Praxis Medical Insights

First-Line Testing: Celiac Disease Serology

The American Gastroenterological Association recommends starting with IgA tissue transglutaminase (tTG-IgA) as the primary screening test, with 93% sensitivity and 98% specificity, while the patient is consuming gluten 3, 1
Total serum IgA level must be measured simultaneously because IgA deficiency occurs 10-15 times more frequently in celiac patients and causes false-negative IgA-based testing, according to the American College of Gastroenterology 1, 2, 4
If IgA deficient, the European Society for Pediatric Gastroenterology, Hepatology and Nutrition recommends ordering IgG tTG and deamidated gliadin peptide antibodies instead 5, 1

The American College of Gastroenterology advises that never starting a gluten-free diet before completing testing is crucial, as serologic and histologic features normalize after diet initiation, making diagnosis impossible 1, 2
Patients must consume at least 10g of gluten daily for 6-8 weeks before testing, as recommended by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition 2, 4

The American Gastroenterological Association states that if serology is positive, upper endoscopy with duodenal biopsies is mandatory to confirm celiac disease before implementing significant dietary changes 1, 2
Obtain 6 total biopsies: 1-2 from the duodenal bulb and at least 4 from the second part of duodenum, as recommended by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition 2, 4

The American College of Gastroenterology recommends checking for common nutritional deficiencies that occur with malabsorption, including iron studies, vitamin D level, vitamin B12, folate, and complete blood count 1

The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition suggests that only after properly excluding celiac disease with both negative serology and negative duodenal biopsies can you consider non-celiac gluten sensitivity 2, 4
Consider HLA-DQ2/DQ8 genetic testing if diagnosis remains uncertain, as absence of both alleles has >99% negative predictive value for celiac disease, according to the American Gastroenterological Association 2, 4

The American Thyroid Association recommends checking TSH and free T4, given the strong association between gluten-related disorders and autoimmune thyroid disease 1
If abnormal, add thyroid peroxidase antibodies (TPO) and thyroglobulin antibodies, as recommended by the American Association of Clinical Endocrinologists 1