for Health Care Providers
Gastroesophageal Reflux Disease (GERD)
Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary. Consult VA pharmacists for alternatives.
- Typical symptoms of GERD are heartburn and regurgitation.
- Less common GERD symptoms (eg, cough) may mimic other conditions.
- Evaluation of GERD in patients with HIV depends on the stage of infection.
- In patients with a CD4 count of >350 cells/µL with typical GERD symptoms, a trial of empiric acid suppression therapy may be undertaken in lieu of other diagnostic testing.
- In patients with more advanced HIV infection, evaluation for OIs affecting the esophagus should be considered, along with empiric GERD therapy.
- Patients with GERD symptoms lasting >5 years should be evaluated by endoscopy for Barrett esophagus because of the increased risk of esophageal carcinoma.
- Patients with alarm symptoms (eg, unexplained dysphagia or weight loss, hematemesis) should be evaluated by endoscopy for malignancy or other GERD complications.
- GERD is defined by the American College of Gastroenterology as "symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus." However, there is no universally accepted definition of the condition, and no gold standard for its diagnosis.
- Uncomplicated GERD is characterized by typical symptoms of heartburn, regurgitation, or both.
- Complicated GERD includes Barrett esophagus (see below), esophageal strictures, hemorrhage or perforation, and extraesophageal complications such as aspiration, asthma, chronic coughing, chest pain, and laryngopharyngitis.
- Etiology involves lower esophageal sphincter (LES) dysfunction with reflux of acidic gastric contents into the esophagus, often resulting in damage to esophageal mucosa. Decreased esophageal motility and abdominal distention also may play a role.
- Symptoms of heartburn are common in Western countries: 25% of the general population is reported to have heartburn at least once a month, 12% has heartburn at least weekly. GERD can have a very negative impact on quality of life.
- There is no reported association of GERD with HIV infection. For HIV-infected patients, however, the differential diagnosis of GERD symptoms includes several HIV-related conditions (see Partial differential diagnosis, below).
- Diagnosis usually depends on the presence of symptoms and/or the confirmation of esophagitis with esophagogastroduodenoscopy (EGD) or other testing.
- Esophagitis (esophageal erosions or other mucosal damage) is seen on EGD or histology in <50% of patients. The majority of patients with GERD symptoms have no evidence of esophagitis on EGD (ie, nonerosive reflux disease, or NERD).
- The severity and course of symptoms of esophagitis and NERD are similar.
- The condition is often chronic, with remissions and relapses, but usually not progressive. Possible complications include:
- Esophageal stricture
- Esophageal ulcers
- Barrett esophagus
- The symptoms and esophageal mucosal injuries caused by GERD usually respond to acid-suppressive treatment, though some complications (eg, Barrett esophagus) may not improve with treatment.
Veterans with HIV*
Esophageal disease: 19%
- There is no gold standard for diagnosis of GERD.
- Uncomplicated GERD may be diagnosed by clinical symptoms alone.
- EGD should be considered at presentation for patients with symptoms of complicated GERD (extraesophageal or alarm symptoms; see below) and those at risk of Barrett esophagus (see below).
- The differential diagnosis of symptoms referable to the esophagus in patients with HIV depends on the stage of infection.
- In patients with CD4 counts of <350 cells/mL, the differential diagnosis should include esophageal OIs, such as candidiasis and CMV infection.
- In patients with higher CD4 counts, evaluation should focus on GERD, and on Barrett esophagus and alarm symptoms that suggest malignancy or other conditions (see below); however, the possibility of OIs should be considered as well.
- Patients with symptoms lasting for >5 years should be evaluated for Barrett esophagus because of the associated increase in risk of esophageal adenocarcinoma.
Check for alarm symptoms:
- Unexplained weight loss
- GI bleeding (hematemesis, melena, bloody stool)
- Chest pain
- Failure to improve with therapy
In HIV-infected patients with relatively high CD4 counts, these suggest malignancy, ulceration, or stricture. If present, refer for immediate evaluation via EGD. Consider starting trial of acid suppression therapy while awaiting further evaluation.
- Metaplasia, with replacement of esophageal squamous epithelium by abnormal columnar epithelium
- Associated with severe GERD, but may occur in asymptomatic patients
- Increases risk of esophageal adenocarcinoma 50-fold compared with GERD alone
- Unclear whether acid suppression prevents progression of Barrett esophagus or development of adenocarcinoma
- Patients with a history of GERD symptoms for >5 years, especially those ≥50 years of age, should be evaluated for Barrett esophagus by EGD
- Reflux symptoms should be controlled before EGD to maximize sensitivity and specificity of EGD
- The surveillance interval for Barrett esophagus is determined by the grade of dysplasia at initial EGD
- For low-grade dysplasia, EGD should be repeated within 6 months to exclude higher-grade dysplasia
- For high-grade dysplasia, EGD should be repeated within 3 months
|History||History is usually the basis of GERD diagnosis; however:
| Empiric proton pump inhibitor (PPI) therapy|
| Ambulatory pH monitoring|
| Barium esophagram|
|Partial differential diagnosis|
Goals of therapy:
- Symptom relief
- Healing of esophageal erosions (if present)
- Prevention of complications (data demonstrate reduction in esophageal strictures, but do not clearly show that treatment prevents or slows development of Barrett esophagus or adenocarcinoma)
As discussed in the Evaluation section, empiric acid-suppressing treatment may be initiated on the basis of GERD symptoms. The rate of symptom response to adequate therapy is high (>80%), so patients whose symptoms do not improve should be evaluated for other causes.
- Mainstay of GERD treatment.
- Primary acid-suppressive treatments are PPIs and H2 receptor antagonists (H2RAs).
- For symptom control and healing of esophagitis, the order of efficacy is: high-dose PPI > standard-dose PPI > half-dose PPI > high-dose H2RA > standard-dose H2RA.
- Patients with erosive esophagitis, extraesophageal symptoms, or a history of failure to respond to H2RAs should be started on standard-dose PPI rather than an H2RA.
- For patients with NERD, the optimal initial treatment strategy has not been defined. Some authorities prefer to start with PPIs at maximal doses and step down to less-intensive therapy after symptom remission; others prefer to start with less-intensive therapy and step up if symptom relief or esophageal healing is incomplete.
- PPIs and H2RAs may affect serum levels of some ARVs; these drug-drug interactions may influence which type of medication is selected for initial treatment of GERD (see Potential ARV Interactions below).
- Most GERD patients (>60%) gain symptom relief, and approximately 80% have healing of esophagitis at 8-12 weeks.
- No role as primary therapy (typically, patients have self-treated with antacids without symptom relief).
- May be helpful for some patients as supplement to PPI therapy, to be used as needed for breakthrough symptoms.
- Metoclopramide is the only prokinetic agent available in the United States.
- Increases LES resting tone, esophageal peristalsis, and gastric emptying.
- Less effective than PPIs; similar to but perhaps less effective than H2RAs.
- Associated with CNS adverse effects (eg, irreversible tardive dyskinesia).
- Should be used only as adjunct to acid suppression, not monotherapy.
- Generally aimed at avoiding decreases in LES function, or increases in abdominal pressure or position, which promote reflux of acid above the LES.
- Adjunct to acid suppression in selected patients; not suitable for sole therapy.
- Limited data on efficacy from randomized controlled trials for most measures.
- Specific modifications should be based on individual circumstances and identified triggers.
|Generic Drug Name||Dosage Range||Comments|
|Dexlansoprazole||30-60 mg QD||If difficulty swallowing, can open capsule and sprinkle contents on applesauce|
|Esomeprazole||20-40 mg QD||If difficulty swallowing, can open capsule and sprinkle contents on applesauce|
|Lansoprazole||15-30 mg QD or 30 mg BID||If difficulty swallowing, can open capsule and sprinkle contents on applesauce|
|Omeprazole||20-40 mg QD||If difficulty swallowing, can open capsule and sprinkle contents on applesauce; immediate-release form contraindicated with hypocalcemia or alkalosis|
|Pantoprazole||40 mg QD or 40 mg BID||No dosage adjustment needed for hepatic impairment; may cause false-positive THC result on urine toxicology screen|
|Rabeprazole||20 mg QD or 20 mg BID||Delayed-release tablet|
|Cimetidine||800 mg BID or 800 mg TID||Multiple drug interactions (see Potential ARV Interactions)|
|Famotidine||20 mg BID or 40 mg BID||May decrease ATV absorption|
|Nizatidine||150 mg BID or 300 mg BID||May decrease ATV absorption|
|Ranitidine||150 mg BID or 150 mg QID||May decrease ATV absorption; may decrease FPV, LPV, RTV levels|
|Metoclopramide||10-15 mg QID (after meals and at bedtime)||Associated with irreversible tardive dyskinesia, other CNS effects; may consider metoclopramide as adjunctive therapy (add-on to PPI)|
|Dietary and Lifestyle Modification|
|Possible responses to treatment||Options for treatment and evaluation|
|Adequate control of symptoms|
|Partial control of symptoms|
|Lack of response|
More than 60% of patients respond to adequate therapy. Most authorities recommend that all patients who do not respond to a trial of PPI therapy be referred for further evaluation. In patients with low CD4 counts, consider candidiasis or CMV esophagitis, and other HIV-associated conditions.
- Restart the medication at the dosage that was effective in controlling the patient's symptoms.
- If relapse occurs on H2RA, step up therapy to PPI.
- Consider referral for further diagnostic testing.
Chronic GERD Symptoms
Goals: Suppress symptoms, prevent relapses.
- Limited data on optimal strategy for long-term acid suppression
- Chronic maintenance: consider for frequent or rapid relapses, severe disease
- Episodic treatment as needed for relapses: consider for patients with mild GERD
- It is rational to use the lowest possible dosage of PPI or H2RA that controls symptoms, but recurrences are common with decreased intensity or discontinuation of medications; some data suggest that efficacy of H2RAs may decline over time.
- Chronic PPI therapy appears to be safe, but data from controlled trials are not available and risks are not fully known.
- May decease absorption of vitamin B12; use with caution for patients with risk factors for B12 deficiency.
- May decrease serum Mg levels, consider periodic monitoring.
- May increase risk of fractures; use with caution for patients with risk factors for osteoporosis.
Most surgical and endoscopic therapies (eg, fundoplication) alter LES function, and have variable success. Criteria for selecting patients are not completely defined, but usually include those with large-volume reflux, good responses to medical therapy, or intolerance to medical treatment. Following surgery, a high proportion of patients continue to require acid-lowering medications for control of symptoms. Refer to GI for evaluation.
When to Refer
Potential ARV Interactions
Acid-lowering medications have interactions with various ARVs. Consult dosing information, as certain combinations require specific dosing strategies, and some are contraindicated.
PPIs: interactions with ARVs are incompletely studied
|ARV-Naive Patients||ARV-Experienced Patients|
|Source: Reyataz package label|
- DeVault KR, Castel DO; American College of Gastroenterology. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol. 2005 Jan;100(1):190-200.
- Ip S, Bonis P, Tatsioni A, et al. Comparative Effectiveness of Management Strategies for Gastroesophageal Reflux Disease. Evidence Report/Technology Assessment No. 1. (Prepared by Tufts-New England Medical Center. Evidence-based Practice Center under Contract No. ***********.) Rockville, MD: Agency for Healthcare Research and Quality; December 2005. Accessed November 6, 2008.
- Moayyedi P, Talley NJ. Gastro-oesophageal reflux disease. Lancet. 2006 Jun 24;367(9528):2086-100.
- van Pinxteren B, Numans ME, Bonis PA, et al. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev. 2010 Nov 10;(11):CD002095.
- Spechler SJ, Lee E, Ahnen D, et al. Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease: follow-up of a randomized controlled trial. JAMA. 2001 May 9;285(18):2331-8.
- VA/DoD Clinical Practice Guideline Working Group. Management of Adults with Gastroesophageal Reflux Disease in Primary Care Practice. Washington, D.C.: Pharmacy Benefits Management Strategic Healthcare Group and the Medical Advisory Panel, Veterans Health Administration, Department of Veterans Affairs, and the Pharmacoeconomic Center, Department of Defense; March 12, 2003.
- Wang KK, Sampliner RE; Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett esophagus. Am J Gastroenterol. 2008 Mar;103(3):788-97.