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Gastroenterology›Condition·Updated Jun 27, 2026·v1

Gastroesophageal Reflux Disease

Gastroesophageal reflux disease is a common condition characterized by reflux of gastric contents causing symptoms or esophageal injury. Diagnosis relies on endoscopy and pH-impedance monitoring. Management includes acid suppression with PPIs or P-CABs, lifestyle modifications, and procedural options for refractory cases. Complications include Barrett's esophagus and esophageal adenocarcinoma, necessitating surveillance in high-risk patients.

High Evidence337 references·12,436 words·50 min read·v1
Gastroesophageal reflux diseaseGERDgastroenterologyheartburnerosive esophagitisBarrett's esophagusproton pump inhibitorspH monitoring

Quick Reference

RxDrug of choiceProton pump inhibitor (e.g., esomeprazole 20-40 mg daily)
AltAlternativesPotassium-competitive acid blockers (vonoprazan 10-20 mg, tegoprazan 50 mg), H2 receptor antagonists (famotidine 20-40 mg BID)
⊘AvoidDomperidone (no benefit), non-dihydropyridine CCBs, Stretta procedure
DxTest of choice24-hour ambulatory pH-impedance monitoring off PPI
ScKey scoreLyon Score (≥4.5 predicts treatment response)
→When to referRefractory symptoms despite twice-daily PPI, alarm features (dysphagia, weight loss, bleeding), consideration of antireflux surgery
GERD is diagnosed by endoscopy and pH monitoring; management starts with PPI or P-CAB, with lifestyle modifications; refractory cases require objective testing to guide add-on therapy or procedural intervention.
Gastroesophageal reflux disease (GERD) is a common condition defined by troublesome symptoms or esophageal injury due to reflux of gastric contents. It affects 10-20% of adults in Western populations and is the primary risk factor for Barrett's esophagus and esophageal adenocarcinoma. Diagnosis is confirmed by endoscopy and pH-impedance monitoring. Management centers on acid suppression with PPIs or P-CABs, lifestyle modifications, and, in selected cases, antireflux surgery. This page provides a comprehensive overview of GERD evaluation and management.

Overview and Recommendations

Background

  • •GERD is defined by the Montreal Consensus as a condition that develops when reflux of stomach contents causes troublesome symptoms, esophageal injury, or both. It affects an estimated 10-20% of adults in Western populations, with a global prevalence of 13.3% for weekly symptoms. The disease burden has doubled over the past two decades, driven largely by rising obesity rates.
  • •The pathophysiology involves failure of the anti-reflux barrier at the esophagogastric junction, primarily through transient LES relaxations (TLESRs) and, in severe disease, a hypotensive LES or hiatal hernia. Refluxate contains acid, pepsin, and bile salts that trigger immune-mediated mucosal injury rather than direct chemical burn.
  • •Modern classification divides GERD into distinct phenotypes: erosive reflux disease (ERD) with LA grade A-D esophagitis, non-erosive reflux disease (NERD) with abnormal acid exposure but normal endoscopy, reflux hypersensitivity, and functional heartburn. The Lyon Consensus 2.0 provides conclusive diagnostic criteria: LA grade C/D esophagitis, long-segment Barrett's esophagus, or distal AET >6% on pH monitoring.
  • •Major risk factors include obesity (OR 2.2 for BMI ≥30), central obesity (OR 2.8), hiatal hernia (OR 3.7), tobacco smoking (OR 1.7), and first-degree family history. GLP-1 receptor agonists and substance use disorders are emerging risk factors. Protective factors include regular physical activity and dietary fiber.
  • •Complications include esophageal stricture (incidence 1.1/10,000 person-years), Barrett's esophagus (prevalence 8% in GERD patients), and esophageal adenocarcinoma (0.5% per year in Barrett's). PPI therapy heals esophagitis but does not eliminate cancer risk.

Evaluation

  • •Suspect GERD in any patient with retrosternal burning (heartburn) and/or regurgitation, especially postprandial or when recumbent. Ask about alarm symptoms: dysphagia, odynophagia, weight loss, hematemesis, melena, or anemia.
  • •Examine for signs of chronic reflux: dental erosions, hoarseness, or wheezing. In patients with extraesophageal symptoms (chronic cough, laryngitis, asthma), the pretest probability of GERD is low (<50%), so objective testing is essential.
  • •For patients without alarm symptoms, an empiric trial of once-daily PPI (e.g., esomeprazole 40 mg) for 2-8 weeks is appropriate. A positive response (≥50% improvement) supports clinical diagnosis.
  • •Perform upper endoscopy (EGD) in all patients with alarm symptoms, PPI non-responders, or those with long-standing GERD (≥5 years) for Barrett's screening. Grade erosive esophagitis using the Los Angeles classification: LA A/B are supportive, LA C/D are conclusive for GERD.
  • •Obtain distal esophageal biopsies to exclude eosinophilic esophagitis (≥15 eos/HPF) in patients with dysphagia or atypical symptoms.
  • •If endoscopy is normal, perform 24-hour ambulatory pH-impedance monitoring off PPI. Conclusive GERD: distal AET >6% or >80 reflux episodes/24h. Borderline: AET 4-6% or 40-80 episodes. No GERD: AET <4% and <40 episodes.
  • •Use the Lyon Score (integrating AET, reflux episodes, baseline impedance, and endoscopic findings) to predict response to antireflux therapy; a score ≥4.5 has 78% sensitivity and 72% specificity for treatment response.
  • •Consider high-resolution manometry before antireflux surgery to exclude achalasia or major motility disorders.
  • •In PPI-refractory patients, perform on-therapy pH-impedance monitoring (while on double-dose PPI) to differentiate ongoing acid reflux from functional heartburn or reflux hypersensitivity.
  • •Salivary pepsin testing (Peptest) has modest specificity (59%) and is not recommended as a standalone diagnostic tool.
  • •Also consider alternative diagnoses: eosinophilic esophagitis, achalasia, rumination syndrome, supragastric belching, functional dyspepsia, and celiac disease.

Management

  • •Initiate acid suppression with a PPI (e.g., esomeprazole 40 mg once daily before breakfast) or a P-CAB (e.g., vonoprazan 10-20 mg, tegoprazan 50 mg) for 8 weeks in erosive esophagitis. For LA grade C/D, extend to 8 weeks; healing rates exceed 85%.
  • •For non-erosive reflux disease (NERD), a 4-week trial of PPI or P-CAB is appropriate. Tegoprazan 50 mg daily achieved complete symptom resolution in 42% vs 24% placebo (NNT=6).
  • •If symptoms persist after 4-8 weeks of once-daily PPI, escalate to twice-daily dosing (e.g., esomeprazole 40 mg BID) for an additional 8 weeks. Add a wedge pillow for nocturnal symptoms (noninferior to evening PPI).
  • •For refractory regurgitation despite twice-daily PPI, consider adding baclofen 5-10 mg three times daily to reduce TLESRs (reduces reflux episodes by 40-50%). Monitor for drowsiness.
  • •For refractory heartburn with normal pH-impedance (functional heartburn or reflux hypersensitivity), start a neuromodulator: desipramine 25-50 mg nightly or imipramine 25 mg nightly (NNT=4-5).
  • •Lifestyle modifications: weight loss (5-10% reduces symptoms by 30-40%), head-of-bed elevation with wedge pillow, low-carbohydrate diet (reduces AET by 1.8%), and diaphragmatic breathing exercises (10 min twice daily reduces GerdQ scores by 4 points).
  • •Avoid non-dihydropyridine CCBs (diltiazem, verapamil) as they exacerbate reflux. Do not use domperidone as add-on (no benefit over PPI alone). Do not use Stretta (radiofrequency ablation) - meta-analysis shows no efficacy.
  • •For patients who fail medical therapy and have objective GERD (AET >6%, no large hiatal hernia), consider endoscopic antireflux mucosal ablation (ARMA) - 70% clinical success at 1 year - or laparoscopic fundoplication (durable but 10-50% dysphagia risk).
  • •For Barrett's esophagus, maintain indefinite PPI therapy and perform surveillance endoscopy every 3-5 years. Endoscopic eradication therapy for dysplasia.
  • •Deprescribe PPIs when no clear indication: step-down to lowest effective dose, then on-demand therapy. A cluster-randomized trial reduced inappropriate PPI use by 24% at 12 months without worsening GERD control.
  • •Refer to gastroenterology for refractory symptoms, alarm features, or consideration of antireflux surgery. Refer to surgery for large hiatal hernia or failed medical therapy.

Board Review — High Yield

  • •Montreal Definition - GERD is defined by troublesome symptoms or esophageal injury due to reflux of gastric contents.
  • •Lyon Consensus 2.0 - Conclusive GERD: LA grade C/D esophagitis, long-segment Barrett's, or AET >6% on pH monitoring.
  • •Los Angeles Classification - Grades A-D based on mucosal break size and extent; grade C/D are conclusive for GERD.
  • •NERD vs Functional Heartburn - NERD has abnormal AET; functional heartburn has normal AET and negative symptom association.
  • •PPI Dosing - Start once daily before breakfast; escalate to BID for refractory symptoms; P-CABs offer faster onset.
  • •Baclofen - Reduces TLESRs by 40-50%; used for refractory regurgitation; side effects include drowsiness.
  • •ARMA - Endoscopic mucosal ablation achieves 70% clinical success at 1 year for PPI-dependent GERD without large hiatal hernia.
  • •Barrett's Screening - Recommended for chronic GERD (≥5 years) with additional risk factors (age >50, male, white, obesity, smoking).
  • •Deprescribing - Step-down to lowest effective dose or on-demand PPI; structured interventions reduce inappropriate use by 24%.

Deep Dive — Evidence Details

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