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Diagnosis and management of chronic laryngitis associated with reflux
Diagnosis and Management of Chronic Laryngitis Associated with Reflux David G. Hanson, MD, Jack J. Jiang, MD, PhD
Chronic laryngitis symptoms are commonly seen in otherwise healthy people. This article reviews recent progress in our understanding and effective treatment of chronic laryngitis. Clinical experience and prospective treatment and outcome studies have demonstrated objective evidence of the efficacy of treating patients with chronic laryngitis symptoms with nocturnal antireflux precautions and acid-suppressing medications. The role of pH testing and most common errors in treatment are reviewed. Am J Med. 2000;108(4A):112S–119S. © 2000 by Excerpta Medica, Inc.
amel et al1 reported treatment of chronic posterior laryngitis with omeprazole in 1992, addressing the hypothesis that if chronic laryngitis were related to reflux, it should substantially improve when acid secretion was profoundly suppressed. That study demonstrated that treatment with a proton pump inhibitor, along with lifestyle modifications, alleviates most chronic laryngitis symptoms, as well as the visible evidence of chronic inflammation.2 A prospective case study subsequently examined the outcomes of a progression of treatment—from antireflux precautions, to H2 blockers, to proton pump inhibitors in progressively higher dosage—for chronic laryngitis symptoms. The study also assessed degree of laryngeal inflammation and recurrence rate in relation to the progressively more intense treatment modalities.3 That study demonstrated that there is a range of inflammation associated with chronic laryngitis that responds to antireflux treatment and demonstrated that for 50% of patients with chronic laryngitis symptom, antireflux precautions alone are sufficient for resolution of symptoms. Our experience since that report has been substantially greater, has not significantly changed our conclusions reported in 1996, but has added some new insights, which we will discuss in this overview. Our practices are situated in an urban environment with a population of business professionals who tend to work late, who usually eat later in the evening, and who admit to notable stress. It seems that this group of patients has a relatively high incidence of chronic laryngitis symptoms.
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From the Department of Otolaryngology, Head and Neck Surgery, Northwestern University Medical School, Chicago, Illinois, USA. Requests for reprints should be addressed to David G. Hanson, MD, Department of Otolaryngology, Head and Neck Surgery, Northwestern University Medical School, 303 East Chicago Avenue, Searle 12-580, Chicago, Illinois 60610. 112S © 2000 by Excerpta Medica, Inc. All rights reserved.
Symptoms of discomfort of the throat, change in voice, cough, dysphagia, and secretion stasis can occur with any cause of inflammation. Symptoms can be classified as acute or chronic, and can occur from infection, from exposure to toxic irritants, or from other factors that provoke an inflammatory reaction. Patients who complain of long-term chronic symptoms that relate to the throat may have varying degrees of symptom intensity, duration, and visible inflammation of the structures in the hypopharynx and pharynx. The signs of inflammation on examination of the larynx and pharynx can vary from subtle erythema of the posterior larynx to severe mucosal changes with ulceration and formation of granulation tissue. Historically, ulcerative changes with granulation for0002-9343/00/$20.00 PII S0002-9343(99)00349-6
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mation were the first manifestations of chronic laryngitis to be recognized.
ULCERATION OF LARYNGEAL EPITHELIUM The most severe manifestation of chronic laryngeal irritation is actual ulceration of the laryngeal epithelium with granulation. Jackson4 first called attention to contact ulcers of the posterior larynx and attributed the injury to mechanical trauma. Other authors also supported a primarily traumatic etiology.5–10 Cherry and Margulies11 first identified acidification of the larynx as a probable factor in contact ulcers, and Delahunty and Cherry12 demonstrated that ulcers could be produced experimentally by application of gastric acid. Treatments for contact ulcers and granulomas have included surgical excision, “vocal reeducation,” and other forms of speech therapy, but these therapies have had disappointing variations in success.13–15 Ward et al16 in 1979 concluded after study of 28 patients with contact granulomas “that habitual throat clearing . . . and most important, acid regurgitation secondary to hiatal hernia are the causal factors of contact ulcers.” There developed a growing appreciation that gastroesophageal reflux could be associated with extraesophageal disease.17 Jacob et al in 199118 reported that chronic laryngitis symptoms and posterior laryngitis without ulceration could be associated with evidence of gastropharyngeal reflux documented by pH monitoring. Koufman19 also reported in 1991 a large series of patients with laryngeal inflammatory diseases that were associated with pH monitoring evidence of reflux. He supplemented the clinical experience with experimental evidence that supports the concept that application of gastric juices could cause laryngeal mucosal injury. It was with the advent of medications that profoundly suppress gastric acid secretion that argument for a relationship between gastric acid reflux and chronic laryngeal inflammation really started to become convincing. Kamel et al2 reported the elimination of symptoms and signs of chronic posterior laryngitis during treatment with omeprazole in a prospective study in 1994. Figure 1 reproduces data for a symptom index that patients recorded before, during, and after cessation of treatment with omeprazole. Whereas contact ulcers that occur over the cartilage of the vocal processes are painful and problematic because they can form large granulomas, circumferential ulcerative damage to the epithelium of the posterior and subglottic larynx causes more severe damage to function. Little et al20 reported in 1985 a case of acquired subglottal stenosis associated with reflux and described an animal experiment in which application of gastric juices to the subglottal larynx produced stenosis. As discussed elsewhere in this issue, reflux-related stenosis of the larynx and subglottic area is now a well-recognized problem in neonates. Acquired stenosis of the larynx in adults who
Figure 1. Kamel et al reported that laryngeal symptoms documented daily by patients with chronic laryngitis changed significantly after 6 to 9 weeks of treatment with omeprazole with antireflux precautions. Symptoms recurred to a smaller degree after omeprazole was discontinued. (Adapted from Am J Med.2)
have no history of long-term intubation is less common but does occur. We have been involved in the care of five adults who developed subglottic or glottic stenosis in association with reflux. Subglottal stenosis and posterior glottic stenosis are the most difficult to treat of the complications of supraesophageal reflux and, fortunately, are rare. Other manifestations of chronic supraesophageal reflux, some of which can be life-threatening, also have been subjects of clinical interest in the past decade and are discussed in other papers from this conference. The most common forms of laryngitis that can be associated with reflux can be present for months to years before the individual seeks and finds effective treatment. The following is a summary overview of our clinical experience over the last decade with diagnosis and treatment of the more common symptoms of chronic irritative laryngitis.
POSTNASAL DRIP AND SENSATION OF SECRETIONS Symptoms of chronic irritative laryngitis occur from injury to the normal function of the epithelium and adjacent structures of the pharynx and larynx. The earliest symptoms to manifest with mild injury (and the last to resolve with treatment) are associated mainly with damage to the ciliary clearance function of the ciliated respiratory epithelium. Patients most often describe these symptoms as postnasal drip. However, the symptoms of constant secretions in the back of the throat usually are
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Figure 2. The posterior larynx and interarytenoid area of the posterior glottic wall lies directly above and adjacent to the opening of the esophagus posteriorly. This area is red in patients with chronic laryngitis.
the result of ciliary dysfunction in the posterior larynx and pharynx rather than the nose. In the normally functioning larynx, the outflow of mucous secretion from the entire tracheal bronchial tree is directed by normal ciliary beating cephalad toward and through the posterior wall of the glottic aperture. The epithelium of the vocal folds is a stratified squamous epithelium that is more suited to resist the vibratory effects of phonation, and although better suited to mechanical vibration, the vocal fold epithelium provides a barrier to effective mucous transport. Therefore, the posterior larynx is particularly important in mucous flow out of the tracheobronchial tree. When the ciliary function of the posterior laryngeal mucosa is damaged by chemical irritation, or by mechanical trauma, mucous stasis at the outflow of the trachea becomes an annoying and prominent symptom.
COUGH AND THROAT CLEARING The neural organization of laryngeal sensory and motor systems has an important life-saving role, represented by cross brainstem reflexes, which protect the airway from aspiration. Clumping of mucous in the posterior larynx and strings of mucous across the vocal folds can provoke cough and laryngospasm at an unconscious reflex level as well as provoking throat clearing at a conscious level. Cough and laryngospasm appear to be more likely if the sensitivity of laryngeal sensory endings is upregulated by local inflammation. Other articles in this supplement discuss important aspects of that sensory system. Throat clearing behavior is directed at trying to remove secretions from the larynx but also is traumatic to the epithelium of the vocal process and the posterior glottic 114S March 6, 2000 THE AMERICAN JOURNAL OF MEDICINE威
wall. Physiologically, throat clearing is accomplished by firm closure of the vocal folds and forcing of airflow through the posterior aperture of the glottis behind the vocal folds. This is the area of ciliated respiratory epithelium where mucous is transported through the larynx. However, repeated mechanical trauma associated with frequent throat clearing appears, in itself, to cause damage to the delicate ciliary function of the posterior larynx. In patients who chronically clear their throats, this area of mucosa can appear rough, thickened, and callous-like. An unusual amount of throat clearing is commonly observed in patients with posterior laryngitis. Often, this is a habituated behavior that is done unconsciously. The laryngeal structures are important articulators in speech, and the neural control of these structures appears to be susceptible to relatively rapid habituation of automatic unconscious response to stimuli. This may explain why throat clearing and cough so easily become habits. Anatomically, this area of the larynx is directly in front of the opening of the esophagus into the pharynx. Figure 2 shows a picture of how the larynx would appear in a patient lying on the back and breathing quietly. It becomes apparent that very small amounts of refluxed material, if only in the form of a bubble of liquid film, could easily get to the posterior laryngeal wall. This is the area in which we first see signs of inflammation in patients with chronic laryngitis symptoms.
SORE THROAT The second most common manifestation of irritative laryngitis is sensation of discomfort that may be described as a dry, scratchy feeling, tightness in the throat, or sore
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throat. If there is ulceration of the epithelium, most commonly over the vocal processes and usually associated with chronic throat clearing, there may be localized pain that may radiate to the ear. Patients who have recurrent severe sore throats without other typical symptoms of an upper respiratory infection syndrome are likely to have irritative laryngitis as an underlying cause. The complaint of soreness, irritation, or pain usually is associated with visible signs of inflammation on laryngeal examination. The cardinal manifestation of this inflammation is erythema and visible increase in surface vascularity. Hanson et al21 recently reported a study of a large group of patients with chronic laryngitis symptoms in which videodocumented images of the laryngeal examination were digitized and subjected to digital color analysis. Color value for red, green, and blue was determined in multiple 5 ⫻ 5 pixel areas and averaged for measurement of the degree of redness of the epithelium over the posterior larynx and the epithelium on the vocal folds. The values for red color were related as a percent to the overall values for red ⫹ green ⫹ blue to define a red index
冉
red index ⫽
冊
red value . red ⫹ green ⫹ blue
The study showed a significant difference in red index between normal subjects and individuals who complained of chronic laryngitis symptoms. Figure 3 reproduces data on difference in redness between patients with laryngitis and normal subjects. In addition, during treatment, serial examinations of the larynges of patients with chronic laryngitis showed a significant treatment effect as the larynges became significantly less red with antisecretory and antireflux therapy. Figure 4 reproduces data on change in redness during treatment with omeprazole. Therefore, it appears that the visible inflammation manifested by erythema is a hallmark of posterior irritative laryngitis that responds to treatment for nocturnal reflux. In some situations, it may be advantageous to recognize the signs of laryngeal inflammation even when the patient does not volunteer complaints. Ellis et al22 reported on a prospective study of video-documented laryngeal examinations in 75 patients who were scheduled to have open heart surgery with prolonged intubation. Blinded analysis of the pre- and postintubation laryngeal examinations indicated that patients who had visible evidence of inflammation of the larynx in the pre-intubation examination were likely to have more severe postintubation injuries manifested by impressive edema, ulceration, granulation, and paresis. We now recommend that patients who will have prolonged intubation be covered with antisecretory acid suppression.
HOARSENESS AND CHANGE IN VOICE The third most common complaint of chronic laryngitis is deterioration in voice quality with voice use. Progres-
Figure 3. Hanson et al reported that between patients with chronic laryngitis symptoms and normal individuals with no laryngeal complaints, there was a significant difference in red value measured from digital color images of the larynx. Post ⫽ posterior; Voc ⫽ vocal. (Adapted from J Voice.21)
Figure 4. Change in redness of the vocal folds was documented with treatment by Hanson et al. (Adapted from J Voice.21)
sively impaired voice quality may be the primary complaint of posterior irritative laryngitis without soreness or other symptoms. In order to examine the complaint of hoarseness, Hanson et al23 studied patients with chronic laryngitis symptoms as they were being treated with omeprazole and antireflux precautions. Voice recordings
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Figure 5. Hanson et al reported that percent jitter and shimmer, and the ratio of clear signal to noise in the voice, changed significantly during treatment with omeprazole for patients with hoarseness associated with chronic laryngitis. (Time in weeks). (Adapted from Ann Otolol Rhinol Laryngol.23)
were made in a sound-protected room with a high-quality microphone and recording system. The recordings were digitized, and representative segments from stable mid phonation were analyzed blindly for perturbation of the voice signal. Jitter is a measure of the cycle-to-cycle variability in the period of the acoustic signal and detects irregularity of frequency of cycles in the acoustic signal. There was a significant decrease in jitter during treatment in the voices of patients with chronic laryngitis who complained of the symptom of hoarseness. Shimmer is a measure of cycle-to-cycle variation in the amplitude of the acoustic signal envelope and is a measure of how much intensity of the phonation is perturbed from cycle to cycle. During treatment for reflux, there was a significant decrease in the shimmer in the voices of patients who had complained of hoarseness. Signal-to-noise ratio of the acoustic signal is another measure of cycle-to-cycle regularity or irregularity. The measure uses an autocorrelation technique to compare how well the acoustic signal 116S March 6, 2000 THE AMERICAN JOURNAL OF MEDICINE威
matches from cycle to cycle versus random noise in the signal. A significant improvement in signal-to-noise ratio was demonstrated during antireflux and antisecretory treatment for patients who had complained of vocal hoarseness. Figure 5 shows data for percent jitter, percent shimmer, and signal-to-noise ratio from that study.
TREATMENT Prospective study of patients with chronic laryngitis complaints has demonstrated that approximately 50% of such patients will have symptoms resolve if they can be convinced to reliably follow nocturnal antireflux precautions (avoid food and liquids 2 to 3 hours before retiring and sleep with head and shoulders consistently elevated during sleep so that the throat area is elevated higher than the stomach).3 Patient education is key to successful treatment. Individuals are unlikely to make lifestyle changes unless they are convinced that so doing is important to resolution of symptoms. Most patients with mild chronic
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posterior laryngitis do not complain of significant amounts of heartburn and do not have gastropharyngeal reflux during the day; therefore, it is not intuitive that their symptoms might be caused by silent reflux episodes during sleep. Comparison of laryngeal examination data and demographic information with treatment outcome data suggests that patients who are most likely to respond to nocturnal antireflux precautions alone are patients who are young, whose lifestyle and habits put them at risk for reflux. These patients also usually have relatively mild evidence of inflammation on examination. Typical of this group is an individual who eats late at night, has alcohol in the evening, and sleeps flat. The incidence of hiatal hernia in this population is similar to that of the general population, approximately 20%, and these patients usually do not demonstrate any esophageal disease or any reflux on barium swallow examination. Another 25% of patients who complain of chronic laryngitis symptoms require an H2 blocker, in addition to observing nocturnal antireflux precautions. These tend to be patients who have mild to moderate changes on laryngeal examination and who have had onset of symptoms in association with stress. These patients are more likely to demonstrate increased episodes of reflux on pH studies but may have “normal” pH monitoring patterns at the time that they are studied. Approximately 25% of patients with chronic laryngitis symptoms require prolonged treatment with a proton pump inhibitor in order to achieve acceptable improvement in their symptoms and signs of laryngitis. These patients usually have evidence of more severe laryngeal inflammation on initial examination and may have evidence of inflammation of upper pharynx and nasopharynx. These patients are more likely to be aware of heartburn and gastropharyngeal reflux episodes during the day or night, and they are more likely to have relapse of symptoms and evidence of inflammation when acid suppression is discontinued. A few patients require high-dosage proton pump inhibitor to suppress acid secretion. Monitoring of esophageal pH while on medication can be helpful in patients who do not appear to be responding to what should be adequate dosages of acid suppression medication. These patients may demonstrate repeated acidification of the upper esophagus, even though they are taking a dosage of proton pump inhibitor that is usually adequate to provide effective suppression. This group of patients is more likely to have relapse of symptoms and recurrence of laryngitis when they stop taking medication and are more likely to have recurrent and prolonged problems. Patients with reflux and acidity that is resistant to treatment with usual dosage of proton pump inhibitors are probably candidates for fundoplication. Successful fundoplication is cost-effective in comparison with long-term high-dose proton pump inhibitor suppression, but many patients
are reluctant to have surgery if they can have their symptoms controlled with medication that seems to have relatively little side effect. A small percentage of patients cannot tolerate proton pump inhibitors or may not have acid production adequately suppressed even on high dosage of inhibitors yet will usually have complete resolution of both symptoms and laryngeal evidence of inflammation after fundoplication.
ROLE OF pH MONITORING STUDIES IN OUR PRACTICE Approximately 75% of the patients that we see with chronic laryngitis will achieve resolution of laryngitis symptoms by following nocturnal antireflux precautions with or without a relatively inexpensive H2 blocker. Therefore, we think that routine pH studies are not costeffective for the diagnosis and management of posterior laryngitis. This author’s personal experience with nocturnal reflux and our clinical practice experience suggest that the reflux associated with chronic irritative laryngitis may occur very intermittently, as well as silently. Therefore, pH monitoring studies suffer from a sampling problem. We have treated many patients who demonstrated “normal” patterns of esophageal acidification during the period that they had pH monitoring but who, nevertheless, had complete resolution of symptoms and laryngitis with nocturnal antireflux precautions and acid suppression. Some degree of reflux occurs in most individuals, and some reflux into the esophagus at night is normal. While in a healthy condition, the laryngeal and esophageal mucosa appear to tolerate some level of reflux. However, it seems that once there is some injury to the epithelium, further exposure to gastric acid is not tolerated well. We find that patients who have had radiation to the larynx do not tolerate acid exposures that would fall within pH data expected for normal subjects. Therefore, although pH monitoring has had an important place in the understanding of chronic irritative laryngitis and reflux, in most cases that have an appearance and symptoms characteristic of chronic irritative type of laryngitis, we would not withhold acid suppression simply based on a “normal” pH study. Probe monitoring of esophageal acidification, therefore, is not obtained routinely for patients who present with only laryngitis symptoms. In our practice, all patients who require long-term or high-dosage proton pump suppression, and all patients who have esophageal symptoms, are treated and observed in conjunction with a gastroenterologist.
TREATMENT OF VOCAL GRANULOMAS In an ongoing prospective study of patients presenting with vocal process granulomas at Northwestern University Medical School, treatment with antireflux precau-
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tions and suppression of gastric acid secretion with proton pump inhibitors has been uniformly successful in the complete resolution of vocal process ulcers and granulomas. This study, which represents a notable departure from the generally unsuccessful experience with surgical excision and speech therapy as primary treatments for vocal granulomas, will be completed and reported in the near future. To date, 12 patients have been followed for at least a year after resolution of their granuloma. The treatment period averaged 5 months to resolution of the lesions. Duration of treatment required to reach resolution appears related to the size of the granuloma and the degree to which throat clearing behavior can be eliminated.
trast, we know from 24-hour pH monitoring data that some degree of reflux is tolerated without evidence of injury by patients who do not have laryngeal symptoms. Commonly chronic laryngeal symptoms can be traced back to an episode of severe coughing, vomiting, or other trauma to the laryngeal epithelium. This may suggest that the laryngeal mucosa tolerates some degree of reflux until it is injured by some other form of trauma, but once injured, subsequent episodes of reflux on the inflamed epithelium cause progressive damage. Once evidence of laryngitis has healed, many patients may resume their previous lifestyle habits without recurrence of symptoms for prolonged periods of time.
TREATMENT FAILURES
LONG-TERM FAILURE OF TREATMENT AND LARYNGEAL CANCER
The most common error of chronic laryngitis symptom treatment that is observed in our tertiary referral practice is treatment of the sore throat with antibiotics alone. Patients with chronic laryngitis usually do feel better on antibiotics. Unfortunately, the symptoms recur as soon as antibiotic is discontinued. The second most common error is failure of physicians to explain adequately the rationale for treatment to patients, with the result that patients do not follow antireflux precautions. Patient education is a key factor in inducing patients to change significant sleeping, eating, and drinking aspects of their lifestyle. Although acid suppression clearly has an important role in the treatment of chronic irritative laryngitis, acid suppression alone may not be adequate to achieve long-term resolution of laryngeal inflammation and symptoms. Therefore, precautions to minimize the likelihood of nocturnal reflux appear to be important in the prevention of further laryngeal injury and also may be the only treatment needed for the majority of patients with mild symptoms and signs of inflammation. The third most common error of treatment that we see is inadequate length of treatment. It is not unusual for patients to take medication and follow precautions for 2 to 3 weeks but then to stop treatment because they do not feel significant improvement. It is important that patients understand that the injury to the epithelium of the larynx and hypopharynx that is associated with reflux is a chemical burn. Antireflux precautions and acid suppression do not reverse injury to the laryngeal epithelium. Rather, prolonged prevention of further injury is needed to allow healing of the tissues and eventual resolution of symptoms. Some vocal granulomas in our currently ongoing series have required 9 months of preventive treatment. Once injured, refluxed materials may further irritate the laryngeal epithelium even if pH is relatively high. Neither acid suppression nor antireflux precautions completely controls the possibility of intermittent reflux of gastric material up into the hypopharynx. It seems that once chronically inflamed, the epithelium of the larynx may be injured by very episodic small amounts of reflux. In con118S March 6, 2000 THE AMERICAN JOURNAL OF MEDICINE威
In 1988, Ward and Hanson reported a retrospective study of all patients in the UCLA/Wadsworth Veterans Affairs tumor registries over a 30-year period who had developed carcinoma of the laryngopharynx and who never had smoked.24 Long history of reflux was the common unifying risk factor identified in these patients. Some of the patients had been followed with chronic laryngitis for 8 to 12 years before they developed cancer. Subsequent to those observations, we have frequently identified irritative laryngitis that responds to antireflux and antisecretory therapy during the follow-up of patients whom we have successfully treated for laryngeal carcinoma. Postradiation patients may be much more susceptible to mucosal injury from reflux, and it has been our experience that antireflux treatment may be important in such patients even if they have normal pH studies. Individual patients who have had normal pH studies, nevertheless, have demonstrated evidence of severe ongoing chronic inflammation, which did respond to acid suppression and antireflux precautions. Although a causative relationship between chronic irritative laryngitis from reflux and cancer has not been established experimentally, it seems likely that chronic laryngeal irritation from reflux may be a risk factor for carcinoma. Olson5 recently reviewed evidence that reflux of gastric contents outside of the stomach might be related to development of cancer in the esophagus, larynx, or lungs. Finally, we would insert a word about terminology. Laryngitis, or inflammation of the larynx, can be caused by infection with viruses, with other organisms, by trauma or thermal injury, or by exposure to toxic materials. Infectious acute laryngitis, usually from virus infection, rarely lasts more than 10 to 14 days at the most. Acute bacterial infection, supraglottitis, is also not a chronic condition. Generally, chronic infections, with tuberculosis, Candida, or exotic infections are rare and usually occur in association with other evidence of disease. Therefore, chronic laryngitis that lasts more than a few weeks and is not associated with systemic disease usually
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is associated with recurrent exposure of the larynx to an irritant. Tobacco smoke is the most commonly inhaled irritant, but laryngitis can occur with cannabis smoking and other inhaled smoke sources. For patients with chronic laryngitis who do not smoke, it appears that the most common source of irritant is reflux of gastric contents. Historical evidence suggests that this most commonly occurs during sleep and usually is silent at the time the exposure occurs. Symptoms of chemical burn injury may vary from very mild to severe, but usually the exposure does not awaken patients. In its most common and mild form, reflux causes injury isolated to the posterior part of the larynx, but any part of the upper respiratory tract epithelium will become inflamed if exposed to sufficient gastric liquids to cause injury. Because the visible evidence of mucous membrane injury (specifically redness, loss of surface mucous layer, granularity, and ulceration) is not specific for a cause of the inflammation, we prefer to use the term chronic laryngitis, which may be mainly confined to the posterior larynx . After a careful history, assessment for other causes of irritation, successful treatment trial, or positive pH study, we may determine that the chronic irritative laryngitis is the result of reflux. Only then is the term “reflux laryngitis” accurate. In summary, it is our experience that chronic laryngitis, which may or may not be confined to the posterior larynx, and which usually responds to treatment aimed at reducing nocturnal reflux of acid containing gastric juices, is a very common cause of throat and voice complaints. The large majority of patients with chronic laryngitis complaints can be adequately evaluated and treated based on history of symptoms and a simple examination of their larynx. Although many patients with mild laryngitis will recover by following simple life-style precautions, the availability of potent acid-suppressing medications has greatly expanded our ability to treat successfully chronic irritative laryngitis that is associated with reflux.
ACKNOWLEDGMENT
3.
4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
14. 15. 16.
17. 18.
19.
20.
This review of experience in the diagnosis and treatment of chronic irritative laryngitis at Northwestern University Medical School has benefited from collaboration of several colleagues who have shared in studies related to reflux and laryngitis. Particularly, we acknowledge the important contributions of Peter Kahrilas and Perry Kamel in gastroenterology, Jack Jiang, Emily Lin, Barbara Pauloski, and Jerilynn Logemann in speech science, and the valuable participation of the patients who have provided the basis of our experience.
21.
22.
23.
REFERENCES 1. Kamel PL, Karhilas PJ, Hanson DG. A prospective study of posterior laryngitis treatment with omeprazole. Gastroenterology. 1992;102:A93. Abstract. 2. Kamel PL, Hanson DG, Kahrilas PJ. Omeprazole for the
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treatment of posterior laryngitis. Am J Med. 1994;96:321– 326. Hanson DG, Kamel P, Kahrilas P. Outcomes of anti-reflux therapy for the treatment of chronic laryngitis. Ann Otol Rhinol Laryngol. 1995;104:550 –555. Jackson C. Contact ulcer of the larynx. Ann Otol Rhinol Laryngol. 1928;37:227–230. Olson NR. Aerodigestive malignancy and gastroesophageal reflux disease. Am J Med. 1997;103:97S–99S. Review. Woodruff GH. Contact ulcers of the larynx. JAMA. 1936; 106:1562–1569. Peach G, Holinger P. Contact ulcer of the larynx: II. The role of vocal re-education. Arch Otolaryngol 1947;46:617– 623. New GB, Devine KD. Contact ulcer granuloma. Ann Otol Rhinol Laryngol. 1949;58:548 –558. Baker DC Jr. Contact ulcer of the larynx. Laryngoscope. 1954;64:73–78. von Leden H, Moore P. Contact ulcer of the larynx: experimental observations. Arch Otolaryngol. 1960;72:746 –752. Cherry J, Margulies SI. Contact ulcer of the larynx. Laryngoscope. 1968;73:1937–1940. Delahunty JE, Cherry J. Experimentally produced vocal cord granulomas. Laryngoscope. 1968;78:1941–1947 Jackson C. Contact ulcer granuloma and other laryngeal complications of endotracheal anesthesia. Anesthesiology. 14:425– 436. Snow GC, Arano M, Balogh K. Post intubation granuloma of the larynx. Anesth Analg. 1966;45:425– 436. Holinger PH, Johnston KC. Contact ulcer of the larynx. JAMA. 1960;172:511–515. Ward PH, Zwitman D, Hanson D, Berci G. Contact ulcers and granulomas of the larynx: new insights into their etiology as a basis for more rational treatment. Otolaryngol Head Neck Surg. 1980;88:262–269. Gaynor EE. Otolaryngologic manifestations of gastroesophageal reflux. Am J Gastroenterol. 1991;86:801– 808. Jacob P, Kahrilas PJ, Herzon G. Proximal esophageal pHmetry in patients with “reflux laryngitis.” Gastroenterology. 1991;100:305–310. Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope. 1991; 101(suppl 53):1–78. Little FB, Koufman JA, Kohut RI, Marshall RB. Effect of gastric acid on the pathogenesis of subglottic stenosis. Ann Otol Rhinol Laryngol. 1985;94:516 –519. Hanson DG, Jiang J, Chi W. Quantitative color analysis of laryngeal erythema in chronic posterior laryngitis. J Voice. 1998;12:78 – 83. Ellis S, Pollak AC, Hanson DG, Jiang JJ. Videolaryngoscopic evaluation of laryngeal intubation: incidence and predictive factors. Otolaryngol Head Neck Surg. 1996;114: 729 –731. Hanson DG, Jiang JJ, Chen J, Pauloski B. Acoustic measurement of change in voice quality with treatment for chronic posterior laryngitis. Ann Otolol Rhinol Laryngol. 1997;106:279 –285. Ward PH, Hanson DG. Reflux as an etiological factor of carcinoma of the laryngopharynx. Laryngoscope. 1988;98: 1195–1199.
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Chronic laryngitis symptoms are commonly seen in otherwise healthy people. This article reviews recent progress in our understanding and effective treatment of chronic laryngitis. Clinical experience and prospective treatment and outcome studies have demonstrated objective evidence of the efficacy of treating patients with chronic laryngitis symptoms with nocturnal antireflux precautions and acid-suppressing medications. The role of pH testing and most common errors in treatment are reviewed. Am J Med. 2000;108(4A):112S–119S. © 2000 by Excerpta Medica, Inc.
amel et al1 reported treatment of chronic posterior laryngitis with omeprazole in 1992, addressing the hypothesis that if chronic laryngitis were related to reflux, it should substantially improve when acid secretion was profoundly suppressed. That study demonstrated that treatment with a proton pump inhibitor, along with lifestyle modifications, alleviates most chronic laryngitis symptoms, as well as the visible evidence of chronic inflammation.2 A prospective case study subsequently examined the outcomes of a progression of treatment—from antireflux precautions, to H2 blockers, to proton pump inhibitors in progressively higher dosage—for chronic laryngitis symptoms. The study also assessed degree of laryngeal inflammation and recurrence rate in relation to the progressively more intense treatment modalities.3 That study demonstrated that there is a range of inflammation associated with chronic laryngitis that responds to antireflux treatment and demonstrated that for 50% of patients with chronic laryngitis symptom, antireflux precautions alone are sufficient for resolution of symptoms. Our experience since that report has been substantially greater, has not significantly changed our conclusions reported in 1996, but has added some new insights, which we will discuss in this overview. Our practices are situated in an urban environment with a population of business professionals who tend to work late, who usually eat later in the evening, and who admit to notable stress. It seems that this group of patients has a relatively high incidence of chronic laryngitis symptoms.
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LARYNGITIS
From the Department of Otolaryngology, Head and Neck Surgery, Northwestern University Medical School, Chicago, Illinois, USA. Requests for reprints should be addressed to David G. Hanson, MD, Department of Otolaryngology, Head and Neck Surgery, Northwestern University Medical School, 303 East Chicago Avenue, Searle 12-580, Chicago, Illinois 60610. 112S © 2000 by Excerpta Medica, Inc. All rights reserved.
Symptoms of discomfort of the throat, change in voice, cough, dysphagia, and secretion stasis can occur with any cause of inflammation. Symptoms can be classified as acute or chronic, and can occur from infection, from exposure to toxic irritants, or from other factors that provoke an inflammatory reaction. Patients who complain of long-term chronic symptoms that relate to the throat may have varying degrees of symptom intensity, duration, and visible inflammation of the structures in the hypopharynx and pharynx. The signs of inflammation on examination of the larynx and pharynx can vary from subtle erythema of the posterior larynx to severe mucosal changes with ulceration and formation of granulation tissue. Historically, ulcerative changes with granulation for0002-9343/00/$20.00 PII S0002-9343(99)00349-6
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mation were the first manifestations of chronic laryngitis to be recognized.
ULCERATION OF LARYNGEAL EPITHELIUM The most severe manifestation of chronic laryngeal irritation is actual ulceration of the laryngeal epithelium with granulation. Jackson4 first called attention to contact ulcers of the posterior larynx and attributed the injury to mechanical trauma. Other authors also supported a primarily traumatic etiology.5–10 Cherry and Margulies11 first identified acidification of the larynx as a probable factor in contact ulcers, and Delahunty and Cherry12 demonstrated that ulcers could be produced experimentally by application of gastric acid. Treatments for contact ulcers and granulomas have included surgical excision, “vocal reeducation,” and other forms of speech therapy, but these therapies have had disappointing variations in success.13–15 Ward et al16 in 1979 concluded after study of 28 patients with contact granulomas “that habitual throat clearing . . . and most important, acid regurgitation secondary to hiatal hernia are the causal factors of contact ulcers.” There developed a growing appreciation that gastroesophageal reflux could be associated with extraesophageal disease.17 Jacob et al in 199118 reported that chronic laryngitis symptoms and posterior laryngitis without ulceration could be associated with evidence of gastropharyngeal reflux documented by pH monitoring. Koufman19 also reported in 1991 a large series of patients with laryngeal inflammatory diseases that were associated with pH monitoring evidence of reflux. He supplemented the clinical experience with experimental evidence that supports the concept that application of gastric juices could cause laryngeal mucosal injury. It was with the advent of medications that profoundly suppress gastric acid secretion that argument for a relationship between gastric acid reflux and chronic laryngeal inflammation really started to become convincing. Kamel et al2 reported the elimination of symptoms and signs of chronic posterior laryngitis during treatment with omeprazole in a prospective study in 1994. Figure 1 reproduces data for a symptom index that patients recorded before, during, and after cessation of treatment with omeprazole. Whereas contact ulcers that occur over the cartilage of the vocal processes are painful and problematic because they can form large granulomas, circumferential ulcerative damage to the epithelium of the posterior and subglottic larynx causes more severe damage to function. Little et al20 reported in 1985 a case of acquired subglottal stenosis associated with reflux and described an animal experiment in which application of gastric juices to the subglottal larynx produced stenosis. As discussed elsewhere in this issue, reflux-related stenosis of the larynx and subglottic area is now a well-recognized problem in neonates. Acquired stenosis of the larynx in adults who
Figure 1. Kamel et al reported that laryngeal symptoms documented daily by patients with chronic laryngitis changed significantly after 6 to 9 weeks of treatment with omeprazole with antireflux precautions. Symptoms recurred to a smaller degree after omeprazole was discontinued. (Adapted from Am J Med.2)
have no history of long-term intubation is less common but does occur. We have been involved in the care of five adults who developed subglottic or glottic stenosis in association with reflux. Subglottal stenosis and posterior glottic stenosis are the most difficult to treat of the complications of supraesophageal reflux and, fortunately, are rare. Other manifestations of chronic supraesophageal reflux, some of which can be life-threatening, also have been subjects of clinical interest in the past decade and are discussed in other papers from this conference. The most common forms of laryngitis that can be associated with reflux can be present for months to years before the individual seeks and finds effective treatment. The following is a summary overview of our clinical experience over the last decade with diagnosis and treatment of the more common symptoms of chronic irritative laryngitis.
POSTNASAL DRIP AND SENSATION OF SECRETIONS Symptoms of chronic irritative laryngitis occur from injury to the normal function of the epithelium and adjacent structures of the pharynx and larynx. The earliest symptoms to manifest with mild injury (and the last to resolve with treatment) are associated mainly with damage to the ciliary clearance function of the ciliated respiratory epithelium. Patients most often describe these symptoms as postnasal drip. However, the symptoms of constant secretions in the back of the throat usually are
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Figure 2. The posterior larynx and interarytenoid area of the posterior glottic wall lies directly above and adjacent to the opening of the esophagus posteriorly. This area is red in patients with chronic laryngitis.
the result of ciliary dysfunction in the posterior larynx and pharynx rather than the nose. In the normally functioning larynx, the outflow of mucous secretion from the entire tracheal bronchial tree is directed by normal ciliary beating cephalad toward and through the posterior wall of the glottic aperture. The epithelium of the vocal folds is a stratified squamous epithelium that is more suited to resist the vibratory effects of phonation, and although better suited to mechanical vibration, the vocal fold epithelium provides a barrier to effective mucous transport. Therefore, the posterior larynx is particularly important in mucous flow out of the tracheobronchial tree. When the ciliary function of the posterior laryngeal mucosa is damaged by chemical irritation, or by mechanical trauma, mucous stasis at the outflow of the trachea becomes an annoying and prominent symptom.
COUGH AND THROAT CLEARING The neural organization of laryngeal sensory and motor systems has an important life-saving role, represented by cross brainstem reflexes, which protect the airway from aspiration. Clumping of mucous in the posterior larynx and strings of mucous across the vocal folds can provoke cough and laryngospasm at an unconscious reflex level as well as provoking throat clearing at a conscious level. Cough and laryngospasm appear to be more likely if the sensitivity of laryngeal sensory endings is upregulated by local inflammation. Other articles in this supplement discuss important aspects of that sensory system. Throat clearing behavior is directed at trying to remove secretions from the larynx but also is traumatic to the epithelium of the vocal process and the posterior glottic 114S March 6, 2000 THE AMERICAN JOURNAL OF MEDICINE威
wall. Physiologically, throat clearing is accomplished by firm closure of the vocal folds and forcing of airflow through the posterior aperture of the glottis behind the vocal folds. This is the area of ciliated respiratory epithelium where mucous is transported through the larynx. However, repeated mechanical trauma associated with frequent throat clearing appears, in itself, to cause damage to the delicate ciliary function of the posterior larynx. In patients who chronically clear their throats, this area of mucosa can appear rough, thickened, and callous-like. An unusual amount of throat clearing is commonly observed in patients with posterior laryngitis. Often, this is a habituated behavior that is done unconsciously. The laryngeal structures are important articulators in speech, and the neural control of these structures appears to be susceptible to relatively rapid habituation of automatic unconscious response to stimuli. This may explain why throat clearing and cough so easily become habits. Anatomically, this area of the larynx is directly in front of the opening of the esophagus into the pharynx. Figure 2 shows a picture of how the larynx would appear in a patient lying on the back and breathing quietly. It becomes apparent that very small amounts of refluxed material, if only in the form of a bubble of liquid film, could easily get to the posterior laryngeal wall. This is the area in which we first see signs of inflammation in patients with chronic laryngitis symptoms.
SORE THROAT The second most common manifestation of irritative laryngitis is sensation of discomfort that may be described as a dry, scratchy feeling, tightness in the throat, or sore
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throat. If there is ulceration of the epithelium, most commonly over the vocal processes and usually associated with chronic throat clearing, there may be localized pain that may radiate to the ear. Patients who have recurrent severe sore throats without other typical symptoms of an upper respiratory infection syndrome are likely to have irritative laryngitis as an underlying cause. The complaint of soreness, irritation, or pain usually is associated with visible signs of inflammation on laryngeal examination. The cardinal manifestation of this inflammation is erythema and visible increase in surface vascularity. Hanson et al21 recently reported a study of a large group of patients with chronic laryngitis symptoms in which videodocumented images of the laryngeal examination were digitized and subjected to digital color analysis. Color value for red, green, and blue was determined in multiple 5 ⫻ 5 pixel areas and averaged for measurement of the degree of redness of the epithelium over the posterior larynx and the epithelium on the vocal folds. The values for red color were related as a percent to the overall values for red ⫹ green ⫹ blue to define a red index
冉
red index ⫽
冊
red value . red ⫹ green ⫹ blue
The study showed a significant difference in red index between normal subjects and individuals who complained of chronic laryngitis symptoms. Figure 3 reproduces data on difference in redness between patients with laryngitis and normal subjects. In addition, during treatment, serial examinations of the larynges of patients with chronic laryngitis showed a significant treatment effect as the larynges became significantly less red with antisecretory and antireflux therapy. Figure 4 reproduces data on change in redness during treatment with omeprazole. Therefore, it appears that the visible inflammation manifested by erythema is a hallmark of posterior irritative laryngitis that responds to treatment for nocturnal reflux. In some situations, it may be advantageous to recognize the signs of laryngeal inflammation even when the patient does not volunteer complaints. Ellis et al22 reported on a prospective study of video-documented laryngeal examinations in 75 patients who were scheduled to have open heart surgery with prolonged intubation. Blinded analysis of the pre- and postintubation laryngeal examinations indicated that patients who had visible evidence of inflammation of the larynx in the pre-intubation examination were likely to have more severe postintubation injuries manifested by impressive edema, ulceration, granulation, and paresis. We now recommend that patients who will have prolonged intubation be covered with antisecretory acid suppression.
HOARSENESS AND CHANGE IN VOICE The third most common complaint of chronic laryngitis is deterioration in voice quality with voice use. Progres-
Figure 3. Hanson et al reported that between patients with chronic laryngitis symptoms and normal individuals with no laryngeal complaints, there was a significant difference in red value measured from digital color images of the larynx. Post ⫽ posterior; Voc ⫽ vocal. (Adapted from J Voice.21)
Figure 4. Change in redness of the vocal folds was documented with treatment by Hanson et al. (Adapted from J Voice.21)
sively impaired voice quality may be the primary complaint of posterior irritative laryngitis without soreness or other symptoms. In order to examine the complaint of hoarseness, Hanson et al23 studied patients with chronic laryngitis symptoms as they were being treated with omeprazole and antireflux precautions. Voice recordings
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Figure 5. Hanson et al reported that percent jitter and shimmer, and the ratio of clear signal to noise in the voice, changed significantly during treatment with omeprazole for patients with hoarseness associated with chronic laryngitis. (Time in weeks). (Adapted from Ann Otolol Rhinol Laryngol.23)
were made in a sound-protected room with a high-quality microphone and recording system. The recordings were digitized, and representative segments from stable mid phonation were analyzed blindly for perturbation of the voice signal. Jitter is a measure of the cycle-to-cycle variability in the period of the acoustic signal and detects irregularity of frequency of cycles in the acoustic signal. There was a significant decrease in jitter during treatment in the voices of patients with chronic laryngitis who complained of the symptom of hoarseness. Shimmer is a measure of cycle-to-cycle variation in the amplitude of the acoustic signal envelope and is a measure of how much intensity of the phonation is perturbed from cycle to cycle. During treatment for reflux, there was a significant decrease in the shimmer in the voices of patients who had complained of hoarseness. Signal-to-noise ratio of the acoustic signal is another measure of cycle-to-cycle regularity or irregularity. The measure uses an autocorrelation technique to compare how well the acoustic signal 116S March 6, 2000 THE AMERICAN JOURNAL OF MEDICINE威
matches from cycle to cycle versus random noise in the signal. A significant improvement in signal-to-noise ratio was demonstrated during antireflux and antisecretory treatment for patients who had complained of vocal hoarseness. Figure 5 shows data for percent jitter, percent shimmer, and signal-to-noise ratio from that study.
TREATMENT Prospective study of patients with chronic laryngitis complaints has demonstrated that approximately 50% of such patients will have symptoms resolve if they can be convinced to reliably follow nocturnal antireflux precautions (avoid food and liquids 2 to 3 hours before retiring and sleep with head and shoulders consistently elevated during sleep so that the throat area is elevated higher than the stomach).3 Patient education is key to successful treatment. Individuals are unlikely to make lifestyle changes unless they are convinced that so doing is important to resolution of symptoms. Most patients with mild chronic
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posterior laryngitis do not complain of significant amounts of heartburn and do not have gastropharyngeal reflux during the day; therefore, it is not intuitive that their symptoms might be caused by silent reflux episodes during sleep. Comparison of laryngeal examination data and demographic information with treatment outcome data suggests that patients who are most likely to respond to nocturnal antireflux precautions alone are patients who are young, whose lifestyle and habits put them at risk for reflux. These patients also usually have relatively mild evidence of inflammation on examination. Typical of this group is an individual who eats late at night, has alcohol in the evening, and sleeps flat. The incidence of hiatal hernia in this population is similar to that of the general population, approximately 20%, and these patients usually do not demonstrate any esophageal disease or any reflux on barium swallow examination. Another 25% of patients who complain of chronic laryngitis symptoms require an H2 blocker, in addition to observing nocturnal antireflux precautions. These tend to be patients who have mild to moderate changes on laryngeal examination and who have had onset of symptoms in association with stress. These patients are more likely to demonstrate increased episodes of reflux on pH studies but may have “normal” pH monitoring patterns at the time that they are studied. Approximately 25% of patients with chronic laryngitis symptoms require prolonged treatment with a proton pump inhibitor in order to achieve acceptable improvement in their symptoms and signs of laryngitis. These patients usually have evidence of more severe laryngeal inflammation on initial examination and may have evidence of inflammation of upper pharynx and nasopharynx. These patients are more likely to be aware of heartburn and gastropharyngeal reflux episodes during the day or night, and they are more likely to have relapse of symptoms and evidence of inflammation when acid suppression is discontinued. A few patients require high-dosage proton pump inhibitor to suppress acid secretion. Monitoring of esophageal pH while on medication can be helpful in patients who do not appear to be responding to what should be adequate dosages of acid suppression medication. These patients may demonstrate repeated acidification of the upper esophagus, even though they are taking a dosage of proton pump inhibitor that is usually adequate to provide effective suppression. This group of patients is more likely to have relapse of symptoms and recurrence of laryngitis when they stop taking medication and are more likely to have recurrent and prolonged problems. Patients with reflux and acidity that is resistant to treatment with usual dosage of proton pump inhibitors are probably candidates for fundoplication. Successful fundoplication is cost-effective in comparison with long-term high-dose proton pump inhibitor suppression, but many patients
are reluctant to have surgery if they can have their symptoms controlled with medication that seems to have relatively little side effect. A small percentage of patients cannot tolerate proton pump inhibitors or may not have acid production adequately suppressed even on high dosage of inhibitors yet will usually have complete resolution of both symptoms and laryngeal evidence of inflammation after fundoplication.
ROLE OF pH MONITORING STUDIES IN OUR PRACTICE Approximately 75% of the patients that we see with chronic laryngitis will achieve resolution of laryngitis symptoms by following nocturnal antireflux precautions with or without a relatively inexpensive H2 blocker. Therefore, we think that routine pH studies are not costeffective for the diagnosis and management of posterior laryngitis. This author’s personal experience with nocturnal reflux and our clinical practice experience suggest that the reflux associated with chronic irritative laryngitis may occur very intermittently, as well as silently. Therefore, pH monitoring studies suffer from a sampling problem. We have treated many patients who demonstrated “normal” patterns of esophageal acidification during the period that they had pH monitoring but who, nevertheless, had complete resolution of symptoms and laryngitis with nocturnal antireflux precautions and acid suppression. Some degree of reflux occurs in most individuals, and some reflux into the esophagus at night is normal. While in a healthy condition, the laryngeal and esophageal mucosa appear to tolerate some level of reflux. However, it seems that once there is some injury to the epithelium, further exposure to gastric acid is not tolerated well. We find that patients who have had radiation to the larynx do not tolerate acid exposures that would fall within pH data expected for normal subjects. Therefore, although pH monitoring has had an important place in the understanding of chronic irritative laryngitis and reflux, in most cases that have an appearance and symptoms characteristic of chronic irritative type of laryngitis, we would not withhold acid suppression simply based on a “normal” pH study. Probe monitoring of esophageal acidification, therefore, is not obtained routinely for patients who present with only laryngitis symptoms. In our practice, all patients who require long-term or high-dosage proton pump suppression, and all patients who have esophageal symptoms, are treated and observed in conjunction with a gastroenterologist.
TREATMENT OF VOCAL GRANULOMAS In an ongoing prospective study of patients presenting with vocal process granulomas at Northwestern University Medical School, treatment with antireflux precau-
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tions and suppression of gastric acid secretion with proton pump inhibitors has been uniformly successful in the complete resolution of vocal process ulcers and granulomas. This study, which represents a notable departure from the generally unsuccessful experience with surgical excision and speech therapy as primary treatments for vocal granulomas, will be completed and reported in the near future. To date, 12 patients have been followed for at least a year after resolution of their granuloma. The treatment period averaged 5 months to resolution of the lesions. Duration of treatment required to reach resolution appears related to the size of the granuloma and the degree to which throat clearing behavior can be eliminated.
trast, we know from 24-hour pH monitoring data that some degree of reflux is tolerated without evidence of injury by patients who do not have laryngeal symptoms. Commonly chronic laryngeal symptoms can be traced back to an episode of severe coughing, vomiting, or other trauma to the laryngeal epithelium. This may suggest that the laryngeal mucosa tolerates some degree of reflux until it is injured by some other form of trauma, but once injured, subsequent episodes of reflux on the inflamed epithelium cause progressive damage. Once evidence of laryngitis has healed, many patients may resume their previous lifestyle habits without recurrence of symptoms for prolonged periods of time.
TREATMENT FAILURES
LONG-TERM FAILURE OF TREATMENT AND LARYNGEAL CANCER
The most common error of chronic laryngitis symptom treatment that is observed in our tertiary referral practice is treatment of the sore throat with antibiotics alone. Patients with chronic laryngitis usually do feel better on antibiotics. Unfortunately, the symptoms recur as soon as antibiotic is discontinued. The second most common error is failure of physicians to explain adequately the rationale for treatment to patients, with the result that patients do not follow antireflux precautions. Patient education is a key factor in inducing patients to change significant sleeping, eating, and drinking aspects of their lifestyle. Although acid suppression clearly has an important role in the treatment of chronic irritative laryngitis, acid suppression alone may not be adequate to achieve long-term resolution of laryngeal inflammation and symptoms. Therefore, precautions to minimize the likelihood of nocturnal reflux appear to be important in the prevention of further laryngeal injury and also may be the only treatment needed for the majority of patients with mild symptoms and signs of inflammation. The third most common error of treatment that we see is inadequate length of treatment. It is not unusual for patients to take medication and follow precautions for 2 to 3 weeks but then to stop treatment because they do not feel significant improvement. It is important that patients understand that the injury to the epithelium of the larynx and hypopharynx that is associated with reflux is a chemical burn. Antireflux precautions and acid suppression do not reverse injury to the laryngeal epithelium. Rather, prolonged prevention of further injury is needed to allow healing of the tissues and eventual resolution of symptoms. Some vocal granulomas in our currently ongoing series have required 9 months of preventive treatment. Once injured, refluxed materials may further irritate the laryngeal epithelium even if pH is relatively high. Neither acid suppression nor antireflux precautions completely controls the possibility of intermittent reflux of gastric material up into the hypopharynx. It seems that once chronically inflamed, the epithelium of the larynx may be injured by very episodic small amounts of reflux. In con118S March 6, 2000 THE AMERICAN JOURNAL OF MEDICINE威
In 1988, Ward and Hanson reported a retrospective study of all patients in the UCLA/Wadsworth Veterans Affairs tumor registries over a 30-year period who had developed carcinoma of the laryngopharynx and who never had smoked.24 Long history of reflux was the common unifying risk factor identified in these patients. Some of the patients had been followed with chronic laryngitis for 8 to 12 years before they developed cancer. Subsequent to those observations, we have frequently identified irritative laryngitis that responds to antireflux and antisecretory therapy during the follow-up of patients whom we have successfully treated for laryngeal carcinoma. Postradiation patients may be much more susceptible to mucosal injury from reflux, and it has been our experience that antireflux treatment may be important in such patients even if they have normal pH studies. Individual patients who have had normal pH studies, nevertheless, have demonstrated evidence of severe ongoing chronic inflammation, which did respond to acid suppression and antireflux precautions. Although a causative relationship between chronic irritative laryngitis from reflux and cancer has not been established experimentally, it seems likely that chronic laryngeal irritation from reflux may be a risk factor for carcinoma. Olson5 recently reviewed evidence that reflux of gastric contents outside of the stomach might be related to development of cancer in the esophagus, larynx, or lungs. Finally, we would insert a word about terminology. Laryngitis, or inflammation of the larynx, can be caused by infection with viruses, with other organisms, by trauma or thermal injury, or by exposure to toxic materials. Infectious acute laryngitis, usually from virus infection, rarely lasts more than 10 to 14 days at the most. Acute bacterial infection, supraglottitis, is also not a chronic condition. Generally, chronic infections, with tuberculosis, Candida, or exotic infections are rare and usually occur in association with other evidence of disease. Therefore, chronic laryngitis that lasts more than a few weeks and is not associated with systemic disease usually
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is associated with recurrent exposure of the larynx to an irritant. Tobacco smoke is the most commonly inhaled irritant, but laryngitis can occur with cannabis smoking and other inhaled smoke sources. For patients with chronic laryngitis who do not smoke, it appears that the most common source of irritant is reflux of gastric contents. Historical evidence suggests that this most commonly occurs during sleep and usually is silent at the time the exposure occurs. Symptoms of chemical burn injury may vary from very mild to severe, but usually the exposure does not awaken patients. In its most common and mild form, reflux causes injury isolated to the posterior part of the larynx, but any part of the upper respiratory tract epithelium will become inflamed if exposed to sufficient gastric liquids to cause injury. Because the visible evidence of mucous membrane injury (specifically redness, loss of surface mucous layer, granularity, and ulceration) is not specific for a cause of the inflammation, we prefer to use the term chronic laryngitis, which may be mainly confined to the posterior larynx . After a careful history, assessment for other causes of irritation, successful treatment trial, or positive pH study, we may determine that the chronic irritative laryngitis is the result of reflux. Only then is the term “reflux laryngitis” accurate. In summary, it is our experience that chronic laryngitis, which may or may not be confined to the posterior larynx, and which usually responds to treatment aimed at reducing nocturnal reflux of acid containing gastric juices, is a very common cause of throat and voice complaints. The large majority of patients with chronic laryngitis complaints can be adequately evaluated and treated based on history of symptoms and a simple examination of their larynx. Although many patients with mild laryngitis will recover by following simple life-style precautions, the availability of potent acid-suppressing medications has greatly expanded our ability to treat successfully chronic irritative laryngitis that is associated with reflux.
ACKNOWLEDGMENT
3.
4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
14. 15. 16.
17. 18.
19.
20.
This review of experience in the diagnosis and treatment of chronic irritative laryngitis at Northwestern University Medical School has benefited from collaboration of several colleagues who have shared in studies related to reflux and laryngitis. Particularly, we acknowledge the important contributions of Peter Kahrilas and Perry Kamel in gastroenterology, Jack Jiang, Emily Lin, Barbara Pauloski, and Jerilynn Logemann in speech science, and the valuable participation of the patients who have provided the basis of our experience.
21.
22.
23.
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treatment of posterior laryngitis. Am J Med. 1994;96:321– 326. Hanson DG, Kamel P, Kahrilas P. Outcomes of anti-reflux therapy for the treatment of chronic laryngitis. Ann Otol Rhinol Laryngol. 1995;104:550 –555. Jackson C. Contact ulcer of the larynx. Ann Otol Rhinol Laryngol. 1928;37:227–230. Olson NR. Aerodigestive malignancy and gastroesophageal reflux disease. Am J Med. 1997;103:97S–99S. Review. Woodruff GH. Contact ulcers of the larynx. JAMA. 1936; 106:1562–1569. Peach G, Holinger P. Contact ulcer of the larynx: II. The role of vocal re-education. Arch Otolaryngol 1947;46:617– 623. New GB, Devine KD. Contact ulcer granuloma. Ann Otol Rhinol Laryngol. 1949;58:548 –558. Baker DC Jr. Contact ulcer of the larynx. Laryngoscope. 1954;64:73–78. von Leden H, Moore P. Contact ulcer of the larynx: experimental observations. Arch Otolaryngol. 1960;72:746 –752. Cherry J, Margulies SI. Contact ulcer of the larynx. Laryngoscope. 1968;73:1937–1940. Delahunty JE, Cherry J. Experimentally produced vocal cord granulomas. Laryngoscope. 1968;78:1941–1947 Jackson C. Contact ulcer granuloma and other laryngeal complications of endotracheal anesthesia. Anesthesiology. 14:425– 436. Snow GC, Arano M, Balogh K. Post intubation granuloma of the larynx. Anesth Analg. 1966;45:425– 436. Holinger PH, Johnston KC. Contact ulcer of the larynx. JAMA. 1960;172:511–515. Ward PH, Zwitman D, Hanson D, Berci G. Contact ulcers and granulomas of the larynx: new insights into their etiology as a basis for more rational treatment. Otolaryngol Head Neck Surg. 1980;88:262–269. Gaynor EE. Otolaryngologic manifestations of gastroesophageal reflux. Am J Gastroenterol. 1991;86:801– 808. Jacob P, Kahrilas PJ, Herzon G. Proximal esophageal pHmetry in patients with “reflux laryngitis.” Gastroenterology. 1991;100:305–310. Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope. 1991; 101(suppl 53):1–78. Little FB, Koufman JA, Kohut RI, Marshall RB. Effect of gastric acid on the pathogenesis of subglottic stenosis. Ann Otol Rhinol Laryngol. 1985;94:516 –519. Hanson DG, Jiang J, Chi W. Quantitative color analysis of laryngeal erythema in chronic posterior laryngitis. J Voice. 1998;12:78 – 83. Ellis S, Pollak AC, Hanson DG, Jiang JJ. Videolaryngoscopic evaluation of laryngeal intubation: incidence and predictive factors. Otolaryngol Head Neck Surg. 1996;114: 729 –731. Hanson DG, Jiang JJ, Chen J, Pauloski B. Acoustic measurement of change in voice quality with treatment for chronic posterior laryngitis. Ann Otolol Rhinol Laryngol. 1997;106:279 –285. Ward PH, Hanson DG. Reflux as an etiological factor of carcinoma of the laryngopharynx. Laryngoscope. 1988;98: 1195–1199.
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