title: Patients with refractory reflux symptoms often do not have GERD.
abstract: BACKGROUND
  In patients with typical reflux symptoms that persist despite proton pump inhibitors (PPIs) it is sometimes overlooked that treatment fails due to the presence of other disorders than gastroesophageal reflux disease (GERD). The aim of this study was to determine the underlying cause of reflux symptoms not responding to PPI therapy in tertiary referral patients.
  
  
  METHODS
  Patients with reflux symptoms refractory to PPI therapy who underwent 24-h pH-impedance monitoring were analyzed. Patients in whom a diagnosis was already established before referral, who had previous esophageal or gastric surgery, or who had abnormalities on gastroscopy other than hiatus hernia, were excluded.
  
  
  RESULTS
  In total, 106 patients were included. Esophageal manometry showed achalasia in two patients and distal esophageal spasm in another two. Twenty-four-hour pH-impedance monitoring revealed a total acid exposure time <6% in 60 patients (56.6%) of which 25 had a positive symptom association probability (SAP) while 35 showed a negative SAP. Sixty-nine patients ended up with a final diagnosis of GERD while 32 patients (30.2%) were diagnosed with functional heartburn (FH), two with functional chest pain, two with achalasia, and one with rumination. A trend toward an association with a final diagnosis of FH was found with the atypical symptom epigastric pain (p = 0.059) and with a secondary diagnosis of functional dyspepsia (p = 0.083).
  
  
  CONCLUSIONS
  Approximately one-third of the patients referred with refractory reflux symptoms suffer from disorders other than GERD, predominantly FH. This explains, at least partly, why many patients will not benefit from acid inhibitory treatment.
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: T V K
authors.initials: TV
authors.lastname: Herregods
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Troelstra
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: P W
authors.initials: PW
authors.lastname: Weijenborg
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Bredenoord
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: A J P M
authors.initials: AJ
authors.lastname: Smout
mesh_terms: D002637:Chest Pain / Q000175:diagnosis; D017097:Electric Impedance; D004931:Esophageal Achalasia / Q000175:diagnosis; D050782:Esophageal pH Monitoring; D004947:Esophagus / Q000503:physiopathology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology*; D006356:Heartburn / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D063189:Symptom Assessment
chemical_list: D054328:Proton Pump Inhibitors
keywords: PPI; functional heartburn; refractory reflux symptoms; treatment failure; unresponsive