Gastroesophageal Reflux Disease – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

Reflux of gastroduodenal contents into the esophagus, larynx, or lungs, with or without resultant esophageal inflammation

Pediatric Considerations

Symptoms (vomiting, weight loss, failure to thrive) usually resolve by 18 months.

Epidemiology

Incidence

Pediatric Considerations

Children affected: 1/300–1,000

Prevalence

• Prevalence of gastroesophageal reflux disease (GERD): 10–20% in the US
• Prevalence of Barrett esophagus: 1.5%
• 65% adults have had heartburn; 15% have weekly symptoms
• In an European population-based study, reflux symptoms were found only in 40% of subjects with Barrett esophagus, and in one-third of patients with documented esophagitis (1)

Risk Factors

• Obesity
• Alcohol use
• Smoking (2)
• Caffeine use
• Position of the acid pocket above the diaphragm in patients with hiatal hernia (see below) (3,4)

Genetics

Gene polymorphism identified

General Prevention

Pediatric Considerations

• Positional treatment: Use infant seat for 2–3 hours after meals; thickened feedings
• Avoid alcohol, nicotine, and caffeine.
• Avoid lying down immediately after a meal.
• Elevate head of bed.

Etiology

• Occurs with loss of the normal pressure gradient between the lower esophageal sphincter (LES) and the stomach
• Most commonly due to inappropriate relaxation of LES:
  • Foods (high fat, spicy, citrus, chocolate, peppermint, onions)
  • Medications (anticholinergic, smooth muscle relaxants, i.e., calcium channel blockers, nitrates)
• Other contributing factors include:
  • Pregnancy (progestational hormones decrease LES pressure)
  • Ineffective peristalsis
  • Scleroderma
  • Delayed gastric emptying
  • Positional: Recumbency, bending
• Obesity

Commonly Associated Conditions

• Reflux esophagitis: Due to exposure to acid, pepsin; classified as erosive (mucosal damage apparent, ulcers, friability) or nonerosive
• Extraesophageal reflux:
  • Aspiration
  • Chronic cough
  • Laryngitis, vocal cord granuloma
  • Sinusitis
  • Otitis media
• Halitosis
• Hiatal hernia: The position of the acid pocket (the zone of high acidity detected in the proximal stomach after a meal) above the diaphragm in patients with hiatal hernia is a major risk factor (3,4).
• Peptic stricture: In 10% with GERD
• Barrett esophagus
• Esophageal adenocarcinoma

Diagnosis

• Heartburn (70–85%)
• Regurgitation of digested food (60%)
• Anginalike chest pain (33%)
• Abdominal pain (29%)
• Hoarseness (21%)
• Dysphagia (for solids; if solids and liquids, consider another cause) (20%)
• Bronchospasm (asthma) (15–20%)
• Aspiration (14%)
• Chronic cough
• Loss of dental enamel

History

• Heartburn: Retrosternal burning
• Regurgitation; sour or acid taste in mouth
• Symptoms with bending or recumbency
• Extraesophageal symptoms (e.g., cough)
• Diet, alcohol, smoking, and caffeine
• Diagnosis often made based on history alone, followed by a 1-week empiric trial with an antacid regimen

Diagnostic Tests & Interpretation

• Treated empirically if no red flags (dysphagia odynophagia, weight loss, early satiety, anemia, new onset, male >45 years) suggesting need to screen for more serious disease
• 24-hour pH monitoring: Gold standard for diagnosis; records number of reflux episodes and number that occur supine or upright; can be correlated with symptom diary
• Esophageal manometry records pressure of LES and effectiveness of peristalsis.

Lab

Check for anemia due to bleeding esophageal erosions or due to poor B₁₂absorption on proton pump inhibitor (PPI).

Imaging

Barium swallow:

• Presence of a sliding hiatal hernia appears to be a predictor of reflux esophagitis.
• Mucosal irregularity due to inflammation and edema

Diagnostic Procedures/Surgery

• Endoscopy:
  • Not part of initial workup, unless anemia, unintentional weight loss, progressive dysphagia, gastrointestinal bleeding, persistent vomiting, palpable epigastric mass, suspicion based on imaging study
  • Recommended for patients >55 who continue with symptoms after 4 weeks of treatment
  • Confirm mucosal injury; look for Barrett esophagus; biopsy for adenocarcinoma
  • ∼50–70% of patients with heartburn have negative findings on endoscopy (nonerosive or endoscopy-negative reflux disease).
• Savary-Miller classification:
  • For grading esophagitis based on endoscopic findings:
    • Grade I: ≥1 nonconfluent reddish spots, with or without exudate
    • Grade II: Erosive and exudative lesions in the distal esophagus; may be confluent, but not circumferential
    • Grade III: Circumferential erosions in the distal esophagus
    • Grade IV: Chronic complications such as deep ulcers, stenosis, or scarring with Barrett metaplasia

Pathological Findings

• Acute inflammation (especially eosinophils)
• Hyperplasia of the basal zone of the epithelium seen in 85%
• Barrett epithelial change: Gastric columnar epithelium replaces squamous epithelium in distal esophagus

Differential Diagnosis

• Infectious esophagitis (Candida, herpes, HIV, cytomegalovirus)
• Chemical esophagitis (lye ingestion)
• Pill-induced esophagitis
• Radiation injury
• Crohn disease
• Angina
• Stricture
• Esophageal carcinoma
• Achalasia
• Scleroderma
• Peptic ulcer disease

Treatment

Medication

First Line

• Stepped therapy (5):
  • Phase I: Lifestyle and diet modifications, antacids plus H₂ blockers or PPIs
  • Phase II: Symptoms persist, consider endoscopic evaluation
  • Phase III: Surgery
• H₂ blockers in equipotent oral doses (e.g., cimetidine 800 mg b.i.d. or 400 mg q.i.d., or ranitidine 150 mg b.i.d., or famotidine 20 mg b.i.d., or nizatidine 150 mg b.i.d.)
• PPIs: Irreversibly bind proton pump, onset of effect 4 days. Include omeprazole 20 mg/d, lansoprazole 30 mg/d, pantoprazole 40 mg/d, rabeprazole 20 mg/d, esomeprazole 40 mg/d
• Erosive esophagitis: PPI given for 8 weeks will be effective for healing in 90%. PPI more effective than H₂ blocker for healing erosive esophagitis.

Pediatric Considerations

Antacids or liquid histamine type 2 blockers, omeprazole, metoclopramide

Second Line

• Antacids and agents like Sucralfate may relieve breakthrough symptoms.
• Metoclopramide: 5–10 mg before meals
• Precautions:
  • Blood dyscrasias with PPIs and H₂ blockers
  • H₂ blockers must be renally dosed.
  • Metoclopramide is a dopamine blocker; risk of dystonia and tardive dyskinesia
  • On PPI, monitor B₁₂; B₁₂ and iron absorption and calcium absorption compromised on PPI
• Significant possible interactions:
  • PPIs and H₂ blockers: Multiple cytochrome P450 drug interactions; examples include warfarin, phenytoin, antifungals

Additional Treatment

General Measures

Lifestyle changes are 1st intervention:

• Elevate head of bed and avoid lying down soon after meals.
• Avoid stooping, bending, tight-fitting garments.
• Avoid medications that relax the LES (anticholinergic, calcium channel blockers).
• Lose weight.
• Stop smoking.
• Avoid alcohol.

Surgery/Other Procedures

Open or laparoscopic Nissen fundoplication to increase pressure gradient between stomach and esophagus by wrapping gastric fundus around distal esophagus, often circumferential (360-degree fundoplication) (6):

• Indications: Evidence of severe esophageal injury, incomplete response to medical treatment, medication treatment that has been or is expected to be prolonged
• Rule out esophageal dysmotility prior to surgery. If motility problems, consider a partial (270-degree, Toupet) wrap.
• Open and laparoscopic procedures both produce >90% response, equally effective for symptom reduction, quality of life, and decreased need for medications (6)[B],(7)[A].
• Cost analysis has indicated that if patient requires >10 years of PPI treatment, surgery may be more cost-effective.

Pediatric Considerations

• Surgery for severe symptoms (apnea, choking, persistent vomiting)

Ongoing Care

Follow-Up Recommendations

Patient Monitoring

• Follow symptomatically.
• Repeat endoscopy at 4–8 weeks for poor symptomatic response to medical therapy, especially in older patients.
• Current guideline is endoscopic surveillance every 2–5 years in patients with Barrett esophagus, assuming treatment if cancer is detected.

Diet

Avoid foods that make symptoms worse.

Patient Education

• Chocolate, peppermint, citrus, onions, spicy foods, and foods high in fat can make GERD symptoms worse.
• Eat small meals.
• Avoid lying down soon after meals.
• Elevate head of bed.
• Lifestyle changes, such as losing weight and smoking cessation, avoiding alcohol and caffeine helps.

Prognosis

• Symptoms and esophageal inflammation often return promptly when treatment is withdrawn; to prevent relapse of symptoms, patients should be treated with continued antisecretory therapy:
  • PPI maintenance therapy may improve quality of life better than H₂blocker maintenance.
  • Full-dose PPIs more effective than 1/2 dose for maintenance (7)[A]
  • In erosive esophagitis, daily maintenance therapy with a PPI has been proven to prevent relapse; intermittent PPI therapy has not been proven effective (8)[A].
• In terms of symptom reduction, medical and surgical therapy is equally effective (7)[A].
• Antireflux surgery:
  • 90–94% symptom response
  • 5% continued symptoms, should have anatomy evaluated by esophagram
  • Long-term follow-up shows some surgically treated patients may eventually require medical therapy.
• Regression of Barrett epithelium does not routinely occur, despite aggressive medical or surgical therapy (9).

Complications

• Peptic stricture: 10–15%
• Barrett esophagus: 10%:
  • Adenocarcinoma from Barrett epithelium (rate of cancer development 0.5% annually)
• Extraesophageal symptoms: 5–10%, including hoarseness, aspiration, including aspiration pneumonia
• Bleeding due to mucosal injury
• Noncardiac chest pain

Geriatric Considerations

Complications more likely (e.g., aspiration pneumonia)

References

1. Ronkainen J, Aro P, Storskrubb T, Johansson SE, Lind T, Bolling-Sternevald E, Vieth M, Stolte M, Talley NJ, Agréus L et al. Prevalence of Barrett’s esophagus in the general population: an endoscopic study. Gastroenterology.2005;129:1825–31.

2. Dent J, El-Serag HB, Wallander MA, et al. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2005;54:710–7.

3. Beaumont H, Bennink RJ, de Jong J, Boeckxstaens GE et al. The position of the acid pocket as a major risk factor for acidic reflux in healthy subjects and patients with GORD. Gut. 2010;59:441–51.

4. McColl KE, Clarke A, Seenan J et al. Acid pocket, hiatus hernia and acid reflux. Gut. 2010;59:430–1.

5. Mine S, Iida T, Tabata T, et al. Management of symptoms in step-down therapy of gastroesophageal reflux disease. J Gastroenterol Hepatol.2005;20:1365–70.

6. Bais JE, Bartelsman JF, Bonjer HJ, et al. Laparoscopic or conventional Nissen fundoplication for gastro-oesophageal reflux disease: randomised clinical trial. The Netherlands Antireflux Surgery Study Group. Lancet.2000;355:170–4.

7. Agency for Healthcare Research and Quality. Comparing effectiveness of management strategies for gastroesophageal reflux disease. An update to the 2005 report. Available at: http://effectivehealthcare.ahrq.gov. Accessed July 7, 2010.

8. Zacny J, Zamakhshary M, Sketris I, et al. Systematic review: the efficacy of intermittent and on-demand therapy with histamine H2-receptor antagonists or proton pump inhibitors for gastro-oesophageal reflux disease patients.Aliment Pharmacol Ther. 2005;21:1299–312.

9. Spechler SJ, Lee E, Ahnen D, Goyal RK, Hirano I, Ramirez F, Raufman JP, Sampliner R, Schnell T, Sontag S, Vlahcevic ZR, Young R, Williford W et al. Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease: follow-up of a randomized controlled trial. JAMA.2001;285:2331–8.

10. Chang AB, Lasserson TJ, Kiljander TO, Connor FL, Gaffney JT, Garske LA et al. Systematic review and meta-analysis of randomised controlled trials of gastro-oesophageal reflux interventions for chronic cough associated with gastrooesophageal reflux. BMJ. 2006;332:11–7.

Additional Reading

Fuccio L, Zagari RM, Eusebi LH, Laterza L, Cennamo V, Ceroni L, Grilli D, Bazzoli F et al. Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Ann Intern Med. 2009;151:121–8.

12. Reid BJ, Li X, Galipeau PC, Vaughan TL et al. Barrett’s oesophagus and oesophageal adenocarcinoma: time for a new synthesis. Nat Rev Cancer.2010;10:87–101.

See Also (Topic, Algorithm, Electronic Media Element)

Algorithms: Dyspepsia; Epigastric Pain; Esophageal Regurgitation

Codes

ICD9

• 530.11 Reflux esophagitis
• 530.81 Esophageal reflux

Snomed

• 235595009 Gastroesophageal reflux disease (disorder)
• 266433003 Gastroesophageal reflux disease with esophagitis (disorder)

Clinical Pearls

• There is no evidence to support that treatment with PPI causes regression of Barrett esophagus or inhibits progression of esophageal dysplasia beyond benefits of symptomatic relief.
• GERD treatments are used to treat chronic cough. Meta-analysis of randomized clinical trials suggest PPIs help with cough resolution in some adults (10)[A].
• The role of H. pylori as an etiologic agent in GERD remains controversial.