Structural Abnormalities of Endoscopy-Negative Reflux Disease – Real or Perceived?

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.

Diagnosis and Management of Non-Erosive Reflux Disease – The Vevey NERD Consensus Group

“…These include basal zone hyperplasia, papillary elongation, inflammatory infiltrates and dilated intercellular spaces. There are significant limitations with each of these criteria, as recently described [49, 50]. However, dilation of intercellular spaces is consistently found more often in NERD patients than in controls.…”

“…The dilated intercellular spaces occur preferentially in the stratum below the surface squamous epithelium and may allow hydrogen ions to interact with sensory nerves in patients with NERD [75]. Dilated intercellular spaces may be useful in the objective diagnosis of NERD though there is some uncertainty left concerning their functional role [50, 76, 77]. There are also concerns regarding the specificity of dilated intercellular spaces as they are also found in association with psychological stress in animal models [78].…”

“…However, these abnormalities are also found in patients without symptoms and they have limited accuracy for the diagnosis of NERD since there is poor agreement on these observations by pathologists and no clear criteria have been described for diagnosis or therapeutic response [50]. Moreover, inflammatory cells are rarely seen in NERD [49].…”

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“…As biópsias devem ser obtidas no momento da endoscopia, independentemente de anormalidades visíveis, para avaliar esofagite eosinofílica; devem ser obtidas cinco biópsias da mucosa (12)(13) . Embora também possam ser detectados os critérios histológicos para esofagite (hiperplasia de célula basal, pregas do plexo prolongando em direção à superfície), esses achados carecem de especificidade para doença do refluxo gastroesofágico (DRGE) (14) . 5.…”

Differences in the Definitions Used for Esophageal and Gastric Diseases in Different Countries

“…Furthermore, it has been reported that palisade vessels are not always evident in Western patients. In particular, US and European authors have reported that palisade vessels cannot always be observed upon endoscopy in patients with minimal-change esophagitis [9], characterized endoscopically by a mucosal cloudy whiteness and redness at deep inspiration [14,15], gastroesophageal reflux disease (GERD), CLE, and BE. In such cases in Japan, proton pump inhibitor therapy is recommended before endoscopic examination to reveal the presence of palisade vessels.…”