What is the approach to diagnosing and treating urticarial vasculitis?

Urticarial Vasculitis Diagnosis

Lesional skin biopsy extending to the subcutis is essential to confirm urticarial vasculitis, and should be performed when urticarial lesions persist beyond 24 hours—the key clinical feature distinguishing this condition from ordinary urticaria. 1, 2

Clinical Features That Trigger Diagnostic Workup

• Individual urticarial lesions lasting >24 hours is the cardinal feature that should prompt consideration of urticarial vasculitis rather than chronic spontaneous urticaria (where lesions typically last 2-24 hours) 1, 2, 3
• Painful or burning quality of lesions occurs in approximately 32% of cases, contrasting with the pruritic nature of ordinary urticaria 4
• Residual purpura or hyperpigmentation after lesion resolution is seen in 35% of patients and strongly suggests vasculitis 4
• Non-blanching quality when pressure is applied with a glass slide distinguishes vasculitic lesions from typical urticaria 5

Essential Diagnostic Testing

Skin Biopsy Technique

• A deep punch biopsy extending to the subcutis (not superficial) must be performed by a dermatologist to capture the affected medium-sized dermal vessels 2, 5
• Target the most tender, reddest, or purpuric lesion for optimal diagnostic yield 2, 5
• Superficial biopsies are inadequate and will miss diagnostic vascular changes, resulting in false-negative results 5

Key Histological Features to Confirm

• Leukocytoclastic vasculitis with fibrinoid necrosis of vessel walls 1, 2
• Endothelial cell damage and perivascular fibrin deposition 1, 2
• Red cell extravasation (hemorrhage into surrounding tissue) 1, 2
• Leucocytoclasia (nuclear debris from neutrophil fragmentation) 1
• Note: No single feature is pathognomonic; the constellation of findings confirms diagnosis 1

Direct Immunofluorescence

• Should be performed on biopsy specimens, particularly when hypocomplementemia is present 4
• Immunoglobulin or C3 deposition in vessel walls is found in 87% of hypocomplementemic cases 4
• Basement membrane zone fluorescence occurs in 70% of hypocomplementemic patients 4

Comprehensive Laboratory Workup

Initial Screening Tests

• Serum complement levels (C3 and C4) are mandatory to distinguish normocomplementemic from hypocomplementemic disease 1, 2
• Hypocomplementemic urticarial vasculitis carries a worse prognosis with 5-year and 10-year survival rates of 92% and 83% respectively, with mortality from COPD, septicemia, and end-stage renal disease 6
• Complete blood count with differential to detect eosinophilia, leukopenia, or other hematologic abnormalities 1
• Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) is usually elevated in urticarial vasculitis (unlike chronic ordinary urticaria where it's typically normal) 1, 7

Additional Testing for Systemic Involvement

• Full vasculitis screen including ANA, anti-dsDNA, rheumatoid factor, ANCA, cryoglobulins 1
• Thyroid function tests and anti-thyroid peroxidase antibodies to assess for autoimmune associations 1
• Urinalysis to screen for renal involvement 1
• Chest imaging if pulmonary symptoms present (occurs in 21% of cases) 4

Assessment of Systemic Involvement

Common Extracutaneous Manifestations to Screen For

• Arthralgias (present in 43-49% of patients) 4, 7
• Angioedema (occurs in 42-75% of cases) 4, 7
• Pulmonary disease including COPD (21% of patients) 4
• Abdominal pain (17% of cases) 4
• Renal involvement particularly in hypocomplementemic disease 4

Features Associated with Hypocomplementemia

Patients with low complement levels are significantly more likely to have:

• Dermal neutrophilic infiltrate on histology (70% of hypocomplementemic cases) 4
• Lesions resolving with purpura 4
• Chronic obstructive pulmonary disease 4
• More severe systemic symptoms requiring multidisciplinary management 3

Identifying Underlying Triggers

Common Associations to Investigate

• Medication triggers: Analgesics (especially NSAIDs, aspirin), antibiotics, and codeine are the most common precipitants (56% of cases) 1, 7
• Autoimmune diseases: Systemic lupus erythematosus, Sjögren's syndrome 8
• Infections: Including COVID-19 and COVID-19 vaccines (emerging association) 6
• Malignancy: Screen if clinically indicated, though statistical association is weak 1
• Autoinflammatory syndromes: VEXAS syndrome and adenosine deaminase deficiency (newly recognized associations) 6

Critical Diagnostic Pitfalls to Avoid

• Do not rely on superficial punch biopsy—it must extend to subcutis to sample affected vessels 5
• Do not dismiss lesions lasting >24 hours as ordinary urticaria—this duration mandates biopsy consideration 2, 3
• Do not skip complement testing—hypocomplementemic disease requires different monitoring and has worse prognosis 1, 2
• Do not overlook systemic screening in confirmed cases—nearly half have extracutaneous involvement requiring multidisciplinary care 4

Emerging Diagnostic Tools

• Dermoscopy showing purpuric patches and globules can help differentiate urticarial vasculitis from chronic spontaneous urticaria, potentially reducing need for biopsy in some cases 6
• Clinical-dermoscopic models are being developed but biopsy remains the gold standard 6