What is the approach to an Inflammatory Bowel Disease (IBD) workup?

IBD Workup: A Systematic Diagnostic Approach

The diagnosis of IBD requires a multidisciplinary approach combining clinical history, laboratory testing (including negative stool cultures for infectious agents), endoscopy with multiple biopsies from different colonic segments and terminal ileum, and histopathologic confirmation. 1

Initial Clinical Assessment

Key Historical Features to Elicit

• Onset and duration of symptoms, particularly chronic diarrhea (>4 weeks), rectal bleeding, abdominal pain, and weight loss 2
• Pattern of symptoms: Relationship between abdominal pain and bowel habit changes, nocturnal symptoms, and extraintestinal manifestations 1
• Age of onset: Consider genetic testing for monogenic disorders if symptoms began before age 5 years or if presentation is particularly aggressive or refractory 1
• Family history of IBD or colorectal cancer 1
• Recent infections or antibiotic use to distinguish post-infectious functional symptoms from true IBD 3

Red Flag Symptoms Requiring Investigation

• Unintentional weight loss with objective documentation 1
• Nocturnal diarrhea 2
• Rectal bleeding 2
• Perianal disease 2

Laboratory Investigations

First-Line Blood Tests

• Complete blood count to assess for anemia (common in IBD but absent in functional disease) 3
• C-reactive protein or erythrocyte sedimentation rate (note: approximately 20% of active Crohn's disease patients may have normal CRP) 3, 1
• Coeliac serology to exclude celiac disease 1

Fecal Studies

• Stool culture first to exclude infectious causes, as fecal calprotectin will be elevated in acute infectious gastroenteritis 3
• Fecal calprotectin is the cornerstone non-invasive test:
  • Levels <50 μg/g effectively rule out IBD 3
  • Levels ≥250 μg/g indicate high suspicion for IBD and warrant colonoscopy 1
  • Indeterminate levels (100-249 μg/g): repeat testing off NSAIDs and proton pump inhibitors, then proceed to colonoscopy if remains indeterminate or abnormal 1
• C. difficile testing as infection can mimic IBD flares 4

Endoscopic Evaluation

Colonoscopy with Ileoscopy

Total colonoscopy with ileoscopy and multiple biopsies is essential for diagnosis. 1

Biopsy Protocol

• Multiple biopsies from each colonic segment (at least 2 per site) stored in separate containers to map inflammation distribution 1
• Rectal biopsies are mandatory to confirm or exclude rectal involvement 1
• Terminal ileum biopsies have highest diagnostic value, as 10-20% of UC patients have backwash ileitis, and ileoscopy helps differentiate UC from Crohn's disease 1
• Two to three tissue levels should be examined histologically, each consisting of five or more sections 1

Endoscopic Findings to Document

• Distribution and extent of inflammation 1
• Presence of ulceration, strictures, or fistulas 2
• Mucosal appearance (continuous vs. skip lesions) 2

Histopathologic Confirmation

Essential Histologic Features

The pathology report should follow the "PAID" structure: Pattern, Activity, Interpretation, and Dysplasia 1

• Pattern: Chronic changes with distribution, presence of granulomas (suggestive of Crohn's disease), architectural distortion 1
• Activity: Degree of acute inflammation 1
• Interpretation: Confirmation of IBD, differentiation between UC and Crohn's disease, or classification as "IBD unclassifiable" if distinction impossible 1

Histologic Confirmation Requirements

• Immediate fixation in buffered formalin upon biopsy collection 1
• Serial sectioning superior to step sectioning for detecting focal lesions 1
• Expert gastrointestinal pathologist review recommended for confirmation, especially for dysplasia 1

Cross-Sectional Imaging

When to Obtain Imaging

• Suspected small bowel Crohn's disease not accessible by endoscopy 4
• Obstructive symptoms: abdominal distention, pain, nausea, vomiting, or constipation suggesting strictures or complications 1
• Suspected abscess or fistula formation 5

Imaging Modalities

• MR enterography preferred to minimize radiation exposure, especially in young patients 1
• CT enterography when MRI unavailable or contraindicated 2
• Ultrasound can be used for initial assessment 1

Differential Diagnosis Considerations

Alternative Diagnoses to Exclude

• Infectious colitis: Ensure negative stool cultures before diagnosing IBD 1
• Celiac disease: Check serology 1
• Bile acid diarrhea: Consider SeHCAT testing or therapeutic trial in diarrhea-predominant cases 1
• Small intestinal bacterial overgrowth 1
• Carbohydrate intolerance 1
• Microscopic colitis: Requires histologic diagnosis 2

Post-Infectious IBS vs. IBD

This distinction is particularly challenging, as up to 27% of patients develop post-infectious IBS after bacterial gastroenteritis, and 39% of IBD patients have overlapping functional symptoms 3. Serial fecal calprotectin monitoring every 3-6 months can detect emerging inflammation in uncertain cases. 3

Common Pitfalls to Avoid

• Do not rely on symptoms alone to guide diagnosis; always use objective markers of inflammation 4
• Do not skip terminal ileum intubation and biopsy, as this significantly impacts diagnostic accuracy 1
• Do not use single-site biopsies; segmental biopsies increase diagnostic accuracy from 66% to 92% 1
• Do not dismiss the possibility of IBD with normal CRP, as 20% of active Crohn's disease patients have normal inflammatory markers 3
• Do not perform endoscopy in fulminant colitis without careful risk-benefit assessment; limit biopsies if performed 1

Multidisciplinary Team Involvement

Diagnosis should involve gastroenterologists, pathologists, and radiologists working collaboratively. 1 The minimum MDT per 250,000 population should include two gastroenterologists, two colorectal surgeons, 2.5 IBD nurses, one histopathologist, one radiologist, and one pharmacist 1.