What is the treatment approach for a patient with relapsing polychondritis and VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome?

Treatment Approach for Relapsing Polychondritis with VEXAS Syndrome

For patients with relapsing polychondritis and VEXAS syndrome, high-dose systemic corticosteroids should be initiated as first-line therapy, with addition of IL-6 inhibitors (tocilizumab or siltuximab) as the preferred biologic agent for maintenance therapy and steroid-sparing effect. 1, 2

Initial Treatment Strategy

Acute Phase Management

• High-dose systemic corticosteroids:
  • Oral prednisolone/prednisone (1 mg/kg/day) for significant inflammation
  • Consider IV methylprednisolone pulses (500-1000 mg) for severe respiratory involvement or life-threatening manifestations 1
  • Target rapid control of systemic inflammation

Assessment of Disease Severity

1. Evaluate for organ-threatening manifestations:

   • Respiratory tract involvement (most critical prognostic factor)
   • Cardiovascular involvement
   • Renal manifestations (including C3 glomerulonephritis)
   • Neurological involvement

2. Laboratory evaluation:

   • Complete blood count (monitor for cytopenias)
   • Inflammatory markers (CRP, ESR)
   • Genetic testing for UBA1 mutation to confirm VEXAS diagnosis

Maintenance Therapy

For Moderate to Severe Disease

• IL-6 pathway inhibitors as preferred biologic agents:

  • Tocilizumab (8 mg/kg IV every 4 weeks or 162 mg SC weekly) 2, 3
  • Siltuximab (11 mg/kg IV every 3 weeks) has shown efficacy in refractory cases 2

• Alternative immunosuppressants if IL-6 inhibitors fail:

  • Rituximab (375 mg/m² weekly for 4 weeks) particularly effective for relapsing disease 1, 4
  • Methotrexate (15-25 mg/week) 5
  • Azathioprine (2 mg/kg/day) 5
  • Mycophenolate mofetil (1-2 g/day) 5

For Mild Disease

• Corticosteroid-sparing agents:
  • Colchicine (0.5-1.0 mg daily) for milder cases 5
  • NSAIDs for minor manifestations (with caution due to potential renal effects)

Special Considerations for VEXAS Syndrome

• Monitor for hematologic complications:

  • Regular blood counts to assess for myelodysplastic syndrome progression
  • Bone marrow evaluation if cytopenias worsen

• Thrombosis prevention:

  • Consider prophylactic anticoagulation as VEXAS increases thrombosis risk

• Vascular complications:

  • Vigilance for arteriovenous fistulas or aneurysms that may require surgical intervention 3

Monitoring and Follow-up

• Initial monitoring: Every 1-4 weeks until remission is achieved 1

• Maintenance monitoring: Every 3-6 months once stable 1

• Imaging surveillance:

  • CT scanning of airways for patients with respiratory symptoms
  • Pulmonary function tests with flow-volume curves to detect subtle airway involvement
  • Cardiac evaluation if symptoms suggest involvement

• Bone health:

  • Bone densitometry
  • Calcium and vitamin D supplementation
  • Consider bisphosphonates for long-term corticosteroid use 1

Treatment Failure or Relapse

• For refractory disease:
  • Switch between IL-6 inhibitors (tocilizumab to siltuximab or vice versa) 2
  • Consider JAK inhibitors (tofacitinib) though evidence is limited 4
  • TNF-α inhibitors (infliximab or adalimumab) may be effective but efficacy can wane over time 4

Prognosis

The prognosis for patients with relapsing polychondritis with VEXAS syndrome is generally poor without appropriate treatment, with respiratory complications being the leading cause of mortality 1. Early aggressive intervention with corticosteroids and appropriate biologic therapy significantly improves outcomes and quality of life.