What labs should be ordered to screen for celiac disease in a patient with iron deficiency without anemia?

Celiac Disease Screening for Iron Deficiency Without Anemia

For patients with iron deficiency without anemia, order IgA tissue transglutaminase antibody (tTG-IgA) along with total IgA level to screen for celiac disease. 1, 2

Recommended Laboratory Panel

The essential tests to order are:

• IgA tissue transglutaminase antibody (tTG-IgA) - This is the preferred first-line screening test with 90-96% sensitivity and >95% specificity 1, 2, 3
• Total IgA level - Must be measured concurrently to rule out IgA deficiency, which occurs in 2-3% of celiac patients and causes false-negative tTG-IgA results 1, 2, 4

Additional Testing if IgA Deficiency is Present

If total IgA is low or absent:

• IgG deamidated gliadin peptide (DGP-IgG) antibodies 1, 2
• IgG tissue transglutaminase antibody (tTG-IgG) 1

Note that IgG isotype testing is not specific in the absence of IgA deficiency 1

Confirmatory Testing

If tTG-IgA is positive:

• Endomysial antibody (EMA-IgA) can be added for confirmation, as it has 99.6% specificity 1, 4
• When tTG-IgA is >10 times the upper normal limit combined with positive EMA in a second blood sample, the positive predictive value for celiac disease is virtually 100% 1

Critical Pre-Test Requirements

The patient MUST be consuming gluten at the time of testing - at least 10g daily (approximately 3 slices of wheat bread) for 6-8 weeks prior to testing to avoid false-negative results 1, 2, 4. Testing on a gluten-free diet significantly reduces sensitivity and is a common pitfall 2, 3, 4

Clinical Context and Rationale

Iron deficiency without anemia warrants celiac screening because:

• Approximately 5% of patients with iron deficiency anemia have celiac disease, and this prevalence likely extends to iron deficiency without anemia 1, 4
• Iron deficiency is one of the most common extraintestinal manifestations of celiac disease 2, 5
• The British Society of Gastroenterology guidelines specifically recommend celiac serology (tTG or endomysial antibody) at presentation for iron deficiency 1
• Studies show 10-14% of patients with iron deficiency anemia have celiac disease in some populations 6, 7

When to Proceed to Biopsy

If celiac serology is positive, refer for upper endoscopy with duodenal biopsies to confirm the diagnosis 1, 2. Small intestinal biopsy remains the gold standard, showing villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes 2

However, if tTG-IgA is negative, the post-test probability of celiac disease drops to 0.3% (less than the general population), making duodenal biopsy unnecessary unless other features like diarrhea are present 1

Common Pitfalls to Avoid

• Testing while gluten-free - This is the most common error and leads to false-negative results 2, 3, 4
• Failing to check total IgA - Missing IgA deficiency results in false-negative tTG-IgA tests 1, 2, 4
• Using IgG tests without IgA deficiency - IgG-based tests lack specificity when IgA is normal 1