What is the diagnostic and treatment approach for a patient with suspected coeliac disease, including the use of coeliac serology (blood tests for tissue transglutaminase antibody, endomysial antibody, and deamidated gliadin peptide antibody)?

Diagnostic and Treatment Approach for Suspected Coeliac Disease

For patients with suspected coeliac disease, serologic testing with IgA tissue transglutaminase antibody (tTG-IgA), IgA endomysial antibody (EMA-IgA), and deamidated gliadin peptide antibodies (DGP) should be performed as the initial diagnostic step, followed by duodenal biopsy for confirmation if serology is positive. 1, 2

Initial Diagnostic Evaluation

Serologic Testing

• First-line serologic tests:

  • IgA tissue transglutaminase antibody (tTG-IgA) - sensitivity 97.7%, specificity 70.2% 2
  • IgA endomysial antibody (EMA-IgA) - sensitivity 94.5%, specificity 93.8% 2
  • IgA/IgG deamidated gliadin peptide antibodies (DGP) - sensitivity 91-92.9%, specificity 98-100% 3, 4

• Total IgA level measurement:

  • Essential to rule out selective IgA deficiency which occurs in 2-3% of coeliac patients 2
  • If IgA deficiency is present, IgG-based tests should be used:
    • IgG tissue transglutaminase (tTG-IgG)
    • IgG deamidated gliadin peptide (DGP-IgG) 2

Important Considerations for Serologic Testing

1. Ensure adequate gluten exposure:

   • Patients should not avoid gluten before diagnostic testing 2
   • If already on a gluten-free diet, a gluten challenge is required (1-3 slices of gluten-containing bread daily for 1-3 months) 2

2. Combination testing approach:

   • Using tTG-IgA first followed by EMA-IgA provides sensitivity 85.7%, specificity 98.6% 5
   • Combining DGP and tTG tests offers the best sensitivity without loss of specificity 3

3. HLA testing:

   • HLA DQ2/DQ8 testing can be valuable - negative results effectively rule out coeliac disease (<1% chance if negative) 2
   • Particularly useful in seronegative cases with suspected coeliac disease 1

Confirmatory Testing

Duodenal Biopsy

• Gold standard for diagnosis if serology is positive 2
• At least 6 duodenal biopsy specimens should be obtained 2
• Histologic findings should be reviewed by experienced GI pathologists 1
• Villous atrophy (Marsh class 3) confirms diagnosis 6

Special Scenarios

Seronegative Enteropathy

For patients with suspected coeliac disease but negative serology:

1. Confirm adequate gluten exposure
2. Test for IgA deficiency
3. Perform HLA DQ2/DQ8 testing (negative results rule out coeliac disease)
4. Consider duodenal biopsy if clinical suspicion remains high 1
5. If villous atrophy is present with negative serology:
   • Review medication history (especially angiotensin II receptor blockers like olmesartan)
   • Obtain travel history to identify other potential causes of enteropathy 1

Treatment Approach

Gluten-Free Diet

• Primary treatment: Strict, lifelong gluten-free diet with complete elimination of wheat, rye, and barley 2
• Monitoring response:
  • Clinical assessment for symptom resolution
  • Nutritional status evaluation
  • Weight management 2

Follow-up Evaluation

1. Serologic monitoring:

   • Anti-tTG antibodies at 6 months, 12 months, and annually thereafter 2
   • Antibody levels typically decline within 3 months of starting a gluten-free diet 7

2. Follow-up biopsy:

   • For seronegative patients with villous atrophy and genetic risk factors, endoscopic evaluation after 1-3 years on a gluten-free diet 1
   • Important to note: Normal tTG levels do not guarantee intestinal healing (44% of patients with persistent villous atrophy may have normal tTG) 5

3. Nutritional assessment:

   • Evaluate and supplement any deficiencies (iron, folate, vitamin B12)
   • Bone mineral density assessment for osteoporosis 2

Common Pitfalls and Caveats

• False negative serology: Can occur with IgA deficiency or insufficient gluten intake
• Isolated DGP positivity: Can identify coeliac disease in tTG-negative individuals (15.5% of cases) 6
• Persistent symptoms despite negative serology: Consider follow-up biopsy as serology has low sensitivity (<50%) for detecting persistent villous atrophy 2
• Non-coeliac gluten sensitivity: Should only be considered after coeliac disease has been ruled out with negative serology, normal duodenal biopsies while on gluten-containing diet, symptom improvement on gluten-free diet, and symptom recurrence with gluten challenge 2

By following this diagnostic and treatment algorithm, clinicians can effectively identify and manage patients with coeliac disease, including challenging cases with seronegative presentations.