Marie Robert, MD, Professor of Pathology, Medicine (Digestive Diseases) and Human and Translational Immunology, and a leading diagnostic pathologist in the study of celiac disease, authored an invited review on celiac disease recently published online in the prestigious medical journal, Gastroenterology. In addition, a 13-center study on celiac disease that Dr. Robert originated and brought to fruition was recently published in another premier medical publication, the American Journal of Surgical Pathology.
Dr. Robert is lead author on the invited review in Gastroenterology, entitled, “Opportunities for Improving Biopsy and Non-Biopsy-Based Diagnosis of Celiac Disease.” Her co-authors are Carolina Ciacci, MD, Extraordinary Professor of Gastroenterology at the University of Salerno, Italy; and Benjamin Lebwohl, MD, MS, Louis and Gloria Flanzer Scholar at Columbia University Irving Medical Center.
The review summarizes the current evidence both for and against a non-biopsy approach for the initial diagnosis of celiac disease, focusing on opportunities to improve both methods. It also presents challenges to histology analysis and ways to improve biopsy analysis in the pathology laboratory, introducing the concept of the molecular microscope to combine dynamic spatial transcriptomics with standard histology data in the future.
The authors conclude that an increasing body of data supports the accuracy of a non-biopsy approach in the context of a highly elevated TTG IgA in diagnosing celiac disease, a common autoimmune disorder affecting 3.2 million Americans. However, caution is warranted to ensure that widespread adoption of a biopsy-free approach follows strict serology cutoffs to avoid over or underdiagnosis of this life altering diagnosis.
The 13-center correlative study published in AJSP focuses on follow-up (not diagnosis) of established patients with celiac disease. It is entitled, “Clinical Data Do Not Reliably Predict Duodenal Histology at Follow-up in Celiac Disease.” Most providers utilize clinical data as surrogates of mucosal status to avoid additional esophagogastroduodenoscopy. The study notes that validated non-biopsy methods to assure duodenal mucosal healing in celiac disease are lacking, yet ongoing mucosal injury is associated with anemia, osteoporosis, and lymphoma.
“The aim of this study was to rigorously assess patterns of histologic mucosal recovery at follow-up in celiac disease and to correlate findings with clinical data,” the authors wrote.
In the study, gastrointestinal pathologists from 13 centers evaluated initial and follow-up duodenal biopsies from 181 patients with celiac disease using stringent histology methodology. The authors found that neither symptoms, serology, nor degree of gluten free diet adherence reliably predicted mucosal status in follow-up duodenal biopsies.
They note that intraepithelial lymphocytes frequently remain elevated in follow-up biopsies despite normalization of villous architecture, even in patients with resolution of symptoms and serology, a nuance that should be shared with clinicians in pathology reports.
In addition, “Proximal and distal duodenal mucosal biopsies show histologic concurrence for the most part, but significant villous injury can be missed if the proximal duodenum is not sampled at follow-up.”
Finally, the study advises that “numerous celiac disease clinical trials are underway, most of which have a histologic endpoint. We suggest pathologists should be aware that, once medications are approved, duodenal mucosal inflammatory status documented in pathology reports may become a criterion to determine eligibility for medication use.” In their conclusion, the authors expressed hope that the data they present “will be of immediate practical value to practicing pathologists in their routine assessments of mucosal injury in celiac disease, especially as relates to follow-up biopsies.”