eMedicine Feature Series

Gastroesophageal Reflux Disease Newsletter _________ Series 1, Issue 9, 2007

LARYNGITIS AND GERD

Andrea Duchini, MD
The Methodist Hospital

Gulchin A Ergun, MD
The Methodist Hospital

INTRODUCTION

Classical manifestations of gastroesophageal reflux disease (GERD) are heartburn and regurgitation with or without any or a combination of the alarm symptoms of dysphagia, odynophagia, weight loss, anemia, and bleeding. In recent years, various atypical extra-esophageal symptoms have become established as manifestations of GERD. These symptoms include chronic cough, hoarseness, globus sensation, throat clearing, throat soreness, sialorrhea, hiccup, belching, halitosis, wheezing, and noncardiac chest pain. These symptoms have been established as manifestations of GERD that lead to a wide variety of related conditions secondary to the primary mechanism of reflux, including laryngitis, pharyngitis, laryngeal stenosis, laryngeal cancer, sleep apnea, sinusitis, dental erosion, asthma, pulmonary fibrosis, and microaspiration.

EPIDEMIOLOGY

The aforementioned atypical symptoms occur frequently in patients with GERD. In a recent study from Europe, atypical symptoms were predominant in up to 27% of patients who consulted a gastroenterologist for GERD.¹ In a group from Spain, typical and atypical symptoms coexisted in up to 79% of patients.² Frequency distribution ranges from 1% for sialorrhea, 4.5% for hiccups, 15.5% for chest pain, 23% for hoarseness, 24.4% for cough, to 38% for globus sensation. Elderly patients (>65 yrs) frequently present with atypical symptoms, particularly chest pain and respiratory complications.³ Since the prevalence of GERD in the Western population ranges from 10-30%,⁴ atypical symptoms are more likely to be encountered on a daily basis in busy practices throughout the United States.

LARYNGEAL SYMPTOMS

Chronic or intermittent hoarseness, excessive throat clearing, recurrent throat pain in the absence of infection, throat discomfort during swallowing (cervical dysphagia), vocal fatigue, dysphonia, and a lump in the throat (globus sensation) are all examples of laryngeal symptoms. These symptoms have been noted as some of the most common reasons for patients to visit an otolaryngologist. However, the prevalence of reflux in conditions such as laryngitis is not known with any degree of certainty based on traditional definitions, as the typical symptoms of GERD (ie, heartburn and regurgitation) have been shown in some studies to be present in less than 50% of patients with established otolaryngologic disorders and suspected GERD.⁵ Since patients with throat symptoms often do not report heartburn, physicians depend on various diagnostic tests, including the empiric use of acid suppressive medications such as proton pump inhibitors (PPIs), barium swallows, upper endoscopy, ambulatory pH level monitoring, and laryngoscopy, in an effort to ascribe the development of laryngitis or other laryngeal symptoms to acid exposure.

DIAGNOSTIC TESTING FOR GERD-RELATED LARYNGITIS

Up to 10% of patients seen by otolaryngologists report symptoms that may be related to GERD. The symptoms of many of these patients do not respond when treated empirically with medications specific for reflux disease, such as aggressive acid suppression by twice-daily PPIs. This situation prompts the need for further diagnostic testing to help establish the possibility of reflux as the etiology of the symptoms in many cases. Unfortunately, no diagnostic test can accurately identify patients whose laryngeal symptoms are caused by acid exposure. This is primarily because most tests lack the sensitivity required to make the diagnosis. This situation has led to controversy among specialties regarding how to best diagnose this problem.

The barium swallow has fallen out of favor because of poor sensitivity in diagnosing any but the most severe esophagitis, a degree of esophageal involvement that exists in only 25-35% of patients with GERD.⁽⁶⁾ The barium swallow probably has no role in evaluating a patient with suspected reflux laryngitis. The utility of endoscopy in the evaluation of the patient with suspected reflux laryngitis is limited by a low sensitivity; the likelihood of an abnormal endoscopic finding is only about 25%.⁽⁷⁾ Even treatment trials have demonstrated that most patients (70%) have a normal esophagus at study entry, highlighting the difficulty of using upper endoscopy as a test in demonstrating reflux as a cause of laryngeal symptoms or findings.⁽⁷⁾ Ambulatory pH level monitoring that examines either distal or proximal esophageal acid exposure is also not sensitive in detecting GERD. While sensitivity for distal acid exposure is about 70-80%, the sensitivity of the proximal probe is about 50-55%.⁽⁸⁾ Even hypopharyngeal pH level monitoring is only 48% sensitive when it comes to detecting GERD, and no agreement exists as to how much reflux is normal in the hypopharynx.^(9,10) Hence, pretherapy ambulatory pH level monitoring has been ineffective in identifying patients with reflux-induced laryngitis and in predicting response to therapy.

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The role of laryngoscopy and the specificity of laryngeal signs for GERD in establishing reflux as the etiology of laryngitis have been subject to much recent attention. In a recent prospective study of 1,209 patients, an examination of the laryngopharyngeal area was videotaped during upper endoscopy and reviewed by both gastroenterologists and an otolaryngologist blinded to endoscopy results. Patients with reflux were compared with control subjects. No significant differences were found between the 2 groups, and more than 85% of patients displayed at least one sign of irritation, most commonly posterior pharyngeal wall abnormalities such as cobblestoning, erythema, and edema.⁽¹¹⁾

Although otolaryngologists often consider various laryngoscopic findings to be diagnostic of reflux-induced laryngitis, recent studies have challenged the specificity of a number of these findings.^(12,13) Taken together, these laryngoscopic studies suggest that what have been previously suggested as “classical findings” of reflux laryngitis occur infrequently. These findings of “classic posterior laryngitis” on the posterior aspect of the vocal cords include diffuse laryngitis, which may be either a simple hyperemia or a hyperplastic response of the laryngeal mucosa and keratosis (ie, white lesions typified by keratin excess). Additionally, early research found inflammatory lesions associated with extended exposure to gastric acid to be the “contact ulcer,” which occurs over the vocal processes on the medial edge of the vocal cord, and vocal cord granuloma.^(14,15) Thirty years later, more subtle and subjective findings, such as edema or erythema, on the vocal cords were suggested as the most common findings associated with reflux but, despite symptomatic severity, were not specific for GERD-related laryngitis.⁽⁵⁾

MANAGEMENT OF PATIENTS WITH GERD-RELATED LARYNGITIS

If posterior laryngitis is the consequence of acid injury, then it should improve with empiric antireflux treatment. Despite this hypothesis, only limited controlled data are available regarding the effectiveness of antireflux therapy in treating posterior laryngitis. Eight randomized controlled trials have evaluated the effect of acid suppression in patients with suspected reflux laryngitis.^16-23 Of these studies, results have been mixed. In a meta-analysis of PPIs for suspected reflux laryngitis, Qadeer and colleagues pooled the data from 8 separate trials and examined the proportion of patients with a 50% or larger reduction in self-reported laryngeal symptoms.²⁴ They concluded that PPI therapy for suspected reflux laryngitis did not result in symptom reduction when compared with placebo. Furthermore, no clinical predictors of PPI response were identified in this analysis.

Since specific laryngeal signs or specific testing to identify this patient group are not yet available, clinicians are forced to use empiric therapy as a method to identify patients whose symptoms are caused by GERD. Most clinicians would agree that if a patient is suspected of having reflux-induced laryngitis, best practice would include the initiation of PPI therapy twice a day for 3-4 months. If the symptoms respond, then the clinician should attempt to titrate the dose as low as possible while still keeping symptoms controlled. If symptoms persist despite PPI therapy, then the clinician should consider pH level and impedance testing to identify any persistent acid exposure or nonacid reflux. If acid exposure is found, more aggressive acid suppressive therapy should be pursued in addition to searching for causes of abnormal acid production. If non-acid reflux is found, consideration may be given to an antireflux surgical repair. If the diagnostic test results do not suggest acid reflux as the etiology of the laryngitis, the clinician should search for other confounding causes of laryngeal irritation, such as allergies, sinus disease, pulmonary disease, smoking, or vocal abuse.

CONCLUSION

The classically described manifestations of GERD are heartburn and regurgitation with or without any alarm symptoms. In recent years, extra-esophageal symptoms such as chronic cough, hoarseness, globus sensation, throat clearing, and throat soreness have become established as manifestations of GERD. These symptoms have led to the establishment of a percentage of cases of certain other medical conditions as secondary to GERD. These other medical conditions especially include those related to the larynx, such as laryngitis, pharyngitis, laryngeal stenosis, and laryngeal cancer. Diagnostic and treatment options for patients with GERD have advanced dramatically over the last few years, but much progress still needs to be made before clinicians can easily diagnose and treat patients with otolaryngologic conditions that are the results of GERD.

REFERENCES

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24. Qadeer MA, Phillips CO, Lopez AR, et al. Proton pump inhibitor therapy for suspected GERD-related chronic laryngitis: a meta-analysis of randomized controlled trials. Am J Gastroenterol. 2006;101(11):2646-54.

AUTHOR SPOTLIGHT

	Andrea Duchini, MD Associate Medical Director of Liver Transplantation Department of Surgery The Methodist Hospital
	Gulchin A Ergun, MD Director, The Methodist Hospital Reflux Center The Methodist Hospital Clinical Associate Professor of Medicine Baylor College of Medicine