Experts weigh in on need for biopsy to diagnose celiac disease

August 21, 2017

Experts weigh in on need for biopsy to diagnose celiac disease


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Some say biopsy still needed, others say blood tests alone are sufficient if antibody levels are high enough

role of biopsy in celiac disease diagnosis debated

By Amy Ratner, Beyond Celiac Medical and Science News Analyst

The role of a biopsy in diagnosis of celiac disease remains a controversial topic, with experts reacting both in favor of and against a large international study’s conclusion that the biopsy is not always needed to determine whether children have celiac disease.

Those most opposed to moving away from the biopsy as the gold standard for diagnosis are gastroenterologists who treat patients with celiac disease that does not respond to the gluten-free diet. But others who have studied use of the biopsy maintained that celiac disease can be safely diagnosed in some patients, including adults, without it.

In a study published in the journal Gastroenterology in July, researchers from the Prospective Celiac Disease Diagnostic Evaluation group (ProCeDE) looked at data collected from 2011 to 2014 from 33 pediatric gastroenterology centers in 21 countries. They found that patients 18 years old or younger can be accurately diagnosed without an intestinal biopsy when they have at least one symptom of celiac disease, their tissue-transglutaminase (TGA-IgA) results are 10 times the upper limit of normal, and they have confirming positive results from an anti-endomysial test (EMA).

More: The International Study


The study, overseen by the Dr. von Hauner Children’s Hospital, Munich, Germany, was done to investigate the performance of European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines (ESPGHAN) that allow diagnosis of celiac disease without a biopsy using the same standards researchers applied.

The study did not address the role of the biopsy in adult diagnosis, but celiac disease experts who treat both children and adults responded to the study’s conclusion.

Biopsy still necessary

When patients on the gluten-free diet for 6 to 12 months continue to have symptoms, positive blood test results, or evidence of intestinal damage, they are considered to have non-responsive celiac disease. Studies show about 30 percent of patients fall into this category, though some experts put the number closer to 50 percent when those who don’t have symptoms but continue to have damage to the intestine are included.

Refractory celiac disease is marked by the characteristics of non-responsive celiac disease, plus an abnormal population of white blood cells in the gut. These cells, called abnormal intraepithelial lymphocytes, are unique immune cells found in the lining of the small intestine. Their presence is the distinguishing and disturbing characteristic of refractory celiac disease because they can be the beginning of cancer. Patients are categorized as having Type I, which affects about 1 in 100 of those who have celiac disease, or Type II, the more severe form, which affects 1 in 200.

Paul Ciclitira, M.D., who directs the gastroenterology research unit at the Rayne Institute, St.Thomas’ Hospital in London, said he treats about 100 patients with Type II refractory celiac disease. When left undiagnosed and untreated, these patients face a 50 percent chance of death.

“Should a small intestinal biopsy not be part of the diagnosis of celiac disease with appropriate follow-up endoscopy and biopsy many of these individuals would die,” he said. He noted that lack of a biopsy can lead to misdiagnosis, particularly in 9 percent of celiac disease patients whose blood tests are negative. False positive tTG tests are also a problem, especially for those who have diabetes and thyroid disease, Ciclitira said.

Abdul Al-Toma, M.D., a gastroenterologist at St. Antonius Hospital, the Netherlands, agreed a biopsy to confirm celiac disease is still necessary. “The biopsy is indispensable for a patient with non-responsive celiac disease,” he noted, because the one taken at diagnosis is compared to another taken during follow-up to determine if and how well the patient is recovering.

In general, he added, a biopsy shows the severity of damage to the villi in the intestine, which can predict the potential for complications, including osteoporosis. “And from our own experience, patients without a definite histological diagnosis tend to be less compliant strict (gluten-free) diet,” Al-Toma said.

He called for a thorough discussion about use of the biopsy. “This is certainly a hot-debate issue,” he said. “The results need to be scrutinized before accepting them and making a significant change in our practice.”

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The North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) continues to require a biopsy to confirm a diagnosis of celiac disease in all children. Additionally, the group’s guidelines don’t rely as heavily on the EMA test, saying that while it “may also be reliable” it is subject to errors of interpretation and adds cost. If tTG blood tests are positive but biopsy results are negative, NASPGHAN says the EMA test should be considered.

Biopsy not always needed

Geoffrey Holmes, M.D., a gastroenterologist at The Royal Derby Hospital in the U.K., is one of the authors of a study published in 2016 that concluded diagnosis of celiac disease can be “reliably made in a high proportion of adults based on serology alone” using a specific IgA-tTG antibody.

Study authors said the results added to a body of evidence that the biopsy should no longer be considered mandatory and prompted diagnostic guidelines at Derby Hospital to be revised even though the British Society of Gastroenterology still requires the biopsy for adults.

“If a patient has a very high level of TGA, with characteristic symptoms, what else could the diagnosis be other than celiac disease,” Holmes asked in response to the ProCeDe study. “Under these circumstances, why carry out a biopsy?”

Holmes noted that several important considerations have to be taken into account. Blood tests need to reach a level at which damage to small intestine is always found, meaning they have a positive predictive value of 100 percent. “Above these levels celiac disease patients do not require biopsy,” he said, adding that the blood tests need to be done by labs using a brand of test that has been validated and has a high performance level. “Not all tests perform to the same high standard,” he said. When blood test levels do not meet specific criteria, then biopsy remains mandatory, Holmes said.

He noted that biopsies can be difficult to interpret, leaving the question of whether they indicate celiac disease or not. “In the days before serology became available, I wonder how many times errors in diagnosis were made,” he said.

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