Optimization of serologic diagnosis of celiac disease in the pediatric setting

The clinical presentation of celiac disease (CD) varies between children. The objective of this study was to document the pre-test probability for CD based on symptoms and routine laboratory test and to evaluate the performance of two IgA anti-tissue transglutaminase (tTG) assays. We critically reviewed the concept of using multiples of the manufacturer's upper limit of normal (ULN), as proposed in the ESPGHAN guidelines (if IgA tTG is >10 times ULN, no biopsy is needed).

The retrospective study included 91 children with newly diagnosed CD and 605 controls (<16 years). All underwent upper endoscopy with small bowel biopsies. Four laboratory parameters and 16 symptoms were registered. All patients were tested for IgA anti-tTG antibodies with assays from Inova Diagnostics and Thermo Fisher Scientific.

Some combinations of clinical symptoms and laboratory parameters had a high pre-test probability for CD, such as (combinations of) anorexia, failure to thrive, low ferritin level and elevated AST. The diagnostic performance of both IgA anti-tTG assays was excellent and comparable (no difference in ROC curve area under the curve). At a threshold that corresponds to a specificity of 100% (5 times ULN for Inova Diagnostics and 2 times ULN for Thermo Fisher), the sensitivity was 82% for both assays. At the 10 times ULN threshold, the sensitivity differed between the assays (77% vs. 57%), indicating that such threshold does not completely align interpretation across companies.

Our study showed that some combinations of symptoms and aberrant laboratory parameters had a high pre-test probability. The use of the ESPGHAN non-biopsy approach could reduce small bowel biopsies, but thresholds for IgA-tTG levels are not aligned across assays and should be based on predefined likelihood ratios or specificity.