risk of colectomy (31–33) and response to therapy (32–34). However, up to a quarter of patients with endoscopically active disease may have a normal CRP, and the frequency of elevation is lower in individuals with mild endoscopic activity. Measurement of hemoglobin and serum albumin levels at diagnosis can be helpful in assessing disease severity and prognosis. Demonstration of fecal leukocytes alone is not sufficiently sensitive, nor is it specific for the diagnosis or assessment of the activity of UC. FC is a nonspecific neutrophilic marker of inflammation and is elevated in infectious and inflammatory colitis but not in noninflammatory causes of diarrhea such as irritable bowel syndrome. Several studies have confirmed its utility in differentiating IBD from irritable bowel syndrome using cutoffs that vary from 6 to 280 μg/g of stool (35). The pooled sensitivity and specificity of elevated FC for diagnosis of UC are 0.88 and 0.79, respectively, with a modest positive likelihood ratio of 4.2 and a more clinically meaningful negative likelihood ratio of 0.15. In a primary care population, FC in patients with suspected UC (diarrhea and rectal bleeding) can be used to prioritize patients for colonoscopic evaluation, particularly among children (36,37). The utility of FC as a marker of inflammation and treatment target is discussed in the management section. Serologic markers such as perinuclear antineutrophil cytoplasmic antibodies (pANCAs) may be found in up to 70% of patients with UC, and combination of negative anti–Saccharomyces cerevisiae antibodies with elevated pANCA levels has been proposed to facilitate establishing a diagnosis of UC (38,39). However, the pooled sensitivity of antibody testing for diagnosis of UC is low, and such markers are not used for establishing or ruling out a diagnosis of UC (38). Although pANCA positivity has also been associated with treatment refractory UC, the evidence supporting this is limited, and there is currently no role for such testing to determine the likelihood of disease evolution and prognosis (40,41). Determination of the extent and severity of disease is important to select the appropriate treatment algorithm. Extent of the disease should be characterized according to the Montreal classification as proctitis (E1), left-sided colitis (E2), or extensive colitis (E3) (extension proximal to the splenic flexure) (42,43). Commonly, severity of UC has been classified according to the Truelove and Witts' (44) criteria published in 1955. Mild colitis is defined as fewer than 4 bowel movements daily, normal temperature, heart rate, hemoglobin (>11 g/dL), and ESR (<20 mm/hr). Severe disease is defined by bowel frequency greater than 6 times a day in conjunction with fever, tachycardia, anemia, or an elevation in ESR. Although simple to use and useful in defining the need for hospitalization, the index does not provide a quantitative or longitudinal measure of severity, excludes other important symptoms such as nocturnal symptoms and extraintestinal manifestations, and does not consider endoscopic severity. Several quantitative disease activity indexes are available (45), including the Mayo score (Table 5) (46), Seo Index (47), Rachmilewitz Index (48), Simple Clinical Colitis Activity Index (SCCAI) (Table 6) (49), PRO2 (50), and the Pediatric UC Activity Index (PUCAI) (51). Although disease extent broadly affects prognosis, it should not limit therapeutic options. Although most clinical activity indexes have not been rigorously validated, there is broad