Dilated intercellular spaces as a marker of GERD

Abstract

Gastroesophageal reflux disease (GERD) is typically heralded by the substernal burning pain of heartburn. On endoscopic examination, about one third of GERD subjects with heartburn have erosive disease, and the remainder have nonerosive reflux disease (NERD). Unlike patients with erosive disease, those with NERD (approximately 50%) often do not respond to therapy with proton pump inhibitors (PPIs), raising the question of whether they have NERD and, if they do, whether the cause of their symptoms is similar to those who respond to PPIs. Recently, biopsies established that subjects with heartburn and PPI-responsive NERD, like those with erosive esophagitis, have lesions within the esophageal epithelium known as dilated intercellular space (DIS). In this article, we discuss the physicochemical basis for DIS in acid-injured esophageal epithelium and its significance in GERD. Although DIS is not pathognomic of GERD, it is a marker of a break in the epithelial (junctional) barrier reflecting an increase in paracellular permeability.

Expression of claudin-3 in the esophagus and larynx of rat reflux model

“…Failure of intrinsic defense in the larynx may cause changes in laryngeal epithelia [13]. DIS arises as a morphological feature of acid-induced damage to the squamous epithelium [14,15].…”

The Relationship of the Post-reflux Swallow-induced Peristaltic Wave Index and Esophageal Baseline Impedance with Gastroesophageal Reflux Disease Symptoms

“…Dilated intercellular space (DIS) in the esophageal squamous epithelium is generally regarded as a structural marker of GERD and potentially as an early injury of esophageal mucosal integrity. 8 DIS occurs in association with a decrease in TER. 9 Photomicrographs of intercellular spaces in patients with reflux esophagitis and NERD showed more dilation compared with that of controls.…”

Esophageal Impedance Monitoring: Clinical Pearls and Pitfalls

“…Consequently, the assessment of a persistently impaired mucosal integrity associated with nonerosive mucosal damage may provide a better surrogate for the evaluation of GERD. Altered mucosal integrity occurs through dilated epithelial intercellular spaces that are fi lled with electrolyte-rich fl uid, a good conductor of electrical current, leading to a low-impedance signal (82)(83)(84)(85)(86)(87). Indeed, controlled acid exposure in vivo leads to decreased transepithelial electrical impedance in controls and NERD patients.…”