What is the initial test for a patient suspected of having celiac disease?

Initial Testing for Celiac Disease

The initial test for a patient suspected of having celiac disease is IgA tissue transglutaminase antibody (tTG-IgA) combined with total IgA level measurement, performed while the patient is consuming a gluten-containing diet. 1, 2

Primary Screening Test

• IgA tissue transglutaminase (tTG-IgA) is the single most efficient and accurate screening test, with sensitivity of 90-96% and specificity >95% in adults 1, 2
• This test must be performed while the patient consumes at least 10g of gluten daily (approximately 3 slices of wheat bread) for 6-8 weeks prior to testing 1, 2, 3
• Starting a gluten-free diet before testing dramatically reduces sensitivity and leads to false-negative results 1, 2, 3

Essential Concurrent Testing

• Total IgA level must be measured simultaneously with tTG-IgA to identify IgA deficiency 1, 2
• IgA deficiency occurs in 1-3% of celiac disease patients and causes falsely negative IgA-based antibody tests 1, 2, 4
• If IgA deficiency is confirmed, switch to IgG-based testing: IgG deamidated gliadin peptide (DGP-IgG) or IgG tTG 1, 2

Confirmatory Serologic Testing

• When tTG-IgA is elevated (especially >10× upper limit of normal), IgA endomysial antibody (EMA-IgA) should be performed as confirmatory testing 1, 2
• EMA-IgA has excellent specificity of 99.6% but is more operator-dependent and time-consuming than tTG-IgA 1
• The combination of tTG-IgA >10× upper limit of normal plus positive EMA-IgA approaches 100% positive predictive value for celiac disease 1, 2, 4

Tests to Avoid for Initial Screening

• Antigliadin antibody (AGA) tests are not recommended due to poor sensitivity and specificity compared to tTG-IgA and EMA-IgA 1, 5
• IgG tTG testing should not be used in patients with normal IgA levels, as it has markedly lower accuracy (sensitivity 40.6-84.6%, specificity 78.0-89.0%) 1, 2
• There is no advantage to using a panel of multiple tests over the single tTG-IgA test for initial screening 1, 5

Next Steps After Positive Serology

• All seropositive adults must undergo upper endoscopy with duodenal biopsies for definitive diagnosis 1, 2, 4
• At least 6 biopsy specimens should be obtained: 1-2 from the duodenal bulb and at least 4 from the second part of the duodenum or beyond 1, 2, 4
• Biopsy remains mandatory in adults despite high antibody levels to establish definitive diagnosis and exclude other causes of villous atrophy 1, 2, 4

Special Populations Requiring Testing

• First-degree relatives of celiac disease patients should be tested even without symptoms 1, 2, 4
• Patients with type 1 diabetes mellitus, autoimmune thyroid disease, or Down syndrome require testing 1, 2
• Unexplained iron deficiency anemia, premature osteoporosis, or unexplained liver transaminase elevations warrant testing 1, 2, 4

Critical Pitfalls to Avoid

• Never initiate a gluten-free diet before completing diagnostic testing, as this leads to false-negative serology and inconclusive biopsies 1, 2, 3
• Do not rely on serology alone without biopsy confirmation in adults, as this can lead to misdiagnosis 1, 2, 3
• If the patient has already reduced gluten intake, they must resume consuming at least 10g of gluten daily for 1-3 months before repeat testing 1, 2, 3
• Measuring only tTG-IgA without total IgA level risks missing IgA-deficient patients who will have falsely negative results 1, 2, 4

When Serology is Negative Despite High Clinical Suspicion

• Confirm the patient was consuming adequate gluten (≥10g daily for 6-8 weeks) when tested 1, 2, 3
• Verify total IgA level was measured to exclude IgA deficiency 1, 2, 4
• Consider HLA-DQ2/DQ8 testing, which has >99% negative predictive value—absence of both alleles essentially rules out celiac disease 1, 2, 4
• If clinical suspicion remains high despite negative serology and positive HLA, proceed directly to upper endoscopy with duodenal biopsies 1, 2, 3