Alimentary TractMisuse of serological screening tests for celiac disease in children: A prospective study in Italy
Introduction
Celiac disease (CD) is a systemic immune-mediated disorder triggered by the ingestion of gluten in genetically susceptible subjects, and characterized by the development of serum specific autoantibodies (e.g. the IgA class anti-tissue transglutaminase antibody), damage of the small intestinal mucosa, and a variable clinical picture [1]. It is one of the most common lifelong disorders, affecting approximately 1% of the European population [2].
The European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) revised the CD diagnostic algorithm in 2012. According to this protocol, total serum IgA (tIgA) determination plus serum class A anti-tissue transglutaminase (tTG), or IgG anti-deamidated gliadin peptide (DGP) antibodies in children with selective IgA deficiency (SIgAD), is the first-line screening test for CD. IgA class antiendomysial antibody (EMA) and HLA-DQ2 and -DQ8 determinations are second-line (confirmatory) tests to be performed only in children with IgA anti-tTG positivity. IgG class anti-DGP test can be included in the initial CD screening of children younger than 2 years, since data suggest that this test may occasionally show higher sensitivity than IgA anti-tTG in early-onset CD [3,4]. Finally, determination of HLA genotype may be performed in the initial screening of children belonging to at-risk groups, e.g. CD first-degree family members, due to the high negative predictive value (NPV) of this test [5].
Several studies, including a large European, prospective, multicenter study, recently confirmed the validity and the generalizability of the ESPGHAN CD diagnostic guidelines, not only in symptomatic but also in symptomless cases [6,7]. In Italy, the ESPGHAN protocol has been widely adopted by third-level Centers of Pediatric Gastroenterology and largely promoted by the Italian Society for Pediatric Gastroenterology (SIGENP). Despite this favorable situation, in our daily practice we got the feeling that blood testing requests for CD screening were largely inaccurate and often redundant. For this reason, we decided to undertake a prospective study aimed to analyze test prescriptions for CD screening/case-finding in children.
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Materials and methods
We prospectively enrolled children seen at the Celiac Clinic of two referral Centers (Pediatric Department of Ancona and Cava de’ Tirreni, Salerno, respectively) between September 2017 and September 2018. We included newly seen subjects younger than 18 years who had already performed their first-line CD serological testing before referral to our celiac clinic. We excluded (a) children with a prescription from a specialized/third-level referral Center, and (b) children that were already on a
Study population
Overall, we obtained data from 202 children. They were 119 girls (59%) and 83 boys (41%), with an age range of 7 months–16 years (mean age 7.1 years ±4.1). CD tests were performed at a mean age of 6.7 years ±4.1 SD. Eighteen children were younger than 2 years of age at the time of CD testing.
Reasons for CD testing
The reason for CD testing were typical symptoms in 94 cases (46.5%), atypical in 99 (49%), or belonging to a CD at-risk group in 9 children (4.5%). Reasons for CD testing (cumulative %) were: failure to
Discussion
Despite a high level of CD awareness in Italy, this survey confirms that the ESPGHAN diagnostic guidelines, at an early stage of the diagnostic algorithm, are largely disregarded and that the misuse of CD screening tests is very common in this country. We indeed found that the recommended prescription of anti-tTG IgA plus tIgA occurred only in a minority of children undergoing a first CD screening (11.4%), while redundancy of test prescription was very common in clinical practice.
IgA
Conflict of interest
Prof. Carlo Catassi has served as scientific consultant for Dr. Schaer, NOOS, and Takeda. The other authors have no conflict of interest to declare.
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