Ulcerative Colitis Workup

Updated: Oct 31, 2023
  • Author: Marc D Basson, MD, PhD, MBA, FACS; Chief Editor: BS Anand, MD  more...
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Approach Considerations

See also the American College of Gastroenterology recommendations in the Guidelines section.

The diagnosis of ulcerative colitis (UC) is best made with endoscopy and mucosal biopsy for histopathology. Laboratory studies are helpful to exclude other diagnoses and assess the patient's nutritional status, but serologic markers can assist in the diagnosis of inflammatory bowel disease. Radiographic imaging has an important role in the workup of patients with suspected inflammatory bowel disease and in the differentiation of ulcerative colitis from Crohn disease by demonstrating fistulae or the presence of small bowel disease seen only in Crohn disease.

Capsule endoscopy is sensitive for early mucosal inflammation, but it can only detect mucosal changes, whereas magnetic resonance imaging (MRI) and intestinal ultrasonography are able to reveal transmural inflammation as well as identify complications. [10, 44] Furthermore, MRI detects fistulas, deep ulcerations, and a thickened bowel wall. [44] Ultrasonography is inexpensive and can be performed at the point of care by the treating gastroenterologist.

Ultrasonography, computed tomography (CT) scanning, and MRI can determine pre- and posttreatment disease activity or identify disease complications. [10] Cross-sectional imaging should be used to detect strictures in the case of complications. [44] Because of radiation associated with CT scanning, the preferred methods are MRI and intestinal ultrasonography. Cross-sectional imaging is also recommended for the detection of abscesses. [44]

Colonoscopy can confirm the diagnosis of suspected ulcerative colitis; it is also the technique of choice to assess disease activity in patients with symptomatic colonic Crohn disease or ulcerative colitis. [44] Note that colonoscopy findings of diffuse inflammatory changes and negative stool cultures are not sufficient for the diagnosis of ulcerative colitis but requires chronic changes over time (ie, 6 months, in the absence of other emerging diagnoses) in addition to histologic signs of chronic inflammation. [4] Complementary cross-sectional imaging can be used to assess phenotype and as an alternative to evaluate disease activity. [44]

As noted, laboratory studies are useful principally for helping to exclude other diagnoses and to assess the patient's nutritional status. However, serologic markers can assist in the diagnosis of inflammatory bowel disease.

Plain abdominal radiographs are a useful adjunct to imaging in cases of ulcerative colitis of acute onset. In severe cases, the images may show colonic dilatation, suggesting toxic megacolon, evidence of perforation, obstruction, or ileus.

Radiologic findings in cases of acute enterocolitis from infection caused by Entamoeba histolytica (amebiasis), cytomegaloviral colitis, and Isospora, Salmonella, Shigella, or Yersinia may be similar to the findings seen in cases of ulcerative colitis; this is especially true with CT scans.

Double-contrast barium enema examination is a valuable technique for diagnosing ulcerative colitis and Crohn disease, even in patients with early disease, because of its ability to depict fine mucosal detail. Traditionally, barium enema examination has been the mainstay of radiologic investigation for suspected ulcerative colitis. [45, 46, 47, 48]

Colonic biopsy samples from patients with ulcerative colitis may show significantly increased levels of platelet-activating factor (PAF). PAF release, stimulated by leukotrienes, endotoxin, or other factors, may be responsible for the mucosal inflammation; however, this process is not clear.


Serologic Markers

Much work in the past decade has focused on the development of serologic markers for inflammatory bowel disease. Antineutrophil cytoplasmic antibodies (ANCA) and anti–Saccharomyces cerevisiae antibodies (ASCA) have been the most intensely studied.

ANCA is most commonly associated with ulcerative colitis (UC). Specifically, perinuclear ANCA (pANCA), found on the inside of the nuclear membrane, is highly associated with ulcerative colitis. Positive pANCA and negative ASCA findings suggest ulcerative colitis, whereas negative pANCA and positive ASCA suggest Crohn disease. [4] ANCA assay results are positive in 60%-80% of patients with ulcerative colitis. The presence of pANCA is associated with an earlier need for surgery. The finding of ANCA is roughly 50% sensitive, is 94% specific, and has a 76% positive predictive value for ulcerative colitis. [16, 17, 19]

ASCA is more highly associated with Crohn disease and is present in 60% of cases, whereas ASCA is present in only 12% of patients with ulcerative colitis. ANCA is present in only about 40% of patients with Crohn disease. ANCA and ASCA titers are not correlated with disease activity.

In children with ambiguous and mild complaints in whom ulcerative colitis is part of the differential diagnosis, algorithms have been proposed in which the presence of ANCA is used to identify those who may require more invasive diagnostic tests. [18]

Attempts have been made to correlate ANCA titers with postoperative complications, although this association has not been proven. [20]


Other Laboratory Studies

Complete blood cell (CBC) count

Findings on CBC count may include the following:

  • Anemia (ie, hemoglobin < 14 g/dL in males and < 12 g/dL in females)

  • Thrombocytosis (ie, platelet count >350,000/µL)

Comprehensive metabolic panel

Findings on the comprehensive metabolic panel may include the following:

  • Hypoalbuminemia (ie, albumin < 3.5 g/dL)

  • Hypokalemia (ie, potassium < 3.5 mEq/L)

  • Hypomagnesemia (ie, magnesium < 1.5 mg/dL)

  • Elevated alkaline phosphatase: More than 125 U/L suggests primary sclerosing cholangitis (usually >3 times the upper limit of the reference range).

Inflammatory markers

Elevation of the erythrocyte sedimentation rate (variable reference ranges, usually 0-33 mm/h) and C-reactive protein level (ie, >100 mg/L) correlates with disease activity. [10] Fecal calprotectin is a marker of activity of inflammation [4, 10] ; it can also be used to determine mucosal healing 3-6 months after treatment initiation. [44] Fecal lactoferrin and alpha-1-antitrypsin studies are used to exclude intestinal inflammation. [4]

Stool assays

Stool studies are used to exclude other causes (see Differentials) and to rule out infectious enterocolitis. [10] These tests include evaluation of fecal blood or leukocytes, ova and parasite studies, viral studies, culture for bacterial pathogens, and Clostridium difficile titer. [4]


Endoscopy and Biopsy

Once ulcerative colitis (UC) is suspected, endoscopy must be performed. Flexible sigmoidoscopy may be performed if the symptoms are mild, and the physician is likely to initiate therapy on the basis of the results obtained. However, most physicians perform a full colonoscopy if inflammation is found with flexible sigmoidoscopy. Therefore, in most circumstances in which ulcerative colitis is suspected, directly proceeding to full colonoscopy is more cost effective. [49] This practice may be especially applicable in young children, in whom flexible sigmoidoscopy is likely to require the same degree of sedation as that of colonoscopy.

Endoscopic findings of ulcerative colitis include the following [10] :

  • Loss of vascular pattern
  • Granular and fragile mucosa
  • Ulceration, erosions, and/or pseudopolyposis

Multiple biopsy samples should be obtained from both inflamed and normal-appearing mucosa. Despite reports that biopsy results are sensitive and specific in the diagnosis of ulcerative colitis, the inherent failure rates of rectal reconstruction in ulcerative colitis due to the late diagnosis of Crohn disease or indeterminate colitis indicate that biopsy results may not be as accurate as originally thought. However, the diagnosis of Crohn disease on the basis of granuloma identification is reliable. [50]

Findings on colonoscopy with biopsy confirm a diagnosis (see the image below). Also, this evaluation is useful for documenting the extent of the disease, for monitoring disease activity, and for surveillance for dysplasia or cancer. However, be cautious in attempting colonoscopy with biopsy in a patient with severe disease because of the possible risk of perforation or other complications. Although diagnostic colonoscopy has been, [51] and continues to be, a relatively safe procedure, [52] the rate of perforation is higher in patients with severe colitis. [53]

Ulcerative Colitis. Increased postrectal space is Ulcerative Colitis. Increased postrectal space is a known feature of ulcerative colitis.

The extent of disease is defined by the following:

  • Extensive disease: Evidence of ulcerative colitis proximal to the splenic flexure

  • Left-sided disease: Ulcerative colitis present in the descending colon up to, but not proximal to, the splenic flexure

  • Proctosigmoiditis: Disease limited to the rectum with or without sigmoid involvement

Guidelines on the use of endoscopy in the diagnosis and management of inflammatory bowel disease are available from the American Society for Gastrointestinal Endoscopy. [54]


Histologic Findings

Histologically, most of the pathology in ulcerative colitis (UC) is limited to the mucosa and submucosa. In fulminant cases, the muscularis propria can be affected. Pathologic features that are typically seen include intense infiltration of the mucosa and submucosa with neutrophils and crypt abscesses, lamina propria with lymphoid aggregates, plasma cells, and mast cells and eosinophils, as well as shortening and branching of the crypts. Goblet cell depletion is also notable. These features are not unique to ulcerative colitis [10] : Except for crypt distortion, the same cellular response can be seen in acute infectious colitis or Crohn disease.


Radiologic Assessment of Ulcerative Colitis

Imaging has an important role in the workup of patients with suspected inflammatory bowel disease and in the differentiation of ulcerative colitis (UC) and Crohn disease.

Plain abdominal radiographs are a useful adjunct to imaging in cases of ulcerative colitis of acute onset. Because of its ability to depict fine mucosal detail, double-contrast barium enema examination also is a valuable technique for diagnosing ulcerative colitis and Crohn disease, even in patients with early disease.

Cross-sectional imaging studies (eg, ultrasonography [US], magnetic resonance imaging [MRI], computed tomography [CT] scanning) are useful for showing the effects of these conditions on the bowel wall.

Radionuclide studies are useful in cases of acute fulminant colitis when colonoscopy or barium enema examination is contraindicated.

Angiography may be helpful because evidence suggests microcirculatory disturbances may play an important role in the pathophysiology of ulcerative colitis.

See Ulcerative Colitis Imaging for more detailed information.