Reinke Edema

Etiology

Risk factors for developing Reinke edema include smoking, phonotrauma, and laryngopharyngeal reflux. Of these risk factors, smoking is the most significant.[5] Exposure to cigarette smoke over prolonged periods leads to the development and recurrence of the disease.[7]

Epidemiology

Reinke edema is most prevalent between the fifth and sixth decades.[1] Up to 80% of patients are female, and nearly half of those present between the ages of 40 to 59.[8] Why Reinke edema preferentially affects females is not understood, but several hypotheses have been put forward.

Females may be more likely to self-perceive voice differences and, therefore, more likely to seek care.[1] Females naturally have higher hyaluronic acid (HA) concentrations within the vocal folds, and patients with Reinke edema have higher HA concentrations than those without.[9] Exposure to cigarette smoke upregulates HA production within VFFs.[4] It is plausible that an increased amount of HA may contribute to the development of Reinke edema, although further research is needed.[9] 

Pathophysiology

The exact mechanism by which smoking causes Reinke edema is poorly understood. However, it has been demonstrated that chronic exposure to cigarette smoke alters the phenotypic expression of vocal fold fibroblasts (VFF) in the lamina propria. It is hypothesized that increased phenotypic expression of the VFF leads to alterations in the extracellular matrix (ECM) comprising the superficial lamina propria resulting in the development and progression of the disease.[4] Furthermore, phonotrauma exacerbates the effects of smoking on a cellular and molecular level.[10] 

The role of laryngopharyngeal reflux (LPR) in Reinke edema is less well-defined. Several studies have documented an increased prevalence of LPR in patients with Reinke edema, suggesting an association between the two conditions.[11]

History and Physical

Patients with Reinke edema most commonly present with a chief complaint of dysphonia, the alteration of vocal quality, pitch, loudness, or effort.[12] More specifically, patients with Reinke edema tend to notice a slowly progressive deepening in the tone of their voice with associated hoarseness. Given that Reinke edema is a rare diagnosis, a comprehensive medical history should be obtained.

Important historical factors include:

• Duration
• Onset
• Inciting events
• Associated symptoms (swallowing, breathing issues, throat pain, ear pain, hemoptysis)
• Constitutional symptoms such as fever or weight loss
• Effect on daily life
• Modifying factors
• Medical history
• Social history with attention to smoking and alcohol use
• Current medications
• History of prior surgery or recent endotracheal intubation
• History of prior radiation

A comprehensive physical examination of the head and neck should be performed with particular attention to the oral cavity, oropharynx, neck, thyroid gland, nasal airway, and perceptual evaluation of the voice.[12] 

In a patient with Reinke edema as the sole cause of their dysphonia, a comprehensive head and neck examination will not reveal any remarkable findings other than vocal alteration. Following the history and physical examination, the clinician must decide whether to escalate care to a practitioner who can perform a diagnostic laryngoscopy.

Clinical practice guidelines strongly recommend that clinicians escalate care for expedited laryngeal examination when dysphonia is detected in patients who have undergone recent endotracheal intubation or surgical procedures of the head, neck, or chest; if a neck mass, stridor, or respiratory distress is present; a history of tobacco abuse; or if they are a professional voice user. Guidelines further recommend referral of patients to a provider who can perform diagnostic laryngoscopy if the dysphonia lasts longer than 4 weeks or a more concerning underlying cause is suspected.[12] 

Because of the longevity of dysphonia and history of tobacco exposure in nearly all patients with Reinke edema, diagnostic laryngoscopy becomes an essential portion of the evaluation in patients with symptomatic Reinke edema.

Evaluation

The evaluation of patients with Reinke edema is augmented with visualization of the larynx, perceptual evaluation of the voice, and documentation of vocal outcomes.

Diagnostic laryngoscopy is necessary to evaluate suspected Reinke edema through visualization and analysis of the larynx. Reinke edema is a rare condition, and dysphonia in a patient with significant smoking history necessitates a laryngeal examination to assess for possible malignancy. Diagnostic laryngoscopy is most commonly performed in the office using indirect visualization with flexible fiberoptic endoscopy.

In a patient with Reinke edema, the laryngoscopic examination will demonstrate a balloon-like swelling of the vocal folds secondary to subepithelial expansion of the superficial layer of the lamina propria.[13] Several classification systems have been described to standardize grading and reporting of the severity of Reinke edema. Most recently, de Vincentiis et al proposed a classification system tying previous systems into a single arrangement. This system describes 4 types of Reinke edema.[14]

• Type 1: Reinke edema of one vocal fold
• Type 2: Reinke edema of both vocal folds
• Type 3: Reinke edema of one vocal fold with a polypoid lesion on either fold
• Type 4: Reinke edema of both vocal folds with a polypoid lesion on one or both folds

Otolaryngologists trained in videostroboscopy can use this technique to understand any asymmetry present and the degree of mucosal wave propagation and amplitude change.[1] Significant findings include asymmetric periodicity of the mucosal wave, prolonged closure phase, increased amplitude, and a posterior glottic gap.[15] 

In addition to indirect visualization, perceptual voice assessment by the treating practitioner is an important evaluative measure. The GRBAS scale was developed in the 1980s to provide a perceptual assessment of the grade, roughness, breathiness, asthenia, and strain of the voice.[16] The provider assigns a specific rating from 0 to 3 for each category; 0 represents no deficit, and 3 represents a severe deficit based on the overall gestalt of the vocal impairment. This perceptual evaluation can compare and contrast voice outcomes over time and pre-intervention and post-intervention.

A similar tool is the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V). This tool measures parameters similar to the GRBAS scale, except for asthenia. The CAPE-V score is assigned based on specific tasks, including reading aloud predetermined phrases. An overall severity ranging from mild, moderate, and severe are assigned regarding the perceptual evaluation.[16] The CAPE-V can be used similarly to the GRBAS, tracking the progression or regression of vocal outcomes over time.

Finally, several measures exist to quantify any self-perceived handicap from vocal limitations. The Voice Handicap Index-10 (VHI-10) is a validated abbreviation of the original Voice Handicap Index developed by Jacobsen et al in 1997. Again, this vocal evaluation tool helps quantify and track longitudinal vocal outcomes but is a patient-driven questionnaire rather than a provider perceptual assessment.[17]

Treatment / Management

Treatment of Reinke edema is nuanced, with many available options. As with other forms of benign laryngeal pathology causing dysphonia, successful treatment of Reinke edema is primarily characterized by restoring and improving vocal function rather than treating the gross appearance of the disease process. Due to the relative rarity of this disease process, treatment selection largely depends on provider training and available resources. Treatments can be administered in an office-based environment or the operating room. Additionally, adjunct measures, including speech therapy and smoking cessation, play an integral role in achieving and maintaining results.[6] Procedural treatment options for Reinke edema include cold steel excision, CO₂ laser, microdebridement, photoangiolytic laser, and intralesional injection.(A1)

Cold Steel Excision

Cold steel excision is performed under microlaryngoscopy in the operating room. The patient is placed into suspension, and either an operating microscope or endoscope is used to visualize the larynx through a laryngoscope. An epithelial incision is made with a cold steel instrument on the superior lateral surface of the true vocal fold along the arcuate line, exposing the superficial lamina propria. The gelatinous, edematous superficial layer of the lamina propria is removed using either suction or a grasping instrument. After adequate debulking, the flap is laid back down and allowed to heal via primary intention.[18] 

Microdebridement

The microdebridement technique is similar to that of cold steel excision. Suspension microlaryngoscopy provides adequate exposure of the true vocal cords. Next, an incision is made along the superior medial aspect of the vocal cord to allow the introduction of the microdebrider into the Reinke space. While keeping the blades of the microdebrider away from the vocal ligament, the excess gelatinous tissue of the superficial lamina propria is removed. The mucosal incision is allowed to heal via primary intention.[15]

Laser Therapy

Several lasers are available to perform office-based and operating theater-based procedures. The CO₂ laser is commonly used in endolaryngeal procedures. The CO₂ laser is used similarly to cold steel when treating Reinke edema. However, the CO₂ laser is used to make the incision to access the Reinke space, which is evacuated with suction or a grasping instrument. The CO₂ laser is also used to ablate any redundant mucosa remaining after the evacuation of the superficial lamina propria layer. The CO₂ laser can also be used with a microdebrider, mainly for the initial incision.[6](A1)

Given that one of the defining characteristics of Reinke edema is vascular congestion, using photoangiolytic lasers to treat Reinke edema has been evaluated. The potassium titanyl phosphate (KTP) laser, thulium fiber laser (TFL), pulsed dye laser (PDL), and more recently, a 445-nm blue-light diodelaser are all described in the literature as office-based therapies for Reinke edema.[19] Results generally indicate that these laser therapies provide reliable, effective outcomes for patients with Reinke edema. However, office-based treatments can be limited by patient selection and tolerance and the ability to precisely access certain areas, such as the medial portion of the vocal fold.[20]

Intralesional Injection

Only two studies evaluate therapeutic intralesional injection for the primary treatment of Reinke edema. One study evaluates intralesional triamcinolone injection for mild bilateral Reinke edema, demonstrating improved functional outcomes.[6] Another small case series evaluates the use of intralesional hyaluronidase injection. The patients in this series demonstrated improvement in their edema and did not require additional procedures.[21](A1)

Differential Diagnosis

The differential diagnosis for Reinke edema includes almost any diagnosis that can cause dysphonia. Neurologic, infectious, inflammatory, neoplastic, congenital, traumatic, and behavioral factors should all be considered in a patient with dysphonia. However, certain conditions may more closely mimic the presentation of Reinke edema. These conditions include acute and chronic laryngitis, benign and malignant tumors such as papilloma or squamous cell carcinoma, unilateral or bilateral vocal cord paresis or paralysis, presbyphonia, phonotraumatic lesions such as vocal fold nodules or hemorrhagic polyps, or functional dysphonia such as that seen in muscle tension dysphonia.[22] 

Because Reinke edema is a relatively rare and benign condition, due diligence is required, even if, demographically, Reinke edema seems the most likely diagnosis.

Prognosis

Patients with Reinke edema generally have a good prognosis. Although Reinke edema is a naturally benign process, the primary cause, smoking, is commonly associated with the development of laryngeal malignancy. However, the synchronous presence of Reinke edema with dysplastic or premalignant lesions is exceedingly rare, and there are few reports of concomitant malignancy.[23] 

Reported voice outcomes differ among various treatment techniques, and more prospective randomized controlled trials are needed to assess functional vocal outcomes further.

Complications

Significant complications from Reinke edema are almost exclusively related to the potential for airway obstruction. Preexisting Reinke edema may complicate extubation or impair the ability to use positive pressure ventilation in cases of respiratory failure due to laryngeal edema.[24] Reinke edema may narrow the glottic aperture and increase the difficulty of intubation.[25] 

Providers should use caution when managing the airway of a patient with suspected or confirmed Reinke edema and have a low threshold for aggressive airway management. Severe Reinke edema may make patients susceptible to postobstructive pulmonary edema in the postoperative period. Caution and close monitoring are paramount to successful airway management in this patient population.