How should gastro‑oesophageal reflux disease be diagnosed?

How to Diagnose GERD

For patients with typical symptoms of heartburn and regurgitation, start with a 4-8 week trial of once-daily PPI therapy—this serves as both treatment and diagnostic confirmation, with symptom response supporting (but not confirming) the diagnosis. 1, 2

Initial Clinical Assessment

Identify symptom pattern to determine diagnostic pathway:

• Typical symptoms (heartburn, acid regurgitation) have the highest specificity for GERD and warrant empiric PPI trial first 1, 3
• Atypical/extraesophageal symptoms (chronic cough, laryngitis, chest pain, asthma, dental erosions) require early objective testing rather than empiric therapy, as 50-60% of these patients do not have GERD 4, 2
• Alarm symptoms (dysphagia, weight loss, epigastric mass, bleeding) mandate immediate endoscopy before any empiric treatment 2

Diagnostic Algorithm Based on Presentation

For Typical GERD Symptoms (Heartburn/Regurgitation)

Step 1: Empiric PPI Trial

• Start once-daily PPI for 4-8 weeks 1, 2
• If inadequate response, increase to twice daily 1
• PPI trial has 71-78% sensitivity and 41-54% specificity compared to objective testing 4, 2

Step 2: If Symptoms Persist Despite PPI

• Proceed directly to upper endoscopy to evaluate for erosive esophagitis, Barrett's esophagus, or alternative diagnoses 1, 2
• Do NOT perform multiple empiric trials of different PPIs—additional trials are low yield 4, 2

Step 3: If Endoscopy is Normal

• Perform esophageal manometry to exclude achalasia or other motility disorders that mimic GERD 4, 1, 2
• Follow with ambulatory reflux monitoring (pH or pH-impedance) OFF PPI therapy 4, 1, 2

For Atypical/Extraesophageal Symptoms

Proceed directly to objective testing rather than empiric PPI trial 4

Testing sequence:

1. Upper endoscopy to evaluate for erosive disease and exclude alternative diagnoses 1, 2
2. Ambulatory pH monitoring OFF PPI therapy (wireless pH capsule for ≥96 hours preferred) to establish pathologic acid exposure 4, 2
3. Esophageal manometry if considering anti-reflux surgery or if alternative motility disorders suspected 4, 2

Objective Diagnostic Tests

Upper Endoscopy

• Identifies erosive esophagitis, Barrett's esophagus, strictures, and alternative diagnoses 1, 2
• Assess diaphragmatic hiatus for hiatal hernia 1
• Biopsy distal to Z-line when Barrett's esophagus suspected 1
• Critical caveat: Normal endoscopy does NOT exclude GERD—50-70% of GERD patients have non-erosive reflux disease 4, 5

Ambulatory Reflux Monitoring

OFF PPI therapy (for initial diagnosis):

• Wireless pH capsule for ≥96 hours is the definitive test for pathologic acid exposure 2
• Catheter-based pH monitoring is an alternative 4, 1
• Combined pH-impedance detects both acid and non-acid reflux 4, 1

ON PPI therapy (for refractory symptoms in proven GERD):

• pH-impedance monitoring determines if persistent symptoms are due to ongoing acid reflux, non-acid reflux, or non-reflux causes 4, 1
• Helps identify phenotypes: non-erosive reflux disease, hypersensitive esophagus, or functional heartburn 4

Esophageal Manometry

• Mandatory before anti-reflux surgery to confirm adequate peristalsis and exclude achalasia or major motility disorders 4, 1, 2
• Localizes lower esophageal sphincter for proper pH probe placement 1, 2
• Rules out achalasia, diffuse esophageal spasm, and other conditions that mimic GERD 4, 2

Symptom-Reflux Association Analysis

For patients with atypical symptoms, assess temporal correlation between symptoms and reflux episodes using:

• Symptom Association Probability (SAP) 4
• Symptom Index (SI) 4
• Both metrics together provide best assessment for heartburn, regurgitation, or chest pain 4

Critical Diagnostic Pitfalls to Avoid

Do NOT rely on PPI response alone to confirm GERD diagnosis:

• Symptom improvement may result from placebo effects or non-acid mechanisms 4, 2
• PPI response supports but does not confirm GERD 1, 2

Do NOT perform multiple empiric PPI trials in non-responders:

• After one failed 12-week trial, proceed to objective testing 4, 2
• Additional trials of different PPIs are low yield 4, 2

Do NOT assume extraesophageal symptoms are GERD-related without objective testing:

• 50-60% of patients with chronic cough, laryngitis, or asthma do NOT have GERD as the cause 4, 2
• No single test conclusively identifies GERD as the cause of extraesophageal symptoms 4

Do NOT skip manometry before anti-reflux surgery:

• Essential to exclude achalasia and confirm adequate peristalsis 4, 2
• High-resolution manometry provides diagnostic information not obtainable by standard manometry 4

Global Clinical Assessment

The diagnosis of GERD requires integrating multiple factors, not relying on any single test: 4, 2

• Patient symptom pattern and severity
• Response to GERD treatment (recognizing limitations)
• Endoscopic findings (erosive esophagitis, Barrett's esophagus)
• Ambulatory reflux monitoring results (acid exposure time, symptom correlation)
• Exclusion of alternative diagnoses