What is the recommended treatment for vocal cord paralysis in a patient with granulomatosis with polyangiitis (GPA)?

Treatment of Vocal Cord Paralysis in Granulomatosis with Polyangiitis

Vocal cord paralysis in GPA requires aggressive systemic immunosuppression with high-dose glucocorticoids combined with either rituximab or cyclophosphamide, as laryngeal involvement represents severe, organ-threatening disease that demands the same treatment approach as other life-threatening GPA manifestations.

Disease Severity Classification

Vocal cord paralysis in GPA should be classified as severe disease requiring immediate aggressive therapy, as laryngeal involvement can progress to life-threatening airway compromise 1, 2.

• The presence of subglottic or laryngeal involvement with functional impairment (such as vocal cord paralysis) constitutes organ-threatening disease by definition 1.
• This manifestation falls outside the "non-severe" category and requires treatment protocols reserved for severe GPA 1.

Immediate Systemic Immunosuppression

Induction Therapy

Initiate pulsed intravenous methylprednisolone (500-1000 mg daily for 3 days) followed by high-dose oral glucocorticoids (0.75-1 mg/kg/day) combined with either rituximab or cyclophosphamide 1.

• Rituximab: Administer 1-gram pulses 2 weeks apart, which is non-inferior to cyclophosphamide and preserves fertility—particularly important in younger patients 1.
• Cyclophosphamide: Use 2 mg/kg/day oral or 15 mg/kg IV pulse every 2-3 weeks if rituximab is unavailable or contraindicated 1.
• Continue induction therapy until remission is achieved, typically within 6 months 1.

Glucocorticoid Tapering

• Taper prednisone to 5 mg/day by weeks 19-52, targeting 7.5-10 mg/day by 3 months 1.
• The goal is to minimize glucocorticoid toxicity while maintaining disease control 1.

Airway Management Considerations

While systemic immunosuppression is the definitive treatment, concurrent airway intervention may be necessary for severe stenosis or imminent airway compromise 2.

• Emergency tracheostomy may be required for life-threatening airway obstruction 2.
• Intratracheal interventions (CO2 laser surgery, intralesional steroid injection via laryngomicroscopy) can provide temporary relief but must be combined with systemic immunosuppression 2.
• Laryngotracheal resection with remodeling may be considered for refractory cases, but only after achieving systemic disease control 2.

Maintenance Therapy

Once remission is achieved, transition to maintenance therapy 1:

• Rituximab 500 mg IV every 6 months is the preferred maintenance agent, significantly reducing relapse rates 1.
• Alternative agents include azathioprine (2 mg/kg/day), methotrexate (20-25 mg weekly), or mycophenolate mofetil (2000 mg/day) 1.

Mandatory Prophylaxis and Monitoring

• Pneumocystis jirovecii prophylaxis with sulfamethoxazole-trimethoprim is mandatory during cyclophosphamide or rituximab therapy 1.
• Screen for hepatitis B, HIV, and tuberculosis before initiating immunosuppression 1.
• Monitor complete blood count weekly, serum creatinine, and urinalysis during induction 1.

Management of Refractory Disease

If vocal cord paralysis persists or worsens after 4 weeks of appropriate induction therapy 1:

• Switch to rituximab if initial treatment was cyclophosphamide-based 1.
• Switch to cyclophosphamide if initial treatment was rituximab-based 1.
• Consider plasma exchange for severe refractory cases 3.

Critical Pitfalls to Avoid

• Do not rely solely on local airway interventions without systemic immunosuppression—this approach leads to recurrent disease and progressive airway damage 2.
• Do not delay treatment while awaiting biopsy confirmation if clinical presentation and ANCA serology are compatible with GPA 1.
• Do not mistake vocal cord paralysis for isolated ENT disease—it represents severe organ involvement requiring aggressive systemic therapy, not the stepwise approach used for sinusitis or rhinitis 3, 1.
• Laryngeal involvement in GPA can be the initial manifestation of systemic disease that later progresses to renal or pulmonary involvement, emphasizing the need for close monitoring even when other organs appear uninvolved initially 4.

Multidisciplinary Approach

• Coordinate care with otolaryngology for airway assessment and potential surgical intervention 3, 2.
• Maintain rheumatology as the primary service directing systemic immunosuppression 5.
• The otolaryngologist's role is critical for airway management, but systemic immunosuppression remains the definitive treatment 2, 5.