What diagnostic test involving a biopsy diagnoses coeliac disease?

Duodenal Biopsy is the Diagnostic Test for Coeliac Disease

The definitive diagnostic test for coeliac disease is upper endoscopy with multiple duodenal biopsies, which remains the gold standard for diagnosis in adults. 1

Diagnostic Process for Coeliac Disease

Initial Serological Testing

• IgA tissue transglutaminase (TTG) antibody is the preferred first-line serological test for patients older than two years 1
• Total IgA levels should be measured, especially in patients with high probability of coeliac disease, to rule out IgA deficiency which could affect test interpretation 1, 2
• IgG-based testing should be performed in patients with low IgA levels or selective IgA deficiency 1
• All serological testing must be performed while the patient is on a gluten-containing diet (for at least six weeks) to avoid false-negative results 3

Confirmatory Biopsy Testing

• Upper endoscopy with small bowel biopsy is a critical component of the evaluation and cannot be replaced by serology alone 1
• Multiple duodenal biopsies are required: at least 4-6 specimens should be obtained, including:
  • One or two biopsies from the duodenal bulb 1
  • At least four biopsies from the distal duodenum 1
• The biopsies must be properly oriented for accurate assessment of villous height to crypt depth ratio 1

Histopathological Features

• Diagnostic histological changes include:
  • Increased intraepithelial lymphocytes (≥25 per 100 enterocytes)
  • Crypt hyperplasia
  • Villous atrophy 1
• The Marsh classification is commonly used to describe the spectrum of histological changes 1

Special Considerations

Discordant Results

• If serological tests are negative but clinical suspicion remains high, duodenal biopsy should still be pursued 1
• In patients with persistently positive coeliac serology but normal mucosa, repeat small intestinal biopsy should be considered, including biopsies from the jejunum 1, 4

Alternative Approaches

• Capsule endoscopy may have a supportive role in patients unable or unwilling to undergo endoscopy, but should not be used for initial diagnosis except in specific circumstances 1
• HLA-DQ2 and HLA-DQ8 testing may be useful to rule out coeliac disease in select patients due to its high negative predictive value (>99% when both test results are negative) 1, 3

Diagnostic Pitfalls

• Lymphocytic infiltration of the intestinal epithelium without villous atrophy is not specific for coeliac disease and other causes should be considered 1
• A biopsy finding of villous atrophy is not specific for coeliac disease; therefore, positive coeliac-specific serology is needed to seal the diagnosis 1
• Duodenal biopsies are sufficient to diagnose full-blown coeliac disease (Marsh III), but milder lesions (Marsh I-II) may be missed in some cases, requiring jejunal biopsies 4

Diagnostic Algorithm

1. Perform serological testing (IgA-TTG) while patient is on gluten-containing diet
2. Measure total IgA levels to rule out IgA deficiency
3. Proceed to upper endoscopy with multiple duodenal biopsies regardless of serological results if clinical suspicion is high
4. Confirm diagnosis based on combination of clinical, serological, and histopathological findings
5. Consider HLA-DQ2/DQ8 testing in select cases with equivocal results

The combination of positive serology and characteristic histological changes on duodenal biopsy provides the most definitive diagnosis of coeliac disease 1.