GASTROENTEROLOGY 1982;83:818-23 Intraepithelial Eosinophils: A New Diagnostic Criterion for Reflux Esophagitis HARLAND S. WINTER, JAMES 1. MADARA, RICHARD J. STAFFORD, RICHARD J. GRAND, JO-ELLEN QUINLAN, and HARVEY GOLDMAN Department of Medicine, Division of Gastroenterology, Children's Hospital Medical Center; Departments of Pathology, Children's Hospital Medical Center, Brigham and Women's Hospital and Beth Israel Hospital; Departments of Pediatrics and Pathology, Harvard Medical School, Boston, Massachusetts Intraepithelial eosinophils in esophageal biopsy specimens were noted to be an indicator of pro- longed acid reflux. The presence of even a few intraepithelial eosinophils correlated with abnor- mal acid clearance determined by overnight intra- esophageal pH probe study. This new marker also appeared to be an early lesion, as evidenced by its presence in children under age 2 yr, and in biopsy specimens from the proximal esophagus where tra- ditional histometric features (basal zone thickening and papillary lengthening) were lacking. Further- more, when intraepithelial eosinophils were seen in the proximal 75% of the esophagus, they served to identify more severe disease by correlation with greater abnormalities in the pH probe study. Al- though this new marker is a histologic indication of prolonged acid reflux and may be appreciated in routine endoscopic biopsy specimens in children, it has been observed in patients over 18 yr of age and may be applicable to the adult population. Received October 20, 1981. Accepted May 7, 1982. Address requests for reprints to: Harland S. Winter, M.D., Division of Gastroenterology-Enders 6, Children's Hospital Medi- cal Center, 300 Longwood Avenue, Boston, Massachusetts 02115. Supported in part by Pediatric Gastroenterology Research Training Grant AM-07333, National Institutes of Health (NIH) New Investigator Research Award (HSW) 1-R23-AM-31070-01, NIH Research Award (JLM) AM-27972, and Clinical Research Center Grant RR-00128. The authors thank Ms. Shirley Lerner and Ms. Wendy Gross for expert technical assistance; Ms. Elizabeth Allred and Ms. Peggy Morrison for statistical analysis of data; Ms. Natalie Daniels, Mr. Aniviel V. deSousa, Ms. Vera Daniels, and Ms. Bernice Oliver for histological preparations; and Drs. Mark Peppercorn and Jerry S. Trier for their critical review of the manuscript. © 1982 by the American Gastroenterological Association 0016-5085/82/100818-06$02.50 Gastroesophageal acid reflux and its sequelae have been associated with many clinical symptoms in children (1-3). While the histologic consequences in the esophagus of acid reflux have not been critically evaluated in children, in adults prolonged acid re- flux is associated with basal zone thickening and papillary hyperplasia (4,5), as well as inflammation and ulceration. In the course of evaluating patients for esophageal disease, we frequently noted the presence of intraepithelial eosinophils in esophageal mucosal biopsy specimens. To determine the signifi- cance and potential usefulness of intraepithelial eosinophils, we correlated their presence with basal zone thickening and papillary hyperplasia and with a sensitive test of acid clearance, continuous intra- esophageal pH monitoring (6). Methods Patient Population There were 46 patients; 28 men and 18 women, ranging in age from 3 mo to 19 yr (mean 4.4 yr); 32 of the patients were under age 5 yr. The principal clinical prob- lems were those of chronic pulmonary disease (asthma, recurrent pneumonia, and apnea) in 25 patients, recurrent vomiting or hematemesis in 10, dysphagia or pyrosis in 8, abdominal pain in 2, and melena in 1. pH Probe Study Continuous intraesophageal pH monitoring (Micro- electrodes, probe MI-506, Londonderry, N.H.) was per- formed on all patients for 14-20 h, including an overnight period. Infants were fasted for 4 h, and older children for 6 h before placement of the pH probe. During the study, patients were instructed to eat their usual diet and sleep in a flat position, usually prone. Antacids, cimetidine, and when possible, theophylline,