Professional Documents
Culture Documents
CLINICAL REVIEWS
ABSTRACT
Gastroesophageal reflux disease is felt to be associated with
a variety of laryngeal conditions and symptoms of which
reflux laryngitis is perhaps the most common. The most
likely mechanism for laryngeal injury and symptoms is
secondary to direct acid and pepsin contact, although studies
concerning the cause and effect between gastroesophageal
reflux disease and laryngeal disorders are conflicting. Likewise, the most effective method to diagnose such patients is
unclear. Empiric treatment of patients with reflux laryngitis
has been shown to be effective though none of the studies
are controlled. (Am J Gastroenterol 1999;94:28122817.
1999 by Am. Coll. of Gastroenterology)
INTRODUCTION
Dr. L. A. Coffin, in 1903, was one of the first to associate
gastroesophageal reflux (GER) with laryngeal disorders. He
speculated that the eructation of gases from the stomach
and hyperacidity were responsible for the symptoms in
many of his patients with postnasal catarrh, and stated that
this problem was overlooked because many patients had no
gastrointestinal symptoms. Years later, in 1968, Cherry and
Margulies (1) reported three patients with contact ulcers of
the larynx and gastroesophageal reflux disease (GERD)
diagnosed by acid barium studies. Treatment with antacids,
dietary modification, and elevation of the head of the bed
resulted in resolution of the contact ulcers. Ohman et al. (2),
in 1978, used 24-h pH monitoring to document GERD in 43
men with either a history of or current laryngeal contact
ulcers, and noted that 51% of their patients had abnormal
GER.
It is estimated that 4 10% of patients presenting to an
otolaryngology practice will have symptoms and/or findings
related to GERD (3, 4). The most common symptoms associated with reflux laryngitis are hoarseness, vocal fatigue,
chronic throat clearing, excessive throat mucus, chronic
cough, dysphagia, and globus sensation. Though not the
focus of this article, several other laryngeal conditions (see
Table 1) have also been associated with GERD and some of
Disclaimer: The opinions and assertions expressed in this report contained herein
are the private ones of the authors and are not to be construed as official policy or
reflecting the views of the Department of Defense.
PATHOPHYSIOLOGY
There are two schools of thought concerning how gastric
acid causes laryngeal pathology. The first implicates a direct
acid-peptic injury to the larynx and surrounding tissues via
EPR (710). Data to support this hypothesis come from
animal studies (7, 8, 11, 12). The second hypothesis suggests that acid in the distal esophagus stimulates vagally
mediated reflexes resulting in chronic throat clearing and
coughing which eventually lead to laryngeal lesions and
symptoms (1316). Perhaps a combination of these mechanisms could be present in the same patient. Lastly, it may
be that EPR only results in laryngeal injury and symptoms
when acting in concert with other risk factors for laryngitis,
such as voice overuse and chronic throat clearing behavior.
The notion that significant laryngeal injury occurs with
only minute amounts of acid is based on the canine and
rabbit model where acid and pepsin are applied directly to
the laryngeal mucosa (4, 7). Because the laryngeal apparatus
is not continually coated by saliva, the gastric refluxate
cannot be neutralized, diluted, or mechanically washed off
of the mucosa, resulting in a greater propensity for injury
(17). Also, because laryngeal mucosa is not normally exposed to acid and pepsin, the intrinsic cellular mechanism to
protect against chemical injury may not be present, although
this has not been well studied. Kambic and Radsel (12)
biopsied the larynx of 44 patients with posterior laryngitis
and noted that the laryngeal epithelium was often thickened
due to hyperplasia of the prickle cell layer, and in some the
epithelium was keratinized. In patients with laryngeal ulcers, there were abundant lymphocytes and plasma cells
infiltrating the epithelium. These changes are similar to
esophageal biopsies of reflux esophagitis patients.
Reflux Laryngitis
2813
DIAGNOSIS
Patients with reflux laryngitis most commonly present with
hoarseness, globus sensation, frequent throat clearing, halitosis, frequent sore throats, chronic cough, and prolonged
vocal warm-up. Hoarseness is noted in 92% of patients (29,
30), but the differential diagnosis of hoarseness is broad.
Koufman (30) speculates that GERD plays a contributing
role in approximately 55% of patients seen with the complaint of hoarseness, though this prevalence has not been
verified in any studies. Patients with refractory chronic or
intermittent symptoms are often referred to an otolaryngologist.
Because the differential diagnosis of the symptoms of
reflux laryngitis is broad, a careful history is imperative.
Risk factors associated with these symptoms include frequent voice use, concurrent tobacco use, history of upper
respiratory tract infections with coughing, chronic idiopathic cough, allergic type symptoms, pets, recent air conditioner, postnasal drip, and new environmental conditions
that contain synthetic materials. A reflux history is important to obtain, but patients may deny associated heartburn as
has been mentioned.
Early in the evaluation of patients with laryngitis and
2814
associated symptoms, most patients will undergo laryngoscopic examination. There are several different instruments
used by laryngologists to evaluate the hypopharynx and
larynx, ranging from indirect mirror laryngoscopy to the
more sophisticated videostroboscopy, which is able to identify subtle mucosal abnormalities enhancing the ability to
evaluate laryngeal pathology and function. Indirect laryngoscopy may be used as a screening tool, but videostroboscopy is considered to be the best technique to study the
larynx. Unfortunately, videostroboscopy is expensive, and
the technology is limited to modern voice laboratories.
The term reflux laryngitis refers to a constellation
which includes classic posterior laryngitis with red arytenoids and piled-up interarytenoid mucosa but is not seen in
the majority of patients with reflux laryngitis (31). Rather,
laryngeal edema is the most common finding, which can
easily be missed because both indirect mirror and fiberoptic
laryngoscopy may not identify this lesion. In a group of 46
patients with the diagnosis of reflux laryngitis based on
symptoms of hoarseness and/or an abnormal laryngeal examination, the most common laryngeal findings were:
edema, 89%; erythema, 87%; granuloma/granulation, 19%;
and ulceration, 2% (30). Abnormalities, such as erythema
and edema, are more often seen on the posterior aspect of
the larynx, which may relate to its proximity to the esophagus and hence may be most exposed to acid-peptic refluxate. Table 2 lists some of the laryngeal findings associated
with GERD.
Reflux Laryngitis
2815
Table 3. Results of Studies in the Treatment of Patients With Suspected Reflux Laryngitis
No. of
Patients
Percent of
Patients
With
Heartburn
Percent of
Patients
With
Esophagitis
McNalley
89
11
82%
55%
yes/55%
Kamel
94
12
83%
19%
no
Hanson
95
182
NA
NA
no
Waring
95
27
100%
59%
Jasperson
96
21
100%
100%
Metz 97
10
50%
20%
Shaw 97
96
39%
NA
no
Wo 97
22
55%
NA
no
Study*
pH Testing/
Percent With
Positive
Results
yes/no mention
of % with
pH test
no
yes/60%
Rx/Dose and
Duration
Outcome
Parameters
H2RA 150 mg
b.i.d. 12 wk
symptoms, voice
parameters
prior H2RA-PPI
40 mg/d up to
24 wk
H2RA, PPI or
surgery, dose
and duration
variable
PPI or Nissan
40 mg/d
variable
duration
PPI 40 mg/d 4
wk
symptoms and
laryngoscopic
exam
symptoms and
laryngoscopic
exam
PPI 40 mg/d 4
wk
PPI 40 mg/d 12
wk
PPI 40 mg/d 8
wk
Percent of
Patients With
Improvement in
Symptoms
50% by voice
analysis; 50%
got worse
92%
96%
symptoms
80%
symptoms and
laryngoscopic
exam
symptoms
100%
symptoms,
acoustic voice
analysis, and
laryngoscopic
exam
symptoms,
laryngoscopic
exam
60%
60%
67%
2816
SUMMARY
Reflux laryngitis is a common disease and is probably only
one of several laryngeal manifestations associated with
GERD. The hypothesis that GER causes laryngeal symptoms and conditions remains to be definitively proven. In
many patients, the cause of laryngeal symptoms may well be
multifactorial, and definitively identifying in which patients
GER may be playing a role remains a challenge. Documentation of GER using 24-h pH monitoring in those with
laryngeal findings attributed to GER may assist in identifying such patients. Pharyngeal pH probe monitoring, although not without limitations, may be the optimal method
to evaluate such patients in terms of documenting the presence of EPR.
A suggested algorithm based on the available data in
evaluating and treating patients with suspected reflux laryn-
gitis is to first perform simultaneous esophageal and pharyngeal pH monitoring, if available, as this test will most
likely establish or rule out the presence of EPR. If pharyngeal pH monitoring is not available or undertaken, empiric
treatment with PPIs has been shown to be effective in the
majority of patients though as mentioned, none of the trials
to date have been placebo-controlled. In any case, whether
PPI treatment is initiated based on the results of pharyngeal
pH monitoring or begun empirically, treatment with high
dose PPIs (i.e., 40 60 mg/day) and for relatively long
periods (i.e., 3 6 months) may be required for laryngeal
injury to heal and symptoms to completely resolve. In addition, some of these patients may benefit from the concept
of total acid blockade requiring supplementation of their
PPI therapy with H2RAs at bedtime (47, 49, 50). Lastly,
patients with other risk factors for chronic laryngitis, such as
voice overuse, may benefit from concomitant voice therapy.
Reprint requests and correspondence: Roy K. H. Wong, COL.,
M.C., Chief, Gastroenterology Service, Building #2, Room 7F47,
Walter Reed Army Medical Center, 6900 Georgia Avenue, N.W.,
Washington, D.C. 20307.
Received Mar. 5, 1999; accepted May 21, 1999.
REFERENCES
1. Cherry J, Margulies SI. Contact ulcer of the larynx. Laryngoscope 1968;78:1937 40.
2. Ohman L, Olofsson J, Tibbling L, et al. Esophageal dysfunction in patients with contact ulcer of the larynx. Ann Otol
Rhinol Laryngol 1978;92:228 30.
3. Koufman JA, Wiener GJ, Wallace CW, et al. Reflux laryngitis
and its sequela: The diagnostic role of ambulatory 24-hour
monitoring. J Voice 1988;2:78 9.
4. Toohill RJ, Mushtag E, Lehman RH. Otolaryngologic manifestations of gastroesophageal reflux. In: Sacristan T, AlvarezVincent JJ, Bartual J, et al., eds. Proceedings of XIV World
Congress of Otololaryngology head and neck surgery.
Amsterdam: Kugler & Ghedini Publications, 1990:30059.
5. Ward PH, Hanson DG. Reflux as an etiological factor of
carcinoma of the laryngopharynx. Laryngoscope 1988;98:
11959.
6. Chen MY, Ott DJ, Casolo BJ, et al. Correlation of laryngeal
and pharyngeal carcinomas and 24-hour pH monitoring of the
esophagus and pharynx. Otolaryngol Head Neck Surg 1998;
119:460 2.
7. Little FB, Koufman JA, Kohut RI, et al. Effect of gastric acid
on the pathogenesis of subglottic stenosis. Ann Otol Rhinol
Laryngol 1985;94:516 9.
8. Gaynor EB. Gastroesophageal reflux as an etiologic factor in
laryngeal complications of intubation. Laryngoscope 1988;98:
9729.
9. Lillemoe KD, Johnson LF, Harmon JW. Role of the components of the gastrodudenal contents in experimental acid
esophagitis. Surgery 1982;92:276 84.
10. Johnson LF, Harmon JW. Experimental esophagitis in a rabbit
model. Clinical relevance. J Clin Gastroenterol 1986;(Suppl)8:
26 44.
11. Ludeman JP, Manoukian J, Shaw K, et al. Effects of simulated
gastroesophageal reflux on the untraumatized rabbit larynx. J
Otololaryngol 1998;27:12731.
12. Kambic V, Radsel Z. Acid posterior laryngitis. Aetiology,
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
Reflux Laryngitis
2817