Ulcerative colitis

Gastrointestinal People with ulcerative colitis usually present with diarrhea mixed with blood, 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 lead to anemia, 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. 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.). The disease is classified by the extent of involvement, depending on how far the disease extends: Ileitis more commonly occurs in the setting of pancolitis (occurring in 20% of cases of pancolitis), Severity of disease In addition to the extent of involvement, UC is also characterized by the severity of the disease. Mild disease correlates with fewer than four stools daily; in addition, mild urgency and rectal bleeding may occur intermittently. Other complications include hemorrhage, venous thromboembolism, and secondary infections of the colon including C. difficile or cytomegalovirus colitis. The frequency of such extraintestinal manifestations has been reported as between 6 and 47%. involving the tongue, lips, palate, and pharynx. with large ulcerations affecting the back. UC may affect the mouth. About 8% of individuals with UC develop oral manifestations. The two most common oral manifestations are aphthous stomatitis and angular cheilitis. Uveitis can cause blurred vision and eye pain, especially when exposed to light (photophobia). Untreated, uveitis can lead to permanent vision loss. 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, which may affect a few large joints (oligoarthritis), the vertebra (ankylosing spondylitis), or several small joints of the hands and feet (peripheral arthritis). Another skin condition associated with UC is pyoderma gangrenosum, which presents as deep skin ulcerations. Pyoderma gangrenosum is seen in about 1% of patients with UC, and its formation is usually independent of bowel inflammation. Ulcerative colitis may affect the circulatory and endocrine systems. 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, while difficulty breathing may be a result of pulmonary embolism (blood clots in the lungs). The risk of blood clots is about threefold higher in individuals with IBD. PSC is more common in men, and often begins between 30 and 40 years of age. 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. ==Causes==

Ulcerative colitis is an autoimmune disease characterized by T-cells 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 markers and linkages. In addition, the identical twin concordance rate is 10%, whereas the dizygotic twin concordance rate is only 3%. Between 8 and 14% of people with ulcerative colitis have a family history of inflammatory bowel disease. Some of the putative regions encode transporter proteins such as OCTN1 and OCTN2. Other potential regions involve cell scaffolding proteins such as the MAGUK family. Human leukocyte antigen associations may even be at work. In fact, this linkage on chromosome 6 may be the most convincing and consistent of the genetic candidates. psoriasis, lupus erythematosus, rheumatoid arthritis, episcleritis, and scleritis. Environmental factors Many hypotheses have been raised for environmental factors contributing to the pathogenesis of ulcerative colitis, including diet, breastfeeding, and medications. Breastfeeding may have a protective effect on the development of ulcerative colitis. One study of isotretinoin found a small increase in the rate of UC. As the colon is exposed to many dietary substances which may encourage inflammation, dietary factors have been hypothesized to play a role in the pathogenesis of both ulcerative colitis and Crohn's disease. However, 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 of refined sugar on the number of people affected by ulcerative colitis. High intake of unsaturated fat and vitamin B6 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, three epidemiologists 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 exposure and six health outcomes, one of which was ulcerative colitis. Alternative theories Levels of sulfate-reducing bacteria tend to be higher in people with ulcerative colitis, which could indicate higher levels of hydrogen sulfide in the intestine. An alternative theory suggests that the symptoms of the disease may be caused by the toxic effects of the hydrogen sulfide on the cells lining the intestine. Infection by Mycobacterium avium, subspecies paratuberculosis, 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 short-chain fatty acid n-butyrate gets oxidized through the beta oxidation pathway into carbon dioxide and ketone bodies. It has been shown that n-butyrate helps supply nutrients to this epithelial barrier. Studies have proposed that hydrogen sulfide plays a role in impairing this beta-oxidation pathway by interrupting the short-chain acetyl-CoA dehydrogenase, an enzyme within the pathway. Furthermore, it has been suggested that the protective effect of smoking in ulcerative colitis is due to the hydrogen cyanide 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. However, in ulcerative colitis, aberrant activity of dendritic cells and macrophages results in them phagocytosing bacteria of the normal gut microbiome. After ingesting the microbiome bacterium, the APCs release the cytokine TNFα, which stimulates inflammatory signaling and recruits inflammatory cells to the intestines, leading to the inflammation that is characteristic of ulcerative colitis. The TNF inhibitors, including infliximab, adalimumab, and golimumab, are used to inhibit this step during the treatment of ulcerative colitis. After phagocytosing the microbe, the APCs then enter the mesenteric lymph nodes where they present antigens to naive T-cells while also releasing the pro-inflammatory cytokines IL-12 and IL-23 which lead to T cell differentiation into Th1 and Th17 T-cells. IL-12 and IL-23 signaling is blocked by the biologic ustekinumab and IL-23 is blocked by guselkumab, mirikizumab and risankizumab, medications that are used in the treatment of ulcerative colitis. From the mesenteric lymph node, the T-cells then enter the intestinal lymphatic venule, which provides transport to the intestinal epithelium, where they mediate further inflammation characteristic of ulcerative colitis. The T-cells exit the lymphatic venule via the adhesion protein mucosal vascular addressin cell adhesion molecule 1 MAdCAM-1, the ulcerative colitis biologic treatment vedolizumab inhibits T-cell migration out of the lymphatic venules by blocking binding to MAdCAM-1. While the medications ozanimod and etrasimod inhibit the sphingosine-1-phosphate receptor to prevent T-cell migration into the efferent lymphatic venules. Once the mature Th1 and Th17 T-cells exit the efferent lymphatic venule, they travel to the intestinal mucosa and cause further inflammation. T-cell mediated inflammation is thought to be driven by the JAK-STAT intracellular T-cell signaling pathway, leading to the transcription, translation and release of inflammatory cytokines. This T-cell JAK-STAT signaling is inhibited by the medications tofacitinib, filgotinib, and upadacitinib, which are used in the treatment of ulcerative colitis. ==Diagnosis==

image of ulcerative colitis affecting the left side of the colon. The image shows confluent superficial ulceration and loss of mucosal architecture. Crohn's disease may be similar in appearance, a fact that can make diagnosing UC a challenge. The initial diagnostic 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 is done to check for anemia; thrombocytosis, a high platelet count, is occasionally seen • Electrolyte studies and kidney function tests are done, as chronic diarrhea may be associated with hypokalemia, hypomagnesemia, and kidney injury. • Liver function tests are performed to screen for bile duct involvement: primary sclerosing cholangitis. • Imaging such as x-ray or CT scan to evaluate for possible perforation or toxic megacolon • Stool culture and Clostridioides difficile stool assay to rule out infectious colitis Endoscopic of a person with intractable UC, colectomy specimen The best test for the diagnosis of ulcerative colitis remains endoscopy, which is the examination of the internal surface of the bowel using a flexible camera. Initially, a flexible sigmoidoscopy may be completed to establish the diagnosis. Endoscopic findings in ulcerative colitis include: erythema (redness of the mucosa), friability 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 involved. Perianal disease is rare. The degree of involvement endoscopically ranges from proctitis (rectal inflammation) to left-sided colitis (extending to the descending colon) to extensive colitis (extending proximal to the descending colon). 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 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. Imaging Overall, imaging tests, such as x-ray or CT scan, may help assess 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 studies demonstrated that bowel ultrasound is an accurate tool for assessing disease activity in people with ulcerative colitis. Imaging is otherwise of limited use in diagnosing ulcerative colitis. 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 distinguish, 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 similarly to ulcerative colitis. Endoscopic findings are also often similar. One can discern whether a patient has infectious colitis by employing tissue cultures and stool studies. A biopsy of the colon is another beneficial test, but it 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. This condition often shows increased growth of lymphoid tissue on histology. 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 a 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 inducing and maintaining remission is crucial. The medications used to induce and maintain 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. For acute stages of the disease, a low fiber diet may be recommended. Medication The first-line maintenance medication for ulcerative colitis in remission is mesalazine (also known as mesalamine or 5-ASA). For patients with active disease limited to the left colon (descending colon) or proctitis, mesalazine is also the first-line agent, and a combination of suppositories and oral mesalazine may be tried. Adding corticosteroids such as prednisone is also common in active disease, especially if remission is not achieved through mesalazine monotherapy, Guselkumab, mirikizumab, and risankizumab are monoclonal antibodies that target the p19 subunit of IL-23 and are approved for the treatment of moderately to severely active UC. As an alternative to mesalazine, one of its prodrugs such as sulfasalazine may be chosen for treatment of active disease or maintenance therapy, but the prodrugs have greater potential for serious side effects and have not been demonstrated to be superior to mesalazine in large trials. A formulation of budesonide was approved by the U.S. Food and Drug Administration (FDA) for treatment of active ulcerative colitis in January 2013. In 2018, tofacitinib 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 is effective for severe UC Etrasimod was approved for medical use in the United States in October 2023. 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/mesalamine) was the therapeutically active component in sulfasalazine. Many 5-ASA drugs have been developed to deliver 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 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 are effective, especially when combined with oral treatment. Biologics Biologic treatments such as the TNF inhibitors infliximab, adalimumab, and golimumab are commonly used to treat people with UC who are no longer responding to corticosteroids. Tofacitinib and vedolizumab can also produce good clinical remission and response rates in UC. Unlike aminosalicylates, biologics can cause serious side effects such as an increased risk of developing extra-intestinal cancers, heart failure; 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. For this reason, people on these treatments are closely monitored and are often tested for hepatitis and tuberculosis annually. Etrasimod, a once-daily oral sphingosine 1-phosphate (S1P) receptor modulator that selectively activates S1P receptor subtypes 1, 4, and 5 with no detectable activity on S1P 2 or 3, is in development for treatment of immune-mediated diseases, including ulcerative colitis, and was shown in 2 randomized trials to be effective and well tolerated as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. 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, 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 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 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. Anticholinergics Anticholinergic drugs, more specifically muscarinic antagonists, are sometimes used to treat abdominal cramps in connection with ulcerative colitis through their calming effect on colonic peristalsis (reducing both amplitude and frequency) and intestinal tone. Some medical authorities suggest over-the-counter anticholinergic drugs as potential helpful treatments for abdominal cramping in mild ulcerative colitis. However, their use is contraindicated especially in moderate to severe disease states because of the potential for anticholinergic treatment to induce toxic megacolon in patients with colonic inflammation. Toxic megacolon is a state in which the colon is abnormally distended, and may in severe or untreated cases lead to colonic perforation, sepsis, and death. Immunosuppressant therapies, infection risks, and vaccinations Many patients affected by ulcerative colitis need immunosuppressant therapies, which may be associated with a higher risk of contracting opportunistic infectious diseases. Many of these potentially harmful diseases, such as Hepatitis B, Influenza, chickenpox, herpes zoster virus, pneumococcal pneumonia, or human papilloma virus, can be prevented by vaccines. Each drug used in the treatment of IBD should be classified according to the degree of immunosuppression induced in the patient. Several guidelines suggest investigating patients' vaccination status before starting any treatment and performing vaccinations against vaccine-preventable diseases when required. Compared to the rest of the population, patients affected by IBD are known to be at higher risk of contracting some vaccine-preventable diseases. Patients treated with Janus kinase inhibitor showed a higher risk of Shingles. Nevertheless, despite the increased risk of infections, vaccination rates in IBD patients are known to be suboptimal and may also be lower than vaccination rates in the general population. 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, 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 their quality of life. 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 a 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. The risk of cancer arising from an ileal pouch anal anastomosis is low. Bacterial recolonization In several randomized clinical trials, probiotics have demonstrated the potential to be helpful in the treatment of ulcerative colitis. Specific types of probiotics, such as Escherichia coli Nissle, have been shown to induce remission in some people for up to a year. A Cochrane review of controlled trials using various probiotics found low-certainty evidence that probiotic supplements may increase the probability of clinical remission. People receiving probiotics were 73% more likely to experience disease remission and over 2x as likely to report improvement in symptoms compared to those receiving a placebo, with no clear difference in minor or serious adverse effects. Fecal microbiota transplant involves the infusion of human probiotics through fecal enemas. Ulcerative colitis typically requires a more prolonged bacteriotherapy treatment than Clostridioides difficile infection does 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 or sulfasalazine, may be effective and safe for maintaining remission in people with quiescent ulcerative colitis. Treatments using cannabis or cannabis oil are uncertain. So far, studies have not determined its effectiveness and safety. Abdominal pain management Many interventions have been considered to manage abdominal pain in people with ulcerative colitis, including low-FODMAP diet, relaxation training, yoga, kefir diet, and stellate ganglion block treatment. It is unclear whether any of these are safe or effective at improving pain or reducing anxiety and depression. Nutrition Diet can play a role in the symptoms of patients with ulcerative colitis. The most avoided foods and drinks by patients are spicy foods, dairy products, alcohol, fruits, vegetables, and carbonated beverages; these foods are mainly avoided during remission and to prevent relapse. In some cases, especially during the flare period, the dietary restrictions of these patients can be very severe and can lead to a compromised nutritional state. Some patients tend to eliminate gluten spontaneously, despite not having a definite diagnosis of coeliac disease, because they believe that gluten can exacerbate gastrointestinal symptoms. Many patients with ulcerative colitis tend to follow restrictive diets to control symptoms. Usually, lactose-free diets are the most common diet followed by patients with ulcerative colitis (21.3%% vs 11.6% controls), followed by gluten-free diet (23.4% vs 9.3% in controls). Low-FODMAP dietadoption is usually minimal. Fibre avoidance is higher in patients with Crohn's disease (45%) compared to controls (5%). Mental health Many studies found that patients with IBD reported a higher frequency of depressive and anxiety disorders than the general population, and most studies confirm that women with IBD are more likely than men to develop affective disorders and show that up to 65% of them may have depression disorder and anxiety disorder. A meta-analysis of interventions to improve mood (including talking therapy, antidepressants, and exercise) in people with inflammatory bowel disease found that they reduced inflammatory markers such as C-reactive protein and faecal calprotectin. Psychological therapies reduced inflammation more than antidepressants or exercise. ==Prognosis==

Poor prognostic factors include: age < 40 years upon diagnosis, extensive colitis, severe colitis on endoscopy, prior hospitalization, elevated CRP, and low serum albumin. 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. Those people with only proctitis usually have no increased risk. Mortality People with ulcerative colitis are at similar 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 ==Epidemiology==

The first description of ulcerative colitis occurred around the 1850s, Together with Crohn's disease, about 11.2 million people were affected , and about one million were affected in the United States as of 2012. Each year, ulcerative colitis newly occurs in 1–20 per 100,000 people (incidence), and there are a total of 5–500 per 100,000 with the disease (prevalence). The peak onset is between 30 and 40 years of age, Ulcerative colitis is equally common among men and women. The disease is more common in North America and Europe than other regions. and the United States. UC is more common in western Europe compared with eastern Europe. Worldwide, the prevalence of UC varies from 2 to 299 per 100,000 people. As with Crohn's disease, the rates of UC are greater among Ashkenazi Jews and decreases progressively in other persons of Jewish descent, non-Jewish Caucasians, Africans, Hispanics, and Asians. and current tobacco use are protective against development of UC. The number of people affected in the United States in 2004 was between 37 and 246 per 100,000. United Kingdom In the United Kingdom, 10 per 100,000 people 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 term ulcerative colitis was first used by Samuel Wilks in 1859. The term entered general medical vocabulary afterwards in 1888 with William Hale-White publishing a report of various cases of "ulcerative colitis". UC was the first subtype of IBD to be identified. ==Research==

Helminthic therapy using the whipworm Trichuris suis has been shown in a randomized control trial from Iowa to show benefit in people with ulcerative colitis. The therapy tests the hygiene hypothesis, which argues that the absence of helminths 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. ICAM-1 propagates an inflammatory response promoting the extravasation and activation of leukocytes (white blood cells) into inflamed tissue. This suggests that ICAM-1 is a potential therapeutic target in the treatment of ulcerative colitis. Gram-positive bacteria present in the lumen may 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 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-α and decreased colon inflammation as effectively as sulfasalazine. 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. 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 the involved gastrointestinal mast cells and alleviate the inflammation. Etrolizumab is a humanized monoclonal antibody that targets the β7 subunit of integrins α4β7 and αEβ7, ultimately blocking migration and retention of leukocytes in the intestinal mucosa. A type of leukocyte apheresis, 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==