What is the initial step in a celiac (celiac disease) workup?

Initial Step in Celiac Disease Workup

The initial step is IgA tissue transglutaminase antibody (tTG-IgA) testing combined with total IgA level measurement, performed while the patient is actively consuming a gluten-containing diet. 1, 2

Primary Serologic Testing

• tTG-IgA is the preferred screening test with sensitivity of 90-96% and specificity >95%, making it the most reliable initial diagnostic tool 1, 2, 3
• Total IgA level must be measured simultaneously to identify IgA deficiency, which occurs in 1-3% of celiac patients and causes false-negative tTG-IgA results 2, 4
• Testing must occur while consuming adequate gluten: at least 10g daily (approximately 3 slices of wheat bread) for 6-8 weeks prior to testing 2, 4

Critical Pitfall to Avoid

• Never allow patients to start a gluten-free diet before completing diagnostic testing, as this leads to false-negative serologic and histologic results 2, 4
• If a patient has already eliminated gluten, they must resume a gluten-containing diet for 1-3 months before testing, though some may require several years for histologic relapse 2

When to Measure Total IgA

• Measure total IgA in all patients being tested for celiac disease, particularly those with first-degree relatives who have the disease 1
• If IgA deficiency is detected, switch to IgG-based testing: IgG deamidated gliadin peptide (DGP-IgG) or IgG tissue transglutaminase (tTG-IgG) 1, 2
• Do not use IgG-based tests in patients with normal IgA levels, as they are markedly less accurate in this setting 2

Age-Specific Considerations

• For children under 2 years: Combine tTG-IgA with IgG and IgA deamidated gliadin peptides to improve sensitivity 1, 2
• For adults and children over 2 years: tTG-IgA alone is sufficient as the initial test 1

Next Steps After Initial Testing

If tTG-IgA is Elevated

• When tTG-IgA is >10× upper limit of normal: Perform IgA endomysial antibody (EMA-IgA) as confirmatory testing, which has excellent specificity of 99.6% 1, 2, 4
• The combination of tTG-IgA >10× upper limit of normal plus positive EMA-IgA approaches 100% positive predictive value for celiac disease 2, 4
• Proceed to upper endoscopy with multiple duodenal biopsies (at least 6 specimens: 1-2 from duodenal bulb and 4+ from second part of duodenum or beyond) for definitive diagnosis in adults 2, 4

If tTG-IgA is Negative but Clinical Suspicion Remains High

• Confirm adequate gluten intake and verify total IgA level is normal 2
• Consider HLA-DQ2 and HLA-DQ8 testing, which has >99% negative predictive value—absence of both alleles essentially rules out celiac disease 1, 2, 4
• If HLA is positive, proceed to biopsy despite negative serology, as seronegative celiac disease can occur 1, 2

High-Risk Groups Warranting Testing

Even without typical symptoms, test patients with:

• First-degree relatives of celiac patients (7.5% risk) 1, 2, 3
• Type 1 diabetes mellitus (5-10% prevalence) 1, 2, 3
• Autoimmune thyroid disease 2, 3
• Down syndrome or Turner syndrome 1, 2, 3
• Unexplained iron deficiency anemia 2, 3
• Premature osteoporosis 2, 3
• Unexplained liver transaminase elevations 2, 3

Common Diagnostic Errors

• Do not rely on symptoms alone to differentiate celiac disease from other gastrointestinal disorders, as clinical presentation is highly variable 1, 5
• Do not use symptom improvement on gluten-free diet as diagnostic evidence without serologic and histologic confirmation, as this has very low positive predictive value 1
• Do not combine multiple antibody tests in low-risk populations, as this marginally increases sensitivity but reduces specificity 1
• Do not use stool studies, small-bowel follow-through, intestinal permeability testing, D-xylose testing, or salivary testing for diagnosis, as these are not validated 1