Patients with refractory reflux symptoms often do not have GERD

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. 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. 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). 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