Alimentary Pharmacology and Therapeutics
Comparison of eotaxin-3 biomarker in patients with eosinophilic oesophagitis, proton pump inhibitor-responsive oesophageal eosinophilia and gastro-oesophageal reflux disease F. J. Moawad*, J. M. Wells†, R. L. Johnson†, B. J. Reinhardt‡, C. L. Maydonovitch* & T. P. Baker†
*Gastroenterology Service, Walter Reed National Military Medical Center, Bethesda, MD, USA. † Department of Pathology, Walter Reed National Military Medical Center, Bethesda, MD, USA. ‡ Department of Research Programs, Walter Reed National Military Medical Center, Bethesda, MD, USA.
Correspondence to: Dr F. J. Moawad, Gastroenterology Service, Department of Medicine, Walter Reed National Military Medical Center, 8901 Wisconsin Ave., Bethesda, MD 20889, USA. E-mail: [email protected]
Publication data Submitted 26 March 2015 First decision 20 April 2015 Resubmitted 21 April 2015 Resubmitted 4 May 2015 Accepted 4 May 2015 EV Pub Online 24 May 2015 This article was accepted for publication after full peer-review.
SUMMARY Background Proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) is a recently described entity which resembles oeosinophilic oesophagitis (EoE), yet responds to acid suppressive treatment.
Aim To determine whether EoE shares similar staining features with PPI-REE or with gastro-oesophageal reflux disease (GERD).
Methods This retrospective study consisted of patients with an established diagnosis of EoE, PPI-REE, or GERD identified from a database during a 1-year period. Immunohistochemistry (IHC) analysis was performed specifically targeting eotaxin-3 antibodies. All sections were qualitatively (intensity) and quantitatively (percentage of cells stained) assessed independently by two blinded pathologists.
Results The cohort consisted of three groups of patients: EoE (n = 22), PPI-REE (n = 23) and GERD (n = 23) for a total of 68 patients. Study demographics included mean age 39 (14) years, 75% male and 77% Caucasian. There was a significant difference in the eotaxin-3 staining among EoE, PPI-REE and GERD groups [mean score (s.d.): 1.2 (1.2), 0.8 (1.0), 0.3 (0.7), P = 0.006]. Staining scores of EoE patients were significantly higher compared with GERD (P = 0.002) and a trend towards significance was seen between EoE and PPI-REE (P = 0.054). There was also a significant difference in EoE staining intensity score among the three groups (P = 0.006). Intensity scores of EoE were significantly higher compared with GERD [1.0 (0.9) vs. 0.22 (0.52), P < 0.001]. There was no significant difference between EoE and PPI-REE groups [1.0 (0.0) vs. 0.52 (0.75) P = 0.094].
Conclusions A difference in eotaxin-3 staining was seen in the three groups of patients with oesophageal eosinophilia. Eotaxin-3 can distinguish EoE from GERD, but not from proton pump inhibitor responsive-oesophageal eosinophilia.
Aliment Pharmacol Ther 2015; 42: 231–238
Published 2015. This article is a U.S. Government work and is in the public domain in the USA doi:10.1111/apt.13258
231
F. J. Moawad et al. INTRODUCTION Several clinical and histological features of eosinophilic oesophagitis (EoE), proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) and gastro-oesophageal reflux dissease (GERD) overlap. All three conditions present with symptoms of oesophageal dysfunction and may have dense eosinophilia on oesophageal biopsies. A complex interaction exists between EoE and GERD,1 and PPI-REE is a condition which resembles EoE, yet responds to acid suppressants.2, 3 A recent study determined that PPI-REE has significant molecular overlap with EoE with reversal of gene expression after a course of acid suppressants.4 Previous studies have demonstrated the complexities of distinguishing EoE from GERD based on eosinophil count,5–7 ambulatory pH monitoring,8 and response to PPI.9 On the other hand, certain biomarkers have been useful in distinguishing EoE from GERD.10–13 Specifically, eotaxin-3 is an important biomarker in EoE that correlates with disease severity.14 It functions as a potent chemo-attractant that plays a major role in activation, recruitment and degranulation of eosinophils in EoE.15 Eotaxin-3 has been demonstrated to have a higher epithelial staining and expression in EoE patients compared to patients with GERD.11 These results were confirmed in a separate case–control study in which eotaxin-3 staining was higher in EoE than in GERD.10 PPI-REE is a recently described entity which shares nearly identical clinical, endoscopic and histological features with EoE.2, 3, 16 While some biomarkers are capable of distinguishing EoE from GERD, it would be of interest to determine whether PPI-REE would share similarities or distinguishing features through biomarker staining. In the only study to date to include PPI-REE patients in biomarker analysis, Dellon et al. demonstrated that EoE and PPI-REE had significantly higher staining levels of eotaxin-3, major basic protein (MBP) and tryptase than controls, however, the two could not be distinguished from each other.17 The aims of this study were to determine whether EoE shares similar staining features with PPI-REE or with GERD and to compare demographic, clinical, endoscopic and histological features between the three conditions. We hypothesised that patients with EoE and PPI-REE will demonstrate higher level of staining for eotaxin-3 compared with GERD patients.
232
METHODS Study population This retrospective study consisted of 68 patients with symptoms of oesophageal dysfunction and dense oesophageal eosinophilia on tissue biopsies. The study population included male and female military health care beneficiaries age 18 and older who had an established diagnosis of EoE, PPI-REE or GERD. To improve diagnostic accuracy, all patients in the cohort had at least eight oesophageal biopsies, four from the distal oesophagus and four from the mid-proximal oesophagus. During a 1-year period, consecutively enrolled PPI-REE cases were identified from a prospective database registry that was approved by the Walter Reed Institutional Review Board (IRB). During this same time period, the same number of EoE and GERD cases was identified from the database registry to establish a study cohort of three groups of equal sample size. EoE was defined by the most recent consensus statements, i.e. symptoms of oesophageal dysfunction, ≥15 eosinophils in peak high power field and lack of response to at least an 8-week course of high dose PPIs.18, 19 PPI-REE was defined as sharing identical clinical (dysphagia/food impaction), endoscopic (rings/furrows/plaques) and histological features with EoE (≥15 eos/hpf), yet achieving clinical and histological response (
Comparison of eotaxin-3 biomarker in patients with eosinophilic oesophagitis, proton pump inhibitor-responsive oesophageal eosinophilia and gastro-oesophageal reflux disease F. J. Moawad*, J. M. Wells†, R. L. Johnson†, B. J. Reinhardt‡, C. L. Maydonovitch* & T. P. Baker†
*Gastroenterology Service, Walter Reed National Military Medical Center, Bethesda, MD, USA. † Department of Pathology, Walter Reed National Military Medical Center, Bethesda, MD, USA. ‡ Department of Research Programs, Walter Reed National Military Medical Center, Bethesda, MD, USA.
Correspondence to: Dr F. J. Moawad, Gastroenterology Service, Department of Medicine, Walter Reed National Military Medical Center, 8901 Wisconsin Ave., Bethesda, MD 20889, USA. E-mail: [email protected]
Publication data Submitted 26 March 2015 First decision 20 April 2015 Resubmitted 21 April 2015 Resubmitted 4 May 2015 Accepted 4 May 2015 EV Pub Online 24 May 2015 This article was accepted for publication after full peer-review.
SUMMARY Background Proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) is a recently described entity which resembles oeosinophilic oesophagitis (EoE), yet responds to acid suppressive treatment.
Aim To determine whether EoE shares similar staining features with PPI-REE or with gastro-oesophageal reflux disease (GERD).
Methods This retrospective study consisted of patients with an established diagnosis of EoE, PPI-REE, or GERD identified from a database during a 1-year period. Immunohistochemistry (IHC) analysis was performed specifically targeting eotaxin-3 antibodies. All sections were qualitatively (intensity) and quantitatively (percentage of cells stained) assessed independently by two blinded pathologists.
Results The cohort consisted of three groups of patients: EoE (n = 22), PPI-REE (n = 23) and GERD (n = 23) for a total of 68 patients. Study demographics included mean age 39 (14) years, 75% male and 77% Caucasian. There was a significant difference in the eotaxin-3 staining among EoE, PPI-REE and GERD groups [mean score (s.d.): 1.2 (1.2), 0.8 (1.0), 0.3 (0.7), P = 0.006]. Staining scores of EoE patients were significantly higher compared with GERD (P = 0.002) and a trend towards significance was seen between EoE and PPI-REE (P = 0.054). There was also a significant difference in EoE staining intensity score among the three groups (P = 0.006). Intensity scores of EoE were significantly higher compared with GERD [1.0 (0.9) vs. 0.22 (0.52), P < 0.001]. There was no significant difference between EoE and PPI-REE groups [1.0 (0.0) vs. 0.52 (0.75) P = 0.094].
Conclusions A difference in eotaxin-3 staining was seen in the three groups of patients with oesophageal eosinophilia. Eotaxin-3 can distinguish EoE from GERD, but not from proton pump inhibitor responsive-oesophageal eosinophilia.
Aliment Pharmacol Ther 2015; 42: 231–238
Published 2015. This article is a U.S. Government work and is in the public domain in the USA doi:10.1111/apt.13258
231
F. J. Moawad et al. INTRODUCTION Several clinical and histological features of eosinophilic oesophagitis (EoE), proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) and gastro-oesophageal reflux dissease (GERD) overlap. All three conditions present with symptoms of oesophageal dysfunction and may have dense eosinophilia on oesophageal biopsies. A complex interaction exists between EoE and GERD,1 and PPI-REE is a condition which resembles EoE, yet responds to acid suppressants.2, 3 A recent study determined that PPI-REE has significant molecular overlap with EoE with reversal of gene expression after a course of acid suppressants.4 Previous studies have demonstrated the complexities of distinguishing EoE from GERD based on eosinophil count,5–7 ambulatory pH monitoring,8 and response to PPI.9 On the other hand, certain biomarkers have been useful in distinguishing EoE from GERD.10–13 Specifically, eotaxin-3 is an important biomarker in EoE that correlates with disease severity.14 It functions as a potent chemo-attractant that plays a major role in activation, recruitment and degranulation of eosinophils in EoE.15 Eotaxin-3 has been demonstrated to have a higher epithelial staining and expression in EoE patients compared to patients with GERD.11 These results were confirmed in a separate case–control study in which eotaxin-3 staining was higher in EoE than in GERD.10 PPI-REE is a recently described entity which shares nearly identical clinical, endoscopic and histological features with EoE.2, 3, 16 While some biomarkers are capable of distinguishing EoE from GERD, it would be of interest to determine whether PPI-REE would share similarities or distinguishing features through biomarker staining. In the only study to date to include PPI-REE patients in biomarker analysis, Dellon et al. demonstrated that EoE and PPI-REE had significantly higher staining levels of eotaxin-3, major basic protein (MBP) and tryptase than controls, however, the two could not be distinguished from each other.17 The aims of this study were to determine whether EoE shares similar staining features with PPI-REE or with GERD and to compare demographic, clinical, endoscopic and histological features between the three conditions. We hypothesised that patients with EoE and PPI-REE will demonstrate higher level of staining for eotaxin-3 compared with GERD patients.
232
METHODS Study population This retrospective study consisted of 68 patients with symptoms of oesophageal dysfunction and dense oesophageal eosinophilia on tissue biopsies. The study population included male and female military health care beneficiaries age 18 and older who had an established diagnosis of EoE, PPI-REE or GERD. To improve diagnostic accuracy, all patients in the cohort had at least eight oesophageal biopsies, four from the distal oesophagus and four from the mid-proximal oesophagus. During a 1-year period, consecutively enrolled PPI-REE cases were identified from a prospective database registry that was approved by the Walter Reed Institutional Review Board (IRB). During this same time period, the same number of EoE and GERD cases was identified from the database registry to establish a study cohort of three groups of equal sample size. EoE was defined by the most recent consensus statements, i.e. symptoms of oesophageal dysfunction, ≥15 eosinophils in peak high power field and lack of response to at least an 8-week course of high dose PPIs.18, 19 PPI-REE was defined as sharing identical clinical (dysphagia/food impaction), endoscopic (rings/furrows/plaques) and histological features with EoE (≥15 eos/hpf), yet achieving clinical and histological response (
