ulcerative colitis ulcerative colitis ulcerative colitis (uc) is a long-term condition that results in inflammation and ulcers of the colon and rectum. the primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). weight loss, fever, and anemia may also occur. often, symptoms come on slowly and can range from mild to severe. symptoms typically occur intermittently with periods of no symptoms between flares. complications may include abnormal dilation of the colon (megacolon), inflammation of the eye, joints, or liver, and colon cancer. ulcerative colitisendoscopic image of a colon affected by ulcerative colitis. the internal surface of the colon is blotchy and broken in places. mild-moderate disease.specialtygastroenterologysymptomsabdominal pain, diarrhea mixed with blood, weight loss, fever, anemia, dehydration, loss of appetite, fatigue, sores on the skin, urgency to defecate, inability to defecate despite urgency, rectal paincomplicationsmegacolon, inflammation of the eye, joints, or liver, colon cancerusual onset15–30 years or > 60 yearsdurationlong termcausesunknowndiagnostic methodcolonoscopy with tissue biopsiesdifferential diagnosisdysentery, crohn's disease, ischemic colitistreatmentdietary changes, medication, surgerymedicationsulfasalazine, mesalazine, steroids, immunosuppressants such as azathioprine, biological therapyfrequency2-299 per 100,000deaths47,400 together with crohn's (2015) the cause of uc is unknown. theories involve immune system dysfunction, genetics, changes in the normal gut bacteria, and environmental factors. rates tend to be higher in the developed world with some proposing this to be the result of less exposure to intestinal infections, or to a western diet and lifestyle. the removal of the appendix at an early age may be protective. diagnosis is typically by colonoscopy with tissue biopsies. it is a type of inflammatory bowel disease (ibd) along with crohn's disease and microscopic colitis. dietary changes, such as maintaining a high-calorie diet or lactose-free diet, may improve symptoms. several medications are used to treat symptoms and bring about and maintain remission, including aminosalicylates such as mesalazine or sulfasalazine, steroids, immunosuppressants such as azathioprine, and biologic therapy. removal of the colon by surgery may be necessary if the disease is severe, does not respond to treatment, or if complications such as colon cancer develop. removal of the colon and rectum generally cures the condition. together with crohn's disease, about 11.2 million people were affected as of 2015. each year it newly occurs in 1 to 20 per 100,000 people, and 5 to 500 per 100,000 individuals are affected. the disease is more common in north america and europe than other regions. often it begins in people aged 15 to 30 years, or among those over 60. males and females appear to be affected in equal proportions. it has also become more common since the 1950s. together, ulcerative colitis and crohn's disease affect about a million people in the united states. with appropriate treatment the risk of death appears the same as that of the general population. the first description of ulcerative colitis occurred around the 1850s. signs and symptoms signs and symptoms crohn's diseaseulcerative colitis defecationoften porridge-like, sometimes steatorrheaoften mucus-like and with blood tenesmusless commonmore common fevercommonindicates severe disease fistulaecommon seldom weight lossoftenmore seldom gastrointestinal people with ulcerative colitis usually present with diarrhea mixed with blood, of gradual onset that persists for an extended period of time (weeks). additional symptoms may include fecal incontinence, increased frequency of bowel movements, mucus discharge, and nocturnal defecations. with proctitis (inflammation of the rectum), people with uc may experience urgency or rectal tenesmus, which is the urgent desire to evacuate the bowels but with the passage of little stool. 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. the severity of abdominal pain with uc varies from mild discomfort to very painful bowel movements and abdominal cramping. high frequency of bowel movements, weight loss, nausea, fatigue, and fever are also common during disease flares. chronic bleeding from the gi tract, chronic inflammation, and iron deficiency often leads to anemia, which can affect quality of life. the clinical presentation of ulcerative colitis depends on the extent of the disease process. up to 15% of individuals may have severe disease upon initial onset of symptoms. a substantial proportion (up to 45%) of people with a history of uc without any ongoing symptoms (clinical remission) have objective evidence of ongoing inflammation. ulcerative colitis is associated with a generalized inflammatory process that can affect many parts of the body. sometimes, these associated extra-intestinal symptoms are the initial signs of the disease. extent of involvement 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. 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.). in contrast, inflammation with crohn's disease is often patchy, with so-called "skip lesions" (intermittent regions of inflamed bowel). the disease is classified by the extent of involvement, depending on how far the disease extends: proctitis (rectal inflammation), left sided colitis (inflammation extending to descending colon), and extensive colitis (inflammation proximal to the descending colon). proctosigmoiditis describes inflammation of the rectum and sigmoid colon. pancolitis describes involvement of the entire colon, extending from the rectum to the cecum. while usually associated with crohn's disease, ileitis (inflammation of the ileum) also occurs in uc. about 17% of individuals with uc have ileitis. ileitis more commonly occurs in the setting of pancolitis (occurring in 20% of cases of pancolitis), and tends to correlate with the activity of colitis. this so-called "backwash ileitis" can occur in 10–20% of people with pancolitis and is believed to be of little clinical significance. severity of disease in addition to the extent of involvement, uc is also characterized by severity of disease. severity of disease is defined by symptoms, objective markers of inflammation (endoscopic findings, blood tests), disease course, and the impact of the disease on day-to-day life. most patients are categorized through endoscopy and fecal calprotectin levels. indicators of low risk for future complications in mild and moderate uc include the following parameters: exhibiting less than 6 stools daily and lack of fever/weight loss. other indicators include lack of extraintestinal symptoms, none to little elevation in crp, esr, and calprotectin, and later age of diagnosis (over 40 years). mild disease correlates with fewer than four stools daily; in addition, mild urgency and rectal bleeding may occur intermittently. mild disease lacks systemic signs of toxicity (eg. fever, chills, weight changes) and exhibits normal levels of serum inflammatory markers (erythrocyte sedimentation rate and c-reactive protein). moderate to severe disease correlates with more than six stools daily, frequent bloody stools and urgency. moderate abdominal pain, low-grade fever, 38 to 39 °c (100 to 102 °f), and anemia may develop (75% of normal). toxicity is present, as demonstrated by fever, tachycardia, anemia or an elevated esr or crp. fulminant disease correlates with more than 10 bowel movements daily, continuous bleeding, toxicity, abdominal tenderness and distension, blood transfusion requirement, and colonic dilation (expansion). people with fulminant uc may have inflammation extending beyond just the mucosal layer, causing impaired colonic motility and leading to toxic megacolon. toxic megacolon is defined by diameter of colon (>6 cm) or cecum (>9 cm) and represents a medical emergency, one often treated surgically. if the serous membrane is involved, a colonic perforation may ensue, which has a 50% mortality rate in patients afflicted with uc. ulcerative colitis may improve and enter remission. remission of disease is characterized by formed stools, the absence of bloody diarrhea, resolution of urgency, and normal levels of serum inflammatory markers. extraintestinal manifestations and complications complications crohn's diseaseulcerative colitis nutrient deficiencyhigher risk colon cancer riskslightconsiderable prevalence of extraintestinal complications iritis/uveitisfemales2.2%3.2% males1.3%0.9% primary sclerosing cholangitisfemales0.3%1% males0.4%3% ankylosing spondylitisfemales0.7%0.8% males2.7%1.5% pyoderma gangrenosumfemales1.2%0.8% males1.3%0.7% erythema nodosumfemales1.9%2% males0.6%0.7% aphthous ulcers involving the tongue, lips, palate, and pharynx. pyoderma gangrenosum with large ulcerations affecting the back. uc is characterized by immune dysregulation and systemic inflammation, which may result in symptoms and complications outside the colon. commonly affected organs include: eyes, joints, skin, and liver. the frequency of such extraintestinal manifestations has been reported as between 6 and 47%. uc may affect the mouth. about 8% of individuals with uc develop oral manifestations. the two most common oral manifestations are aphthous stomatitis and angular cheilitis. aphthous stomatitis is characterized by ulcers in the mouth, which are benign, noncontagious and often recurrent. angular chelitis is characterized by redness at the corners of the mouth, which may include painful sores or breaks in the skin. very rarely, benign pustules may occur in the mouth (pyostomatitis vegetans). uc may affect the eyes manifesting in scleritis, iritis, and conjunctivitis. patients may be asymptomatic or experience redness, burning, or itching in eyes (cite cmdp). inflammation may occur in the interior portion of the eye, leading to uveitis and iritis. uveitis can cause blurred vision and eye pain, especially when exposed to light (photophobia). untreated, uveitis can lead to permanent vision loss. inflammation may also involve the white part of the eye (sclera) or the overlying connective tissue (episclera), causing conditions called scleritis and episcleritis. ulcerative colitis is most commonly associated with uveitis and episcleritis. uc may cause several joint manifestations, including a type of rheumatologic disease known as seronegative arthritis, which may affect few large joints (oligoarthritis), the vertebra (ankylosing spondylitis) or several small joints of the hands and feet (peripheral arthritis). often the insertion site where muscle attaches to bone (entheses) becomes inflamed (enthesitis). inflammation may affect the sacroiliac joint (sacroiliitis). it is estimated that round 50% of ibd patients suffer from migratory arthritis. synovitis, or inflammation of the synovial fluid surrounding a joint, can occur for months and recur in later times but usually does not erode the joint. the symptoms of arthritis include joint pain, swelling, and effusion, and often leads to significant morbidity. the severity of joint symptoms often does not correspond with severity of ibd. ulcerative colitis may affect the skin. the most common type of skin manifestation, erythema nodosum, presents in up to 3% of uc patients and almost 8% in patients afflicted with crohn's disease. it develops as raised, tender red nodules usually appearing on the outer areas of the arms or legs, especially in the anterior tibial area (shins). the nodules have diameters that measure approximately 1–5 cm. erythema nodosum is due to inflammation of the underlying subcutaneous tissue (panniculitis), and biopsy will display focal panniculitis (although is often unnecessary in diagnosis). in contrast to joint-related manifestations, erythema nodosum often occurs alongside intestinal disease. thus, treatment of uc can often lead to resolution of skin nodules. a lesser common skin complication associated with uc, pyoderma gangrenosum, is typically more severe. one study discovered this skin manifestation in only 0.75% pf patients. pyoderma gangrenosum is characterized by painful lesions or nodules that become ulcers which progressively grow. it often starts as many small raised red spots (papules) or pus-filled lesions (pustules) that are usually detected on lower extremities. the inner layer of the skin, or dermis, slowly undergoes necrosis (process of dying) causing the ulcerations that are typical of pyoderma gangrenosum. the ulcers are often filled with sterile pus-like material, so biopsy often displays an abscess that is sterile. whereas erythema nodosum tends to correlate with the activity of the ulcerative colitis and often improves with treatment of the colonic inflammation, pyoderma gangrenosum may occur independently of uc disease activity. in some cases, pyoderma gangrenosum may require injection with corticosteroids. treatment may also involve inhibitors of tumor necrosis factor (tnf), a cytokine that promotes cell survival. other associations determined between the skin and ulcerative colitis include a skin condition known as hidradenitis suppurativa (hs). this condition represents a chronic process in which follicles become occluded leading to recurring inflammation of nodules and abscesses and even tunnels in the skin that drain fluid. ulcerative colitis