What are the extra-gastric (beyond the stomach) manifestations of gastroesophageal reflux disease (GERD)?

Extraesophageal Manifestations of GERD

The primary extraesophageal manifestations of GERD include laryngitis, chronic cough, asthma, and dental erosions, with additional possible manifestations including pulmonary fibrosis, sinus disease, ear disease, post-nasal drip, and throat clearing. 1

Recognized Extraesophageal Manifestations

The 2023 AGA guidelines explicitly identify the following conditions as potential extraesophageal reflux (EER) manifestations 1:

Primary Manifestations (Strongest Evidence)

• Laryngitis (laryngeal hoarseness and dysphonia) 1
• Chronic cough 1
• Asthma 1
• Dental erosions/caries 1

Additional Recognized Manifestations

• Pulmonary fibrosis 1
• Sinus disease 1
• Ear disease 1, 2
• Post-nasal drip 1, 3
• Throat clearing 1

Critical Clinical Context

Absence of Typical Symptoms

Up to 75% of patients with extraesophageal manifestations may not experience heartburn or regurgitation, placing the diagnostic burden entirely on the clinician to recognize GERD as a potential contributor 4. This is a critical pitfall—the absence of typical reflux symptoms does not exclude GERD as the underlying cause 2.

Multifactorial Nature

These conditions are often multifactorial, meaning GERD may be a contributing factor rather than the sole cause 1. The relationship between GERD and extraesophageal symptoms can be bidirectional—conditions like asthma may themselves worsen reflux 3.

Pathophysiologic Mechanisms

Extraesophageal symptoms occur through two distinct pathways 3, 2:

• Direct reflux pathway: Gastric acid refluxes through the lower esophageal sphincter, continues proximally through the upper esophageal sphincter into the pharynx and potentially the nasopharynx, documented by dual-pH probe monitoring 3
• Reflex pathway: Acid in the esophagus triggers vagally-mediated airway reactions through neurologic mechanisms without requiring direct contact with the upper airway 3, 2

Diagnostic Approach

Initial Assessment

Gastroenterologists should actively inquire about laryngitis, chronic cough, asthma, and dental erosions in all GERD patients to determine whether GERD contributes to these conditions 1.

Testing Strategy

• Consider objective testing BEFORE initiating PPI therapy in patients with extraesophageal manifestations who lack typical GERD symptoms, as 50-60% will not have GERD as the underlying cause 4, 2
• No single diagnostic tool can conclusively identify GERD as the cause of extraesophageal symptoms 1
• Diagnosis requires global clinical assessment integrating symptoms, endoscopy findings, reflux monitoring results, and treatment response 1, 4
• pH-impedance monitoring off PPI is the preferred test, as it detects both acid and non-acid reflux episodes that can cause extraesophageal symptoms 4, 2

Multidisciplinary Collaboration

A multidisciplinary approach is essential because extraesophageal manifestations require input from non-gastroenterology specialties (otolaryngology, pulmonology, dentistry) 1. Results from bronchoscopy, thoracic imaging, and laryngoscopy should be incorporated into the diagnostic assessment 1.

Treatment Considerations

PPI Trial Approach

• For patients WITH typical GERD symptoms: Initial single-dose PPI trial, titrating up to twice daily, is reasonable 1
• Extraesophageal manifestations typically require 8-12 weeks of treatment, longer than typical GERD 4

Critical Pitfall

Symptom improvement on PPI therapy may result from mechanisms other than acid suppression (such as anti-inflammatory effects) and should not be regarded as confirmation that GERD is the cause 1, 2.

When PPI Fails

If one PPI trial fails (up to 12 weeks), pursue objective testing for pathologic reflux rather than trying additional PPIs, as further empiric trials are low yield 1, 3, 2. Continued PPI therapy in PPI-unresponsive patients with extraesophageal symptoms is not recommended 5.

Alternative Therapies

Alternative treatment methods beyond acid suppression may serve a role in managing extraesophageal symptoms, including lifestyle modifications, alginate-containing antacids, upper esophageal sphincter compression devices, cognitive-behavioral therapy, and neuromodulators 1.

Surgical Considerations

Lack of response to PPI therapy predicts lack of response to anti-reflux surgery and should be incorporated into surgical decision-making 1, 2. Shared decision-making is essential before referral for anti-reflux surgery, and patients must have clear, objectively defined evidence of GERD 1.