Laryngopharyngeal Reflux

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% complain of hoarseness at presentation, even without 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 1 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] On the other hand, patients with esophageal dysmotility typically present with supine or nocturnal symptoms.[12] Patients with GERD may have symptoms similar to those with LPR other than hoarseness. Still, 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 to track therapy outcomes.

Reflux Symptom Index[13]

The RSI is a validated, patient-reported outcome measure that reliably assesses the severity of LPR. The instrument is a 9-item questionnaire given to patients to score each symptom on a scale of 0 to 5 (5 being the most severe). An RSI score greater than 10 correlates with a high likelihood of reflux pathology, although the maximum score is 45. The 9 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 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 a scar to the vocal ligament beneath it tethers the mucosa. Common causes of sulcus vocalis include trauma, surgery, infection, cyst rupture, etc.

Evaluation

Detection of retrograde flow of stomach acid into the upper aerodigestive tract is considered the gold standard for diagnosing LPR. This is accomplished by monitoring pH via nasal catheter for 24 hours. Various methods may be used, including up to 3 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. Medications such as histamine H2-receptor antagonists and proton pump inhibitors can suppress acid production if these measures fail to achieve symptomatic relief. Since 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.(B2)

Differential Diagnosis

Laryngeal complaints similar to LPR manifestations have myriad etiologies. LPR may be commonly misdiagnosed as GERD, although the consistent presence of hoarseness in LPR and absence in GERD helps differentiate the 2 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, which results in scarring of the true vocal folds and hoarseness. Rarely, LPR may lead to subglottic stenosis or squamous cell carcinoma.[20] Laryngopharyngeal reflux may also be related to untreated GERD, which, if left untreated, can lead to Barrett's esophagitis and subsequent malignant degeneration to adenocarcinoma.

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]