A review of the evidence shows the tests used in the US have a high rate of accuracy (part one of a two part story)
Part one of a two-part story
By Amy Ratner, Beyond Celiac Medical and Science News Analyst
The tests most commonly used to diagnose celiac disease in the United States held up to scrutiny in a broad review of research published by the federal agency charged with producing evidence to make healthcare safer.
But the accuracy of both the blood test and the biopsy used for diagnosis depends on where they’re done, who does them and who reads the results.
The Agency for Healthcare Research and Quality (AHRQ), which works within the U.S. department of Health and Human Services, did a systematic review of 60 individual studies and 13 previous systematic reviews of research into the methods used to diagnose celiac disease. A clinical summary of the report was recently released.
“We hope clinicians will use the information to make evidence-informed decisions when ordering tests to diagnose celiac disease,” said Alison Hunt, AHRQ communications specialist.
“The fact that celiac disease has been given a comprehensive evidence review indicates an acknowledgement by Health and Human Services that there is a need for increased celiac disease diagnosis,” said Ciaran Kelly, MD, medical director of the Celiac Center at Beth Israel Deaconess Medical Center and Beyond Celiac Scientific/Medical Advisory Council Member.
He said the report may not have as much impact on the way patients are diagnosed as intended, but it is likely to be used by epidemiologists, researchers, healthcare planners, health network administrators and guideline developers.
The AHRQ review included studies published from January 1990 through March 2015. It aimed to assess the accuracy and potential harm of blood and gene tests, biopsies and video capsule endoscopies by looking at numerous studies to evaluate the strength of a large body of evidence. Patients have to be consuming gluten for all but the gene test to be accurate.
The agency concluded that anti-tissue transglutaminase immunoglobulin A (tTG IgA) testing results in accurate positive and negative results. Researchers call this sensitivity and specificity.
Sensitivity – The ability of a test to correctly classify a person as having a disease
Specificity – The ability of a test to correctly classify a person as not having a disease
TTG is the single blood test preferred by the American College of Gastroenterology (ACG) for the detection of celiac disease in patients two years of age and older, the healthcare research agency said, noting that other tests might be needed for those who are IgA deficient.
For patients, the tTG test has the advantages of being simple, inexpensive, widely available and covered by insurance, in addition to being very accurate in cases of untreated celiac disease, Dr. Kelly said.
Peter Green, MD, president of the North American Society for the Study of Celiac Disease (NASSCD), called the tTG Iga “a very good test.”
“If it was used more, more people with celiac disease would be diagnosed,” he said. “But nothing is 100 percent.”
The test works best when it’s used in patients in whom celiac disease is highly suspected, including family members of those who have celiac disease, those who have diarrhea or type 1 diabetes, Green said. It is less effective in the general population – for example in patients who have lower risk symptoms such bloating, headaches or arthritis.
False positive – A test reading that incorrectly indicates a person has a disease
False negative – A test reading that incorrectly indicates a person does not have a disease
“The test is skewed not to miss anyone, so in this group it can result in more false positives,” said Green who is also director of the Celiac Disease Center at Columbia University.
“Of all of the blood tests, the tTG IgA has the best overall performance in terms of its ability to pick up most patients with celiac disease,” said Benjamin Lebwohl, MD, assistant professor of clinical medicine and epidemiology at Columbia. “But it is not perfect, as some patients with celiac disease will have a normal tTG IgA level and some people without celiac disease will have an abnormally elevated level.”
The study review also concluded that the endomysial immunoglobulin A (EMA IgA) test is highly specific, but less sensitive than the tTG test. The EMA test is not widely used in the US and is less useful when a patient is IgA deficient. The test is expensive, not widely available and often has to be sent to specialty labs where its interpretation may be more variable than other tests.
A review of research into the use of deamidated gluten peptide (DGP) antibody testing showed it may be more accurate than tTG tests in children younger than 24 months of age. However, the strength of the evidence was low and the findings need to be replicated in future studies, the study review said.
The study review set out to determine the accuracy of celiac disease diagnosis when a combination of tTG and other tests is used. It concluded a combination appears to be accurate but that increased accuracy is “rarely clinically significant.”
The accuracy of blood tests can depend on the laboratory and the manufacturer, the review found. It points to a 2009 study in which 150 samples from patients with known celiac disease status were used to compare the accuracy of tTG tests at 20 laboratories in the U.S. and Europe. Sensitivity was less than 75 percent at four laboratories, the review notes. A similar 2012 study found differences in the performance of tTG tests across various manufacturers.
The review included only studies in which all participants had a biopsy, regardless of their blood test results. Because a biopsy is invasive, some accuracy studies required that only participants with positive tests for celiac disease undergo biopsy. These studies were excluded from the review because the false-negative rate, and thus overall accuracy, of the blood tests they evaluated could not be determined.
Although blood tests coupled with a biopsy have proven to accurately diagnosis celiac disease, most people with celiac disease remain undiagnosed. This points to a critical need for more research and more funding for research from both the government and the private sector to improve the diagnosis rate. You can keep up to date on research and participate by signing up here.
The second part of this story details what the AHRQ study review found about the use of gene testing, biopsies and video capsule endoscopy in celiac disease diagnosis. Read part two here.