Gastroesophageal reflux disease (GERD)

Overview

• Definition: GERD is retrograde reflux of gastric contents into the esophagus, occurring when the mechanisms that limit esophageal acid exposure, salivary bicarbonate, peristaltic clearance, a competent lower esophageal sphincter (LES), and timely gastric emptying, become ineffective.
• Cardinal symptoms: heartburn and regurgitation, with chest pain also common and requiring a cardiac cause to be excluded first.
• Diagnosis is clinical: classic symptoms without alarm features get an empiric proton pump inhibitor (PPI) trial rather than upfront testing; there is no single gold-standard test.
• Alarm features change the pathway: dysphagia, unintentional weight loss, hematemesis, or melena mandate upper endoscopy instead of an empiric trial.
• Chronic consequences: long-standing GERD can progress to esophagitis, stricture, Barrett esophagus, and adenocarcinoma, so refractory symptoms are investigated rather than treated indefinitely.

Epidemiology

• Prevalence: GERD affects 10 to 20 percent of the Western world, one of the most common gastrointestinal diagnoses.
• Obesity association: a strong relationship between GERD and obesity, with elevated BMI and intra-abdominal fat distribution both linked to increased reflux.
• Pregnancy: GERD can occur in any trimester, may worsen as pregnancy progresses, and typically resolves after delivery.
• Barrett esophagus progression: about 10 percent of GERD patients are found to have Barrett esophagus on endoscopy, more likely beyond 5 years of GERD.
• Extraesophageal disease: chronic cough, hoarseness, wheezing, and dental erosions are commonly attributed to reflux, though non-GERD causes must be excluded first.

Risk factors

• Obesity and elevated BMI: the strongest and most consistently reproduced association, particularly with intra-abdominal fat distribution.
• Hiatal hernia: disrupts the anatomic and pressure barrier at the gastroesophageal junction and is an additional risk factor for Barrett esophagus when GERD is chronic (hiatal hernias).
• Dietary and lifestyle triggers: large or fatty meals, caffeine, chocolate, spicy and acidic foods (including citrus), alcohol, and tobacco use.
• Pregnancy: hormonal LES relaxation combined with increased intra-abdominal pressure from the gravid uterus.
• Tight-fitting clothing and recumbency: mechanical increases in intra-abdominal pressure and nocturnal supine positioning; eating within 3 hours of lying down is a specific, modifiable trigger.

Pathophysiology

• Failure of the antireflux barrier: the LES and crural diaphragm normally prevent retrograde flow; transient LES relaxations and hypotensive LES pressure allow gastric contents to reflux.
• Impaired esophageal clearance: ineffective peristalsis prolongs contact time of refluxed acid and pepsin with esophageal mucosa.
• Reduced protective mechanisms: diminished salivary bicarbonate blunts neutralization of refluxed acid, compounding mucosal exposure.
• Delayed gastric emptying: prolongs gastric distension and volume available to reflux, particularly after large or fatty meals.
• Chronic mucosal injury: repeated acid and pepsin exposure produces reflux (erosive) esophagitis, and in a subset drives metaplasia of squamous into columnar epithelium with goblet cells, that is, Barrett esophagus, a precursor lesion for adenocarcinoma.

Clinical features

• Heartburn: a retrosternal burning sensation, typically postprandial and worse when supine, the most common and most specific symptom.
• Regurgitation: effortless return of sour or bitter gastric contents into the mouth, often worse bending forward or lying flat.
• Chest pain: GERD is the most common cause of noncardiac chest pain, but a cardiac cause must be excluded first.
• Globus sensation: a lump-in-the-throat sensation, usually unrelated to meals; not diagnosed if dysphagia or odynophagia are also present, which point instead to a structural or inflammatory process.
• Extraesophageal symptoms: chronic cough, laryngitis-type hoarseness, and asthma-like wheezing; a PPI trial is reasonable with typical symptoms, but laryngoscopy should not diagnose GERD-related laryngitis because edema and erythema are nonspecific.
• Alarm features override the clinical pathway: dysphagia, odynophagia, weight loss, hematemesis, melena, or iron-deficiency anemia signal possible stricture, erosive disease, or malignancy and require endoscopy rather than empiric treatment.

Differential diagnosis

• Acute coronary syndrome: exertional or crushing chest pain with cardiac risk factors and ECG or troponin abnormalities; excluded first in any reflux-type chest pain.
• Esophageal or gastric malignancy: progressive dysphagia and weight loss with long-standing GERD, hiatal hernia, obesity, and tobacco use.
• Eosinophilic esophagitis: dysphagia and food bolus impaction, often a younger atopic patient, confirmed by biopsy showing 15 or more eosinophils per high-power field (eosinophilic esophagitis).
• Peptic (reflux-related) stricture: progressive solid-food dysphagia after years of untreated reflux, a smooth tapered narrowing on endoscopy and biopsy distinguishing it from malignancy (esophageal stricture).
• Pill-induced or infectious esophagitis: odynophagia predominates over heartburn; infectious (typically Candida) occurs in immunosuppressed patients, often with oral thrush.
• Achalasia and other motility disorders: progressive dysphagia to solids and liquids, sometimes with regurgitation of undigested food, distinguished on manometry.
• Peptic ulcer disease or functional dyspepsia: epigastric pain related to meals, evaluated with endoscopy for alarm features or new dyspepsia after age 60.
• Functional heartburn: persistent symptoms with normal endoscopy and normal esophageal acid exposure on pH testing, reflecting hypersensitivity rather than true reflux.
• Systemic sclerosis-related dysmotility: GERD with dysphagia, skin hardening, telangiectasias, sclerodactyly, and Raynaud phenomenon points to a connective tissue cause.

Diagnosis

• GERD is a clinical diagnosis established by classic symptoms and confirmed by response to therapy; there is no single gold-standard test. Heartburn and regurgitation without alarm features strongly suggest the diagnosis, and symptom response to an empiric PPI trial supports it.
• First step, risk-stratify for alarm features: dysphagia, unintentional weight loss, hematemesis, or melena. Their absence permits an empiric PPI trial as initial management; their presence mandates upper endoscopy before any empiric trial.
• If no alarm features, empiric PPI trial: an 8-week once-daily PPI trial is both diagnostic and therapeutic; symptom resolution supports the diagnosis without further testing.
• If alarm features are present, refractory to an adequate PPI trial, or diagnosis is uncertain, proceed to upper endoscopy: evaluates for erosive esophagitis, peptic stricture, rings or webs, eosinophilic esophagitis, and Barrett esophagus, and grades esophagitis by the Los Angeles classification (grade A through D by extent and circumferential involvement of mucosal breaks), grade C or D indicating severe disease. Most patients have normal findings, so a normal endoscopy does not exclude the diagnosis.
• Reserve ambulatory pH or pH-impedance monitoring for confirmation when uncertain, refractory to optimized PPI therapy, or before antireflux surgery: quantifies esophageal acid exposure over 24 hours by transnasal catheter (or 48 to 96 hours by wireless capsule); impedance-pH also detects nonacid reflux. Testing off therapy supports diagnosis; testing on PPI therapy assesses adequacy of suppression.
• Add esophageal manometry for dysphagia, atypical symptoms, or before antireflux surgery: excludes a motility disorder such as achalasia that would change the surgical plan.

Clinical pearl. Do not order upper endoscopy as the default first test for typical, uncomplicated heartburn: in the absence of alarm features, an empiric 8-week PPI trial is both the recommended initial diagnostic step and the first treatment, and most patients who do undergo endoscopy have normal mucosa.

Management

• Start with lifestyle modification in every patient: weight loss if overweight or recently gained weight, head-of-bed elevation, avoiding meals within 3 hours of lying down, and eliminating only the specific foods (caffeine, chocolate, spicy or acidic foods, alcohol) the patient identifies as triggers; advise smoking and alcohol cessation.
• Begin a PPI trial for symptom relief and, when present, healing of erosive esophagitis: omeprazole 20 mg PO once daily, 30 to 60 minutes before breakfast, for 8 weeks (esomeprazole 20 to 40 mg PO once daily is an equivalent alternative).
• If response is partial, escalate to twice-daily dosing before switching classes: omeprazole 20 mg PO twice daily, 30 to 60 minutes before breakfast and dinner, for a further 8 to 12 weeks, confirming adherence and timing before labeling the patient refractory.
• If still unresponsive, investigate rather than continue empiric treatment: upper endoscopy to exclude eosinophilic esophagitis or erosive disease, plus impedance-pH testing on therapy to confirm adequacy of suppression, or off therapy if endoscopy is unrevealing.
• Use an H2-receptor antagonist for breakthrough symptoms or mild nonerosive disease: famotidine 20 mg PO twice daily for up to 6 weeks, or 20 mg PO at bedtime as needed for documented nocturnal breakthrough on an optimized PPI, reassessing because nightly use can lose effect within about a month; PPIs remain preferred for erosive disease.
  • Vonoprazan for failure of twice-daily PPI or severe Los Angeles grade C or D esophagitis: 20 mg PO once daily for 8 weeks for healing, or 10 mg PO once daily for 4 weeks for nonerosive heartburn; not routine first-line.
• Do not use prokinetic agents such as metoclopramide unless gastroparesis is present.
• Maintenance: lowest effective PPI dose, including on-demand dosing once controlled, with an attempt at discontinuation or dose reduction once yearly in uncomplicated GERD; continue indefinitely, or offer surgery, for Los Angeles grade C or D esophagitis.
• Offer laparoscopic fundoplication for medication-refractory disease, regurgitation-predominant symptoms, desire to stop medication, or intolerable PPI side effects: obtain pH monitoring and manometry first; most effective when typical symptoms already respond to PPI therapy. Magnetic sphincter augmentation or bariatric surgery (with obesity) are alternatives.
• For functional heartburn with normal pH testing off acid suppression, consider a neuromodulator (tricyclic antidepressant, SSRI, or SNRI) instead.

Complications

• Reflux (erosive) esophagitis: mucosal breaks graded by the Los Angeles classification, grade C or D at highest risk of bleeding and stricture.
• Peptic stricture: progressive solid-food dysphagia from fibrotic narrowing after chronic untreated reflux (esophageal stricture).
• Barrett esophagus: metaplastic squamous-to-columnar change with goblet cells, in about 10 percent of GERD patients, more likely with GERD beyond 5 years, male sex, white race, tobacco use, obesity, and age over 50 (barrett esophagus).
• Esophageal adenocarcinoma: end point of the Barrett metaplasia-dysplasia-carcinoma sequence; annual progression risk about 0.2 to 0.5 percent without dysplasia, 0.7 percent with low-grade dysplasia, 7 percent with high-grade dysplasia.
• Upper gastrointestinal bleeding: erosive esophagitis is common on endoscopy but an infrequent cause of significant bleeding, so an alternative source should be sought.
• Extraesophageal injury: chronic cough, laryngitis, dental erosions, and asthma-like symptoms from repeated proximal or aspirated reflux.

Prognosis

• Most uncomplicated GERD responds well to PPI therapy and lifestyle change, with symptom control achieved within the standard 8-week trial.
• Erosive esophagitis severity predicts outcome: Los Angeles grade A or B heals with standard-dose PPI therapy, whereas grade C or D carries higher risk of bleeding, stricture, and need for indefinite therapy or surgery.
• Barrett esophagus prognosis tracks with dysplasia grade: cancer risk rises from under 0.5 percent per year without dysplasia to 7 percent per year with high-grade dysplasia, driving surveillance intensity.
• Quality of life is impaired by uncontrolled disease: poor sleep, reduced productivity, and work absences are reversible with effective acid suppression.
• Fundoplication outcomes depend on patient selection: most effective, with least residual symptoms, when typical symptoms already respond to PPI therapy before surgery.

Prevention

• Weight management: weight loss in overweight or obese patients reduces reflux burden, a primary modifiable measure given the strong GERD-obesity association.
• Barrett esophagus screening in selected high-risk patients: screening endoscopy for men over 50 with GERD for more than 5 years plus additional risk factors (nocturnal reflux, hiatal hernia, elevated BMI, intra-abdominal fat distribution, tobacco use); routine screening on symptoms alone is not supported for the general population, and women are selected case-by-case.
• Nocturnal symptom prevention: avoid eating within 3 hours of lying down and elevate the head of the bed.
• Trigger avoidance targeted to the individual: eliminate only the specific foods a patient identifies as provoking symptoms, plus tobacco and alcohol cessation.
• Judicious long-term PPI use: lowest effective dose, including on-demand dosing, with an attempt at discontinuation or reduction once yearly in uncomplicated GERD.

Key points

• GERD is retrograde reflux of gastric contents into the esophagus, presenting with heartburn and regurgitation and affecting 10 to 20 percent of the Western world.
• Diagnosis is clinical: an empiric 8-week once-daily PPI trial is the initial step for classic symptoms without alarm features; there is no single gold-standard test.
• Alarm features (dysphagia, weight loss, hematemesis, melena, anemia) mandate upper endoscopy rather than an empiric trial, with esophagitis graded by the Los Angeles classification.
• Ambulatory pH or pH-impedance monitoring confirms the diagnosis when uncertain, refractory to optimized PPI therapy, or before antireflux surgery.
• Management sequences from lifestyle change through an 8-week PPI trial, dose escalation or agent switch for partial response, and fundoplication for refractory or regurgitation-predominant disease after objective testing.
• Untreated chronic GERD can progress to esophagitis, stricture, Barrett esophagus, and adenocarcinoma, driving the alarm-feature threshold for endoscopy and selective Barrett screening.