Amin Madani, HBSc; Leigh Sowerby, MD; James C. Gregor, MD, Detecting the other refl ux FRCPC; Eric Wong, MD, MClSc(FM), CCFP; Kevin Fung, MD, disease FRCSC, FACS Schulich School of Laryngopharyngeal refl ux is a disorder, unlike GERD, Medicine & Dentistry (Mr. Madani and that few patients (and too few physicians) are familiar Dr. Wong); Department of Otolaryngology–Head and with. Misdiagnosis is common—unless you know what Neck Surgery (Dr. Sowerby); Department of Otolaryngology, to look for. Division of Head and Neck Oncology and Reconstructive Surgery (Dr. Fung); and Department of Medicine (Dr. Gregor), aryngopharyngeal refl ux (LPR), the retrograde move- University of Western Ontario, PRACTICE ment of gastric content into the upper aerodigestive London, ON, Canada RECOMMENDATIONS tract, is a common—and commonly underdiagnosed— kevin.fung@ L lhsc.on.ca › Suspect laryngopharyngeal condition. Characterized by infl ammation of the laryngophar- refl ux (LPR) in a patient ynx, LPR can coexist with gastroesophageal refl ux disease The authors reported no potential with chronic laryngitis; confl ict of interest relevant to this (GERD), but it is a distinct disorder.1 In GERD, the lower article. 50% to 60% of such cases esophageal sphincter malfunctions, whereas LPR involves a are related to LPR. B dysfunctional upper esophageal sphincter. › Refer patients with risk fac- Because both conditions involve acid refl ux, LPR is some- tors for head and neck cancer times mistaken for GERD. Often, too, patients and physicians or whose symptoms persist alike attribute LPR’s signs and symptoms, which are largely despite lifestyle modification and medical management nonspecifi c, to other causes. Th e hoarseness and laryngitis to an otolaryngologist. A that are characteristic of LPR may be blamed on vocal cord abuse or smoking, for instance; the chronic cough and throat › While symptoms of LPR clearing associated with LPR thought to be caused by allergies; should show improvement and the sore throat and postnasal drip that often accompany after 6 to 8 weeks of proton pump inhibitor therapy, LPR attributed to infection. Another reason LPR is underdiag- advise patients to continue nosed: Primary care physicians, who are often the fi rst clini- treatment for 4 to 6 months cians from whom symptomatic patients seek treatment, are to ensure that laryngeal often unfamiliar with this lesser-known refl ux disease.2 lesions and edema resolve. B Th e failure to recognize and provide timely treatment for LPR may increase patients’ risk for a number of conditions, Strength of recommendation (SOR) including laryngeal ulcers, granulomas, subglottic stenosis, A Good-quality patient- oriented evidence chronic sinusitis, laryngospasm, nasal congestion, and asth- 1 B Inconsistent or limited-quality ma. Evidence suggests that LPR increases the risk for esopha- patient-oriented evidence geal and laryngeal carcinomas,3,4 and for laryngeal injury from C Consensus, usual practice, opinion, disease-oriented intubation, as well.1 To minimize these risks, it is important evidence, case series for primary care physicians to promptly identify this disorder, treat it appropriately, and recognize red fl ags that warrant re- ferral to a specialist. How LPR develops, what to look for Th ere is no gold standard for the diagnosis of LPR. Nonethe- 102 THE JOURNAL OF FAMILY PRACTICE | FEBRUARY 2010 | VOL 59, NO 2 102_JFP0210 102 1/21/10 1:54:44 PM Patients with LPR are particularly prone to developing hoarseness, globus pharyngeus— a sensation of a foreign body in the larynx— and sore throat. less, a review of the pathophysiology and clin- ical presentation of this refl ux disorder and the ways in which it diff ers from GERD will help you identify cases of LPR. Th e prevalence of LPR in the general population is uncertain. But reports suggest that as many as 10% of otolaryngology referrals are for patients with a classic presentation of LPR, and that 50% to refl exes through irritation of the esophagus, 60% of cases of chronic laryngitis are related leading to vagally mediated changes such as to LPR.1,5,6 chronic cough and bronchoconstriction. ❚ Enzyme production declines. Under The laryngopharynx becomes normal circumstances, carbonic anhydrase irritated and infl amed isoenzyme III (CAIII) is produced in the When the physiological barriers protecting posterior aspect of the larynx, catalyzing the the laryngopharynx from the retrograde fl ow production of bicarbonate and neutralizing of gastric content break down, gastric con- stomach acid.9-11 In LPR, however, the produc- tents can directly irritate the ciliated colum- tion of CAIII decreases signifi cantly, thereby nar epithelial cells of the upper respiratory exposing the larynx to stomach acid without tract, leading to ciliary dysfunction. A lack of the enzyme’s protective eff ect.9,10 At the same mucous clearance leads to mucous stasis time, a marked increase in pepsin levels inten- and, subsequently, to excessive throat clear- sifi es laryngeal injury.10,12,13 ing and the sensation of postnasal drip.7 In ❚ The larynx is highly vulnerable. Th e la- addition, the laryngopharyngeal epithelium ryngopharynx is much more susceptible to pa- becomes infl amed, and this aff ects the sensi- thology from gastric refl ux than the esophagus, tivity of laryngeal sensory endings and leads for a number of reasons. Damage can occur to laryngospasm and coughing.8 Th e infl am- with much less exposure to acid,1 not only be- IMAGE © KIMBERLY MARTENS IMAGE © KIMBERLY matory reaction in turn leads to vocal fold cause of the decrease in CAIII, but also because edema, contact ulcers, and granulomas. Th ese of the absence of peristalsis in the larynx. changes make patients with LPR particularly What’s more, the esophagus has the prone to developing hoarseness, globus pha- ability to clear gastric refl ux and minimize ryngeus—a sensation of a foreign body in the damage to the epithelial layer.9,10,14,15 In most larynx—and sore throat.5,7 Th e gastric content patients who develop signs and symptoms of can also act indirectly by initiating laryngeal LPR, there has been enough gastric refl ux to JFPONLINE.COM VOL 59, NO 2 | FEBRUARY 2010 | THE JOURNAL OF FAMILY PRACTICE 103 103_JFP0210 103 1/20/10 12:53:05 PM FIGURE Fiberoptic laryngoscopy: Before and after treatment Fiberoptic laryngoscopy reveals evidence of Two months after the initiation of twice-daily proton laryngopharyngeal refl ux (LPR), including post-cricoid pump inhibitor therapy, the physical manifestations edema (black arrow), ventricular edema (gray arrow), of LPR had resolved. Heartburn, and vocal fold edema (white arrow). esophagitis, and night- damage the laryngopharynx but not enough further assess the probability and sever- time refl ux, to overcome the protective mechanisms of the ity of LPR, use the Refl ux Symptom Index18 characteristics esophagus. Th at’s why most LPR patients have (TABLE 1). A recent cohort study validated the of GERD, are little or none of the heartburn and esophagitis index, with an average score of 21.2 for those not common in that are classic symptoms of GERD. with LPR, vs an average of 11.6 for controls patients with (P<.001). A score >13 is suggestive of LPR LPR. Common signs and symptoms (odds ratio=9.19), the researchers found.18 that signal LPR If the diagnosis remains uncertain and LPR is primarily a clinical diagnosis based on the patient continues to be troubled by signs signs and symptoms—which are also used and symptoms suggestive of LPR, refer him or to rule out GERD. Notably, less than 50% of her to an otolaryngologist for further inves- patients with LPR suff er from heartburn and tigation. A referral is needed, too, to rule out regurgitation.16 Th ose who do have heartburn malignancy in any patient with 3 or more of and regurgitation typically suff er with refl ux the following red fl ags: older than 50 years, during the day, when they’re in an upright po- otalgia, weight loss, progressive hoarseness, sition, whereas refl ux associated with GERD neck mass, a signifi cant history of alcohol use, develops primarily at night.16 Th e results of and a history of smoking.7 a recent survey of members of the American Bronchoesophagological Association high- light the most common signs and symptoms Diagnostic tools the of LPR, listed below from the most to the least specialists will use frequent:17 ❚ Fiberoptic laryngoscopy is the most com- • throat clearing mon test used by otolaryngologists to con- • persistent cough fi rm LPR and rule out other pathology. Th e • globus sensation test reveals infl ammatory fi ndings (FIGURE), • hoarseness such as erythema, edema, granulomas, and • choking episodes. contact ulcers, in several anatomical loca- Additional signs and symptoms include tions of the larynx—especially the posterior excessive and chronic throat clearing, sore aspect and the true vocal folds. It is important throat, postnasal drip, and dysphagia. to note, however, that as many as 70% of the ❚ Use a validated symptom index. To general population will have some laryngeal OF AMIN MADANI, HBSC, UNIVERSITY WESTERN ONTARIO IMAGES COURTESY 104 THE JOURNAL OF FAMILY PRACTICE | FEBRUARY 2010 | VOL 59, NO 2 104_JFP0210 104 1/20/10 12:53:13 PM LARYNGOPHARYNGEAL REFLUX TABLE 1 Th e Refl ux Symptom Index for laryngopharyngeal refl ux Within the last month, how did the 0 = NO PROBLEM 5 = SEVERE PROBLEM following problems affect you? (CIRCLE THE APPROPRIATE RESPONSE) 1. Hoarseness or a problem with your voice 0 1 2 3 4 5 2. Clearing your throat 0 1 2 3 4 5 3. Excess throat mucus or postnasal drip 0 1 2 3 4 5 4. Diffi culty swallowing food, liquids, or pills 0 1 2 3 4 5 5. Coughing after you ate or after lying down 0 1 2 3 4 5 6.