Los Angeles classification of reflux oesophagitis is the internationally accepted standard endoscopic grading system used to categorize the severity of mucosal injury resulting from gastro-oesophageal reflux disease (GERD)1,2. Developed to eliminate the subjectivity and poor reproducibility of earlier grading scales, the Los Angeles (LA) classification grades oesophageal mucosal breaks from Grade A (minimal) to Grade D (severe, circumferential) based on the length, number, and confluence of lesions visualized during upper gastrointestinal endoscopy2. It serves as a cornerstone in gastroenterological practice, correlating strongly with oesophageal acid exposure, predicting therapeutic response to acid-suppressive pharmacotherapy, and guiding longitudinal management strategies in clinical trials and routine care1,2.

Etiology & Risk Factors

  • Transient Lower Oesophageal Sphincter Relaxations (TLOSRs): The primary physiological mechanism underlying reflux oesophagitis, triggered by gastric distension or vagal stimulation independently of swallowing, permitting retrograde flow of gastric contents.
  • Lower Oesophageal Sphincter (LOS) Hypotension: Basal resting pressure of the LOS falling below normal thresholds (typically <10 mmHg), predisposing to unhindered reflux.
  • Anatomical Factors: Sliding hiatus hernia, which disrupts the mechanical barrier of the crural diaphragm, traps gastric acid within the hernia sac, and impairs oesophageal clearance mechanisms.
  • Delayed Gastric Emptying & Impaired Oesophageal Motility: Conditions such as diabetic gastroparesis or scleroderma decrease clearance of refluxed acid, prolonging mucosal contact time.
  • Dietary & Lifestyle Triggers: Consumption of high-fat meals, chocolate, caffeine, ethanol, and peppermint, which lower LOS pressure, alongside obesity (increased intra-abdominal pressure) and cigarette smoking.
  • Iatrogenic & Pharmacological Causes: Medications that decrease LOS pressure or irritate the mucosa, including calcium channel blockers, nitrates, phosphodiesterase inhibitors, anticholinergics, and non-steroidal anti-inflammatory drugs (NSAIDs)1,2.

Pathophysiology

Reflux oesophagitis develops when the aggressive noxious factors of refluxed gastric juice—principally hydrochloric acid, pepsin, and occasionally bile salts and pancreatic enzymes—overwhelm the defensive mechanisms of the distal oesophageal squamous epithelium1,2. Under normal physiological conditions, mucosal defence is maintained by a multi-tiered system comprising pre-epithelial barriers (mucin layer and salivary bicarbonate), epithelial structural resistance (intercellular tight junctions, membrane transport proteins, and cellular buffers), and post-epithelial factors (submucosal blood supply providing nutrients and clearing hydrogen ions). When barrier integrity is breached by prolonged or recurrent acid exposure, hydrogen ions back-diffuse into the intracellular space, causing cellular acidification, intracellular oedema, basal cell hyperplasia, elongation of lamina propria papillae, and eventual cellular necrosis and sloughing, culminating in endoscopically visible mucosal breaks (erosions and ulcers)2.

Los Angeles classification of reflux oesophagitis — Pathophysiological Cascade & Clinical Flowchart 1 Transient lower oesophageal sphincter relaxations Increased frequency of TLOSRs leads to gastric acid reflux into the distal oesophagus. 2 Cellular / Pathophysiological Cascade Acid-peptic mucosal injury and hydrogen ion back-diffusion causing cellular necrosis. 3 Target Organ / Structural Change Endoscopic mucosal breaks categorized into Grades A through D based on length and confluence. 4 Hallmark Clinical & Diagnostic Manifestation Typical reflux symptoms correlating directly with endoscopically confirmed LA mucosal grades. 5 Complications if Untreated & Therapeutic Target Prevention of peptic strictures, Barrett's oesophagus, and adenocarcinoma through PPI suppression.

Clinical Presentation & Classic Clinical Signs

  • History & Cardinal Symptoms: Patients classically present with retrosternal burning discomfort (heartburn) radiating upward toward the throat, often provoked by heavy meals, bending over, or recumbency. Acid regurgitation—the effortless perception of bitter or sour gastric fluid in the mouth or pharynx—is highly specific. Additional manifestations include non-cardiac chest pain, dysphagia or odynophagia (suggesting severe grades or stricture formation), chronic cough, hoarseness, globus sensation, and adult-onset asthma.
  • Physical Examination & Named Clinical Signs: General physical examination is frequently unremarkable except in advanced cases or those complicated by severe malnutrition secondary to chronic dysphagia. Assessment for abdominal obesity (increased waist circumference) and signs of chronic pulmonary aspiration (wheezing, rhonchi) is essential. Named clinical signs are generally absent in uncomplicated reflux oesophagitis, though eliciting tenderness in the epigastric region upon deep palpation is common.

Diagnostic Workup & Interpretation (Laboratory, Imaging & ECG/Pathology)

Diagnostic Modality / Test Expected Clinical & Radiological / Laboratory Finding
Gold-Standard InvestigationUpper gastrointestinal endoscopy (EGD) demonstrating mucosal breaks categorized from Grade A to Grade D according to the Los Angeles classification2.
Laboratory PanelComplete Blood Count (CBC) to evaluate for microcytic anaemia secondary to chronic occult blood loss from oesophageal erosions; basic metabolic panel to assess renal function prior to initiation of long-term proton pump inhibitor therapy.
Imaging / Radiology (X-ray, US, CT, MRI)Barium swallow radiography may identify sliding hiatus hernias, large peptic strictures, or tertiary contractions, though it lacks sensitivity for low-grade oesophagitis. Chest CT is utilized selectively to exclude malignant strictures or structural mimics in atypical presentations.
ECG / Histopathology / ProceduralStandard 12-lead ECG is mandatory in acute retrosternal chest pain to rule out acute coronary syndrome. Oesophageal mucosal biopsies (histopathology) during EGD reveal basal cell hyperplasia, papillary elongation, and intraepithelial eosinophils/neutrophils; primarily used to rule out eosinophilic oesophagitis or Barrett's oesophagus. Ambulatory 24-hour pH or pH-impedance monitoring confirms pathological acid exposure in non-erosive disease or atypical symptoms.

Staging, Classification & Clinical Scoring Systems

Criterion / Stage / Score Component Clinical Threshold, Points & Management Implication
Los Angeles Grade AOne or more mucosal breaks restricted to the mucosal folds, each no longer than 5 mm. Management: Standard-dose PPI therapy for 4-8 weeks.
Los Angeles Grade BOne or more mucosal breaks greater than 5 mm in length, restricted to the mucosal folds, without continuity across the tops of two or more folds. Management: Standard-dose to high-dose PPI therapy.
Los Angeles Grade CMucosal breaks that are continuous between the tops of two or more mucosal folds, but which involve less than 75% of the oesophageal circumference. Management: High-dose PPI therapy; maintenance therapy indicated upon healing.
Los Angeles Grade DMucosal breaks that involve at least 75% of the oesophageal circumference. Management: Intensive high-dose or twice-daily PPI therapy, endoscopic surveillance for Barrett's oesophagus, and evaluation for potential anti-reflux surgery.

Differential Diagnosis

Differential Condition Distinguishing Clinical, Biochemical & Imaging Features
Eosinophilic Oesophagitis (EoE)Presents with dysphagia and food impaction in younger patients; endoscopy reveals trachealisation, furrows, and exudates; histology demonstrates >15 eosinophils per high-power field unresponsive to high-dose PPIs.
Infectious OesophagitisCommon in immunocompromised hosts (HIV, immunosuppression); caused by Candida (white plaques), HSV (shallow ulcerations with multinucleated giant cells), or CMV (deep linear ulcers with intranuclear inclusions).
Pill-Induced OesophagitisHistory of medication ingestion without adequate water (e.g., doxycycline, bisphosphonates, NSAIDs) while recumbent; acute, sharp odynophagia with discrete, punched-out mid-oesophageal ulcers and normal surrounding mucosa.
Cardiac Ischaemia / Acute Coronary SyndromeRetrosternal chest pain that may mimic heartburn; distinguished by exertion-related symptoms, ECG dynamic ST-T wave changes, elevated cardiac troponins, and lack of response to antacids.

Management & Treatment Protocol

  • Initial Stabilization & Resuscitation: Assess airway, breathing, and circulation in patients presenting with acute massive gastrointestinal bleeding from deep oesophageal ulceration. Administer intravenous fluid resuscitation and prepare for urgent endoscopic haemostasis if active bleeding or haemodynamic instability is present.
  • First-Line Medical / Pharmacological Therapy (with exact adult dosing): Proton pump inhibitors (PPIs) are the mainstay of treatment. Standard initial therapy consists of esomeprazole 40 mg PO once daily, omeprazole 20-40 mg PO once daily, lansoprazole 30 mg PO once daily, or pantoprazole 40 mg PO once daily administered 30–60 minutes before the first meal of the day for 4 to 8 weeks. For maintenance therapy in healed severe oesophagitis (LA Grades C and D), esomeprazole 20 mg PO once daily or lansoprazole 15 mg PO once daily significantly superiorly maintains endoscopic remission compared to lower doses1. Potassium-competitive acid blockers (P-CABs) such as vonoprazan (20 mg PO daily) represent effective alternatives. Adjunctive lifestyle modifications include weight loss, elevating the head of the bed by 15–20 cm, and avoiding meals within 3 hours of recumbency.
  • Surgical / Interventional Indications: Indications for anti-reflux surgery (e.g., laparoscopic Nissen fundoplication) or endoscopic interventions (e.g., transoral incisionless fundoplication, magnetic sphincter augmentation) include medically refractory GERD, severe regurgitation unresponsive to PPIs, patient preference to avoid lifelong pharmacotherapy, or presence of large sliding hiatus hernias complicated by recurrent aspiration.

Complications & Prognosis

  • Peptic Stricture Formation: Chronic transmural inflammation leads to fibrosis and scar tissue formation in the distal oesophagus, resulting in progressive solid-food dysphagia requiring periodic endoscopic balloon dilation.
  • Barrett's Oesophagus & Adenocarcinoma: Prolonged acid-peptic injury induces metaplasia of normal distal squamous epithelium into specialized columnar intestinal epithelium (Barrett's oesophagus), a well-established premalignant precursor to oesophageal adenocarcinoma.
  • Haemorrhage & Perforation: Deep ulcerations may erode into submucosal blood vessels, causing acute upper gastrointestinal bleeding (haematemesis, melaena) or, rarely, transmural perforation (Boerhaave-like presentation or free rupture).
  • Prognosis: Uncomplicated LA Grades A and B heal rapidly (>90%) with standard once-daily PPI therapy and carry an excellent long-term prognosis. LA Grades C and D exhibit higher relapse rates, require long-term maintenance therapy, and mandate structured endoscopic surveillance protocols to monitor for neoplastic progression.