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Basic Information ⬇

AUTHOR: Fred F. Ferri, MD

Definition

Gastroesophageal reflux disease (GERD) is a motility disorder characterized primarily by heartburn and caused by the reflux of gastric contents into the esophagus. A current definition is a condition that develops when the reflux of stomach contents causes at least two heartburn episodes per week and/or complications. Table 1 describes a classification system for esophagitis.

TABLE 1 Los Angeles Endoscopic Classification System for Esophagitis

Grade AOne or more mucosal breaks confined to folds, ≤5 mm
Grade BOne or more mucosal breaks >5 mm confined to folds but not continuous between the tops of mucosal folds
Grade CMucosal breaks continuous between tops of two or more mucosal folds but not the circumferential
Grade DCircumferential mucosal break

From Feldman M et al: Sleisenger and Fordtran’s gastrointestinal and liver disease, ed 10, Philadelphia, 2016, Elsevier.

Synonyms

Peptic esophagitis

Reflux esophagitis

GERD

ICD-10CM CODES
K21.9Gastroesophageal reflux disease without esophagitis
R12Heartburn
Epidemiology & Demographics

  • GERD is one of the most prevalent gastrointestinal disorders. It is the most common GI diagnosis recorded during visits to outpatient clinics. From 18% to 28% of adults are affected.
  • The estimated prevalence of GERD is 13.3% of the population worldwide and 15.4% in North America. Costs related to GERD in the U.S. are estimated at $10 billion annually.1
  • Nearly 7% of persons in the United States have heartburn daily, 20% have it monthly, and 60% have it intermittently. Incidence in pregnant women exceeds 80%.
  • Nearly 20% of adults use antacids or over-the-counter H2 blockers at least once a week for relief of heartburn.
  • The phenotypic presentations of GERD include nonerosive reflux disease (in 60% to 70% of patients), erosive esophagitis (in 30%), and Barrett esophagus (in 5% to 12%).1
Physical Findings & Clinical Presentation

  • Physical examination: Generally unremarkable
  • Clinical signs and symptoms: Heartburn, dysphagia, sour taste, regurgitation of gastric contents into the mouth
  • Chronic cough and bronchospasm
  • Chest pain, laryngitis, early satiety, abdominal fullness, and bloating with belching
  • Dental erosions in children
ETIOLOGY

  • Incompetent lower esophageal sphincter (LES) (see Fig. E1)
  • Medications that lower LES pressure (calcium channel blockers, alpha-adrenergic antagonists, nitrates, theophylline, anticholinergics, sedatives, prostaglandins)
  • Foods that lower LES pressure (chocolate, yellow onions, peppermint). Table 2 summarizes modulators of lower esophageal sphincter (LES) pressure
  • Tobacco abuse, alcohol, coffee
  • Pregnancy
  • Gastric acid hypersecretion
  • Hiatal hernia (controversial) present in >70% of patients with GERD; however, most patients with hiatal hernia are asymptomatic
  • Obesity is associated with a statistically significant increase in the risk for GERD symptoms, erosive esophagitis, and esophageal carcinoma

TABLE 2 Modulators of Lower Esophageal Sphincter (LES) Pressure

Increase LES PressureDecrease LES Pressure
Hormones/peptidesGastrinCCK
MotilinSecretin
Substance PSomatostatin
Vasoactive intestinal peptide
Neural agentsα-Adrenergic agonistsα-Adrenergic antagonists
β-Adrenergic antagonistsβ-Adrenergic agonists
Cholinergic agonistsCholinergic antagonists
Foods and nutrientsProteinChocolate
Fat
Peppermint
Other factorsAntacidsBarbiturates
BaclofenCalcium channel blockers
CisaprideDiazepam
DomperidoneDopamine
HistamineMeperidine
MetoclopramideMorphine
Prostaglandin F2αProstaglandins E2 and I2
Serotonin
Theophylline

CCK, Cholecystokinin.

From Feldman M et al: Sleisenger and Fordtran’s gastrointestinal and liver disease, ed 10, Philadelphia, 2016, Elsevier.

Figure E1 Pathogenesis of Gastroesophageal Reflux Disease: (1) Impaired Lower Esophageal Sphincter-Low Pressures or Frequent Transient Lower Esophageal Sphincter Relaxation; (2) Hypersecretion of Acid; (3) Decreased Acid Clearance Resulting from Impaired Peristalsis or Abnormal Saliva Production; (4) Delayed Gastric Emptying or Duodenogastric Reflux of Bile Salts and Pancreatic Enzymes

From Andreoli TE et al: Andreoli and Carpenter’s Cecil essentials of medicine, ed 8, Philadelphia, 2010, WB Saunders.

Diagnosis ⬆ ⬇

Differential Diagnosis

  • Peptic ulcer disease
  • Unstable angina
  • Esophagitis (from infections such as herpes, Candida), medication induced (doxycycline, potassium chloride), eosinophilic esophagitis
  • Esophageal spasm (nutcracker esophagus)
  • Cancer of esophagus
Workup

  • Aimed at eliminating the conditions noted in the differential diagnosis and documenting the type and extent of tissue damage (Fig. E2). Generally, when symptoms of GERD are typical and the patient responds to therapy, there is no need for further diagnostic tests to verify the diagnosis.
  • Upper GI endoscopy (Fig. E3) is useful to document the type and extent of tissue damage in persistent GERD and to exclude eosinophilic esophagitis and potentially malignant conditions such as Barrett esophagus. The American College of Physicians recommends endoscopy in the setting of GERD in people with heartburn and alarm symptoms (dysphagia, bleeding, anemia, weight loss, and recurrent vomiting). It is also indicated in people with GERD symptoms that persist despite a therapeutic trial of 4 to 8 wk of bid proton pump inhibitor (PPI) therapy in patients with severe erosive esophagus after a 2-mo course of PPI therapy to assess healing and rule out Barrett esophagus.

Figure E2 Treatment Algorithm for Extraesophageal Manifestations of Gastroesophageal Reflux Disease (GERD)

bid, Twice Daily; Prn, as Needed; qd, Once Daily; Ppis, Proton Pump Inhibitors.

From Flint PW et al: Cummings otolaryngology, head and neck surgery, ed 7, Philadelphia, 2021, Elsevier.

Figure E3 Endoscopic Photographs of the Four Grades of Esophagitis (A to D), Using the Los Angeles Classification System as Outlined in Table 1

From Feldman M et al: Sleisenger and Fordtran’s gastrointestinal and liver disease, ed 10, Philadelphia, 2016, Elsevier.

Laboratory Tests

  • 24-hr esophageal pH monitoring with transnasal catheter or a 48-h wireless capsule are sensitive diagnostic tests to assess the degree of acid exposure in the esophagus in patients not responding to acid-reducing therapy; however, they are not practical and generally not done. They are useful in patients with atypical manifestations of GERD, such as chest pain or chronic cough.
  • High-resolution esophageal manometry (HRM) is indicated in patients with refractory reflux in whom surgical therapy is planned.
  • Helicobacter pylori testing is not indicated in GERD.

An upper GI series is useful in patients unwilling to have endoscopy or with medical contraindications to the procedure. It can identify ulcerations and strictures; however, it may miss mucosal abnormalities. Only one third of patients with GERD have radiographic signs of esophagitis on an upper GI series.

Treatment ⬆ ⬇

Nonpharmacologic Therapy

  • Lifestyle modifications with avoidance of foods (e.g., citrus- and tomato-based products, onions, spicy foods, carbonated beverages, mint, chocolate, fried foods) and drugs that exacerbate reflux (e.g., caffeine, β-blockers, calcium channel blockers, α-adrenergic agonists, theophylline)
  • Avoidance of tobacco and alcohol use
  • Elevation of head of bed (4 to 8 in) with blocks
  • Avoidance of lying down for at least 2h after eating or drinking, especially after late or large evening meals
  • Weight reduction to BMI <25, decreased fat intake
  • Avoidance of clothing that is tight around the waist
  • A trial in women revealed that adherence to diet and lifestyle changes reduced the risk of GERD to half compared with women who adhered to none2
General Rx

  • An empirical 8 wk trial of a PPI given once/day is recommended for patients with classic heartburn and regurgitation but no alarm symptoms. PPIs should be taken 30 to 60 min before a meal because they bind to protein pumps that have been stimulated by meals.3
  • PPIs (esomeprazole 40 mg qd, omeprazole 20 mg qd, lansoprazole 30 mg qd, rabeprazole 20 mg qd, pantoprazole 40 mg qd, or dexlansoprazole 30 mg) are generally safe, tolerated, and highly effective in most patients (Table E3). Omeprazole and esomeprazole are inhibitors of CYP2C19 and can increase serum concentrations of phenytoin and diazepam. Concomitant use of clopidogrel should also be avoided with omeprazole and esomeprazole. Increased risk of pneumonia has been documented in hospitalized patients. Long-term use of PPIs has been associated with increased risk of osteoporosis, and patients should be warned about an increased risk of fractures with long-term use. Use of PPIs in patients with cirrhosis increases risk of spontaneous bacterial peritonitis and hepatic encephalopathy. Rare side effects of PPIs include acute interstitial nephritis, hypomagnesemia, and QT prolongation.
  • H2 blocker (famotidine 40 mg qhs) can be used but is generally much less effective than PPIs.
  • Antacids (may be useful for relief of mild symptoms; however, they are generally ineffective in severe cases of reflux).
  • Prokinetic agents (metoclopramide) are indicated only when PPIs are not fully effective. They can be used in combination therapy; however, side effects limit their use.
  • Combination of PPE with an agent that reduces esophageal sphincter relaxation (baclofen) plus a neuromodulator (desipramine) may be tried in patients with refractory heartburn before considering surgery.
  • For refractory cases: Think first, cut last. Some patients will respond to twice-daily PPIs or as-needed addition of a H2 receptor blocker at bedtime. However, clinicians should be vigilant for alternative conditions that may be mistaken for GERD (e.g., achalasia).3 Surgery with Nissen fundoplication (Fig. E4). Potential surgical candidates should have reflux esophagitis documented by esophagogastroduodenoscopy and normal esophageal motility as evaluated by manometry. Surgery generally consists of reduction of hiatal hernia when present and placement of a gastric wrap around the gastroesophageal (GE) junction (fundoplication). Although laparoscopic fundoplication is now widely used, long-term medical therapy is a better choice for most patients who are willing to remain on daily acid-reduction medication. In patients preferring surgical intervention, surgery should not be advised with the expectation that patients with GERD will no longer need to take anti-secretory medications or that the procedure will prevent esophageal cancer among those with GERD and Barrett esophagus. Approximately 17.7% of patients who undergo primary laparoscopic antireflux surgery will experience recurrent gastroesophageal reflux requiring long-term medication use or secondary antireflux surgery. Risk factors for recurrence are older age, female sex, and comorbidity.
  • Endoscopic radiofrequency heating of the GE junction (Stretta procedure) is a treatment modality for GERD patients unresponsive to traditional therapy. Its mechanism of action remains unclear. Endoscopic gastroplasty (EndoCinch procedure) is also aimed at treating GERD. Initial results appear encouraging; however, long-term studies are needed before recommending these procedures.
  • Lifestyle modification must be followed for life because GERD is generally an irreversible condition in most patients.

TABLE E3 Drug Therapy for Esophageal Disorders

AgentDose
Antacids: Liquid (to Buffer Acid and Increase LESP)
For example, Mylanta II/Maalox TC (acid-neutralizing capacity, 25 mEq/5 ml)∗15 ml qid 1 hr after meals and at bedtime or as needed
Gaviscon (to Decrease Reflux via a Viscous Mechanical Barrier and Buffer Acid)
Al(OH)3, NaHCO3, Mg trisilicate, alginic acid2-4 tablets qid at bedtime or as needed
H2-Receptor Antagonists (to Decrease Acid Secretion)
Famotidine20-40 mg bid or 2.5-5 ml bid
Proton Pump Inhibitors (to Decrease Acid Secretion and Gastric Volume)†
Omeprazole20 mg/day; maintenance dose, 20 mg/day
Lansoprazole30 mg/day; maintenance dose, 15 mg/day
Pantoprazole40 mg/day; maintenance dose, 40 mg/day
Rabeprazole20 mg/day; maintenance dose, 20 mg/day
Esomeprazole20-40 mg/day; maintenance dose, 20 mg/day
Dexlansoprazole30-60 mg/day; maintenance dose, 30 mg/day

bid, Twice a day; LESP, lower esophageal sphincter pressure; mEq, milliequivalent; qid, four times a day.

∗Patients with reflux are not generally hypersecretors of gastric acid, so the therapeutic doses of antacids are based on their capacity to buffer (normal) basal acid secretion rates of approximately 1-7 mEq/hr (mean, 2 mEq/hr) and peak meal-stimulated acid secretion rates of about 10-60 mEq/hr (mean, 30 mEq/hr).

† High-dose therapy is a twice-daily administration of the usual daily dose.

Modified from Goldman L, Schafer AI: Goldman’s Cecil medicine, ed 24, Philadelphia, 2012, Saunders.

Figure E4 Three Types of Fundoplication

A, A 360-Degree Fundoplication. B, Partial Anterior Fundoplication. C, Partial Posterior Fundoplication.

From Yates RB et al: Gastroesophageal reflux disease and hiatal hernia. In Townsend CM et al [eds]: Sabiston textbook of surgery, ed 20, Philadelphia, 2017, Elsevier.

DISPOSITION

  • Recurrence of reflux is common if treatment is discontinued. Preliminary trials have shown that in patients with severe reflux esophagitis successfully treated with PPI therapy, stopping PPI medication was associated with T lymphocyte-predominant esophageal inflammation and basal cell and papillary hyperplasia without loss of surface cells.
  • The majority of patients respond well to therapy. In patients with chronic GERD, long-term outcomes are similar between medical therapy with PPIs and antireflux surgery. Prolonged use of PPIs is associated with increased risk of fractures of hip, wrist, and spine; increased risk of diarrhea from Clostridium difficile; pneumonia; and possible iron deficiency from impaired iron absorption. PPIs also block the effects of clopidogrel by inhibiting cytochrome P450 2C19 isozyme. Therefore all PPIs (other than pantoprazole) should be avoided in patients using clopidogrel. H2 blockers can be used for patients with GERD taking clopidogrel.
  • Postsurgical complications occur in nearly 20% of patients (dysphagia, gas, bloating, diarrhea, nausea). Long-term follow-up studies also reveal that within 3 to 5 yr, 52% of patients who had undergone antireflux surgery are taking antireflux medications again.
Referral

  • There is a strong and probably causal relation between symptomatic prolonged and untreated GERD, Barrett esophagus, and esophageal adenocarcinoma. GI referral for upper endoscopy is needed when there are concerns about associated peptic ulcer disease, Barrett esophagus, or esophageal cancer.
  • Patients with Barrett esophagus should undergo surveillance endoscopy with mucosal biopsy every 2 yr or less because the risk of developing adenocarcinoma of esophagus is at least 30 times greater than that of the general population.
  • Testing and treating for Helicobacter pylori in patients with GERD has not been shown to improve symptoms.
  • All children with dental erosions should be evaluated for GERD.
Related Content

Gastroesophageal Reflux Disease (GERD) (Patient Information)

Achalasia (Related Key Topic)

Dysphagia (Related Key Topic)

Related Content ⬆

    1. Fass R. : Gastroesophageal reflux diseaseN Engl J Med. ;387:1207-1216, 2022.
    2. Mehta R.S. : Association of diet and lifestyle with the risk of gastroesophageal reflux disease symptoms in US womenJAMA Intern Med. ;181(4):552-554, 2021.
    3. Katz P.O. : ACG clinical guideline for the diagnosis and management of gastroesophageal reflux diseaseAm J Gastroenterol. ;117(1):27-56, 2022.
    4. Dunbar K.B. : Association of acute gastroesophageal reflux disease with esophageal histologic changesJ Am Med Assoc. ;315(19):2104-2112, 2016.
    5. Lacy B.E. : The diagnosis of GERDAm J Med. ;123:583-592, 2010.
    6. Maret-Ouda J. : Association between laparoscopic antireflux surgery and recurrence of gastroesophageal refluxJ Am Med Assoc. ;318(10):939-946, 2017.
    7. Mittal R., Vaezi M.F. : Esophageal motility disorders and gastroesophageal reflux diseaseN Engl J Med. ;383:1961-1972, 2020.
    8. Shaheen N.J. : Upper endoscopy for GERD: best practice advice from the Clinical Guidelines Committee of the American College of PhysiciansAnn Intern Med. ;157:808-816, 2012.
    9. Spechler S.J. : Randomized trial of medical versus surgical treatment for refractory heartburnN Engl J Med. ;381(16):1513-1523, 2019.