Laryngopharyngeal reflux is different from classic gastroesophageal reflux disease.

Abstract

The patterns, mechanisms, manifestations, and treatment of laryngopharyngeal reflux (LPR) and gastroesophageal reflux disease (GERD) differ, and the gastroenterology model of reflux disease does not apply to LPR. LPR patients have head and neck symptoms, but heartburn is uncommon. Consequently, LPR is often called silent reflux. LPR patients have predominantly upright (daytime) reflux and normal esophageal motility; most do not have esophagitis, which is the diagnostic sine qua non of GERD. Moreover, the laryngopharyngeal epithelium is far more susceptible to reflux-related tissue injury than is the esophageal epithelium. Because of these differences, treatment algorithms for LPR and GERD vary.

Introduction

The term reflux literally means backflow (Latin, re back + fluere to flow). The term gastroesophageal reflux (GER) refers to the backflow of stomach contents into the esophagus. GER may be physiologic; indeed, the occurrence of as many as 50 GER episodes a day, usually after meals, is accepted as being within the normal range. (1) Gastroesophageal reflux disease (GERD) is a clinical term that refers to GER that is excessive and that causes symptoms and tissue damage, usually heartburn and esophagitis. (1)

Laryngopharyngeal reflux (LPR) refers to the backflow of stomach contents into the throat--that is, into the laryngopharynx. In most cases, patients who see gastroenterologists have GERD, and patients who have LPR see otolaryngologists. During the past 25 years, it has become increasingly apparent that LPR differs in many ways from classic GERD. (1-10)

How is LPR different from GERD? Patients with LPR appear to have different

symptoms, findings, and patterns of reflux, as well as different diagnostic criteria and responses to treatment than do patients with GERD (table). (1-16)

Symptoms of LPR

Patients with LPR usually deny symptoms of heartburn and regurgitation. (1-3,8-10) In a landmark article, Ossakow et al compared the symptoms and findings of reflux disease in two discrete groups of reflux patients: otolaryngology (ORL) patients (n = 63) and gastroenterology (GI) patients (n = 36). (2) They reported that hoarseness was present in 100% of the ORL patients and 0% of the GI patients, but heartburn was present in 89% of the GI patients and only 6% of the ORL patients. Other authors have also reported a relatively low incidence of heartburn as a symptom in ORL patients with LPR; in no series did more than 50% of patients with LPR have heartburn. (1,4,8,9)

Instead of GI symptoms, most LPR patients have throat symptoms. In a large series of ORL patients with LPR, 71% of patients had dysphonia, 51% had chronic cough, 47% had globus pharyngeus, 42% experienced chronic throat clearing, and 35% had dysphagia. (1)

Mechanisms and reflux patterns of LPR and GERD

Why do LPR patients usually deny heartburn? In the late 1980s, ambulatory 24-hour double-probe (simultaneous esophageal and pharyngeal) pH monitoring was first used to study ORL patients with LPR. Wiener et al studied 32 LPR patients with hoarseness and found that although pH monitoring was abnormal in 78%, esophageal manometry was normal in 100% and findings on esophagoscopy with biopsy were normal in 72%. (3) Koufman found that only 18% (23/128) of ORL patients with LPR had any findings of esophagitis on barium esophagography. (1)

Most LPR patients do not have esophagitis, which is the diagnostic sine qua non of GERD. (1-3,8,9) In a recent prospective study of 58 ORL patients with pH-documented LPR, only 12% (7/58) had esophagitis and another 7% (4/58) had Barrett's esophagus--thus, 81% had normal esophageal epithelium on esophagoscopy with biopsy. (8)

It is important to note that because patients with LPR usually do not have esophagitis, traditional diagnostic tests for GERD lack sensitivity and specificity for LPR. The diagnosis of LPR depends on symptoms, laryngeal findings, and the results of pH monitoring (the details of LPR diagnostics are covered elsewhere in this supplement).

In summary, it appears that the mechanisms of LPR are different from those of GERD. LPR patients are predominantly upright (daytime) refluxers, while GERD patients are predominantly supine (nocturnal) refluxers. Patients experience prolonged periods of acid exposure in GERD but not in LPR. (1,2) In addition, patients with GERD have dysmotility and prolonged esophageal acid clearance, while those with LPR do not. (1,7) It is believed that the primary defect in GERD is lower esophageal dysfunction, whereas the primary defect in LPR might be upper esophageal sphincter dysfunction. (1,17,18) It is likely that these differences in mechanisms and patterns account for the differences in symptoms and manifestations of LPR and GERD. It is important to note that while most patients with LPR do not have GERD, some patients do have both.

Clinical implications of cell biology in LPR

Compared with the esophagus, the larynx is exquisitely sensitive to peptic injury. (1,19-22) According to normative pH-monitoring data, the upper limit of normal (mean plus two standard deviations) for the total number of esophageal reflux episodes per 24 hours is approximately 50. (1,14) In contrast, it has been shown experimentally that as few as three reflux episodes per week can result in significant laryngeal damage. (1,19) It takes much less acid/pepsin exposure to cause tissue damage in the pharynx and larynx than in the esophagus. (22) In a manner of speaking, the larynx is approximately 100 times more sensitive to peptic injury than is the esophagus.

The esophagus has certain protective mechanisms that prevent mucosal injury (bicarbonate production, mucosal barrier, and peristalsis), whereas the pharynx and larynx do not. (2) Both LPR and GERD are caused by mucosal injury from acid and pepsin exposure. (1,19,21-23) Actually, activated pepsin causes much more tissue damage than does acid alone; however, some acid must be present to activate pepsin. (1) Unlike esophageal epithelium that exhibits cell injury at a pH level of less than 4.0, peptic damage (cell injury) to laryngeal epithelium occurs at pH levels up to 5.0. (1,21-23)

As a consequence of the relative laryngeal hypersensitivity to reflux damage, even if a patient does not have enough reflux to develop esophagitis (and its principal symptom, heartburn), he or she might still develop symptomatic LPR. This laryngopharyngeal sensitivity has important implications for the treatment of LPR.

Treatment of LPR

The treatment of LPR usually must be more aggressive and prolonged than the treatment of GERD. The traditional treatment of GERD includes dietary and lifestyle modifications and the use of an antacid, an [H.sub.2] antagonist, and/or a once-daily proton-pump inhibitor (PPI). (1) Such treatment fails to control LPR in as many as 50% of LPR patients. (1) In many cases of LPR, the GERD dosage is inadequate and the duration of therapy is too short. (10)

Many clinicians believe that a therapeutic trial of antireflux therapy of several weeks' duration is adequate, but that is not the case. Because the larynx is far more susceptible to injury from the refluxate than is the esophagus, acid must be suppressed as much as possible around the clock. To optimize antireflux coverage for LPR, medication should be taken when the patient arises in the morning and again late in the afternoon, prior to the evening meal. Patients with long-standing LPR often require months of treatment with twice-daily (or more often) PPI therapy to resolve their symptoms. (10)

PPIs are not effective in all reflux patients, especially with once-daily dosing. Some studies of once-a-day dosing have found significant failure rates, while others have demonstrated that the average morning dose of a PPI lasts an average of only about 14 hours. (11,16,24-26) LPR treatment failures have been seen even with high-dose PPI therapy; a medical treatment failure rate of 10% in LPR patients receiving PPIs (up to four times per day) has been reported. (16)

Unlike GERD symptoms, LPR symptoms do not resolve in a matter of days or weeks; often it takes several months for resolution to occur. One follow-up study revealed that fewer than half of patients treated with PPIs were completely well (all symptoms and findings resolved) 4 months after the initiation of treatment. (27)

Despite the fact that PPIs are not completely effective in all patients, they are still considered to be the cornerstone of treatment for patients with moderate to severe LPR. A recent position statement on LPR of the American Academy of Otolaryngology--Head and Neck Surgery recommended a minimum of twice-daily dosing for an initial course of 6 months. (10)

Table

Summary of typical differences between GERD and LPR *

                                    GERD  LPR

Symptoms

Heartburn and/or regurgitation      ++++   +
Hoarseness, cough, dysphagia,        +    ++++
 globus

Findings

Esophagitis                         ++++   +
Laryngeal inflammation               +    ++++

Test results

Erosive or Barrett's esophagitis    +++    +
Abnormal esophageal pH monitoring   ++++   ++
Abnormal pharyngeal pH monitoring    +    ++++
Esophageal dysmotility              +++    +
Abnormal esophageal acid clearance  ++++   +

Pattern of reflux

Supine (nocturnal) reflux           ++++   +
Upright (daytime) reflux             +    ++++
Both                                 +     ++

Response to treatment

Effectiveness of dietary and         ++    +
  lifestyle modifications
Successful treatment with a         +++    +
 single-dose PPI +
Successful treatment with a         ++++  +++
 twice-daily PPI

* This table represents the author's integration of three sources: (1)
available data in the gastroenterology and otorhinolaryngology
literature, (2) discussions of these specific issues with
gastroenterologists and otorhinolaryngology colleagues, and (3) clinical
experience.

+ PPI = proton-pump inhibitor.

References

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