Reinke Oedema

Reinke oedema (polypoid corditis, polypoid degeneration) is a benign, diffuse, bilateral, sessile, gelatinous swelling of the vocal folds. It is due to accumulation of oedematous, myxoid fluid in the superficial lamina propria (Reinke space), the layer between the epithelium and the vocal ligament.

It occurs predominantly in middle aged and older women (age 40 to 70 years; female-to-male ratio of about 2 to 4:1 in some series). It is strongly linked to heavy cigarette smoking: over 90 percent of patients are smokers, and the risk increases with pack years.

Other contributing factors:

• laryngopharyngeal reflux
• vocal abuse and overuse (singers, teachers)
• hypothyroidism
• chronic irritants (occupational chemical and dust exposure)
• allergic inflammation

The mechanism includes capillary leakage and increased vascular permeability with inflammation from chronic irritation. The extracellular matrix is disrupted (decreased hyaluronic acid and collagen, increased vascular endothelial growth factor). Fluid accumulates, the superficial lamina propria hypertrophies, and the mucosal wave becomes abnormal.

The vocal folds are enlarged and appear translucent, pale and pink (grey to yellow), and gelatinous. The swelling is usually symmetric, producing a low pitched voice.

The risk of malignant transformation is low (it is not premalignant), though the smoking exposure itself carries a risk of laryngeal cancer. A lesion that appears different (leukoplakia or erythroplakia) needs biopsy.

• Chronic, progressive hoarseness with a low pitched, rough, husky, "gravelly" voice. A woman's voice lowers to the male range, with a fundamental frequency of 100 to 130 Hz. Vocal range is reduced and there is voice fatigue. Onset is often longstanding (over months to years).
• Throat clearing, a sensation of a lump in the throat, and cough.
• In severe cases, dyspnoea, stridor, and airway obstruction (from large polypoid masses that obstruct the glottis, particularly with exertion; sleep disordered breathing). Respiratory compromise is uncommon.
• The patient is often a long term smoker.
• Laryngoscopy (stroboscopy): bilateral, diffuse, translucent, grey white to pink, sac like swelling of the entire membranous length of both vocal folds ("elephant ear" or "floppy" folds), with a pale, gelatinous aspect.
• The folds billow on respiration: the polypoid vocal folds prolapse into the subglottis with inspiration and into the supraglottis on expiration.
• Stroboscopy shows a reduced vibration amplitude and mucosal waves. Classification is by Yonekawa (grade I to IV).

• History: smoking (pack years), voice use, reflux symptoms, and thyroid symptoms.
• Flexible or rigid laryngoscopy and stroboscopy: the characteristic appearance, with assessment of the extent and the mucosal wave (decreased or absent), and exclusion of malignant lesions.
• Voice assessment: perceptual evaluation (GRBAS), acoustic analysis (low fundamental frequency, increased jitter and shimmer), aerodynamic measures, and voice handicap index.
• Thyroid function tests (TSH, free thyroxine) to exclude hypothyroidism.
• Biopsy or microlaryngoscopy for suspicious features: asymmetry, leukoplakia, erythroplakia, ulceration, or a firm mass.
• Histopathology shows oedematous, myxoid stroma with thick walled capillaries and fibrin, with a thin epithelium (keratosis in some).
• Evaluation for laryngopharyngeal reflux (reflux symptom index), allergy, and airway assessment (spirometry with flow volume loop, in cases with dyspnoea).

• Smoking cessation is the most important therapeutic step (and essential before surgery). Options:
  • counselling and behavioural support
  • nicotine replacement therapy (patch 21 mg daily, tapering, plus gum or lozenge)
  • varenicline 0.5 mg daily for 3 days, 0.5 mg twice daily for 4 days, then 1 mg twice daily for 12 weeks
  • bupropion 150 mg daily for 3 days then 150 mg twice daily
  Early cessation may result in partial regression of the oedema, but complete resolution is uncommon in established disease.
• Treat contributing factors: treat laryngopharyngeal reflux (proton pump inhibitor trial, e.g., omeprazole 20 to 40 mg twice daily for 8 to 12 weeks, and lifestyle measures). Give thyroid replacement (levothyroxine) for hypothyroidism. Advise vocal hygiene (hydration, avoiding vocal strain and throat clearing) and voice rest around surgery. Avoid irritants and treat allergy.
• Voice therapy (with speech language pathologist): vocal hygiene education, breathing and resonance training, semi-occluded vocal tract exercises. It is useful for mild disease and as an adjunct before and after surgery, to improve voice efficiency, but unlikely to resolve the oedema.
• Surgical treatment (indicated for bothersome dysphonia, airway obstruction, or diagnostic uncertainty), after smoking cessation: microlaryngoscopic surgery under general anaesthesia (suspension microlaryngoscopy) using cold steel instruments, microdebrider, or CO2 laser.
  • An incision is made along the superior surface of the vocal fold (a lateral to medial approach).
  • The oedematous gelatinous material is suctioned or aspirated through the incision (with a micro suction, preserving the epithelium and the vocal ligament).
  • The redundant mucosa is trimmed and re-draped.
  • Do not strip both vocal folds simultaneously (risk of anterior commissure web). For severe bilateral disease, a staged operation 4 to 6 weeks apart (one fold at a time) is recommended, to prevent a web and airway compromise.
  • Avoid stripping the whole mucosa, to prevent scarring, loss of vibration and permanent dysphonia. A radical microflap technique with preservation of the epithelium gives better outcomes.
  • Perioperative care: dexamethasone, 10 mg intravenously, intraoperative; voice rest for 5 to 7 days, hydration, steam inhalation, and a gradual return to voice use with voice therapy; the PPI during the healing period.
• Adjunctive treatment: intracordal injection of corticosteroid (triamcinolone 10 to 40 mg/mL, 0.1 to 0.3 mL per fold, in the superficial lamina propria) or steroid injection with the microlaryngoscopy. Pulsed dye laser (photoangiolytic) is used for polypoid changes, and bevacizumab injection in research settings.
• Airway emergency: with stridor and severe airway obstruction, urgent microlaryngoscopic reduction of the oedema.
• Follow up: laryngoscopy at 2 weeks, 6 weeks and 3 months, and annually for those who continue to smoke. Persistent smoking raises the risk of recurrent oedema and laryngeal cancer. Recurrence (about 10 to 20 percent) occurs in those who continue to smoke.
• Prognosis: excellent voice and airway improvement after surgery with smoking cessation (voice improvement in 80 to 90 percent). The pitch may remain lowered, and many women have a persistent lower pitch.