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. antibodies against saccharomyces cerevisiae 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 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 is an additional nonspecific marker of intestinal inflammation. imaging overall, imaging tests, such as x-ray 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 enteropathy, and irritable bowel syndrome. 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), or chemical colitis. pseudomembranous colitis may occur due to clostridioides difficile infection following administration of antibiotics. entamoeba histolytica 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. diagnostic findings crohn's diseaseulcerative colitis terminal ileum involvementcommonlyseldom colon involvementusuallyalways rectum involvementseldomusually (95%) involvement around the anuscommon seldom bile duct involvementno increase in rate of primary sclerosing cholangitishigher rate distribution of diseasepatchy areas of inflammation (skip lesions)continuous area of inflammation endoscopydeep geographic and serpiginous (snake-like) ulcers continuous ulcer depth of inflammationmay be transmural, deep into tissues shallow, mucosal stenosiscommonseldom granulomas on biopsymay have non-necrotizing non-peri-intestinal crypt granulomas non-peri-intestinal crypt granulomas not seen management main article: management of ulcerative colitis 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 and mesalazine. corticosteroids such as prednisone 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 and biological agents such as infliximab and adalimumab are given only if people cannot achieve remission with 5-asa and corticosteroids. infliximab, ustekinumab, or vedolizumab are recommended in those with moderate or severe disease. 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 and tacrolimus 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/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 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. 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; 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. surgery management crohn's diseaseulcerative colitis mesalazineless usefulmore useful antibioticseffective in long-termgenerally not useful surgeryoften returns following removal of affected partusually cured by removal of colon 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