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Invited Commentaries

Coeliac Disease

Time for a New Diagnostic Approach in Symptomatic Children

Volta, Umberto

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Journal of Pediatric Gastroenterology and Nutrition: March 2013 - Volume 56 - Issue 3 - p 241
doi: 10.1097/MPG.0b013e3182798744
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See “Celiac Disease: The New Proposed ESPGHAN Diagnostic Criteria Do Work Well in a Selected Population” by Klapp et al on page 251.

Small bowel biopsy has remained the undisputed criterion standard for coeliac disease (CD) diagnosis until now (1); however, growing evidence indicates that histology by itself is not always diagnostic and it may hide some pitfalls linked to the number, size, site, and orientation of biopsy samples. Nowadays, CD diagnosis relies not only on histology, but also on increasingly important serological and genetic tests. It has been shown that both IgA anti-endomysial (EmA) and high-titre tissue transglutaminase antibodies (tTGA) are closely related to gluten-dependent flat mucosa (2). According to these findings, the recently published European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines proposed that CD can be diagnosed in symptomatic children and adolescents on the basis of IgA tTGA at a high titre (>10 times upper limit of normal [ULN]), together with IgA EmA and HLA-DQ2 and/or -DQ8 positivity, without the need for duodenal biopsy (3).

In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Klapp et al (4) retrospectively evaluated the efficiency of the new ESPGHAN diagnostic criteria for CD in symptomatic IgA-competent children (about half were younger than 2 years) with positivity for serological tests at the time of small intestinal biopsy. More than two-thirds (116/150) of these children fulfilled the above-mentioned criteria of the triple test (TT), including tTGA >10 times ULN, EmA, and HLA positivity. Positive predictive value (PPV) of the TT for CD was 97.4% because histology showed severe mucosal damage in 113 children and normal mucosa in the remaining 3. After follow-up from 7 months to 5 years on a gluten-containing diet, these 3 children developed a villous atrophy leading the PPV of the TT to 100%. Intestinal biopsy confirmed CD diagnosis in 25 of the 34 TT-negative children, ruling out CD in the remaining 9. On the whole, TT sensitivity and specificity for CD were 82% and 100%, respectively. It is also noteworthy that CD was excluded only in 1 child with tTGA >10 times ULN, but negative for EmA. The use of a lower threshold value for tTGA (≥5 instead of >10 times ULN) would have increased the sensitivity to 88% without changing the PPV of the TT, but further studies on large series of patients are needed before decreasing the threshold value of tTGA suggested by ESPGHAN. Although in the Klapp study the sensitivity of both EmA and tTGA for CD in the younger than 2-year-old group has been satisfactory (only 1 coeliac was negative for both antibodies, but positive for the anti-gliadin antibodies), in this age interval the detection of deamidated gliadin peptide antibodies (DGP) is advisable, because they are regarded as the best CD marker in first infancy (5). In extremely young children, it would be relevant to correlate DGP titre with intestinal damage because we have observed that DGP >10 times ULN always indicate a partial/subtotal villous atrophy (unpublished data).

In conclusion, the study by Klapp et al validates the indications of the new ESPGHAN guidelines, confirming that duodenal biopsy can be optional in children and adolescents with symptoms suggestive of CD in the presence of TT positivity.


1. Volta U, Villanacci V. Celiac disease: diagnostic criteria in progress. Cell Mol Immunol 2011; 8:96–102.
2. Hill PG, Holmes GK. Coeliac disease: a biopsy is not always necessary for diagnosis. Aliment Pharmacol Ther 2008; 27:572–577.
3. Husby S, Koletzko S, Korponay-Szabo IR, et al. ESPGHAN guidelines for the diagnosis of celiac disease in children and adolescents: an evidence-based approach. J Pediatr Gastroenterol Nutr 2012; 54:136–160.
4. Klapp G, Masip E, Bolonio M, et al. Coeliac disease: the new proposed ESPGHAN diagnostic criteria do work well in a selected population. J Pediatr Gastroenterol Nutr 2013; 56:251–256.
5. Barbato M, Maiella G, Di Camillo C, et al. The anti-deamidated gliadin peptide antibodies unmask celiac disease in small children with chronic diarrhoea. Dig Liver Dis 2011; 43:465–469.
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