Improving Celiac Disease Diagnosis and Management, with Daniel Leffler, MD, MS

Recent years have seen considerable advances in the understanding of celiac disease biology, pathogenesis, and clinical implications. Despite this progress, it remains underdiagnosed and frequently mismanaged.

Research presented at Digestive Disease Week (DDW) 2025 by Daniel Leffler, MD, MS, Executive Medical Director and Celiac Disease Global Clinical Development Lead at Takeda Pharmaceuticals, a gastroenterologist and a founding member of the Celiac Center at Beth Israel Deaconess Medical Center, and an associate professor of medicine at Harvard Medical School, sheds light on celiac disease practice patterns and educational needs among US healthcare providers.1

“We've really evolved a great deal in many ways over the last few decades,” Leffler told HCPLive, citing a better understanding of the biology of celiac disease, what triggers it, and how it leads to intestinal damage, malabsorption, and GI symptoms. “I think it's become abundantly clear how prevalent this disorder is, how undiagnosed it is, and how poorly diagnosed and poorly managed celiac disease is today.”

An estimated 1 in 133 people in the US, or about 1% of the population, has celiac disease, but recent screening studies suggest this prevalence may actually exceed 1%. Additionally, an estimated 83% of people in the US who have celiac disease are undiagnosed or misdiagnosed with other conditions.2

Leffler points to the disease’s heterogeneity as one of the key barriers to diagnosis, describing how although celiac disease can manifest with classic gastrointestinal symptoms, many patients present with non-GI symptoms such as anemia, rashes, joint pain, and headaches, making it difficult for primary care providers and other frontline clinicians to know when to consider celiac disease as part of the differential diagnosis. Although the use of tissue transglutaminase IgA testing is relatively cheap and effective, it is often underutilized in appropriate clinical scenarios.

“When any patient is having ongoing issues that you don't really have a handle on or seem a little out of place for what they are, it just should be one of those reflexes to ask ‘Why don't we just test that?” Leffler said. “The same way people do a lot with thyroid disease… we need celiac disease testing to get to that level of awareness by frontline practitioners.”

He goes on to describe related diagnostic challenges with the premature initiation of a gluten-free diet before formal testing, which can complicate the process of making a formal diagnosis. Leffler says this was one of many challenges that emerged in his research at DDW, with others being awareness of diagnostic guidelines, when to refer for a biopsy, and what to do when a patient has been diagnosed with celiac disease.1

Looking ahead, Leffler expresses interest in research on why only some patients have ongoing intestinal damage and a wide range of sensitivities to gluten, ways to facilitate more childhood diagnoses, and potential interventions to delay or prevent celiac disease onset.

“There's a bias in medicine that things that can be treated with diet aren't that serious, and I think celiac disease unfortunately falls into that category sometimes,” Leffler explained. “We need to get people to understand that this is actually a serious condition that can have life-threatening complications, so it really is something that they should be diagnosing and taking seriously, like any other immune-mediated condition.”

Editors’ note: Leffler has relevant disclosures with Takeda Pharmaceuticals.

References

1. Cazzetta S, Salinas G, Renfroe A, et al. CHALLENGES AND OPPORTUNITIES IN THE MULTIDISCIPLINARY MANAGEMENT OF CELIAC DISEASE IN THE UNITED STATES: RESULTS OF A CASE-BASED SURVEY. Abstract presented at Digestive Disease Week 2025 in San Diego, CA, from May 3 - May 6, 2025.

2. Beyond Celiac. Celiac Disease: Fast Facts. Accessed May 12, 2025. https://www.beyondceliac.org/celiac-disease/facts-and-figures/