How do you distinguish between Crohn's disease and ulcerative colitis?

Distinguishing Crohn's Disease from Ulcerative Colitis

Perform a complete ileocolonoscopy with biopsies from at least five sites (including ileum and rectum) combined with cross-sectional imaging (MRI or CT enterography) to definitively distinguish Crohn's disease from ulcerative colitis. 1

Diagnostic Algorithm

Step 1: Complete Ileocolonoscopy with Systematic Biopsies

• Obtain at least two biopsies from five different sites, including the terminal ileum and rectum, even from normal-appearing mucosa 1
• Biopsies from unaffected areas are essential to document histologically the spared segments between inflammatory areas 1
• Systematically examine the terminal ileum and all colonic segments with detailed description of lesion type, location, depth, and extent 1

Step 2: Assess Anatomical Distribution Patterns

Ulcerative Colitis:

• Always begins in the rectum (>97% of untreated cases) and extends proximally in a continuous, diffuse pattern with gradually decreasing severity 1, 2
• Rectal sparing occurs in only up to 3% of cases 1
• Inflammation limited to mucosa and occasionally submucosa 1, 3

Crohn's Disease:

• Patchy, discontinuous distribution with skip lesions throughout the gastrointestinal tract 1, 2
• Rectal sparing is common and serves as a key distinguishing feature 1
• Transmural inflammation affecting all layers of the intestinal wall 1, 3

Step 3: Cross-Sectional Imaging (MRI or CT Enterography)

• Perform systematic cross-sectional imaging in all patients at diagnosis to evaluate small intestine involvement and rule out complications 1
• This is indispensable because approximately one-third of Crohn's disease patients have small intestine involvement not detectable by colonoscopy 1

Step 4: Histopathological Features

Crohn's Disease:

• Non-cryptolytic granulomas present (absent in ulcerative colitis) 1
• Inflammatory infiltrate varies in intensity within and between biopsies 1
• Crypt abscesses less common (19%) 1
• Perianal fistulas and ulcers are common 3

Ulcerative Colitis:

• Granulomas absent 1
• Diffuse inflammatory infiltrate without variations in intensity 1
• Crypt abscesses more common (41%) 1
• Fibrosis restricted to mucosa or submucosa 1

Step 5: Clinical Presentation Patterns

Ulcerative Colitis:

• Bloody diarrhea with urgency and tenesmus as dominant features 2
• Rectal bleeding is the primary symptom 2

Crohn's Disease:

• More heterogeneous symptoms with abdominal pain as the dominant symptom 2
• Diarrhea, weight loss, and systemic symptoms more common than in ulcerative colitis 2

Step 6: Laboratory Assessment

• Obtain complete blood count, CRP, albumin, liver function tests, iron studies, renal function, and vitamin B12 1
• Fecal calprotectin (sensitivity 93%, specificity 96% for inflammatory bowel disease; optimal threshold 100 μg/g) 1
• CRP broadly correlates with clinical severity in ulcerative colitis (except proctitis) 4
• Approximately 20% of active Crohn's disease patients may have normal CRP 5

Special Diagnostic Situations

Indeterminate Colitis (5-15% of Cases)

When endoscopic and histological evaluation cannot differentiate between the two diseases:

• Capsule endoscopy of the small intestine can establish a definitive diagnosis by demonstrating small intestine lesions compatible with Crohn's disease in 17-70% of patients with unclassified inflammatory bowel disease 1
• A negative capsule endoscopy does not definitively exclude a future diagnosis of Crohn's disease 1

Additional Distinguishing Features

• Primary sclerosing cholangitis is more commonly associated with ulcerative colitis than Crohn's disease 1
• Macroscopic cobblestoning, segmental colitis, ileal stenosis and ulceration strongly suggest Crohn's disease 6

Critical Pitfalls to Avoid

• Do not rely on rectal biopsy alone for Crohn's disease diagnosis, as it is a patchy disease with many changes deep within the bowel wall 7
• Do not diagnose based on serological markers (pANCA, ASCAs) alone, as their accuracy is limited and they are ineffective at differentiating colonic Crohn's from ulcerative colitis 5
• Do not skip terminal ileum examination, even if sigmoidoscopy suggests ulcerative colitis, as complete ileocolonoscopy is imperative to establish differential diagnosis 1
• Exclude infectious causes (C. difficile, Cytomegalovirus, Campylobacter, amoebae) before finalizing diagnosis, as these can mimic inflammatory bowel disease 4, 5
• Medical treatment can induce discontinuous inflammation in ulcerative colitis, reminiscent of Crohn's disease, so review original biopsies in cases of diagnostic doubt 8