{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:43:57Z","timestamp":1792604637403,"version":"4.5.0"},"reference-count":21,"publisher":"FapUNIFESP (SciELO)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arq. Gastroenterol."],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:p>CONTEXT: Gastroesophageal reflux disease (GERD) is a condition which develops when the reflux of stomach contents causes troublesome symptoms and\/or complications. Its pathophysiology, diagnosis and treatment have frequently been analyzed but it is interesting to review some aspects of the GERD refractory patients to the proton pump inhibitors treatment. The treatment encompasses behavioral measures and pharmacological therapy. The majority of the patients respond well to proton pump inhibitors treatment but 20%-42% of them may not do so well. Patients who are unresponsible to 4-8 weeks' treatment with proton pump inhibitors (omeprazole, pantoprazole, rabeprazole, lansoprazole, esomeprazole, pantoprazole-Mg) might have so-called refractory GERD. RESULTS: In some cases the patients are not real refractory because either they do not have GERD or the disease was not correctly treated, but the term refractory is still employed. Although debatable, the Brazilian GERD Consensus based upon evidences recommends as first step in the diagnosis, the upper digestive endoscopy to exclude the diagnosis of peptic ulcer and cancer and in some cases identify the presence of esophageal mucosa erosions. CONCLUSIONS: The main causes of the so-called refractory GERD are: (1) functional heartburn; (2) low levels of adherence to proton pump inhibitors treatment; (3) inadequate proton pump inhibitors dosage; (4) wrong diagnosis; (5) co-morbidities and pill-induced esophagitis; (6) genotypic differences; (7) nonacid gastroesophageal reflux; (8) autoimmune skin diseases; (9) eosinophilic esophagitis.<\/jats:p>","DOI":"10.1590\/s0004-28032012000400012","type":"journal-article","created":{"date-parts":[[2013,1,16]],"date-time":"2013-01-16T03:26:02Z","timestamp":1358306762000},"page":"296-301","source":"Crossref","is-referenced-by-count":17,"title":["Refractory gastroesophageal reflux disease"],"prefix":"10.1590","volume":"49","author":[{"given":"Joaquim Prado P.","family":"Moraes-Filho","sequence":"first","affiliation":[{"name":"University of Sao Paulo School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"530","reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1055\/s-2005-870129","article-title":"Pill induced esophageal injury: endoscopic features and clinical outcomes","volume":"37","author":"Abid S","year":"2005","journal-title":"Endoscopy","ISSN":"https:\/\/id.crossref.org\/issn\/0013-726X","issn-type":"print"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1007\/s10620-005-3001-2","article-title":"A prospective study of gastric acid analysis and esophageal acid exposure in patients with gastroesophageal reflux refractory to medical therapy","volume":"50","author":"Ahlawat SK","year":"2005","journal-title":"Dig Dis Sci","ISSN":"https:\/\/id.crossref.org\/issn\/0163-2116","issn-type":"print"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/nrgastro.2009.45","article-title":"Eosinophilic esophagitis: the newest esophageal inflammatory disease","volume":"6","author":"Atkins D","year":"2009","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0002-9343(01)00901-9","article-title":"Patterns of proton pump inhibitor use in clinical practice","volume":"111","author":"Barrison AF","year":"2001","journal-title":"Am J Med","ISSN":"https:\/\/id.crossref.org\/issn\/0002-9343","issn-type":"print"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1053\/j.gastro.2010.04.051","article-title":"Effects of lesogaberan on reflux and lower esophageal sphincter functions in patients with gastroesophageal reflux disease","volume":"139","author":"Boeckxstaens GE","year":"2010","journal-title":"Gastroenterology","ISSN":"https:\/\/id.crossref.org\/issn\/0016-5085","issn-type":"print"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1442-2050.2011.01227.x","article-title":"Low levels of adherence with proton pump inhibitor therapy contribute to therapeutic failure in gastroesophageal reflux disease","volume":"25","author":"Dal-Paz K","year":"2012","journal-title":"Dis Esophagus","ISSN":"https:\/\/id.crossref.org\/issn\/1120-8694","issn-type":"print"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1442-2050.2006.00581.x","article-title":"Evaluation of the health-related quality of life in gastroesophageal reflux disease patients before and after treatment with pantoprazole","volume":"19","author":"de Sousa Cury M","year":"2006","journal-title":"Dis Esophagus","ISSN":"https:\/\/id.crossref.org\/issn\/1120-8694","issn-type":"print"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1590\/S0004-28032011000100006","article-title":"Impact of prolonged 48-h wireless capsule esophageal pH monitoring on diagnosis of gastroesophageal reflux disease and evaluation of the relationship between symptoms and reflux episodes","volume":"48","author":"Domingues GR","year":"2011","journal-title":"Arq Gastroenterol","ISSN":"https:\/\/id.crossref.org\/issn\/0004-2803","issn-type":"print"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1067\/mcp.2002.127637","article-title":"Effect of the cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole","volume":"72","author":"Furuta T","year":"2002","journal-title":"Clin Pharmacol Ther","ISSN":"https:\/\/id.crossref.org\/issn\/0009-9236","issn-type":"print"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1053\/j.gastro.2005.08.060","article-title":"Functional esophageal disorders","volume":"130","author":"Galmiche JP","year":"2006","journal-title":"Gastroenterology","ISSN":"https:\/\/id.crossref.org\/issn\/0016-5085","issn-type":"print"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1038\/ajg.2009.718","article-title":"Arbaclofen placarbil decreases postprandial reflux in patients with gastroesophageal reflux disease","volume":"105","author":"Gerson LB","year":"2010","journal-title":"Am J Gastroenterol","ISSN":"https:\/\/id.crossref.org\/issn\/0002-9270","issn-type":"print"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1136\/gut.52.10.1397","article-title":"Effect of the GABA(B) agonist baclofen in patients with symptoms and duodeno-gastro-esophageal reflux refractory to proton pump inhibitors","volume":"52","author":"Koek GH","year":"2003","journal-title":"Gut","ISSN":"https:\/\/id.crossref.org\/issn\/0017-5749","issn-type":"print"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1053\/j.gastro.2006.08.033","article-title":"A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis","volume":"131","author":"Konikoff MR","year":"2006","journal-title":"Gastroenterology","ISSN":"https:\/\/id.crossref.org\/issn\/0016-5085","issn-type":"print"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1590\/S0004-28032005000200011","article-title":"Prevalence of heartburn and gastroesophageal reflux disease in the urban Brazilian population","volume":"42","author":"Moraes-Filho JP","year":"2005","journal-title":"Arq Gastroenterol","ISSN":"https:\/\/id.crossref.org\/issn\/0004-2803","issn-type":"print"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1590\/S1807-59322009000800013","article-title":"Comorbidities are frequent in patients with gastroesophageal reflux disease in a tertiary health care hospital","volume":"64","author":"Moraes-Filho JP","year":"2009","journal-title":"Clinics","ISSN":"https:\/\/id.crossref.org\/issn\/1807-5932","issn-type":"print"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1590\/S0004-28032010000100017","article-title":"Guidelines for the diagnosis and management of gastrosophageal reflux disease: an evidence-based consensus","volume":"47","author":"Moraes-Filho JPP","year":"2010","journal-title":"Arq Gastroenterol","ISSN":"https:\/\/id.crossref.org\/issn\/0004-2803","issn-type":"print"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/ncpgasthep0979","article-title":"How to manage refractory GERD","volume":"4","author":"Richter J","year":"2007","journal-title":"Nat Clin Pract Gastroenterol Hepatol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1053\/gast.2001.24841","article-title":"Acid, nonacid, and gas reflux in patients with gastroesophageal disease during ambulatory 24-hour pH-impedance recordings","volume":"120","author":"Sifrim D","year":"2001","journal-title":"Gastroenterology","ISSN":"https:\/\/id.crossref.org\/issn\/0016-5085","issn-type":"print"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1053\/j.gastro.2010.07.048","article-title":"Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis","volume":"139","author":"Straumann A","year":"2010","journal-title":"Gastroenterology","ISSN":"https:\/\/id.crossref.org\/issn\/0016-5085","issn-type":"print"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1111\/j.1572-0241.2006.00630.x","article-title":"The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus","volume":"101","author":"Vakil van N","year":"2006","journal-title":"Am J Gastroenterol","ISSN":"https:\/\/id.crossref.org\/issn\/0002-9270","issn-type":"print"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1111\/j.1572-0241.2006.00711.x","article-title":"Esophageal pH-impedance monitoring and symptom analysis in GERD: a study in patients off and on therapy","volume":"101","author":"Zerbib F","year":"2006","journal-title":"Am J Gastroenterol","ISSN":"https:\/\/id.crossref.org\/issn\/0002-9270","issn-type":"print"}],"container-title":["Arquivos de Gastroenterologia"],"original-title":[],"link":[{"URL":"http:\/\/www.scielo.br\/pdf\/ag\/v49n4\/12.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2017,5,27]],"date-time":"2017-05-27T11:49:21Z","timestamp":1495885761000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_arttext&pid=S0004-28032012000400012&lng=en&tlng=en"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["S0004-28032012000400012"],"URL":"https:\/\/doi.org\/10.1590\/s0004-28032012000400012","relation":{},"ISSN":["0004-2803"],"issn-type":[{"value":"0004-2803","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12]]}}}