Celiac affects an estimated 3 percent of children in the Denver area, according to University of Colorado researchers. They uncovered this startlingly high figure while evaluating screening children for celiac and type 1 diabetes. This is the highest prevalence detected anywhere. Previous data have suggested that 1 in 100 North Americans has celiac, and its prevalence is increasing. However, most people affected do not know they have it. To find the hidden patients, some experts advocate celiac screening for all people with risk factors or even the general population.
Standard heath care responds to patients who present complaints. Screening takes a more active approach, looking for signs of disease in patients who lack symptoms. This might help doctors detect celiac in people before they report painful problems such as indigestion, diarrhea and bloating. Early diagnosis could prevent long-term health problems and occasionally fatal complications.
However, these benefits remain theoretical. Medical research has yet to prove general screening programs would benefit patients in the long term. That does not even begin to address the potential public health cost of widespread screening.
In 2017, the U.S. Preventive Services Task Force (USPSTF) issued a recommendation that research has not given enough evidence to support screening patients who lack celiac symptoms. General screening in the United States is not out of the question, but the key questions still need answers.
Still, the task force’s conclusion surprised some patients and experts.
“I agree with the overall conclusion that more evidence needs to be collected for [screening] the general population,” says Marian Rewers, Ph.D., executive director of the Barbara Davis Center for Diabetes in Aurora, Colorado. He is a principal investigator in the Denver studies. “However, the USPSTF missed a lot of published information from high-risk groups.”
Joseph Murray, MD, professor of medicine in charge of the celiac program at Mayo Clinic in Rochester, Minnesota agrees: “The task force took their charge very seriously but also took it quite narrowly.”
The USPSTF specifically asked, “What is the role for testing in patients who are asymptomatic?” Murray explains. In combing through medical research, the panel carefully excluded studies screening the general population because they might include people with symptoms who had not yet complained about them. Few studies have focused explicitly on people who lack symptoms.
Murray proposes trying to convince the USPSTF to ask a different question: “Is there evidence to support screening people who are at risk for celiac disease who may or may not have symptoms?”
Edwin Liu, MD, director of the Colorado Center for Celiac Disease and a colleague of Rewers’ at the University of Colorado, is concerned that the recommendation sends an incorrect message about the importance of celiac symptoms.
“Does it mean that if I’ve got celiac disease and I have symptoms, I only need to treat myself enough to control my symptoms? I don’t think that’s what they mean, but it might lead someone to start thinking this way,” Liu argues.
In some gastrointestinal diseases, the treatment focuses only on reducing symptoms, Liu explains.
However, that is not the case with celiac. Patients must maintain a gluten-free diet for life even after the condition is effectively controlled.
Public disappointment about the task force’s recommendation prompted the Celiac Disease Foundation (CDF) based in Woodland Hills, California, to post its position earlier this year on its website. The patient advocacy group supports the call for more research, but chief executive officer Marilyn Geller understands the community’s concern.
“A tremendous amount of unnecessary patient suffering occurs with undiagnosed celiac disease,” explains Geller. The average patient suffers painful symptoms for six to 10 years prior to a correct diagnosis. They may view this recommendation from the government as a step away from recognizing serious impacts of celiac.
It is a difficult but important challenge to design research to investigate screening people who have no symptoms, says Murray. Rigorous studies would be fraught with problems.
For example, he describes a theoretical study in which researchers would recruit volunteers without symptoms who agree to be tested for celiac but go untreated and not be informed of the results for five years. This would demonstrate the long-term health outcome in people who have celiac without knowing it. Not only would this be expensive, but it presents ethical problems for doctors who pledge to prevent harm.
The diabetes link
However, the ongoing Denver research that found a high celiac prevalence in children is providing an opportunity. The charitable organization JDRF, which funds research to prevent type 1 diabetes, has supported the program through the University of Colorado and Barbara Davis Center for Diabetes. The Autoimmunity Screening for Kids (ASK) study is recruiting 55,000 children ages 2 to 17 from Denver over three years to find out what happens when they are screened for type 1 diabetes and celiac.
Diabetes receives greater public awareness and funding. The two conditions share genetics and other risk factors, and patients with one appear to be predisposed for the other, so it is useful to study them together.
ASK was set up primarily to screen for type 1 diabetes, explains Rewers: “Celiac disease screening was added as a relatively easy and important secondary goal.”
Celiac disease autoimmunity
Asymptomatic children will undergo testing for what researchers call celiac disease autoimmunity (CDA). It means their immune systems have begun making antibodies against gluten but without causing any obvious symptoms. At this stage, some patients still might not show damage to the intestinal lining, the essential test for celiac.
The Denver celiac prevalence study identified 1,339 children with celiac risk factors born at St. Joseph’s Hospital between 1993 and 2004 and followed them for up to 20 years. Eventually, 66 developed CDA and also celiac, while 46 met criteria for CDA only.
The health-care community considers CDA a precursor to celiac. It remains unclear what triggers the onset of disease damage to the intestine, how long this takes and why a significant proportion of cases never appear to progress beyond producing antibodies. Some people only test positive for antibodies temporarily.
A blood test to screen newborn children for celiac might seem simple and inexpensive, but it is not enough to settle the question. People with a genetic predisposition require continual follow-up to watch for the onset of CDA or celiac at any age. Often it does not appear until adulthood.
Geller points out that infant screening would fail to detect most cases.
Some gastroenterologists recommend people with CDA adopt a gluten-free diet to prevent potential complications once the disease gets going.
Here Liu puts a positive spin on the USPSTF recommendation. In the recent past many pediatricians like himself tended to screen children at risk and treat them for CDA even if they did not have symptoms. However, it was difficult for families of children who felt fine at the outset to have their doctors impose a gluten-free diet.
Liu adds, “These official recommendations say exactly what we already know: that there’s not enough data to support this. It allows us to step back and be more thoughtful about how we approach each patient.”
This shift can also help research.
“Several years ago, I thought that we had lost our window of opportunity to study kids who are asymptomatic without treatment, because everyone was leaning toward screening them and treating them,” says Liu. “Now, with the conclusions by the USPSTF, this gives us more permission to not treat these kids but monitor them. We will be able to get some studies of the natural history of untreated, asymptomatic celiac disease.”
The ASK study should shed some light on what happens from early childhood through adolescence.
“We’re going to look at the acceptability of large-scale screening,” says Liu. “We’ll look at the potential harms that we can cause by screening, like are we going to cause kids to get a lot of unnecessary endoscopies? Are we causing a lot more anxiety and depression in families? And we are also looking at the benefits.”
He expects the study to identify about 1,000 children with celiac. An estimated one-half of them will have no symptoms.
Rather than concealing their CDA status, as in the study design Murray described, it will rely on patients’ autonomy and right to choose. Everyone is different. Some patients have more risk tolerance than others.
Liu says, “We find somebody who’s antibody-positive, and we don’t treat them, but we monitor them carefully to make sure they don’t get themselves into trouble. They come in every six months. They find out they’re still antibody-positive.
“At some point, a lot of these individuals may say, ‘You know what? These antibodies aren’t going away. Let’s just chase this and take care of it, OK?’ Or they may eventually recognize they have symptoms. I anticipate that the majority of people who continue to follow up and monitor, knowing that they’re still antibody-positive, may end up choosing to be on a gluten-free diet. There’s just no rush if you’re asymptomatic.”
Regardless of their decision, the study will continue to follow their progress. The data will allow researchers to compare people who choose early treatment with those who do not. It will indicate how earlier diagnosis and treatment through a screening program might improve long-term health outcomes.
Rewers says he believes adequate evidence will eventually prove the value of screening.
Murray says, “A lot of people who have celiac disease have no symptoms now but will get symptoms in the future. They might even get serious or fatal complications of celiac disease before they are ever diagnosed. We could prevent those if we found them and treated them early.” But, he adds, “How do we predict who is going to go on to complications and who’s not? That’s something
that’s really not understood.”
In patients with risk factors such as a first-degree family member with celiac, research has proven the benefit of screening. Murray says he tells his newly diagnosed patients their family members should undergo testing because they have a substantial risk for celiac.
In other cases, experts simply feel strongly about recommending it, for example, in children with type 1 diabetes. According to Diabetes Canada, they have a 4 to 9 percent risk of having celiac but up to 70 percent show no symptoms of it.
Murray says, “There isn’t yet enough evidence to say people with type 1 diabetes benefit from being tested, but a lot of us actively support testing in that context because we know people with atypical symptoms are often hidden from view.”
CDF works to raise awareness among doctors about who should receive testing for celiac, based on good evidence. Based on CDF’s advice, Anthem Health Insurance recently adopted guidelines to encourage testing symptomatic patients and screening their first-degree relatives.
“The real key is simply educating physicians on what to look for,” says Geller. “My son wasn’t diagnosed until he was 15. He had clear symptoms from when he was very little, but they weren’t classic symptoms. I think we’ve come a long way now in terms of realizing this broad array of symptoms.”
In the absence of screening, the broader public must rely on their doctors’ awareness of celiac risk and willingness to test for it.
Van Waffle has a Bachelor of Science degree in biology. He is research editor for Gluten-Free Living. He blogs about nature, gardening and local food at vanwaffle.com.