Heterogeneous lab reference values hamper diagnosis of pediatric celiac disease

Last Updated: 2017-05-18

By Will Boggs MD

NEW YORK (Reuters Health) - Heterogeneous upper limits of normal for anti-tissue transglutaminase (anti-tTG) hamper the diagnosis of pediatric celiac disease using the revised ESPGHAN (European Society for Pediatric Gastroenterology, Hepatology and Nutrition) guidelines, according to a new survey.

ESPGHAN guidelines allow for diagnosing celiac disease without small-bowel biopsies in children who have anti-tTG titers more than 10 times the upper limit of normal, positive antiendomysial antibodies (EMA), and positive HLA-DQ2/DQ2 genotype.

Satisfaction of these guidelines requires clear upper limit of normal (ULN) values, as well as information on total IgA concentration, because both antibody tests are IgA-based.

After observing that ULNs for anti-tTG titers from different referring centers varied, Dr. Siba Prosad Paul from Bristol Royal Hospital for Children, in the U.K., and colleagues conducted a national survey to understand the diversity of the serological screening available for celiac disease from centers providing pediatric services in England.

Values for the ULN for anti-tTG titers range from 4 to 30 IU/mL, the most common value nationally being 10 IU/mL, they report in the Archives of Disease in Childhood, online May 8.

There were also significant variations in the ULN by different laboratories using the same assay.

“Although the serological pathway accommodates for these variations, the range of 4–30 IU/mL needs interpretation for 10 times the ULN value which will therefore vary from 40 to 300 IU/mL,” the researchers note. “Critically, these variations occur within a region served by a single tertiary center.”

Only 29.6% of the laboratories provided automatic reporting of total IgA concentration.

“Non-reporting of IgA concentration by nearly two-thirds of laboratories poses the risk of missing a number of children with celiac disease (CD) who also have coexistent IgA deficiency,” the authors explain. “All these factors are likely to affect the standards of care provided for children with CD.”

“Standardization of laboratory assay and ULN values across the National Health Service hospitals at least within the regional networks is necessary for safe implementation of the ESPGHAN guidelines for diagnosing CD in children,” they conclude.

Dr. Maureen M. Leonard from Harvard Medical School and MassGeneral Hospital for Children, in Boston, told Reuters Health by email, “The heterogeneity in testing for celiac disease, especially regarding the different anti-tTG assays used, range in manufacturer cut-off levels, and variability in laboratory practices is known and also common in countries outside of England.”

“Clinicians working with children with suspected celiac disease must know that a diagnosis of celiac disease cannot be made based on one or two elevated anti-tTG tests,” she explained. “Instead, according to the ESPGHAN guidelines, a child must have signs and symptoms suggestive of celiac disease, two elevated serology tests (anti-tTG and anti-EMA) obtained at different time points, and genetics compatible with celiac disease in order to be considered to forgo the confirmatory intestinal biopsy.”

“Children suspected to have celiac disease should be referred to a pediatric gastroenterologist for interpretation of serology results and confirmatory testing for celiac disease,” concluded Dr. Leonard, who was not involved in the new research. “Pediatric gastroenterologists must carefully consider the clinical case and serology results when determining which children meet the ESPGHAN criteria.”

Dr. Paul did not respond to a request for comments.

SOURCE: http://bit.ly/2qyYcRm

Arch Dis Child 2017.