What are the steps for diagnosing and treating celiac disease (CD)?

Diagnosing and Treating Celiac Disease

The diagnosis of celiac disease requires serological testing with IgA-tissue transglutaminase (IgA-tTG) as the preferred initial test, followed by duodenal biopsy while the patient is on a gluten-containing diet, with treatment consisting of a strict lifelong gluten-free diet. 1

Diagnostic Algorithm

Step 1: Serological Testing

• Initial test: IgA-tissue transglutaminase (IgA-tTG) antibody test (sensitivity 90-96% in adults) 1
• Simultaneously measure: Total IgA levels to rule out IgA deficiency 1
• If IgA deficient: Use IgG-based testing (IgG deamidated gliadin peptide antibodies and TG2-IgG) 2, 1

Step 2: Confirmatory Testing

• If IgA-tTG positive: Proceed to duodenal biopsy via upper endoscopy 2
• If very high IgA-tTG (>10x upper limit): Consider adding endomysial antibody (EMA) testing for confirmation 2
  • When strongly positive tTG-IgA is combined with positive EMA, the positive predictive value approaches 100% 2
• If clinical suspicion remains high despite negative serology: Proceed with duodenal biopsy 1

Step 3: Duodenal Biopsy

• Timing: Must be performed while patient is on a gluten-containing diet 2, 1
• Collection: Multiple biopsies (at least 4-6) from different parts of the duodenum 2
• Histological analysis: Look for:
  • Increased intraepithelial lymphocytes (≥25 IELs per 100 enterocytes)
  • Crypt hyperplasia
  • Villous atrophy 2
• Classification: Use Marsh classification system to grade histological changes 2

Step 4: Genetic Testing (in select cases)

• HLA-DQ2/DQ8 testing: Useful in:
  • Equivocal cases
  • Patients already on gluten-free diet without prior testing
  • Screening high-risk individuals 1
• Negative predictive value: Over 99% of celiac patients carry either HLA-DQ2 (95%) or HLA-DQ8 (5%) 1

Treatment Protocol

Primary Treatment

• Strict lifelong gluten-free diet (GFD): Complete elimination of wheat, rye, barley, and contaminated oats 2, 1
• Nutritional consultation: Refer to a dietitian with expertise in celiac disease 1
• Evaluate for deficiencies: Test for iron, folate, vitamin B12, and vitamin D deficiencies 1

Monitoring Response

• Follow-up serology: Test IgA-tTG at 6 and 12 months after starting GFD, then annually 1
• Repeat biopsy: Consider in patients with persistent symptoms despite adherence to GFD 2
• Monitor for complications: Regular follow-up to assess for refractory celiac disease, ulcerative jejunoileitis, and small intestinal malignancies 3

Special Considerations

IgA Deficiency

• IgA deficiency is 10-15 times more common in celiac patients 1
• IgG-based testing (IgG-DGP, IgG-tTG) should be used in these patients 2, 1

High-Risk Groups for Screening

• First-degree relatives (7.5% risk) 1
• Patients with:
  • Type 1 diabetes
  • Autoimmune thyroid disease
  • Down syndrome
  • Turner syndrome
  • Unexplained iron deficiency anemia 1

Common Pitfalls to Avoid

• Starting GFD before testing: Can lead to false-negative results 1
• Relying solely on symptoms: Not accurate for differentiating celiac disease from other disorders 1
• Missing IgA deficiency: Always check total IgA levels with initial testing 2, 1
• Using IgG-tTG in patients with normal IgA levels: Not specific and can lead to false positives 2
• Inadequate biopsy sampling: Multiple samples from different duodenal sites are necessary 2

By following this structured approach to diagnosis and management, celiac disease can be accurately identified and effectively treated, reducing the risk of complications and improving quality of life.