Shoib Sana, DO; Munib Sana, MD; Nikki Johnston, PhD; Hoarseness and chronic : Sumeet K. Mittal, MD Otolaryngology – Head and Neck Surgery, Detroit Would you suspect reflux? Medical Center, Detroit (Dr. Shoib Sana); Department of Radiology, disease is often misdiagnosed Maine Medical Center, Portland (Dr. Munib Sana); as an upper respiratory or allergic rhinitis—or Department of Otolaryngology and confused with GERD. This review will help you diagnose Communication Sciences, Medical College and treat it. of Wisconsin, Milwaukee (Dr. Johnston); Esophageal Center, Creighton University School of Medicine, Omaha, Neb (Dr. Mittal) CASE c When Joan C, a 35-year-old patient whom you’ve Practice known for years, comes in for a physical, you notice that she’s recommendations [email protected] coughing frequently. Upon questioning, Joan says she first › Recommend dietary and The authors reported no noticed the cough several months ago; she also reports that potential conflict of interest behavioral modifications as she’s frequently hoarse, but has no other symptoms. Joan is a relevant to this article. a first step in treating patients former smoker, and quit 4 years ago. with symptoms sugges- If Joan were your patient, would you suspect that she had tive of laryngopharyngeal an upper respiratory infection and prescribe an antibiotic such reflux disease (LPRD). C as azithromycin? Would you include laryngopharyngeal reflux › When medications are disease in the differential diagnosis? needed, prescribe a high- dose proton-pump inhibitor, aryngopharyngeal reflux disease (LPRD) is a com- a histamine-2 blocker at bedtime, and prophylactic mon condition that most primary care physicians en- antacids for reflux-inducing L counter frequently. It is also frequently misdiagnosed activities, such as exercis- by clinicians who are unfamiliar with the differences between ing and eating. B LPRD and gastroesophageal reflux disease (GERD). The American Academy of Otolaryngology–Head and › Avoid the rebound effect associated with abrupt Neck Surgery defines laryngopharyngeal reflux as the retro- cessation of medications grade movement of gastric contents into the laryngophar- prescribed for LPRD with a ynx.1 Common symptoms include hoarseness/dysphonia, gradual, 16-week taper. C chronic throat clearing, dysphagia, globus pharyngeus, and chronic cough, as well as postnasal drip, paroxysmal la- Strength of recommendation (SOR) ryngospasm, odynophagia, excessive throat mucus, and a A Good-quality patient-oriented strange taste in the mouth.2 evidence B  Inconsistent or limited-quality The diversity and vagueness of these symptoms, as well patient-oriented evidence as the lack of a gold standard diagnostic test for LPRD, make C  Consensus, usual practice, opinion, disease-oriented it difficult to estimate its prevalence. In addition, signs of gas- evidence, case series troesophageal reflux can be found in the laryngopharynx of up to 86% of healthy individuals, further complicating the clinical picture.3 To avoid missing this often overlooked reflux disease, you need to know how it develops, what signs and symptoms to look for, and which distinguishing features to keep in mind.

458 The Journal of Family Practice | August 2011 | Vol 60, No 8 TABLE 1 When to suspect laryngopharyngeal reflux disease1,5,24

Finding Frequency among patients with LPRD (%)*

Dysphonia/hoarseness (intermittent) 71

Chronic cough 51

Globus pharyngeus 47

Chronic throat clearing 42

Dysphagia 35

Heartburn 35

*The frequency of other symptoms associated with LPRD is not known.

Pathophysiology function and upper esophageal sphincter and distinguishing features dysfunction. The fact that only a minimal The precise way in which LPRD develops is amount of reflux enters the laryngopharynx not known, but there are 2 proposed means may be part of the reason heartburn is less The timing of of laryngeal injury—direct and indirect. In likely in patients with LPRD. reflux—whether the first case, chemical irritants in the- gas z Onset of symptoms. When reflux oc- it occurs when tric refluxate enter the laryngopharynx and curs is another thing that distinguishes LPRD the patient is cause local mucosal injury. In the second, and GERD. Symptoms of GERD typically standing or gastric reflux irritates the esophageal tissue worsen when the individual is supine, while supine— enough to evoke laryngeal reflexes without laryngopharyngeal reflux usually occurs can aid in ever reaching the —a vagally mediated when he or she is upright.7 The frequency differentiating response associated with symptoms such as with which these 2 conditions overlap is de- between LPRD chronic cough, throat-clearing sensations, batable, as there are few studies differentiat- and GERD. and bronchoconstriction.4 ing LPRD and GERD based on standardized Unlike the esophageal lining, laryngeal signs and symptoms.7 epithelium is not protected against chemical injury from gastric acid, as it lacks both the stripping motion of esophageal peristalsis Making sense of signs and the neutralizing bicarbonate in saliva.4 and symptoms Thus, while far smaller amounts of gastric re- Most patients with LPRD seek treatment flux make it into the laryngopharynx, the acid from their primary care physician, typically remains there longer and may cause greater reporting symptoms that they don’t associ- injury.5 In some cases, this occurs as often as ate with gastric reflux, such as hoarseness, a 50 times a day, although as few as 3 episodes chronic cough or sore throat, or the sensation per week have been known to cause LPRD.5 of a lump in the throat (TABLE 1). Less com- mon manifestations include “water brash”— Heartburn is not the rule excessive mucus in the mouth caused by a Heartburn is a primary complaint of patients release of salivary bicarbonate to help neu- with GERD. It is reported by little more than tralize acidity8—otitis media, sinus disease, a third (35%) of those with LPRD,5,6 how- and dental caries.5 ever, (which is why it is sometimes called z Laryngeal endoscopy may reveal the “silent” reflux disease). This is because many changes from diffuse irritation. Diffuse heartburn is caused by esophagitis due to erythema, edema, and interarytenoid hy- esophageal dysmotility and lower esophageal pertrophy/cobblestoning are the most use- sphincter dysfunction,3 while most patients ful findings for an LPRD diagnosis.9,10 But in with LPRD have normal esophageal motor most cases, only a few nonspecific signs with

jfponline.com Vol 60, No 8 | AUGUST 2011 | The Journal of Family Practice 459 TABLE 2 and studies have found the RFS to have poor Recommend these lifestyle specificity and inter-rater reliability.12-14 modifications19 z Ambulatory dual probe pH monitor- ing was considered to be the gold standard test for LPRD at one time, but newer stud- Stop smoking ies have raised questions about its validity Avoid: and usefulness, especially in patients taking • alcohol proton-pump inhibitors (PPIs).1,5,7 Newer • caffeine advanced probes featuring less invasive data • carbonated beverages • chocolate collection and greater sensitivity are under • citrus fruits development. Ambulatory 24-hour multi- • spicy/acidic foods channel intraluminal impedance with pH monitoring is the most promising new diag- Eat smaller, more frequent meals nostic tool, as it can monitor both acidic and Avoid eating within 3 hours of bedtime nonacidic reflux and distinguish between gas 15 Lose weight and liquid.

a number of possible causes (infection, envi- Treatment, like diagnosis, Only about a ronmental irritants, allergies, temperature/ is not clear-cut third of patients climate change, among others) are seen on LPRD is often called a diagnosis of exclusion, with laryngo- endoscopic examination, with little correla- because of the nonspecific nature of its signs pharyngeal tion with symptom severity. In fact, 74% of and symptoms and the importance of consid- reflux suffer otolaryngologists responding to a recent sur- ering a range of other etiologies. The differen- from heartburn. vey said they relied more on patient symp- tial diagnosis includes excessive voice use, toms than on laryngeal signs for an LPRD postnasal drip, upper respiratory infection, diagnosis.10 habitual throat clearing, allergic rhinitis, en- z The Reflux Finding Score (RFS), vironmental irritants, temperature/climate available at http://www.nature.com/gimo/ change, chronic or episodic use of alcohol contents/pt1/fig_tab/gimo46_T3.html, is a and/or tobacco, and psychological problems clinical tool developed to quantify laryngeal related to tics, such as habitual throat clear- inflammation and standardize objective en- ing or coughing.5 doscopic findings. The RFS incorporates the Diagnosis is often based on an empiric following endolaryngeal signs: trial of high-dose PPIs, with confirmation • subglottic edema dependent on symptom relief. Because there • ventricular obliteration have been few placebo-controlled trials with • erythema/hyperemia PPIs and those that have been completed • vocal cord edema had conflicting results, diagnosis based on • diffuse laryngeal edema a combination of medical history and endo- • posterior commissure hypertrophy scopic laryngeal examination may be a better • granuloma/granulation tissue approach.16,17 • thick endolaryngeal mucus. z Acid suppression therapy with either PPIs or histamine-2 (H2) receptor block- A numeric value is assigned to each, ers such as ranitidine or famotidine is the based on whether it is present or absent; par- mainstay of treatment for LPRD. But medi- tial or complete; local or diffuse; or mild or cal societies offer conflicting advice. The severe. However, the RFS, too, is an imperfect American Gastroenterological Association tool. Clinicians who have used the RFS report cautions clinicians not to prescribe acid- that a score higher than 7 identifies LPRD suppression therapy for patients with LPRD with 95% sensitivity.11 But laryngeal findings unless they also have GERD. 6 The American may be due to other causes, such as infec- Academy of Otolaryngology–Head and Neck tion, autoimmune reaction, or even allergies, Surgery recommends twice-daily PPI use for

460 The Journal of Family Practice | AUGUST 2011 | Vol 60, No 8 WOULD YOU SUSPECT reflux disease?

≥6 months.1,13 The general consensus, based z Fundoplication surgery, a procedure on clinical experience alone, is that patients in which the gastric fundus of the stom- should be treated with high doses of PPIs (eg, ach is wrapped around the lower end of the 40 mg omeprazole twice a day) for ≥6 months, esophagus and stitched in place to prevent with the addition of an H2 receptor blocker reflux, may be an option for patients who to help reduce overnight acid production.1,18 do not respond to, or cannot tolerate, ag- Prophylactic antacid use is also recommend- gressive medical treatment for LPRD. A 2006 ed in anticipation of reflux, such as before ex- prospective controlled study found that sur- ercising and right after a meal. gical fundoplication did not consistently re- Symptoms should start to improve lieve laryngeal symptoms. 20 But other studies within 6 to 8 weeks, and patients should be have found that a carefully selected popula- reassessed in about 3 months. To avoid a tion with medically unresponsive laryngo- rebound effect from the abrupt cessation pharyngeal symptoms can benefit from this of medications, we suggest a gradual ta- procedure.21,22 One study showed a signifi- per over 16 weeks. For the first 8 weeks, the cant improvement within one month of fun- H2 blocker should be discontinued and the doplication, with continued improvement PPI decreased from twice a day to once. If observed during a 3-year follow-up.21 In an- symptoms are still controlled, the PPI dose can other prospective study, researchers showed be reduced to once every other day for another that while LPRD-related laryngeal symptoms 8 weeks, then stopped if symptoms do not such as coughing and throat-clearing im- An empiric trial recur.18 proved with both medical therapy and lapa- with high-dose z Lifestyle and dietary changes roscopic fundoplication, voice quality and proton-pump (TABLE 2), such as smoking cessation, weight endoscopic laryngeal/pharyngeal findings inhibitor loss, and avoidance of alcohol, are an impor- improved significantly only with the surgical therapy is a tant part of LPRD treatment, and may be used procedure.23 JFP commonly as a first-line therapy before prescribing med- used means 19 ication. In fact, some studies have found PPI Correspondence of diagnosing therapy to be inferior to behavioral/lifestyle Shoib Sana, DO, Detroit Medical Center, Otolaryngology- Head and Neck Surgery, 6533 East Jefferson Avenue, LPRD, with modifications.17 Apartment 316, Detroit, MI 48207; [email protected] confirmation based on symptom relief.

References 1. Koufman JA, Aviv JE, Casiano RR, et al. Laryngopharyngeal tis. Gastroenterology. 1998;94:1394-1398. reflux: position statement of the committee on speech, voice, 9. Belafsky PC. Abnormal endoscopic pharyngeal and laryngeal and swallowing disorders of the American Academy of Oto- findings attributable to reflux. Am J Med 2003,116(suppl 3A): laryngology-Head and Neck Surgery. Otolaryngol Head Neck 91S-97S. Surg. 2002;127:32-35. 10. Ahmed TF, Khandwala F, Abelson et al. Chronic laryngitis as- 2. Papakonstantinou L, Leslie P, Gray J, et al. Laryngopharyngeal sociated with gastroesophageal reflux: prospective assessment reflux: a prospective analysis of a 34 item symptom question- of differences in practice patterns between gastroenterologists naire. Clin Otolaryngol. 2009;34:455-459. and ENT physicians. Am J Gastroenterol. 2006;102:470-478. 3. Hicks DM, Ours TM, Abelson TI, et al. The prevalence of hy- 11. Belafsky PC, Postma GN, Koufman JA. The validity and re- popharynx findings associated with gastroesophageal reflux in liability of the reflux finding score (RFS). Laryngoscope. normal volunteers. J Voice. 2002;16:564. 2001;111:1313-1317. 4. Johnston N, Bulmer D, Gill GA, et al. Cell biology of laryngeal 12. Koufman JA, Sataloff RT, Toohill R. Laryngopharyngeal reflux: epithelial defenses in health and disease: further studies. Ann consensus conference report. J Voice. 1996;10:215-216. Otol Rhinol Laryngol. 2003;112:481-491. 13. Belafsky PC, Postma GN, Koufman JA. Laryngopharyngeal 5. Koufman JA. The otolaryngologic manifestations of gastro- reflux symptoms improve before changes in physical findings. esophageal reflux disease (GERD): a clinical investigation of Laryngoscope 2001;111:979-981. 225 patients using ambulatory 24 hour pH monitoring and an 14. Reichel O, Dressel H, Wiederanders K, et al. Double-blind, experimental investigation of the role of acid and pepsin in the placebo-controlled trial with esomeprazole for symptoms and development of laryngeal injury. Laryngoscope. 1991;101:1-78. signs associated with laryngopharyngeal reflux. Otolaryngol 6. Kahrilas PJ, Shaheen,NJ, Vaezi M, et al. American Gastro- Head Neck Surg. 2008;139:414-420. enterological Association Institute (AGAI) medical position 15. Muderris T, Gokcan MK, Yorulmaz I. The clinical value of pha- statement: management of gastroesophageal reflux disease. ryngeal pH monitoring using a double-probe, triple-sensor Gastroenterology. 2008;135:1383. catheter in patients with laryngopharyngeal reflux. Arch Oto- 7. Postma GN, Tomek MS, Belafsky PC, et al. Esophageal motor laryngol Head Neck Surg. 2009;135:163-167. function in laryngopharyngeal reflux is superior to that in clas- 16. Steward DL, Wilson KM, Kelly DH, et al. Proton pump in- sic gastroesophageal reflux disease.Ann Otol Rhinol Laryngol. hibitor therapy for chronic laryngo-pharyngitis: a randomized 2001;111:1114-1116. placebo-control trial. Otolaryngol Head Neck Surg. 2004;131: 8. Helen JF, Dodds WJ, Hogan WJ. Salivary response to esopha- 342-350. geal acid in normal subjects and patients with reflux esophagi- 17. Wo JM, Koopman J, Harrell SP, et al. Double-blind, pla-

jfponline.com Vol 60, No 8 | AUGUST 2011 | The Journal of Family Practice 461 cebo-controlled trial with single-dose pantoprazole for 2006;4:433-441. laryngopharyngeal reflux. Am J Gastroenterol. 2006;101: 21. Catania RA, Kavic SM, Roth JS, et al. Laparoscopic Nissen 1972-1978. fundoplication effectively relieves symptoms in patients 18. Park W, Hicks DM, Khandwala F, et al. Laryngopharyngeal with laryngopharyngeal reflux. J Gastrointest Surg. 2007;11: reflux: prospective cohort study evaluating optimal dose of 1579-1587. proton-pump inhibitor therapy and pretherapy predictors of 22. Ogut F, Ersin S, Engin EZ, et al. The effect of laparoscopic Nis- response. Laryngoscope. 2005;116:1230-1238. sen fundoplication on laryngeal findings and voice quality. 19. Maceri DR, Zim S. Laryngospasm: an atypical manifesta- Surg Endosc. 2007;21:549-554. tion of severe gastroesophageal reflux disease. Laryngoscope. 23. Sala E, Salminen P, Simberg S, et al. Laryngopharyngeal reflux 2001;111:1976-1979. disease treated with laparoscopic fundoplication. Dig Dis Sci. 20. Swoger J, Ponsky J, Hicks DM, et al. Surgical fundoplication 2008;53:2397-2404. in laryngopharyngeal reflux unresponsive to aggressive acid 24. Koufman JA, Sataloff RT, Toohill R. Laryngopharyngeal reflux: suppression: a controlled study. Clin Gastroenterol Hepatol. consensus conference report. J Voice. 1996;10:215-216.

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