What is the treatment approach for relapsing polychondritis with associated vasculitis?

Treatment Approach for Relapsing Polychondritis with Associated Vasculitis

For relapsing polychondritis with associated vasculitis, treatment should consist of high-dose glucocorticoids combined with either rituximab or cyclophosphamide for induction therapy, followed by maintenance therapy with rituximab, azathioprine, methotrexate, or mycophenolate mofetil for at least 18-24 months.

Initial Assessment and Diagnosis

• Confirm diagnosis through clinical features:

  • Auricular chondritis (88% of cases)
  • Nasal chondritis
  • Respiratory tract involvement (>50% of cases)
  • Arthralgias (81% of cases)
  • Ocular inflammation
  • Signs of vasculitis

• Perform tissue biopsy when possible to confirm vasculitis

• Check for ANCA status (particularly p-ANCA)

• Assess organ involvement through:

  • Pulmonary function tests with flow-volume curves
  • CT scanning of chest (to identify tracheobronchial wall thickening/stenosis)
  • Renal function tests (especially with ANCA-associated vasculitis)

Induction Therapy

For Organ-Threatening or Life-Threatening Disease:

1. High-dose glucocorticoids:

   • Initial dose: 40-60 mg/day prednisone or equivalent 1
   • Consider IV methylprednisolone pulses for severe disease

2. Combined with ONE of the following:

   • Rituximab: 375 mg/m² weekly for 4 weeks 1, 2

     • Preferred for patients with relapsing disease 1
     • Higher remission rates in PR3-ANCA positive patients

   • Cyclophosphamide:

     • IV regimen: 15 mg/kg every 2-3 weeks (adjusted for age and renal function)
     • Oral regimen: 2 mg/kg/day (maximum 200 mg/day)

3. Consider plasma exchange for patients with:

   • Serum creatinine >3.4 mg/dL (>300 μmol/L)
   • Rapidly progressive glomerulonephritis
   • Diffuse alveolar hemorrhage with hypoxemia 1

For Non-Organ-Threatening Disease:

• Combination of glucocorticoids with methotrexate or mycophenolate mofetil 1
• NSAIDs may be used for milder manifestations 1

Maintenance Therapy

After achieving remission (typically 3-6 months):

1. Duration: 18 months to 4 years 1

2. Medication options:

   • Rituximab:

     • 500 mg every 6 months 1, 2
     • Superior to azathioprine for preventing relapses

   • Azathioprine:

     • 1.5-2 mg/kg/day initially
     • Taper to 1 mg/kg/day after 18-24 months

   • Methotrexate:

     • 15-25 mg weekly (avoid if GFR <60 ml/min)

   • Mycophenolate mofetil:

     • 2000 mg/day in divided doses

3. Glucocorticoid taper:

   • Gradually taper to 5-7.5 mg/day
   • Maintain for at least 12-18 months
   • Slow taper thereafter (1 mg every 2 months) 1

Management of Relapses

1. Major relapse:

   • Treat as new-onset disease with high-dose glucocorticoids (40-60 mg/day)
   • Add rituximab (preferred) or cyclophosphamide 1
   • Consider switching from cyclophosphamide to rituximab or vice versa if previously used

2. Minor relapse:

   • Increase glucocorticoid dose to last effective dose or 5-15 mg above current dose 1
   • Consider adding or modifying immunosuppressive therapy

Special Considerations

• Respiratory involvement: Requires long-term systemic immunosuppression as it's the leading cause of mortality in relapsing polychondritis 1, 3
• Renal involvement: Common with ANCA-associated vasculitis; monitor renal function closely
• Monitoring:
  • Regular clinical assessment every 1-3 months during first year
  • Monitor inflammatory markers (ESR, CRP)
  • Repeat imaging for respiratory involvement as needed
  • Do not rely solely on ANCA titers for treatment decisions 1

Prognosis and Follow-up

• Mortality is frequently related to respiratory complications 1
• Long-term follow-up is essential due to high relapse risk
• Continue monitoring for at least 2 years after discontinuation of therapy
• Assess for cardiovascular risk factors regularly 1

This treatment approach aligns with current guidelines for ANCA-associated vasculitis while addressing the specific needs of patients with relapsing polychondritis, focusing on reducing mortality and morbidity through aggressive management of inflammation and prevention of organ damage.