How should I evaluate and manage a patient with urticarial vasculitis?

Evaluation and Management of Urticarial Vasculitis

Urticarial vasculitis requires skin biopsy for definitive diagnosis when wheals persist beyond 24 hours, and treatment should be stratified by disease severity using the UVAS7 score, with mild cases (UVAS7 ≤7) managed like chronic urticaria and severe cases requiring immunomodulatory therapy. 1, 2

Diagnostic Evaluation

Clinical Features That Distinguish UV from Ordinary Urticaria

• Individual wheals lasting >24 hours are the single most critical diagnostic feature separating urticarial vasculitis from ordinary urticaria (which lasts 2-24 hours). 3, 1, 4
• Look for painful or tender lesions rather than purely pruritic ones. 5, 6
• Check for residual hyperpigmentation after lesions resolve—this strongly suggests UV rather than ordinary urticaria. 1, 5, 6
• Examine for purpuric or dusky changes within the urticarial plaques. 7

Essential Diagnostic Workup

Skin biopsy is mandatory when clinical features suggest UV—specifically when wheals persist beyond 24 hours with pain, purpura, or post-inflammatory changes. 1, 4, 6

The biopsy should demonstrate:

• Leucocytoclastic vasculitis with neutrophil infiltration of vessel walls 1
• Endothelial cell damage 1
• Perivascular fibrin deposition 1
• Red cell extravasation 1

Important caveat: Only 13.6% of clinically suspected UV cases show classic leukocytoclastic vasculitis on histology; 86.4% show predominantly lymphocytic infiltrates with eosinophils and red cell extravasation, which still represents a form of vasculitis. 7

Laboratory Assessment

Order the following tests to distinguish normocomplementemic from hypocomplementemic disease and assess systemic involvement:

• Complement levels (C3, C4) to classify disease subtype 1, 6
• Complete blood count with differential 4, 6
• ESR or CRP to assess inflammatory activity 4, 6
• Antinuclear antibodies to screen for underlying systemic lupus erythematosus 6
• C1q levels and anti-C1q antibodies if hypocomplementemia is present, as this indicates more severe systemic disease 5

Hypocomplementemic UV carries higher risk of systemic involvement including renal and joint disease, and requires more aggressive management. 8, 5

Management Algorithm Based on Disease Severity

Mild UV (UVAS7 ≤7 of 70): Skin-Limited Disease

For patients with occasional UV lesions, skin-limited manifestations, or mild arthralgia/malaise:

First-line: Second-generation H1-antihistamines at standard doses 2, 6

• Approximately two-thirds of physicians use this as initial therapy 6
• This follows the same stepwise approach as chronic spontaneous urticaria 2

Second-line: If antihistamines fail, escalate to:

• Omalizumab (anti-IgE therapy), which has shown success in normocomplementemic UV 2, 9
• Cyclosporine A as an alternative immunosuppressant 2

Moderate to Severe UV (UVAS7 >7): Systemic or Hypocomplementemic Disease

For patients with more severe symptoms, especially hypocomplementemic UV or systemic involvement:

Multidisciplinary evaluation is required to identify underlying diseases:

• Systemic lupus erythematosus 2, 6
• Malignancy 2
• Infection 2

Immunomodulatory therapy based on clinical severity and drug availability:

1. Systemic corticosteroids for acute control 2, 5
2. Dapsone as a steroid-sparing agent 2, 5, 9
3. Hydroxychloroquine particularly when autoimmune features are present 2, 5, 9
4. Colchicine as an alternative anti-inflammatory 5, 9
5. Anti-interleukin-1 agents for refractory cases 2
6. Cytotoxic agents (cyclophosphamide, azathioprine) reserved for severe systemic disease 5

Common Pitfalls to Avoid

• Do not treat clinically suspected UV as ordinary chronic urticaria without biopsy confirmation—this leads to inadequate treatment and misdiagnosis. 6
• Do not rely solely on classic leukocytoclastic vasculitis on histology—lymphocytic vasculitis with eosinophils and red cell extravasation still represents UV and requires appropriate management. 7
• Do not overlook complement testing—hypocomplementemic disease requires more aggressive therapy and monitoring for systemic complications. 1, 5
• Recognize that NSAIDs and aspirin may be therapeutic in UV (unlike ordinary urticaria where they worsen symptoms). 5

Key Evidence Gaps

The level of evidence for all UV treatments remains low, with no established clinical guidelines or treatment algorithms until recently. 2, 6 The proposed UVAS7-based algorithm represents expert consensus rather than randomized controlled trial data. 2