A novel histologic scoring system to evaluate mucosal biopsies from patients with eosinophilic esophagitis

Clin Gastroenterol Hepatol. 2009 Jul;7(7):749-755.e11. doi: 10.1016/j.cgh.2009.03.022. Epub 2009 Apr 1.

Abstract

Background & aims: Eosinophilic esophagitis (EoE) is characterized by medically/surgically-resistant gastroesophageal reflux symptoms and dense squamous eosinophilia. Studies suggest that histologic assessment of esophageal eosinophilia alone cannot reliably separate patients with EoE from those with gastroesophageal reflux disease (GERD). Our goal was to develop an assay to identify EoE patients and perhaps differentiate EoE from other causes of esophageal eosinophilia.

Methods: A monoclonal antibody specific for an eosinophil secondary granule protein (eosinophil peroxidase [EPX]) was developed and shown to specifically identify intact eosinophils and detect eosinophil degranulation in formalin-fixed specimens. A histopathologic scoring algorithm was developed to analyze data from patient evaluations; the utility of this algorithm was assessed by using archived esophageal tissues from patients with known diagnoses of EoE and GERD as well as controls from 2 tertiary care centers.

Results: Intraobserver/interobserver blinded evaluations demonstrated a significant difference (P < .001) between scores of samples taken from control subjects, from patients with esophageal eosinophilia who had a diagnosis of EoE, and from patients with GERD (P < .001). This algorithm also was able to identify patients whose clinical course was suggestive of a diagnosis of EoE, but that nonetheless failed to reach the critical threshold number of > or =15 eosinophils in a high-power (40x) microscopy field.

Conclusions: A novel immunohistochemical scoring system was developed to address an unmet medical need to differentiate histologic specimens from patients with EoE relative to those with GERD. The availability of a unique anti-EPX-specific monoclonal antibody, combined with the ease/rapidity of this staining method and scoring system, will provide a valuable strategy for the assessment of esophageal eosinophilia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Animals
  • Biopsy*
  • Child
  • Child, Preschool
  • Diagnosis, Differential
  • Eosinophilia / diagnosis*
  • Eosinophilia / immunology
  • Eosinophilia / pathology*
  • Esophagitis / diagnosis*
  • Esophagitis / immunology
  • Esophagitis / pathology*
  • Gastroesophageal Reflux / diagnosis
  • Gastroesophageal Reflux / pathology
  • Humans
  • Immunohistochemistry / methods
  • Infant
  • Mice
  • Middle Aged
  • Severity of Illness Index*
  • Staining and Labeling