What is the initial workup for a patient presenting with urticarial vasculitis?

Workup for Urticarial Vasculitis

The essential workup for urticarial vasculitis requires a lesional skin biopsy to confirm small-vessel vasculitis, followed by inflammatory markers (ESR/CRP), complete blood count with differential, and serum complement levels (C3, C4) to distinguish normocomplementemic from hypocomplementemic disease. 1

Initial Clinical Assessment

Key Historical Features to Identify

• Duration of individual wheals: Ask specifically "For how long does each individual wheal last?" – lesions persisting >24 hours strongly suggest urticarial vasculitis rather than chronic spontaneous urticaria 1
• Quality of symptoms: Painful or burning lesions (rather than purely pruritic) occur in 32% of urticarial vasculitis cases 2
• Residual changes: Lesions resolving with purpura or postinflammatory hyperpigmentation suggest vasculitis (35% of cases) 2
• Systemic symptoms: Specifically inquire about joint/bone pain, malaise, fever, abdominal pain, and pulmonary symptoms 1

Physical Examination Findings

• Document wheal duration and distribution 3
• Look for residual purpura or hyperpigmentation after lesions resolve 2
• Assess for angioedema (present in 42% of urticarial vasculitis cases) 2

Essential Diagnostic Tests

Confirmatory Testing

Lesional skin biopsy is mandatory – this is the only way to definitively diagnose urticarial vasculitis 1, 3. The biopsy must show:

• Leucocytoclasia (neutrophil fragmentation) 1
• Endothelial cell damage 1
• Perivascular fibrin deposition 1
• Red cell extravasation 1

Important caveat: No single histologic feature is pathognomonic; the constellation of findings establishes the diagnosis 1

Initial Laboratory Panel

• Inflammatory markers: ESR and/or CRP (elevated in 37.5% of cases; usually normal in simple chronic urticaria) 1, 4
• Complete blood count with differential: To detect eosinophilia, leukopenia (suggesting systemic lupus erythematosus), or neutrophilia 1, 5
• Serum complement levels (C3 and C4): Critical for distinguishing normocomplementemic from hypocomplementemic disease 1, 3

Full Vasculitis Screen (Required for All Confirmed Cases)

Once biopsy confirms urticarial vasculitis, perform comprehensive evaluation 1, 3:

• Complement studies: C3, C4 (hypocomplementemia occurs in 32% of cases and indicates worse prognosis) 2
• Autoantibodies: ANA (positive in 26.7% of cases), anti-dsDNA if ANA positive 4
• Direct immunofluorescence (if available): Shows immunoglobulin/C3 deposition in blood vessels and basement membrane zone in 87% of hypocomplementemic cases 2

Additional Testing Based on Clinical Suspicion

• C1q levels: If hypocomplementemic urticarial vasculitis syndrome (HUVS) suspected 5
• Paraprotein screen: In adults with systemic symptoms 1
• Urinalysis and renal function: To assess for systemic involvement 6
• Chest imaging: If pulmonary symptoms present (21% have pulmonary disease) 2

Distinguishing Features from Chronic Spontaneous Urticaria

The diagnostic algorithm clearly separates these entities 1:

• Chronic spontaneous urticaria: Individual wheals last 2-24 hours, typically pruritic, no residual changes 3
• Urticarial vasculitis: Individual wheals last >24 hours, often painful/burning, may leave purpura or hyperpigmentation 3, 2

Clinical Significance of Hypocomplementemia

Hypocomplementemic urticarial vasculitis carries significantly worse prognosis and requires more aggressive management 1, 3. These patients are more likely to have:

• Systemic manifestations (arthralgias 49%, pulmonary disease 21%, abdominal pain 17%) 2
• Interstitial neutrophilic dermal infiltrate on histology 2
• Positive immunofluorescence (87% show vascular immunoglobulin/C3 deposition) 2
• Association with systemic lupus erythematosus or other connective tissue diseases 6, 5

Common Pitfalls to Avoid

• Do not rely on clinical appearance alone: 64% of urticarial vasculitis cases have lesions lasting >24 hours, but 36% do not – biopsy is essential 2
• Do not skip complement testing: This single test determines prognosis and treatment intensity 1, 3
• Do not perform routine extensive testing in simple urticaria: If wheals last <24 hours and respond to antihistamines, extensive workup is not indicated 1
• Do not delay biopsy: The window for optimal histologic diagnosis is during active lesions 1

Disease Activity Monitoring

Once diagnosed, use the Urticarial Vasculitis Activity Score assessed for 7 days (UVAS7) to guide treatment decisions 6:

• UVAS7 ≤7 of 70: Skin-limited disease, may respond to urticaria treatment algorithm 6
• UVAS7 >7: More severe disease requiring immunomodulatory therapy, especially if hypocomplementemic 6