Objectives: Dilated intercellular spaces (DIS) in the esophageal epithelium have been identified by electron microscopy as marker of acid reflux damage in experimental animals and adults with gastroesophageal reflux disease (GERD). We aimed to identify and quantify DIS by light microscopy in pediatric GERD and esophagitis.
Methods: We prospectively took esophageal biopsies in 70 consecutive pediatric patients, 48 of whom had GERD symptoms. On hematoxylin and eosin-stained sections esophagitis was scored histologically, and DIS were graded as 0 (absent), + (small and focal), ++ (moderate) or +++ (large and diffuse). A computerized image analysis identified total, cellular and nuclear areas and DIS were quantified as percentage of total minus cellular area.
Results: Forty of 48 GERD patients had histological esophagitis (33 G1, 4 G2, 3 G3, 1 of which with Barrett esophagus), and all 40 had DIS (33 +, 4 ++, 3 +++) with 100% interobserver agreement; 15 of 29 (55%) had abnormal pH study (reflux index, 5.7%-36%). In 30 patients the esophagus was histologically normal. DIS values were 2.21% +/- 2.60% (range, 0.11%-12%) in patients with esophagitis and 0.44% +/- 0.13% (0.2%-0.7%) in patients with normal histology (P < 0.00001), with 0.71% bearing 70% sensitivity and 100% specificity for GERD versus controls. Five other children with esophagitis unrelated to GERD (eosinophilic, Candida, food allergy) also had DIS + to +++, and median DIS area was 5% (1.3%-12%).
Conclusions: DIS can be detected and evaluated by light microscopy, and the image analysis used provides an objective quantification of DIS and supports the light microscopy evaluation. DIS are a morphological feature of GERD and esophagitis in infancy and childhood.