Gastroesophageal reflux disease

Description of Medical Condition

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

System(s) affected: Gastrointestinal

Genetics: N/A

Incidence/Prevalence in USA: 65% of adults have suffered heartburn; 24% have had symptoms for > 10 years. 17% of adults use indigestion aids at least once weekly, only 24% of sufferers have consulted a physician. Children affected 1/300-1000. 30-80% of pregnant women report heartburn.

Predominant age: All ages

Predominant sex: Male = Female

Medical Symptoms and Signs of Disease

• Heartburn (pyrosis) 70-85%
• Regurgitation 60%
• Dysphagia (possible stricture) 15-20%
• Angina-like chest pain 33%
• Bronchospasm (asthma) 15-20%
• Laryngitis (dysphonia)
• Chronic cough
• Globus sensation
• Loss of dental enamel
• In infants: Recurrent emesis, failure to thrive, apnea syndrome

What Causes Disease?

•  Inappropriate relaxation of lower esophageal sphincter (LES) (idiopathic, food- or drug-related)
• Chronic eructation (belching), aerophagia
• Pregnancy (progestational hormones cause decreased LES pressure)
• Scleroderma (reduced esophageal motility and incompetent LES)
• Chalasia of infancy
• Delayed gastric emptying (impaired acid clearance)
• Acid hypersecretion (e.g., Zollinger-Ellison syndrome)
• Heller’s myotomy for achalasia

Risk Factors

• Foods that lower LES pressure (high-fat content, yellow onions, chocolate, peppermint)
• Foods that irritate esophageal mucosa (citrus fruits, spicy tomato drinks)
• Hiatal hernia — acid trapping
• Chronic belching, aerophagia
• Medications that lower LES pressure (e.g., theophylline, anticholinergics, progesterone, calcium channel blockers (nifedipine, verapamil), alpha adrenergic agents, diazepam, meperidine
• Indwelling nasogastric tube
• Chest trauma
• In children: Down syndrome, mental retardation, cerebral palsy, repaired tracheoesophageal fistula
• Eradication of H. pylori infection (resulting in increased acid production, loss of acid buffering, etc.)
• Risks for erosive esophagitis: male, Caucasian, hiatal hernia, basal metabolic index (BMI) >30 and NSAIDs

Diagnosis of Disease

Differential Diagnosis

• Infectious esophagitis (Candida, herpes, HIV, cyto-megalovirus)
• Chemical esophagitis (lye ingestion)
• Radiation injury
• Crohn disease of esophagus
• Angina pectoris
• Esophageal carcinoma
• Pill-induced esophagitis (e.g., doxycycline, ascorbic acid, quinidine, potassium chloride, bisphosphonates. etc.)
• Achalasia
• Ulcer disease
• Alkaline reflux

Drugs that may alter lab results: N/A

Disorders that may alter lab results: N/A

Pathological Findings

• Acute inflammation (especially eosinophils)
• Hyperplasia (thickening) of the basal zone of the epithelium seen in 85%
• Lengthening of vascular channels within vascular papillae so that they approach the luminal surface
• Barrett’s epithelial change — gastric columnar epithelium (intestinal metaplasia) migrates upward into the distal esophagus; may be associated with strictures and peptic ulceration; dysplasia and malignant transformation

Special Tests

• Esophageal pH monitoring (antacids, H2 blockers. proton pump inhibitors and other antisecretory agents can give false negative pH monitoring)
• Esophageal manometry (anticholinergics, theophylline, calcium channel blockers, meperidine, diazepam may give falsely low LES pressure on manometry)

Imaging

• Barium swallow: Presence of a sliding hiatal hernia appears to be a predictor of reflux esophagitis; mucosal irregularity due to inflammation and edema; prominent longitudinal folds, erosions, ulcers; smoothly tapered strictures; pseudodiverticula
• Radionuclide scintigraphy

Diagnostic Procedures

• “Once in a lifetime” endoscopy in chronic GERD patients to exclude Barrett’s and adenocarcinoma is becoming an accepted practice
• Endoscopy (or upper Gl series), pH monitoring to evaluate patients with warning symptoms (dysphagia, hematemesis, unexplained weight loss, chest pain, etc.)
• 50-70% of patients with heartburn have negative findings on endoscopy (nonerosive or endoscopy-negative reflux disease [ENRD])
• Patients with esophagitis are graded according to the LA (Los Angeles) Classification as follows:

– Grade A: one or more mucosal breaks < 5 mm in maximal length (30-35% of patients) – Grade B: one or more mucosal breaks > 5 mm in length but not continuous between the tops of two mucosal folds (40% of patients)

– Grade C: mucosal breaks continuous between the tops of two or more mucosal folds but involving < 75% of the esophageal circumference (20% of patients) – Grade D: mucosal breaks involving > 75% of the esophageal circumference (5-7% of patients)

• Barrett’s change suspected when salmon colored mucosa extends > 2 cm above normal squamocolumnar junction (in up to 10%).
• Mucosal biopsy
• Cytology for Barrett’s dysplasia (flow cytometry useful adjunct when available)
• Metoclopramide or cisapride may give falsely negative gastric emptying results
• Empiric trial of proton pump inhibitor compares well to pH monitoring as a diagnostic tool in diagnosing reflux in patients without alarm symptoms

Treatment (Medical Therapy)

Appropriate Health Care

Outpatient (typical heartburn history has a positive predictive value of > 80%; warrants empiric therapy in absence of alarm symptoms)

General Measures

• Elevate head of bed, avoid lying down directly after meals; avoid stooping, bending, tight-fitting garments
• Avoid drugs that decrease LES pressure
• Weight loss
• Avoid voluntary eructation

Stepped therapy

– Phase I: lifestyle and diet modifications plus antacids or OTC H2 blockers

– Phase II: H2 blockers in prescription doses; proton pump inhibitors

– Phase III: (1) proton pump inhibitor or high-dose H2 blocker or (2) H2 blockers or proton pump inhibitor plus promotility agent

– Phase IV: surgery

Endoscopic therapy — designed to increase pressure and/or improve the antireflux barrier

– Radiofrequency energy delivered to LES area (Stretta procedure) improved symptoms, but did not reduce acid exposure or need for medications when compared to a sham procedure

– Plication of the LES by endoscopic suturing system

– Injection of microspheres into the LES

Surgical Measures

– pen or laparoscopic Nissen ot Toupet fundoplication. Good-excellent response: if abnormal 24 hr pH score, typical primary symptom and poor prior response to medical treatment; poor response: if normal 24 hr pH score, poor esophageal motility, aerophagia

Activity

Full activity

Diet

Avoid chocolate, peppermint, onions, high-fat foods, alcohol, tobacco, coffee, citrus

Medications (Drugs, Medicines)

Drug(s) of Choice

Mild to moderate disease: H2 blockers in equipotent oral doses, eg, cimetidine (Tagamet) 800 mg bid or 400 mg qid or ranitidine (Zantac) 150 bid orfamotidine (Pepcid) 20 mg bid or nizatidine (Axid) 150 mg bid. Proton pump inhibitors (eg, omeprazole (Prilosec) 20 mg/d, lansoprazole (Prevacid) 30 mg/d, pantoprazole (Protonix) 40 mg/d, rabeprazole (Aciphex) 20 mg/d, esomeprazole (Nexium) 40 mg/d may be used as initial therapy for symptomatic GERD.

Erosive esophagitis: Proton pump inhibitors are significantly more effective than the H2 blockers in ulcer healing doses

Severe disease (refractory to initial therapy): Proton pump inhibitor given once or twice daily or higher

Extraesophageal symptoms (eg laryngitis, asthma) often require higher doses of proton pump inhibitors (PPI) for prolonged duration

Nonerosive reflux disease (NERD): PPIs more effective than H2 blockers

Pantoprazole available in intravenous formulation for patients who cannot take po

Contraindications: Known hypersensitivity to H2 blockers, omeprazole, lansoprazole, cisapride

Precautions:

Dose reduction of H2 blockers for renal failure

Avoid cimetidine when potentially interacting drugs are co-administered (or closely monitor prothrombin time or serum theophylline levels, etc.)

Significant possible interactions:

• Cimetidine interacts with > 60 drugs (e.g., theophylline. warfarin, phenytoin, lidocaine). Refer to manufacturer’s profile.
• Omeprazole

– May prolong the elimination of diazepam, warfarin and phenytoin

– Prolonged PPI use associated with hypergastrinemia and potential for vitamin B12 deficiency

Alternative Drugs

• Antacids; alginates e.g., alumina-magnesium (Gaviscon)
• Metoclopramide (Reglan) 5-10 mg before meals used adjunctively with H2 blockers (neuropsychiatric side effects in 30% limits its usefulness)
• Cisapride (Propulsid) 10-20 mg qid (before meals and at bedtime) available only for investigational limited access program through the manufacturer
• Baclofen 40 mg/d has reduced acid reflux episodes and belching

Patient Monitoring

Follow symptomati-cally; repeat endoscopy at 4-8 weeks for poor symptomatic response; endoscopy and biopsy for Barrett’s esophagus (to detect dysplasia) every 1-2 years

Prevention / Avoidance

• Nocturnal breakthrough of heartburn treated with hs dose of H2 blocker or bid PPI
• Long-term maintenance therapy with H2 blockers or proton pump inhibitors along with lifestyle and diet modifications to prevent symptomatic relapse
• Peptic strictures may require periodic dilatation (although frequency of dilatation is reduced by PPI maintenance)
• Proton pump inhibitors are most effective in acute healing doses for chronic maintenance in severe GERD
• Consider antireflux surgery (laparoscopic approach increasingly being used) in patients with severe disease in lieu of chronic drug therapy
• Annual or every other year endoscopy, biopsy and cytology to detect dysplasia in Barrett’s epithelium (more frequently if dysplasia present)
• Photodynamic therapy for Barrett’s esophagus with dysplasia

Possible Complications

• Peptic stricture (10-15%)
• Hemorrhage (3%)
• Barrett’s esophagus (10%)
• Pulmonary or ear, nose, throat complications (5-10%)
• Noncardiac chest pain
• Adenocarcinoma from Barrett’s epithelium

Expected Course / Prognosis

Majority of patients respond well to antisecretory therapy. Overall healing rate at < 12 weeks for PPIs = 84% vs H2 blockers 52%. Speed of healing is 12% per week for PPI vs 6% per week for H2 blockers. Complete freedom from heartburn is 77% for PPI vs 48% for H2 blockers.

Symptoms and esophageal inflammation often return promptly when treatment withdrawn

Relapse prevention therapy with H2 blockers/proton pump inhibitor often requires the full healing dose to be maintained

Antireflux surgery (e.g., fundoplication) for complications or “refractory” disease; excellent short-term results. But long-term follow up shows many patients eventually require medical therapy for acid suppression; doses of 40 mg/d omeprazole or equivalent yield similar long-term results compared to surgery.

Regression of Barrett’s epithelium does not routinely occur despite aggressive medical or surgical therapy

Cost effectiveness of long-term maintenance therapy has been shown for PPIs and H2 blockers (PPI more cost effective than high dose H2 blockers)

Successful eradication of Helicobacter pylori associated with worsening of GERD in some patients

Long-term safety of omeprazole (up to 11 years) recently demonstrated

Miscellaneous

Associated Conditions

• Extraesophageal reflux
• Reflux-induced asthma
• Pulmonary aspiration
• Chronic cough/throat clearing
• Loss of dental enamel
• Halitosis
• Laryngitis, laryngeal carcinoma
• Globus sensation
• Vocal cord granulomas

Age-Related Factors

Pediatric:

• Reflux symptoms usually resolve by 18 mo
• Vomiting, weight loss, failure to thrive more common than heartburn
• Positional treatment = use of infant seat for 2-3 hours after meals; thickened feedings
• Drug treatment = antacids or liquid H2 blockers (e.g. Zantac syrup); omeprazole
• Surgery for severe symptoms (apnea, choking, persistent vomiting) successful in 85-95%

Geriatric:

Complications more likely

Pregnancy

• Heartburn (when first experienced): 52% 1st trimester. 24% 2nd trimester, 9% 3rd trimester
• Tends to recur in subsequent pregnancies
• Symptomatic therapy includes multiple small meals, avoid lying down for 2-3 hours after meals, elevating the head of the bed at night
• Antacids, alginates, sucralfate appear safe in all trimesters
• Ranitidine, cimetidine, and omeprazole also appear safe in early as well as late pregnancy

Synonyms

• Reflux esophagitis
• Peptic esophagitis
• Barrett’s esophagus
• Symptomatic hiatal hernia
• Nonerosive reflux disease
• Supraesophageal reflux disease
• GERD

International Classification of Diseases

530.10 Esophagitis, unspecified

750.6 Congenital hiatus hernia

787.1 Heartburn

530.81 Esophageal reflux

530.11 Reflux esophagitis

See Also

Peptic ulcer disease Esophageal tumors Dysphagia

Other Notes

Alkaline (bile) reflux accounts for up to 15% of Barrett’s esophagus and severe esophagitis; promotility agent or surgery may be required in this setting

Abbreviations

LES = lower esophageal sphincter

GER = gastroesophageal reflux

GERD = gastroesophageal reflux disease

PPI = proton pump inhibitor

NERD = nonerosive reflux disease