The Laryngoscope
Lippincott Williams & Wilkins, Inc., Philadelphia
2002 The American Laryngological,
Rhinological and Otological Society, Inc.
Association of Laryngopharyngeal
Symptoms With Gastroesophageal
Reflux Disease
Stefan Tauber, MD; Manfred Gross, MD; Wolfgang J. Issing, MD
Objectives: The prevalence of gastroesophageal re-
flux disease (GERD) in patients with laryngopharyn-
geal disorders is probably greater than realized. Study
Design: Prospective study. Methods: To investigate the
incidence of gastroenterological diseases including
GERD in patients complaining of nonspecific laryngo-
pharyngeal symptoms, laryngological examinations
and gastroenterological evaluation with esophagogas-
troduodenoscopy were performed in 30 patients who
refused to undergo 24-hour pH monitoring. Therapeutic
intervention by behavioural and dietary modifications,
antireflux medication, and eradication of Helicobacter
pylori were assessed for changes in laryngeal findings
and relief of symptoms. Results: Posterior laryngitis was
present in 26 patients and in 19 of them was accompa-
nied by erythema and edema of the interarytenoid re-
gion. Gastroenterological diseases such as GERD (43%),
hiatal hernia (43%), and Helicobacter pyloripositive an-
trum gastritis (23%) were confirmed in 22 (73%) cases by
esophagogastroduodenoscopy and histological exami-
nation of biopsy specimens. Medical antireflux treat-
ment and eradication of Helicobacter pylori resulted in
a remarkably therapeutic success rate of 90% because
there was resolution of laryngopharyngeal symptoms
and laryngeal findings in 20 of 22 patients with gastro-
enterological diseases for the mean follow-up period of
8 months. Conclusions: Laryngopharyngeal symptoms
can be predictors of gastroesophageal diseases and
GERD because the most frequent underlying cause is
supposed to be associated with posterior laryngitis.
Medical antireflux treatment is effective for relief of
symptoms and mucosal healing of posterior laryngitis.
Key Words: Gastroesophageal reflux disease, gastritis,
hiatal hernia, laryngopharyngeal symptoms, dyspha-
gia, hoarseness, globus pharyngeus, Helicobacter pylori.
Laryngoscope, 112:879886, 2002
From the Departments of OtolaryngologyHead and Neck Surgery
(S.T., W.J.I.) and Internal Medicine, Gastroenterology Service (M.G.),
Medizinische Poliklinik, Ludwig-Maximilians-University Munich, Munich,
Germany.
Editors Note: This Manuscript was accepted for publication November
26, 2001.
Send Correspondence to Wolfgang J. Issing, MD, Department of
OtolaryngologyHead and Neck Surgery, University of Munich, Mar-
chioninistreet. 15, 81377 Munich, Federal Republic of Germany. E-mail:
wissing@hno.med.uni-muenchen.de
Laryngoscope 112: May 2002
INTRODUCTION
It has been well documented that gastroesophageal
reflux disease (GERD), defined as retrograde flow of gas-
tric contents into the esophagus, frequently leads to dis-
orders in organs other than the esophagus .1,2 In contrast
to the typical presentation of classic GERD with heart-
burn and distal esophageal acid regurgitation after tran-
sient relaxation of the lower esophageal sphincter, extrae-
sophageal reflux disease, termed laryngopharyngeal
reflux (LPR), often results in atypical manifestations with
oral, pharyngeal, laryngeal, and pulmonary disor-
ders.1,3 8 Laryngopharyngeal reflux is known to contrib-
ute to posterior acid laryngitis and laryngeal contact ul-
ceration or granuloma formation, laryngeal cancer,
chronic hoarseness, pharyngitis, asthma, pneumonia, noc-
turnal choking, and dental diseases.3 6,8 14 Mainly, those
laryngopharyngeal manifestations of extraesophageal re-
flux disease are believed to be caused by proximal esoph-
ageal reflux of gastric contents with direct contact and
subsequent injury of the pharyngeal or laryngeal mucosal
surfaces. However, there is increasing evidence that not
only is the anatomical proximity of the larynx to the
hypopharynx and proximal esophagus responsible for
LPR-induced injuries to the pharyngeal mucosae, but also,
it is acid reflux inside the distal esophagus itself that
stimulates vagally mediated reflexes leading to the disor-
der (e.g., reflex bronchospasm, coughing).1,4,6 8,14
In addition to the characteristic gastroenterological
symptoms of GERD (e.g., heartburn and regurgitation4),
LPR-associated disorders are of diagnostic interest and
are being increasingly recognized. Because many patients
are not aware of GERD as a possible causative factor for
their varying medical complaints, they may present to
cardiologists, pulmonologists, and primary care physi-
cians. Frequently, patients with GERD present to otolar-
yngologists with symptoms such as dry or sore throat,
globus sensation, hoarseness, chronic cough, dysphagia, or
buccal burning.14 However, otolaryngological examina-
tions merely demonstrate striking pathological findings,
and the underlying disease of LPR is not primarily diag-
nosed.9 Frequently, the misdiagnosed patients are com-
monly treated for (nonallergic) rhinitis with postnasal
drip, nonspecific rhinopharyngitis, or recurrent sinusitis.
Tauber et al.: Gastroesophageal Reflux Disease
879
 The aim of the current prospective study was to de-
termine in patients presenting with various laryngopha-
ryngeal symptoms to the otolaryngologist the prevalence
of gastrointestinal diseases with evaluation of the success
rates for specific therapies. The hypothesis of the investi-
gation was that even if extraesophageal symptoms of
GERD and other gastrointestinal (GI) tract diseases are
merely present, laryngopharyngeal disorders are often the
first symptoms patients notice.
PATIENTS AND METHODS
Thirty patients presenting to the Department of Otolaryn-
gology (Ludwig-Maximilians-University Munich, Germany) be-
tween November 1998 and November 1999 were included in the
study (Table I). Primary complaints of all patients were rhino-
pharyngeal or laryngeal disorders, or both, for 3 months or longer
(Table II). The patients were not receiving any medical treatment
for those symptoms at the time of presentation and did not relate
their symptoms to any acute gastroenterological disease. The
group consisted of 16 men (53%) and 14 women (47%) with a
mean age of 51.3 15.2 (mean standard deviation) years.
Twenty patients (67%) were nonsmokers, 2 patients (7%) were
moderate smokers, and 8 patients (27%) were heavy smokers,
smoking more than one pack a day (Table I). Alcohol intake was
variable but moderate in the majority of patients. Sixteen pa-
tients had a positive history of gastroenterological disease includ-
ing gastritis (n 11), gastric or duodenal ulcers (n 2), and
GERD (n 3), with their last acute symptomatic episodes having
been treated more than 3 years earlier.
Patients were initially evaluated by complete medical his-
tory and physical examination with clinical examination of head
and neck. Nasopharyngeal endoscopy and endoscopic laryngos-
copy, allergy testing, and a Waters view x-ray or computed to-
mography scan of the paranasal sinuses were performed on all
patients. Laryngeal examinations were performed by direct rigid
angulated laryngoscopy (magnifying the view of the involved
areas at 7090) and fiberoptic laryngoscopy with careful and
complete assessment (function, shape, color, appearance) of the
mucosa lining the vocal and ventricular folds, the laryngeal car-
tilages, the posterior commissure, the interarytenoid area, and
hypopharyngeal regions. Laryngeal lesions were diagnosed by the
presence of inflammation, edema, ulceration, and granuloma for-
mation. Laryngeal changes with erythema of the posterior vocal
folds and arytenoid area were graded as posterior laryngitis.
Mucosal changes of posterior laryngitis were often accompanied
by edema of the vocal folds and inflammatory reactions with or
without a cobblestone appearance of the interarytenoid area.
Informed consent was obtained before treatment. Gastroen-
terological evaluation was performed with esophagogastroduode-
noscopy (EGD), and the endoscopist was blinded for the laryngeal
findings. Gastric biopsy specimens were taken for histological
TABLE I.
Patient Characteristics.
Patients n 30
Mean age 51.3 15.2 y
Sex M:F 1.1 (16 male, 14 female)
Duration of symptoms 3 months
Nonsmokers 20
Smokers 10 (2 moderate, 8 heavy)
Allergic rhinitis 5 Inflammatory disorders of the nose and the parana-
Mean follow-up 8 2 mo
Laryngoscope 112: May 2002
880
examination and analysis of infection with Helicobacter pylori.
Esophagogastroduodenoscopy is a well-established diagnostic
test to evaluate mucosal injury and define the severity of esoph-
agitis. In addition, it has been recommended that the diagnosis of
GERD (and eventually LPR) should be confirmed by 24-hour pH
monitoring.3,6,8 Nevertheless, in the present study, pH monitor-
ing was not performed because patients refused to undergo this
procedure.
The prevalence of gastroenterological diseases in the
present study was compared with age- and gender-matched pa-
tients who underwent EGD for various reasons other than laryn-
gopharyngeal symptoms. The main indications for EGD in those
patients were dyspeptic symptoms, ulcer-type epigastric pain,
noncardiac chest pain, nausea, vomiting, and the like.
Patients were followed up for 6 to 10 months at 2-month
intervals with head and neck examinations including direct and
indirect laryngoscopy and were questioned regarding the spec-
trum of their symptoms. In patients with H pyloripositive an-
trum gastritis eradication was performed by medical triple regi-
men with 20 mg omeprazole twice daily, 400 mg metronidazole
twice daily, and 250 mg clarithromycin twice daily for at least 10
days. Patients with reflux disease or hiatal hernia, or both, re-
ceived 20 (for grade I reflux disease) to 40 (for grades IIIV reflux
disease) mg omeprazole daily for at least 4 weeks, depending on
the severity of the mucosal finding according to Savary.15 In five
cases of persisting laryngopharyngeal symptoms and laryngeal
findings after a 4-week period of treatment, the intake of ome-
prazole was extended to a duration of 4 months. Because of good
clinical response in the past, two patients who had GERD with
hiatal hernia preferred to be treated with 150 mg ranitidine
(histamine type 2 [H2] blocker) twice a day. All patients were
advised to follow general antireflux precautions including elevat-
ing the head of the bed and not eating for 2 or 3 hours before
bedtime.
In cases with regular results of EGD and histological exam-
inations (n 8), medical treatment on trial with 150 mg raniti-
dine twice daily was suggested to all patients. However, only
three patients accepted treatment with ranitidine; other patients
preferred to follow general antireflux precautions.
RESULTS
Patients and Symptoms
The patients presented with varying oral, rhinopha-
ryngeal, laryngeal, and pulmonary symptoms lasting for
at least 3 months. They included rhinopharyngeal and
laryngeal manifestations such as dysphagia (n 20), sen-
sation of globus pharyngeus (n 20), hoarseness (n 16),
odynophagia (n 15), sore throat (n 14), recurrent or
chronic postnasal drip and throat mucus (n 11), cough
(n 8), throat clearing (n 6), laryngospasm (n 3), and
voice fatigue (n 2). In addition, some patients com-
plained of characteristic reflux symptoms such as heart-
burn (n 11) or acid regurgitation (n 1) (Table II). For
pretherapeutic and post-therapeutic comparison, the pa-
tients were asked to characterize the degree of their symp-
toms as mild, moderate, or severe, according to the pro-
posed clinical classification of symptom severity.16 Results
are shown for all patients with confirmed GI diseases in
Table IIA.
Otolaryngological Examination
sal sinuses could not be confirmed by history, nasal en-
doscopy, and Waters view x-ray or computed tomography
Tauber et al.: Gastroesophageal Reflux Disease
scan of the paranasal sinuses in all patients. Allergic
rhinitis has been diagnosed and treated in 5 of 30 pa-
tients. The laryngopharyngeal findings were subtle be-
cause different diseases of the mucosae in 28 cases could
be diagnosed only by meticulous examination (Table III).
Frequently, posterior laryngitis with mild to moderate
pathological change of the posterior part of the vocal folds
(n 26) was found. Posterior laryngitis was often accom-
panied by erythema and edema of the arytenoid cartilages
and the posterior commissure (n 19); in a few cases,
even a cobblestone appearance of the interarytenoid area
was observed. In patients with GERD (n 13), posterior
laryngitis was present in 11 (85%) cases, which was com-
bined with moderate interarytenoid erythema in 9 (69%)
patients. Hyperplastic laryngitis was diagnosed in one
(8%) patient with GERD. In non-GERD cases (patients
either without any gastroenterological disease or with ei-
ther hiatal hernia or H pyloripositive antrum gastritis or
both) the erythematous and edematous interarytenoid
changes of posterior laryngitis seemed to be less frequent
(59%) than in patients with GERD (69%). There was no
statistical significance between those results. Typical pre-
therapeutic laryngoscopic findings with mild posterior lar-
yngitis (Fig. 1) and severe posterior laryngitis with aryte-
noid and interarytenoid erythema (Fig. 2) in the
endolarynx are shown.
Gastroenterological and Medical Examination
Eight of 30 patients showed regular mucosae of the
gastroenterological tract without any GI tract disease,
which was confirmed by EGD and biopsy specimens. Gas-
troenterological diseases, including GERD, H. pylori
positive antrum gastritis, and hiatal hernia, were diag-
nosed in 22 of 30 cases based on EGD and histological
examination of biopsy specimens. Gastroesophageal re-
flux disease was confirmed in 13 patients. The mucosa
was examined visually and was subdivided according to
Savary15 as reflux disease grades I (single peptic lesions
[n 8]), II (confluent erosions [n 4]), III (circular
epithelial defects [n 1]), and IV (organic alterations
with stenosis, strictures, ulcer, and Barretts esophagus
[n 0]). In the present study, the prevalence of GERD
(13 of 30 patients [43%]) was significantly higher (P
.05, 2 test) than in age- and gender-matched patients
(3 of 30 patients [10%]) who underwent EGD for various
reasons other than laryngopharyngeal symptoms. The
main indications for EGD in those patients were dys-
peptic symptoms, ulcer-type epigastric pain, noncardiac
chest pain, nausea, vomiting, and the like.
Helicobacter pylori-positive antrum gastritis was
present in 7 (23%) patients, whereas 13 patients (43%)
had hiatal hernia either alone or in combination with
GERD and/or H pyloripositive antrum gastritis (Table
IV). In the present study, 16 of the total of 30 patients had
a positive history of gastroenterological diseases, includ-
ing GERD (n 3), gastritis (n 11), or gastric or duode-
nal ulcer (n 2). However, in only four patients had a
recurrence of the same GI tract disease been detected
(Table IV).
Treatment Outcome
In eight patients the mucosae of the upper GI tract
had been diagnosed as regular. However, during follow-
up, four (including three patients with intake of raniti-
dine) of those eight patients described only a slight and
intermittent symptomatic improvement that was not
marked enough for a change in the degree of symptoms,
according to the classification of severity.16 Laryngeal le-
sions remained unchanged in those eight patients.
Therapeutic medical regimen in conjunction with the
above-mentioned behavioral modifications relieved and
improved laryngopharyngeal symptoms in 20 of 22 pa-
tients diagnosed with GERD, hiatal hernia, or H pylori
positive antrum gastritis, with a clinical success rate be-
ing approximately 90%. In 13 (59%) of those 20 patients
with GI tract diseases the laryngopharyngeal symptoms

TABLE II.
Laryngopharyngeal Symptoms Associated With GERD.
Total (n 30) GERD (n 13) Non-GERD (n 17)

Symptoms No. Percent No. Percent No. Percent

Dysphagia 20 67 7 54 13 76
Globus pharyngeus 20 67 8 62 12 71
Hoarseness 16 53 6 46 10 59
Odynophagia 15 50 7 54 8 47
Sore throat 14 47 3 23 4 24
Heartburn* 11 37 7 54 4 24
Postnasal drip 11 37 6 46 5 29
Cough 8 27 3 23 4 24
Throat clearing/throat mucus 6 20 4 31 2 12
Laryngospasm 3 10 0 0 3 18
Voice fatigue 2 7 1 8 1 6
Regurgitation* 1 3 1 8 0 0
*Characteristic reflux symptoms (Koufman et al., 1991)4.
GERD gastroesophageal reflux disease.

Laryngoscope 112: May 2002 Tauber et al.: Gastroesophageal Reflux Disease

881
completely disappeared after treatment, whereas 7 pa-
tients (32%) described marked attenuation of their symp-
toms, often from a moderate or severe to a mild degree
during follow-up (Table IIA). However, 2 of 20 patients
had an exacerbation of symptoms without laryngeal le-
sions within 3 weeks of discontinuing medication. The
symptomatic improvement of all 20 patients was not sig-
nificantly different among any diagnosed GI tract disease.
Laryngeal findings resolved or decreased signifi-
cantly in 20 (90%) of 22 patients by medical treatment of
hiatal hernia and GERD, but also by eradication of H
pylori infection. In 18 patients (81%) with GI tract dis-
eases (12 of them diagnosed with GERD and 6 of them
diagnosed as non-GERD), the laryngeal lesions disap-
peared by means of treatment procedures. Posterior lar-
yngitis and hyperplastic laryngitis healed completely in
all 12 (100%) GERD-positive patients in whom laryngeal
lesions were found. In non-GERD patients, laryngitis re-
solved in only six cases; four of these patients had ery-
thema and edema of the interarytenoid region. The ther-
apeutic success rate was approximately 37% for all non-
GERD patients with laryngeal lesions. In another two
non-GERD patients (9%), posterior laryngitis with inter-
arytenoid erythema and edema was only attenuated (mod-
erate erythema or edema changing to slight erythematous
mucosae). Posterior laryngitis with erythema or edema of
the interarytenoid region represented in GERD-positive
and non-GERD patients the most frequently cured laryn-
geal finding (100% and 60%) compared with posterior
laryngitis without changes of the interarytenoid region
(100% and 40%).
The pretherapeutic observed severe posterior laryn-
gitis in a patient with GERD (grade III) and hiatal hernia
with its severe erythema and edema of the interarytenoid
region was significantly attenuated and resolved by treat-
ment procedures after 2 months (Fig. 3).
DISCUSSION
There is increasing evidence that GERD may cause
rhinological and laryngopharyngeal symptoms.1 6 How-
ever, both patients and physicians often do not seem to be
aware of the extent of GERD-associated extraesophageal
diseases presenting with laryngopharyngeal symptoms.
This fact is especially important because patients with
GERD often may become symptomatic in the upper respi-
ratory tract, and laryngopharyngeal findings are subtle
TABLE III.
Laryngeal Findings Associated With Gastroesophageal Reflux.
Total (n 30)
No. Percent
Laryngeal Lesions 28 93
Posterior laryngitis 26 87
With interarytenoid erythema/edema 19 63
Without interarytenoid erythema/edema 7 23
Hyperplastic laryngitis 2 7
GERD gastroesophageal reflux disease.
Laryngoscope 112: May 2002
882
and sometimes hard to detect. At least 10% of all patients
presenting to otolaryngologists have symptoms related to
GERD4; in primary care practices the incidence is approx-
imately 1%.9
For years, GERD has been known as a causative
factor in a wide range (approximately 18% to 80%) of
patients with laryngeal diseases.1720 Later, dual-probe
and triple-probe 24-hour pH monitoring has been per-
formed with measurements in the distal esophagus, or
hypopharynx, and an additional electrode in the proximal
esophagus, respectively. In different studies, the authors
found abnormal proximal esophageal pH studies indicat-
ing GERD in a range of 62% to 100% of patients with
laryngopharyngeal symptoms and posterior laryngitis
whereas laryngopharyngeal reflux occurred in 30% to 86%
of those patients, as demonstrated by changes in the elec-
trodes above and/or distal from the upper esophageal
sphincter.4,6,8 In general, the wide ranges of prevalence,
which have been documented for GERD and LPR in sev-
eral earlier studies, can be explained by patient selection
criteria, various laryngeal lesions, different definitions of
reflux disease, and various methods of diagnosis such as
EGD, 24-hour pH monitoring with single, double, or even
triple probes, radiographic and manometric evaluation,
and symptomatic assessment. In the present study, we
detected GERD by EGD in 43% of patients (13 of 28) with
hypopharyngeal or laryngeal mucosal changes. These re-
sults are in good concordance with similar investigations
using the same diagnostic method; Deveney et al.3 re-
ported GERD in 43% of patients with inflammatory laryn-
geal lesions, and Paterson1 described GERD in 26% of
patients with laryngeal symptoms.
Our current investigation demonstrated that some of
the above-mentioned laryngopharyngeal symptoms can be
predictors of occult gastroesophageal diseases, including
GERD or hiatal hernia. Symptoms such as dysphagia,
sensation of globus pharyngeus, postnasal drip, hoarse-
ness, and other laryngeal disorders are not always caused
by any primary otorhinolaryngological disease. A careful
history and thorough knowledge of the disease syndromes
are important for diagnosing GERD.14 In 22 of 30 pa-
tients, such conditions were associated with at least one of
the following gastroenterological diseases: GERD in 13
cases (43%), hiatal hernia in 13 cases (43%), and H pylori
positive antrum gastritis in 7 cases (23%) (Table IV).
Our data are consistent with the results of other stud-
GERD (n 13) Non-GERD (n 17)
No. Percent No. Percent
12 92 16 94
11 85 15 88
9 69 10 59
2 15 5 29
1 8 1 6
Tauber et al.: Gastroesophageal Reflux Disease
Fig. 1. Mild posterior laryngitis before therapy in the endolarynx in a patient with
grade II gastroesophageal reflux disease. Edema and erythema of the posterior vocal
folds (white arrow) and arytenoid area (black arrow) are accompanied by cobble-
stone appearance of the interarytenoid area (x).
Fig. 2. Endolarynx during phonation (A) and respiration (B), demonstrating severe
posterior laryngitis before therapy in a patient with grade III gastroesophageal reflux
disease with hiatal hernia. The posterior wall of the larynx with the posterior com-
missure and arytenoid and interarytenoid area is inflamed with prominent edema,
erythema, and string signs on the mucosal surface. The posterior parts of the vocal
folds are covered by marked edematous mucosae.
Laryngoscope 112: May 2002
Fig. 3. The same larynx as shown in Figure 2 during phonation (A) and respiration
(B), 2 months after treatment. The severe, edematous and erythematous poste-
rior laryngitis before therapy was significantly attenuated by treatment proce-
dures, and string signs have been disappeared. Consequently, the posterior
parts of the vocal folds could be completely assessed showing regular mucosae.
ies. Koufman4 defined GERD as the primary cause in
62% of otolaryngological patients with laryngeal and voice
disorders. The prevalence of H pyloripositive antrum
gastritis in the present study (23%) was not higher than
expected in our population. However, the prevalence of
GERD (43%) was significantly higher in this study than in
age- and gender-matched patients (10%) who underwent
endoscopy for gastroenterological indications other than
laryngopharyngeal symptoms (P .05). These results are
in concordance with the prevalence of GERD diagnosed in
patients referred to receive EGD for either typical reflux
symptoms (37%) such as heartburn, regurgitation, and
dyspepsia or for other gastroenterological indications
(15%) in a recent study.21
In patients with otolaryngological disorders, Kouf-
man4 described abnormal esophageal reflux (GERD) in
62% and pharyngeal reflux in 30% by 24-hour pH moni-
Tauber et al.: Gastroesophageal Reflux Disease
883
toring. More recent studies confirmed in 50% and 86% of
patients with laryngopharyngeal symptoms and posterior
laryngitis, gastroesophagopharyngeal reflux by double- or
triple-probe 24-hour pH monitoring, compared with 43%
GERD-positive patients diagnosed by EGD in the current
study.6,8 Consequently, 24-hour pH monitoring by double-
or triple-sensor pH probes should be preferred for deter-
mination of GERD and confirmation of any LPR because
this procedure is known to be the most sensitive test for
diagnosing GERD-related otolaryngological disor-
ders.3,4,8,10 Although the procedure is expensive, invasive,
and uncomfortable to patients and can lead to false-
positive or false-negative results, it is recommended for
assessment of distal gastroesophageal and proximal la-
ryngopharyngeal reflux in certain laryngeal diseases.8,9
The evaluation of the esophageal mucosae by EGD can
also produce false-negative results because in patients
with laryngopharyngeal disorders the mucosae of the dis-
tal esophagus can often be visually regular, whereas prox-
imal acid reflux into the larynx is evident.4,8,20 In the
present study, in the eight patients with regular mucosae
of the upper GI tract it remained questionable whether
GERD or LPR was present. When results of adequate
studies for GERD or LPR, or both, are negative and la-
ryngeal acid reflux is still suspected as cause of laryngo-
pharyngeal signs and symptoms, a therapeutic trial
should be used. In the present study, patients refused to
undergo 24-hour pH monitoring. For this reason, we sug-
gested medical treatment, at least with H2 receptor an-
tagonists, for the eight patients with regular results of
EGD and biopsy specimens. The prevalence of LPR in
those patients was not clear because the few patients who
accepted medication reported merely symptomatic and
only intermittent relief of their symptoms, whereas laryn-
geal lesions remained unchanged.
The patients included in the current study primarily
presented to the otolaryngologist. Their complaints con-
cerned the head and neck region, whereas the typical
symptoms of GERD such as heartburn (37%) and regur-
gitation (3%) were not of marked prevalence. Koufman4
reported that 50% of patients with GERD-related laryn-
gopharyngeal disorders do not have classic reflux symp-
toms and present to their physician with sore throat or
cough. A variety of atypical extraesophageal manifesta-
tions, defined as disease processes in organs other than
the esophagus, has been attributed to extraesophageal
reflux disease (Table II). For example, regurgitation and
aspiration of gastric contents can be also associated with
asthma or even dental disease.4,5,13 Hoarseness has been
described as the most significant laryngeal complaint of
GERD9; Wilson et al.12 observed this symptom in 55% of
patients with posterior laryngitis and abnormal esopha-
geal reflux. In the current study, 6 of 13 GERD-positive
patients (46%) complained about chronic hoarseness. The
symptom postnasal drip has been considered a misno-
mer because patients are likely to be having reflux.11
Indeed, in the present study, 6 of 11 patients (54%) com-
plaining of postnasal drip were diagnosed with GERD.
Interestingly, there was a higher prevalence of some
laryngopharyngeal symptoms in GERD-positive patients
compared with non-GERD patients. The most striking
Laryngoscope 112: May 2002
884
difference could be observed in symptoms such as throat
clearing (31% vs. 12%), heartburn (54% vs. 24%), postna-
sal drip (46% vs. 29%), and regurgitation (8% vs. 0%)
(Table II). Former studies also demonstrated that typical
reflux symptoms such as heartburn and atypical symp-
toms such as throat clearing and postnasal drip should be
particularly regarded in clinical evaluation of patients
suspected of having GERD.4,9,22 The prevalence of abnor-
mal gastroesophageal reflux in patients with globus sen-
sation is approximately 15%,23 and the association is de-
scribed to be purely coincidental. We diagnosed GERD in
40% of patients (8 of 20) complaining of this symptom.
Dysphagia has been documented in more than 50% of
patients with GERD as another frequent laryngopharyn-
geal symptom.24 We found dysphagia in 54% of patients
with GERD. Nevertheless, the symptoms dysphagia, glo-
bus sensation, hoarseness, and laryngospasm seemed not
to be specific for reflux disease because the prevalence in
non-GERD patients was even higher than in patients with
GERD.
The cause of globus symptoms and dysphagia in
GERD is still discussed. Possible mechanisms for symp-
tom production are discomfort from esophagitis and
esophageal dysmotility, acid irritation of laryngopharyn-
geal structures, or even upper esophageal sphincter dys-
function.1,4,7 Paterson1 described two main pathophysio-
logical mechanisms considered to be causative for
extraesophageal symptoms of GERD as follows. The con-
tact of refluxed acid and pepsin with esophageal and tra-
cheal mucosa activates vasovagal reflexes leading to re-
flux or spasm. In addition, there is direct irritation of
laryngopharyngeal and pulmonary mucosa by refluxed
acid and pepsin. The etiology for acid-related laryngopha-
ryngeal symptoms has been well discussed, the most likely
factor being microaspiration occurring at night, when the
upper esophageal sphincter pressure is low.4,25 Intermit-
tent acid reflux can lead to injuries of the laryngeal mu-
cosa in animals and humans.4,25 Cherry and Margulies17
first postulated in 1968 that acidification of the laryngeal
mucosa may be an etiological factor in vocal process ulcer-
ation and granuloma formation. Later studies reported
reflux of gastric acid as a cause of laryngeal diseases such
as posterior laryngitis or laryngeal ulceration.9,12,18,26
Koufman4 described posterior laryngitis in 74% and laryn-
geal edema and erythema in 60% of all patients with
GERD. In addition, GERD seems to be associated more
frequently with erythematous and edematous mucosal
changes of the interarytenoid area, compared with non-
GERD patients.4,9 These data are consistent with our
current study, in which 85% of GERD-positive patients
had posterior laryngitis and 69% had posterior laryngitis
with an interarytenoid erythema and edema, whereas er-
ythema and edema was present in only 59% of non-GERD
patients (Table III).
Gastroesophageal reflux disease may be an impor-
tant etiological cofactor in the development of leukoplakia
and upper aerodigestive tract squamous cell carcinoma, in
particular, laryngeal carcinoma, because there is a high
association of pharyngeal reflux in patients with carci-
noma of the larynx.3,4,10,11,14 It has also been assumed
that cigarette smoking and ethanol (alcohol) are synergis-
Tauber et al.: Gastroesophageal Reflux Disease
tic etiological risk factors in the development of laryngeal
carcinoma.27 Both tobacco and ethanol can cause exacer-
bation of GERD by decreasing lower esophageal sphincter
tone, delaying gastric emptying, stimulating gastric acid
secretion, and impairing esophageal motility.28 31 GERD
is assumed to be a possible cocarcinogen potentiating the
risk of acquiring squamous cell carcinoma of the larynx.
Therefore, the early diagnosis and treatment of gastro-
esophageal and laryngopharyngeal reflux disease is of
major importance.
Standard therapeutic intervention for GERD and
GERD-associated laryngeal disorders includes behav-
ioural and dietary modifications and antireflux treatment
with H2 receptor antagonists and proton pump inhibitors
(e.g., omeprazole).4,14,16,22,3234 In previous studies, the
positive outcome of this therapeutic regimen ranged from
60% to 100% of treated patients,4,22,33 which is in good
concordance with our therapeutic success rate of approx-
imately 90%. Symptomatic improvements have been de-
scribed in patients who followed the above-mentioned be-
havioural modifications because compliance with a drug
regimen is even worse.32
In the present study, there was improvement of la-
ryngopharyngeal symptoms with antireflux treatment
and behavioural modifications in 20 patients with con-
firmed GI tract diseases, whereas even in 13 of those 20
patients the symptoms disappeared. The symptomatic im-
provement of all 20 patients was not significantly different
among any of the diagnosed GI tract diseases. However,
the assessed patient group of the present study was small.
Moreover, 24-hour pH monitoring could not be performed
in any patient to confirm the prevalence of underlying
LPR, which is known to be responsible for laryngopharyn-
geal symptoms.6,8
Laryngeal lesions, which were been found in 12 of 13
GERD-positive patients, healed completely by medical
treatment with a therapeutic success rate of 100%. In the
non-GERD group, healing of laryngeal lesions was less
frequent: in only 37% of patients did those findings re-
solve. Posterior laryngitis with erythema and edema of the
interarytenoid region represented the most frequent la-
ryngeal finding (69% and 59%) with the highest therapeu-
tic success rate (100% and 60%) in both GERD-positive
and non-GERD patients. Posterior laryngitis without er-
ythematous and edematous mucosae was less frequent
and healed in 100% and 40% of GERD-positive and non-
GERD patients, respectively.
Hyperplastic laryngitis has been rarely diagnosed
and resolved only in the GERD-positive patient. In the
non-GERD patient, hyperplastic laryngitis remained un-
changed, which presumably was developing by mecha-
nisms other than GI tract disease.
Medical treatment was performed in the present
study with omeprazole in a range of dosages similar to
former studies.2,22,3234 In comparison to our investiga-
tion, Hanson et al.22 observed satisfactory clinical re-
sponse in 83% of GERD-positive patients with moderate
and severe posterior laryngitis after a 6-week treatment
with 20 mg omeprazole per day. However, 79% of patients
had recurrent symptoms after stopping the medication.22
Jaspersen et al.33 demonstrated complete (100%)
Laryngoscope 112: May 2002
symptom-free healing of GERD and associated posterior
laryngitis after a 4-week treatment with 40 mg omepra-
zole per day, which is in good concordance with our
results.
There are still not enough data concerning controlled
clinical trials using antireflux therapy for the treatment of
posterior laryngitis and defining the optimal dose and
duration of treatment. Laryngopharyngeal refluxinduced
posterior laryngitis sometimes does not respond to stan-
dard antireflux therapy. At minimum, a 4-week medical
treatment is required before a diagnosis of no response
can be made. To obtain optimal therapeutic effects, treat-
ment for 6 months may be required, as has been reported
in a recent consensus conference statement.35 In refrac-
tory patients, the use of more effective medication with an
increased or double dose of proton pump inhibitors from
20 to 40 mg twice daily16,34; antireflux surgery with Nis-
sen fundoplication or the Toupet partial fundoplication
has also been demonstrated.2
CONCLUSION
There is an important relationship between GERD
and laryngopharyngeal manifestations that should be ac-
knowledged by physicians and patients to achieve im-
proved diagnostic and therapeutic management. Laryngo-
pharyngeal symptoms in GI tract diseases represent a
wide spectrum, whereas a few symptoms seem to demon-
strate a marked association with GERD. The laryngo-
scopic findings of GERD- and LPR-associated posterior
laryngitis are often subtle, despite more severe and per-
sistent laryngopharyngeal symptoms. In addition, pa-
tients with various laryngopharyngeal disorders resulting
from LPR do not consistently complain of the typical
symptoms of classic GERD, such as heartburn and
regurgitation.
Special attention should be paid to other laryngopha-
ryngeal symptoms, such as throat clearing or postnasal
drip. Meticulous laryngoscopic examination should be ex-
ercised as an additional noninvasive diagnostic measure
in patients suspected of having GERD with LPR. This is
especially important because empirical therapeutic trials
with proton pump inhibitors are often recommended be-
TABLE IV.
Comparison of GI Diseases
Present Study Recurrence
(n 22) (n 4)
GI disease
R 5 1
H 4
G 3 3
RH 6
RG 1
GH 2
RHG 1
Duodenal ulcer
R gastroesophageal reflux disease; G Helicobacter pylori-positive
antrumgastritis; H Hiatal hernia.
Tauber et al.: Gastroesophageal Reflux Disease
885
fore or without diagnosis of GERD and LPR by usual
diagnostic procedures (e.g., EGD or pH monitoring). How-
ever, 24-hour pH monitoring is still regarded as the gold
standard for reflux detection and appropriate definition of
LPR because EGD can often produce false-negative re-
sults. In the present study, evaluation with only EGD
seemed not to be sufficient because in some cases with
regular biopsy specimens in EGD the underlying GERD
and LPR probably was not detected.
Laryngopharyngeal assessment by otolaryngologists
must be discussed and developed as an additional, reli-
able, and noninvasive monitoring of gastroesophageal and
supraesophageal diseases that are associated with laryn-
geal diseases. This evaluation could also be important for
control and prevention of LPR-induced injury to laryngo-
pharyngeal or pulmonary mucosae.
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