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© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
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© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
in the clinic
Gastroesophageal
reflux disease
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
What causes GERD?
 Prolonged exposure to reflux of gastric contents
 Transient relaxations of lower esophageal sphincter expose
esophagus to stomach acid and contents
 Factors that increase exposure
 Increased intra-abdominal pressure (obesity, pregnancy)
 Decreased esophageal or gastric motility
 Xerostomia
 Hiatal hernia
 Increased esophageal sensitivity may predispose to more
severe symptoms or tissue damage
 Increased acid production is not an important cause of GERD
 Zollinger-Ellison syndrome the rare exception
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
What symptoms and signs should prompt
clinicians to consider GERD?
 Typical esophageal symptoms
 Heartburn
 Regurgitation
 Atypical esophageal symptoms
 Epigastric discomfort
 Noncardiac chest pain
 Nausea, satiety, dysphagia, globus, eructation, hematemesis
 Extraesophageal symptoms
 Cough, wheezing
 Sore throat, hoarseness
 Dental erosions
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
When should clinicians try an empirical
therapeutic trial of acid suppression
therapy to support a preliminary diagnosis?
 When upper GI complaints are vague and symptom
questionnaire is suggestive of GERD
 Reflux Disease Questionnaire: 12-question instrument
 When esophageal & extraesophageal symptoms present
 Trial of PPI: take once or twice daily for 1 to 2 weeks
 Assure proper dosing and compliance
 If only partial improvement occurs, consider twice-daily
dosing or switch to another PPI before declaring nonresponder
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
When should clinicians consider upper
endoscopy in evaluating patients with
possible GERD?
Indications for EGD in Known or Suspected GERD
 Typical GERD symptoms that persist after a PPI trial
 Alarm symptoms (dysphagia, bleeding, unexplained iron
deficient anemia, weight loss, vomiting, epigastric mass)
 Atypical GERD symptoms (epigastric pain, early satiety,
food impaction): to exclude other upper GI diseases
 Confirm healing after severe erosive esophagitis
 Screen for Barrett esophagus in men >50 years with
chronic GERD and additional risk factors
 Surveillance of known Barrett esophagus
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
What other diagnoses should clinicians
consider in patients with suspected GERD?
 Esophageal disorders
 Cancer (squamous or adenocarcinoma)
 Eosinophilic esophagitis
 Functional heartburn
 Motility disorders (achalasia, spastic disorders,
hypotensive lower esophageal sphincter)
 Nonreflux esophagitis (infectious, pill- or radiationinduced)
 The rumination syndrome
 Strictures, webs, or rings
 Zenker’s diverticulum
 Continued
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
 Other gastrointestinal disorders
 Biliary colic
 Gastritis
 Gastroparesis
 Hiatal hernia
 Nonulcer dyspepsia
 Peptic ulcer disease
 Nongastrointestinal disorders
 Chest wall pain
 Coronary artery disease
 Oropharyngeal and laryngeal disorders
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
What other lab tests should clinicians
consider when the diagnosis is uncertain?
 Ambulatory reflux monitoring
 Esophageal manometry
 For refractory cases
 For pre-op testing for anti-reflux surgery
 Barium radiography (esophagram &/or upper GI series)
 For primary complaint of dysphagia
 For pre-op or post-op testing for anti-reflux surgery
 Laryngoscopy
 Presence of laryngeal erythema, edema, or other
abnormalities not specific for GERD
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
Is there any connection between GERD and
Helicobacter pylori infection?
 Diagnose and manage as separate entities
 Both may present with dyspepsia
 No reason to test for H. pylori in patients with typical
symptoms of heartburn or regurgitation
 Patients with H. pylori gastritis may experience increased
GERD symptoms even when H. pylori is eradicated
 Long-term PPI use may increase risk for atrophic gastritis
in patients with undiagnosed H. pylori infection
 Routinely checking H. pylori status in patients on longterm PPIs is not recommended
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
When should clinicians consider
gastroenterology consultation during the
evaluation of GERD?
 Typical symptoms do not respond to an empiric PPI trial
 Atypical symptoms overlap with those of other
esophageal or gastric disorders
 Alarm symptoms
 High risk of Barrett esophagus and adenocarcinoma
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
CLINICAL BOTTOM LINE: Diagnosis...
 Empiric diagnosis of GERD is based on
 Presence of typical esophageal symptoms
 Response to a PPI trial
 Use of patient-reported questionnaires
 If no response to PPI trial or if symptoms are
extraesophageal or atypical: consider other disease
possibilities
 Consider EGD when alarm signs are present (dysphagia,
bleeding, weight loss, vomiting or epigastric mass)
 Don’t use barium radiography or laryngoscopy for GERD Dx
 Reserve other tests for refractory or complex cases
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
What is the role of dietary modification in
the treatment of GERD?
 Dietary modifications may improve symptoms or reduce
complications, but evidence isn’t strong
 Some foods may lower LES tone (carminatives)
 Other foods may irritate inflamed esophageal mucosa
(citrus)
 Patients may report improvement when avoiding
particular substances
 May control uncomplicated GERD without medical therapy
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
Are behavioral interventions effective in
the treatment of GERD?
 Weight loss
 Smoking cessation
 Elevating head by 6-8 inches when in bed
 Avoiding meals in the last 2-3 hours before bed
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
Which medications cause or exacerbate
GERD, and how should clinicians counsel
patients regarding their use?
 Medications that exacerbate GERD
 By decreasing LES pressure and/or slowing esophageal clearance
 CCBs, nitrates, anticholinergics, α-adrenergic antagonists,
prostaglandins, theophylline, sedatives
 Medications that irritate already inflamed tissue
 Aspirin, NSAIDs, bisphosphonates
 Decide whether to avoid these medications on a case
by case basis
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
Which non-prescription medications are
effective in the management of GERD?
 Antacids neutralize stomach acid to relieve heartburn
 Best used “on-demand” for infrequent symptoms
 Regular or frequent use a marker of uncontrolled GERD
 H2-receptor antagonists (H2RAs)
 Inhibit histamine binding on gastric parietal cell receptor
 Help heal erosive esophagitis and improve symptoms
 Best used “on-demand” for infrequent symptoms in
patients with symptoms after stopping initial PPI therapy
 Use when PPIs not tolerated or contraindicated
 Use limited by tachyphylaxis
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
When should clinicians consider
prescription medications?
 PPIs
 First-line agents for patients with erosive disease or with
typical esophageal symptoms
 Irreversibly inhibit parietal cell proton pump
 Most efficacious when taken 30 to 60 minutes before eating
 More potent acid suppressors than H2RAs
 Initial therapy: 8-week course of once daily PPI
 Maintenance therapy indicated if GERD symptoms persist
 Continued
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
 tLESR inhibitors (baclofen)
 GABA-B agonist increases lower esophageal sphincter tone
 Prokinetic agents (metoclopramide)
 Promote gastric emptying
 Mucosal protectant (sucralfate)
 Binds to inflamed mucosa
 Antidepressants (SSRIs, tricyclic antidepressants)
 May modulate visceral pain sensation due to acid exposure
especially in hypersensitive patients
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
How should clinicians select from among
available antireflux medications?
 No real efficacy differences within same medication class
 Modest superiority for esomeprazole vs. other PPIs
 Dexlansoprazole can be dosed at any time of day
 Immediate release omeprazole-sodium bicarbonate may
improve nighttime gastric pH compared to other PPIs
 Few data to support high- or double-dose of any PPI other
than acute healing of esophagitis
 Idiopathic side effects (diarrhea, constipation, headache)
may occur with one PPI but not another
 Pregnancy may affect medication selection
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
How long should patients continue
pharmacologic therapy for GERD?
 Complicated GERD
 Erosive disease, stricture, or Barrett esophagus
 Indefinite PPI maintenance therapy avoids relapse
 Decreases risk of dysplasia development
 Uncomplicated GERD
 Consider maintenance therapy if symptoms recur
 Make every attempt to taper and minimize medication use
 Manage with intermittent or on-demand PPI therapy
 Consider ‘step-down’ approach by using H2RAs on-demand
 Balance symptom control against cost, inconvenience, and
potential side effects of chronic PPI use
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
What are the adverse effects of long-term
acid suppression therapy?
 Gastric acid aids in vitamin and mineral absorption
 PPIs may increase iron deficiency or pernicious anemia risk
 PPIs may increase hip fracture risk
 Gastric acid aids in destruction of ingested potentially
pathogenic bacteria
 PPIs may increase risk for enteric infections (C. difficile)
 Pneumonia may be more common during sh-term PPI use
 PPI + clopidogrel may increase cardiovascular risk
 Long-term PPI use could predispose to intestinal
metaplasia or gastric malignancy
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
When should clinicians consider surgical
therapy for GERD?
 Surgical anti-reflux therapy: laparoscopic fundoplication
 Long-term treatment option with similar efficacy to
medical Rx for some
 Those with typical symptoms who respond to PPIs but wish
to discontinue use
 Those with continued symptoms / damage despite PPIs
 Evidence doesn’t support surgery for other patients
 Those with atypical symptoms or who don’t respond to PPIs
 Those with Barrett esophagus who wish to prevent cancer
 Bariatric surgery may be a treatment option for morbidly
obese patients with GERD
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
Is it necessary to evaluate for Barrett
esophagus periodically?
 Estimated to occur in up to 10% with chronic GERD
 Annual risk of esophageal adenocarcinoma is low
(≈ 0.12%) even in patients with Barrett esophagus
 Consider endoscopy for men >50 who have had GERD
≥5 yrs and who are overweight or have other risk factors
 No role for periodic screening endoscopy in patients
with uncomplicated GERD
 No role for periodic screening endoscopy in patients
with normal index endoscopy performed for above
indications
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
How should clinicians manage patients
once Barrett esophagus is present?
 Periodic surveillance can lead to earlier cancer Dx
 In absence of dysplasia, use endoscopy every 3-5 years
 Continue PPIs
 Document presence of absence of dysplasia
 Risk of progression to adenocarcinoma 0.1% to 0.5% per
patient-year for non-dysplastic Barrett esophagus
 Risk of progression to adenocarcinoma 5%-20% for
dysplastic tissue
 Data support endoscopic eradication therapy with radiofrequency ablation for high- and low-grade dysplasia
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
How frequently should clinicians see
patients with GERD and what are the
components of good follow-up?
 At least annually if chronically taking PPIs or H2RAs
 Assess symptom character, frequency, and severity
 Check for alarm signs
 Provide counseling to reduce exacerbating factors
 Taper medical therapy to lowest effective dose
 Reassure patients that risk for developing complicated
disease is very low in uncomplicated GERD
 Even with continued symptoms of heartburn and reflux
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
When should clinicians consider
gastroenterology referral for treatment of a
patient with GERD?
 Alarm symptoms develop in context of previously wellmanaged GERD
 Patients are interested in anti-reflux procedures
 Patients are at high risk of Barrett esophagus and
adenocarcinoma
 Patients have prior documented severe esophagitis or
Barrett esophagus
 Most gastroenterologists happy to assist in all aspects
of care
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
CLINICAL BOTTOM LINE: Treatment...
 Nonmedication treatment
 Weight loss for obese persons
 Head-of-bed elevation for people with reflux at night
 Dietary changes not universally recommended
 Medication treatment
 Initial Rx: PPIs once daily (30-60 mins before meal) for 8 wks
 For those responsive to PPIs, taper to lowest effective dose
 For those unable to taper or with significant erosive disease,
Barrett esophagus, or peptic stricture Hx: Continue PPIs
 H2RAs and antacids may be used for occasional symptoms
 Surgery is an effective option for some patients with GERD
 Refer for specialty evaluation when alarm symptoms develop
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.