Lugol chromoendoscopy as a diagnostic tool in so-called endoscopy-negative GERD
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Updated: Aug 15, 2026

Simultaneous Laryngopharyngeal and Conventional Esophageal pH Monitoring
Published on: December 14, 2020
Ichiro Yoshikawa1, Masahiro Yamasaki, Takuji Yamasaki
1The Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Iseigaika, Kitakyushu.
Background:
Esophageal mucosal breaks are found in less than half of patients with typical reflux symptom. Thus, endoscopy appears to be an insensitive test for GERD. Lugol chromoendoscopy has been used to detect early esophageal cancer, which is difficult to recognize by routine observation without dye staining. The aim of this study was to determine the efficacy of Lugol chromoendoscopy in the diagnosis of so-called endoscopy-negative GERD (ENRD).
Methods:
The study was conducted with 61 patients (21 women; mean age of 59.8 years) with reflux symptoms and 42 controls (15 women; mean age, 65.0 years). In the absence of any esophageal mucosal abnormalities at conventional endoscopy, Lugol's iodine solution was sprayed onto the esophageal surface, followed by evaluation of the staining pattern. When Lugol-unstained streaks were observed at chromoendoscopy, biopsy specimens were obtained from unstained streaks and from adjacent stained mucosa. Histologic evaluation included basal cell hyperplasia, papillary length, and cellular infiltration.
Results:
Twenty-two (36%) of 61 patients with reflux, and 4 (10%) of 42 controls had visible esophagitis by conventional endoscopy. Lugol chromoendoscopy was performed in the remaining 39 patients and 38 controls. The entire esophageal mucosa was uniformly stained dark brown in 20 patients with reflux and 37 controls. In the remaining 19 patients with reflux and in one control, several unstained streaks were observed in the distal esophagus (p < 0.0001). Histologically, Lugol-unstained mucosa showed a significantly thicker basal cell layer (30.9% +/- 7.6% vs. 12.3% +/- 4.5% of total epithelial thickness, mean +/- standard deviation [SD], p < 0.01) and longer papillae (57.9% +/- 12.6% vs. 38.1% +/- 12.6% of total epithelial thickness, mean [SD], p < 0.01) compared with stained mucosa. In addition, infiltration of lymphocytes in the epithelium was significantly increased in unstained mucosa than in stained mucosa (p < 0.01).
Conclusions:
Visible unstained streaks by Lugol chromoendoscopy seem to be indicative of mucosal injury, which was not detectable by conventional endoscopy. Lugol chromoendoscopy is simple and could be useful for the diagnosis of ENRD. This method could be appealing for the endoscopist as it is easy, safe, and can be performed at the same endoscopic session.
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