What is the recommended approach for celiac serology testing and diagnosis?

Recommended Approach for Celiac Disease Serology Testing and Diagnosis

The recommended approach for celiac disease diagnosis begins with IgA tissue transglutaminase antibody (tTG-IgA) as the first-line serological test, followed by duodenal biopsy for definitive diagnosis if serology is positive. 1

Initial Serological Testing

• First-line test: tTG-IgA (sensitivity 90-96% in adults, 97.7% in children) 1
• Total IgA level: Should be checked concurrently to rule out IgA deficiency 1
• For IgA deficiency: Order IgG-based tests (IgG-tTG, IgG-EMA, or IgG-DGP) 1
• For weakly positive tTG-IgA: Order IgA endomysial antibody (EMA-IgA) as a confirmatory test (sensitivity 88%, specificity 99.6% in adults) 1

Important Testing Considerations

• Patients must maintain regular gluten consumption before testing (1-3 slices of gluten-containing bread daily for at least 6 weeks) 1
• Premature gluten restriction can lead to false-negative results by reducing lesion severity 1
• Avoid using antigliadin antibodies (AGA) as primary screening due to inferior accuracy 1
• Commercial laboratory variability exists - sensitivity can range from 40% to 86.4% between different labs 2

Diagnostic Algorithm

1. High clinical suspicion + positive tTG-IgA: Proceed to duodenal biopsy
2. High clinical suspicion + negative serology: Consider HLA-DQ2/DQ8 genetic testing
   • If HLA-DQ2/DQ8 positive: Proceed to intestinal biopsy
   • If HLA-DQ2/DQ8 negative: Celiac disease virtually excluded 1
3. High tTG-IgA levels (≥10x upper limit of normal) + positive EMA-IgA:
   • In children: May diagnose without biopsy
   • In adults: Still require biopsy confirmation 1

Biopsy Procedure and Interpretation

• Obtain multiple biopsy specimens (ideally 6) from the second part of duodenum or beyond 1
• Characteristic histological findings:
  • Villous atrophy
  • Crypt hyperplasia
  • Increased intraepithelial lymphocytes
  • Increased lamina propria lymphocytes 1

Biopsy Pitfalls to Avoid

• Inadequate sampling (celiac disease can be patchy) 1
• Performing biopsy while patient is on a gluten-free diet (can lead to false negatives) 1
• Relying solely on serology without biopsy in adults 1

Special Considerations

• Sensitivity of tTG-IgA is significantly lower in patients with partial villous atrophy (42.3%) compared to total villous atrophy (90%) 2
• Some research suggests that very high tTG-IgA levels (>70 IU/ml or >12 times the upper limit of normal) have high correlation with diagnostic biopsy findings (sensitivity 83.9%, specificity 56.1%) 3
• At-home celiac tests should be avoided due to lower accuracy and lack of professional oversight 1

Post-Diagnosis Monitoring

• Implement strict gluten-free diet under dietitian guidance 1
• Monitor with serological testing at 6 and 12 months after diagnosis, then yearly 1
• Consider repeat biopsies for patients with persistent symptoms despite negative serology 1

Accurate diagnosis is crucial for preventing complications including osteoporosis, infertility, and small bowel cancer in untreated celiac disease 1.