What are the recommended investigations for celiac disease?

Recommended Investigations for Celiac Disease

The diagnosis of celiac disease requires a combination of serological testing with IgA-tissue transglutaminase (IgA-tTG) as the initial test, followed by duodenal biopsies via upper endoscopy while the patient is on a gluten-containing diet. 1

Initial Diagnostic Testing Algorithm

First-line Serological Testing

• IgA-tissue transglutaminase (IgA-tTG) - primary screening test with sensitivity of 90-96% in adults 1
• Total IgA levels - should be measured simultaneously to rule out IgA deficiency 1, 2

For IgA-deficient Patients

• IgG deamidated gliadin peptide antibodies (IgG-DGP) 2, 1
• IgG tissue transglutaminase (IgG-tTG) - only in IgA deficiency 2, 1

Important: IgG isotype testing for TG2 antibody is not specific in patients with normal IgA levels and can lead to false positives 2, 1

Confirmatory Testing

• Endomysial antibody (EMA-IgA) - highly specific (>90%) confirmatory test 1
  • When a strongly positive TG2-IgA (>10× upper limit of normal) is combined with positive EMA-IgA in a second blood sample, the positive predictive value for celiac disease approaches 100% 2

Histological Assessment

Endoscopic Biopsy Requirements

• Multiple duodenal biopsies (at least 4-6) from different parts of the duodenum 1
• Patient must be on a gluten-containing diet during testing 2, 1
• Avoid gluten reduction prior to diagnostic testing as it reduces sensitivity of both serology and biopsy 2

Histological Evaluation

• Marsh classification should be used to grade intestinal damage 2, 1
• Look for:
  • Increased intraepithelial lymphocytes (≥25 IELs per 100 enterocytes)
  • Crypt hyperplasia
  • Villous atrophy 1

Special Diagnostic Situations

When Patient Has Already Started Gluten-Free Diet

• Return to normal diet with three slices of wheat bread daily for 1-3 months before repeat testing 2

When Biopsies Are Negative but Suspicion Remains High

• Perform TG2-IgA testing if not already done
• Consider repeat biopsies at a later date 2

Role of HLA Testing

• HLA-DQ2/DQ8 typing has limited diagnostic role but high negative predictive value 2
• Useful in three specific scenarios:
  1. Seronegative patients with histologic changes
  2. Patients without serologic confirmation at time of diagnosis
  3. Patients with historic diagnosis of celiac disease (especially young children diagnosed before celiac-specific serology) 2

Monitoring After Diagnosis

• Anti-tTG antibody levels at 6 months, 12 months, and annually thereafter 1
• Annual clinical assessment for symptom resolution, nutritional status, and complications 1
• Persistently positive or non-decreasing anti-tTG levels suggest poor adherence or gluten contamination 1

Caution: Serological tests have low sensitivity (below 50%) for detecting persistent villous atrophy in patients already on a gluten-free diet 3

High-Risk Groups Requiring Screening

• First-degree relatives of celiac disease patients (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 gluten-free diet before testing - leads to false-negative results 1
• Inadequate biopsy sampling - can lead to misdiagnosis 1
• Overlooking IgA deficiency - causes false-negative IgA-based test results 1
• Relying solely on symptoms - not accurate for differentiating celiac disease from other disorders 1
• Using IgG-tTG in patients with normal IgA levels - leads to false positives 1
• Assuming negative serology guarantees mucosal healing - serology has poor sensitivity for persistent villous atrophy 1, 3