What laboratory tests should be ordered for a patient with chronic diarrhea and dyspepsia when celiac disease is being considered?

Laboratory Testing for Chronic Diarrhea and Dyspepsia When Considering Celiac Disease

Order IgA tissue transglutaminase (tTG-IgA) plus total IgA level as your first-line serologic screen for celiac disease. 1

Initial Screening Panel

• IgA tissue transglutaminase (tTG-IgA) is the preferred first-line test with 90.7% sensitivity and 87.4% specificity in adults at 15 U/mL threshold 1
• Total IgA level must be measured simultaneously because IgA deficiency occurs in 1-3% of celiac patients and causes falsely negative IgA-based tests 1
• Complete blood count (CBC) to screen for iron deficiency anemia, which is present in 2-6% of celiac disease patients 2
• C-reactive protein (CRP) or fecal calprotectin/lactoferrin to screen for inflammatory bowel disease, though the AGA suggests against using ESR or CRP specifically for IBD screening (conditional recommendation) 1, 2
• Basic metabolic panel to assess for electrolyte abnormalities from chronic diarrhea 2

Confirmatory Testing When tTG-IgA Is Positive

• IgA endomysial antibody (EMA) should be added when tTG-IgA is elevated, providing superior specificity of 99.6% in adults 1
• When tTG-IgA exceeds 10 times the upper limit of normal and EMA is positive in a second blood sample, the positive predictive value for celiac disease approaches 100% 1

Testing for IgA-Deficient Patients

• If total IgA is low or absent, switch to IgG deamidated gliadin peptide (DGP-IgG), which demonstrates 93.6% sensitivity and 99.4% specificity in adults 1
• IgG tTG has limited utility (40.6-84.6% sensitivity, 78.0-89.0% specificity) and should not be used as a primary screen when IgA is normal 1, 3

Additional Testing for Chronic Diarrhea

• Stool test for Giardia (strong recommendation, high-quality evidence) because Giardia is a common cause of chronic diarrhea and fatty diarrhea 1
• Fecal calprotectin or fecal lactoferrin to screen for inflammatory bowel disease (conditional recommendation, low-quality evidence) 1
• Consider bile acid diarrhea testing (conditional recommendation, low-quality evidence), though tests are limited in North America; an empiric trial of bile acid sequestrants is reasonable when suspected 1

Critical Pre-Test Requirements

• Patients must consume at least 10g of gluten daily for 6-8 weeks before serologic testing to avoid false-negative results 1
• Never initiate a gluten-free diet before completing diagnostic workup, as this invalidates both serology and biopsy results 1

Common Pitfalls to Avoid

• Do not order IgG tTG as a primary screen when total IgA is normal—it generates frequent false-positives with poor specificity 1, 3
• Do not rely on isolated positive tTG IgG with negative tTG IgA; this pattern has only 3% diagnostic utility for celiac disease 3
• Do not skip measuring total IgA when ordering tTG-IgA, as IgA deficiency is 10-fold more common in celiac patients (2.6% vs 0.2% general population) 1
• Do not diagnose celiac disease based on serology alone in adults—duodenal biopsy with at least 6 specimens from the second part of the duodenum remains mandatory for confirmation 1