Patients with symptoms suggestive of
gastroesophageal reflux disease (
GERD), such as
chest pain,
heartburn, regurgitation, and
dysphagia, are typically treated initially with a course of
proton pump inhibitors (PPIs). The evaluation of patients who have either not responded at all or partially and inadequately responded to such
therapy requires a more detailed history and may involve an endoscopy and esophageal biopsies, followed by esophageal manometry, ambulatory esophageal pH monitoring, and gastric emptying scanning. To assess the merits of a multimodality 'structural' and 'functional' assessment of the esophagus in patients who have inadequately controlled
GERD symptoms despite using empiric PPI, a retrospective cohort study of patients without any response or with poor symptomatic control to empiric PPI (>2 months duration) who were referred to an Esophageal Studies Unit was conducted. Patients were studied using symptom questionnaires, endoscopy (+ or - for erosive disease, or Barrett's
metaplasia) and multilevel esophageal biopsies (
eosinophilia,
metaplasia), esophageal motility (aperistalsis, dysmotility), 24-hour ambulatory esophageal pH monitoring (+ if % total time pH < 4 > 5%), and gastric emptying scanning (+ if >10% retention at 4 hours and >70% at 2 hours). Over 3 years, 275 patients (147 men and 128 women) aged 16-89 years underwent complete multimodality testing. Forty percent (n= 109) had nonerosive reflux disease (esophagogastroduodenoscopy [EGD]-, biopsy-, pH+); 19.3% (n= 53) had erosive
esophagitis (EGD+); 5.5% (n= 15)
Barrett's esophagus (EGD+,
metaplasia+); 5.5% (n= 15)
eosinophilic esophagitis (biopsy+); 2.5% (n= 7) had
achalasia and 5.8% (n= 16) other dysmotility (motility+, pH-); 16% (n= 44) had functional
heartburn (EGD-, pH-), and 5.8% (n= 16) had
gastroparesis (gastric scan+). Cumulative symptom scores for
chest pain,
heartburn, regurgitation, and
dysphagia were similar among the groups (mean range 1.1-1.35 on a 0-3 scale). Multimodality evaluation changed the diagnosis of
GERD in 34.5% of cases and led to or guided
alternative therapies in 42%. Overlap diagnoses were frequent: 10/15 (67%) of patients with
eosinophilic esophagitis, 12/16 (75%) of patients with
gastroparesis, and 11/23 (48%) of patients with
achalasia or dysmotility had concomitant pathologic
acid reflux by pH studies. Patients with persistent
GERD symptoms despite empiric PPI
therapy benefit from multimodality evaluation that may change the diagnosis and guide
therapy in more than one third of such cases. Because symptoms are not specific and overlap diagnoses are frequent and multifaceted, objective evidence-driven
therapies should be considered in such patients.