What are the diagnostic workups for inflammatory bowel disease (IBD)?

Diagnostic Workup for Inflammatory Bowel Disease (IBD)

The diagnosis of IBD requires a comprehensive combination of clinical evaluation, laboratory tests, endoscopic procedures, radiological imaging, and histological assessment to confirm the diagnosis and differentiate between Crohn's disease (CD) and ulcerative colitis (UC).

Initial Clinical Assessment

History and Examination

• Detailed symptom history: Stool frequency/consistency, urgency, rectal bleeding, abdominal pain, malaise, fever, weight loss 1
• Travel history: Recent travel that may suggest infectious causes 1
• Medication history: NSAIDs and other medications that can mimic IBD 1
• Family history: IBD in relatives increases risk 1
• Smoking status: Particularly relevant for CD 1
• Physical examination: Assess for:
  • Vital signs (pulse, BP, temperature)
  • Signs of anemia or fluid depletion
  • Abdominal tenderness/distension
  • Palpable masses
  • Perineal examination for fistulae or abscesses 1
  • Extraintestinal manifestations (joint, skin, eye) 1

Laboratory Investigations

First-line Tests

• Complete blood count (CBC): To assess for anemia, leukocytosis, thrombocytosis 1
• Inflammatory markers:
  • C-reactive protein (CRP)
  • Erythrocyte sedimentation rate (ESR) 1, 2
• Liver function tests and renal function: Baseline assessment and to monitor for treatment toxicity 1
• Serum albumin: Assess nutritional status and disease severity 1
• Iron studies: Serum ferritin, transferrin saturation (particularly important if anemia is present) 1
  • Note: In active inflammation, serum ferritin up to 100 μg/L may still indicate iron deficiency 1

Stool Tests

• Microbiological testing: To exclude infectious causes including:
  • Clostridium difficile toxin (essential in all cases)
  • Stool culture for bacterial pathogens
  • Ova and parasites when indicated 1, 2
• Fecal calprotectin: Helpful to prioritize patients for endoscopic evaluation and distinguish IBD from functional disorders 1, 2
  • Values <50 mg/g have high sensitivity (88%) for ruling out inflammation
  • Values >250 mg/g have higher specificity (74%) for active inflammation 2

Endoscopic Evaluation

Ileocolonoscopy

• Gold standard for diagnosis of IBD 1, 2
• Biopsy protocol:
  • At least two biopsies from terminal ileum
  • At least two biopsies from each of four different colonic segments
  • At least two biopsies from rectum 1
  • Biopsies should be taken from both inflamed and uninflamed areas 1, 2
  • Sites should be clearly identified for pathological assessment 1
• Endoscopic features:
  • UC: Loss of vascular pattern, granularity, friability, ulceration (typically continuous from rectum) 1
  • CD: Skip lesions, cobblestone appearance, longitudinal ulcers, strictures 2

Upper GI Endoscopy

• Not routinely indicated in adult patients with suspected IBD unless upper GI symptoms are present 1
• Recommended in pediatric patients (<17 years) with suspected CD 1

Radiological Imaging

Plain Abdominal Radiography

• Essential in initial assessment of severe suspected IBD 1
• Helps exclude toxic megacolon/colonic dilatation
• May help assess disease extent in UC or identify proximal constipation
• May show mass in right iliac fossa or small bowel dilatation in CD 1

Cross-sectional Imaging

• CT enterography/CT with IV contrast:
  • Useful for detecting abscesses, strictures, fistulae, and extraluminal complications 1, 2
  • Particularly valuable in acute presentations 1
• MR enterography:
  • Preferred for small bowel assessment when available
  • Reduces radiation exposure (important for young patients) 2
• Small bowel imaging:
  • Small bowel follow-through or small bowel enema for assessing small intestine 1
  • Consider capsule endoscopy when high clinical suspicion but inconclusive ileocolonoscopy (after ruling out strictures) 2

Ultrasound

• Can identify thickened small bowel loops in CD
• Useful for detecting abscesses or free peritoneal fluid 1

Histopathological Assessment

Key Histological Features

• Ulcerative colitis:
  • Diffuse mucosal inflammation
  • Continuous involvement from rectum
  • Crypt architectural distortion
  • Basal plasmacytosis
  • Mucin depletion 1
• Crohn's disease:
  • Transmural, discontinuous inflammation
  • Focal crypt irregularities
  • Non-cryptolytic granulomas (when present, strongly favor CD)
  • Skip lesions 1

Important Considerations

• Provide complete clinical details to pathologist including:
  • Duration of symptoms
  • Endoscopic findings
  • Past IBD history
  • Current treatments 1
• Early disease may show preserved architecture without all classic features 1

Special Considerations

Elderly Patients

• Higher likelihood of other conditions mimicking IBD:
  • Colorectal cancer
  • Ischemic colitis
  • Segmental colitis associated with diverticulosis
  • NSAID-induced pathology
  • Radiation enteritis/colitis
  • Microscopic colitis 1
• Lower threshold for CT imaging as presentation may be atypical 2

Differential Diagnosis

• Infectious colitis (bacterial, viral, parasitic)
• Diverticular disease
• Microscopic colitis
• Ischemic colitis
• Radiation enteritis
• Medication-induced colitis
• Tuberculosis (especially with ileal involvement)
• Behçet's disease
• Lymphoma
• Vasculitis 1

Diagnostic Algorithm

1. Initial presentation with suspected IBD symptoms
2. Laboratory assessment: CBC, CRP/ESR, liver/renal function, albumin, stool studies
3. Fecal calprotectin if available (to prioritize further testing)
4. Endoscopic evaluation:
   • Mild-moderate symptoms: Complete ileocolonoscopy with biopsies
   • Severe symptoms: Limited flexible sigmoidoscopy initially, with complete colonoscopy when condition improves
5. Imaging:
   • Abdominal X-ray for severe presentations
   • Cross-sectional imaging (CT/MRI) based on clinical presentation
6. Histopathological assessment of biopsies
7. Integration of findings to establish diagnosis and disease classification

Common Pitfalls to Avoid

• Inadequate biopsy sampling: Always obtain multiple biopsies from different segments including terminal ileum and rectum 1
• Failure to exclude infection: Always test for C. difficile and other infectious causes before confirming IBD diagnosis 1
• Premature diagnosis: Indeterminate colitis may be appropriate when features are not clearly UC or CD 3
• Overlooking medication effects: NSAIDs and other drugs can cause enteropathy mimicking IBD 1
• Inadequate imaging in CD: Small bowel assessment is essential in suspected CD 1
• Misinterpreting iron studies: In inflammation, ferritin up to 100 μg/L may still indicate iron deficiency 1