Editing Ulcerative colitis (section)

===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" />