Guidelines for 'No-Biopsy' Celiac Diagnosis in Children Continue to Evolve

The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) suggest that guidelines could be modified to propose that children with TGA-IgA ≥5× the Upper Limit of Normal (ULN) can be diagnosed as having Celiac Disease (CD) via No-biopsy pathway (NBP) without need for endoscopy and biopsy.

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What is already known on this topic?

Serological diagnosis of coeliac disease (CD) is highly sensitive, specific, less invasive and more economical than biopsy-based pathway.
No-biopsy pathway (NBP) for diagnosing CD in children with antitissue transglutaminase (TGA-IgA) titre ≥10× upper limit of normal (ULN) has now become established clinical practice.

What this study adds?

In our centre, a lower threshold of TGA-IgA ≥5×ULN can be used to reliably diagnose CD in children via the NBP.

How this study might affect research, practice or policy?

Additional studies testing the optimal threshold of TGA-IgA to diagnose CD using different assays in different populations would be of value.
Evolving evidence suggests that the European Society for Paediatric Gastroenterology Hepatology and Nutrition guidelines could be modified to propose that children with TGA-IgA ≥5×ULN can be diagnosed as having CD via NBP without need for endoscopy and biopsy.

The Study

Objective

European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines on coeliac disease (CD) recommend that children who have IgA-based antitissue transglutaminase (TGA-IgA) titre ≥10× upper limit of normal (ULN) and positive antiendomysial antibody, can be reliably diagnosed with CD via the no-biopsy pathway. The aim of this study was to examine the relationship between TGA-IgA ≥5×ULN and histologically confirmed diagnosis of CD.

Methods

Data including TGA-IgA levels at upper gastrointestinal endoscopy and histological findings from children diagnosed with CD following endoscopy from 2006 to 2021 were analysed. CD was confirmed by Marsh-Oberhuber histological grading 2 to 3 c. Statistical analysis was performed using χ² analysis (p<0.05= significant).

Results

722 of 758 children had histological confirmation of CD. 457 children had TGA-IgA ≥5×ULN and 455 (99.5%) of these had histological confirmation for CD; the two that did not had eventual diagnosis of CD based on clinicopathological features. 114 of 457 had between TGA-IgA ≥5×ULN and <10×ULN, all had confirmed CD. The likelihood of a positive biopsy with TGA-IgA ≥5×ULN (455/457) compared with TGA-IgA <5×ULN (267/301) has strong statistical significance (p<0.00001). The optimal TGA-IgA cut-off from receiver operating characteristic curve analysis was determined to be below 5×ULN for the two assays used.

Conclusion

99.5% of children with TGA-IgA ≥5×ULN had histological confirmation of CD, suggesting that CD diagnosis can be made securely in children with TGA-IgA ≥5×ULN. If other studies confirm this finding, there is a case to be made to modify the ESPGHAN guidelines to a lower threshold of TGA-IgA for serological diagnosis of CD.

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Siba Prosad Paul, Daniyal Isam Raja, Bhupinder Kaur Sandhu, Srinivasa R Rao, Christine H Spray, Anthony Edward Wiskin, Lakshmipriya Selvarajan, Eleni Volonaki, Pramila Ramani, Lina Bourhan Tashtoush, Dharamveer Basude