LAUSR

BACKGROUND Whilst intraepithelial lymphocytes (IELs) are considered normal within the distal esophageal mucosa, there is an appreciation of the potential role of excess lymphocytic infiltration in the pathogenesis of mucosal damage in reflux esophagitis. Furthermore, the diagnosis of lymphocytic esophagitis depends on quantification of the IEL density. There is a lack of knowledge regarding the upper limit of a normal IEL count in healthy volunteers, and this definition may identify abnormal infiltration in various forms of esophageal inflammation. METHODS We studied 117 non-healthcare seeking adult volunteers from a random community sample (the Kalixanda study) with esophageal biopsies 2cm above the gastroesophageal junction. Subjects were divided into four groups based on the presence or absence of gastro-esophageal reflux symptoms and/or esophagitis on endoscopy. Asymptomatic subjects with no endoscopic esophagitis were selected as controls, and the cell counts in this group were used to define the upper limit of normal of IELs, eosinophils and neutrophils. The entire sample was used to identify independent predictors of increased cellular counts by logistic regression analysis. RESULTS None of the healthy controls had an IEL count of more than three per five high power fields (HPF), and therefore this was considered as the upper limit of normal; no controls had eosinophils or neutrophils in esophageal biopsies. Independent predictors of an elevated IEL count were spongiosis on histology (OR 11.17, 95% CI 3.32-37.58, p<0.01) and current smoking (OR 4.84, 95% CI 1.13-2-.71, p=0.03). A receiver operating characteristics analysis concluded that a threshold of 3 IELs/5HPFs performs best in predicting symptoms when a normal esophageal mucosa is visualized on endoscopy (sensitivity=100.0%, specificity=35.2%) CONCLUSION: The healthy esophageal mucosa does not contain more than three IELs per five HPF in the distal esophagus, and a higher count is a sensitive but a non-specific marker that can be used to rule out esophageal mucosal inflammation in symptomatic individuals.