Dilated intercellular Spaces: A Major Morphological Feature of Esophagitis

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 eosinYstained 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%Y36%). In 30 patients the
esophagus was histologically normal. DIS values were
2.21% T 2.60% (range, 0.11%Y12%) in patients with
esophagitis and 0.44% T 0.13% (0.2%Y0.7%) in patients
with normal histology (P G 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%Y12%).
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.