Ulcerative Colitis Differential Diagnoses

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

Diagnostic Considerations

Differentiation between ulcerative colitis (UC) and Crohn disease is critical to developing a treatment plan (see Table 1 below). In addition, prolonged use of cathartics, especially cascara, over many years may lead to a condition known as cathartic colon. Other problems to be considered include collagenous colitis and lymphocytic colitis (rarely requires surgery, low risk for malignancy), infectious colitis, ischemic colitis in elderly patients, and radiation colitis.

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 computed tomography (CT) scans.

Ulcerative colitis versus Crohn disease

Grossly, Crohn disease is characteristically noncontiguous, with intervening, or skipped, areas of normal mucosa. The ulcerations in Crohn disease tend to be linear and often lead to the classic cobblestone appearance of the mucosa. Crohn disease may involve the entire gastrointestinal tract, whereas ulcerative colitis involves only the large bowel.

Microscopically, the inflammation in ulcerative colitis and Crohn disease can appear similar, but noncaseating granulomas are present only in Crohn disease (in 60% of Crohn disease specimens; never present in ulcerative colitis specimens); therefore, their presence is specific for Crohn disease. The inflammation of Crohn disease may be transmural, whereas it is confined to the mucosa and submucosa in ulcerative colitis. Unfortunately, the differentiation is not always possible preoperatively. All large series of proctocolectomies include a subset of patients (approximately 10%) who were preoperatively thought to have ulcerative colitis but were subsequently diagnosed with Crohn disease.

The traditional idea that ulcerative colitis involves only the large bowel has been challenged. Significant gastroduodenal inflammation in children with ulcerative colitis has been reported. However, aphthous ulceration is considered unique to Crohn disease. [9] In addition, patchy inflammation of the colonic mucosa suggestive of skip lesions may occur during the treatment phase of ulcerative colitis, leading one to question the diagnosis. These patchy areas may be seen endoscopically in as many as 38% of patients with ulcerative colitis who undergo medical therapy. Rectal sparing may also occur at some point during medical treatment of ulcerative colitis in as many as 44% of cases. [41] Proximal disease may be seen even after proctocolectomy. Capsule endoscopy has demonstrated patchy inflammation in the proximal bowel in patients with chronic pouchitis following proctocolectomy with ileal pouch reconstruction. [42]

Table 1. Distinguishing Ulcerative Colitis from Crohn Disease (Open Table in a new window)

Ulcerative Colitis

Crohn Disease

Only colon involved


Continuous inflammation extending proximally from rectum

Skip-lesions with intervening normal mucosa

Inflammation in mucosa and submucosa only

Transmural inflammation


Perianal lesions

No granulomas

Noncaseating granulomas

Perinuclear ANCA (pANCA) positive

ASCA positive

Bleeding (common)

Bleeding (uncommon)

Fistulae (rare)

Fistulae (common)

ANCA = antineutrophil cytoplasmic antibodies; ASCA = anti– Saccharomyces cerevisiae antibodies.

Cathartic colon

The radiologic appearance of cathartic colon is similar to that of ulcerative colitis. In cathartic colon, the changes are more marked in the right hemicolon than in the left. The bowel is distensible, and there are inconstant areas of bowel narrowing and haustral loss.

Other diagnostic considerations

In addition to excluding Crohn disease, guidelines from the World Gastroenterology Organization recommend ruling out the following in the differential diagnosis of ulcerative colitis [4, 43] :

  • Chronic schistosomiasis

  • Amebiasis

  • Intestinal tuberculosis

  • Infectious, ischemic, or radiation colitis

  • Acute self-limiting colitis (ASLC)

  • Colon cancer

  • Irritable bowel syndrome (IBS) (if inflammatory changes are present, it is not IBS)

  • Nonsteroidal anti-inflammatory drug (NSAID) enteropathy

Differential Diagnoses