Investigations Required for Celiac Disease in Children
Initial Serological Testing
Begin with IgA tissue transglutaminase antibody (tTG-IgA) plus total IgA level measurement while the child is consuming a gluten-containing diet (at least 10g daily for 6-8 weeks). 1, 2, 3
- tTG-IgA is the preferred first-line screening test with sensitivity of 97.7% and specificity of 70.2% in children 1
- Total IgA must be measured simultaneously to identify IgA deficiency, which affects 2-3% of celiac patients and causes false-negative IgA-based results 1, 2
- Never start a gluten-free diet before completing diagnostic testing, as this leads to false-negative results and makes subsequent evaluation unreliable 4, 1, 2
Confirmatory Serological Testing
When tTG-IgA is elevated (especially ≥10× upper limit of normal), perform IgA endomysial antibody (EMA-IgA) as confirmatory testing. 1, 2, 3
- EMA-IgA has excellent specificity of 93.8% in children 1
- The combination of tTG-IgA >10× upper limit of normal plus positive EMA-IgA approaches 100% positive predictive value 3
Special Considerations for Young Children
In children under 2 years of age, combine tTG-IgA with deamidated gliadin peptide (DGP) IgG and IgA testing to improve sensitivity. 1, 2, 3
- Younger children (≤3 years) reveal higher concentrations of tTG-IgA and DGP antibodies than older children 5
Testing in 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). 1, 2
HLA Genetic Testing
HLA-DQ2/DQ8 testing should be performed in specific scenarios, particularly when considering biopsy avoidance or when celiac disease is strongly suspected despite negative serology. 1, 2, 3
- HLA testing has a negative predictive value >99%, and absence of both DQ2 and DQ8 alleles virtually excludes celiac disease 1, 2, 3
- This test is essential for the biopsy-avoidance pathway in children 1
Biopsy-Avoidance Pathway (Pediatric-Specific)
Symptomatic children can avoid intestinal biopsy if ALL of the following criteria are met: 4, 1, 6
- tTG-IgA ≥10× upper limit of normal
- EMA-IgA positive
- HLA-DQ2/DQ8 positive
- Symptoms compatible with celiac disease
This biopsy-avoidance approach is supported by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines and has a positive predictive value of 100% when all criteria are met. 1, 6
When Biopsy Remains Necessary
Upper endoscopy with multiple duodenal biopsies is required when: 1, 2
- Children do not meet all strict biopsy-avoidance criteria
- tTG-IgA is positive but <10× upper limit of normal
- EMA-IgA is negative despite elevated tTG-IgA
- HLA-DQ2/DQ8 is negative
High-Risk Groups Requiring Screening
Screen for celiac disease even without symptoms in children with: 1, 3
- Type 1 diabetes mellitus (prevalence 5-10%) - test at diagnosis, after 2 years, and after 5 years 1
- First-degree relatives of celiac patients (risk 7.5%) 1
- Down syndrome or Turner syndrome 1, 3
- Unexplained iron deficiency anemia 3
- Autoimmune thyroid disease 3
Critical Pitfalls to Avoid
- Do not rely solely on symptoms for diagnosis, as height and weight are not reliable predictors, and many children with celiac disease do not report intestinal symptoms 1, 7
- Do not initiate gluten-free diet before measurement of antibodies and biopsy completion, as this makes subsequent tests unreliable 4, 2
- Do not skip total IgA measurement, as IgA deficiency will cause false-negative tTG-IgA results 1, 2
- Do not assume negative serology excludes celiac disease in children with measurable but low IgA levels - children with relative IgA deficiency (measurable but below age reference) can still have elevated tTG-IgA and celiac disease 7
Interpretation of Antibody Levels
tTG-IgA >100 units or EMA >1:1280 are highly specific (>98%) for Marsh 3a or higher intestinal lesions. 1
- High antibody concentrations are predictive of villous atrophy with sensitivities ranging from 92.8% to 97.9% 5