Abstract
About two thirds of individuals affected by gastroesophageal reflux disease suffer from endoscopy-negative esophageal reflux disease. Often, these individuals do not receive adequate medication. In contrast, erosive reflux disease is much better defined and even subclassified as mucosal breaks of the esophageal epithelium. It is known from large trials that gastroesophageal reflux disease is probably not a categorical disease without further progression. On the other hand, the first structural changes of the esophageal epithelium indicating the beginning of reflux disease are unknown. Furthermore, it is not known when reflux esophagitis is structurally healed (besides symptom relief). Histological markers are based on observations made without clinical correlation. It has gradually become clear that there are no specific reflux-induced esophageal lesions. All described histological criteria can be also observed in other esophageal conditions. Structural abnormalities are believed to be found more often close to the lesser gastric curvature or the right esophageal wall. Furthermore, it could be shown with a standardized biopsy protocol that a good correlation with clinical findings is possible. Conventional histological criteria include thickness of basal cell layer, length of papillae and inflammatory infiltrates. New criteria include dilation of intercellular spaces and changes of protein distribution within intercellular spaces. All changes are reversible with PPI therapy. In conclusion, structural abnormalities are not specific for gastroesophageal reflux disease or NERD but are reversible with PPI, which underlines their relevance.
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