What is the recommended testing and treatment approach for a patient suspected of having celiac disease, particularly those presenting with gastrointestinal symptoms or malabsorption?

Celiac Disease Antibody Testing

Primary Screening Test

IgA anti-tissue transglutaminase (tTG-IgA) is the single preferred screening test for celiac disease in patients over 2 years of age, and must be performed while the patient is actively consuming gluten. 1, 2

Essential Testing Algorithm

Step 1: Initial Screening

• Order tTG-IgA PLUS total IgA level simultaneously 1, 3, 2
  • The total IgA is critical because IgA deficiency occurs in 1-3% of celiac disease patients (versus 1 in 500 in general population), causing falsely negative tTG-IgA results 1
  • No fasting is required before blood draw 3

Step 2: Critical Pre-Test Requirement

• Patient must consume at least 10g of gluten daily (approximately 3 slices of wheat bread) for 6-8 weeks before testing 3, 2, 4
  • Testing patients already on a gluten-free diet will produce false-negative results 1, 2
  • This is the most common diagnostic pitfall to avoid 2

Step 3: Confirmatory Testing Based on Results

If tTG-IgA is positive:

• Add IgA endomysial antibody (EMA) for confirmation 1
  • EMA has 99.6% specificity and is ideal for second-line confirmation 2
  • When tTG-IgA is >10 times upper normal limit AND EMA is positive, the positive predictive value approaches 100% 3
• Proceed to upper endoscopy with duodenal biopsies (1-2 from bulb, at least 4 from distal duodenum) for definitive diagnosis 1, 4

If total IgA is low or deficient:

• Switch to IgG-based testing: IgG anti-tissue transglutaminase or IgG deamidated gliadin peptides 1
• IgA-based tests are unreliable in IgA deficiency 1

In children under 2 years:

• Combine tTG-IgA with both IgG and IgA deamidated gliadin peptides to improve sensitivity 1, 2

Tests NOT Recommended

• Anti-gliadin antibodies (IgA or IgG) are less specific than tTG or EMA and should not be used for screening 1
• Isolated tTG-IgG when tTG-IgA is negative has only 3% utility in diagnosing celiac disease 5
• Point-of-care tests have quality control issues and offer no decisive advantage 1

Performance Characteristics

The evidence strongly supports tTG-IgA as the optimal screening test:

• Sensitivity: 89-92% 6, 7
• Specificity: 98-99% 6, 7
• Positive likelihood ratio: 37.7-171 7
• Negative likelihood ratio: 0.11 7

EMA performs similarly but is more labor-intensive and operator-dependent 1

Who Should Be Tested

Target patients with pre-test probability of 5-10% or higher to maximize positive predictive value 1:

Symptomatic patients with:

• Chronic diarrhea, weight loss, steatorrhea, abdominal pain/bloating 1, 2, 4
• Iron deficiency anemia (5% have celiac disease) 3, 2
• Unexplained liver enzyme elevations 2
• Malabsorption symptoms 1

High-risk asymptomatic patients:

• First-degree relatives (7.5% prevalence) 1, 2
• Type 1 diabetes (5-10% prevalence) 1
• Autoimmune thyroid disease 1
• Down syndrome or Turner syndrome 1
• Premature osteoporosis 2

Additional Baseline Testing at Diagnosis

Once celiac disease is suspected or confirmed, assess for malabsorption-related deficiencies 2, 4:

• Complete blood count (iron deficiency anemia) 1, 2
• Iron studies, folate, vitamin B12 1, 2
• Vitamin D and calcium (for bone health) 2, 4
• Liver function tests 1
• Albumin (hypoalbuminemia predicts mortality) 2

Role of HLA-DQ2/DQ8 Testing

Do NOT order HLA-DQ2/DQ8 testing routinely 1, 4

HLA testing has limited utility because:

• HLA-DQ2 is present in 25-30% of the general white population 1
• It has >99% negative predictive value but poor positive predictive value 1, 4

Reserve HLA testing only for:

• Patients with equivocal biopsy findings 1
• Patients already on gluten-free diet without prior testing 1
• Patients with discrepant serology and histology 1

Common Pitfalls to Avoid

1. Testing patients already avoiding gluten - this dramatically reduces test sensitivity 1, 3, 2
2. Failing to check total IgA level - missing IgA deficiency leads to false-negative results 1, 2
3. Using anti-gliadin antibodies for screening - these are outdated and less accurate 1
4. Relying on symptoms alone - symptoms cannot differentiate celiac disease from other GI disorders 1
5. Ordering HLA testing as first-line - this is not a diagnostic test 1, 4