Celiac Disease Autoimmunity Common Among Children Not Considered At Risk
By Van Waffle
Initial findings of the first mass screening study for U.S. children show a high prevalence of celiac disease autoimmunity (CDA) among those without symptoms and no family history of the condition. CDA indicates an abnormally high level of tissue transglutaminase (tTG) antibodies in the blood, which can return to normal, but often leads to celiac disease, damaging the small intestine.
The Autoimmunity Screening for Kids (ASK) study based at the University of Colorado reported that of 9,973 children aged 2 to 17, 242 (2.4%) tested positive for tTG antibodies. So far, 185 have returned for a confirmatory blood test, with 149 (1.5%) confirming a positive result.
The actual prevalence of CDA in children is probably even higher because the ASK Study is under-recruiting non-Hispanic white children, who are already known to have a greater risk for celiac disease. Research in 2017 estimated that CDA affects 2% to 3% of adolescents in Colorado. Although the 2.4% found in the ASK Study cannot be extended to the general population, it adds evidence that number is high.
Significantly, 90% of those with CDA did not have a close relative with celiac disease, and most did not report classic symptoms of celiac disease. In initial screening, parents and children completed a questionnaire to report recent diarrhea, stomach aches, bloating, constipation, vomiting, difficulty gaining weight, and poor growth. Currently, doctors are only advised to order blood tests for people with these risk factors, causing a large percentage of celiac disease patients to remain undiagnosed.
A co-investigator on the study, Marisa Stahl, MD, assistant professor of pediatrics at the School of Medicine, University of Colorado, Anschutz Medical Campus in Aurora, says only 30% who tested positive for CDA had classic celiac symptoms, and about 30% who tested negative also had symptoms: “So we rely too heavily on symptoms right now. You’re still not catching most people who test positive for antibodies.”
90% of those with CDA did not have a close relative with celiac disease, and most did not report classic symptoms of celiac disease.
Stahl says doctors and patients should set the bar lower on when to get tested. “In our study, most children who tested positive did not have classic gastrointestinal symptoms or a family history of celiac disease. The absence of classic gastrointestinal symptoms or family history should not preclude people from getting tested and providers should also have heightened awareness for testing of people with non-classic symptoms such as headaches, rash, brain fog.”
Stahl says ASK aims to eventually test 50,000 children in Colorado to explore the feasibility of mass screening for autoimmune disease. It is studying both celiac disease and type 1 diabetes. This initial report in The American Journal of Gastroenterology was based on participants recruited as of 2018.
Stahl says, “This study is extremely timely in the sense that it started right around the time that the USPSTF (United States Preventive Services Task Force) released statements saying that there’s insufficient evidence for screening asymptomatic individuals for celiac disease, which is essentially what this study is doing: screening lots of asymptomatic individuals for celiac disease. We’re trying to accumulate evidence to see if this is worth doing on a wider scale.”
The evidence for mass screening must balance the health benefits of early diagnosis against psychological, social, and economic costs to people with CDA who might never develop celiac disease. The study will assess individual symptoms, development, quality of life, anxiety, and depression in screened individuals.
"Targeted screening may not be the way to find people, because symptoms and family history won’t find everybody, and, currently, these are the main factors used to recommend who should get tested."
The benefits of screening must also balance costs to the healthcare system. For example, early diagnosis might reduce prescription drug use, hospital visits, and missed days of school or work, while increasing costs such as repeated testing and close monitoring of people with CDA who choose to continue eating gluten.
“Based on our preliminary results, we cannot make any recommendations regarding policy for screening in asymptomatic individuals. We need longer follow up of outcomes of these individuals who are identified through screening to determine if it is beneficial (if we see improvements in physical and psychosocial health) and whether screening is cost-effective. Hopefully in the future we will have this answer,” says Stahl.
This paper presents only the first glimpse of data to come out of the ASK Study. “It’s already interesting because it suggests that targeted screening may not be the way to find people, because symptoms and family history won’t find everybody, and, currently, these are the main factors used to recommend who should get tested,” says Jocelyn Silvester, MD, PhD, Director of Celiac Disease Program Research at Boston Children’s Hospital, who is not involved in the research.