Celiac Disease Serology for Iron Deficiency Anemia
Order IgA tissue transglutaminase antibody (tTG-IgA) along with total IgA level as the initial screening test for celiac disease in all patients with iron deficiency anemia. 1, 2
Recommended Serologic Tests
Primary Screening Panel
- tTG-IgA (tissue transglutaminase IgA antibody) is the first-line test with 90.9% sensitivity and specificity, and a negative predictive value of 99.6% 1
- Total IgA level must be ordered simultaneously to detect IgA deficiency, which occurs in 1-3% of celiac patients and causes false-negative results 2, 3
Confirmatory Testing (When Needed)
- Endomysial antibody (EMA-IgA) can be added for confirmation when tTG-IgA is positive, providing 99.6% specificity 1, 2
- When tTG-IgA is >10 times the upper limit of normal combined with positive EMA-IgA, the positive predictive value approaches 100% 1, 2
Critical Pre-Test Requirements
Patients must consume at least 10g of gluten daily (approximately 3 slices of wheat bread) for 6-8 weeks before testing to avoid false-negative results 2, 3. This is a common pitfall—reduction or avoidance of gluten significantly reduces test sensitivity 3.
No fasting is required before drawing blood for celiac serology 2, 3.
Clinical Context and Prevalence
Celiac disease is found in 3-5% of patients with unexplained IDA, making routine screening essential 1. This prevalence extends to iron deficiency without anemia 2. Even asymptomatic patients warrant screening, as iron deficiency is one of the most common extraintestinal manifestations of celiac disease 1.
Age-Related Considerations
Younger Patients
- In younger patients with IDA, celiac serology has high sensitivity and the risk of other serious pathology is lower 1
- If serology is negative, gastroscopy with biopsy may not be immediately necessary unless other risk factors are present 1
Older Patients (>50-70 years)
- Sensitivity of celiac serology falls with age, potentially as low as 74% in older patients presenting with IDA 1
- Seronegative celiac disease accounts for up to 10% of celiac cases, with the highest relative prevalence in the elderly 1
- Bidirectional endoscopy with duodenal biopsy is more appropriate in older patients regardless of serology results, given higher risk of GI malignancy and dual pathology 1
Next Steps After Positive Serology
If tTG-IgA is positive, proceed to upper endoscopy with duodenal biopsies (at least 6 biopsies from the second and third portions of the duodenum) for histologic confirmation 1, 2, 3. Small intestinal biopsy remains the gold standard, showing villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes 2.
Common Pitfalls to Avoid
- Never start a gluten-free diet before completing diagnostic testing (both serology and confirmatory biopsy if positive), as this will render subsequent testing unreliable 2, 3
- Do not skip total IgA testing—IgA deficiency will cause false-negative tTG-IgA results 2, 3
- Do not rely solely on serology in older patients—proceed to endoscopy with duodenal biopsy given reduced sensitivity 1
- Do not assume negative serology excludes celiac disease in patients with persistent IDA despite iron replacement, especially in older adults 1