Continuing Education Activity

Laryngopharyngeal reflux typically results from the effects of reflux on the glottis and vocal cords. Patients may present with a multitude of symptoms ranging from hoarseness, globus sensation, and chronic throat clearing to heartburn and regurgitation. In contrast to patients with gastroesophageal reflux, which is associated with the lower esophageal sphincter, patients with laryngopharyngeal reflux typically have pathologic changes of the upper esophageal sphincter. This activity describes the pathophysiology, evaluation, and management of laryngopharyngeal reflux and highlights the role of the interprofessional team in the care of affected patients.

Objectives:

• Identify the anatomic etiology of laryngopharyngeal reflux.
• Outline the differences between clinical presentations of patients with laryngopharyngeal reflux and gastroesophageal reflux.
• Review the management options available for laryngopharyngeal reflux.
• Explain the role of the interprofessional team in care coordination and clinical outcome improvement in patients with laryngopharyngeal reflux.

Introduction

The term "laryngopharyngeal reflux" (LPR) describes the anatomical location of the disease process as well as its cause. According to Sataloff, “laryngopharyngeal reflux incorporates a complex spectrum of abnormalities,” but what brings most patients in for evaluation is the effect of reflux on the vocal cords or the glottis.[1] Gastric acid is normally sequestered within the stomach, but when it escapes into the distal esophagus, it can spill over into the pharynx and larynx, causing hoarseness and a litany of other symptoms.

In healthy individuals, there are four barriers to reflux encroaching on the larynx: the lower esophageal sphincter, upper esophageal sphincter, esophageal peristalsis, and epithelial resistance factors. Dysfunction in any of the above will lead to symptoms of LPR. The upper esophageal sphincter is the final gatekeeper against reflux of gastric contents. The distal pharynx and upper esophageal sphincter should only open under specific physiologic conditions, such as swallowing, and should otherwise remain closed. The complex of muscles that constitute this barrier to acid consist of the cricopharyngeus, the thyropharyngeus, and the proximal cervical esophageal musculature, forming a c-shaped sling that attaches to the cricoid cartilage. The tonic pressure induced by these muscles can be decreased, however, with general anesthesia, sleep, and cigarette consumption.

The lower esophageal sphincter is located at the gastroesophageal junction, and its contraction leads to circular closure and prevention of stomach acid egress. The diaphragmatic crura constitute a critical part this antireflux mechanism, which is why the presence of a hiatal hernia can be so instrumental in the development of gastroesophageal reflux disease (GERD). The esophagus, with the help of gravity and peristalsis, can generally clear the acid that makes its way proximally past the lower esophageal sphincter. A mucus layer is also present on the esophageal mucosa and serves as a barrier to large molecules, such as pepsin, but does not help prevent acid penetration. Lying on the mucus layer, there is an additional aqueous layer, which further helps protect the tissue by forming an alkaline buffer.

Etiology

Direct exposure to gastric acid damages the laryngeal epithelium. Ciliary flow is impeded below a pH of 5.0 and halted at pH 2.0. With decreased ciliary flow, there is also a decrease in infection resistance. Risk factors for LPR parallel those of GERD, including consuming a diet heavy in acidic or fatty foods and caffeine or alcohol, eating large meals before going to sleep, obesity, and smoking - the latter of which is also a risk factor for Reinke's edema, which causes hoarseness and a lowering of the fundamental frequency of the voice, similar to LPR.[2][3] Even though tobacco use is well recognized as the primary cause of Reinke's edema in most patients, the condition can arise solely from chronic acid reflux onto the vocal cords.[3][4] The primary differences between LPR and GERD are the symptoms manifested and the underlying anatomical defect, which tends to be the lower esophageal sphincter in GERD and the upper esophageal sphincter in LPR.[5][6]

Epidemiology

It is thought that 10% of patients visiting otolaryngology clinics have symptoms attributable to laryngopharyngeal reflux, and LPR causes or contributes to hoarseness in up to 55% of patients with dysphonia.[7] In patients with LPR, nearly 100% will complain of hoarseness at presentation, even in the absence of other classic reflux-associated symptoms.[1]

Pathophysiology

The retrograde flow of gastric acid and pepsin induces laryngeal mucosal damage and impaired mucociliary clearance. This may occur in isolation, but symptoms may be worsened when LPR is exacerbated by vocal abuse, development of mucosal lesions, or a chronic cough caused by the esophageal-bronchial reflex, in which acid within the distal esophagus causes vagal stimulation and thereby induces a cough response.[8]

Histopathology

In one study, post-cricoidectomy epithelial cells from patients suffering from LPR were examined and shown to contain pepsin, while the control group cells did not. Even when the pH of the refluxate is neutral, inactivated pepsin at pH 7 is taken into cells and subsequently reactivated, causing mitochondrial and overall cell damage.[8]

History and Physical

Laryngopharyngeal reflux causes various symptoms that may result in a patient presenting for evaluation. Hoarseness is the most prevalent of these, occurring in nearly 100% of patients with LPR, in contrast to patients with GERD, of whom essentially none report hoarseness.[1] The clinical picture may be clouded, however, when patients suffer from both GERD and LPR.

Patients may also experience many other symptoms, including globus sensation, chronic throat clearing, post-nasal drip, Eustachian tube dysfunction, heartburn, other voice changes, and regurgitation.[9][10] Patients with LPR typically have upright, or daytime, reflux and good esophageal motor function.[11] Patients with esophageal dysmotility, on the other hand, typically present with supine or nocturnal symptoms.[12] Patients with GERD may have similar symptoms to those with LPR - other than hoarseness - but their anatomical dysfunction occurs at the lower esophageal sphincter rather than the upper esophageal sphincter, as in LPR.[5] For patients with LPR, the reflux symptom index questionnaire (RSI) may be used for tracking the outcomes of therapy.

Reflux Symptom Index[13]

The RSI is a validated, patient-reported outcome measure that reliably assesses the severity of LPR. The instrument is a nine-item questionnaire given to patients to score each of their symptoms on a scale of 0 to 5 (5 being the most severe). An RSI score of greater than ten is correlated with a high likelihood of reflux pathology, although the maximum score is 45. The nine domains are:

• Hoarseness
• Throat clearing
• Mucus or postnasal drip
• Dysphagia
• Coughing after eating or lying down
• Breathing difficulties or choking episodes
• Chronic cough
• Globus sensation
• Heartburn, indigestion, or regurgitation

On physical examination, laryngoscopy and/or videostroboscopy can be very helpful for raising suspicion for LPR in patients with hoarseness and other symptoms consistent with the diagnosis. Thickening and pachydermia of the posterior laryngeal commissure and post-cricoid mucosa have been associated with laryngopharyngeal reflux.[14] Granulomas of the vocal processes of the arytenoid cartilages have also been highly associated with LPR.[15] Other physical findings of LPR include edema of the false and true vocal cords with or without ventricular obliteration, diffuse laryngeal and pharyngeal edema, erythema, hyperemia, thickened mucus, mucosal ulcers, and even subglottic stenosis in extreme cases. Edema along the undersurface of the vocal fold that extends from the anterior commissure to the posterior commissure is also frequently seen in LPR.[12] This edema pushes the mucosa medially and up over the free margin of the vocal fold, causing a ripple and a groove, referred to as pseudosulcus vocalis, which is essentially pathognomonic for LPR.[16] It is important, however, to differentiate this finding from a true sulcus vocalis, in which a groove is visible where the mucosa is tethered by scar to the vocal ligament beneath it. Common causes of sulcus vocalis include trauma, surgery, infection, cyst rupture, and others.

Evaluation

Detection of retrograde flow of stomach acid into the upper aerodigestive tract is considered the gold standard for diagnosis of LPR. This is accomplished by monitoring pH via nasal catheter for 24 hours. Various methods may be used, including up to three probes that test pH continuously just above the lower esophageal sphincter, below the upper esophageal sphincter, and in the pharynx. Pathologic reflux is considered present when there is a pH of less than 4.0 for at least 1% of the study time.[17] While imaging may also be performed, it has not been shown to increase the sensitivity of diagnosis. A 1996 study published by Johnston et al. compared pH probe monitoring to swallow studies and reported that videofluoroscopy's sensitivity of reflux diagnosis ranged from 25% to 33%.[18] In that same study, barium esophagography had a sensitivity of 20% and a specificity of 64% to 90%.[18]

Treatment / Management

Lifestyle modifications are the first step in management. These include weight loss, decreased meal size, refraining from lying down within 3 hours after a meal, eating a low-fat and low-acid diet, avoiding carbonated or caffeinated beverages, stopping tobacco use, and reducing alcohol intake. If these measures fail to achieve symptomatic relief, medications such as histamine H2-receptor antagonists and proton pump inhibitors can suppress acid production. Given that not all reflux is acidic, additional measures that protect the mucosa from alkaline or neutral refluxate, such as alginate and magaldrate, may also be effective.[19] Surgical therapy such as Nissen fundoplication can also be employed to decrease symptoms.

Differential Diagnosis

Laryngeal complaints similar to LPR manifestations have myriad etiologies. Most commonly, LPR may be misdiagnosed as GERD, although the consistent presence of hoarseness in LPR and absence in GERD is helpful for differentiating the two clinical entities. Other causes of chronic cough and globus sensation include post-nasal drip (which may be caused by allergies, LPR, rhinosinusitis, or vasomotor rhinitis), viral or autoimmune laryngitis, esophageal dysmotility, myasthenia gravis or other neurological disorders, vagal nerve injury, functional voice disorders, and tumors of the larynx, pharynx, or esophagus.

Prognosis

Long-term untreated laryngopharyngeal reflux can lead to chronic vocal injury with resultant scarring of the true vocal folds and hoarseness. In rare cases, LPR may lead to subglottic stenosis or squamous cell carcinoma.[20] Laryngopharyngeal reflux may also be related to untreated GERD, leading to Barrett's esophagitis and subsequent malignant degeneration to adenocarcinoma if left untreated.

Complications

As stated above, significant long-term complications of LPR can occur if the disease is left untreated or goes unrecognized. Common complications include:

• Chronic cough
• Recurrent laryngitis
• Oral cavity disorders/ulcers
• Recurrent bronchopulmonary injury/infections, such as pneumonia

LPR has been identified as a risk factor for laryngeal carcinoma, though this association is under investigation and remains unclear.[21]

Consultations

If a patient continues to have symptoms of hoarseness, dyspnea, and chronic sore throat despite lifestyle changes, an otolaryngologic referral is a good option. The otolaryngologist will be able to perform fiberoptic laryngoscopy with or without stroboscopy. A gastroenterologist may need to be consulted for possible esophagoscopy to rule out malignancy, if the laryngoscopy is suggestive of additional pathology.

Deterrence and Patient Education

Laryngopharyngeal reflux can usually be treated with lifestyle modifications, though LPR can be frustrating because it often does not respond as readily to lifestyle changes as GERD does. With time and appropriate intervention, LPR symptoms can resolve, and the need for anti-reflux medication will abate. For this reason, patient education becomes a crucial aspect of management. Patients should be counseled regarding lifestyle modifications including weight loss, reduction in meal portion size, and refraining from lying down within 3 hours after a meal. Dietary modifications including adherence to a low fat and low acid diet, avoiding carbonated or caffeinated beverages, and reducing alcohol intake are imperative.

Enhancing Healthcare Team Outcomes

Laryngopharyngeal reflux appears to be a common, yet under-diagnosed condition. Despite the available medications and surgical procedures to manage this condition, it is important to recognize that lifestyle modifications constitute the first-line therapy. To achieve this goal, an interprofessional team approach is needed. In addition to astute clinicians, treatment and management of LPR requires specialty-trained nurses and dieticians to help educate patients regarding lifestyle and dietary modifications. When medical therapy is required, clinical pharmacists determine the lowest effective therapeutic dose of the prescribed medication and assist in adjusting other medications to minimize drug-drug interactions. A collaborative interprofessional team can help improve outcomes in patients with LPR. [Level V]