• Clinical science

Gastroesophageal reflux disease

Abstract

Gastroesophageal reflux disease (GERD) is a chronic condition in which retrograde flow of stomach contents into the esophagus causes irritation to the epithelial lining. Reflux episodes are primarily caused by inappropriate, transient relaxation of the lower esophageal sphincter (LES). Risk factors include smoking, alcohol consumption, stress, obesity, and anatomical abnormalities of the esophagogastric junction (e.g., hiatal hernia). The chief complaint is retrosternal burning pain (heartburn), but a variety of other symptoms, such as dysphagia and a feeling of increased pressure, are also common. Suspected GERD should already receive empirical treatment, but further diagnostic steps, such as an upper endoscopy and/or 24-hour pH test, may be indicated to confirm the diagnosis. Management involves lifestyle modifications, medications, and possibly surgery. Proton pump inhibitors (PPIs) are the treatment of choice, although other agents – such as histamine H2-receptor antagonists (H2RAs) – may also be helpful. In addition to relieving symptoms, treating esophagitis is especially important, as chronic mucosal damage can lead to a premalignant condition known as Barrett's esophagus, further progressing to adenocarcinoma of the esophagus.

Definition

  • Gastroesophageal reflux: regurgitation of stomach contents into the esophagus (can also occur in healthy individuals, e.g., after consuming greasy foods or wine)
  • Gastroesophageal reflux disease (GERD): A condition in which reflux causes troublesome symptoms (typically including heartburn or regurgitation) and/or esophageal injury/complications. The most common endoscopic finding associated with esophageal mucosal injury is reflux esophagitis.
    • NERD (non-erosive reflux disease): characteristic symptoms of gastroesophageal reflux disease in the absence of esophageal injury, such as reflux esophagitis, on endoscopy (50–70% of GERD patients)
    • ERD (erosive reflux disease): gastroesophageal reflux with evidence of esophageal injury, such as reflux esophagitis, on endoscopy (30–50% of GERD patients)

References:[1][2][3][4]

Epidemiology

  • Prevalence: ∼ 15–30% in the US (increases with age)
  • Sex: =

References:[3][4]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • Main mechanism: transient lower esophageal sphincter relaxations (tLESRs)
    • The dysfunctional LES loosens independent of swallowing and has a decreased ability to constrict, which allows stomach contents to uncontrollably flow back into the esophagus (otherwise known as sphincter insufficiency).
    • Causes ∼⅔ of reflux episodes
  • Risk factors/associations

References:[5][6][2][7][3][8][9][10]

Classification

There are two major grading classifications to assess the severity of reflux esophagitis, both of which are based on macroscopic findings on upper endoscopy. While the Savary-Miller classification is still commonly used, the newer Los Angeles classification has gained widespread acceptance. Although GERD can lead to mucosal changes, most individuals present with unremarkable endoscopic findings (NERD).

Los Angeles classification of reflux esophagitis

Grade Morphology
A
  • ≥ 1 mucosal lesion no longer than 0.5 cm
B
  • Lesions > 0.5 cm
  • But not continuous between two mucosal folds
C
  • Lesions continuous between two or more mucosal folds
  • But no circumferential lesions < 75% of the esophageal circumference
D
  • Circumferential lesions > 75% of the esophageal circumference

Savary-Miller classification of reflux esophagitis

Grade Morphology
0

Reflux without mucosal damage

I

Single or multiple non-confluent mucosal erosions

II

Non-circumferential erosions

III

Circumferential erosions

IV

Complications (ulcerations, strictures, intestinal differentiation with columnar epithelium)

Clinical features

  • Chief complaint: retrosternal burning pain (heartburn) that worsens while lying down (e.g., at night) and after eating
  • Pressure sensation in the chest
  • Belching, regurgitation
  • Dysphagia
  • Chronic non-productive cough and nocturnal cough
  • Nausea and vomiting
  • Halitosis
  • Triggers:
    • Bending down, supine position
    • Habits: smoking and/or alcohol consumption
    • Psychological factors: especially stress

References:[3][4][11]

Diagnostics

  • Empirical therapy: If GERD is clinically suspected and there are no indications for endoscopy, empiric therapy – ranging from lifestyle modifications to a short trial with PPIs – should be initiated. A GERD diagnosis is assumed in patients who respond to this therapeutic regimen.
  • Upper endoscopy (esophagogastroduodenoscopy (EGD))
    • Used to classify reflux esophagitis (see “Classification” above) and conduct biopsies
    • Indications for endoscopy
  • Esophageal pH monitoring
    • Measured over 24 hours via nasogastric tube with a pH probe
    • Sudden drops to a pH ≤ 4 are consistent with episodes of acid reflux into the esophagus
    • Event diary: Patients are asked to record the time and duration of relevant events, including food intake, sleep, exercise, and other activities.
    • Indications
      • To confirm suspected NERD
      • Before endoscopic or surgical treatment options are initiated in patients with NERD
    • GERD is diagnosed when drops in esophageal pH correlate with symptoms of acid reflux and precipitating activities noted in the patient's event diary.
  • Esophageal manometry
    • A pressure-sensitive nasogastric tube measures the muscle contractions in several sections of the esophagus while the patient swallows.
    • Indications:
      • Ensure correct placement of pH probes
      • Evaluate peristaltic function prior to anti-reflux surgery
      • Exclude motor disorders that may mimic the symptoms of GERD

References:[7][12][4][13][14][15][16]

Pathology

The histopathological findings vary depending on the severity of mucosal damage:

References:[4][3]

Differential diagnoses

Other forms of esophagitis

Conditions not involving esophagitis

The differential diagnoses listed here are not exhaustive.

Treatment

Lifestyle modifications

  • Dietary
    • Small portions; avoid eating (< 3 hours) before bedtime
    • Avoid foods with high fat content
  • Physical
    • Normalize body weight
    • Elevate the head of the bed for patients with nighttime symptoms.
  • Avoid toxins: nicotine, alcohol, coffee, and certain drugs (e.g., calcium channel blockers, diazepam)

Medical therapy

  • Treatment of choice; : Standard-dose of PPI for at least 8 weeks (once daily therapy)
    • No response: further diagnostic evaluation
    • Partial response: increase the dose (to twice daily therapy) or switch to a different PPI
    • Good response: discontinue PPI after 8 weeks
  • Maintenance therapy: if symptoms recur after discontinuation of PPIs and in the case of complications (see “Complications” below)
    • After 8 weeks of initial treatment, reduce PPI to lowest effective dose or switch to H2RAs (only in patients without complications!)
    • Relapses may require a step-up

Surgical therapy

  • Indications
  • Fundoplication
    • Symptoms resolve in 85% of cases, but recurrence is possible.
    • Technique: The gastric fundus is wrapped around the lower esophagus and secured with stitches to form a cuff, leading to a narrowing of the distal esophagus and the gastroesophageal junction (GEJ)and prevents reflux.
    • Fundoplication types differ in:
      • Surgical technique (most commonly laparoscopic vs. open surgery)
      • Surgical approach (transthoracic vs. abdominal)
      • Part of the stomach wall that is used to form the cuff (posterior vs. anterior)
      • Completeness of the cuff (complete vs. partial)
      • Looseness and length of the cuff
    • Nissen fundoplication (= complete fundoplication)
    • Complications
  • If hiatal hernia is present
    • Hiatoplasty: margins of the widened hiatus are sutured together, possibly inserting mesh for extra support (e.g., if extremely widened or high risk of symptom recurrence)
    • Fundopexy or gastropexy: the protruding part of the stomach is tethered to the diaphragm → keeps it in place and relieves the tension placed on the cuff

References:[3][7][13][18][6][19][20][21][22]

Complications

References:[23][3]

We list the most important complications. The selection is not exhaustive.