Last September, the Italian Parliament approved national screening for celiac disease in children aged 1-17 years. The decision followed the publication of findings from a screening trial that was led by Carlo Catassi, professor of pediatrics at Marche Polytechnic University in Ancona, on the east coast of Italy.
Celiac disease is one of the most common chronic autoimmune disorders, affecting 1 in 70 people worldwide, with some significant but unexplained geographical differences.
Most European countries follow a case-finding approach, with general practitioners looking for suggestive symptoms, family history, and a history of autoimmune illnesses. While this strategy can effectively improve the diagnostic rate of celiac disease, many patients will continue to go undiagnosed unless actively searched for by proactive policies.
Catassi told Medscape Medical News that population screening, which aims to uncover undiagnosed cases within a larger population, regardless of symptoms or known risk factors, could help better clarify the actual burden of celiac disease. "Even in a country with a good healthcare system like Italy, a high percentage of cases remain undiagnosed. This was true many years ago and still is true today," he said.
The Italian multicenter study screened children aged 5-11 years for celiac disease in six cities and found a prevalence of 1.65% in a sample of almost 4500 children, which is nearly 1 in every 60 children. This was higher than expected and represented a doubling of the prevalence of celiac disease in Italy in 25 years.
Most importantly, only 40% of children with celiac disease had been diagnosed prior to the trial, indicating that, without a mass screening strategy, 60% of patients with celiac disease remain currently undetected in Italy.
A Three-Decade-Long Debate
The debate about whether to screen for celiac disease began nearly 30 years ago. In 1996, Catassi conducted the first large-scale screening study in Italy. At that time, for every diagnosed case of celiac disease, there were approximately seven undiagnosed cases.
According to David Sanders, professor of gastroenterology at the University of Sheffield, Sheffield, England, the situation in the United Kingdom in the 1990s was similar. However, growing awareness of the disease polymorphism among doctors has increased its incidence. "We're getting better at finding cases. In the UK, the more we pushed for case finding, the more patients we diagnosed."
Nonetheless, at least two thirds of cases remain undiagnosed, potentially putting a significant number of people at risk for complications associated with untreated disease.
Sanders wondered if some people might not need to be aware of their celiac disease because the symptoms are so minimal. "Are there some out there who don't need to know? I don't think we can answer that question at present."
Catassi, on the other hand, argued that even silent celiac disease, over time, could lead to serious health issues, such as infertility, anemia, osteopenia, osteoporosis, neurological problems, and even certain types of cancer. "Therefore, we believe that early diagnosis is important," he said.
Weighing in on Population-Wide Screening
One argument against population-wide screening is the likelihood of false positives with the serologic tests. However, in a 2021 study published in the journal Nutrients, Catassi and his team demonstrated that anti-tissue transglutaminase immunoglobulin A (anti-tTG IgA) tests have a sensitivity of 93% and specificity of 98% for diagnosing celiac disease in children, making them a reliable screening tool.
"We didn't have a single case of false positive. If anything, the problem might be with false negatives," Catassi said. In fact, 2%-3% of people with celiac disease have IgA deficiency, which can lead to false negative results.
Genetic markers can help identify patients with a predisposition for celiac disease and yet turn a negative anti-tTG IgA test, he explained. "We suggest that children who receive a negative diagnosis today but have a genetic predisposition reconsider serologic tests later in life if they present any symptoms."
A second argument against screening is that a seemingly healthy patient may undergo screening, be diagnosed with the condition, and be placed on a strict and lifelong gluten-free diet despite a lack of robust evidence that it would improve their health and quality of life.
Sanders said: "You turn a healthy person into a patient, and we don't actually know whether those individuals will truly benefit from treatment."
Evidence suggests that undiagnosed patients might suffer long-term health consequences, while a population-based screening in Norway found that the majority of undiagnosed people with the condition improved their quality of life on a gluten-free diet.
"This is very difficult to demonstrate because you should do a long-term study where you screen people and then treat only 50% of them," Catassi said. "But indirect evidence shows that, when people start treatment, their quality of life usually improves, despite the limitation of the gluten-free diet, which, of course, is cumbersome."
Building Up the Evidence
In 2017, the US Preventive Services Task Force reviewed the scientific literature and concluded that the evidence was insufficient to assess the balance of harms and benefits of screening for celiac disease.
Wanda Nicholson, professor of prevention and community health at George Washington University's Milken Institute School of Public Health, Washington, DC, and the current chair of the US Preventive Services Task Force, told Medscape Medical News that numerous research gaps remain to be filled.
She emphasized the importance of more studies comparing the outcomes of average-risk individuals screened for celiac disease with those who were not screened, as well as the impact of gluten-free diets on those who tested positive. "The Italian program could provide valuable insights into these questions," she said.
Catassi argued that the benefits of early diagnosis outweigh the drawbacks of screening. "We are very much excited about the program. But we will evaluate the results and decide in a few years if this needs to be done forever or changes need to be made."
Despite his reservations about the outcomes of a nationwide screening program, questioning how many people would participate and its cost-effectiveness, Sanders welcomed the Italian endeavor, saying, "I'm very glad that somebody is doing this on a country-wide basis because it will inform all the rest of us about future policy."
Catassi served as president of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition from 2013 to 2016. He also served as a scientific consultant for Dr Schaer Food and Noos s.r.l.
Sanders is the current chair of the Celiac UK Health Advisory Council, a board member of the European Society for Study of Celiac Disease, former British Society of Gastroenterology council member from 2016 to 2019, and former president of the International Society for the Study of Celiac Disease from 2016 to 2019.
Nicholson is the senior associate dean for Diversity, Equity, and Inclusion; director of the Office of Inclusive Excellence; and professor of Prevention and Community Health at the Milken Institute School of Public Health at the George Washington University. She is the current chair of the US Preventive Services Task Force.