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VA Study Questions Pathogenesis of GERD

by U.S. Medicine

July 6, 2016

DALLAS—A small, single-center study led by researchers from the Dallas VAMC suggests that gastroesophageal reflux disease (GERD) might be caused by an immune reaction, rather than direct chemical injury from stomach acids.

Results were published online recently as a “Preliminary Communication” online by the Journal of the American Medical Association.1

graphic sidebar“In this preliminary study of 12 patients with severe reflux esophagitis successfully treated with PPI therapy, stopping PPI medication was associated with T lymphocyte–predominant esophageal inflammation and basal cell and papillary hyperplasia without loss of surface cells,” wrote first author Kerry Dunbar, MD, PhD, from the Dallas VAMC and colleagues. “If replicated, these findings suggest that the pathogenesis of reflux esophagitis may be cytokine-mediated rather than the result of chemical injury.”

“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 senior author Stuart Spechler, MD, chief of gastroenterology at the Dallas VAMC.

The small study included 12 patients, all but one male, with a mean age of 57.6 treated successfully treated at the Dallas VAMC for severe reflux esophagitis from May 2013 to July 2015. After being instructed to discontinue PPIs, study participants received evaluations at baseline, as well as one and two weeks after stopping medication. Assessments included 24-hour esophageal pH and impedance monitoring and esophagoscopy with high-resolution confocal laser endomicroscopy. Noneroded areas of the esophagus, where immune activity was assumed to be lower than in eroded areas, were biopsied.

While almost all participants (11/12) had no visible evidence of esophagitis at baseline, by two weeks after stopping PPIs, all participants developed esophagitis—five of them had severe cases. In addition, all participants developed abnormalities characteristic of GERD within two weeks of ending drug therapy. Results indicated that, between baseline and two weeks, acid exposure increased by 16.2%.

Significant increases in infiltration of intraepithelial lymphocytes one and two weeks after stopping PPIs were identified through biopsies, with predomination of T cells and few or no neutrophils and eosinophils, according to the report.

“[E]sophageal basal cell and papillary hyperplasia developed in areas without surface erosions. If the traditional notion were true, that acute GERD is caused by refluxed acid directly inflicting lethal, chemical injury to surface epithelial cells, then basal cell and papillary hyperplasia would have been expected only in areas with surface erosions, and the infiltrating inflammatory cells would have been granulocytes primarily,” the researchers pointed out, calling for further studies to confirm their results.

“A chemical burn should develop immediately, as it does if you spill battery acid on your hand,” Spechler explained.

Commenting in a linked editorial, Peter Kahrilas, MD, from Northwestern Feinberg School of Medicine in Chicago, called the findings “provocative.”2

He suggested, however, that the participants— mainly men with high-grade erosive GERD and hiatal hernias—aren’t typical of most GERD patients and that the results might not apply to all patients with the condition.

1 Dunbar KB, Agoston AT, Odze RD, Huo X, Pham TH, Cipher DJ, Castell DO, Genta RM, Souza RF, Spechler SJ. Association of Acute Gastroesophageal Reflux Disease With Esophageal Histologic Changes. JAMA. 2016 May 17;315(19):2104-12. doi: 10.1001/jama.2016.5657. PubMed PMID: 27187303.2 Kahrilas PJ. Turning the Pathogenesis of Acute Peptic Esophagitis Inside Out. JAMA. 2016 May 17;315(19):2077-8. doi: 10.1001/jama.2016.5827. PubMed PMID: 27187299.


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