Ulcerative Colitis
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Ulcerative colitis (UC) is a long-term condition that results in
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
and
ulcer An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
s of the colon and
rectum The rectum is the final straight portion of the large intestine in humans and some other mammals, and the Gastrointestinal tract, gut in others. The adult human rectum is about long, and begins at the rectosigmoid junction (the end of the s ...
. The primary symptoms of active disease are
abdominal pain Abdominal pain, also known as a stomach ache, is a symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than ...
and
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
mixed with
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
(
hematochezia Haematochezia is the passage of fresh blood through the anus path, usually in or with stools (contrast with melena). The term is from Greek αἷμα ("blood") and χέζειν ("to defaecate"). Hematochezia is commonly associated with lower gastro ...
).
Weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...
,
fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
, and
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
may also occur. Often, symptoms come on slowly and can range from mild to severe. Symptoms typically occur intermittently with periods of no symptoms between flares. Complications may include abnormal dilation of the colon (
megacolon Megacolon is an abnormal dilation of the colon (also called the large intestine). This leads to hypertrophy of the colon. The dilation is often accompanied by a paralysis of the peristaltic movements of the bowel. In more extreme cases, the feces ...
), inflammation of the eye, joints, or liver, and
colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...
. The cause of UC is unknown. Theories involve immune system dysfunction,
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
, changes in the normal gut bacteria, and environmental factors. Rates tend to be higher in the developed world with some proposing this to be the result of less exposure to intestinal infections, or to a
Western diet The Western pattern diet is a modern dietary pattern that is generally characterized by high intakes of pre-packaged foods, refined grains, red meat, processed meat, high-sugar drinks, candy and sweets, fried foods, conventionally-raised anim ...
and lifestyle. The removal of the appendix at an early age may be protective. Diagnosis is typically by colonoscopy with tissue biopsies. It is a type of inflammatory bowel disease (IBD) along with Crohn's disease and
microscopic colitis Microscopic colitis refers to two related medical conditions which cause diarrhea: collagenous colitis and lymphocytic colitis. Both conditions are characterized by the presence of chronic non-bloody watery diarrhea, normal appearances on colonos ...
. Dietary changes, such as maintaining a high-calorie diet or lactose-free diet, may improve symptoms. Several medications are used to treat symptoms and bring about and maintain remission, including aminosalicylates such as
mesalazine Mesalazine, also known as mesalamine or 5-aminosalicylic acid (5-ASA), is a medication used to treat inflammatory bowel disease, including ulcerative colitis and Crohn's disease. It is generally used for mildly to moderately severe disease. I ...
or
sulfasalazine Sulfasalazine, sold under the brand name Azulfidine among others, is a medication used to treat rheumatoid arthritis, ulcerative colitis, and Crohn's disease. It is considered by some to be a first-line treatment in rheumatoid arthritis. It is ...
, steroids,
immunosuppressants Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified int ...
such as
azathioprine Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, ...
, and
biologic therapy A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, t ...
. Removal of the colon by surgery may be necessary if the disease is severe, does not respond to treatment, or if complications such as colon cancer develop. Removal of the colon and rectum generally cures the condition. Together with Crohn's disease, about 11.2 million people were affected . Each year it newly occurs in 1 to 20 per 100,000 people, and 5 to 500 per 100,000 individuals are affected. The disease is more common in North America and Europe than other regions. Often it begins in people aged 15 to 30 years, or among those over 60. Males and females appear to be affected in equal proportions. It has also become more common since the 1950s. Together, ulcerative colitis and Crohn's disease affect about a million people in the United States. With appropriate treatment the risk of death appears the same as that of the general population. The first description of ulcerative colitis occurred around the 1850s.


Signs and symptoms


Gastrointestinal

People with ulcerative colitis usually present with
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
mixed with
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
, of gradual onset that persists for an extended period of time (weeks). Additional symptoms may include fecal incontinence, increased frequency of bowel movements, mucus discharge, and nocturnal defecations. With proctitis (inflammation of the rectum), people with UC may experience urgency or
rectal tenesmus Rectal tenesmus is a feeling of incomplete defecation. It is the sensation of inability or difficulty to empty the bowel at defecation, even if the bowel contents have already been evacuated. Tenesmus indicates the feeling of a residue, and is not ...
, which is the urgent desire to evacuate the bowels but with the passage of little stool. Tenesmus may be misinterpreted as
constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
, due to the urge to defecate despite small volume of stool passage. Bloody diarrhea and abdominal pain may be more prominent features in severe disease. The severity of abdominal pain with UC varies from mild discomfort to very painful bowel movements and abdominal cramping. High frequency of bowel movements, weight loss, nausea, fatigue, and fever are also common during disease flares. Chronic bleeding from the GI tract, chronic inflammation, and iron deficiency often leads to
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
, which can affect quality of life. The clinical presentation of ulcerative colitis depends on the extent of the disease process. Up to 15% of individuals may have severe disease upon initial onset of symptoms. A substantial proportion (up to 45%) of people with a history of UC without any ongoing symptoms (clinical remission) have objective evidence of ongoing inflammation. Ulcerative colitis is associated with a generalized inflammatory process that can affect many parts of the body. Sometimes, these associated extra-intestinal symptoms are the initial signs of the disease.


Extent of involvement

In contrast to Crohn's disease, which can affect areas of the gastrointestinal tract outside of the colon, ulcerative colitis is usually confined to the colon. Inflammation in ulcerative colitis is usually continuous, typically involving the rectum, with involvement extending proximally (to sigmoid colon, ascending colon, etc.). In contrast, inflammation with Crohn's disease is often patchy, with so-called "skip lesions" (intermittent regions of inflamed bowel). The disease is classified by the extent of involvement, depending on how far the disease extends: proctitis (rectal inflammation), left sided colitis (inflammation extending to descending colon), and extensive colitis (inflammation proximal to the descending colon). Proctosigmoiditis describes inflammation of the rectum and sigmoid colon. Pancolitis describes involvement of the entire colon, extending from the rectum to the cecum. While usually associated with Crohn's disease,
ileitis Ileitis is an inflammation of the ileum, a portion of the small intestine. Crohn's ileitis is a type of Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. ...
(inflammation of the ileum) also occurs in UC. About 17% of individuals with UC have ileitis. Ileitis more commonly occurs in the setting of pancolitis (occurring in 20% of cases of pancolitis), and tends to correlate with the activity of colitis. This so-called "backwash ileitis" can occur in 10–20% of people with
pancolitis Pancolitis, in its most general sense, refers to inflammation of the entire colon. This can be caused by a variety of things. Pancolitis or universal colitis is frequently used in a more specific fashion to denote a very severe form of ulcerativ ...
and is believed to be of little clinical significance.Fauci ''et al.'' ''Harrison's Internal Medicine'', 17th ed. New York: McGraw-Hill Medical, 2008.


Severity of disease

In addition to the extent of involvement, UC is also characterized by severity of disease. Severity of disease is defined by symptoms, objective markers of inflammation (endoscopic findings, blood tests), disease course, and the impact of the disease on day-to-day life. Most patients are categorized through endoscopy and fecal calprotectin levels. Indicators of low risk for future complications in mild and moderate UC include the following parameters: exhibiting less than 6 stools daily and lack of fever/weight loss. Other indicators include lack of extraintestinal symptoms, none to little elevation in CRP, ESR, and calprotectin, and later age of diagnosis (over 40 years). Mild disease correlates with fewer than four stools daily; in addition, mild urgency and rectal bleeding may occur intermittently. Mild disease lacks systemic signs of toxicity (eg. fever, chills, weight changes) and exhibits normal levels of serum inflammatory markers (
erythrocyte sedimentation rate The erythrocyte sedimentation rate (ESR or sed rate) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of ...
and
C-reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin- ...
). Moderate to severe disease correlates with more than six stools daily, frequent bloody stools and urgency. Moderate abdominal pain, low-grade
fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
, , and anemia may develop (75% of normal). Toxicity is present, as demonstrated by fever,
tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
, anemia or an elevated ESR or CRP. Fulminant disease correlates with more than 10 bowel movements daily, continuous bleeding, toxicity, abdominal tenderness and distension, blood transfusion requirement, and colonic dilation (expansion). People with fulminant UC may have inflammation extending beyond just the mucosal layer, causing impaired colonic motility and leading to
toxic megacolon Toxic megacolon is an acute form of colonic distension. It is characterized by a very dilated colon (megacolon), accompanied by abdominal distension (bloating), and sometimes fever, abdominal pain, or shock. Toxic megacolon is usually a complica ...
. Toxic megacolon is defined by diameter of colon (>6 cm) or cecum (>9 cm) and represents a medical emergency, one often treated surgically. If the
serous membrane The serous membrane (or serosa) is a smooth tissue membrane of mesothelium lining the contents and inner walls of body cavities, which secrete serous fluid to allow lubricated sliding movements between opposing surfaces. The serous membrane ...
is involved, a colonic perforation may ensue, which has a 50% mortality rate in patients afflicted with UC. Ulcerative colitis may improve and enter remission. Remission of disease is characterized by formed stools, the absence of bloody diarrhea, resolution of urgency, and normal levels of serum inflammatory markers.


Extraintestinal manifestations and complications

UC is characterized by immune dysregulation and systemic inflammation, which may result in
symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...
s and complications outside the colon. Commonly affected organs include: eyes, joints, skin, and liver. The frequency of such extraintestinal manifestations has been reported as between 6 and 47%. UC may affect the mouth. About 8% of individuals with UC develop oral manifestations. The two most common oral manifestations are
aphthous stomatitis Aphthous stomatitis, or recurrent aphthous stomatitis (RAS), is a common condition characterized by the repeated formation of benign and non-contagious mouth ulcers (aphthae) in otherwise healthy individuals. The informal term ''canker sore'' i ...
and
angular cheilitis Angular cheilitis (AC) is inflammation of one or both corners of the mouth. Often the corners are red with skin breakdown and crusting. It can also be itchy or painful. The condition can last for days to years. Angular cheilitis is a type of ch ...
. Aphthous stomatitis is characterized by ulcers in the mouth, which are benign, noncontagious and often recurrent. Angular chelitis is characterized by redness at the corners of the mouth, which may include painful sores or breaks in the skin. Very rarely, benign pustules may occur in the mouth (pyostomatitis vegetans). UC may affect the eyes manifesting in scleritis, iritis, and conjunctivitis. Patients may be asymptomatic or experience redness, burning, or itching in eyes (CITE CMDP). Inflammation may occur in the interior portion of the eye, leading to
uveitis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and in ...
and
iritis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...
. Uveitis can cause blurred vision and eye pain, especially when exposed to light (
photophobia Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of ...
). Untreated, uveitis can lead to permanent vision loss. Inflammation may also involve the white part of the eye (
sclera The sclera, also known as the white of the eye or, in older literature, as the tunica albuginea oculi, is the opaque, fibrous, protective, outer layer of the human eye containing mainly collagen and some crucial elastic fiber. In humans, and som ...
) or the overlying connective tissue (
episclera The episclera is the outermost layer of the sclera (the white of the eye).Cassin, B. and Solomon, S. ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing Company, 1990. It is composed of loose, fibrous, elastic tissue and atta ...
), causing conditions called
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 granulomatosis with polyangiitis or ...
and
episcleritis Episcleritis is a benign, self-limiting inflammatory disease affecting part of the eye called the episclera. The episclera is a thin layer of tissue that lies between the conjunctiva and the connective tissue layer that forms the white of the e ...
. Ulcerative colitis is most commonly associated with uveitis and episcleritis. UC may cause several joint manifestations, including a type of rheumatologic disease known as
seronegative arthritis Spondyloarthropathy or spondyloarthrosis refers to any joint disease of the vertebral column. As such, it is a class or category of diseases rather than a single, specific entity. It differs from spondylopathy, which is a disease of the vertebra ...
, which may affect few large joints (oligoarthritis), the
vertebra The spinal column, a defining synapomorphy shared by nearly all vertebrates,Hagfish are believed to have secondarily lost their spinal column is a moderately flexible series of vertebrae (singular vertebra), each constituting a characteristic ...
(
ankylosing spondylitis Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine typically where the spine joins the pelvis. Occasionally areas affected may include other joints such as the shoulders or hip ...
) or several small joints of the hands and feet (peripheral arthritis). Often the insertion site where muscle attaches to bone ( entheses) becomes inflamed ( enthesitis). Inflammation may affect the
sacroiliac joint The sacroiliac joint or SI joint (SIJ) is the joint between the sacrum and the ilium bones of the pelvis, which are connected by strong ligaments. In humans, the sacrum supports the spine and is supported in turn by an ilium on each side. Th ...
(
sacroiliitis Sacroiliitis is inflammation within the sacroiliac joint. It is a feature of spondyloarthropathies, such as axial spondyloarthritis (including ankylosing spondylitis), psoriatic arthritis, reactive arthritis or arthritis related to inflammatory b ...
). It is estimated that round 50% of IBD patients suffer from migratory arthritis. Synovitis, or inflammation of the synovial fluid surrounding a joint, can occur for months and recur in later times but usually does not erode the joint. The symptoms of arthritis include
joint pain Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication. According to MeSH, ...
, swelling, and
effusion In physics and chemistry, effusion is the process in which a gas escapes from a container through a hole of diameter considerably smaller than the mean free path of the molecules. Such a hole is often described as a ''pinhole'' and the escape ...
, and often leads to significant morbidity. The severity of joint symptoms often does not correspond with severity of IBD. Ulcerative colitis may affect the skin. The most common type of skin manifestation,
erythema nodosum Erythema nodosum (EN) is an inflammatory condition characterized by inflammation of the fat cells under the skin, resulting in tender red nodules or lumps that are usually seen on both shins. It can be caused by a variety of conditions, and typi ...
, presents in up to 3% of UC patients and almost 8% in patients afflicted with Crohn's disease. It develops as raised, tender red nodules usually appearing on the outer areas of the arms or legs, especially in the anterior tibial area (shins). The nodules have diameters that measure approximately 1–5 cm. Erythema nodosum is due to inflammation of the underlying subcutaneous tissue (
panniculitis Panniculitis is a group of diseases whose hallmark is inflammation of subcutaneous adipose tissue (the fatty layer under the skin – panniculus adiposus). Symptoms include tender skin nodules, and systemic signs such as weight loss and fatigu ...
), and biopsy will display focal panniculitis (although is often unnecessary in diagnosis). In contrast to joint-related manifestations, erythema nodosum often occurs alongside intestinal disease. Thus, treatment of UC can often lead to resolution of skin nodules. A lesser common skin complication associated with UC, pyoderma gangrenosum, is typically more severe. One study discovered this skin manifestation in only 0.75% pf patients. Pyoderma gangrenosum is characterized by painful lesions or nodules that become
ulcer An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
s which progressively grow. It often starts as many small raised red spots (papules) or pus-filled lesions (pustules) that are usually detected on lower extremities. The inner layer of the skin, or dermis, slowly undergoes necrosis (process of dying) causing the ulcerations that are typical of pyoderma gangrenosum. The ulcers are often filled with sterile pus-like material, so biopsy often displays an abscess that is sterile. Whereas erythema nodosum tends to correlate with the activity of the ulcerative colitis and often improves with treatment of the colonic inflammation, pyoderma gangrenosum may occur independently of UC disease activity. In some cases, pyoderma gangrenosum may require injection with corticosteroids. Treatment may also involve inhibitors of tumor necrosis factor (TNF), a cytokine that promotes cell survival. Other associations determined between the skin and ulcerative colitis include a skin condition known as hidradenitis suppurativa (HS). This condition represents a chronic process in which follicles become occluded leading to recurring inflammation of nodules and abscesses and even tunnels in the skin that drain fluid. Ulcerative colitis may affect the blood and endocrine system. UC increases the risk of blood clots in both arteries and veins; painful swelling of the lower legs can be a sign of
deep venous thrombosis Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enla ...
, while difficulty breathing may be a result of
pulmonary embolism Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain p ...
(blood clots in the lungs). The risk of blood clots is about threefold higher in individuals with IBD. The risk of venous thromboembolism is high in ulcerative colitis due to hypercoagulability from inflammation, especially with active or extensive disease. Additional risk factors may include surgery, hospitalization, pregnancy, the use of corticosteroids and tofacitinib, a JAK inhibitor. The immune system may also attack
red blood cells Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''k ...
, leading to
autoimmune hemolytic anemia Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of ...
. In addition to autoimmune destruction, anemia may occur due to chronic blood loss from rectal bleeding and bone marrow suppression due to inflammation (
anemia of chronic disease Anemia of chronic disease (ACD) or anemia of chronic inflammation is a form of anemia seen in chronic infection, chronic immune activation, and malignancy. These conditions all produce elevation of interleukin-6, which stimulates hepcidin product ...
). Anemic patients can present asymptomatically. However, 75% of individuals exhibit symptoms such as shortness of breath, fatigue, and tachycardia (racing heart). About 1/3rd of patients show signs of jaundice (yellowing of the skin) or darkened urine from loss of bilirubin in urine. A smaller percentage may present with chest pain or a concurrent immune cytopenia, most commonly immune thrombocytopenia (ITP) (CITE WAHA).
Osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
may occur related to systemic inflammation, which increases the risk of bone fractures. Clubbing, a deformity of the ends of the fingers, may occur. Amyloidosis may occur, especially with severe and poorly controlled disease, which usually presents with protein in the urine (
proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...
) and
nephritic syndrome Nephritic syndrome is a syndrome comprising signs of nephritis, which is kidney disease involving inflammation. It often occurs in the glomerulus, where it is called glomerulonephritis. Glomerulonephritis is characterized by inflammation and t ...
.


Primary sclerosing cholangitis

Ulcerative colitis has a significant association with
primary sclerosing cholangitis Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts, which normally allow bile to drain from the gallbladder. Affected individuals may ha ...
(PSC), a progressive inflammatory disorder of small and large
bile duct A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. It ...
s. Up to 70-90% of people with primary sclerosing cholangitis have ulcerative colitis. As many as 5% of people with ulcerative colitis may progress to develop primary sclerosing cholangitis. PSC is more common in men, and often begins between 30 and 40 years of age. It can present asymptomatically or exhibit symptoms of itchiness (pruritis) and fatigue. Other symptoms include systemic signs such as fever and night sweats. Such symptoms are often associated with a bacterial episodic version of PSC. Upon physical exam, one may discern enlarged liver contours (hepatomegaly) or enlarged spleen (splenomegaly) as well as areas of excoriation. Yellow coloring of the skin, or jaundice, may also be present due to excess of bile byproduct buildup (bilirubin) from the biliary tract. In diagnosis, lab results often reveal a pattern indicative of biliary disease (cholestatic pattern). This is often displayed by markedly elevated alkaline phosphatase levels and milder or no elevation in liver enzyme levels. Xray results often show bile ducts with thicker walls, areas of dilation or narrowing. In some cases, primary sclerosing cholangitis occurs several years before the bowel symptoms of ulcerative colitis develop. PSC does not parallel the onset, extent, duration, or activity of the colonic inflammation in ulcerative colitis. In addition, colectomy does not have an impact on the course of primary sclerosing cholangitis in individuals with UC. PSC is associated with an increased risk of colorectal cancer and cholangiocarcinoma (bile duct cancer). PSC is a progressive condition, and may result in cirrhosis of the liver. No specific therapy has been proven to affect the long term course of PSC. Other liver-related manifestations of UC include fatty liver disease and autoimmune liver disease.


Causes

Ulcerative colitis is an
autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
characterized by
T-cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
infiltrating the colon. No direct causes for UC are known, but factors such as genetics, environment, and an overactive immune system play a role. UC is associated with comorbidities that produce symptoms in many areas of the body outside the digestive system.


Genetic factors

A genetic component to the cause of UC can be hypothesized based on aggregation of UC in families, variation of prevalence between different ethnicities,
genetic marker A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify individuals or species. It can be described as a variation (which may arise due to mutation or alteration in the genomic loci) that can be ...
s and linkages. In addition, the identical
twin Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of TwinLast Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two em ...
concordance Concordance may refer to: * Agreement (linguistics), a form of cross-reference between different parts of a sentence or phrase * Bible concordance, an alphabetical listing of terms in the Bible * Concordant coastline, in geology, where beds, or la ...
rate is 10%, whereas the
dizygotic twin Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of TwinLast Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two em ...
concordance rate is only 3%. Between 8 and 14% of people with ulcerative colitis have a family history of inflammatory bowel disease. In addition, people with a first degree relative with UC have a four-fold increase in their risk of developing the disease. Twelve regions of the
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
may be linked to UC, including, in the order of their discovery, chromosomes 16, 12, 6, 14, 5, 19, 1, and 3, but none of these loci has been consistently shown to be at fault, suggesting that the disorder is influenced by 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 SLC22A5 is a membrane transport protein associated with primary carnitine deficiency. This protein is involved in the active cellular uptake of carnitine. It acts a symporter, moving sodium ions and other organic cations across the membrane alon ...
. Other potential regions involve cell scaffolding proteins such as the MAGUK family.
Human leukocyte antigen The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for the regulation of the immune system. The HLA system is also known as the human version of th ...
associations may even be at work. In fact, this linkage on chromosome 6 may be the most convincing and consistent of the genetic candidates. Multiple autoimmune disorders are associated with ulcerative colitis, including
celiac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...
,
psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...
,
lupus erythematosus Lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blo ...
,
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
,
episcleritis Episcleritis is a benign, self-limiting inflammatory disease affecting part of the eye called the episclera. The episclera is a thin layer of tissue that lies between the conjunctiva and the connective tissue layer that forms the white of the e ...
, and
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 granulomatosis with polyangiitis or ...
. Ulcerative colitis is also associated with
acute intermittent porphyria Acute intermittent porphyria (AIP) is a rare metabolic disorder affecting the production of heme resulting from a deficiency of the enzyme porphobilinogen deaminase. It is the most common of the acute porphyrias. Signs and symptoms The clinical ...
.


Environmental factors

Many hypotheses have been raised for environmental factors contributing to the pathogenesis of ulcerative colitis, including
diet Diet may refer to: Food * Diet (nutrition), the sum of the food consumed by an organism or group * Dieting, the deliberate selection of food to control body weight or nutrient intake ** Diet food, foods that aid in creating a diet for weight loss ...
,
breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
and medications. Breastfeeding may have a protective effect in the development of ulcerative colitis. One study of
isotretinoin Isotretinoin, also known as 13-''cis''-retinoic acid and sold under the brand name Accutane among others, is a medication primarily used to treat severe acne. It is also used to prevent certain skin cancers ( squamous-cell carcinoma), and in t ...
found a small increase in the rate of UC. As the colon is exposed to many dietary substances which may encourage
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
, dietary factors have been hypothesized to play a role in the
pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
of both ulcerative colitis and Crohn's disease. However, current research does not show a link between diet and the development of ulcerative colitis. Few studies have investigated such an association; one study showed no
association Association may refer to: *Club (organization), an association of two or more people united by a common interest or goal *Trade association, an organization founded and funded by businesses that operate in a specific industry *Voluntary associatio ...
of refined
sugar Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or double ...
on the number of people affected of ulcerative colitis. High intake of
unsaturated fat An unsaturated fat is a fat or fatty acid in which there is at least one double bond within the fatty acid chain. A fatty acid chain is monounsaturated if it contains one double bond, and polyunsaturated if it contains more than one double bond. ...
and
vitamin B6 Vitamin B6 is one of the B vitamins, and thus an essential nutrient. The term refers to a group of six chemically similar compounds, i.e., " vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosp ...
may enhance the risk of developing ulcerative colitis. Other identified dietary factors that may influence the development and/or relapse of the disease include meat protein and alcoholic beverages. Specifically, sulfur has been investigated as being involved in the cause of ulcerative colitis, but this is controversial. Sulfur restricted diets have been investigated in people 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. As a result of a class-action lawsuit and community settlement with
DuPont DuPont de Nemours, Inc., commonly shortened to DuPont, is an American multinational chemical company first formed in 1802 by French-American chemist and industrialist Éleuthère Irénée du Pont de Nemours. The company played a major role in ...
, three
epidemiologists Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population. It is a cornerstone of public health, and shapes policy decisions and eviden ...
conducted studies on the population surrounding a chemical plant that was exposed to PFOA at levels greater than in the general population. The studies concluded that there was an association between
PFOA Perfluorooctanoic acid (PFOA; conjugate base perfluorooctanoate; also known colloquially as C8, for its 8 carbon chain structure) is a perfluorinated carboxylic acid produced and used worldwide as an industrial surfactant in chemical processes a ...
exposure and six health outcomes, one of which being ulcerative colitis.


Alternative theories

Levels of
sulfate-reducing bacteria Sulfate-reducing microorganisms (SRM) or sulfate-reducing prokaryotes (SRP) are a group composed of sulfate-reducing bacteria (SRB) and sulfate-reducing archaea (SRA), both of which can perform anaerobic respiration utilizing sulfate () as termina ...
tend to be higher in persons with ulcerative colitis, which could indicate higher levels of
hydrogen sulfide Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The unde ...
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. Infection by
mycobacterium avium ''Mycobacterium avium ''complex is a group of mycobacteria comprising ''Mycobacterium intracellulare'' and ''Mycobacterium avium'' that are commonly grouped because they infect humans together; this group, in turn, is part of the group of nontu ...
, subspecies
paratuberculosis Paratuberculosis is a contagious, chronic and sometimes fatal infection that primarily affects the small intestine of ruminants. It is caused by the bacterium ''Mycobacterium avium'' subspecies ''paratuberculosis''. Infections normally affect ru ...
, has been proposed as the ultimate cause of both ulcerative colitis and Crohn's disease.


Pathophysiology

An increased amount of colonic sulfate-reducing bacteria has been observed in some people 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 (see
intestinal mucosal barrier The intestinal mucosal barrier, also referred to as intestinal barrier, refers to the property of the intestinal mucosa that ensures adequate containment of undesirable luminal contents within the intestine while preserving the ability to absorb n ...
). N-butyrate, a short-chain fatty acid, gets oxidized through the
beta oxidation In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cyc ...
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 Hydrogen cyanide, sometimes called prussic acid, is a chemical compound with the formula HCN and structure . It is a colorless, extremely poisonous, and flammable liquid that boils slightly above room temperature, at . HCN is produced on an ...
from cigarette smoke reacting with hydrogen sulfide to produce the non-toxic isothiocyanate, thereby inhibiting sulfides from interrupting the pathway. An unrelated study suggested that the sulfur contained in red meats and alcohol may lead to an increased risk of relapse for people in remission.


Diagnosis

The initial
diagnostic Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engine ...
workup for ulcerative colitis consists of a complete history and physical examination, assessment of signs and symptoms, laboratory tests and endoscopy. Severe UC can exhibit high erythrocyte sedimentation rate (ESR), decreased albumin (a protein produced by the liver), and various changes in electrolytes. As discussed previously, UC patients often also display elevated alkaline phosphatase. Inflammation in the intestine may also cause higher levels of fecal calprotectin or lactoferrin. Specific testing may include the following: * A
complete blood count A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cell ...
is done to check for anemia;
thrombocytosis Thrombocythemia is a condition of high platelet (thrombocyte) count in the blood. Normal count is in the range of 150x109 to 450x109 platelets per liter of blood, but investigation is typically only considered if the upper limit exceeds 750x109/L. ...
, a high
platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
count, is occasionally seen *
Electrolyte An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon dis ...
studies and
kidney function tests Assessment of kidney function occurs in different ways, using the presence of symptoms and medical sign, signs, as well as measurements using urine tests, blood tests, and medical imaging. Renal physiology, Functions of a healthy kidney include ...
are done, as chronic diarrhea may be associated with
hypokalemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...
,
hypomagnesemia Magnesium deficiency is an electrolyte disturbance in which there is a low level of magnesium in the body. It can result in multiple symptoms. Symptoms include tremor, poor coordination, muscle spasms, loss of appetite, personality changes, an ...
and kidney injury. *
Liver function tests Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...
are performed to screen for bile duct involvement:
primary sclerosing cholangitis Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts, which normally allow bile to drain from the gallbladder. Affected individuals may ha ...
. * Imaging such as
x-ray An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10  picometers to 10  nanometers, corresponding to frequencies in the range 30&nb ...
or CT scan to evaluate for possible perforation or
toxic megacolon Toxic megacolon is an acute form of colonic distension. It is characterized by a very dilated colon (megacolon), accompanied by abdominal distension (bloating), and sometimes fever, abdominal pain, or shock. Toxic megacolon is usually a complica ...
*
Stool culture A stool test is a medical diagnostic technique that involves the collection and analysis of fecal matter. Microbial analysis (culturing), microscopy and chemical tests are among the tests performed on stool samples. Collection Stool samples shoul ...
and
Clostridioides difficile ''Clostridioides difficile'' ( syn. ''Clostridium difficile'') is a bacterium that is well known for causing serious diarrheal infections, and may also cause colon cancer. Also known as ''C. difficile'', or ''C. diff'' (), is Gram-positive spe ...
stool assay to rule out infectious colitis *
Inflammatory markers Acute-phase proteins (APPs) are a class of proteins whose concentrations in blood plasma either increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the ''acute-p ...
, such as erythrocyte sedimentation rate or
C-reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin- ...
* Lower endoscopy to evaluate the rectum and distal large intestine (
sigmoidoscopy Sigmoidoscopy (from the Greek term for letter " s/ς" + "eidos" + "scopy": namely, to look inside an "s"/"ς"-like object) is the minimally invasive medical examination of the large intestine from the rectum through to the nearest part of the co ...
) or entire colon and end of the
small intestine The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the p ...
(colonoscopy) for ulcers and inflammation
Although ulcerative colitis is a disease of unknown causation, inquiry should be made as to unusual factors believed to trigger the disease. The simple clinical colitis activity index was created in 1998 and is used to assess the severity of symptoms.


Endoscopic

The best test for diagnosis of ulcerative colitis remains
endoscopy An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are insert ...
, which is examination of the internal surface of the bowel using a flexible camera. Initially, a flexible sigmoidoscopy may be completed to establish the diagnosis. The physician may elect to limit the extent of the initial exam if severe colitis is encountered to minimize the risk of
perforation A perforation is a small hole in a thin material or web. There is usually more than one perforation in an organized fashion, where all of the holes collectively are called a ''perforation''. The process of creating perforations is called perfor ...
of the colon. However, a complete colonoscopy with entry into the terminal ileum should be performed to rule out Crohn's disease, and assess extent and severity of disease. Endoscopic findings in ulcerative colitis include:
erythema Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not asso ...
(redness of the
mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...
),
friability Friability ( ), the condition of being friable, describes the tendency of a solid substance to break into smaller pieces under duress or contact, especially by rubbing. The opposite of friable is indurate. Substances that are designated hazardous, ...
of the mucosa, superficial ulceration, and loss of the vascular appearance of the colon. When present, ulcerations may be confluent. Pseudopolyps may be observed. Ulcerative colitis is usually continuous from the rectum, with the rectum almost universally being involved. Perianal disease is rare. The degree of involvement endoscopically ranges from proctitis (rectal inflammation) to left sided colitis (extending to descending colon), to extensive colitis (extending proximal to descending colon).


Histologic

Biopsies A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
of the mucosa are taken during endoscopy to confirm the diagnosis of UC and differentiate it from Crohn's disease, which is managed differently clinically. Histologic findings in ulcerative colitis includes: distortion of
crypt A crypt (from Latin ''crypta'' "vault") is a stone chamber beneath the floor of a church or other building. It typically contains coffins, sarcophagi, or religious relics. Originally, crypts were typically found below the main apse of a chur ...
architecture, crypt abscesses, and inflammatory cells in the mucosa (lymphocytes, plasma cells, and granulocytes). Unlike the transmural inflammation seen in Crohn's disease, the inflammation of ulcerative colitis is limited to the mucosa.


Laboratory tests

Blood and stool tests serve primarily to assess disease severity, level of inflammation and rule out causes of infectious colitis. All individuals with suspected ulcerative colitis should have stool testing to rule out infection. A
complete blood count A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cell ...
may demonstrate anemia, leukocytosis, or thrombocytosis. Anemia may be caused by inflammation or bleeding. Chronic blood loss may lead to iron deficiency as a cause for anemia, particularly microcytic anemia (small red blood cells), which can be evaluated with a serum
ferritin Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. It is the primary ' ...
,
iron Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in f ...
,
total iron-binding capacity Total iron-binding capacity (TIBC) or sometimes transferrin iron-binding capacity is a medical laboratory test that measures the blood's capacity to bind iron with transferrin. Transferrin can bind two atoms of ferric iron (Fe3+) with high affinit ...
and
transferrin saturation Transferrin saturation (TS), measured as a percentage, is a medical laboratory value. It is the value of serum iron divided by the total iron-binding capacity of the available transferrin, the main protein that binds iron in the blood, this value ...
. Anemia may be due to a complication of treatment from azathioprine, which can cause low blood counts, or sulfasalazine, which can result in folate deficiency. Thiopurine metabolites (from azathioprine) and a folate level can help. UC may cause high levels of inflammation throughout the body, which may be quantified with serum inflammatory markers, such as CRP and ESR. However, elevated inflammatory markers are not specific for UC and elevations are commonly seen in other conditions, including infection. In addition, inflammatory markers are not uniformly elevated in people with ulcerative colitis. Twenty five percent of individuals with confirmed inflammation on endoscopic evaluation have a normal CRP level.
Serum albumin Serum albumin, often referred to simply as blood albumin, is an albumin (a type of globular protein) found in vertebrate blood. Human serum albumin is encoded by the ''ALB'' gene. Other mammalian forms, such as bovine serum albumin, are chemical ...
may also be low related to inflammation, in addition to loss of protein in the GI tract associated with bleeding and colitis. Low serum levels of vitamin D are associated with UC, although the significance of this finding is unclear. Specific antibody markers may be elevated in ulcerative colitis. Specifically, perinuclear antineutrophil cytoplasmic antibodies (pANCA) are found in 70 percent of cases of UC. Antibodies against
Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
may be present, but are more often positive in Crohn's disease compared with ulcerative colitis. However, due to poor accuracy of these serolologic tests, they are not helpful in the diagnostic evaluation of possible inflammatory bowel disease. Several stool tests may help quantify the extent of inflammation present in the colon and rectum.
Fecal calprotectin Faecal calprotectin (American and British English spelling differences#ae and oe, or fecal calprotectin) is a stool test, biochemical measurement of the protein calprotectin in the human feces, stool. Elevated faecal calprotectin indicates the mig ...
is elevated in inflammatory conditions affecting the colon, and is useful in distinguishing irritable bowel syndrome (noninflammatory) from a flare in inflammatory bowel disease. Fecal calprotectin is 88% sensitive and 79% specific for the diagnosis of ulcerative colitis. If the fecal calprotectin is low, the likelihood of inflammatory bowel disease are less than 1 percent.
Lactoferrin Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, s ...
is an additional nonspecific marker of intestinal inflammation.


Imaging

Overall, imaging tests, such as
x-ray An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10  picometers to 10  nanometers, corresponding to frequencies in the range 30&nb ...
or CT scan, may be helpful in assessing for complications of ulcerative colitis, such as perforation or toxic megacolon. Bowel ultrasound (US) is a cost-effective, well-tolerated, non-invasive and readily available tool for the management of patients with inflammatory bowel disease (IBD), including UC, in clinical practice. Some recent studies demonstrated that US is an accurate tool for assessing disease activity in patients with UC. Imaging is otherwise of limited use in diagnosing ulcerative colitis. Magnetic resonance imaging (MRI) is necessary to diagnose underlying PSC. Abdominal xray is often the test of choice and may display nonspecific findings in cases of mild or moderate ulcerative colitis. In circumstances of severe UC, radiographic findings may include thickening of the mucosa, often termed "thumbprinting," which indicates swelling due to fluid displacement (edema). Other findings may include colonic dilation and stool buildup evidencing constipation. Similar to xray, in mild ulcerative colitis, double contrast barium enema often shows nonspecific findings. Conversely, barium enema may display small buildups of barium in microulcerations. Severe UC can be characterized by various polyps, colonic shortening, loss of haustrae (the small bulging pouches in the colon),and narrowing of the colon. It is important to note that barium enema should not be conducted in patients exhibiting very severe symptoms as this may slow or stop stool passage through the colon causing ileus and toxic megacolon. Other methods of imaging include computed tomography (CT) and magnetic resonance imaging (MRI). Both may depict colonic wall thickening but have decreased ability to find early signs of wall changes when compared to barium enema. In cases of severe ulcerative colitis, however, they often exhibit equivalent ability to detect colonic changes. Doppler ultrasound is the last means of imaging that may be used. Similar to the imaging methods mentioned earlier, this may show some thickened bowel wall layers. In severe cases, this may show thickening in all bowel wall layers (transmural thickness).


Differential diagnosis

Several conditions may present in a similar manner as ulcerative colitis, and should be excluded. Such conditions include: Crohn's disease, infectious colitis,
nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
enteropathy, and
irritable bowel syndrome Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may ...
. Alternative causes of colitis should be considered, such as ischemic colitis (inadequate blood flow to the colon), radiation colitis (if prior exposure to
radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
), or chemical colitis.
Pseudomembranous colitis Colitis is swelling or inflammation of the large intestine ( colon). Colitis may be acute and self-limited or long-term. It broadly fits into the category of digestive diseases. In a medical context, the label ''colitis'' (without qualificatio ...
may occur due to Clostridioides difficile infection following administration of antibiotics.
Entamoeba histolytica ''Entamoeba histolytica'' is an anaerobic parasitic amoebozoan, part of the genus ''Entamoeba''. Predominantly infecting humans and other primates causing amoebiasis, ''E. histolytica'' is estimated to infect about 35-50 million people worldwid ...
is a protozoan parasite that causes intestinal inflammation. A few cases have been misdiagnosed as UC with poor outcomes occurring due to the use of corticosteroids. 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 their courses and treatments may differ. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as indeterminate colitis. Crohn's disease can be distinguished from ulcerative colitis in several ways. Characteristics that indicate Crohn's include evidence of disease around the anus (perianal disease). This includes anal fissures and abscesses as well as fistulas, which are abnormal connections between various bodily structures. Infectious colitis is another condition that may present in similar manner to ulcerative colitis. Endoscopic findings are also oftentimes similar. One can discern whether a patient has infectious colitis by employing tissue cultures and stool studies. Biopsy of the colon is another beneficial test but is more invasive. Other forms of colitis that may present similarly include radiation and diversion colitis. Radiation colitis occurs after irradiation and often affects the rectum or sigmoid colon, similar to ulcerative colitis. Upon histology radiation colitis may indicate eosinophilic infiltrates, abnormal epithelial cells, or fibrosis. Diversion colitis, on the other hand, occurs after portions of bowel loops have been removed. Histology in this condition often shows increased growth of lymphoid tissue. In patients who have undergone transplantation, graft versus host disease may also be a differential diagnosis. This response to transplantation often causes prolonged diarrhea if the colon is affected. Typical symptoms also include rash. Involvement of the upper gastrointestinal tract may lead to difficulty swallowing or ulceration. Upon histology, graft versus host disease may present with crypt cell necrosis and breakdown products within the crypts themselves.


Management

Standard treatment for ulcerative colitis depends on the 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. 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 remission, which involves relief of symptoms and mucosal healing of the colon's lining, and then longer-term treatment to maintain remission and prevent complications. Acute severe ulcerative colitis requires hospitalisation, exclusion of infections, and corticosteroids. For acute stages of the disease, a low fiber diet may be recommended.


Medication

Ulcerative colitis can be treated with a number of medications, including 5-ASA drugs such as
sulfasalazine Sulfasalazine, sold under the brand name Azulfidine among others, is a medication used to treat rheumatoid arthritis, ulcerative colitis, and Crohn's disease. It is considered by some to be a first-line treatment in rheumatoid arthritis. It is ...
and
mesalazine Mesalazine, also known as mesalamine or 5-aminosalicylic acid (5-ASA), is a medication used to treat inflammatory bowel disease, including ulcerative colitis and Crohn's disease. It is generally used for mildly to moderately severe disease. I ...
. Corticosteroids such as
prednisone Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and ad ...
can also be used due to their immunosuppressive and short-term healing properties, but because their risks outweigh their benefits, they are not used long-term in treatment. Immunosuppressive medications such as
azathioprine Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, ...
and biological agents such as
infliximab Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spon ...
and
adalimumab Adalimumab, sold under the brand name Humira, among others, is a monoclonal antibody used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurati ...
are given only if people cannot achieve remission with 5-ASA and corticosteroids. Infliximab,
ustekinumab Ustekinumab, sold under the brand name Stelara is a monoclonal antibody medication developed by Janssen Pharmaceuticals, for the treatment of Crohn's disease, ulcerative colitis, plaque psoriasis and psoriatic arthritis, targeting both IL-12 an ...
, or
vedolizumab Vedolizumab, sold under the brand name Entyvio, is a monoclonal antibody medication developed by Millennium Pharmaceuticals, Inc. for the treatment of ulcerative colitis and Crohn's disease. It binds to integrin α4β7 ( LPAM-1, lymphocyte Peyer ...
are recommended in those with moderate or severe disease. A formulation of
budesonide Budesonide, sold under the brand name Pulmicort among others, is a medication of the corticosteroid type. It is available as an inhaler, nebulization solution, pill, nasal spray, and rectal forms. The inhaled form is used in the long-term mana ...
was approved by the U.S.
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) for treatment of active ulcerative colitis in January 2013. In 2018,
tofacitinib Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. Common side effects include diarrhea, headache, and high blood pressure. Serious side eff ...
was approved for treatment of moderately to severely active ulcerative colitis in the United States, the first oral medication indicated for long term use in this condition. The evidence on methotrexate does not show a benefit in producing remission in people with ulcerative colitis.
Cyclosporine Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease ...
is effective for severe UC and
tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...
has also shown benefits.


Aminosalicylates

Sulfasalazine has been a major agent in the therapy of mild to moderate ulcerative colitis for over 50 years. In 1977, it was shown that 5-aminosalicylic acid (5-ASA,
mesalazine Mesalazine, also known as mesalamine or 5-aminosalicylic acid (5-ASA), is a medication used to treat inflammatory bowel disease, including ulcerative colitis and Crohn's disease. It is generally used for mildly to moderately severe disease. I ...
/mesalamine) was the therapeutically active component in sulfasalazine. Many 5-ASA drugs have been developed with the aim of delivering the active compound to the large intestine to maintain therapeutic efficacy but with reduction of the side effects associated with the sulfapyridine moiety in sulfasalazine. Oral 5-ASA drugs are particularly effective in inducing and in maintaining remission in mild to moderate ulcerative colitis. Rectal suppository, foam or liquid enema formulations of 5-ASA are used for colitis affecting the rectum, sigmoid or descending colon, and have been shown to be effective especially when combined with oral treatment.


Biologics

Biologic treatments such as the
TNF inhibitor A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response. TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ...
s
infliximab Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spon ...
,
adalimumab Adalimumab, sold under the brand name Humira, among others, is a monoclonal antibody used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurati ...
, and
golimumab Golimumab is a human monoclonal antibody which is used as an immunosuppressive medication and sold under the brand name Simponi. Golimumab targets tumor necrosis factor alpha (TNF-alpha), a pro-inflammatory molecule and hence is a TNF inhibitor. ...
are commonly used to treat people with UC who are no longer responding to corticosteroids.
Tofacitinib Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. Common side effects include diarrhea, headache, and high blood pressure. Serious side eff ...
and
vedolizumab Vedolizumab, sold under the brand name Entyvio, is a monoclonal antibody medication developed by Millennium Pharmaceuticals, Inc. for the treatment of ulcerative colitis and Crohn's disease. It binds to integrin α4β7 ( LPAM-1, lymphocyte Peyer ...
can also produce good clinical remission and response rates in UC. Biologics may be used early in treatment (step down approach), or after other treatments have failed to induce remission (step up approach); the strategy should be individualized. Unlike aminosalicylates, biologics can cause serious side effects such as an increased risk of developing extra-intestinal cancers,
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
; and weakening of the immune system, resulting in a decreased ability of the immune system to clear infections and reactivation of latent infections such as
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
. For this reason, people on these treatments are closely monitored and are often tested for hepatitis and tuberculosis annually.


Nicotine

Unlike Crohn's disease, ulcerative colitis has a lesser chance of affecting smokers than non-smokers. In select individuals with a history of previous tobacco use, resuming low dose smoking may improve signs and symptoms of active ulcerative colitis, but it is not recommended due to the overwhelmingly negative health effects of tobacco. Studies using a transdermal nicotine patch have shown clinical and histological improvement. In one double-blind, placebo-controlled study conducted in the
United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and North ...
, 48.6% of people with UC 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 The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
showed that 39% of people who used the patch showed significant improvement, versus 9% of those given a placebo. However, nicotine therapy is generally not recommended due to side effects and inconsistent results.


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 anemia with blood tests repeated every three months in active disease and annually in quiescent disease. Adequate disease control usually improves anemia of chronic disease, but iron deficiency anemia should be treated with iron supplements. The form in which treatment is administered depends both on the severity of the anemia and on the guidelines that are followed. Some advise that
parenteral iron Iron supplements, also known as iron salts and iron pills, are a number of iron formulations used to treat and prevent iron deficiency including iron deficiency anemia. For prevention they are only recommended in those with poor absorption, ...
be used first because people respond to it more quickly, it is associated with fewer gastrointestinal side effects, and it is not associated with compliance issues. Others require oral iron to be used first, as people eventually respond and many will tolerate the side effects.


Surgery

Unlike in Crohn's disease, the gastrointestinal aspects of ulcerative colitis can generally be cured by surgical removal of the large intestine, though extraintestinal symptoms may persist. This procedure is necessary in the event of: exsanguinating
hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
, frank perforation, or documented or strongly suspected carcinoma. Surgery is also indicated for people with severe colitis or toxic megacolon. People with symptoms that are disabling and do not respond to drugs may wish to consider whether surgery would improve the quality of life. The removal of the entire large intestine, known as a proctocolectomy, results in a permanent ileostomy – where a
stoma In botany, a stoma (from Greek ''στόμα'', "mouth", plural "stomata"), also called a stomate (plural "stomates"), is a pore found in the epidermis of leaves, stems, and other organs, that controls the rate of gas exchange. The pore is bor ...
is created by pulling the terminal ileum through the abdomen. Intestinal contents are emptied into a removable ostomy bag which is secured around the stoma using adhesive. Another surgical option for ulcerative colitis that is affecting most of the large bowel is called the ileal pouch-anal anastomosis (IPAA). This is a two- or three-step procedure. In a three-step procedure, the first surgery is a sub-total colectomy, in which the large bowel is removed, but the rectum remains in situ, and a temporary ileostomy is made. The second step is a proctectomy and formation of the ileal pouch (commonly known as a "j-pouch"). This involves removing the large majority of the remaining rectal stump and creating a new "rectum" by fashioning the end of the small intestine into a pouch and attaching it to the anus. After this procedure, a new type of ileostomy is created (known as a loop ileostomy) to allow the anastomoses to heal. The final surgery is a take-down procedure where the ileostomy is reversed and there is no longer the need for an ostomy bag. When done in two steps, a proctocolectomy – removing both the colon and rectum – is performed alongside the pouch formation and loop ileostomy. The final step is the same take-down surgery as in the three-step procedure. Time taken between each step can vary, but typically a six- to twelve-month interval is recommended between the first two steps, and a minimum of two to three months is required between the formation of the pouch and the ileostomy take-down. While the ileal pouch procedure removes the need for an ostomy bag, it does not restore normal bowel function. In the months following the final operation, patients typically experience 8–15 bowel movements a day. Over time this number decreases, with many patients reporting four-six bowel movements after one year post-op. While many patients have success with this procedure, there are a number of known complications.
Pouchitis Pouchitis is an umbrella term for inflammation of the ileal pouch, an artificial rectum surgically created out of ileum (the last section of the small intestine) in patients who have undergone a proctocolectomy or total colectomy (removal of t ...
, inflammation of the ileal pouch resulting in symptoms similar to ulcerative colitis, is relatively common. Pouchitis can be acute, remitting, or chronic however treatment using antibiotics, steroids, or biologics can be highly effective. Other complications include fistulas, abscesses, and pouch failure. Depending on the severity of the condition, pouch revision surgery may need to be performed. In some cased the pouch may need to be de-functioned or removed and an ileostomy recreated. The risk of cancer arising from a ileal pouch anal anastomosis is low. However, annual surveillance with
pouchoscopy Pouchoscopy is a minimally invasive endoscopic procedure to examine an ileo-anal pouch, a replacement for the colon / rectum which is surgically created from the small intestine (ileum) as treatment for ulcerative colitis, a preventive measure in ...
may be considered in individuals with risk factors for dysplasia, such as a history of dysplasia or colorectal cancer, a history of PSC, refractory pouchitis, and severely inflamed atrophic pouch mucosa.


Bacterial recolonization

In a number of randomized clinical trials,
probiotics Probiotics are live microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the gut microbiota. Probiotics are considered generally safe to consume, but may cause bacteria- host i ...
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 people for up to a year. A probiotic named after its gastroenterologist medical doctor inventor, the
De Simone Formulation The De Simone Formulation is a probiotic formula and manufacturing method developed by medical doctor Professor Claudio De Simone (MD, FAGA). The De Simone Formulation has been clinically studied for a variety of health conditions since the 1990 ...
, may be effective in inducing remission in active ulcerative colitis, and may be as effective as 5-ASAs in preventing relapse of quiescent UC. The De Simone Formulation was sold and researched under the brand name VSL#3 until 2016. Since, it has been sold and researched under various regional brand names including Visbiome in the United States and Vivomixx in Europe. Fecal microbiota transplant involves the infusion of human probiotics through fecal enemas. Ulcerative colitis typically requires a more prolonged bacteriotherapy treatment than ''Clostridium difficile'' infection to be successful, possibly due to the time needed to heal the ulcerated epithelium. The response of ulcerative colitis is potentially very favorable with one study reporting 67.7% of people experiencing complete remission. Other studies found a benefit from using fecal microbiota transplantation.


Alternative medicine

A variety of alternative medicine therapies have been used for ulcerative colitis, with inconsistent results. Curcumin (turmeric) therapy, in conjunction with taking the medications
mesalamine Mesalazine, also known as mesalamine or 5-aminosalicylic acid (5-ASA), is a medication used to treat inflammatory bowel disease, including ulcerative colitis and Crohn's disease. It is generally used for mildly to moderately severe disease. It ...
or
sulfasalazine Sulfasalazine, sold under the brand name Azulfidine among others, is a medication used to treat rheumatoid arthritis, ulcerative colitis, and Crohn's disease. It is considered by some to be a first-line treatment in rheumatoid arthritis. It is ...
, may be effective and safe for maintaining remission in people with quiescent ulcerative colitis. The effect of
curcumin Curcumin is a bright yellow chemical produced by plants of the ''Curcuma longa'' species. It is the principal curcuminoid of turmeric (''Curcuma longa''), a member of the ginger family, Zingiberaceae. It is sold as a herbal supplement, cosmet ...
therapy alone on quiescent ulcerative colitis is unknown. Treatments using
cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: ''Cannabis sativa'', '' C. indica'', and '' C. ruderalis''. Alternatively ...
or cannabis oil are uncertain. So far, studies haven't determined its effectiveness and safety.


Abdominal pain management

Many interventions have been considered to manage abdominal pain in people with ulcerative colitis, including FODMAPs diet, relaxation training,
yoga Yoga (; sa, योग, lit=yoke' or 'union ) is a group of physical, mental, and spiritual practices or disciplines which originated in ancient India and aim to control (yoke) and still the mind, recognizing a detached witness-consciou ...
,
kefir Kefir ( ; also spelled as kephir or kefier; ; ; ) is a fermented milk drink similar to a thin yogurt or ayran that is made from kefir grains, a specific type of mesophilic symbiotic culture. The drink originated in the North Caucasus, in pa ...
diet and stellate ganglion block treatment. It is unclear whether any of these are safe or effective at improving pain or reducing
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
and depression.


Prognosis

Poor prognostic factors include: age < 40 years upon diagnosis, extensive colitis, severe colitis on endoscopy, prior hospitalization, elevated CRP and low serum albumin.


Progression or remission

People with ulcerative colitis usually have an intermittent course, with periods of disease inactivity alternating with "flares" of disease. People 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. A subset of people experience a course of disease progress rapidly. In these cases, there is usually a failure to respond to medication and surgery often is performed within the first few years of disease onset. People with more extensive disease are less likely to sustain remission, but the rate of remission is independent of the severity of the disease. Several risk factors are associated with eventual need for colectomy, including: prior hospitalization for UC, extensive colitis, need for systemic steroids, young age at diagnosis, low serum albumin, elevated inflammatory markers (CRP & ESR), and severe inflammation seen during colonoscopy. Surgical removal of the large intestine is necessary in some cases.


Colorectal cancer

The risk of
colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...
is significantly increased in people with ulcerative colitis after ten years if involvement is beyond the
splenic flexure In the anatomy of the human digestive tract, there are two colic flexures, or curvatures in the transverse colon. The right colic flexure is also known as the hepatic flexure, and the left colic flexure is also known as the splenic flexure. Note ...
. People with backwash ileitis might have an increased risk for colorectal carcinoma. Those people with only proctitis usually have no increased risk. It is recommended that people have screening
colonoscopies Colonoscopy () or coloscopy () is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It can provide a visual diagnosis (''e.g ...
with random biopsies to look for
dysplasia Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs (macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopic ...
after eight years of disease activity, at one to two year intervals.


Mortality

People with ulcerative colitis are at similar or perhaps slightly increased overall risk of
death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
compared with the background population. However, the distribution of causes-of-death differs from the general population. Specific risk factors may predict worse outcomes and a higher risk of mortality in people with ulcerative colitis, including: C. difficile infection and
cytomegalovirus infection ''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpe ...
(due to reactivation).


Epidemiology

Together with Crohn's disease, about 11.2 million people were affected . Each year, ulcerative colitis newly occurs in 1 to 20 per 100,000 people (incidence), and there are a total of 5-500 per 100,000 individuals with the disease (prevalence). In 2015, a worldwide total of 47,400 people died due to inflammatory bowel disease (UC and Crohn's disease). The peak onset is between 30 and 40 years of age, with a second peak of onset occurring in the 6th decade of life. Ulcerative colitis is equally common among men and women. With appropriate treatment the risk of death appears similar to that of the general population. UC has become more common since the 1950s. The geographic distribution of UC and Crohn's disease is similar worldwide, with the highest number of new cases a year of UC found in
Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...
, New Zealand and the United Kingdom. The disease is more common in North America and Europe than other regions. In general, higher rates are seen in northern locations compared to southern locations in
Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...
and the United States. UC is more common in western Europe compared with eastern Europe. Worldwide, the prevalence of UC varies from 2 - 299 per 100,000 people. Together, ulcerative colitis and Crohn's disease affect about a million people in the United States. As with Crohn's disease, the rates of UC are greater among
Ashkenazi Jews Ashkenazi Jews ( ; he, יְהוּדֵי אַשְׁכְּנַז, translit=Yehudei Ashkenaz, ; yi, אַשכּנזישע ייִדן, Ashkenazishe Yidn), also known as Ashkenazic Jews or ''Ashkenazim'',, Ashkenazi Hebrew pronunciation: , singu ...
and decreases progressively in other persons of Jewish descent, non-Jewish Caucasians, Africans, Hispanics, and Asians. Appendectomy prior to age 20 for appendicitis and current tobacco use are protective against development of UC. However, former tobacco use is associated with a higher risk of developing the disease.


United States

, the number of new cases of UC in the United States was between 2.2 and 14.3 per 100,000 per year. The number of people affected in the United States in 2004 was between 37 and 246 per 100,000.


Canada

In Canada, between 1998 and 2000, the number of new cases per year was 12.9 per 100,000 population or 4,500 new cases. The number of people affected was estimated to be 211 per 100,000 or 104,000.


United Kingdom

In the United Kingdom 10 per 100,000 people newly develop the condition a year while the number of people affected is 243 per 100,000. Approximately 146,000 people in the United Kingdom have been diagnosed with UC.


History

The first description of ulcerative colitis occurred around the 1850s.


Research

Helminthic therapy Helminthic therapy, an experimental type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the eggs of a helminth. Helminths are parasitic worms such as hoo ...
using the
whipworm ''Trichuris trichiura, Trichocephalus trichiuris'' or whipworm, is a parasitic roundworm (a type of helminth) that causes trichuriasis (a type of helminthiasis which is one of the neglected tropical diseases) when it infects a human large intes ...
''Trichuris suis'' has been shown in a
randomized control trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
from Iowa to show benefit in people with ulcerative colitis. The therapy tests the
hygiene hypothesis In medicine, the hygiene hypothesis states that early childhood exposure to particular microorganisms (such as the gut flora and helminth parasites) protects against allergic diseases by contributing to the development of the immune system. In pa ...
which argues that the absence of
helminths Parasitic worms, also known as helminths, are large macroparasites; adults can generally be seen with the naked eye. Many are intestinal worms that are soil-transmitted and infect the gastrointestinal tract. Other parasitic worms such as ...
in the colons of people in the developed world may lead to inflammation. Both helminthic therapy and fecal microbiota transplant induce a characteristic Th2 white cell response in the diseased areas, which was unexpected given that ulcerative colitis was thought to involve Th2 overproduction.
Alicaforsen Alicaforsen (trade name Camligo) is an antisense oligonucleotide therapeutic that targets the messenger RNA for the production of human ICAM-1 receptor and is being developed for the treatment of acute disease flares in moderate to severe Inflamm ...
is a first generation antisense oligodeoxynucleotide designed to bind specifically to the human
ICAM-1 ICAM-1 (Intercellular Adhesion Molecule 1) also known as CD54 (Cluster of Differentiation 54) is a protein that in humans is encoded by the ''ICAM1'' gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial ...
messenger
RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
through Watson-Crick base pair interactions in order to subdue expression of ICAM-1. ICAM-1 propagates an inflammatory response promoting the extravasation and activation of
leukocytes White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
(white blood cells) into inflamed tissue. Increased expression of ICAM-1 has been observed within the
inflamed Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecu ...
intestinal mucosa of ulcerative colitis patients, where ICAM-1 over production correlated with disease activity. This suggests that ICAM-1 is a potential therapeutic target in the treatment of ulcerative colitis. Gram positive bacteria present in the lumen could be associated with extending the time of relapse for ulcerative colitis. A series of drugs in development looks to disrupt the inflammation process by selectively targeting an
ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
in the inflammation signaling cascade known as KCa3.1. In a preclinical study in rats and mice, inhibition of KCa3.1 disrupted the production of Th1 cytokines IL-2 and TNF-∝ and decreased colon inflammation as effectively as
sulfasalazine Sulfasalazine, sold under the brand name Azulfidine among others, is a medication used to treat rheumatoid arthritis, ulcerative colitis, and Crohn's disease. It is considered by some to be a first-line treatment in rheumatoid arthritis. It is ...
. Neutrophil extracellular traps and the resulting degradation of the extracellular matrix have been reported in the colon mucosa in ulcerative colitis patients in clinical remission, indicating the involvement of the innate immune system in the etiology.
Fexofenadine Fexofenadine, sold under the brand name Allegra among others, is an antihistamine pharmaceutical drug used in the treatment of allergy symptoms, such as hay fever and urticaria. Therapeutically, fexofenadine is a selective peripheral H1 block ...
, an antihistamine drug used in treatment of allergies, has shown promise in a combination therapy in some studies. Opportunely, low gastrointestinal absorption (or high absorbed drug gastrointestinal secretion) of fexofenadine results in higher concentration at the site of inflammation. Thus, the drug may locally decrease histamine secretion by involved gastrointestinal mast cells and alleviate the inflammation. There is evidence that etrolizumab is effective for ulcerative colitis, with phase 3 trials underway as of 2016. Etrolizumab is a humanized monoclonal antibody that targets he β7 subunit of integrins α4β7 and αEβ7. Etrolizumab decreases lymphocytes trafficking, similar to vedolizumab (another integrin antagonist). A type of
leukocyte apheresis Leukocyte apheresis is a medical device therapy (selective granulocyte/monocyte adsorptive apheresis; GMDN code: 47306) for the treatment of inflammation of the Large intestine, colon. It works by removing from the blood a group of white blood cel ...
, known as granulocyte and monocyte adsorptive apheresis, still requires large-scale trials to determine whether or not it is effective. Results from small trials have been tentatively positive.


Notable cases


References


Further reading

* *


External links


MedlinePlus ulcerative colitis page
{{DEFAULTSORT:Ulcerative Colitis Colitis Abdominal pain Articles containing video clips Autoimmune diseases Conditions diagnosed by stool test Cytomegalovirus-associated diseases Diarrhea Inflammations Noninfective enteritis and colitis Steroid-responsive inflammatory conditions Wikipedia medicine articles ready to translate Wikipedia emergency medicine articles ready to translate