Is acid reflux really caused by acid? Dallas researchers believe they found the answer

Gastroesophageal reflux disease (GERD) may not be due to acid reflux as its name implies, but may actually be caused by a cytokine-mediated inflammatory response that damages the esophagus, according to an article published online May 17, 2016 in the Journal of the American Medical Association.

“This study challenges some of the long-held beliefs about how gastroesophageal reflux damages the esophageal mucosa in patients with gastroesophageal reflux disease,” said first author Kerry Dunbar, MD, PhD, Staff Physician in the Department of Gastroenterology at the Dallas VA Medical Center, in Dallas, TX.

As long ago as 1935, JAMA reported the initial concept of GERD pathogenesis—that gastric acid causes a chemical injury to the esophagus that results in reflux. This concept has been accepted ever since and has remained largely unchanged.

Recent research has now raised another possible cause for GERD—that gastric reflux doesn’t damage esophageal epithelial cells directly, but stimulates them to secrete cytokines that attract immune cells, which is what ultimately damages the esophageal mucosa.

In this small study, the investigators aimed to test the idea in 12 patients whose GERD was successfully controlled by proton pump inhibitors (PPIs). All patients were required to discontinue PPIs, then the researchers observed them to understand how GERD redeveloped.

Two weeks after stopping PPIs, all patients had evidence of esophagitis. However, the changes that re-occurred were not consistent with chemical burns due to stomach acid.

“A chemical burn should develop immediately, as it does if you spill battery acid on your hand,” said senior author Stuart Spechler, MD, Chief of the Department of Gastroenterology at the Dallas VA Medical Center.

An acid reflux chemical burn is thought to damage the luminal surface first and then progress down to the submucosa.

Instead, the researchers found that the esophageal epithelium was not eroded in these patients but was infiltrated by T lymphocytes, along with findings of basal cell hyperplasia and papillary elongation. This matched the new concept that acute GERD is primarily a cytokine-mediated process of inflammation.

“Although this radical change in the concept of how acid reflux damages the esophagus of GERD patients will not change our approach to its treatment with acid-suppressing medications in the near future, it could have substantial long-term implications,” said Dr. Spechler, who is also Professor of Internal Medicine at The University of Texas Southwestern Medical Center, in Dallas, TX.

“We think that it is important for physicians to have an accurate understanding of the mechanisms underlying the diseases that we treat, especially one as common as GERD,” he added. “Furthermore, our study should open up new avenues for novel GERD treatments.”

“Someday we might treat GERD with medications that target the cytokines or inflammatory cells that really cause the damage to the esophagus,” said co-senior author Rhonda Souza, MD, Staff Physician in the Department of Gastroenterology at the Dallas VA Medical Center and Professor of Internal Medicine at UT Southwestern.

Dr. Spechler and Dr. Souza co-direct the Esophageal Diseases Center at the Dallas VA Medical Center, which conducted the research.