immunology was thought to classically involve Th2 overproduction.