What is the management of leukocytoclastic vasculitis?

Management of Leukocytoclastic Vasculitis

The management of leukocytoclastic vasculitis (LCV) requires a combination of glucocorticoids and either cyclophosphamide or rituximab for organ-threatening or life-threatening disease, while skin-limited disease may respond to lower-intensity therapy including colchicine or dapsone.

Initial Assessment and Classification

• Determine if LCV is:

  • Skin-limited (cutaneous only)
  • Systemic with organ involvement
  • Associated with ANCA (ANCA-associated vasculitis)
  • Secondary to underlying causes

• Identify potential triggers:

  • Medications
  • Infections
  • Malignancy
  • Connective tissue diseases
  • Cryoglobulinemia

• Essential diagnostic workup:

  • Skin biopsy with immunofluorescence (to identify IgA, IgG, or IgM immune complexes)
  • Complete blood count
  • Renal function tests and urinalysis
  • Serological tests (ANCA, ANA, complement levels)

Treatment Algorithm

1. Skin-Limited LCV

• First-line treatment:

  • Rest and elevation of affected areas
  • Compression stockings to reduce purpura
  • Colchicine as first-line therapy for chronic or relapsing cases 1
  • Low-dose corticosteroids (prednisone <20 mg/day) for symptomatic relief

• Second-line options:

  • Dapsone (50-200 mg/day) if colchicine is ineffective 1
  • Consider topical dapsone for selected patients with contraindications to systemic therapy 2

2. Organ-Threatening or Life-Threatening LCV

• Induction therapy:

  • High-dose glucocorticoids (40-60 mg/day prednisone equivalent) 3, 4
  • PLUS one of the following:
    • Cyclophosphamide (level of evidence 1A for GPA and MPA) 3, 4
    • Rituximab (level of evidence 1B for GPA and MPA) 3, 4

• Cyclophosphamide administration:

  • Oral: 2 mg/kg/day (maximum 200 mg/day) 3
  • OR Intravenous pulse: 0.6 mg/m² initially every 2 weeks for a month, then every 4 weeks 3
  • Antiemetic therapy should be administered with IV cyclophosphamide 3
  • Encourage hydration to prevent hemorrhagic cystitis 3
  • Consider MESNA to bind toxic metabolites 3

• Rituximab dosing:

  • 375 mg/m² of body surface area, once weekly for four infusions 3

3. Glucocorticoid Tapering Schedule

• Taper high-dose glucocorticoids to 15-20 mg/day within 2-3 months 4
• After 1 year, target ≤5 mg/day for GCA and ≤10 mg/day for other forms 4

4. Maintenance Therapy

• After achieving remission, transition to:
  • Azathioprine or methotrexate 3, 4
  • Consider rituximab for maintenance in selected cases 3

Special Considerations

Prophylaxis

• For patients on cyclophosphamide, rituximab, or high-dose glucocorticoids:
  • Trimethoprim-sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) for Pneumocystis jirovecii pneumonia prophylaxis 3, 4
  • Alternatives if contraindicated: dapsone, atovaquone, or inhaled pentamidine 3

Monitoring

• Monitor blood counts regularly for patients on cyclophosphamide 3
• Monitor serum immunoglobulin concentrations prior to each course of rituximab 4
• Follow-up every 1-3 months during the first year, then every 3-6 months 4

Management of Relapse

• For major relapse:
  • Reinstitute or escalate glucocorticoid therapy 4
  • Consider initiation or modification of adjunctive therapy 4

Refractory Disease

• Consider referral to centers with vasculitis expertise 4
• Alternative immunosuppressants to consider:
  • Mycophenolate mofetil
  • Tocilizumab
  • TNF inhibitors 4

Pitfalls and Caveats

1. Diagnostic challenges:

   • LCV can mimic other conditions including skin malignancies; adequate tissue biopsy is essential when there is diagnostic uncertainty 5
   • IgA-dominant immune complexes suggest higher likelihood of systemic involvement (Henoch-Schönlein purpura) 1

2. Treatment considerations:

   • Delay surgical intervention until disease is quiescent whenever possible 4
   • Self-limited disease may resolve spontaneously within weeks 2
   • Always investigate and treat underlying causes (medications, infections, malignancies) 6

3. Monitoring complications:

   • Regular monitoring for cyclophosphamide toxicity (hemorrhagic cystitis, bone marrow suppression)
   • Monitor for glucocorticoid-related adverse effects and comorbidities 3

By following this structured approach to the management of leukocytoclastic vasculitis, clinicians can optimize outcomes while minimizing treatment-related complications.