View source for Ulcerative colitis

{{Short description|Inflammatory bowel disease that causes ulcers in the colon}}
{{Use dmy dates|date=September 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox medical condition (new)
| name          = Ulcerative colitis
| image         = UC granularity.png
| caption       = [[Colonoscopy|Endoscopic]] image of a colon affected by ulcerative colitis. The internal surface of the colon is blotchy and broken in places. Mild-moderate disease.
| symptoms      = [[Abdominal pain]], [[diarrhea]] mixed with [[blood]], [[weight loss]], [[fever]], [[anemia]],<ref name=NIH2014/> [[dehydration]], loss of appetite, [[fatigue]], sores on the skin, urgency to defecate, inability to defecate despite urgency, [[rectal pain]]<ref name="AR">{{cite web |title=Ulcerative Colitis |url=https://www.autoimmuneregistry.org/ulcerative-colitis |access-date=15 June 2022 |website=Autoimmune Registry Inc. }}{{Dead link|date=November 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>
| field         = [[Gastroenterology]]
| complications = [[Megacolon]], inflammation of the eye, joints, or liver, [[colon cancer]]<ref name=NIH2014/><ref name=Wan2016/>
| onset         = 15–30 years or >60 years<ref name=NIH2014/>
| duration      = Long term<ref name=NIH2014/>
| types         =
| causes        = Unknown<ref name=NIH2014/>
| risks         =
| diagnosis     = [[Colonoscopy]] with [[tissue biopsies]]<ref name=NIH2014/>
| differential  = [[Dysentery]], [[Crohn's disease]], [[ischemic colitis]]<ref>{{cite book| vauthors = Runge MS, Greganti MA | title = Netter's Internal Medicine E-Book|date=2008|publisher=Elsevier Health Sciences|isbn=9781437727722|page=428|url=https://books.google.com/books?id=hiIPDQAAQBAJ&pg=PA428|language=en}}</ref>
| prevention    =
| treatment     = Dietary changes, medication, surgery<ref name=NIH2014/>
| medication    = [[Sulfasalazine]], [[mesalazine]], [[corticosteroids|steroids]], [[immunosuppressants]] such as [[azathioprine]], [[Biological therapy for inflammatory bowel disease|biological therapy]]<ref name=NIH2014/>
| prognosis     =
| frequency     = 2&ndash;299 per 100,000<ref name=Molodecky />
| deaths        = 47,400 together with Crohn's (2015)<ref name=GBD2015De />
| alt           =
}}

'''Ulcerative colitis''' ('''UC''') is one of the two types of [[inflammatory bowel disease]] (IBD), with the other type being [[Crohn's disease]].<ref name=NIH2014/> It is a [[chronic condition|long-term condition]] that results in [[inflammation]] and [[ulcer]]s of the [[Large intestine#Structure|colon]] and [[rectum]].<ref name=NIH2014 /><ref name=BMJ2013 /> The primary symptoms of active disease are [[abdominal pain]] and [[diarrhea]] mixed with [[blood]] ([[hematochezia]]).<ref name="NIH2014" /> [[Weight loss]], [[fever]], and [[anemia]] may also occur.<ref name="NIH2014" /> Often, symptoms come on slowly and can range from mild to severe.<ref name="NIH2014" /> Symptoms typically occur intermittently with periods of no symptoms between flares.<ref name="NIH2014" /> Complications may include abnormal dilation of the colon ([[megacolon]]), inflammation of the eye, joints, or liver, and [[colon cancer]].<ref name=NIH2014/><ref name=Wan2016>{{cite journal | vauthors = Wanderås MH, Moum BA, Høivik ML, Hovde Ø | title = Predictive factors for a severe clinical course in ulcerative colitis: Results from population-based studies | journal = World Journal of Gastrointestinal Pharmacology and Therapeutics | volume = 7 | issue = 2 | pages = 235–241 | date = May 2016 | pmid = 27158539 | pmc = 4848246 | doi = 10.4292/wjgpt.v7.i2.235 | doi-access = free }}</ref>

The cause of UC is unknown.<ref name=NIH2014/> Theories involve [[autoimmune disease|immune system dysfunction]], [[genetics]], changes in the [[gut flora|normal gut bacteria]], and environmental factors.<ref name=NIH2014/><ref name=Hir2015>{{cite journal | vauthors = Akiho H, Yokoyama A, Abe S, Nakazono Y, Murakami M, Otsuka Y, Fukawa K, Esaki M, Niina Y, Ogino H | title = Promising biological therapies for ulcerative colitis: A review of the literature | journal = World Journal of Gastrointestinal Pathophysiology | volume = 6 | issue = 4 | pages = 219–227 | date = November 2015 | pmid = 26600980 | pmc = 4644886 | doi = 10.4291/wjgp.v6.i4.219 | doi-access = free }}</ref> Rates tend to be higher in the developed world with some proposing this to be the result of [[hygiene hypothesis|less exposure to intestinal infections]], or to a [[Western diet]] and lifestyle.<ref name=BMJ2013/><ref name=NEJM2011/> The removal of the appendix at an early age may be protective.<ref name=NEJM2011/> Diagnosis is typically by [[colonoscopy]] with [[tissue biopsies]].<ref name=NIH2014/>

Several medications are used to treat symptoms and bring about and maintain remission, including [[aminosalicylates]] such as [[mesalazine]] or [[sulfasalazine]], [[corticosteroids|steroids]], [[immunosuppressants]] such as [[azathioprine]], and  [[Biological therapy for inflammatory bowel disease|biologic therapy]].<ref name=NIH2014/> [[Colectomy|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.<ref name=NIH2014/> [[Proctocolectomy|Removal of the colon and rectum]] generally cures the condition.<ref name=NIH2014/><!-- Quote = Removal of the entire colon, including the rectum, "cures" ulcerative colitis. --><ref name=NEJM2011/>

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==Signs and symptoms==
{{Symptoms in CD vs. UC}}

===Gastrointestinal===
People with ulcerative colitis usually present with [[diarrhea]] mixed with [[blood]],<ref name=Ungaro /> of gradual onset that persists for an extended period of time (weeks). It is estimated that 90% of people experience rectal bleeding (of varying severity), 90% experience watery or loose stools with increased stool frequency (diarrhea), and 75-90% of people experience bowel urgency.<ref name="Gros 2023" /> Additional symptoms may include fecal incontinence, mucous rectal discharge, and nocturnal defecations.<ref name=Ungaro /> With [[proctitis]] (inflammation of the rectum), people with UC may experience urgency or [[rectal tenesmus]], which is the urgent desire to evacuate the bowels but with the passage of little stool.<ref name=Ungaro /> Tenesmus may be misinterpreted as [[constipation]], 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.<ref name=Ungaro /> The severity of abdominal pain with UC varies from mild discomfort to very painful bowel movements and abdominal cramping.<ref name=":1">{{cite journal | vauthors = Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, Burisch J, Gecse KB, Hart AL, Hindryckx P, Langner C, Limdi JK, Pellino G, Zagórowicz E, Raine T, Harbord M, Rieder F | title = Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders | journal = Journal of Crohn's & Colitis | volume = 11 | issue = 6 | pages = 649–670 | date = June 2017 | pmid = 28158501 | doi = 10.1093/ecco-jcc/jjx008 | doi-access = free }}</ref> 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]], which can affect quality of life.<ref name=Kaitha>{{cite journal | vauthors = Kaitha S, Bashir M, Ali T | title = Iron deficiency anemia in inflammatory bowel disease | journal = World Journal of Gastrointestinal Pathophysiology | volume = 6 | issue = 3 | pages = 62–72 | date = August 2015 | pmid = 26301120 | pmc = 4540708 | doi = 10.4291/wjgp.v6.i3.62 | doi-access = free }}</ref>

The clinical presentation of ulcerative colitis depends on the extent of the disease process.<ref name=Hanauer>{{cite journal | vauthors = Hanauer SB | title = Inflammatory bowel disease | journal = The New England Journal of Medicine | volume = 334 | issue = 13 | pages = 841–848 | date = March 1996 | pmid = 8596552 | doi = 10.1056/NEJM199603283341307 }}</ref> Up to 15% of individuals may have severe disease upon initial onset of symptoms.<ref name=Ungaro /> 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.<ref>{{cite journal | vauthors = Rosenberg L, Lawlor GO, Zenlea T, Goldsmith JD, Gifford A, Falchuk KR, Wolf JL, Cheifetz AS, Robson SC, Moss AC | title = Predictors of endoscopic inflammation in patients with ulcerative colitis in clinical remission | journal = Inflammatory Bowel Diseases | volume = 19 | issue = 4 | pages = 779–784 | date = 2013 | pmid = 23446338 | pmc = 3749843 | doi = 10.1097/MIB.0b013e3182802b0e | doi-access = free }}</ref> 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.<ref name=Colìa>{{cite journal | vauthors = Colìa R, Corrado A, Cantatore FP | title = Rheumatologic and extraintestinal manifestations of inflammatory bowel diseases | journal = Annals of Medicine | volume = 48 | issue = 8 | pages = 577–585 | date = December 2016 | pmid = 27310096 | doi = 10.1080/07853890.2016.1195011 | s2cid = 1796160 }}</ref>

====Extent of involvement====
[[File:Classification of Colitis.jpg|thumb|Classification of colitis, often used in defining the extent of involvement of ulcerative colitis, with proctitis (blue), proctosigmoiditis (yellow), left sided colitis (orange) and pancolitis (red). All classes extend distally to the end of the rectum.]]
[[File:Severe ulcerative colitis.jpg|thumb|Gross pathology of normal colon (left) and severe ulcerative colitis (right), forming pseudopolyps (smaller than the cobblestoning typically seen in Crohn's disease), over a continuous area (rather than skip lesions of Crohn's disease), and with a relatively gradual transition from normal colon (while Crohn's is typically more abrupt).]]
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.).<ref name=ACG_Guidelines_2019 /> In contrast, inflammation with Crohn's disease is often patchy, with so-called "skip lesions" (intermittent regions of inflamed bowel).<ref name="Feuerstein_Crohns">{{cite journal | vauthors = Feuerstein JD, Cheifetz AS | title = Crohn Disease: Epidemiology, Diagnosis, and Management | journal = Mayo Clinic Proceedings | volume = 92 | issue = 7 | pages = 1088–1103 | date = July 2017 | pmid = 28601423 | doi = 10.1016/j.mayocp.2017.04.010 | s2cid = 20223406 | doi-access = free }}</ref>

The disease is classified by the extent of involvement, depending on how far the disease extends:<ref name=":1" /> [[proctitis]] (rectal inflammation), left sided colitis (inflammation extending to descending colon), and extensive colitis (inflammation proximal to the descending colon).<ref name=ACG_Guidelines_2019 /> 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]] (inflammation of the ileum) also occurs in UC. About 17% of individuals with UC have ileitis.<ref>{{cite journal | vauthors = Haskell H, Andrews CW, Reddy SI, Dendrinos K, Farraye FA, Stucchi AF, Becker JM, Odze RD | title = Pathologic features and clinical significance of "backwash" ileitis in ulcerative colitis | journal = The American Journal of Surgical Pathology | volume = 29 | issue = 11 | pages = 1472–1481 | date = November 2005 | pmid = 16224214 | doi = 10.1097/01.pas.0000176435.19197.88 | s2cid = 42108108 }}</ref> Ileitis more commonly occurs in the setting of pancolitis (occurring in 20% of cases of pancolitis),<ref name=Ungaro /> and tends to correlate with the activity of colitis. This so-called "backwash ileitis" can occur in 10–20% of people with [[pancolitis]] and is believed to be of little clinical significance.<ref name="ISBN 0071599916">Fauci ''et al.'' ''Harrison's Internal Medicine'', 17th ed. New York: McGraw-Hill Medical, 2008. {{ISBN|978-0-07-159991-7}}</ref>

====Severity of disease====
In addition to the extent of involvement, UC is also characterized by severity of disease.<ref name=ACG_Guidelines_2019 /> 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.<ref name=ACG_Guidelines_2019 /> 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, low levels of the inflammatory markers [[C-reactive protein]] (CRP), and [[erythrocyte sedimentation rate]] (ESR), and fecal [[calprotectin]], and later age of diagnosis (over 40 years).<ref name=":2">{{cite web |title=UpToDate |url=https://www.uptodate.com/contents/medical-management-of-low-risk-adult-patients-with-mild-to-moderate-ulcerative-colitis?search=ulcerative%20colitis&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2 |access-date=8 November 2022 |website=www.uptodate.com}}</ref> Mild disease correlates with fewer than four stools daily; in addition, mild urgency and rectal bleeding may occur intermittently.<ref name=ACG_Guidelines_2019 />  Mild disease lacks [[Systemic disease|systemic]] signs of toxicity (e.g. fever, chills, weight changes) and exhibits normal levels of the serum inflammatory markers ESR and CRP.<ref name=":2" />

Moderate to severe disease correlates with more than six stools daily, frequent bloody stools and urgency.<ref name=ACG_Guidelines_2019 /> Moderate abdominal pain, low-grade [[fever]], {{convert|38|to|39|C|F}}, and anemia may develop.<ref name=ACG_Guidelines_2019 /> ESR and CRP are usually elevated.<ref name=ACG_Guidelines_2019 />

The Mayo Score, which incorporates a combination of clinical symptoms (stool frequency and amount of rectal bleeding) with endoscopic findings and a physicians assessment of severity, is often used clinically to classify UC as mild, moderate or severe.<ref name="Gros 2023" />

Acute-Severe Ulcerative Colitis (ASUC) is a severe form which presents acutely and with severe symptoms. This fulminant type is associated with severe symptoms (usually diarrhea, rectal bleeding and abdominal pain) and is usually associated with systemic symptoms including fever.<ref name="Gros 2023" /> It is associated with a high mortality rate as compared to milder forms of UC, with a 3-month and 12 month mortality rate of 0.84% and 1% respectively.<ref name="Gros 2023" /> People with fulminant UC may have inflammation extending beyond just the mucosal layer, causing impaired colonic motility and leading to [[toxic megacolon]]. Toxic megacolon represents a medical emergency, one often treated surgically. If the [[serous membrane]] is involved, a colonic [[gastrointestinal perforation|perforation]] may ensue, which has a 50% mortality rate in people with UC.<ref>{{cite web |title=UpToDate |url=https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-prognosis-of-ulcerative-colitis-in-adults?search=clinical%20manifestation%20of%20ulcerative%20colitis&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 |access-date=9 November 2022 |website=www.uptodate.com}}</ref> Other complications include [[hemorrhage]], [[venous thromboembolism]], and secondary infections of the colon including ''[[C. difficile]]'' or [[cytomegalovirus]] colitis.<ref name="Gros 2023" />

Ulcerative colitis may improve and enter remission.<ref name=ACG_Guidelines_2019 />

===Extraintestinal manifestations and complications===
{{Complications of CD vs. UC}}
[[File:Aphtha2.jpg|thumb|left|[[Aphthous ulcers]] involving the [[tongue]], [[lip]]s, [[palate]], and [[pharynx]].]]
[[File:Pyoderma gangrenosum 01.jpg|thumb|left|[[Pyoderma gangrenosum]] with large ulcerations affecting the back.]]
UC is characterized by immune dysregulation and systemic inflammation, which may result in [[symptom]]s and [[complication (medicine)|complications]] outside the colon. Commonly affected organs include: eyes, joints, skin, and liver.<ref name=Feuerstein_UC>{{cite journal | vauthors = Feuerstein JD, Moss AC, Farraye FA | title = Ulcerative Colitis | journal = Mayo Clinic Proceedings | volume = 94 | issue = 7 | pages = 1357–1373 | date = July 2019 | pmid = 31272578 | doi = 10.1016/j.mayocp.2019.01.018 | doi-access = free }}</ref> The frequency of such extraintestinal manifestations has been reported as between 6 and 47%.<ref name=Langan>{{cite journal | vauthors = Langan RC, Gotsch PB, Krafczyk MA, Skillinge DD | title = Ulcerative colitis: diagnosis and treatment | journal = American Family Physician | volume = 76 | issue = 9 | pages = 1323–1330 | date = November 2007 | pmid = 18019875 }}</ref><ref name=Vavricka>{{cite journal | vauthors = Vavricka SR, Schoepfer A, Scharl M, Lakatos PL, Navarini A, Rogler G | title = Extraintestinal Manifestations of Inflammatory Bowel Disease | journal = Inflammatory Bowel Diseases | volume = 21 | issue = 8 | pages = 1982–1992 | date = August 2015 | pmid = 26154136 | pmc = 4511685 | doi = 10.1097/MIB.0000000000000392 }}</ref>

UC may affect the mouth. About 8% of individuals with UC develop oral manifestations.<ref name="uhvić-Urek">{{cite journal | vauthors = Muhvić-Urek M, Tomac-Stojmenović M, Mijandrušić-Sinčić B | title = Oral pathology in inflammatory bowel disease | journal = World Journal of Gastroenterology | volume = 22 | issue = 25 | pages = 5655–5667 | date = July 2016 | pmid = 27433081 | pmc = 4932203 | doi = 10.3748/wjg.v22.i25.5655 | doi-access = free }}</ref> The two most common oral manifestations are [[aphthous stomatitis]] and [[angular cheilitis]].<ref name="uhvić-Urek"/> 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.<ref name="uhvić-Urek"/> Very rarely, benign pustules may occur in the mouth (pyostomatitis vegetans).<ref name="uhvić-Urek"/>

UC may affect the eyes manifesting in scleritis, iritis, and conjunctivitis. Patients may be asymptomatic or experience redness, burning, or itching in eyes. Inflammation may occur in the interior portion of the eye, leading to [[uveitis]] and [[iritis]].<ref name=Troncoso>{{cite journal | vauthors = Troncoso LL, Biancardi AL, de Moraes HV, Zaltman C | title = Ophthalmic manifestations in patients with inflammatory bowel disease: A review | journal = World Journal of Gastroenterology | volume = 23 | issue = 32 | pages = 5836–5848 | date = August 2017 | pmid = 28932076 | pmc = 5583569 | doi = 10.3748/wjg.v23.i32.5836 | doi-access = free }}</ref> Uveitis can cause blurred vision and eye pain, especially when exposed to light ([[photophobia]]). Untreated, uveitis can lead to permanent vision loss.<ref name=Troncoso /> Inflammation may also involve the white part of the eye ([[sclera]]) or the overlying connective tissue ([[episclera]]), causing conditions called [[scleritis]] and [[episcleritis]].<ref>{{cite book | title = Episcleritis | date = January 2020 | pmid = 30521217 | last1 = Schonberg | first1 = S. | last2 = Stokkermans | first2 = T. J.|publisher=StatPearls |url=https://pubmed.ncbi.nlm.nih.gov/30521217/}}</ref> Ulcerative colitis is most commonly associated with uveitis and episcleritis.<ref name="Langholz">{{cite journal |vauthors=Langholz E |date=March 2010 |title=Current trends in inflammatory bowel disease: the natural history |journal=Therapeutic Advances in Gastroenterology |volume=3 |issue=2 |pages=77–86 |doi=10.1177/1756283X10361304 |pmc=3002570 |pmid=21180592}}</ref>

UC may cause several joint manifestations, including a type of rheumatologic disease known as [[seronegative arthritis]], which may affect few large joints (oligoarthritis), the [[Vertebral column|vertebra]] ([[ankylosing spondylitis]]) or several small joints of the hands and feet (peripheral arthritis).<ref name=Feuerstein_UC/> Often the insertion site where muscle attaches to bone ([[entheses]]) becomes inflamed ([[enthesitis]]). Inflammation may affect the [[sacroiliac joint]] ([[sacroiliitis]]).<ref name=Colìa /> It is estimated that around 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]], swelling, and [[joint effusion|effusion]], and often leads to significant morbidity.<ref name=Colìa /> Ankylosing spondylitis and sacroilitis usually occur independent of bowel disease activity in UC.<ref name="Gros 2023" />

Ulcerative colitis may affect the skin. The most common type of skin manifestation, [[erythema nodosum]], presents in up to 3% of UC patients. 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).<ref name=Langholz /> The nodules have diameters that measure approximately 1–5&nbsp;cm. Erythema nodosum is due to inflammation of the underlying subcutaneous tissue ([[panniculitis]]), 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.<ref name=":3">{{cite journal |last1=Farhi |first1=David |last2=Cosnes |first2=Jacques |last3=Zizi |first3=Nada |last4=Chosidow |first4=Olivier |last5=Seksik |first5=Philippe |last6=Beaugerie |first6=Laurent |last7=Aractingi |first7=Selim |last8=Khosrotehrani |first8=Kiarash |date=September 2008 |title=Significance of erythema nodosum and pyoderma gangrenosum in inflammatory bowel diseases: a cohort study of 2402 patients |journal=Medicine |volume=87 |issue=5 |pages=281–293 |doi=10.1097/MD.0b013e318187cc9c |issn=1536-5964 |pmid=18794711|s2cid=6905740 |doi-access=free }}</ref>

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.<ref name="Gros 2023" /> Pyoderma gangrenosum is characterized by painful lesions or [[skin condition|nodules]] that become [[ulcer (dermatology)|ulcer]]s which progressively grow. The ulcers are often filled with sterile pus-like material. In some cases, pyoderma gangrenosum may require injection with corticosteroids.<ref name="Feuerstein_UC" /> Treatment may also involve inhibitors of tumor necrosis factor (TNF), a cytokine that promotes cell survival.<ref name=":3" />

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 [[fistulas]] tunnels in the skin that drain fluid.<ref>{{cite journal |last1=Chen |first1=Wei-Ti |last2=Chi |first2=Ching-Chi |date=1 September 2019 |title=Association of Hidradenitis Suppurativa With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis |journal=JAMA Dermatology |volume=155 |issue=9 |pages=1022–1027 |doi=10.1001/jamadermatol.2019.0891 |issn=2168-6084 |pmc=6625071 |pmid=31290938}}</ref>

Ulcerative colitis may affect the circulatory and endocrine system. UC increases the risk of blood clots in both arteries and veins;<ref name=Cheng_VTE>{{cite journal | vauthors = Cheng K, Faye AS | title = Venous thromboembolism in inflammatory bowel disease | journal = World Journal of Gastroenterology | volume = 26 | issue = 12 | pages = 1231–1241 | date = March 2020 | pmid = 32256013 | pmc = 7109271 | doi = 10.3748/wjg.v26.i12.1231 | s2cid = 214946656 | doi-access = free }}</ref><ref name=Nguyen_DVT>{{cite journal | vauthors = Nguyen GC, Bernstein CN, Bitton A, Chan AK, Griffiths AM, Leontiadis GI, Geerts W, Bressler B, Butzner JD, Carrier M, Chande N, Marshall JK, Williams C, Kearon C | title = Consensus statements on the risk, prevention, and treatment of venous thromboembolism in inflammatory bowel disease: Canadian Association of Gastroenterology | journal = Gastroenterology | volume = 146 | issue = 3 | pages = 835–848.e6 | date = March 2014 | pmid = 24462530 | doi = 10.1053/j.gastro.2014.01.042 }}</ref><ref>{{cite journal | vauthors = Andrade AR, Barros LL, Azevedo MF, Carlos AS, Damião AO, Sipahi AM, Leite AZ | title = Risk of thrombosis and mortality in inflammatory bowel disease | journal = Clinical and Translational Gastroenterology | volume = 9 | issue = 4 | pages = 142 | date = April 2018 | pmid = 29618721 | pmc = 5886983 | doi = 10.1038/s41424-018-0013-8 }}</ref> 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.<ref name=Nguyen_DVT /> The risk of venous thromboembolism is high in ulcerative colitis due to hypercoagulability from inflammation, especially with active or extensive disease.<ref name=Cheng_VTE /> Additional risk factors may include surgery, hospitalization, pregnancy, the use of corticosteroids and tofacitinib, a JAK inhibitor.<ref name=Cheng_VTE />

[[Osteoporosis]] may occur related to systemic inflammation or prolonged steroid use in the treatment of UC, which increases the risk of bone fractures.<ref name="Colìa" /> [[Nail clubbing|Clubbing]], a deformity of the ends of the fingers, may occur.<ref name="Colìa" /> [[Amyloidosis]] may occur, especially with severe and poorly controlled disease, which usually presents with protein in the urine ([[proteinuria]]) and [[nephritic syndrome]].<ref name="Colìa" />

===Primary sclerosing cholangitis===
Ulcerative colitis (UC) has a significant association with [[primary sclerosing cholangitis]] (PSC), a progressive inflammatory disorder of small and large [[bile duct]]s. Up to 70-90% of people with primary sclerosing cholangitis have ulcerative colitis.<ref name=Langholz /> As many as 5% of people with UC may progress to develop primary sclerosing cholangitis.<ref name=Feuerstein_UC/><ref>{{cite journal | vauthors = Olsson R, Danielsson A, Järnerot G, Lindström E, Lööf L, Rolny P, Rydén BO, Tysk C, Wallerstedt S | title = Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis | journal = Gastroenterology | volume = 100 | issue = 5 Pt 1 | pages = 1319–1323 | date = May 1991 | pmid = 2013375 | doi = 10.1016/0016-5085(91)90784-I }}</ref> PSC is more common in men, and often begins between 30 and 40 years of age.<ref name=Feuerstein_UC/> 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. Results of [[endoscopic retrograde cholangiopancreatography|endoscopic retrograde cholangiography]] (ERC) may show bile ducts with thicker walls, areas of dilation or narrowing.  However, some patients with UC and PSC have inflammation that has significantly affected only ramified [[intrahepatic bile ducts]] of smaller diameter, also known as "small ducts", which are not visualized by ERC.<ref name=rasmussen1997>{{cite journal |last1=Rasmussen |first1=H. H. |last2=Fallingborg |first2=J. F. |last3=Mortensen |first3=P. B. |last4=Vyberg |first4=M. |last5=Tage-Jensen |first5=U. |last6=Rasmussen |first6=S. N. |date=June 1997 |title=Hepatobiliary dysfunction and primary sclerosing cholangitis in patients with Crohn's disease |url=https://pubmed.ncbi.nlm.nih.gov/9200295/ |journal=Scandinavian Journal of Gastroenterology |volume=32 |issue=6 |pages=604–610 |doi=10.3109/00365529709025107 |issn=0036-5521 |pmid=9200295}}</ref>{{rp|604, 609}}

In some cases, primary sclerosing cholangitis occurs several years before the bowel symptoms of ulcerative colitis develop.<ref name="Langholz" /> PSC does not parallel the onset, extent, duration, or activity of the colonic inflammation in ulcerative colitis.<ref name="Langholz" /> In addition, colectomy does not have an impact on the course of primary sclerosing cholangitis in individuals with UC.<ref name="Langholz" /> PSC is associated with an increased risk of colorectal cancer and [[cholangiocarcinoma]] (bile duct cancer).<ref name="Langholz" /><ref name="Feuerstein_UC" /> PSC is a progressive condition, and may result in cirrhosis of the liver.<ref name="Feuerstein_UC" /> No specific therapy has been proven to affect the long-term course of PSC.<ref name="Feuerstein_UC" />

==Causes==
{{Risk factors in CD vs. UC}}
Ulcerative colitis is an [[autoimmune disease]] characterized by [[T-cells]] infiltrating the colon.<ref name="Targeting Improves MSC Treatment of Inflammatory Bowel Disease">{{cite journal | vauthors = Ko IK, Kim BG, Awadallah A, Mikulan J, Lin P, Letterio JJ, Dennis JE | title = Targeting improves MSC treatment of inflammatory bowel disease | journal = Molecular Therapy | volume = 18 | issue = 7 | pages = 1365–1372 | date = July 2010 | pmid = 20389289 | pmc = 2911249 | doi = 10.1038/mt.2010.54 }}</ref> No direct causes for UC are known, but factors such as genetics, environment, and an overactive immune system play a role.<ref name=NIH2014>{{cite web|title=Ulcerative Colitis|url=https://www.niddk.nih.gov/health-information/digestive-diseases/ulcerative-colitis|website=NIDDK|access-date=3 August 2016|date=September 2014}}</ref> 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]]s and [[Genetic linkage|linkages]].<ref name=Orholm>{{cite journal | vauthors = Orholm M, Binder V, Sørensen TI, Rasmussen LP, Kyvik KO | title = Concordance of inflammatory bowel disease among Danish twins. Results of a nationwide study | journal = Scandinavian Journal of Gastroenterology | volume = 35 | issue = 10 | pages = 1075–1081 | date = October 2000 | pmid = 11099061 | doi = 10.1080/003655200451207 | s2cid = 218907577 }}</ref> In addition, the identical [[twin studies|twin]] [[Concordance (genetics)|concordance]] rate is 10%, whereas the [[dizygotic twin]] concordance rate is only 3%.<ref name=Orholm /><ref>{{cite journal | vauthors = Tysk C, Lindberg E, Järnerot G, Flodérus-Myrhed B | title = Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking | journal = Gut | volume = 29 | issue = 7 | pages = 990–996 | date = July 1988 | pmid = 3396969 | pmc = 1433769 | doi = 10.1136/gut.29.7.990 }}</ref> Between 8 and 14% of people with ulcerative colitis have a family history of inflammatory bowel disease.<ref name=Ungaro /> In addition, people with a first degree relative with UC have a four-fold increase in their risk of developing the disease.<ref name=Ungaro />

Twelve regions of the [[genome]] may be linked to UC, including, in the order of their discovery, chromosomes 16, 12, 6, 14, 5, 19, 1, and 3,<ref name=Baumgart/> but none of these [[Locus (genetics)|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.<ref>{{cite journal | vauthors = Cho JH, Nicolae DL, Ramos R, Fields CT, Rabenau K, Corradino S, Brant SR, Espinosa R, LeBeau M, Hanauer SB, Bodzin J, Bonen DK | title = Linkage and linkage disequilibrium in chromosome band 1p36 in American Chaldeans with inflammatory bowel disease | journal = Human Molecular Genetics | volume = 9 | issue = 9 | pages = 1425–1432 | date = May 2000 | pmid = 10814724 | doi = 10.1093/hmg/9.9.1425 | doi-access = free }}</ref> Some of the putative regions encode transporter proteins such as [[OCTN1]] and [[OCTN2]]. Other potential regions involve cell scaffolding proteins such as the [[Membrane-associated guanylate kinase|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.<ref name=Baumgart/>

Multiple autoimmune disorders are associated with ulcerative colitis, including [[celiac disease]],<ref name=Shah_Celiac>{{cite journal | vauthors = Shah A, Walker M, Burger D, Martin N, von Wulffen M, Koloski N, Jones M, Talley NJ, Holtmann GJ | title = Link Between Celiac Disease and Inflammatory Bowel Disease | journal = Journal of Clinical Gastroenterology | volume = 53 | issue = 7 | pages = 514–522 | date = August 2019 | pmid = 29762265 | doi = 10.1097/MCG.0000000000001033 | s2cid = 44102071 }}</ref> [[psoriasis]],<ref>{{cite journal | vauthors = Fu Y, Lee CH, Chi CC | title = Association of Psoriasis With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis | journal = JAMA Dermatology | volume = 154 | issue = 12 | pages = 1417–1423 | date = December 2018 | pmid = 30422277 | pmc = 6583370 | doi = 10.1001/jamadermatol.2018.3631 }}</ref> [[lupus erythematosus]],<ref>{{cite journal | vauthors = Katsanos KH, Voulgari PV, Tsianos EV | title = Inflammatory bowel disease and lupus: a systematic review of the literature | journal = Journal of Crohn's & Colitis | volume = 6 | issue = 7 | pages = 735–742 | date = August 2012 | pmid = 22504032 | doi = 10.1016/j.crohns.2012.03.005 | doi-access = free }}</ref> [[rheumatoid arthritis]],<ref name=Chen_RA>{{cite journal | vauthors = Chen Y, Chen L, Xing C, Deng G, Zeng F, Xie T, Gu L, Yang H | title = The risk of rheumatoid arthritis among patients with inflammatory bowel disease: a systematic review and meta-analysis | journal = BMC Gastroenterology | volume = 20 | issue = 1 | pages = 192 | date = June 2020 | pmid = 32552882 | pmc = 7301504 | doi = 10.1186/s12876-020-01339-3 | doi-access = free }}</ref> [[episcleritis]], and [[scleritis]].<ref name=Troncoso /> Ulcerative colitis is also associated with [[acute intermittent porphyria]].<ref>{{cite journal | vauthors = Sieg I, Beckh K, Kersten U, Doss MO | title = Manifestation of acute intermittent porphyria in patients with chronic inflammatory bowel disease | journal = Zeitschrift für Gastroenterologie | volume = 29 | issue = 11 | pages = 602–605 | date = November 1991 | pmid = 1771936 }}</ref>

===Environmental factors===
Many hypotheses have been raised for environmental factors contributing to the pathogenesis of ulcerative colitis, including [[Diet (nutrition)|diet]], [[breastfeeding]] and medications. Breastfeeding may have a protective effect in the development of ulcerative colitis.<ref name=Xu_Breastfeeding_UC>{{cite journal | vauthors = Xu L, Lochhead P, Ko Y, Claggett B, Leong RW, Ananthakrishnan AN | title = Systematic review with meta-analysis: breastfeeding and the risk of Crohn's disease and ulcerative colitis | journal = Alimentary Pharmacology & Therapeutics | volume = 46 | issue = 9 | pages = 780–789 | date = November 2017 | pmid = 28892171 | pmc = 5688338 | doi = 10.1111/apt.14291 }}</ref><ref>{{cite journal | vauthors = Corrao G, Tragnone A, Caprilli R, Trallori G, Papi C, Andreoli A, Di Paolo M, Riegler G, Rigo GP, Ferraù O, Mansi C, Ingrosso M, Valpiani D | title = Risk of inflammatory bowel disease attributable to smoking, oral contraception and breastfeeding in Italy: a nationwide case-control study. Cooperative Investigators of the Italian Group for the Study of the Colon and the Rectum (GISC) | journal = International Journal of Epidemiology | volume = 27 | issue = 3 | pages = 397–404 | date = June 1998 | pmid = 9698126 | doi = 10.1093/ije/27.3.397 | doi-access = free }}</ref> One study of [[isotretinoin]] found a small increase in the rate of UC.<ref>{{cite journal | vauthors = Wolverton SE, Harper JC | title = Important controversies associated with isotretinoin therapy for acne | journal = American Journal of Clinical Dermatology | volume = 14 | issue = 2 | pages = 71–76 | date = April 2013 | pmid = 23559397 | doi = 10.1007/s40257-013-0014-z | s2cid = 918753 }}</ref>

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 (statistics)|association]] of refined [[sugar]] on the number of people affected of ulcerative colitis.<ref>{{cite journal | vauthors = Järnerot G, Järnmark I, Nilsson K | title = Consumption of refined sugar by patients with Crohn's disease, ulcerative colitis, or irritable bowel syndrome | journal = Scandinavian Journal of Gastroenterology | volume = 18 | issue = 8 | pages = 999–1002 | date = November 1983 | pmid = 6673083 | doi = 10.3109/00365528309181832 }}</ref> High intake of [[unsaturated fat]] and [[vitamin B6]] may enhance the risk of developing ulcerative colitis.<ref name="Geerling 2000">{{cite journal | vauthors = Geerling BJ, Dagnelie PC, Badart-Smook A, Russel MG, Stockbrügger RW, Brummer RJ | title = Diet as a risk factor for the development of ulcerative colitis | journal = The American Journal of Gastroenterology | volume = 95 | issue = 4 | pages = 1008–1013 | date = April 2000 | doi = 10.1111/j.1572-0241.2000.01942.x | pmid = 10763951 | s2cid = 11295804 }}</ref> Other identified dietary factors that may influence the development and/or relapse of the disease include meat protein and alcoholic beverages.<ref name="Jowett 2004">{{cite journal | vauthors = Jowett SL, Seal CJ, Pearce MS, Phillips E, Gregory W, Barton JR, Welfare MR | title = Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study | journal = Gut | volume = 53 | issue = 10 | pages = 1479–1484 | date = October 2004 | pmid = 15361498 | pmc = 1774231 | doi = 10.1136/gut.2003.024828 }}</ref><ref name="Andersen 2012">{{cite journal | vauthors = Andersen V, Olsen A, Carbonnel F, Tjønneland A, Vogel U | title = Diet and risk of inflammatory bowel disease | journal = Digestive and Liver Disease | volume = 44 | issue = 3 | pages = 185–194 | date = March 2012 | pmid = 22055893 | doi = 10.1016/j.dld.2011.10.001 }}</ref> Specifically, sulfur has been investigated as being involved in the cause of ulcerative colitis, but this is controversial.<ref name="Tilg 2004">{{cite journal | vauthors = Tilg H, Kaser A | title = Diet and relapsing ulcerative colitis: take off the meat? | journal = Gut | volume = 53 | issue = 10 | pages = 1399–1401 | date = October 2004 | pmid = 15361484 | pmc = 1774255 | doi = 10.1136/gut.2003.035287 }}</ref> [[low-sulfur diet|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.<ref name="Moore 1998">{{cite journal | vauthors = Moore J, Babidge W, Millard S, Roediger W | title = Colonic luminal hydrogen sulfide is not elevated in ulcerative colitis | journal = Digestive Diseases and Sciences | volume = 43 | issue = 1 | pages = 162–165 | date = January 1998 | pmid = 9508519 | doi = 10.1023/A:1018848709769 | s2cid = 20919357 }}</ref><ref name="Jørgensen 2001">{{cite journal | vauthors = Jørgensen J, Mortensen PB | title = Hydrogen sulfide and colonic epithelial metabolism: implications for ulcerative colitis | journal = Digestive Diseases and Sciences | volume = 46 | issue = 8 | pages = 1722–1732 | date = August 2001 | pmid = 11508674 | doi = 10.1023/A:1010661706385 | s2cid = 30373968 }}</ref><ref name="Picton 2007">{{cite journal | vauthors = Picton R, Eggo MC, Langman MJ, Singh S | title = Impaired detoxication of hydrogen sulfide in ulcerative colitis? | journal = Digestive Diseases and Sciences | volume = 52 | issue = 2 | pages = 373–378 | date = February 2007 | pmid = 17216575 | doi = 10.1007/s10620-006-9529-y | s2cid = 22547709 }}</ref>

As a result of [[Perfluorooctanoic acid#Robert Bilott investigation|a class-action lawsuit and community settlement]] with [[DuPont]], three [[Epidemiology|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 [[Perfluorooctanoic acid|PFOA]] exposure and six health outcomes, one of which being ulcerative colitis.<ref>{{cite journal | last1 = Nicole | first1 = W. | title = PFOA and Cancer in a Highly Exposed Community: New Findings from the C8 Science Panel | doi = 10.1289/ehp.121-A340 | journal = Environmental Health Perspectives | volume = 121 | issue = 11–12 | pages = A340 | year = 2013 | pmid = 24284021| pmc = 3855507}}</ref>

===Alternative theories===
Levels of [[sulfate-reducing bacteria]] tend to be higher in persons 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 toxic effects of the hydrogen sulfide on the cells lining the intestine.<ref name=Roediger>{{cite journal | vauthors = Roediger WE, Moore J, Babidge W | title = Colonic sulfide in pathogenesis and treatment of ulcerative colitis | journal = Digestive Diseases and Sciences | volume = 42 | issue = 8 | pages = 1571–1579 | date = August 1997 | pmid = 9286219 | doi = 10.1023/A:1018851723920 | s2cid = 25496705 }}</ref>

Infection by ''[[Mycobacterium avium]]'', subspecies ''[[paratuberculosis]]'', has been proposed as the ultimate cause of both ulcerative colitis and Crohn's disease.<ref>{{cite journal | vauthors = Pierce ES | title = Could ''Mycobacterium avium'' subspecies ''paratuberculosis'' cause Crohn's disease, ulcerative colitis…and colorectal cancer? | journal = Infectious Agents and Cancer | volume = 13 | pages = 1 | date = 2018 | pmid = 29308085 | pmc = 5753485 | doi = 10.1186/s13027-017-0172-3 | doi-access = free }}</ref>
{{clear}}

==Pathophysiology==
{{Pathophysiology in CD vs. UC}}

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.<ref name=Levine>{{cite journal | vauthors = Levine J, Ellis CJ, Furne JK, Springfield J, Levitt MD | title = Fecal hydrogen sulfide production in ulcerative colitis | journal = The American Journal of Gastroenterology | volume = 93 | issue = 1 | pages = 83–87 | date = January 1998 | doi = 10.1111/j.1572-0241.1998.083_c.x | pmid = 9448181 | s2cid = 3141574 | df = dmy-all }}</ref> 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.<ref name=Roediger/>

Other proposed mechanisms driving the pathophysiology of ulcerative colitis involve an abnormal immune response to the normal [[gut microbiota]]. This involves abnormal activity of [[antigen presenting cells]] (APCs) including [[dendritic cells]] and [[macrophages]]. Normally, dendritic cells and macrophages patrol the intestinal epithelium and [[phagocytose]] (engulf and destroy) pathogenic microorganisms and present parts of the microorganism as [[antigens]] to [[T-cells]] to stimulate differentiation and activation of the T-cells.<ref name="Gros 2023">{{cite journal |last1=Gros |first1=Beatriz |last2=Kaplan |first2=Gilaad G. |title=Ulcerative Colitis in Adults: A Review |journal=JAMA |date=12 September 2023 |volume=330 |issue=10 |pages=951–965 |doi=10.1001/jama.2023.15389|pmid=37698559 |s2cid=261696018 }}</ref> 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.<ref name="Gros 2023" /> The TNF inhibitors, including [[infliximab]], [[adalimumab]] and [[golimumab]], are used to inhibit this step during the treatment of ulcerative colitis.<ref name="Gros 2023" /> After phagocytosing the microbe, the APCs then enter the [[superior mesenteric lymph node|mesenteric lymph nodes]] where they present antigens to naive T-cells while also releasing the pro-inflammatory cytokines [[interleukin 12|IL-12]] and [[interleukin-23|IL-23]] which lead to T cell differentiation into [[helper T cell|Th1]] and [[Th17]] T-cells.<ref name="Gros 2023" /> 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.<ref name="Gros 2023" /> 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.<ref name="Gros 2023" /> 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.<ref name="Gros 2023" /> While the medications [[ozanimod]] and [[etrasimod]] inhibit the [[sphingosine-1-phosphate receptor]] to prevent T-cell migration into the efferent lymphatic venules.<ref name="Gros 2023" /> 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 (biology)|transcription]], [[translation (biology)|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.<ref name="Gros 2023" />

==Diagnosis==
[[Image:Ulcerative colitis.jpg|thumb|[[Endoscopic]] 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.]]
[[Image:Ulcerative colitis (2) active.jpg|thumb|H&E stain of a colonic biopsy showing a crypt abscess, a classic finding in ulcerative colitis]]
The initial [[medical diagnosis|diagnostic]] workup for ulcerative colitis consists of a complete history and physical examination, assessment of signs and symptoms, laboratory tests and endoscopy.<ref name=Dassopoulos>{{cite journal | vauthors = Dassopoulos T, Cohen RD, Scherl EJ, Schwartz RM, Kosinski L, Regueiro MD | title = Ulcerative Colitis Care Pathway | journal = Gastroenterology | volume = 149 | issue = 1 | pages = 238–245 | date = July 2015 | pmid = 26025078 | doi = 10.1053/j.gastro.2015.05.036 }}</ref> 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.<ref name=":4">{{cite journal |last1=Nikolaus |first1=Susanna |last2=Schreiber |first2=Stefan |date=November 2007 |title=Diagnostics of inflammatory bowel disease |url=https://pubmed.ncbi.nlm.nih.gov/17983810/ |journal=Gastroenterology |volume=133 |issue=5 |pages=1670–1689 |doi=10.1053/j.gastro.2007.09.001 |issn=1528-0012 |pmid=17983810}}</ref>

Specific testing may include the following:<ref name="ACG_Guidelines_2019" /><ref name="emed2336">{{eMedicine|med|2336|Ulcerative colitis}}</ref>
* A [[complete blood count]] is done to check for anemia; [[thrombocytosis]], a high [[platelet]] count, is occasionally seen
* [[Electrolyte]] studies and [[renal function|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<ref name="Dassopoulos" />
* [[Inflammatory markers]], such as erythrocyte sedimentation rate or [[C-reactive protein]]
* Lower endoscopy to evaluate the rectum and distal large intestine ([[sigmoidoscopy]]) or entire colon and end of the [[small intestine]] (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.<ref name="ACG_Guidelines_2019" />

The [[simple clinical colitis activity index]] was created in 1998 and is used to assess the severity of symptoms.<ref name="WalmsleyAyres1998">{{cite journal | vauthors = Walmsley RS, Ayres RC, Pounder RE, Allan RN | title = A simple clinical colitis activity index | journal = Gut | volume = 43 | issue = 1 | pages = 29–32 | date = July 1998 | pmid = 9771402 | pmc = 1727189 | doi = 10.1136/gut.43.1.29 }}</ref><!-- please retain this historical, non-MEDRS citation -->

===Endoscopic===
[[Image:Chronic Ulcerative Colitis 1.jpg|thumb|Colonic [[pseudopolyps]] of a person with intractable UC, [[colectomy]] specimen]]
The best test for diagnosis of ulcerative colitis remains [[endoscopy]], 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.<ref name="Lamb" /> The physician may elect to limit the extent of the initial exam if severe colitis is encountered to minimize the risk of [[Bowel perforation|perforation]] 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.<ref name="Lamb">{{cite journal | vauthors = Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, Hayee B, Lomer MC, Parkes GC, Selinger C, Barrett KJ, Davies RJ, Bennett C, Gittens S, Dunlop MG, Faiz O, Fraser A, Garrick V, Johnston PD, Parkes M, Sanderson J, Terry H, Gaya DR, Iqbal TH, Taylor SA, Smith M, Brookes M, Hansen R, Hawthorne AB | title = British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults | journal = Gut | volume = 68 | issue = Suppl 3 | pages = s1–s106 | date = December 2019 | pmid = 31562236 | pmc = 6872448 | doi = 10.1136/gutjnl-2019-318484 }}</ref> 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.<ref>{{cite journal | vauthors = Politis DS, Papamichael K, Katsanos KH, Koulouridis I, Mavromati D, Tsianos EV, Christodoulou DK | title = Presence of pseudopolyps in ulcerative colitis is associated with a higher risk for treatment escalation | journal = Annals of Gastroenterology | volume = 32 | issue = 2 | pages = 168–173 | date = March 2019 | pmid = 30837789 | pmc = 6394261 | doi = 10.20524/aog.2019.0357 }}</ref>

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).<ref name=":1" />

===Histologic===
[[Image:Ulcerative colitis (2) endoscopic biopsy.jpg|thumb|left|Biopsy sample ([[H&E stain]]) that demonstrates marked [[lymphocyte|lymphocytic]] infiltration (blue/purple) of the [[intestinal mucosa]] and architectural distortion of the crypts.]]
[[File:Histopathology of a crypt abscess.jpg|thumb|Crypt abscess. H&E stain.]]
[[Biopsy|Biopsies]] 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 [[Intestinal crypt|crypt]] architecture, crypt abscesses, and inflammatory cells in the mucosa (lymphocytes, plasma cells, and granulocytes).<ref name="Feuerstein_UC" /> Unlike the transmural inflammation seen in Crohn's disease, the inflammation of ulcerative colitis is limited to the mucosa.<ref name="Feuerstein_UC" />

===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.<ref name="Ungaro" />

A [[complete blood count]] may demonstrate anemia, leukocytosis, or thrombocytosis.<ref name="Ungaro" /> 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]], [[Serum iron|iron]], [[total iron-binding capacity]] and [[transferrin saturation]]. Anemia may be due to a complication of treatment from azathioprine, which can cause low blood counts,<ref>{{cite web |title=Azathioprine Product Information |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017391s015lbl.pdf |website=Access FDA |publisher=Food and Drug Administration}}</ref> or sulfasalazine, which can result in folate deficiency. Thiopurine metabolites (from azathioprine) and a folate level can help.<ref>{{cite journal | vauthors = Dignass AU, Gasche C, Bettenworth D, Birgegård G, Danese S, Gisbert JP, Gomollon F, Iqbal T, Katsanos K, Koutroubakis I, Magro F, Savoye G, Stein J, Vavricka S | title = European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases | journal = Journal of Crohn's & Colitis | volume = 9 | issue = 3 | pages = 211–222 | date = March 2015 | pmid = 25518052 | doi = 10.1093/ecco-jcc/jju009 | doi-access = free }}</ref>

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.<ref name="ACG_Guidelines_2019">{{cite journal | vauthors = Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD | title = ACG Clinical Guideline: Ulcerative Colitis in Adults | journal = The American Journal of Gastroenterology | volume = 114 | issue = 3 | pages = 384–413 | date = March 2019 | pmid = 30840605 | doi = 10.14309/ajg.0000000000000152 | s2cid = 73473272 | doi-access = free }}</ref> [[Serum albumin]] may also be low related to inflammation, in addition to loss of protein in the GI tract associated with bleeding and colitis. [[Vitamin D deficiency|Low serum levels of vitamin D]] are associated with UC, although the significance of this finding is unclear.<ref>{{cite journal | vauthors = Del Pinto R, Pietropaoli D, Chandar AK, Ferri C, Cominelli F | title = Association Between Inflammatory Bowel Disease and Vitamin D Deficiency: A Systematic Review and Meta-analysis | journal = Inflammatory Bowel Diseases | volume = 21 | issue = 11 | pages = 2708–2717 | date = November 2015 | pmid = 26348447 | pmc = 4615394 | doi = 10.1097/MIB.0000000000000546 | doi-access = free }}</ref>

Specific antibody markers may be elevated in ulcerative colitis. Specifically, [[perinuclear antineutrophil cytoplasmic antibodies]] (pANCA) are found in 70 percent of cases of UC.<ref name="ACG_Guidelines_2019" /> 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.<ref name="ACG_Guidelines_2019" /><ref name="Feuerstein_UC" />

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.<ref name="ACG_Guidelines_2019" /> Fecal calprotectin is 88% sensitive and 79% specific for the diagnosis of ulcerative colitis.<ref name="ACG_Guidelines_2019" /> If the fecal calprotectin is low, the likelihood of inflammatory bowel disease are less than 1 percent.<ref name="Ungaro" /> [[Lactoferrin]] is an additional nonspecific marker of intestinal inflammation.<ref>{{cite journal | vauthors = Mosli MH, Zou G, Garg SK, Feagan SG, MacDonald JK, Chande N, Sandborn WJ, Feagan BG | title = C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis | journal = The American Journal of Gastroenterology | volume = 110 | issue = 6 | pages = 802–19; quiz 820 | date = June 2015 | pmid = 25964225 | doi = 10.1038/ajg.2015.120 | s2cid = 26111716 }}</ref>

=== 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.<ref>{{cite journal | vauthors = Bryant RV, Friedman AB, Wright EK, Taylor KM, Begun J, Maconi G, Maaser C, Novak KL, Kucharzik T, Atkinson NS, Asthana A, Gibson PR | title = Gastrointestinal ultrasound in inflammatory bowel disease: an underused resource with potential paradigm-changing application | journal = Gut | volume = 67 | issue = 5 | pages = 973–985 | date = May 2018 | pmid = 29437914 | doi = 10.1136/gutjnl-2017-315655 | s2cid = 3344377 }}</ref> Some studies demonstrated that bowel ultrasound is an accurate tool for assessing disease activity in people with ulcerative colitis.<ref>{{cite journal |last1=Allocca |first1=Mariangela |last2=Filippi |first2=Elisabetta |last3=Costantino |first3=Andrea |last4=Bonovas |first4=Stefanos |last5=Fiorino |first5=Gionata |last6=Furfaro |first6=Federica |last7=Peyrin-Biroulet |first7=Laurent |last8=Fraquelli |first8=Mirella |last9=Caprioli |first9=Flavio |last10=Danese |first10=Silvio |title=Milan ultrasound criteria are accurate in assessing disease activity in ulcerative colitis: external validation |journal=United European Gastroenterology Journal |date=May 2021 |volume=9 |issue=4 |pages=438–442 |doi=10.1177/2050640620980203 |pmid=33349199 |pmc=8259285 |doi-access=free }}</ref><ref>{{cite journal |last1=Allocca |first1=Mariangela |last2=Fiorino |first2=Gionata |last3=Bonovas |first3=Stefanos |last4=Furfaro |first4=Federica |last5=Gilardi |first5=Daniela |last6=Argollo |first6=Marjorie |last7=Magnoni |first7=Paola |last8=Peyrin-Biroulet |first8=Laurent |last9=Danese |first9=Silvio |title=Accuracy of Humanitas Ultrasound Criteria in Assessing Disease Activity and Severity in Ulcerative Colitis: A Prospective Study |journal=Journal of Crohn's and Colitis |date=28 November 2018 |volume=12 |issue=12 |pages=1385–1391 |doi=10.1093/ecco-jcc/jjy107 |pmid=30085066 |pmc=6260119 |doi-access=free }}</ref> Imaging is otherwise of limited use in diagnosing ulcerative colitis.<ref name="Ungaro" /><ref name="Feuerstein_UC" /> Magnetic resonance imaging (MRI) is necessary to diagnose underlying PSC.<ref name="Feuerstein_UC" />

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.<ref name=":4" />

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.<ref name=":4" />

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.<ref name=":4" />

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).<ref name=":4" />

=== 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|''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.<ref>{{cite journal | vauthors = Shirley DA, Moonah S | title = Fulminant Amebic Colitis after Corticosteroid Therapy: A Systematic Review | journal = PLOS Neglected Tropical Diseases | volume = 10 | issue = 7 | pages = e0004879 | date = July 2016 | pmid = 27467600 | pmc = 4965027 | doi = 10.1371/journal.pntd.0004879 | doi-access = free }}</ref>

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.<ref>{{cite journal | vauthors = Tremaine WJ | title = Is indeterminate colitis determinable? | journal = Current Gastroenterology Reports | volume = 14 | issue = 2 | pages = 162–165 | date = April 2012 | pmid = 22314810 | doi = 10.1007/s11894-012-0244-x | s2cid = 40346031 }}</ref> 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.<ref>{{cite journal |last1=Kim |first1=B. |last2=Barnett |first2=J. L. |last3=Kleer |first3=C. G. |last4=Appelman |first4=H. D. |date=November 1999 |title=Endoscopic and histological patchiness in treated ulcerative colitis |url=https://pubmed.ncbi.nlm.nih.gov/10566726/ |journal=The American Journal of Gastroenterology |volume=94 |issue=11 |pages=3258–3262 |doi=10.1111/j.1572-0241.1999.01533.x |issn=0002-9270 |pmid=10566726|hdl=2027.42/74642 |s2cid=11446833 |hdl-access=free }}</ref>

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.<ref>{{cite journal |last1=Woodruff |first1=J. M. |last2=Hansen |first2=J. A. |last3=Good |first3=R. A. |last4=Santos |first4=G. W. |last5=Slavin |first5=R. E. |date=December 1976 |title=The pathology of the graft-versus-host reaction (GVHR) in adults receiving bone marrow transplants |url=https://pubmed.ncbi.nlm.nih.gov/11596/ |journal=Transplantation Proceedings |volume=8 |issue=4 |pages=675–684 |issn=0041-1345 |pmid=11596}}</ref>

{{Findings in CD vs. UC}}

==Management==
{{Main|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.<ref>{{cite journal | vauthors = Chen JH, Andrews JM, Kariyawasam V, Moran N, Gounder P, Collins G, Walsh AJ, Connor S, Lee TW, Koh CE, Chang J, Paramsothy S, Tattersall S, Lemberg DA, Radford-Smith G, Lawrance IC, McLachlan A, Moore GT, Corte C, Katelaris P, Leong RW | title = Review article: acute severe ulcerative colitis - evidence-based consensus statements | journal = Alimentary Pharmacology & Therapeutics | volume = 44 | issue = 2 | pages = 127–144 | date = July 2016 | pmid = 27226344 | doi = 10.1111/apt.13670 | doi-access = free }}</ref>

For acute stages of the disease, a [[Low-fiber/low-residue diet|low fiber diet]] may be recommended.<ref name=webmd>{{cite web|url=https://www.webmd.com/ibd-crohns-disease/low-residue-diet-foods#2|title=Should You Try a Low-Residue Diet?|website=WebMD|date=25 October 2016|access-date=29 April 2017}}</ref><ref name=manual_cnm>{{cite book|title=Manual of Clinical Nutrition Management|publisher=Compass Group|date=2013|url=https://bscn2k15.weebly.com/uploads/1/2/9/2/12924787/manual_of_clinical_nutrition2013.pdf}}</ref><ref>Roncoroni L, Gori R, Elli L, et al. Nutrition in Patients with Inflammatory Bowel Diseases: A Narrative Review. Nutrients. 2022;14(4):751. Published 2022 Feb 10. doi:10.3390/nu14040751</ref>

===Medication===
The first-line maintenance medication for ulcerative colitis in remission is [[mesalazine]] (also known as mesalamine or 5-ASA).<ref name="Ham Moss 2012 pp. 113–123">{{cite journal | last1=Ham | first1=Maggie | last2=Moss | first2=Alan C | title=Mesalamine in the treatment and maintenance of remission of ulcerative colitis | journal=Expert Review of Clinical Pharmacology | volume=5 | issue=2 | date=2012 | issn=1751-2433 | pmid=22390554 | pmc=3314328 | doi=10.1586/ecp.12.2 | pages=113–123}}</ref><ref name="Raine Bonovas Burisch Kucharzik 2022 pp. 2–17">{{cite journal | last1=Raine | first1=Tim | last2=Bonovas | first2=Stefanos | last3=Burisch | first3=Johan | last4=Kucharzik | first4=Torsten | last5=Adamina | first5=Michel | last6=Annese | first6=Vito | last7=Bachmann | first7=Oliver | last8=Bettenworth | first8=Dominik | last9=Chaparro | first9=Maria | last10=Czuber-Dochan | first10=Wladyslawa | last11=Eder | first11=Piotr | last12=Ellul | first12=Pierre | last13=Fidalgo | first13=Catarina | last14=Fiorino | first14=Gionata | last15=Gionchetti | first15=Paolo | last16=Gisbert | first16=Javier P | last17=Gordon | first17=Hannah | last18=Hedin | first18=Charlotte | last19=Holubar | first19=Stefan | last20=Iacucci | first20=Marietta | last21=Karmiris | first21=Konstantinos | last22=Katsanos | first22=Konstantinos | last23=Kopylov | first23=Uri | last24=Lakatos | first24=Peter L | last25=Lytras | first25=Theodore | last26=Lyutakov | first26=Ivan | last27=Noor | first27=Nurulamin | last28=Pellino | first28=Gianluca | last29=Piovani | first29=Daniele | last30=Savarino | first30=Edoardo | last31=Selvaggi | first31=Francesco | last32=Verstockt | first32=Bram | last33=Spinelli | first33=Antonino | last34=Panis | first34=Yves | last35=Doherty | first35=Glen | title=ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment | journal=Journal of Crohn's and Colitis | volume=16 | issue=1 | date=28 January 2022 | issn=1873-9946 | doi=10.1093/ecco-jcc/jjab178 | pages=2–17| pmid=34635919 }}</ref> For patients with active disease limited to the [[Descending colon|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 [[corticosteroid]]s such as [[prednisone]] is also common in active disease, especially if remission is not achieved through mesalazine monotherapy,<ref name="Ham Moss 2012 pp. 113–123"/><ref name="Raine Bonovas Burisch Kucharzik 2022 pp. 2–17"/> but they are not used in long-term treatment as their risks then outweigh their benefits. Immunosuppressive medications such as [[azathioprine]] and [[Biopharmaceutical|biological agent]]s such as [[infliximab]], [[adalimumab]], [[ustekinumab]], [[vedolizumab]], or [[risankizumab]] are given in severe disease or if a patient cannot achieve remission with mesalazine and corticosteroids.<ref name=AGAClinicalPractice2020>{{cite journal | vauthors = Feuerstein JD, Isaacs KL, Schneider Y, Siddique SM, Falck-Ytter Y, Singh S | title = AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis | journal = Gastroenterology | volume = 158 | issue = 5 | pages = 1450–1461 | date = April 2020 | pmid = 31945371 | pmc = 7175923 | doi = 10.1053/j.gastro.2020.01.006 | doi-access = free }}</ref><ref name="Skyrizi FDA label">{{cite web | title=Skyrizi- risankizumab-rzaa kit | website=DailyMed | date=18 June 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7148c8eb-b39e-e20a-6494-a6df82392858 | access-date=2 November 2024}}</ref> As an alternative to mesalazine, one of its [[prodrug]]s such as [[sulfasalazine]] may be chosen for treatment of active disease or maintenance therapy,<ref name="Sandborn 2002 pp. 2939–2941">{{cite journal | last=Sandborn | first=W | title=Rational selection of oral 5-aminosalicylate formulations and prodrugs for the treatment of ulcerative colitis | journal=The American Journal of Gastroenterology | volume=97 | issue=12 | date=2002 | doi=10.1016/S0002-9270(02)05509-0 | pages=2939–2941| pmid=12492172 }}</ref> but the prodrugs have greater potential for serious side effects and have not been demonstrated to be superior to mesalazine in large trials.<ref name="Ko Singh Feuerstein Falck-Ytter 2019 pp. 748–764">{{cite journal | last1=Ko | first1=Cynthia W. | last2=Singh | first2=Siddharth | last3=Feuerstein | first3=Joseph D. | last4=Falck-Ytter | first4=Corinna | last5=Falck-Ytter | first5=Yngve | last6=Cross | first6=Raymond K. | last7=Crockett | first7=Seth | last8=Falck-Ytter | first8=Yngve | last9=Feuerstein | first9=Joseph | last10=Flamm | first10=Steven | last11=Inadomi | first11=John | last12=Ko | first12=Cynthia | last13=Muniraj | first13=Thiruvengadam | last14=O’Shea | first14=Robert | last15=Pandolfino | first15=John | last16=Patel | first16=Amit | last17=Sharaf | first17=Ravi | last18=Siddique | first18=Shazia | last19=Su | first19=Grace | last20=Wang | first20=Kenneth | last21=Weizman | first21=Adam | title=AGA Clinical Practice Guidelines on the Management of Mild-to-Moderate Ulcerative Colitis | journal=Gastroenterology | volume=156 | issue=3 | date=2019 | pmid=30576644 | pmc=6858922 | doi=10.1053/j.gastro.2018.12.009 | pages=748–764}}</ref>

A formulation of [[budesonide]] was approved by the U.S. [[Food and Drug Administration]] (FDA) for treatment of active ulcerative colitis in January 2013.<ref>{{cite news |title=FDA approves Uceris as ulcerative colitis treatment |url=https://www.healio.com/news/gastroenterology/20130115/santarus_10_3928_1081_597x_20130101_15_997579 |work=Healio Gastroenterology |date=15 January 2013}}</ref><ref>{{cite web |title=UCERIS (budesonide) extended release tablets label |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203634s000lbl.pdf |publisher=FDA}}</ref> 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.<ref>{{cite press release|url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-moderately-severely-active-ulcerative-colitis |title=FDA approves new treatment for moderately to severely active ulcerative colitis|website=U.S. [[Food and Drug Administration]] (FDA) |date=30 May 2018 |access-date=31 May 2018}}</ref> The evidence on [[methotrexate]] does not show a benefit in producing remission in people with ulcerative colitis.<ref>{{cite journal | vauthors = Chande N, Wang Y, MacDonald JK, McDonald JW | title = Methotrexate for induction of remission in ulcerative colitis | journal = The Cochrane Database of Systematic Reviews | volume = 8 | issue = 8 | pages = CD006618 | date = August 2014 | pmid = 25162749 | pmc = 6486224 | doi = 10.1002/14651858.CD006618.pub3 }}</ref> [[Cyclosporine]] is effective for severe UC<ref name=AGAClinicalPractice2020 /> and [[tacrolimus]] has also shown benefits.<ref>{{cite journal | vauthors = Krishnamoorthy R, Abrams KR, Guthrie N, Samuel S, Thomas T |s2cid=74798482 |title=PWE-237 Ciclosporin in acute severe ulcerative colitis: a meta-analysis |journal=Gut |date=28 May 2012 |volume=61 |issue=Suppl 2 |pages=A394.2–A394 |doi=10.1136/gutjnl-2012-302514d.237|doi-access=free }}</ref><ref>{{cite journal | vauthors = Ogata H, Kato J, Hirai F, Hida N, Matsui T, Matsumoto T, Koyanagi K, Hibi T | title = Double-blind, placebo-controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid-refractory ulcerative colitis | journal = Inflammatory Bowel Diseases | volume = 18 | issue = 5 | pages = 803–808 | date = May 2012 | pmid = 21887732 | doi = 10.1002/ibd.21853 | s2cid = 1294555 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lichtiger S, Present DH, Kornbluth A, Gelernt I, Bauer J, Galler G, Michelassi F, Hanauer S | title = Cyclosporine in severe ulcerative colitis refractory to steroid therapy | journal = The New England Journal of Medicine | volume = 330 | issue = 26 | pages = 1841–1845 | date = June 1994 | pmid = 8196726 | doi = 10.1056/NEJM199406303302601 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Weisshof R, Ollech JE, El Jurdi K, Yvellez OV, Cohen RD, Sakuraba A, Dalal S, Pekow J, Rubin DT | title = Ciclosporin Therapy After Infliximab Failure in Hospitalized Patients With Acute Severe Colitis is Effective and Safe | journal = Journal of Crohn's & Colitis | volume = 13 | issue = 9 | pages = 1105–1110 | date = September 2019 | pmid = 30726894 | pmc = 7327272 | doi = 10.1093/ecco-jcc/jjz032 }}</ref> [[Etrasimod]] was approved for medical use in the United States in October 2023.<ref>{{cite press release | title=U.S. FDA Approves Pfizer's Velsipity for Adults with Moderately to Severely Active Ulcerative Colitis (UC) | publisher=Pfizer | via=Business Wire | date=13 October 2023 | url=https://www.businesswire.com/news/home/20231012073213/en/ | access-date=13 October 2023}}</ref>

====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.<ref>{{cite journal | vauthors = Azad Khan AK, Piris J, Truelove SC | title = An experiment to determine the active therapeutic moiety of sulphasalazine | journal = Lancet | volume = 2 | issue = 8044 | pages = 892–895 | date = October 1977 | pmid = 72239 | doi = 10.1016/s0140-6736(77)90831-5 | s2cid = 44785199 }}</ref>  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.<ref>{{cite journal | vauthors = Murray A, Nguyen TM, Parker CE, Feagan BG, MacDonald JK | title = Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 8 | pages = CD000543 | date = August 2020 | pmid = 32786164 | pmc = 8189994 | doi = 10.1002/14651858.CD000543.pub5 }}</ref><ref>{{cite journal | vauthors = Murray A, Nguyen TM, Parker CE, Feagan BG, MacDonald JK | title = Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 8 | pages = CD000544 | date = August 2020 | pmid = 32856298 | pmc = 8094989 | doi = 10.1002/14651858.CD000544.pub5 }}</ref>  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.<ref>{{cite journal | vauthors = Marshall JK, Thabane M, Steinhart AH, Newman JR, Anand A, Irvine EJ | title = Rectal 5-aminosalicylic acid for maintenance of remission in ulcerative colitis | journal = The Cochrane Database of Systematic Reviews | volume = 11 | pages = CD004118 | date = November 2012 | pmid = 23152224 | doi = 10.1002/14651858.CD004118.pub2 }}</ref>

====Biologics====
Biologic treatments such as the [[TNF inhibitor]]s [[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.<ref name=Hir2015/> 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.<ref>{{cite journal | vauthors = Salahudeen MS | title = A review of current evidence allied to step-up and top-down medication therapy in inflammatory bowel disease | journal = Drugs of Today | volume = 55 | issue = 6 | pages = 385–405 | date = June 2019 | pmid = 31250843 | doi = 10.1358/dot.2019.55.6.2969816 | s2cid = 195763151 }}</ref>

Unlike aminosalicylates, biologics can cause serious side effects such as an increased risk of developing extra-intestinal cancers,<ref name=AxelradLichtiger2016>{{cite journal | vauthors = Axelrad JE, Lichtiger S, Yajnik V | title = Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment | journal = World Journal of Gastroenterology | volume = 22 | issue = 20 | pages = 4794–4801 | date = May 2016 | pmid = 27239106 | pmc = 4873872 | doi = 10.3748/wjg.v22.i20.4794 | type = Review | doi-access = free }}</ref> [[heart failure]]; and weakening of the immune system, resulting in a [[Immunodeficiency|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.<ref>{{cite journal | vauthors = Stevens JP, Ballengee CR, Chandradevan R, Thompson AB, Schoen BT, Kugathasan S, Sauer CG | title = Performance of Interferon-Gamma Release Assays for Tuberculosis Screening in Pediatric Inflammatory Bowel Disease | journal = Journal of Pediatric Gastroenterology and Nutrition | volume = 69 | issue = 4 | pages = e111–e116 | date = October 2019 | pmid = 31261245 | doi = 10.1097/MPG.0000000000002428 | s2cid = 195771593 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lee CK, Wong SH, Lui G, Tang W, Tam LS, Ip M, Hung E, Chen M, Wu JC, Ng SC | title = A Prospective Study to Monitor for Tuberculosis During Anti-tumour Necrosis Factor Therapy in Patients With Inflammatory Bowel Disease and Immune-mediated Inflammatory Diseases | journal = Journal of Crohn's & Colitis | volume = 12 | issue = 8 | pages = 954–962 | date = July 2018 | pmid = 29757355 | doi = 10.1093/ecco-jcc/jjy057 | s2cid = 21673794 | doi-access = free }}</ref>

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.<ref>{{cite journal |last1=Sandborn |first1=William J. |last2=Vermeire |first2=Séverine |last3=Peyrin-Biroulet |first3=Laurent |last4=Dubinsky |first4=Marla C. |last5=Panes |first5=Julian |last6=Yarur |first6=Andres |last7=Ritter |first7=Timothy |last8=Baert |first8=Filip |last9=Schreiber |first9=Stefan |last10=Sloan |first10=Sheldon |last11=Cataldi |first11=Fabio |last12=Shan |first12=Kevin |last13=Rabbat |first13=Christopher J. |last14=Chiorean |first14=Michael |last15=Wolf |first15=Douglas C. |date=8 April 2023 |title=Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies |journal=The Lancet |language=English |volume=401 |issue=10383 |pages=1159–1171 |doi=10.1016/S0140-6736(23)00061-2 |issn=0140-6736 |pmid=36871574|s2cid=257286271 |doi-access=free }}</ref>

====Nicotine====
Unlike [[Crohn's disease]], ulcerative colitis has a lesser chance of affecting smokers than non-smokers.<ref>{{cite journal | vauthors = Calkins BM | title = A meta-analysis of the role of smoking in inflammatory bowel disease | journal = Digestive Diseases and Sciences | volume = 34 | issue = 12 | pages = 1841–1854 | date = December 1989 | pmid = 2598752 | doi = 10.1007/BF01536701 | s2cid = 5775169 }}</ref><ref>{{cite journal | vauthors = Lakatos PL, Szamosi T, Lakatos L | title = Smoking in inflammatory bowel diseases: good, bad or ugly? | journal = World Journal of Gastroenterology | volume = 13 | issue = 46 | pages = 6134–6139 | date = December 2007 | pmid = 18069751 | pmc = 4171221 | doi = 10.3748/wjg.13.6134 | doi-access = free }}</ref> In select individuals with a history of previous tobacco use, resuming low dose smoking may improve signs and symptoms of active ulcerative colitis,<ref>{{cite journal | vauthors = Calabrese E, Yanai H, Shuster D, Rubin DT, Hanauer SB | title = Low-dose smoking resumption in ex-smokers with refractory ulcerative colitis | journal = Journal of Crohn's & Colitis | volume = 6 | issue = 7 | pages = 756–762 | date = August 2012 | pmid = 22398093 | doi = 10.1016/j.crohns.2011.12.010 | doi-access = free }}</ref> but it is not recommended due to the overwhelmingly negative [[health effects of tobacco]].<ref name=Cosnes2004>{{cite journal | vauthors = Cosnes J | title = Tobacco and IBD: relevance in the understanding of disease mechanisms and clinical practice | journal = Best Practice & Research. Clinical Gastroenterology | volume = 18 | issue = 3 | pages = 481–496 | date = June 2004 | pmid = 15157822 | doi = 10.1016/j.bpg.2003.12.003 }}</ref> Studies using a [[transdermal nicotine]] patch have shown clinical and histological improvement.<ref>{{cite journal | vauthors = Guslandi M | title = Nicotine treatment for ulcerative colitis | journal = British Journal of Clinical Pharmacology | volume = 48 | issue = 4 | pages = 481–484 | date = October 1999 | pmid = 10583016 | pmc = 2014383 | doi = 10.1046/j.1365-2125.1999.00039.x | df = dmy-all }}</ref> 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.<ref>{{cite journal | vauthors = Sandborn WJ, Tremaine WJ, Offord KP, Lawson GM, Petersen BT, Batts KP, Croghan IT, Dale LC, Schroeder DR, Hurt RD | title = Transdermal nicotine for mildly to moderately active ulcerative colitis. A randomized, double-blind, placebo-controlled trial | journal = Annals of Internal Medicine | volume = 126 | issue = 5 | pages = 364–371 | date = March 1997 | pmid = 9054280 | doi = 10.7326/0003-4819-126-5-199703010-00004 | s2cid = 25745900 }}</ref> However, nicotine therapy is generally not recommended due to side effects and inconsistent results.<ref>{{cite journal | vauthors = Bonapace CR, Mays DA | title = The effect of mesalamine and nicotine in the treatment of inflammatory bowel disease | journal = The Annals of Pharmacotherapy | volume = 31 | issue = 7–8 | pages = 907–913 | date = 1997 | pmid = 9220055 | doi = 10.1177/106002809703100719 | s2cid = 24122049 }}</ref><ref>{{cite journal | vauthors = Kennedy LD | title = Nicotine therapy for ulcerative colitis | journal = The Annals of Pharmacotherapy | volume = 30 | issue = 9 | pages = 1022–1023 | date = September 1996 | pmid = 8876866 }}</ref><ref>{{cite journal | vauthors = Rubin DT, Hanauer SB | title = Smoking and inflammatory bowel disease | journal = European Journal of Gastroenterology & Hepatology | volume = 12 | issue = 8 | pages = 855–862 | date = August 2000 | pmid = 10958212 | doi = 10.1097/00042737-200012080-00004 }}</ref>

====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.<ref name="ReferenceA">{{cite journal | vauthors = Goddard AF, James MW, McIntyre AS, Scott BB | title = Guidelines for the management of iron deficiency anaemia | journal = Gut | volume = 60 | issue = 10 | pages = 1309–1316 | date = October 2011 | pmid = 21561874 | doi = 10.1136/gut.2010.228874 | collaboration = British Society of Gastroenterology | doi-access = free }}</ref> 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.<ref name="pmid17985376">{{cite journal | vauthors = Gasche C, Berstad A, Befrits R, Beglinger C, Dignass A, Erichsen K, Gomollon F, Hjortswang H, Koutroubakis I, Kulnigg S, Oldenburg B, Rampton D, Schroeder O, Stein J, Travis S, Van Assche G | title = Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases | journal = Inflammatory Bowel Diseases | volume = 13 | issue = 12 | pages = 1545–1553 | date = December 2007 | pmid = 17985376 | doi = 10.1002/ibd.20285 | doi-access = free }}</ref> Others require oral iron to be used first, as people eventually respond and many will tolerate the side effects.<ref name="ReferenceA"/><ref name=Mowat2011>{{cite journal | vauthors = Mowat C, Cole A, Windsor A, Ahmad T, Arnott I, Driscoll R, Mitton S, Orchard T, Rutter M, Younge L, Lees C, Ho GT, Satsangi J, Bloom S | title = Guidelines for the management of inflammatory bowel disease in adults | journal = Gut | volume = 60 | issue = 5 | pages = 571–607 | date = May 2011 | pmid = 21464096 | doi = 10.1136/gut.2010.224154 | s2cid = 8269837 }}</ref>

====Anticholinergics====
[[Anticholinergic]] drugs, more specifically [[muscarinic antagonist]]s, 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 [[Muscle tone|intestinal tone]].<ref name="Can Med Assoc J p. ">{{cite journal | title=Drugs for Ulcerative Colitis | journal=Canadian Medical Association Journal | date=1964 | publisher=Can Med Assoc J | volume=91 | issue=21 | issn=0008-4409 | pmid=14229762 | author1=O'SULLIVAN PM | pages=1123–1124 | pmc=1928363 }}</ref><ref name="Camilleri Szarka 2008 pp. 1108–1156">{{cite book | last1=Camilleri | first1=Michael | last2=Szarka | first2=Lawrence | title=Textbook of Gastroenterology | chapter=Dysmotility of the Small Intestine and Colon | publisher=Wiley | date=14 November 2008 | isbn=978-1-4051-6911-0 | doi=10.1002/9781444303254.ch47 | pages=1108–1156| s2cid=83791469 }}</ref> Some medical authorities suggest over-the-counter anticholinergic drugs as potential helpful treatments for abdominal cramping in mild ulcerative colitis.<ref name="Amanda Fernandez, OMS IV Ronald Januchowski, DO, FACOFP 2020 pp. 10–16">{{cite journal | author=Amanda Fernandez, OMS IV | author2=Ronald Januchowski, DO, FACOFP | title=Osteopathic Primary Care Treatment Options for Ulcerative Colitis | journal=Osteopathic Family Physician | volume=12 | issue=3 | date=30 April 2020 | issn=1877-573X | doi=10.33181/12031 | pages=10–16| s2cid=219029672 }}</ref> 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.<ref name="Sedano Quera Simian Yarur 2019 pp. 943–955">{{cite journal | last1=Sedano | first1=Rocío | last2=Quera | first2=Rodrigo | last3=Simian | first3=Daniela | last4=Yarur | first4=Andres J. | title=An approach to acute severe ulcerative colitis | journal=Expert Review of Gastroenterology & Hepatology | publisher=Informa UK Limited | volume=13 | issue=10 | date=3 October 2019 | issn=1747-4124 | doi=10.1080/17474124.2019.1681974 | pages=943–955| pmid=31648574 | s2cid=204891274 }}</ref> 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.<ref name="Desai Elnaggar Hanfy Doshi 2020 pp. 203–210">{{cite journal | last1=Desai | first1=Jiten | last2=Elnaggar | first2=Mohamed | last3=Hanfy | first3=Ahmed A. | last4=Doshi | first4=Rajkumar | title=Toxic Megacolon: Background, Pathophysiology, Management Challenges and Solutions | journal=Clinical and Experimental Gastroenterology | volume=13 | date=19 May 2020 | pmid=32547151 | pmc=7245441 | doi=10.2147/CEG.S200760 | pages=203–210 | doi-access=free }}</ref>

=== 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.<ref>Toruner, M.; Loftus, E.V.; Harmsen, W.S.; Zinsmeister, A.R.; Orenstein, R.; Sandborn, W.J.; Colombel, J.; Egan, L.J. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 2008, 134, 929–936</ref>
Many of these potentially harmful diseases, such as [[Hepatitis B]], [[Influenza]], [[chickenpox]], [[Varicella zoster virus|herpes zoster virus]], [[pneumococcal pneumonia]], or [[Human papillomavirus infection|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.<ref>Farraye, F.A.; Melmed, G.Y.; Lichtenstein, G.R.; Kane, S.V. ACG Clinical Guideline: Preventive Care in Inflammatory Bowel Disease. Am. J. Gastroenterol. 2017, 112, 241–258.</ref><ref>Kucharzik, T.; Ellul, P.; Greuter, T.; Rahier, J.F.; Verstockt, B.; Abreu, C.; Albuquerque, A.; Allocca, M.; Esteve, M.; Farraye, F.A.; et al. ECCO Guidelines on the Prevention, Diagnosis, and Management of Infections in Inflammatory Bowel Disease. J. Crohn’s Colitis 2021, 15, 879–913.</ref> 
Compared to the rest of the population, patients affected by IBD are known to be at higher risk of contracting some vaccine-preventable diseases.<ref>Ananthakrishnan, A.N.; McGinley, E.L. Infection-related hospitalizations are associated with increased mortality in patients with inflammatory bowel diseases. J. Crohn’s Colitis 2013, 7, 107–112.</ref> Patients treated with [[Janus kinase inhibitor]] showed higher risk of  [[Shingles]].<ref>Winthrop, K.L.; Melmed, G.Y.; Vermeire, S.; Long, M.D.; Chan, G.; Pedersen, R.D.; Lawendy, N.; Thorpe, A.J.; Nduaka, C.I.; Su, C. Herpes Zoster Infection in Patients with Ulcerative Colitis Receiving Tofacitinib. Inflamm. Bowel Dis. 2018, 24, 2258–2265</ref>  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.<ref>Malhi, G.; Rumman, A.; Thanabalan, R.; Croitoru, K.; Silverberg, M.S.; Steinhart, A.H.; Nguyen, G.C. Vaccination in inflammatory bowel disease patients: Attitudes, knowledge, and uptake. J. Crohn’s Colitis 2015, 9, 439–444.</ref><ref>Costantino, A.; Michelon, M.; Noviello, D.; Macaluso, F.S.; Leone, S.; Bonaccorso, N.; Costantino, C.; Vecchi, M.; Caprioli, F., on behalf of AMICI Scientific Board. Attitudes towards Vaccinations in a National Italian Cohort of Patients with Inflammatory Bowel Disease. Vaccines 2023, 11, 1591.</ref>

===Surgery===
{{Treatment in CD vs. UC}}
Unlike in Crohn's disease, the gastrointestinal aspects of ulcerative colitis can generally be cured by [[colectomy|surgical removal of the large intestine]], though extraintestinal symptoms may persist. This procedure is necessary in the event of: [[exsanguination|exsanguinating]] [[internal bleeding|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 the quality of life.<ref name=":1" />

The removal of the entire large intestine, known as a [[proctocolectomy]], results in a permanent ileostomy – where a [[Stoma (medicine)|stoma]] is created by pulling the terminal ileum through the abdomen. Intestinal contents are emptied into a removable [[Ostomy pouching system|ostomy bag]] which is secured around the stoma using adhesive.<ref>{{cite web |title=Living with a stoma |url=https://www.ibdrelief.com/living-with-ibd/living-with-a-stoma |publisher=IBD Relief}}</ref>

Another surgical option for ulcerative colitis that is affecting most of the large bowel is called the [[ileo-anal pouch|ileal pouch-anal anastomosis (IPAA)]]. This is a two- or three-step procedure. In a three-step procedure, the first surgery is a [[Subtotal colectomy|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 [[Proctocolectomy|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.<ref name=":1" />

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 4–6 bowel movements after one year post-op. While many patients have success with this procedure, there are a number of known complications. [[Pouchitis]], 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.<ref>{{cite web |title=Colectomy Not a Final Cure for Ulcerative Colitis, Data Show |url=https://www.mdedge.com/internalmedicine/article/11622/gastroenterology/colectomy-not-final-cure-ulcerative-colitis-data |website=www.mdedge.com |access-date=15 December 2019 |language=en}}</ref><ref>{{cite journal | vauthors = Pappou EP, Kiran RP | title = The Failed J Pouch | journal = Clinics in Colon and Rectal Surgery | volume = 29 | issue = 2 | pages = 123–129 | date = June 2016 | pmid = 27247537 | pmc = 4882179 | doi = 10.1055/s-0036-1580724 }}</ref>

The risk of cancer arising from an ileal pouch anal anastomosis is low.<ref name=Clarke /> However, annual surveillance with [[pouchoscopy]] 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.<ref name=Clarke>{{cite journal | vauthors = Clarke WT, Feuerstein JD | title = Colorectal cancer surveillance in inflammatory bowel disease: Practice guidelines and recent developments | journal = World Journal of Gastroenterology | volume = 25 | issue = 30 | pages = 4148–4157 | date = August 2019 | pmid = 31435169 | pmc = 6700690 | doi = 10.3748/wjg.v25.i30.4148 | s2cid = 201114672 | doi-access = free }}</ref>

===Bacterial recolonization===
In a number of randomized clinical trials, [[probiotics]] have demonstrated the potential to be helpful in the treatment of ulcerative colitis. Specific types of probiotics such as [[Escherichia coli Nissle 1917|''Escherichia coli'' Nissle]] have been shown to induce remission in some people for up to a year.<ref name=Fedorak>{{cite journal | vauthors = Fedorak RN | title = Probiotics in the management of ulcerative colitis | journal = Gastroenterology & Hepatology | volume = 6 | issue = 11 | pages = 688–690 | date = November 2010 | pmid = 21437015 | pmc = 3033537 }}</ref>

A [[Cochrane (organisation)|Cochrane]] review of [[controlled trials]] using various probiotics found low-certainty evidence that probiotic supplements may increase the probability of clinical remission.<ref name=":5">{{cite journal |last1=Kaur |first1=Lakhbir |last2=Gordon |first2=Morris |last3=Baines |first3=Patricia Anne |last4=Iheozor-Ejiofor |first4=Zipporah |last5=Sinopoulou |first5=Vasiliki |last6=Akobeng |first6=Anthony K |date=4 March 2020 |editor-last=Cochrane IBD Group |title=Probiotics for induction of remission in ulcerative colitis |journal=Cochrane Database of Systematic Reviews |volume=3 |issue=3 |pages=CD005573 |language=en |doi=10.1002/14651858.CD005573.pub3 |pmc=7059959 |pmid=32128795}}</ref> 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.<ref name=":5" /> Although there was no clear evidence of greater remission when probiotic supplements were compared with [[Mesalazine|5‐aminosalicylic acid]] treatment as a [[monotherapy]], the likelihood of remission was 22% higher if probiotics were used in combination with 5-aminosalicylic acid therapy.<ref name=":5" />

It is unclear whether probiotics help to prevent future relapse in people with stable disease activity, either as a monotherapy or [[combination therapy]].<ref>{{cite journal |last1=Iheozor-Ejiofor |first1=Zipporah |last2=Kaur |first2=Lakhbir |last3=Gordon |first3=Morris |last4=Baines |first4=Patricia Anne |last5=Sinopoulou |first5=Vasiliki |last6=Akobeng |first6=Anthony K |date=4 March 2020 |editor-last=Cochrane IBD Group |title=Probiotics for maintenance of remission in ulcerative colitis |journal=Cochrane Database of Systematic Reviews |volume=3 |issue=3 |pages=CD007443 |language=en |doi=10.1002/14651858.CD007443.pub3 |pmc=7059960 |pmid=32128794}}</ref>

[[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.<ref name="pmid24257037">{{cite journal | vauthors = Borody TJ, Brandt LJ, Paramsothy S | title = Therapeutic faecal microbiota transplantation: current status and future developments | journal = Current Opinion in Gastroenterology | volume = 30 | issue = 1 | pages = 97–105 | date = January 2014 | pmid = 24257037 | pmc = 3868025 | doi = 10.1097/MOG.0000000000000027 }}</ref> Other studies found a benefit from using fecal microbiota transplantation.<ref>{{cite journal | vauthors = Narula N, Kassam Z, Yuan Y, Colombel JF, Ponsioen C, Reinisch W, Moayyedi P | title = Systematic Review and Meta-analysis: Fecal Microbiota Transplantation for Treatment of Active Ulcerative Colitis | journal = Inflammatory Bowel Diseases | volume = 23 | issue = 10 | pages = 1702–1709 | date = October 2017 | pmid = 28906291 | doi = 10.1097/MIB.0000000000001228 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Shi Y, Dong Y, Huang W, Zhu D, Mao H, Su P | title = Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis | journal = PLOS ONE | volume = 11 | issue = 6 | pages = e0157259 | date = 2016 | pmid = 27295210 | pmc = 4905678 | doi = 10.1371/journal.pone.0157259 | doi-access = free | bibcode = 2016PLoSO..1157259S }}</ref><ref>{{cite journal | vauthors = Costello SP, Hughes PA, Waters O, Bryant RV, Vincent AD, Blatchford P, Katsikeros R, Makanyanga J, Campaniello MA, Mavrangelos C, Rosewarne CP, Bickley C, Peters C, Schoeman MN, Conlon MA, Roberts-Thomson IC, Andrews JM | title = Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial | journal = JAMA | volume = 321 | issue = 2 | pages = 156–164 | date = January 2019 | pmid = 30644982 | pmc = 6439766 | doi = 10.1001/jama.2018.20046 }}</ref>

===Alternative medicine===
A variety of alternative medicine therapies have been used for ulcerative colitis, with inconsistent results. [[Turmeric|Curcumin (turmeric)]] therapy, in conjunction with taking the medications [[Mesalazine|mesalamine]] or [[sulfasalazine]], may be effective and safe for maintaining remission in people with quiescent ulcerative colitis.<ref>{{cite journal | vauthors = Hanai H, Iida T, Takeuchi K, Watanabe F, Maruyama Y, Andoh A, Tsujikawa T, Fujiyama Y, Mitsuyama K, Sata M, Yamada M, Iwaoka Y, Kanke K, Hiraishi H, Hirayama K, Arai H, Yoshii S, Uchijima M, Nagata T, Koide Y | title = Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial | journal = Clinical Gastroenterology and Hepatology | volume = 4 | issue = 12 | pages = 1502–1506 | date = December 2006 | pmid = 17101300 | doi = 10.1016/j.cgh.2006.08.008 | url = http://www.cghjournal.org/article/S1542356506008007/pdf }}</ref><ref name=Kumar /> The effect of [[Turmeric|curcumin]] therapy alone on quiescent ulcerative colitis is unknown.<ref name=Kumar>{{cite journal | vauthors = Kumar S, Ahuja V, Sankar MJ, Kumar A, Moss AC | title = Curcumin for maintenance of remission in ulcerative colitis | journal = The Cochrane Database of Systematic Reviews | volume = 10 | pages = CD008424 | date = October 2012 | pmid = 23076948 | pmc = 4001731 | doi = 10.1002/14651858.CD008424.pub2 }}</ref>

Treatments using [[Cannabis (drug)|cannabis]] or cannabis oil are uncertain. So far, studies have not determined its effectiveness and safety.<ref>{{cite journal | vauthors = Kafil TS, Nguyen TM, MacDonald JK, Chande N | title = Cannabis for the treatment of ulcerative colitis | journal = The Cochrane Database of Systematic Reviews | volume = 11 | pages = CD012954 | date = November 2018 | issue = 11 | pmid = 30406638 | pmc = 6516819 | doi = 10.1002/14651858.CD012954.pub2 }}</ref>

=== Abdominal pain management ===
Many interventions have been considered to manage abdominal pain in people with ulcerative colitis, including [[FODMAP]]s diet, [[Relaxation technique|relaxation]] training, [[yoga]], [[kefir]] diet and stellate [[Ganglionic blocker|ganglion block]] treatment. It is unclear whether any of these are safe or effective at improving pain or reducing [[anxiety]] and [[Depression (mood)|depression]].<ref>{{cite journal | vauthors = Sinopoulou V, Gordon M, Dovey TM, Akobeng AK | title = Interventions for the management of abdominal pain in ulcerative colitis | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 7 | pages = CD013589 | date = July 2021 | pmid = 34291816 | pmc = 8407332 | doi = 10.1002/14651858.CD013589.pub2 | collaboration = Cochrane Gut Group }}</ref>

==== Nutrition ====

Diet can play a role in symptoms of patients with ulcerative colitis.<ref>De Souza, H.; Fiocchi, C.; Iliopoulos, D. The IBD interactome: An integrated view of aetiology, pathogenesis and therapy. Nat. Rev. Gastroenterol. Hepatol. 2017, 14, 739–749</ref>

The most avoided foods by patients are spicy foods, dairy products, alcohol, fruits and vegetables and carbonated beverages; these foods are mainly avoided during remission and to prevent relapse. In some cases, especially in the flares 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.<ref>{{cite journal |last1=Roncoroni |first1=Leda |last2=Gori |first2=Rachele |last3=Elli |first3=Luca |last4=Tontini |first4=Gian Eugenio |last5=Doneda |first5=Luisa |last6=Norsa |first6=Lorenzo |last7=Cuomo |first7=Marialaura |last8=Lombardo |first8=Vincenza |last9=Scricciolo |first9=Alice |last10=Caprioli |first10=Flavio |last11=Costantino |first11=Andrea |last12=Scaramella |first12=Lucia |last13=Vecchi |first13=Maurizio |title=Nutrition in Patients with Inflammatory Bowel Diseases: A Narrative Review |journal=Nutrients |date=10 February 2022 |volume=14 |issue=4 |pages=751 |doi=10.3390/nu14040751 |pmid=35215401 |pmc=8879392 |issn=2072-6643 |doi-access=free }}{{Creative Commons text attribution notice|cc=by4|from this source=yes}}</ref>

===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]].<ref name="doi.org">Fracas E, Costantino A, Vecchi M, Buoli M. Depressive and Anxiety Disorders in Patients with Inflammatory Bowel Diseases: Are There Any Gender Differences? International Journal of Environmental Research and Public Health. 2023; 20(13):6255. https://doi.org/10.3390/ijerph20136255</ref><ref>Barberio B, Zamani M, Black CJ, Savarino EV, Ford AC. Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2021 May;6(5):359-370. doi: 10.1016/S2468-1253(21)00014-5</ref>

A meta analysis of interventions to improve mood (including talking therapy, [[antidepressant]]s, 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.<ref>{{Cite journal |last1=Seaton |first1=Natasha |last2=Hudson |first2=Joanna |last3=Harding |first3=Sophie |last4=Norton |first4=Sam |last5=Mondelli |first5=Valeria |last6=Jones |first6=Annie S.K. |last7=Moss-Morris |first7=Rona |date=2 February 2024 |title=Do interventions for mood improve inflammatory biomarkers in inflammatory bowel disease?: a systematic review and meta-analysis |url=https://doi.org/10.1016/j.ebiom.2023.104910 |journal=eBioMedicine |volume=100 |pages=104910 |doi=10.1016/j.ebiom.2023.104910 |issn=2352-3964 |pmc=10878994 |pmid=38272759}}</ref><ref>{{Cite journal |date=17 July 2024 |title=Improving mood reduces inflammation in inflammatory bowel disease |url=https://evidence.nihr.ac.uk/alert/improving-mood-reduces-inflammation-in-inflammatory-bowel-disease/ |journal=NIHR Evidence|doi=10.3310/nihrevidence_63192 }}</ref>

==Prognosis==
Poor prognostic factors include: age < 40 years upon diagnosis, extensive colitis, severe colitis on endoscopy, prior hospitalization, elevated CRP and low serum albumin.<ref name=ACG_Guidelines_2019 />

===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.<ref>{{cite journal | vauthors = Kevans D, Murthy S, Mould DR, Silverberg MS | title = Accelerated Clearance of Infliximab is Associated With Treatment Failure in Patients With Corticosteroid-Refractory Acute Ulcerative Colitis | journal = Journal of Crohn's & Colitis | volume = 12 | issue = 6 | pages = 662–669 | date = May 2018 | pmid = 29659758 | doi = 10.1093/ecco-jcc/jjy028 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Horio Y, Uchino M, Bando T, Chohno T, Sasaki H, Hirata A, Takesue Y, Ikeuchi H | title = Rectal-sparing type of ulcerative colitis predicts lack of response to pharmacotherapies | journal = BMC Surgery | volume = 17 | issue = 1 | pages = 59 | date = May 2017 | pmid = 28526076 | pmc = 5437574 | doi = 10.1186/s12893-017-0255-5 | doi-access = free }}</ref> People with more extensive disease are less likely to sustain remission, but the rate of remission is independent of the severity of the disease.<ref>{{cite book |doi=10.1016/B978-1-4160-6189-2.00112-8 |chapter=Ulcerative Colitis |title=Sleisenger and Fordtran's Gastrointestinal and Liver Disease |year=2010 |last1=Osterman |first1=Mark T. |last2=Lichtenstein |first2=Gary R. |pages=1975–2013.e9 |isbn=9781416061892 }}</ref> 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.<ref name=AGAClinicalPractice2020 /><ref name=ACG_Guidelines_2019 /> Surgical removal of the large intestine is necessary in some cases.<ref name=ACG_Guidelines_2019 />

===Colorectal cancer===
The risk of [[colorectal cancer]] is significantly increased in people with ulcerative colitis after ten years if involvement is beyond the [[splenic flexure]]. People with backwash ileitis might have an increased risk for colorectal carcinoma.<ref>{{cite journal | vauthors = Patil DT, Odze RD | title = Backwash Is Hogwash: The Clinical Significance of Ileitis in Ulcerative Colitis | journal = The American Journal of Gastroenterology | volume = 112 | issue = 8 | pages = 1211–1214 | date = August 2017 | pmid = 28631729 | doi = 10.1038/ajg.2017.182 | s2cid = 10801391 }}</ref> Those people with only proctitis usually have no increased risk.<ref name=ACG_Guidelines_2019 /> It is recommended that people have screening [[colonoscopies]] with random biopsies to look for [[dysplasia]] after eight years of disease activity, at one to two year intervals.<ref>{{cite journal | vauthors = Leighton JA, Shen B, Baron TH, Adler DG, Davila R, Egan JV, Faigel DO, Gan SI, Hirota WK, Lichtenstein D, Qureshi WA, Rajan E, Zuckerman MJ, VanGuilder T, Fanelli RD | title = ASGE guideline: endoscopy in the diagnosis and treatment of inflammatory bowel disease | journal = Gastrointestinal Endoscopy | volume = 63 | issue = 4 | pages = 558–565 | date = April 2006 | pmid = 16564852 | doi = 10.1016/j.gie.2006.02.005 }}</ref>

===Mortality===
People with ulcerative colitis are at similar<ref name=Gamborg /> or perhaps slightly increased overall risk of [[death]] compared with the background population.<ref name="daSilva">{{cite journal | vauthors = da Silva BC, Lyra AC, Rocha R, Santana GO | title = Epidemiology, demographic characteristics and prognostic predictors of ulcerative colitis | journal = World Journal of Gastroenterology | volume = 20 | issue = 28 | pages = 9458–9467 | date = July 2014 | pmid = 25071340 | pmc = 4110577 | doi = 10.3748/wjg.v20.i28.9458 | doi-access = free }}</ref> However, the distribution of causes-of-death differs from the general population.<ref name=Gamborg>{{cite journal | vauthors = Jess T, Gamborg M, Munkholm P, Sørensen TI | title = Overall and cause-specific mortality in ulcerative colitis: meta-analysis of population-based inception cohort studies | journal = The American Journal of Gastroenterology | volume = 102 | issue = 3 | pages = 609–617 | date = March 2007 | doi = 10.1111/j.1572-0241.2006.01000.x | pmid = 17156150 | s2cid = 2086542 }}</ref> Specific risk factors may predict worse outcomes and a higher risk of mortality in people with ulcerative colitis, including ''C. difficile'' infection<ref name=ACG_Guidelines_2019 /> and [[cytomegalovirus infection]] (due to reactivation).<ref>{{cite journal | vauthors = Nguyen M, Bradford K, Zhang X, Shih DQ | title = Cytomegalovirus Reactivation in Ulcerative Colitis Patients | journal = Ulcers | volume = 2011 | pages = 1–7 | date = January 2011 | pmid = 21731826 | pmc = 3124815 | doi = 10.1155/2011/282507 | doi-access = free }}</ref>

==Epidemiology==

Together with [[Crohn's disease]], about 11.2 million people were affected {{as of|2015|lc=yes}}.<ref name="GBD2015Pre">{{cite journal |last1=Vos |first1=Theo |last2=Allen |first2=Christine |last3=Arora |first3=Megha |last4=Barber |first4=Ryan M. |last5=Bhutta |first5=Zulfiqar A. |last6=Brown |first6=Alexandria |last7=Carter |first7=Austin |last8=Casey |first8=Daniel C. |last9=Charlson |first9=Fiona J. |last10=Chen |first10=Alan Z. |last11=Coggeshall |first11=Megan |last12=Cornaby |first12=Leslie |last13=Dandona |first13=Lalit |last14=Dicker |first14=Daniel J. |last15=Dilegge |first15=Tina |date=October 2016 |title=Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015 |journal=Lancet |volume=388 |issue=10053 |pages=1545–1602 |doi=10.1016/S0140-6736(16)31678-6 |pmc=5055577 |pmid=27733282 |collaboration=GBD 2015 Disease and Injury Incidence and Prevalence Collaborators |last16=Erskine |first16=Holly E. |last17=Ferrari |first17=Alize J. |last18=Fitzmaurice |first18=Christina |last19=Fleming |first19=Tom |last20=Forouzanfar |first20=Mohammad H. |last21=Fullman |first21=Nancy |last22=Gething |first22=Peter W. |last23=Goldberg |first23=Ellen M. |last24=Graetz |first24=Nicholas |last25=Haagsma |first25=Juanita A. |last26=Hay |first26=Simon I. |last27=Johnson |first27=Catherine O. |last28=Kassebaum |first28=Nicholas J. |last29=Kawashima |first29=Toana |last30=Kemmer |first30=Laura}}</ref> Each year it newly occurs in 1 to 20 per 100,000 people, and 5 to 500 per 100,000 individuals are affected.<ref name=BMJ2013/><ref name=NEJM2011/> The disease is more common in North America and Europe than other regions.<ref name=NEJM2011>{{cite journal | vauthors = Danese S, Fiocchi C | title = Ulcerative colitis | journal = The New England Journal of Medicine | volume = 365 | issue = 18 | pages = 1713–1725 | date = November 2011 | pmid = 22047562 | doi = 10.1056/NEJMra1102942 }}</ref> Often it begins in people aged 15 to 30 years, or among those over 60.<ref name=NIH2014/> Males and females appear to be affected in equal proportions.<ref name=BMJ2013/> It has also become more common since the 1950s.<ref name=BMJ2013/><ref name=NEJM2011/> Together, ulcerative colitis and Crohn's disease affect about a million people in the United States.<ref name="Elsevier Health Sciences">{{cite book| vauthors = Adams JG |title=Emergency Medicine E-Book: Clinical Essentials (Expert Consult – Online)|date=2012|publisher=Elsevier Health Sciences|isbn=978-1455733941|page=304|url=https://books.google.com/books?id=rpoH-KYE93IC&pg=PA304|language=en}}</ref> With appropriate treatment the risk of death appears the same as that of the general population.<ref name=Wan2016/> The first description of ulcerative colitis occurred around the 1850s.<ref name=NEJM2011/>

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).<ref name=BMJ2013>{{cite journal | vauthors = Ford AC, Moayyedi P, Hanauer SB | title = Ulcerative colitis | journal = BMJ | volume = 346 | pages = f432 | date = February 2013 | pmid = 23386404 | doi = 10.1136/bmj.f432 | s2cid = 14778938 }}</ref><ref name=NEJM2011/> In 2015, a worldwide total of 47,400 people died due to inflammatory bowel disease (UC and Crohn's disease).<ref name=GBD2015De>{{cite journal | title = Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1459–1544 | date = October 2016 | pmid = 27733281 | pmc = 5388903 | doi = 10.1016/s0140-6736(16)31012-1 | collaboration = GBD 2015 Mortality and Causes of Death Collaborators | last1 = Wang | first1 = Haidong | last2 = Naghavi | first2 = Mohsen | last3 = Allen | first3 = Christine | last4 = Barber | first4 = Ryan M. | last5 = Bhutta | first5 = Zulfiqar A. | last6 = Carter | first6 = Austin | last7 = Casey | first7 = Daniel C. | last8 = Charlson | first8 = Fiona J. | last9 = Chen | first9 = Alan Zian | last10 = Coates | first10 = Matthew M. | last11 = Coggeshall | first11 = Megan | last12 = Dandona | first12 = Lalit | last13 = Dicker | first13 = Daniel J. | last14 = Erskine | first14 = Holly E. | last15 = Ferrari | first15 = Alize J. | last16 = Fitzmaurice | first16 = Christina | last17 = Foreman | first17 = Kyle | last18 = Forouzanfar | first18 = Mohammad H. | last19 = Fraser | first19 = Maya S. | last20 = Fullman | first20 = Nancy | last21 = Gething | first21 = Peter W. | last22 = Goldberg | first22 = Ellen M. | last23 = Graetz | first23 = Nicholas | last24 = Haagsma | first24 = Juanita A. | last25 = Hay | first25 = Simon I. | last26 = Huynh | first26 = Chantal | last27 = Johnson | first27 = Catherine O. | last28 = Kassebaum | first28 = Nicholas J. | last29 = Kinfu | first29 = Yohannes | last30 = Kulikoff | first30 = Xie Rachel }}</ref> The peak onset is between 30 and 40 years of age,<ref name=Ungaro /> with a second peak of onset occurring in the 6th decade of life.<ref>{{cite journal | vauthors = Karlinger K, Györke T, Makö E, Mester A, Tarján Z | title = The epidemiology and the pathogenesis of inflammatory bowel disease | journal = European Journal of Radiology | volume = 35 | issue = 3 | pages = 154–167 | date = September 2000 | pmid = 11000558 | doi = 10.1016/s0720-048x(00)00238-2 }}</ref> Ulcerative colitis is equally common among men and women.<ref name=Ungaro>{{cite journal | vauthors = Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF | title = Ulcerative colitis | journal = Lancet | volume = 389 | issue = 10080 | pages = 1756–1770 | date = April 2017 | pmid = 27914657 | pmc = 6487890 | doi = 10.1016/S0140-6736(16)32126-2 }}</ref><ref name=BMJ2013/> With appropriate treatment the risk of death appears similar to that of the general population.<ref name=Wan2016/> UC has become more common since the 1950s.<ref name=BMJ2013/><ref name=NEJM2011/>

The geographic distribution of UC and Crohn's disease is similar worldwide,<ref name=Podolsky>{{cite journal | vauthors = Podolsky DK | title = Inflammatory bowel disease | journal = The New England Journal of Medicine | volume = 347 | issue = 6 | pages = 417–429 | date = August 2002 | pmid = 12167685 | doi = 10.1056/NEJMra020831 }}</ref> with the highest number of new cases a year of UC found in [[Canada]], [[New Zealand]] and the [[United Kingdom]].<ref>{{cite journal | vauthors = Schmidt JA, Marshall J, Hayman MJ | title = Identification and characterization of the chicken transferrin receptor | journal = The Biochemical Journal | volume = 232 | issue = 3 | pages = 735–741 | date = December 1985 | pmid = 3004417 | pmc = 1152945 | doi = 10.1042/bj2320735 }}</ref> The disease is more common in North America and Europe than other regions.<ref name=NEJM2011/> In general, higher rates are seen in northern locations compared to southern locations in [[Europe]]<ref>{{cite journal | vauthors = Shivananda S, Lennard-Jones J, Logan R, Fear N, Price A, Carpenter L, van Blankenstein M | title = Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD) | journal = Gut | volume = 39 | issue = 5 | pages = 690–697 | date = November 1996 | pmid = 9014768 | pmc = 1383393 | doi = 10.1136/gut.39.5.690 | df = dmy-all }}</ref> and the United States.<ref name=Sonneberg>{{cite journal | vauthors = Sonnenberg A, McCarty DJ, Jacobsen SJ | title = Geographic variation of inflammatory bowel disease within the United States | journal = Gastroenterology | volume = 100 | issue = 1 | pages = 143–149 | date = January 1991 | pmid = 1983816 | doi = 10.1016/0016-5085(91)90594-B }}</ref> UC is more common in western Europe compared with eastern Europe.<ref>{{cite journal | vauthors = Burisch J, Pedersen N, Čuković-Čavka S, Brinar M, Kaimakliotis I, Duricova D, Shonová O, Vind I, Avnstrøm S, Thorsgaard N, Andersen V, Krabbe S, Dahlerup JF, Salupere R, Nielsen KR, Olsen J, Manninen P, Collin P, Tsianos EV, Katsanos KH, Ladefoged K, Lakatos L, Björnsson E, Ragnarsson G, Bailey Y, Odes S, Schwartz D, Martinato M, Lupinacci G, Milla M, De Padova A, D'Incà R, Beltrami M, Kupcinskas L, Kiudelis G, Turcan S, Tighineanu O, Mihu I, Magro F, Barros LF, Goldis A, Lazar D, Belousova E, Nikulina I, Hernandez V, Martinez-Ares D, Almer S, Zhulina Y, Halfvarson J, Arebi N, Sebastian S, Lakatos PL, Langholz E, Munkholm P | title = East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort | journal = Gut | volume = 63 | issue = 4 | pages = 588–597 | date = April 2014 | pmid = 23604131 | doi = 10.1136/gutjnl-2013-304636 | hdl-access = free | s2cid = 25069828 | hdl = 2336/325171 }}</ref>  Worldwide, the prevalence of UC varies from 2 to 299 per 100,000 people.<ref name=Molodecky>{{cite journal | vauthors = Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG | title = Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review | journal = Gastroenterology | volume = 142 | issue = 1 | pages = 46–54.e42; quiz e30 | date = January 2012 | pmid = 22001864 | doi = 10.1053/j.gastro.2011.10.001 | url = http://www.gastrojournal.org/article/S0016508511013783/pdf }}</ref> Together, ulcerative colitis and Crohn's disease affect about a million people in the United States.<ref name="Elsevier Health Sciences"/>

As with Crohn's disease, the rates of UC are greater among [[Ashkenazi|Ashkenazi Jews]] and decreases progressively in other persons of Jewish descent, non-Jewish Caucasians, Africans, Hispanics, and Asians.<ref name="ISBN 0071599916"/> Appendectomy prior to age 20 for appendicitis<ref>{{cite journal | vauthors = Andersson RE, Olaison G, Tysk C, Ekbom A | title = Appendectomy and protection against ulcerative colitis | journal = The New England Journal of Medicine | volume = 344 | issue = 11 | pages = 808–814 | date = March 2001 | pmid = 11248156 | doi = 10.1056/NEJM200103153441104 | doi-access = free }}</ref> and current tobacco use<ref name="Boyko">{{cite journal | vauthors = Boyko EJ, Koepsell TD, Perera DR, Inui TS | title = Risk of ulcerative colitis among former and current cigarette smokers | journal = The New England Journal of Medicine | volume = 316 | issue = 12 | pages = 707–710 | date = March 1987 | pmid = 3821808 | doi = 10.1056/NEJM198703193161202 }}</ref> are protective against development of UC.<ref name=Ungaro /> However, former tobacco use is associated with a higher risk of developing the disease.<ref name="Boyko" /><ref name=Ungaro />

===United States===
{{As of|2004}}, the number of new cases of UC in the United States was between 2.2 and 14.3 per 100,000 per year.<ref name=":0">{{cite web|url=https://www.cdc.gov/ibd/ibd-epidemiology.htm|title=Epidemiology of the IBD|website=[[Centers for Disease Control and Prevention]] (CDC)|access-date=23 February 2017|url-status=dead|archive-url=https://web.archive.org/web/20170223213840/https://www.cdc.gov/ibd/ibd-epidemiology.htm|archive-date=23 February 2017}}</ref> The number of people affected in the United States in 2004 was between 37 and 246 per 100,000.<ref name=":0" />

=== 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.<ref>{{cite journal | vauthors = Makhlouf GM, Zfass AM, Said SI, Schebalin M | title = Effects of synthetic vasoactive intestinal peptide (VIP), secretin and their partial sequences on gastric secretion | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 157 | issue = 4 | pages = 565–568 | date = April 1978 | pmid = 349569 | doi = 10.3181/00379727-157-40097 | s2cid = 40543366 }}</ref>

=== 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.<ref>{{cite web |title=Ulcerative colitis: management |url=https://www.nice.org.uk/guidance/ng130 |website=National Institute for Health and Care Excellence |date=3 May 2019 }}</ref>

==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".<ref name = "mnjd">{{cite journal |last1=Mulder |first1=Daniel |last2=Noble |first2=Angela |last3=Justinich |first3=Christopher |last4=Duffin |first4=Jacalyn |title=A tale of two diseases: The history of inflammatory bowel disease |journal=Journal of Crohn's and Colitis |date=1 May 2014 |volume=8 |issue=5 |pages=341–348 |doi=10.1016/j.crohns.2013.09.009|pmid=24094598 |doi-access=free }}</ref>

UC was the first subtype of IBD to be identified.<ref name = "mnjd"/>

==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.<ref name="Trichuris suis therapy">{{cite journal | vauthors = Summers RW, Elliott DE, Urban JF, Thompson RA, Weinstock JV | title = Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial | journal = Gastroenterology | volume = 128 | issue = 4 | pages = 825–832 | date = April 2005 | pmid = 15825065 | doi = 10.1053/j.gastro.2005.01.005 | doi-access = free }}</ref> 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.<ref name="Trichuris suis therapy"/>

[[Alicaforsen]] is a first generation antisense oligodeoxynucleotide designed to bind specifically to the human [[ICAM-1]] messenger [[RNA]] through Watson-Crick base pair interactions in order to subdue expression of ICAM-1.<ref name="Bennett CF, Condon TC, Grimm S, Chan H, Chiang MY 1994 3530–40">{{cite journal|vauthors=Bennett CF, Condon TC, Grimm S, Chan H, Chiang MY |title=Inhibition of endothelial cell-leukocyte adhesion molecule expression with antisense oligonucleotides |journal=The Journal of Immunology |volume=152 |issue=1 |pages=3530–40 |year=1994 |doi=10.4049/jimmunol.152.7.3530 |s2cid=34563008 }}</ref> ICAM-1 propagates an inflammatory response promoting the extravasation and activation of [[leukocytes]] (white blood cells) into inflamed tissue.<ref name="Bennett CF, Condon TC, Grimm S, Chan H, Chiang MY 1994 3530–40"/> Increased expression of ICAM-1 has been observed within the [[inflamed]] intestinal mucosa of ulcerative colitis patients, where ICAM-1 over production correlated with disease activity.<ref>{{cite journal | vauthors = Jones SC, Banks RE, Haidar A, Gearing AJ, Hemingway IK, Ibbotson SH, Dixon MF, Axon AT | title = Adhesion molecules in inflammatory bowel disease | journal = Gut | volume = 36 | issue = 5 | pages = 724–730 | date = May 1995 | pmid = 7541009 | pmc = 1382677 | doi = 10.1136/gut.36.5.724 }}</ref> This suggests that ICAM-1 is a potential therapeutic target in the treatment of ulcerative colitis.<ref>{{cite journal | vauthors = van Deventer SJ, Wedel MK, Baker BF, Xia S, Chuang E, Miner PB | title = A phase II dose ranging, double-blind, placebo-controlled study of alicaforsen enema in subjects with acute exacerbation of mild to moderate left-sided ulcerative colitis | journal = Alimentary Pharmacology & Therapeutics | volume = 23 | issue = 10 | pages = 1415–1425 | date = May 2006 | pmid = 16669956 | doi = 10.1111/j.1365-2036.2006.02910.x | s2cid = 31495688 | doi-access = free }}</ref>

Gram positive bacteria present in the lumen could be associated with extending the time of relapse for ulcerative colitis.<ref name=Ghouri2014>{{cite journal | vauthors = Ghouri YA, Richards DM, Rahimi EF, Krill JT, Jelinek KA, DuPont AW | title = Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease | journal = Clinical and Experimental Gastroenterology | volume = 7 | pages = 473–487 | date = 9 December 2014 | pmid = 25525379 | pmc = 4266241 | doi = 10.2147/CEG.S27530 | doi-access = free }}</ref>

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.<ref name="Strøbæk, D. 2013">{{cite journal | vauthors = Strøbæk D, Brown DT, Jenkins DP, Chen YJ, Coleman N, Ando Y, Chiu P, Jørgensen S, Demnitz J, Wulff H, Christophersen P | title = NS6180, a new K(Ca) 3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease | journal = British Journal of Pharmacology | volume = 168 | issue = 2 | pages = 432–444 | date = January 2013 | pmid = 22891655 | pmc = 3572569 | doi = 10.1111/j.1476-5381.2012.02143.x }}</ref> 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]].<ref name="Strøbæk, D. 2013"/>

Neutrophil extracellular traps<ref name=Bennike>{{cite journal | vauthors = Bennike TB, Carlsen TG, Ellingsen T, Bonderup OK, Glerup H, Bøgsted M, Christiansen G, Birkelund S, Stensballe A, Andersen V | title = Neutrophil Extracellular Traps in Ulcerative Colitis: A Proteome Analysis of Intestinal Biopsies | journal = Inflammatory Bowel Diseases | volume = 21 | issue = 9 | pages = 2052–2067 | date = September 2015 | pmid = 25993694 | pmc = 4603666 | doi = 10.1097/MIB.0000000000000460 }}</ref> and the resulting degradation of the extracellular matrix<ref>{{cite journal | vauthors = Kirov S, Sasson A, Zhang C, Chasalow S, Dongre A, Steen H, Stensballe A, Andersen V, Birkelund S, Bennike TB | title = Degradation of the extracellular matrix is part of the pathology of ulcerative colitis | journal = Molecular Omics | volume = 15 | issue = 1 | pages = 67–76 | date = February 2019 | pmid = 30702115 | doi = 10.1039/C8MO00239H | doi-access = free }}</ref> 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.<ref name=Bennike />

[[Fexofenadine]], an antihistamine drug used in treatment of allergies, has shown promise in a combination therapy in some studies.<ref>{{cite journal | vauthors = Raithel M, Winterkamp S, Weidenhiller M, Müller S, Hahn EG | title = Combination therapy using fexofenadine, disodium cromoglycate, and a hypoallergenic amino acid-based formula induced remission in a patient with steroid-dependent, chronically active ulcerative colitis | journal = International Journal of Colorectal Disease | volume = 22 | issue = 7 | pages = 833–839 | date = July 2007 | pmid = 16944185 | doi = 10.1007/s00384-006-0120-y | s2cid = 2605447 }}</ref><ref name=Gautam>{{cite journal | vauthors = Dhaneshwar S, Gautam H | title = Exploring novel colon-targeting antihistaminic prodrug for colitis | journal = Journal of Physiology and Pharmacology | volume = 63 | issue = 4 | pages = 327–337 | date = August 2012 | pmid = 23070081 |url=http://www.jpp.krakow.pl/journal/archive/08_12/pdf/327_08_12_article.pdf }}</ref> 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.<ref name=Gautam />

There is evidence that [[etrolizumab]] is effective for ulcerative colitis, with phase 3 trials underway as of 2016.<ref name=Hir2015/><ref>{{cite journal | vauthors = Vermeire S, O'Byrne S, Keir M, Williams M, Lu TT, Mansfield JC, Lamb CA, Feagan BG, Panes J, Salas A, Baumgart DC, Schreiber S, Dotan I, Sandborn WJ, Tew GW, Luca D, Tang MT, Diehl L, Eastham-Anderson J, De Hertogh G, Perrier C, Egen JG, Kirby JA, van Assche G, Rutgeerts P | title = Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial | journal = Lancet | volume = 384 | issue = 9940 | pages = 309–318 | date = July 2014 | pmid = 24814090 | doi = 10.1016/S0140-6736(14)60661-9 | s2cid = 7369482 | doi-access = free }}</ref><ref name=":6">{{cite journal | vauthors = Rosenfeld G, Parker CE, MacDonald JK, Bressler B | title = Etrolizumab for induction of remission in ulcerative colitis | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 12 | pages = CD011661 | date = December 2015 | pmid = 26630451 | pmc = 8612697 | doi = 10.1002/14651858.CD011661.pub2 }}</ref><ref>{{cite journal | vauthors = Makker J, Hommes DW | title = Etrolizumab for ulcerative colitis: the new kid on the block? | journal = Expert Opinion on Biological Therapy | volume = 16 | issue = 4 | pages = 567–572 | date = 2016 | pmid = 26914639 | doi = 10.1517/14712598.2016.1158807 | s2cid = 24706213 }}</ref> 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.<ref name=":6" /> As of early 2022, [[Roche]] halted clinical trials for the use of etrolizumab in the treatment of ulcerative colitis.<ref>{{cite web |last=Taylor |first=Nick |date=3 February 2022 |title=Roche lets go of etro, dumping phase 3 Crohn's prospect 18 months after posting weak colitis data |url=https://www.fiercebiotech.com/biotech/roche-lets-go-etro-dumping-phase-3-crohn-s-prospect-18-months-after-posting-weak-colitis |access-date=12 December 2023 |website=Fierce Biotech}}</ref>

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.<ref>{{cite journal | vauthors = Abreu MT, Plevy S, Sands BE, Weinstein R | title = Selective leukocyte apheresis for the treatment of inflammatory bowel disease | journal = Journal of Clinical Gastroenterology | volume = 41 | issue = 10 | pages = 874–888 | date = 2007 | pmid = 18090155 | doi = 10.1097/MCG.0b013e3180479435 | s2cid = 36724094 }}</ref> Results from small trials have been tentatively positive.<ref>{{cite journal | vauthors = Vernia P, D'Ovidio V, Meo D | title = Leukocytapheresis in the treatment of inflammatory bowel disease: Current position and perspectives | journal = Transfusion and Apheresis Science | volume = 43 | issue = 2 | pages = 227–229 | date = October 2010 | pmid = 20817610 | doi = 10.1016/j.transci.2010.07.023 }}</ref>

==Notable cases==
{{main|List of people diagnosed with ulcerative colitis}}

== References ==
{{Reflist}}

== Further reading ==
* {{cite journal | vauthors = Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD | title = ACG Clinical Guideline: Ulcerative Colitis in Adults | journal = The American Journal of Gastroenterology | volume = 114 | issue = 3 | pages = 384–413 | date = March 2019 | pmid = 30840605 | doi = 10.14309/ajg.0000000000000152 | s2cid = 73473272 | doi-access = free }} {{open access}}
* {{cite journal | vauthors = Torpy JM, Lynm C, Golub RM | title = JAMA patient page. Ulcerative colitis | journal = JAMA | volume = 307 | issue = 1 | pages = 104 | date = January 2012 | pmid = 22215172 | doi = 10.1001/jama.2011.1889 | doi-access = free }}

== External links ==
* [https://www.nlm.nih.gov/medlineplus/ulcerativecolitis.html MedlinePlus ulcerative colitis page]
*{{Commons category-inline}}
{{Medical resources
| ICD10         = {{ICD10|K|51||k|50}}
| ICD9          = {{ICD9|556}}
| DiseasesDB    = 13495
| OMIM          = 191390
| eMedicineSubj = med
| eMedicineTopic= 2336
| MedlinePlus   = 000250
| MeshID        = D003093
|ICD11={{ICD11|DD71}}|ICD10CM={{ICD10CM|K51}}}}

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