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Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis
  1. Javier Molina-Infante1,
  2. Albert J Bredenoord2,
  3. Edaire Cheng3,
  4. Evan S Dellon4,
  5. Glenn T Furuta5,
  6. Sandeep K Gupta6,
  7. Ikuo Hirano7,
  8. David A Katzka8,
  9. Fouad J Moawad9,
  10. Marc E Rothenberg10,
  11. Alain Schoepfer11,
  12. Stuart J Spechler12,
  13. Ting Wen10,
  14. Alex Straumann13,
  15. Alfredo J Lucendo14
  16. From the PPI-REE Task Force of the European Society of Eosinophilic Oesophagitis (EUREOS)
  1. 1Department of Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain
  2. 2Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands
  3. 3Department of Pediatrics and Internal Medicine, Children's Health Children's Medical Center, and the University of Texas Southwestern Medical Center, Dallas, Texas, USA
  4. 4Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
  5. 5Section of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, Children's Hospital Colorado, Aurora, USA
  6. 6Section of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, Indiana, USA
  7. 7Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  8. 8Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
  9. 9Gastroenterology Service, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, USA
  10. 10Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
  11. 11Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
  12. 12Department of Internal Medicine, VA North Texas Health Care System, and the University of Texas Southwestern Medical Center, Dallas, Texas, USA
  13. 13Swiss EoE Research Network, Olten, Switzerland
  14. 14Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain
  1. Correspondence to Dr Javier Molina-Infante, Department of Gastroenterology, Hospital San Pedro de Alcantara, C/Pablo Naranjo s/n, Caceres 10003, Spain; xavi_molina{at}


Consensus diagnostic recommendations to distinguish GORD from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPIs) unexpectedly uncovered an entity called ‘PPI-responsive oesophageal eosinophilia’ (PPI-REE). PPI-REE refers to patients with clinical and histological features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that patients with PPI-REE and patients with EoE at baseline are clinically, endoscopically and histologically indistinguishable and have a significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in patients with PPI-REE, similar to the effects of topical steroids in patients with EoE. Additionally, recent series have reported that patients with EoE responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunological mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic and therapeutic features cannot be reliably distinguished. For patients with symptoms and histological features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first-line treatment before diet and topical steroids. The reasons why some patients with EoE respond to PPI, while others do not, remain to be elucidated.


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