How should urticarial vasculitis be diagnosed and managed?

Urticarial Vasculitis: Diagnosis and Management

Diagnostic Approach

Urticarial vasculitis requires lesional skin biopsy for definitive diagnosis when wheals persist beyond 24 hours, leave residual hyperpigmentation or purpura, or are associated with pain or burning rather than pruritus. 1

Clinical Features That Distinguish UV from Ordinary Urticaria

• Individual wheals lasting more than 24 hours are the cardinal feature that should prompt consideration of urticarial vasculitis, whereas ordinary urticaria resolves within 2–24 hours per lesion 1, 2
• Painful or burning lesions (rather than purely pruritic) strongly suggest vasculitis 3, 4
• Residual hyperpigmentation, ecchymosis, or purpura after lesion resolution indicates underlying vascular damage 3, 4, 5
• Palpable purpura may develop as lesions evolve 6

Essential Diagnostic Testing

Skin biopsy of an active lesion (ideally <24 hours old) is mandatory to confirm leukocytoclastic vasculitis histologically, showing endothelial damage, perivascular fibrin deposition, red cell extravasation, and neutrophilic infiltration 1, 4, 5. The biopsy remains the gold standard despite being underutilized in clinical practice 5.

Initial Laboratory Workup

• Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP): typically elevated in UV but normal in ordinary urticaria 1, 4
• Complete blood count with differential to assess for systemic involvement 1
• Complement levels (C3, C4, C1q): critical for prognostic stratification 4, 6
  • Low C4 has high sensitivity for complement consumption 1
  • Hypocomplementemic UV (especially low C1q with anti-C1q antibodies) carries worse prognosis with greater risk of systemic involvement including renal disease 4, 6
  • Normocomplementemic UV typically remains skin-limited with better outcomes 4

Additional Testing for Systemic Disease

• Antinuclear antibodies (ANA) and anti-C1q antibodies to evaluate for systemic lupus erythematosus overlap, as UV can be a presenting feature of SLE 4, 6, 5
• Thyroid autoantibodies (anti-TPO) and thyroid function tests given the autoimmune associations 1
• Consider screening for underlying triggers: malignancy, infection (especially Helicobacter pylori), and drug reactions 2, 5, 7

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Management Algorithm

Stratify by Disease Severity Using UVAS7 Score

For mild UV (UVAS7 ≤7 of 70) with skin-limited disease and minimal systemic symptoms, follow the chronic urticaria treatment ladder 8:

1. Second-generation H₁-antihistamines at standard doses as first-line therapy 8, 7

   • However, antihistamines are ineffective in most UV patients (unlike ordinary urticaria) and should be advanced quickly if no response within 2–4 weeks 7

2. Omalizumab (anti-IgE) can be effective for both skin and systemic symptoms in UV 8, 7

3. Cyclosporine A as third-line option 8, 7

For Moderate-to-Severe UV (UVAS7 >7) or Hypocomplementemic Disease

Systemic corticosteroids are effective in >80% of patients for controlling skin symptoms but require steroid-sparing agents for long-term management 4, 7:

Corticosteroid Regimens

• Initiate with prednisone 0.5–1 mg/kg/day for acute control 4, 6
• Taper as tolerated while introducing steroid-sparing immunomodulatory therapy 4

First-Line Steroid-Sparing Agents (Choose Based on Availability and Safety Profile)

• Dapsone 50–200 mg/day: effective for both skin and systemic symptoms; requires G6PD screening before initiation 4, 8, 7
• Hydroxychloroquine 200–400 mg/day: particularly useful when SLE overlap is suspected 4, 6, 7
• Colchicine 0.6–1.2 mg/day: effective in many patients with acceptable safety profile 4, 6, 7

Second-Line Immunosuppressive Agents for Refractory Disease

• Mycophenolate mofetil: effective for both cutaneous and systemic manifestations 7
• Azathioprine: useful for corticosteroid-resistant cases 4, 6
• Cyclophosphamide: reserved for severe systemic involvement (necrotizing lesions, visceral disease) or life-threatening hypocomplementemic UV 4, 6, 7

Emerging Biologic Therapies

• Anti-IL-1 agents (anakinra, canakinumab): increasingly recognized as effective options, particularly for refractory cases 8
• Omalizumab: can be effective even in moderate-to-severe UV 8, 7

Ineffective Therapies to Avoid

• H₂-antihistamines, montelukast, danazol, pentoxifylline, doxepin, and tranexamic acid are ineffective in most UV patients and should not be used 7
• NSAIDs and aspirin may provide modest benefit in some cases but can also trigger mast cell degranulation and worsen urticaria in aspirin-sensitive patients 2, 4, 6

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Multidisciplinary Approach for Systemic Disease

Patients with hypocomplementemic UV, systemic symptoms (arthralgia, fever, renal involvement), or suspected underlying disease require coordinated care 8:

• Rheumatology consultation for SLE evaluation and management of joint/systemic manifestations 3, 4
• Nephrology referral if proteinuria or renal dysfunction develops 4
• Hematology-oncology evaluation if paraneoplastic syndrome is suspected 3, 4
• Infectious disease workup including H. pylori testing and eradication if positive 2

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Common Pitfalls and Caveats

• Misdiagnosis as chronic spontaneous urticaria is common when skin biopsy is not performed, leading to prolonged ineffective antihistamine therapy 5
• Delaying biopsy beyond 24 hours of lesion onset reduces diagnostic yield; biopsy fresh lesions whenever possible 1
• Long-term corticosteroid monotherapy leads to significant morbidity; always introduce steroid-sparing agents early 4, 7
• Failure to screen for complement levels misses the critical prognostic distinction between normocomplementemic and hypocomplementemic disease 4, 6
• Overlooking systemic involvement: always assess for arthralgia, fever, abdominal pain, and renal symptoms, as these indicate need for more aggressive therapy 4, 8