title: Increased numbers of eosinophils, rather than only etiology, predict histologic changes in patients with esophageal eosinophilia.
abstract: OBJECTIVE
  It can be a challenge to differentiate individuals with eosinophilic esophagitis (EoE) from those with gastroesophageal reflux disease (GERD). We investigated differences in histologic and eosinophil patterns and numbers of mast cells between patients with these disorders.
  
  
  METHODS
  We performed histologic analyses and immunohistochemical assays for eosinophil-derived neurotoxin (EDN), major basic protein (MBP), and tryptase, using biopsy samples from 10 patients with GERD (positive results from a pH study and response to proton pump inhibitors), Barrett's esophagus, or EoE (negative results from a pH study and positive response to budesonide). Patients were matched for degree of eosinophilia.
  
  
  RESULTS
  Samples from patients with EoE, GERD, or Barrett's esophagus had similar increases in concentrations of eosinophils. Patients with GERD or EoE did not differ in amount of basal zone hyperplasia, microabscesses, spongiosis, eosinophil distribution, maximum eosinophils/high-power field (HPF), or composite histologic scores. Samples from all 3 groups had high levels of EDN and MBP; the levels of eosinophil products were correlated (ρ = 0.93). Extracellular staining for EDN was greater than intracellular staining (2.67 of 3 vs 1.86 of 3); levels tended to be greater in samples from patients with EoE than GERD (P = .05) or Barrett's esophagus (P = .06). Detection of EDN correlated with peak numbers of eosinophils/HPF (ρ = 0.6 for intracellular and extracellular staining). Peak numbers of tryptase-positive mast cells/HPF were significantly greater in samples from patients with EoE than GERD or Barrett's esophagus (P = .01 and .005, respectively). The Spearman correlation between eosinophil and mast cell density was a ρ value of 0.2.
  
  
  CONCLUSIONS
  Biopsy samples from patients with GERD and EoE, matched for esophageal eosinophilia, have similar changes in histology and levels of EDN and MBP, whereas mast cells from patients with EoE have higher levels of these products. The presence of esophageal eosinophils, rather than etiology, could be the most important determinant of epithelial response.
authors.affiliation: Division of Allergy and Immunology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Srividya
authors.initials: S
authors.lastname: Sridhara
authors.forename: Karthik
authors.initials: K
authors.lastname: Ravi
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Smyrk
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kita
authors.forename: Gail M
authors.initials: GM
authors.lastname: Kephart
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Weiler
authors.forename: David A
authors.initials: DA
authors.lastname: Katzka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D003937:Diagnosis, Differential; D047093:Eosinophil Major Basic Protein / Q000032:analysis; D047208:Eosinophil-Derived Neurotoxin / Q000032:analysis; D057765:Eosinophilic Esophagitis / Q000175:diagnosis* / Q000473:pathology*; D004804:Eosinophils / Q000473:pathology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000175:diagnosis / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007958:Leukocyte Count; D008297:Male; D008407:Mast Cells / Q000473:pathology; D008875:Middle Aged; D011509:Proteoglycans / Q000032:analysis; D053802:Tryptases / Q000032:analysis; D055815:Young Adult
chemical_list: D011509:Proteoglycans; C074129:PRG2 protein, human; D047208:Eosinophil-Derived Neurotoxin; D047093:Eosinophil Major Basic Protein; D053802:Tryptases