Omeprazole and ultrastructural modifications occurring in reflux esophagitis [1]

Dilated intercellular spaces are a sign of esophageal epithelial damage in acid-perfused rabbits. This alteration can be identified only by transmission electron microscopy (TEM).1,2 The same changes have also been demonstrated in reflux esophagitis in humans, occurring in patients with either erosive or nonerosive esophagitis.3 As yet, we do not know if successful medical therapy induces a regression of these ultrastructural changes. We observed a case of hematemesis and melena occurring in an 11-month-old child. Upper gastrointestinal endoscopy revealed a hemorrhagic erosive esophagitis (stage IV of Savary-Miller modified classification). Eight endoscopic biopsies were taken 5 cm above the Z line. Of these, 4 were stained with H&E, to assess general pathology, and 4 were selected for processing by TEM.4 The latter biopsies showed mean intercellular space diameters of $3.04 mm (mean normal values reported in humans, 0.46 6 0.06 mm SD)3 (Figure 1A). After 6 months of treatment with ranitidine (10 mg z kg21 z d syrup) upper GI endoscopy showed a stage II esophagitis. TEM demonstrated mean intercellular space diameters of $2.5 mm (Figure 1B). As a consequence, the patient was treated with omeprazole 10 mg/day for 18 months (the half granular content of the capsule of 20 mg was administrated in a few milliliters of orange juice, 30 minutes before breakfast). During this period, the patient was asymptomatic, growth was normal, and no side effects were recorded. Upper GI endoscopy at the end of therapy showed a normal esophageal mucosa both endoscopically and histologically. TEM also demonstrated the complete recovery of the ultrastructural changes (Figure 1C) with the mean intercellular space diameters being #0.40. This is the first demonstration that omeprazole is effective not only in inducing the regression of symptoms and macroscopic lesions but in the restoration of normal intercellular space dimensions, whose dilatation must be considered the first alteration of reflux esophagitis. Nevertheless, to date we do not know if such an outcome is achieved in every patient considered clinically and endoscopically cured, nor do we know details of the treatment time interval required to achieve complete ultrastructural recovery.