Evaluation and Management of Refractory Gastroesophageal Reflux Disease

Even if proton pump inhibitor therapy is highly effective for gastroesophageal reflux disease, a substantial number of patients do not respond to optimized therapy. This group of proton pump inhibitor non-responder patients is heterogeneous in terms of the mechanism behind the generation of symptoms. Four phenotypes of proton pump inhibitor non-responders should be distinguished. Phenotype 1 corresponds to persistent acid reflux despite proton pump inhibitor therapy, phenotype 2 to non-acid reflux, phenotype 3 to functional overlap with gastroesophageal reflux disease and phenotype 4 to functional heartburn. Esophageal pH monitoring off therapy and pH impedance monitoring on proton pump inhibitor are the main physiological tests used to distinguish these phenotypes. Whereas phenotypes 1 and 2 may benefit from more aggressive anti-reflux therapy, alternative treatments triggering visceral sensitivity may be offered to patients with phenotypes 3 and 4.