title: Predictors of response to steroid therapy for eosinophilic esophagitis and treatment of steroid-refractory patients.
abstract: OBJECTIVE
  Eosinophilic esophagitis (EoE) is commonly treated with swallowed (topical) corticosteroids (tCS). However, few factors have been described that predict outcomes of steroid therapy. We aimed to identify factors associated with nonresponse to tCS and report outcomes of second-line treatment for patients with steroid-refractory EoE.
  
  
  METHODS
  We performed a retrospective cohort study by using the University of North Carolina EoE Clinicopathologic Database to identify patients who received tCS for EoE from 2006 through 2013. Demographic, symptom, endoscopic, and histologic data were extracted from medical records. Immunohistochemistry was performed on archived biopsies. Responders and nonresponders to tCS were compared.
  
  
  RESULTS
  Of 221 patients with EoE who received tCS, 71% had endoscopic improvement, 79% had symptomatic improvement, and 57% had histologic response (<15 eosinophils/high-power field). After multivariate logistic regression, esophageal dilation at the baseline examination predicted nonresponse (odds ratio, 2.9; 95% confidence interval, 1.4-6.3), and abdominal pain predicted response (odds ratio for nonresponse, 0.31; 95% confidence interval, 0.12-0.83); no other clinical features were predictive. On the basis of immunohistochemical analysis, higher baseline levels of tryptase (244 vs 157 mast cells/mm(2), P = .04) and eotaxin-3 (2425 vs 239 cells/mm(2), P = .02) were associated with steroid response, but levels of major basic protein were not. Among 27 steroid-refractory patients, a mean of 2 additional therapies were tried; only 48% of the patients eventually responded to any second-line therapy.
  
  
  CONCLUSIONS
  On the basis of a retrospective analysis of a large group of patients with EoE, only 57% have a histologic response to steroid therapy. Baseline esophageal dilation and decreased levels of mast cells and eotaxin-3 predicted which patients would not respond to therapy. Combining clinical factors and immunohistochemistry might therefore be used to direct therapy.
authors.affiliation: Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: W Asher
authors.initials: WA
authors.lastname: Wolf
authors.affiliation: Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Cary C
authors.initials: CC
authors.lastname: Cotton
authors.affiliation: Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Green
authors.affiliation: Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Julia T
authors.initials: JT
authors.lastname: Hughes
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: John T
authors.initials: JT
authors.lastname: Woosley
authors.affiliation: Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Shaheen
authors.affiliation: Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina. Electronic address: edellon@med.unc.edu.
authors.forename: Evan S
authors.initials: ES
authors.lastname: Dellon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001706:Biopsy; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D057765:Eosinophilic Esophagitis / Q000188:drug therapy*; D004947:Esophagus / Q000473:pathology; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008407:Mast Cells / Q000276:immunology; D008875:Middle Aged; D009657:North Carolina; D011379:Prognosis; D012189:Retrospective Studies; D013256:Steroids / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D013256:Steroids
keywords: Biomarkers; Corticosteroids; Eosinophilic Esophagitis; Refractory; Therapy
references.citation: J Clin Invest. 2001 Jan;107(1):83-90
references.pmid: 11134183
references.citation: Clin Gastroenterol Hepatol. 2014 Aug;12(8):1272-9
references.pmid: 24440337
references.citation: Gastroenterology. 2009 Oct;137(4):1238-49
references.pmid: 19596009
references.citation: Allergy. 2010 Jan;65(1):109-16
references.pmid: 19796194
references.citation: Gastroenterology. 2006 Nov;131(5):1381-91
references.pmid: 17101314
references.citation: Aliment Pharmacol Ther. 2010 Feb 15;31(4):509-15
references.pmid: 19925501
references.citation: J Allergy Clin Immunol. 2010 Apr;125(4):879-888.e8
references.pmid: 20371398
references.citation: Gastrointest Endosc. 2014 Apr;79(4):577-85.e4
references.pmid: 24275329
references.citation: Clin Gastroenterol Hepatol. 2012 Jul;10(7):750-2
references.pmid: 22366179
references.citation: J Allergy Clin Immunol. 2012 Apr;129(4):1064-75.e9
references.pmid: 22391115
references.citation: Am J Gastroenterol. 2012 Oct;107(10):1503-11
references.pmid: 22777338
references.citation: Am J Gastroenterol. 2013 May;108(5):679-92; quiz 693
references.pmid: 23567357
references.citation: Gastroenterology. 2012 Aug;143(2):321-4.e1
references.pmid: 22561055
references.citation: Clin Gastroenterol Hepatol. 2004 Jul;2(7):568-75
references.pmid: 15224281
references.citation: Gastroenterology. 2013 Dec;145(6):1230-6.e1-2
references.pmid: 23954315
references.citation: J Immunol. 2010 Apr 1;184(7):4033-41
references.pmid: 20208004
references.citation: Dig Dis. 2014;32(1-2):134-8
references.pmid: 24603397
references.citation: Gastroenterology. 2007 Oct;133(4):1342-63
references.pmid: 17919504
references.citation: Gastroenterology. 2010 Nov;139(5):1526-37, 1537.e1
references.pmid: 20682320
references.citation: Clin Gastroenterol Hepatol. 2012 Oct;10(10):1066-78
references.pmid: 22728382
references.citation: J Allergy Clin Immunol. 2011 Jul;128(1):3-20.e6; quiz 21-2
references.pmid: 21477849
references.citation: Am J Gastroenterol. 2011 Feb;106(2):264-71
references.pmid: 20978486
references.citation: Am J Gastroenterol. 2012 May;107(5):698-706
references.pmid: 22310220
references.citation: Clin Gastroenterol Hepatol. 2012 Jul;10(7):742-749.e1
references.pmid: 22475741
references.citation: Clin Gastroenterol Hepatol. 2006 Nov;4(11):1328-36
references.pmid: 17059896
references.citation: Clin Gastroenterol Hepatol. 2009 Dec;7(12):1305-13; quiz 1261
references.pmid: 19733260
references.citation: Gastroenterology. 2010 Aug;139(2):418-29
references.pmid: 20457157