Gastroesophageal reflux disease is a disorder in which gastric contents recurrently reflux into the esophagus, causing troublesome symptoms and/or complications.
It is produced by various mechanisms such as frequent occurrence of transient relaxation of the lower esophageal sphincter or pressure abnormalities in the lower esophageal sphincter (which can be caused by hormonal and neural mediators, food, drugs and patient lifestyle).
Typical symptoms are acid regurgitation and heartburn.
Regurgitation is the perception of flow of refluxed gastric contents into the mouth or hypopharynx.
Heartburn is defined as burning sensation in the retrosternal region.


  • There is no gold standard for the diagnosis of gastroesophageal reflux disease (GERD)
    • An objective diagnostic tool with acceptable specificity and sensitivity is still lacking
    • Endoscopy is positive in only about 40% of cases


Clinical Diagnosis

  • Since GERD occurs with few, if any, abnormal physical findings, a well-taken history is essential in establishing the diagnosis of GERD
  • Manifestations of GERD present in a number of ways:

A. Based on Symptomatology - this classification allows symptoms to define the disease

  • Manifestations of GERD are divided into esophageal and extraesophageal syndromes:

1) Esophageal Syndromes are characterized by the constellation of symptoms that may or may not be defined by further diagnostic tests

  • Esophageal symptomatic syndromes refer to uninvestigated patients with esophageal symptoms but without evidence of esophageal injury
    • Include the Typical reflux syndrome defined by the presence of troublesome heartburn and/or regurgitation which are characteristic symptoms of GERD
    • Typical reflux syndrome can often be diagnosed without diagnostic testing; however, alarm symptoms should be excluded first
    • Alarm symptoms are features which strongly raise suspicion of a complication or a malignancy
      • Include gastrointestinal (GI) bleeding, anemia, abdominal mass, unexplained weight loss, vomiting, progressive dysphagia, odynophagia, persistent pain, lymphadenopathy, family history of esophageal or gastric adenocarcinoma, dysphonia, recurrent cough or bronchial symptoms, onset of symptoms at 45-55 years old (lower in Asian regions)
      • Have low predictive value and suggest advanced, rather than early, malignancy
      • In the Asia-Pacific region, patients with alarm symptoms are likely to have gastric than esophageal cancer due to the higher prevalence of peptic ulcer disease and gastric cancer in this region
      • Their role as a diagnostic tool has limited evidence but individual alarm features with the best performance for identifying esophageal or gastric malignancies are weight loss, dysphagia, and epigastric mass on examination
  • Esophageal syndromes with esophageal injury include patients with demonstrable esophageal injury (eg reflux esophagitis, stricture, Barrett’s esophagus, adenocarcinoma)
2) Extraesophageal Syndromes with Established Associations are defined by conditions with an established association with GERD based on population-based studies
    • Eg Reflux cough syndrome, reflux asthma syndrome, reflux laryngitis syndrome, reflux dental erosion syndrome
    • It is rare for extraesophageal syndromes to occur alone without a concomitant manifestation of typical esophageal syndrome
    • These syndromes are usually multifactorial, with GERD as only one of the many other potential aggravating factors
3) Extraesophageal Syndromes with Proposed Associations are defined by conditions whose causal associations with GERD are unclear or lacking in evidence
    • Eg Sinusitis, pharyngitis, recurrent otitis media, pulmonary fibrosis
B. Based on Endoscopic Findings
  • Erosive Reflux Disease (ERD)
    • Defined by presence of esophageal mucosal damage
    • Eg Erosive esophagitis, Barrett’s esophagus
  • Non-erosive Reflux Disease (NERD)
    • Defined by absence of esophageal mucosal damage (endoscopy-negative reflux disease) in the presence of troublesome reflux-associated symptoms without recent acid-suppressive therapy
    • More common in Asia
Medication History
  • A number of common drugs and hormonal products have been associated with GERD
    • Eg anticholinergics, benzodiazepines, calcium channel blockers, Dopamine, nicotine, nitrates, Theophylline, Estrogens, Progesterone, Glucagon, some prostaglandins, nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, antibiotics


PPI (Proton Pump Inhibitor) Diagnostic Test

  • In patients with classic symptoms and who do not have symptoms suggestive of complications, an empiric trial of anti-secretory therapy may be considered since diagnostic modalities cannot reliably exclude GERD even if they are negative
    • A favorable symptomatic response to a short course of PPI (once daily x 2 weeks) is considered to support a diagnosis of GERD when symptoms of non-cardiac chest pain are present, though a negative test does not rule out GERD

Laboratory Tests

  • Diagnosis of GERD may be confirmed if at least one of the following conditions is met:
    • Presence of a peptic stricture in the absence of malignancy
    • Presence of esophageal mucosal break on endoscopy
    • Barrett’s esophagus on biopsy
    • Positive pH-metry
  • Endoscopy
    • Has a high specificity (95%) but low sensitivity (<50%)
      • 60% of patients with GERD actually have NERD
    • The first diagnostic test to consider in the presence of alarm symptoms or risk factors for Barrett’s esophagus, in evaluating symptom response to twice-daily PPI therapy, and prior to antireflux surgery
    • Most frequent indications for performing endoscopy in Asia are peptic ulcer and gastric cancer 
    • Since PPI therapy is usually started prior to any test, the sensitivity of endoscopy as a diagnostic test for GERD is poor
      • The principal role of endoscopy in suspected GERD is the evaluation of treatment failures and risk management
    • Routine endoscopy in the general population is not recommended
      • Not recommended as routine 1st-line diagnostic modality for non-cardiac chest pain (NCCP) except if with symptoms indicative of an esophageal pathology
      • High-risk patients for esophageal adenocarcinoma (eg males, age ≥50, chronic GERD, high body mass index [BMI], central obesity, hiatal hernia) may, however, warrant endoscopy
    • Endoscopy with biopsy - to target any areas of suspected metaplasia, dysplasia, or malignancy
      • Used in patients with an esophageal GERD syndrome with troublesome dysphagia
      • Biopsy is not indicated when endoscopy is normal
  • Manometry
    • To evaluate patients with suspected esophageal GERD syndrome who have not responded to an empiric trial of twice-daily PPI therapy and have normal findings on endoscopy
    • Recommended in preoperative evaluation of patients but has no role in the diagnosis of GERD
    • Will serve to localize the LES for potential subsequent pH monitoring, to evaluate peristaltic function prior to surgery, and to diagnose subtle presentations of major motor disorders
    • High-resolution manometry is recommended over manual manometry due to the former’s superior sensitivity in identifying atypical cases of achalasia and distal esophageal spasm
  • Ambulatory 24-hour Esophageal pH/Impedance, Catheter pH, or Wireless pH Monitoring
    • To assess patients with a suspected esophageal GERD syndrome who have not responded to an empiric trial of twice-daily PPI therapy, have normal endoscopic findings, and without major abnormality on manometry
    • Indicated prior to consideration of endoscopic or surgical therapy in patients with non-erosive disease
    • The only test that can assess frequency of reflux, presence of abnormal acid exposure of the esophagus, and the reflux symptom association
    • PPI therapy should be discontinued for 7 days prior to its performance
    • Wireless pH monitoring has superior sensitivity in detecting pathological esophageal acid exposure since it has longer period of recording (up to 96 hours) and has shown superior recording accuracy compared with other catheter studies
    • Reflux monitoring is not recommended in the routine investigation of extraesophageal GERD in Asia
  • Other Tests for GERD
    • Barium esophagogram may help in the evaluation of major motor disorders (achalasia, diffuse esophageal spasm) after a normal endoscopy or in preoperative phase of antireflux surgery
    • Consider overlapping of symptoms of GERD, functional dyspepsia and irritable bowel syndrome (IBS) and coexistence of serious GI disorders, eg gastric cancer or peptic ulcer, in planning for further diagnostic tests
Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Gastroenterology - Malaysia digital copy today!
Sign In To Download
Editor's Recommendations
Most Read Articles
3 days ago
New drug application approved by US FDA as of 01 - 15 September 2019 which includes New Molecular Entities (NMEs) and new biologics. It does not include Tentative Approvals. Supplemental approvals may have occurred since the original approval date.