Crohn Disease Differential Diagnoses

Updated: Jul 26, 2019
  • Author: Leyla J Ghazi, MD; Chief Editor: Praveen K Roy, MD, MSc  more...
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Diagnostic Considerations

Patients with Crohn disease frequently present with abdominal pain, nonbloody diarrhea, weight loss, fever, and, sometimes, obstructive symptoms such as nausea, early satiety, and vomiting. World Health Organization diagnostic criteria for Crohn disease include the following [57] :

  • Discontinuous or segmental lesions as well as a cobblestone appearance or longitudinal ulcer noted on radiologic studies, endoscopy, and resected specimens
  •  Transmural inflammation, as evidenced by clinical evaluation, radiologic studies, biopsy findings, and resected specimens
  • Noncaseating granulomas, as revealed on biopsy findings and resected specimens
  • Fissures and fistulas, as evidenced by clinical evaluation, radiologic studies, and resected specimens
  • Perianal disorders on clinical evaluation

A variety of intestinal manifestations and extraintestinal manifestations (EIMs) also may be observed in conjunction with either Crohn disease or ulcerative colitis. Features differentiating the two forms of inflammatory bowel disease (IBD) are summarized in Table 1, below.

Table 1. Characteristics Differentiating Crohn Disease and Ulcerative Colitis (Open Table in a new window)



Crohn Disease

Ulcerative Colitis


Entire gastrointestinal tract

Colon only, though gastritis is recognized

Skip lesions

Continuous involvement proximally from rectum


Full thickness

Mucosa only

Granulomas (15-30% in biopsy specimens; 40-60% in surgically resected bowel)

No granulomas


Entire gastrointestinal tract

Colon only

Skip lesions

Continuous involvement proximally from rectum

Fistulae, abscesses, fibrotic strictures

Mucosal disease only

Cancer risk


Estimated to be 3% at 10 years, 8% at 30 years, and 18% at 30 years after diagnosis [47] ; risk is higher in patients with primary sclerosing cholangitis and long-standing colitis (> 8-10 y); may be lower in subsequent studies (see Intestinal Manifestations).



Crohn Disease

Ulcerative Colitis



Very common







Weight loss



Perianal disease



Other diagnostic considerations

Despite extensive workup, 15% of patients with isolated colitis have an undetermined type of IBD that shows features of both Crohn disease and ulcerative colitis. The distinction is often difficult to make, especially if the patient meets all diagnostic criteria for ulcerative colitis but is a smoker or has rectal sparing—features that suggest the possibility of Crohn disease or IBD of undetermined type.

In addition, there is a subpopulation of patients with Crohn colitis who will not develop small bowel disease in their lifetime. This group represents approximately 20% of the colitis patients.

Tuberculosis is also in the differential diagnosis of Crohn disease. Simple clinical findings (eg, fever, rectal bleeding, diarrhea, symptomatic duration) appear to be most accurate for differentiating Crohn disease from intestinal tuberculosis. [57] Anti–Saccharomyces cerevisiae antibodies (ASCA) do not help in differentiating small bowel tuberculosis from small bowel Crohn disease, but if both ASCA and interferon-gamma release assays are available and the ASCA result is positive, while the interferon gamma release assay result is negative, the specificity for Crohn disease is high, particularly in Asian populations. [57] Endoscopy in combination with radiologic and laboratory findings are also useful for differentiating between Crohn disease and intestinal tuberculosis.

In addition to excluding ulcerative colitis and intestinal tuberculosis, guidelines from the World Gastroenterology Organization recommend ruling out the following in the differential diagnoses of Crohn disease [58, 57] :

  • Behςet disease

  • Celiac disease

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

  • Nonsteroidal anti-inflammatory drug (NSAID) enteropathy

Differential Diagnoses