What are the initial diagnostic tests for celiac disease in pediatric patients?

Diagnostic Testing for Celiac Disease in Children

The initial diagnostic test for celiac disease in pediatric patients is IgA tissue transglutaminase antibody (tTG-IgA) combined with total IgA level measurement, performed while the child is consuming a gluten-containing diet. 1, 2

Initial Serological Testing

• tTG-IgA is the preferred first-line screening test with sensitivity of 97.7% and specificity of 70.2% in children 1
• Total IgA levels must be measured simultaneously to identify IgA deficiency, which affects approximately 2-3% of celiac patients and causes false-negative IgA-based test results 3, 2
• The child must be consuming gluten (at least 10g per day for 6-8 weeks) before testing, as gluten elimination leads to false-negative results 1, 4

Confirmatory Testing When tTG-IgA is Elevated

• When tTG-IgA is ≥10 times the upper limit of normal, obtain IgA endomysial antibody (EMA-IgA) as a confirmatory test with excellent specificity of 93.8% in children 1
• If both tTG-IgA ≥10× upper limit of normal AND EMA-IgA are positive, the diagnosis can be confirmed without intestinal biopsy when combined with positive HLA-DQ2/DQ8 testing and compatible symptoms 1
• This biopsy-avoidance strategy is endorsed by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 1

Testing in Special Populations

IgA-Deficient Children

• In children with confirmed IgA deficiency, use IgG-based tests: IgG deamidated gliadin peptide (DGP-IgG) and IgG tissue transglutaminase (tTG-IgG) 3, 2
• IgG isotype testing for tTG is not specific in the absence of IgA deficiency and should not be used 3, 4

Children Under 2 Years of Age

• Combine tTG-IgA with deamidated gliadin peptides IgG and IgA to improve sensitivity in this age group 1, 2

Genetic Testing (HLA-DQ2/DQ8)

• HLA-DQ2/DQ8 testing has a negative predictive value >99%—absence of both alleles virtually excludes celiac disease 1, 4
• Use HLA testing when celiac disease is strongly suspected despite negative serology or when the child has already started a gluten-free diet before proper testing 4, 2
• HLA testing is also required as part of the biopsy-avoidance pathway in children with high antibody levels 1

High-Risk Groups Requiring Screening

• Children with type 1 diabetes mellitus (prevalence 5-10%) should be tested at diagnosis, after 2 years, and after 5 years 1
• First-degree relatives of celiac patients (risk 7.5%) should be screened 1
• Children with Down syndrome or Turner syndrome should be screened 1
• Children with autoimmune thyroid disease should be tested 4

Intestinal Biopsy Considerations

• Biopsy remains necessary in adults and in children who do not meet the strict biopsy-avoidance criteria 3, 4
• When biopsy is performed, obtain multiple specimens: ideally 1-2 from the duodenal bulb and at least 4 from the second part of the duodenum or beyond 4
• Characteristic histologic findings include villous atrophy, crypt lengthening, and increased intraepithelial lymphocytes 4

Critical Pitfalls to Avoid

• Never start a gluten-free diet before completing diagnostic evaluation—this makes all subsequent serological and histological tests unreliable 1, 2
• Do not rely solely on symptoms for diagnosis—height and weight are not reliable predictors of celiac disease, and many children with celiac disease do not report intestinal symptoms 1, 5
• Do not use IgG-based tests in children with normal IgA levels—they are markedly less accurate in this setting 4
• Recognize that tTG-IgA specificity is insufficient for diagnosis when using standard cutoff values—confirmatory testing with EMA-IgA or biopsy is essential 5