Risk Factors for Developing CD in Genetically Predisposed Children

Non-Invasive Tests Celiac Disease Diagnosis ChildrenResearchers work to assess risk factors for the development of celiac disease in children who are genetically predisposed.

  • Alex Young, healio.com 1

Researchers have developed a new algorithm to help assess risk for villous atrophy in children with potential celiac disease and identify which patients can hold off on immediately switching to a gluten-free diet.

Renata Auricchio, MD, PhD, of the European Laboratory for the Investigation of Food Induced Disease at University Federico II in Italy, and colleagues reported that patients with potential celiac disease (CD) have normal intestinal architecture despite the presence of anti-tissue transglutaminase antibodies (anti-TG2) in their blood. These patients can be asymptomatic, and some might not progress to complete villous atrophy.

“For this reason, the clinical management of this condition remains debated,” they wrote in Gastroenterology. “Until now, there is no way to differentiate from the beginning patients who will develop villous atrophy from those who will not.”

Researchers performed a long-term prospective study to investigate the risk factors associated with the development of villous atrophy in children with suspected celiac disease. They followed 280 Italian children (aged 2–18 years) with suspected celiac disease for up to 12 years.

Each patient had two consecutive positive results from tests for anti-TG2, tested positive for the endomysial antibody (anti-EMA), had total serum levels of IgA in the normal range, normal duodenal architecture (Marsh stages 0–1) in five biopsies, and HLA DQ2- or DQ8-positive haplotypes. Patients had a small bowel biopsy taken every 2 years, as well as serologic tests and clinical analyses every 6 months.

During the follow-up period, researchers found that 42 patients developed villous atrophy (15%), while 89 no longer tested positive for anti-TG2 or anti-EMA. The cumulative incidence of villous atrophy was 43% at 12 years.

Investigators found that the baseline factors of age, homozygosity for the HLA DQB1 and the numbers of gamma delta intraepithelial lymphocyte cells were all strongly associated with development of villous atrophy. They used these risk factors to develop a discriminant score that correctly classified 80% of children who will not develop flat mucosa over follow-up and 69% of children who will.

Auricchio and colleagues wrote that this model can serve as a guide to help physicians decide which patients would benefit from a gluten-free diet and which ones can be monitored while maintaining their normal diet.

“Potential celiac disease is a very heterogenic condition and is not necessarily the first step of overt disease,” they wrote. “Individual features, such as age, genetic profile, mucosal infiltration and inflammation at diagnosis, may help to differentiate a subgroup of patients who will develop villous atrophy over time.” – by Alex Young

Disclosures: The authors report no relevant financial disclosures.

1 https://www.healio.com/gastroenterology/malabsorption/news/online/%7B536c6b77-63fc-499a-9391-e128453db183%7D/novel-algorithm-assesses-risk-for-progression-to-celiac-disease-in-children

SOURCE ARTICLE: Auricchio R, et al. Gastroenterology. 2019;doi:10.1053/j.gastro.2019.04.004.