Why Europe & North America Still Disagree on Diagnosing Celiac Disease

For decades, an intestinal biopsy has been considered the gold standard for diagnosing celiac disease. Yet today, leading medical organizations on either side of the Atlantic continue to disagree on whether some children can be diagnosed without one.

At the center of the debate are two leading pediatric gastroenterology organizations. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) supports a biopsy-free pathway for some children who meet specific criteria, while the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) has historically taken a more cautious approach.

European and North American experts continue to differ on how much evidence is needed before a child can be diagnosed with celiac disease and begin a lifelong gluten-free diet.

Traditionally, diagnosis has relied on a combination of blood tests and an upper endoscopy with biopsy to identify characteristic damage in the small intestine. While that approach remains standard in much of North America, European guidelines have increasingly embraced the idea that some children can be diagnosed accurately without an invasive procedure.

The disagreement is more than academic. Whether a biopsy is required can affect how quickly a diagnosis is made, whether a child must undergo anesthesia and endoscopy, and how healthcare resources are used.

Europe’s Shift Toward Biopsy-Free Diagnosis

In 2012, ESPGHAN introduced criteria allowing some symptomatic children to receive a celiac disease diagnosis without undergoing biopsy. The pathway required tissue transglutaminase IgA (tTG-IgA) levels greater than 10 times the upper limit of normal, confirmation with endomysial antibody (EMA) testing, compatible genetic markers, and symptoms consistent with celiac disease.

The guidelines were updated in 2020 after additional research demonstrated that genetic testing did not substantially improve diagnostic accuracy in children who already met the other criteria. The revised recommendations removed the requirement for HLA testing and expanded the biopsy-free pathway to include certain asymptomatic children with strongly positive serology.

As a result, biopsy-sparing diagnosis has become an increasingly accepted part of pediatric celiac disease care across Europe.

Why North America Has Been More Cautious

NASPGHAN has cited several reasons for its more cautious approach.

One concern involves variability between laboratory assays used to measure tTG antibodies. Because different tests may perform differently, some experts have questioned whether a single antibody threshold can be applied consistently across healthcare systems.

Another concern is that endoscopy can occasionally identify additional conditions beyond celiac disease, including eosinophilic gastrointestinal disorders or Helicobacter pylori infection. Forgoing biopsy could mean missing information that might otherwise influence a patient’s care.

There are also concerns about implementation. Because a diagnosis of celiac disease typically leads to lifelong dietary restrictions and medical follow-up, some experts argue that a biopsy provides an additional layer of diagnostic certainty before recommending permanent changes.

NASPGHAN acknowledged the European approach in its 2016 clinical report but did not endorse it for routine use. More recently, the American College of Gastroenterology’s 2023 guideline suggested that a biopsy-free diagnosis may be appropriate for carefully selected children with strongly positive serology, while continuing to recommend endoscopy with duodenal biopsy as the standard diagnostic approach.

Could New Diagnostic Tools Change the Debate?

Researchers are also exploring new diagnostic tools that could reduce the need for both biopsies and prolonged gluten challenges.

This is particularly important for people who have already started a gluten-free diet before being formally evaluated for celiac disease. Current recommendations often require these individuals to reintroduce gluten for several months before blood tests and biopsies can reliably detect an active immune response. For many patients, that process can be physically uncomfortable and psychologically difficult. 

One promising area of research focuses on measuring rapid immune responses to gluten. Levels of the immune signaling molecule interleukin-2 (IL-2) can rise within hours when gluten-reactive immune cells become activated, raising the possibility of diagnostic approaches that require far less gluten exposure than current protocols.

Researchers are also investigating whether those same immune responses can be measured entirely outside the body. Rather than requiring patients to consume gluten, scientists can expose a blood sample to gluten peptides in a laboratory and measure whether gluten-reactive immune cells respond. If validated in larger studies, such approaches could potentially help diagnose celiac disease in people who are already following a gluten-free diet without requiring a lengthy gluten challenge. 

A Debate That Is Still Evolving

Despite growing interest in biopsy-free diagnosis, there is currently no global consensus on the best approach. For now, the Atlantic Ocean still marks a meaningful divide in how celiac disease is diagnosed. But as new biomarkers and blood-based immune tests move closer to clinical practice, the question may eventually shift from whether a biopsy is necessary to whether either side’s current approach remains the best option.

Until then, children with similar test results may continue to face different diagnostic pathways depending on which guidelines their healthcare team follows.