What is the treatment for urticarial vasculitis?

Treatment of Urticarial Vasculitis

Begin with second-generation H1-antihistamines at standard doses for mild disease, escalate to 4x standard dosing if needed, then add systemic corticosteroids for moderate-to-severe cases, followed by immunomodulatory agents (dapsone, hydroxychloroquine, or omalizumab) for steroid-sparing maintenance therapy. 1

Diagnostic Confirmation Before Treatment

• Confirm diagnosis with lesional skin biopsy showing leucocytoclastic vasculitis (endothelial damage, perivascular fibrin deposition, red cell extravasation) in lesions lasting >24 hours 1
• Obtain serum complement levels (C3, C4) to distinguish normocomplementemic from hypocomplementemic disease, as this affects prognosis and treatment intensity 1
• Perform full vasculitis screen to identify underlying systemic disease (SLE, malignancy, infection) that requires specific treatment 1, 2

Treatment Algorithm by Disease Severity

Mild Disease (UVAS7 ≤7 of 70)

Start with second-generation H1-antihistamines (cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine) at standard doses 1

• Trial at least two different antihistamines, as individual responses vary significantly 1
• If inadequate control after 2-4 weeks, increase dose up to 4x standard dosing (exceeds manufacturer recommendations but supported by guidelines) 1
• Consider adding H2-antihistamines or antileukotrienes for resistant cases, though evidence shows limited efficacy in most UV patients 1, 3

Moderate Disease (UVAS7 >7 or inadequate antihistamine response)

Add short courses of systemic corticosteroids (prednisolone 0.5-1 mg/kg/day) 1

• Taper over 3-4 weeks to minimize adverse effects 1
• Do not use long-term corticosteroids except under specialist supervision, as they are effective in >80% of patients but carry serious toxicity with prolonged use 3
• Begin steroid-sparing immunomodulatory agent early to facilitate tapering 1

Severe or Refractory Disease

Initiate immunomodulatory therapy based on the following hierarchy:

First-line immunomodulatory options:

• Omalizumab 300 mg subcutaneously every 4 weeks for patients following the chronic urticaria algorithm 1, 2

  • Allow up to 6 months for response 1
  • Can updose to 600 mg every 2 weeks if inadequate response 1
  • Systematic review shows omalizumab effective for both skin and systemic symptoms 3

• Dapsone for patients with prominent cutaneous disease 3, 2

  • Associated with long-lasting treatment-free remission 4
  • Check G6PD levels before initiating

• Hydroxychloroquine particularly for patients with autoimmune features or hypocomplementemic disease 3, 2

  • Effective for both skin and systemic manifestations 3

Second-line immunomodulatory options:

• Cyclosporine up to 5 mg/kg/day for patients unresponsive to omalizumab 1

  • Monitor blood pressure and renal function every 6 weeks 1
  • Effective in systematic review but requires close monitoring 3

• Mycophenolate mofetil for maintenance therapy 3

  • Associated with durable remission 4

Third-line options for severe systemic disease:

• Cyclophosphamide for life-threatening systemic involvement 3, 2
• Anti-IL-1 agents (anakinra, canakinumab) for refractory cases 2, 4
• Rituximab for severe refractory disease, particularly hypocomplementemic UV 3, 4
  • Highest success rates and long-lasting remission in recent studies 4
• Tocilizumab (anti-IL-6) emerging as alternative for selected cases 4

Hypocomplementemic UV: Special Considerations

Requires more aggressive multidisciplinary approach due to higher risk of systemic involvement and worse prognosis 2

• Screen for underlying SLE, as treatment should target the primary disease 2
• Monitor complement levels regularly to assess disease activity 1
• Consider earlier initiation of immunomodulatory therapy rather than prolonged corticosteroid use 2
• 5-year and 10-year survival rates are 92% and 83%, with mortality from COPD, septicemia, and end-stage renal disease 4

General Measures and Trigger Avoidance

• Minimize aggravating factors: overheating, stress, alcohol 1
• Avoid NSAIDs, aspirin, and codeine, which worsen urticaria 1
• Withdraw suspected triggering drugs (analgesics and antibiotics are most common triggers) 5
• Treat underlying infections or malignancy if identified 3
• Apply cooling antipruritic lotions (calamine, 1% menthol in aqueous cream) for symptomatic relief 1

Monitoring and Follow-up

• Assess disease activity at every visit using validated tools (UVAS7 score) 1, 2
• Monitor quality of life impact with patient-reported outcome measures 1
• For patients on cyclosporine: check blood pressure and renal function every 6 weeks 1
• Step down therapy after achieving complete control for at least 3 consecutive months 1

Common Pitfalls to Avoid

• Do not rely on antihistamines alone for true urticarial vasculitis—systematic review shows H1-antihistamines are ineffective in most UV patients, unlike chronic urticaria 3
• Do not continue corticosteroids long-term without adding steroid-sparing agents, as this leads to cumulative toxicity 1, 3
• Do not assume all urticarial lesions are UV—lesions must last >24 hours and require biopsy confirmation 1
• Recognize that montelukast, danazol, pentoxifylline, and tranexamic acid show poor efficacy in UV despite use in chronic urticaria 3

Evidence Quality Note

Current UV treatment recommendations are based primarily on case reports, retrospective studies, and expert consensus rather than randomized controlled trials 3, 2. The 2025 expert consensus algorithm 2 and 2019 systematic review 3 provide the strongest available evidence, with the systematic review analyzing 789 patients across 261 studies showing corticosteroids and biologics have the highest efficacy rates.