What is the best approach to manage urticarial vasculitis with systemic symptoms and minimal response to prednisone, dapsone, and colchicine?

Management of Urticarial Vasculitis with Systemic Symptoms

For urticarial vasculitis with systemic symptoms that has shown minimal response to prednisone, dapsone, and colchicine, omalizumab (300mg subcutaneously every 4 weeks) is the recommended next treatment option. 1

Diagnostic Considerations

Before proceeding with advanced therapy, confirm the diagnosis and severity:

• Ensure proper diagnosis of urticarial vasculitis (UV) with:

  • Wheals lasting >24 hours
  • Evidence of leukocytoclastic vasculitis on skin biopsy
  • Presence of systemic symptoms

• Assess disease severity using the Urticarial Vasculitis Activity Score (UVAS7):

  • Scores >7 indicate more severe disease requiring more aggressive therapy 2
  • Normal cryoglobulins and mostly normal ESR with one high ANA (speckled pattern) suggest an autoimmune component

• Check complement levels:

  • Hypocomplementemic UV typically requires more aggressive treatment 3
  • Low complement levels and positive anti-C1q antibodies are markers of more severe disease

Treatment Algorithm

First-line therapies (already tried with minimal response):

• Prednisone (0.5-1 mg/kg/day)
• Dapsone
• Colchicine

Second-line options:

1. Omalizumab (300mg subcutaneously every 4 weeks)

   • Has shown efficacy in cases refractory to standard treatments
   • Clinical improvement often seen within the first month
   • Complete remission possible by the fifth month of treatment 1

2. Cyclosporine A

   • Effective for both skin and systemic symptoms
   • Requires monitoring of blood pressure and renal function every 6 weeks 4
   • Dosage up to 5mg/kg body weight

3. Hydroxychloroquine

   • Particularly useful if there's an autoimmune component (suggested by the ANA positivity)
   • Lower risk of serious side effects compared to other immunosuppressants

4. Anti-IL-1 agents

   • Consider for severe cases with significant systemic involvement 2

For severe, refractory cases:

• Cyclophosphamide with glucocorticoids

  • Recommended for generalized vasculitis with organ involvement
  • Can be administered intravenously or orally (2 mg/kg/day, max 200 mg/day) 5
  • Requires prophylaxis against Pneumocystis jiroveci with trimethoprim/sulphamethoxazole 5

• Intravenous immunoglobulin

• Mycophenolate mofetil

• Plasmapheresis

Monitoring and Follow-up

• Use validated tools to monitor disease activity and treatment response:

  • Urticarial Vasculitis Activity Score (UVAS7)
  • Regular assessment of complement levels if initially low

• Monitor for medication-specific adverse effects:

  • With cyclophosphamide: blood counts, liver function, urinalysis
  • With cyclosporine: blood pressure, renal function
  • With hydroxychloroquine: ophthalmologic examinations

Important Considerations

• Urticarial vasculitis with systemic symptoms often requires a multidisciplinary approach, especially with hypocomplementemic UV 2

• Look for underlying conditions that may be driving the vasculitis:

  • Systemic lupus erythematosus (suggested by ANA positivity)
  • Malignancy
  • Infection

• The level of evidence for all UV treatments is low, with most recommendations based on case reports and retrospective studies 6

• Biologics like omalizumab represent the most promising recent advancement in treatment of refractory cases 1, 6