Ulcerative colitis Disease distribution Ulcerative Colitis Left sided

Ulcerative colitis

Disease distribution Ulcerative Colitis Left sided cloitis Proctosigmoiditis

Disease distribution • The disease typically is most severe distally and progressively less severe more proximally. • In contrast to Crohn's disease, continuous and symmetrical involvement is the hallmark of UC, with sharp transition between diseased and uninvolved segments of bowel

Clinical Features diarrhea tenesmus rectal bleeding passage of mucus urgency abdominal pain

Systemic manifestations Fever Weight loss Peripheral edema Anorexia/vomiting

Clinical Features The onset of UC typically is slow and insidious. Symptoms have usually been present for weeks or months by the time the patient seeks medical attention. The median interval between the onset of symptoms and diagnosis of UC is approximately 9 months. Some patients with UC may present much more acutely, with symptoms mimicking infectious colitis.

Physical findings • mild or even moderately severe disease: - few abnormal physical signs • severe attacks : -tachycardia -fever -orthostasis -weight loss • fulminant colitis: - the abdomen often becomes distended and firm, with absent bowel sounds and signs of peritoneal inflammation.

Laboratory Findings Laboratory findings in UC are nonspecific and reflect the severity of the underlying disease Patients with active proctitis and proctosigmoiditis often have normal laboratory test results Anemia, leukocytosis and thrombocytosis, reflect active disease. Serum inflammatory markers including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may be elevated in active disease. Elevation in these inflammatory parameters is neither sensitive nor specific for UC; however, measuring them may be useful in clinical practice to assess disease activity in individual patients, particularly if these values are normal during periods of inactive disease.

Laboratory findings Hypokalemia, metabolic alkalosis, and elevated serum creatinine may be present in severe flares of UC Hypoalbuminemia may be seen with both acute and chronic disease. Minor elevations in serum levels of aspartate aminotransferase or alkaline phosphatase also are frequently associated with severe disease, but these changes are transient and return to normal when the disease enters into remission. These abnormalities probably reflect a combination of fatty liver, sepsis, and poor nutrition. Persistently elevated liver biochemical tests, especially serum alkaline phosphatase, are seen in about 3% of patients with UC and should lead to further investigation, particularly to exclude the presence of primary sclerosing cholangitis (PSC)

Natural history & Prognosis 80% of patients with UC have a disease course characterized by intermittent flares interposed between variable periods of remission. The duration of relapse-free periods varies greatly from patient to patient. > 50% of patients present with mild disease at their first attack 6% to 19% of patients have severe disease at presentation.

Natural history & Prognosis Following the initial flare, 40% to 65% of patients have an intermittent course, and 5% to 10% of patients have a chronic continuous course. Up to 10% of patients have a severe first attack ultimately requiring colectomy. Twenty-five years after the diagnosis of UC, 90% of patients still have a relapsing course The probability of remaining in remission for 1 year after a relapse has been estimated at 30%. After being in remission for 1 year, the risk of relapse decreases to 20% for the following year. Few patients (1%) diagnosed with UC have only one attack followed by a relapse-free course, and they likely represent misdiagnosed infectious colitis.

Natural history & Prognosis Disease extent may progress over time. In patients initially presenting with proctitis or proctosigmoiditis, disease extension occurs in approximately 10% to 30% of patients at 10 years after diagnosis. Less commonly, extensive colitis regresses over time with treatment

Colectomy in Ulcerative colitis • The probability of colectomy is highest in the first year of diagnosis • the overall colectomy rate is 24% at 10 years and 30% at 25 years • The probability of colectomy is related to the extent of disease at diagnosis.

Exacerbating factors bacterial and viral infections psychosocial stress. seasonality the use of nonsteroidal antiinflammatory drugs (NSAIDs) antibiotics smoking

Diagnosis • No single test allows the diagnosis of UC with acceptable sensitivity and specificity. • the diagnosis relies on a combination of : -compatible clinical features -endoscopic appearances -histologic findings. • Stool cultures should be obtained to exclude infectious colitis

Diagnosis • colonoscopy should be performed to establish the extent of the disease and to exclude Crohn's disease. • Multiple biopsy specimens should be taken from throughout the colon to map the histologic extent of disease and to confirm the diagnosis if there is concern about Crohn's disease. • Additionally, intubation and biopsy of the terminal ileum should be attempted to exclude the presence of Crohn's disease.

Endoscopic findings The hallmark of UC is symmetrical and continuous inflammation that begins in the rectum and extends proximally without interruption for the entire extent of disease.

Endoscopic findings The earliest endoscopic sign of UC is a decrease or loss of the normal vascular pattern, with erythema and edema of the mucosa As the disease progresses, the mucosa becomes granular and friable With more severe inflammation, the mucosa may be covered by yellow-brown mucopurulent exudates associated with mucosal ulcerations. severe UC is associated with mucosa that bleeds spontaneously, and there may be extensive areas of denuded mucosa from severe mucosal ulcerations with diffuse colitis. Marked edema may at times lead to luminal narrowing.

ENDOSCOPIC SPECTRUM OF SEVERITY

Endoscopic findings In patients with long-standing UC, pseudopolyps may be present. Inflammatory pseudopolyps develop in active disease and result from inflamed, regenerating epithelium that is interposed among ulcerations. These inflammatory pseudopolyps give the colonic mucosa a cobblestone appearance. With repeated inflammation that is followed by healing, these pseudopolyps remain during quiescent disease and usually do not regress with treatment. Endoscopically, pseudopolyps typically are small, soft, pale, fleshy, and glistening; however, they may be large, sessile, or pedunculated and may have surface ulcerations. Differentiation of these benign pseudopolyps from neo-plastic polyps may be difficult and requires histologic confirmation.

Endoscopic findings • Strictures occasionally may be present in patients with chronic UC • Caused by focal muscular hypertrophy associated with inflammation. • Malignancy must be excluded in patients with UC who have strictures, particularly those with long strictures without associated inflammation and those proximal to the splenic flexure.

Radiology: Barium enema • less frequently used in the care of patients with UC • may be superior to colonoscopy for certain indications Stricture Location Length Diameter

Radiology: Plain film of the abdomen Patients with a severe attack of UC should have a supine plain film of the abdomen The presence of marked colonic dilatation suggests fulminant colitis or toxic megacolon

Assessment of disease severity • Mild <4 stools/day, without or with only small amounts of mucus No blood No fever No tachycardia Mild anemia ESR < 30 mm/hr • Moderate Intermediate between mild and severe • Severe >6 stools/day, with blood Fever > 37. 5°C Heart rate > 90 beats/min Anemia with hemoglobin < 75% of normal

Mayo score • A numerical disease activity instrument • It is the sum of scores from four components stool frequency rectal bleeding sigmoidoscopic findings physician's global assessment. • It ranges from 0 to 12, with the higher total score indicating a more severe disease

Mayo score Variable Score Stool frequency 0 Normal 1 1 -2 stools/day > normal 2 3 -4 stools/day > normal 3 >4 stools/day > normal Rectal Bleeding 0 None 1 Streaks of blood 2 Obvious blood 3 Mostly blood Variable Score Mucosal Appearance 0 Normal 1 Mild friability 2 Moderate friability 3 Exudation, spontaneous bleeding Physician Global Assessment 0 Normal 1 Mild 2 Moderate 3 Severe

Mayo score • Remission: score <2 • severe disease: score> 10 • Clinical response: decrease by 3 points from the patient's initial baseline score.

Fulminant colitis • Patients with severe fulminant colitis: - appear toxic -fever higher than 101°F -tachycardia - abdominal distention -signs of localized or generalized peritonitis -leukocytosis • Toxic megacolon: radiologic evidence of colon dilatation to greater than 6 cm in an acutely ill patient. • Fulminant colitis and toxic megacolon are clinical diagnoses, and endoscopic examination should be avoided in patients with severe or fulminant colitis because of the risk of inducing megacolon or perforation.

Differentiating crohn’s disease from ulcerative colitis Variable Crohn’s disease Ulcerative colitis Distribution Often discontinuous and asymmetric with skipped segments and normal intervening mucosa, especially in early disease Continuous, symmetric, and diffuse, with granularity or ulceration found throughout the involved segments of colon; periappendiceal inflammation (cecal patch) is common even when the cecum is not involved Rectum Completely, or relatively, spared Typically involves the rectum with proximal involvement to a variable extent Ileum Often involved (≈75% of cases of Crohn's disease Not involved, except as “backwash” ileitis in ulcerative pancolitis Depth of Submucosal, and inflammation transmural Mucosal; not transmural except in fulminant disease

Differentiating crohn’s disease from ulcerative colitis Variable Crohn’s disease Ulcerative colitis Strictures Often present Rarely present; suggestive of adenocarcinoma Fistulas Perianal, enterocutaneous, rectovaginal, enterovesicular, and other fistulas may be present Not present, except rarely for rectovaginal fistula Granulomas Present in 15 -60% of patients (higher frequency in surgical specimens than in mucosal pinch biopsies) Generally not present Serology p. ANCA positive in 20 -25%; ASCA positive in 41 -76% p. ANCA positive in 60 -65%; ASCA positive in 5%

Extraintestinal manifestations of IBD

Extraintestinal manifestations • numerous complications may occur distant from the bowel • Many of these complications are common to both Crohn's disease and ulcerative colitis • In large series, extraintestinal manifestations are found to occur more frequently in Crohn's disease than in ulcerative colitis and are more common among patients with colonic involvement than in patients with no colonic inflammation • one fourth of all patients with Crohn's disease will have an extraintestinal manifestation of IBD.

Extraintestinal manifestations of IBD Extraintestinal manifestations Related to disease activity Unrelated to colitis

Musculoskeletal Manifestations • Among the most common extraintestinal manifestations are disorders of the bones and joints • In most patients, joint symptoms occurred in the setting of a relapse of bowel symptoms • Among patients with Crohn's disease, nearly one half had joint symptoms in association with a relapse in bowel disease.

Musculoskeletal Manifestations Type 1 Peripheral Type 2 Arthropathy Sacroilitis Axial Spondylitis

Peripheral arthropathy Features Number of joints affected Type 1 Type 2 <5 >5 Joints affected Mainly large joints Joints affected Asymmetrical Symmetrical Parallel Independent <10 wk (median 5 wk) Months to years (median 3 yr) Association with bowel disease activity Duration of attacks Mainly small joints

Musculoskeletal Manifestations • Axial arthropathy occurs less frequently than does peripheral arthropathy in patients with IBD, and includes sacroiliitis and spondylitis. • Spondylitis associated with IBD presents as insidious low back pain and morning stiffness that is improved by exercise. • Does not parallel the activity of bowel disease

Skin: pyoderma gangrenosum • The most common skin lesions associated with IBD are pyoderma gangrenosum and erythema nodosum. • Neither condition is found solely in IBD, and the finding of one or the other lesion is not specific for either major form of IBD.

Skin: pyoderma gangrenosum • Pyoderma gangrenosum appears first as a papule, pustule, or nodule and progresses to an ulcer with undermined borders. The ulcer typically has a violaceous rim and crater-like holes pitting the base • most often appears on the leg however it can occur virtually anywhere on the body. • Rare, occurs in 1 -2% of patients • In Crohn's disease pyoderma gangrenosum often occurs without an associated flare of bowel symptoms.

Skin: pyoderma gangrenosum

Skin: erythema nodosum The classic appearance is of tender subcutaneous nodules with an erythematous or dusky appearance, most often seen on the pretibial region. erythema nodosum is much more frequently seen in women than in men, occurs in 2% to 4% of patients with UC often presents during exacerbations of bowel disease and tends to improve with treatment of the underlying bowel disease. Severe or refractory cases may require systemic glucocorticoids or immunosuppressive therapy. There is a strong association with arthropathy If possible, erythema nodosum lesions should not be biopsied because biopsied lesions tend to scar, whereas spontaneously resolving lesions heal without scar formation.

Erythema nodosum

Mucocutaneous Manifestations • Aphthous ulcers of the mouth are common among patients with Crohn's disease and ulcerative colitis • These lesions usually occur with flares of colitis and resolve on control of the bowel disease • Angular cheilitis is seen in nearly 8% of patients with Crohn's disease. • Angular stomatitis and a sore tongue may be seen in patients with deficiencies of iron or other micronutrients

Ocular Manifestations: episcleritis • estimated to occur in 6% of patients with Crohn's disease, 5% of patients with ulcerative colits • consists of painless hyperemia of the sclera and conjunctiva with no affection of visual acuity. • It typically parallels the activity of bowel disease and usually responds to anti-inflammatory therapy

Ocular Manifestations: uveitis • uveitis presents as an acute or subacute painful eye with visual blurring and often photophobia and headache. Visual acuity is preserved unless the posterior segment becomes involved. • Temporal correlation of uveitis with the activity of the colitis is less predictable than with episcleritis. • Uveitis should receive prompt treatment with local steroid ocular drops to prevent progression to blindness.

Hepatobiliary Manifestations • Gallstones are found in more than 25% of men and women with Crohn's disease, representing a relative risk of 1. 8 compared with the general population. • Asymptomatic and mild elevations of liver biochemical tests often are seen in IBD. In most cases, the levels return to normal once remission is achieved. These abnormalities are thought to be related to a combination of factors, including malnutrition, sepsis, and fatty liver. • Primary sclerosing cholangitis more often is associated with ulcerative colitis but may occur in 4% of patients with Crohn's disease, usually those with colonic involvement.

Hepatobiliary Manifestations : PSC • PSC should be excluded in patients with UC who have persistently abnormal liver tests or evidence of chronic liver disease. • PSC is independent of the underlying colitis and it usually follows a progressive course after many years of stable disease. • Unfortunately, no treatment has been shown definitively to be effective.

Renal and Genitourinary Manifestations • uric acid and oxalate stones are common in patients with Crohn's disease. In the setting of fat malabsorption resulting from intestinal resection or extensive small bowel disease, luminal calcium binds free fatty acids, thereby decreasing the calcium that is available to bind and clear oxalate. Increased oxalate is absorbed as the sodium salt, resulting in hyperoxaluria and calcium oxalate stone formation. • Uric acid stones are believed to result from volume depletion and a hypermetabolic state. • More rare complications include membranous nephropathy, glomerulonephritis, and renal amyloidosis. .

Coagulation and Vascular Complications • The occurrence of hypercoagulability is a well-recognized complication of IBD. • Patients may present with venous thromboembolism or, much less commonly, arterial thrombosis. • The hypercoagulable state is multifactorial. • A variety of coagulation and platelet abnormalities may be present in patients with UC, particularly those with severe disease, and include: - thrombocytosis - increased levels of fibrinogen, coagulation factors V and VIII and plasminogen activator inhibitor -decreased levels of antithrombin III, proteins C and S, factor V Leiden, and tissue plasminogen activator.

Serological markers in IBD • CRP • P-ANCA • ASCA

Serological markers in IBD • May be useful in predicting the phenotype of crohn’s disease • There association between ASCA and Small bowel diseae Fibrostenotic disease Perforation Small bowel surgery

Serological markers in IBD • Patient with positive serology and high titer are more likely to have complications: strictures surgery requirements perforating disease