What are the differential diagnoses and evaluation approach for a patient with a colonic ulcer identified during colonoscopy?

Differential Diagnoses and Evaluation of Colonic Ulcers

Primary Differential Diagnoses

When encountering a colonic ulcer on colonoscopy, obtain biopsies from at least two sites of the ulcer and surrounding tissue, and systematically exclude infectious causes before considering inflammatory bowel disease or other etiologies. 1

Major Diagnostic Categories

Inflammatory Bowel Disease (IBD)

• Crohn's disease: Discrete ulcers with skip lesions, rectal sparing, longitudinal or aphthous ulcers, cobblestone appearance, anorectal lesions, and potential strictures of terminal ileum or ileocecal valve 1, 2
• Ulcerative colitis: Continuous inflammation starting from rectum extending proximally, diffuse mucosal involvement, absence of skip lesions, rectal involvement in >97% of untreated cases 2
• In 5-15% of cases, differentiation between Crohn's and UC is impossible, resulting in IBD-unclassified 2, 3

Infectious Colitis

• Accounts for 38% of acute hemorrhagic colitis presentations 1
• Stool cultures positive in only 40-60% of cases, making endoscopy essential 1
• CMV colitis: Variable findings from patchy erythema and micro-erosions to deep ulcers and pseudotumors, particularly in immunocompromised patients 1
• Intestinal tuberculosis: Localized involvement, patulous ileocecal valve, transverse ulcers, scars or pseudopolyps (88.9% positive predictive value for TB) 1

Ischemic Colitis

• Normal rectum with sharply defined segments of involvement, particularly "watershed territories" (sigmoid to splenic flexure) 1, 4
• Petechial hemorrhages, longitudinal ulcerations, rapid resolution on serial examinations 1
• Colonoscopy establishes diagnosis in >90% of cases 1
• Non-gangrenous form accounts for 80-85% of cases 4

NSAID-Induced Ulcers

• Sharply demarcated ulcers with predilection for terminal ileum and proximal colon 1, 5
• Diaphragm-like strictures are pathognomonic when present 1
• Multiple strictures with normal intervening mucosa 1

Other Important Causes

• Radiation colitis: Characteristic telangiectasias at colonoscopy 1
• Solitary rectal ulcer syndrome (SRUS): Related to local tissue ischemia, often in elderly 6, 5
• Stercoral ulceration: From fecal impaction, can cause perforation 6, 5
• Medication-induced: Calcium polystyrene sulfonate with sorbitol can cause severe ulceration 7

Systematic Evaluation Approach

Immediate Endoscopic Assessment

Complete the colonoscopy with ileoscopy whenever possible, even if initial findings suggest a diagnosis, as disease extent and small bowel involvement critically alter management. 2, 3

• Perform complete ileocolonoscopy to terminal ileum, not just sigmoidoscopy 2, 3
• Document ulcer characteristics: location, depth, extent, distribution pattern (continuous vs. skip lesions) 2, 3
• Assess for rectal involvement or sparing (rectal sparing strongly suggests Crohn's over UC) 2
• Identify specific features: strictures, fistulae, perianal disease, cobblestoning 3

Biopsy Protocol

Obtain at least two biopsies from five different sites including the ulcer, surrounding tissue, uninflamed areas, terminal ileum, and rectum—even from normal-appearing mucosa. 1, 2, 3

• Biopsies from unaffected areas document spared segments between inflammatory areas 2, 3
• Histology distinguishes infectious colitis (preserved crypt architecture, acute inflammation) from IBD 1
• Look for granulomas (specific for Crohn's), crypt abscesses (more common in UC at 41% vs. 19% in Crohn's), basal plasmacytosis (earliest UC feature) 1, 2

Mandatory Infectious Workup

Before finalizing any IBD diagnosis, obtain stool specimens for bacterial pathogens and C. difficile toxin testing, as negative cultures do not exclude infection. 1, 3

• Stool cultures, ova and parasites, C. difficile toxin 3
• Consider CMV testing (serology, tissue immunohistochemistry) if immunocompromised or severe colitis 1
• Tuberculosis testing if epidemiologically relevant 1

Laboratory Assessment

Perform comprehensive baseline laboratory evaluation including CBC, CRP, albumin, liver function tests, iron studies, renal function, vitamin B12, and fecal calprotectin. 1, 3

• Fecal calprotectin: 93% sensitivity, 96% specificity for IBD at threshold 100 μg/g 2, 3
• Anemia workup: ferritin <30 μg/L indicates iron deficiency without inflammation; up to 100 μg/L may indicate deficiency with inflammation 1
• CRP correlates with clinical severity in UC (except proctitis) 3

Cross-Sectional Imaging

Systematically perform MRI or CT enterography in all patients at diagnosis to evaluate small bowel involvement, transmural disease, strictures, fistulae, and extraluminal complications not visible endoscopically. 2, 3

• MRI enterography preferred over CT due to lack of radiation and superior detection of active inflammation 3
• Essential because one-third of Crohn's patients have small bowel involvement undetectable by colonoscopy 2
• Abdominal CT or ultrasound can define disease extent and complications in acute presentations 1

Critical Diagnostic Pitfalls

In indeterminate cases after complete evaluation, consider capsule endoscopy of the small intestine, which establishes Crohn's diagnosis in 17-70% of IBD-unclassified patients by demonstrating small bowel lesions. 2, 3

• A negative capsule endoscopy does not definitively exclude future Crohn's disease diagnosis 2, 3
• Backwash ileitis (mild inflammation of terminal ileum without ulceration in 20% of UC pancolitis patients) can mimic Crohn's 1
• Once IBD therapy starts, inflammation may appear segmental with rectal sparing, confounding diagnosis 1
• NSAID use must be specifically queried and discontinued before attributing ulcers to other causes 1, 5
• Colonoscopy itself rarely causes ischemic colitis; be aware of this iatrogenic possibility 8