Gastroesophageal Reflux Disease (GERD)

Risk factors

• Obesity (especially central adiposity) and pregnancy
• Hiatal hernia
• Tobacco and alcohol use
• Dietary triggers: caffeine, chocolate, peppermint, fatty or spicy foods, citrus, carbonated beverages
• Medications that lower LES tone: calcium channel blockers, nitrates, anticholinergics, benzodiazepines, opioids
• Connective tissue disease (especially scleroderma)
• Delayed gastric emptying (diabetic gastroparesis)

Pathophysiology

Transient lower esophageal sphincter relaxations (TLESRs) and/or reduced resting LES tone allow gastric acid, pepsin, and bile to reflux into the distal esophagus. Impaired esophageal clearance, hiatal hernia, and increased intra-abdominal pressure amplify exposure. Chronic exposure damages squamous mucosa, producing erosive esophagitis, stricture, or columnar (Barrett) metaplasia.

Clinical presentation

Differential diagnosis

• Eosinophilic esophagitis — Dysphagia and food impaction in younger patients with atopy; rings and furrows on EGD; ≥15 eosinophils/HPF on biopsy; PPI response does not exclude EoE (PPI is a first-line EoE treatment)
• Peptic ulcer disease — Epigastric pain with food relation (gastric vs duodenal); confirmed on EGD; test for H. pylori
• Esophageal motility disorder (achalasia, spasm) — Progressive dysphagia to solids AND liquids; bird-beak on barium swallow; manometry diagnostic
• Cardiac chest pain / ACS — Exertional or persistent pressure with radiation; ECG and troponin first when atypical features present
• Functional dyspepsia — Postprandial fullness or epigastric pain without reflux symptoms or mucosal findings on EGD
• Gastroparesis — Early satiety, nausea, postprandial vomiting; diabetic or post-surgical; gastric emptying scintigraphy
• Esophageal cancer — Progressive solid-food dysphagia, weight loss, anemia in long-standing GERD/Barrett; alarm features warrant EGD
• Pill esophagitis — Sudden retrosternal pain after taking doxycycline, bisphosphonate, KCl, or NSAID with little water

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Typical heartburn<br/>or regurgitation] --> B{Alarm features?<br/>Dysphagia, weight loss,<br/>bleeding, anemia, age ≥60}
  B -->|Yes| C[EGD]
  B -->|No| D[8-week PPI trial<br/>+ lifestyle]
  D --> E{Symptom<br/>response?}
  E -->|Yes| F[Step down to<br/>lowest effective dose]
  E -->|No| G[Optimize PPI:<br/>BID dosing, timing<br/>30-60 min pre-meal]
  G --> H{Still<br/>refractory?}
  H -->|Yes| I[EGD + pH-impedance<br/>off PPI]
  I --> J{Acid exposure<br/>abnormal?}
  J -->|Yes| K[Anti-reflux surgery<br/>candidate]
  J -->|No| L[Consider functional<br/>heartburn / reflux<br/>hypersensitivity]

Treatment

Complications

• Erosive esophagitis (LA grade A-D)
• Peptic stricture — solid-food dysphagia; treat with endoscopic dilation plus PPI
• Barrett esophagus — intestinal metaplasia of distal esophagus; risk of adenocarcinoma
• Esophageal adenocarcinoma
• Extraesophageal complications: laryngitis, chronic cough, asthma exacerbation, dental erosion, aspiration pneumonia
• Schatzki (lower esophageal) ring — thin mucosal ring at the GEJ, associated with GERD and hiatal hernia; intermittent solid-food (steakhouse) dysphagia; treat with endoscopic dilation plus PPI (not fundoplication or botulinum toxin)

PANCE pearls

• Empiric 8-week PPI trial is both diagnostic and therapeutic for typical symptoms without alarm features.
• PPIs must be taken 30-60 minutes before the first meal of the day — they bind only active proton pumps.
• Long-term PPI risks (modest, often confounded): C. difficile, pneumonia, hypomagnesemia, B12 deficiency, hip fracture, CKD — use lowest effective dose.
• Barrett esophagus screening: consider one-time EGD in patients with chronic GERD plus ≥3 risk factors (age ≥50, male, white, obesity, smoking, family history of Barrett/EAC).
• Surveillance Barrett: no dysplasia — EGD every 3-5 yr; low-grade dysplasia — endoscopic eradication preferred; high-grade dysplasia — endoscopic eradication.
• Refractory symptoms on BID PPI: if GERD is unproven, EGD plus reflux monitoring OFF PPI to confirm the diagnosis; if GERD is proven (LA grade B or worse, Barrett, peptic stricture, or prior abnormal pH study), pH-impedance ON PPI to find why symptoms persist.

References

• ACG 2022 — Katz PO et al. ACG Clinical Guideline for the Diagnosis and Management of GERD. Am J Gastroenterol 2022;117:27-56
• ACG 2022 Barrett — Shaheen NJ et al. Diagnosis and Management of Barrett's Esophagus: An Updated ACG Guideline. Am J Gastroenterol 2022;117:559-587
• AGA 2022 — Yadlapati R, Gyawali CP, Pandolfino JE; CGIT GERD Consensus Conference Participants. AGA Clinical Practice Update on the Personalized Approach to the Evaluation and Management of GERD: Expert Review. Clin Gastroenterol Hepatol 2022;20:984-994
• Lyon 2.0 — Gyawali CP, Yadlapati R, Fass R, et al. Updates to the modern diagnosis of GERD: Lyon consensus 2.0. Gut 2024;73:361-371