What is the treatment approach for an adult patient with cutaneous small vessel vasculitis, potentially with a history of autoimmune conditions or recent medication use?

Treatment of Cutaneous Small Vessel Vasculitis

For isolated cutaneous small vessel vasculitis without systemic involvement, first-line treatment consists of removing any identifiable trigger (drugs, infections) combined with conservative measures, reserving colchicine or dapsone for chronic or recurrent disease, while systemic vasculitis with cutaneous manifestations requires immediate high-dose glucocorticoids (prednisone 1 mg/kg/day) combined with cyclophosphamide or rituximab. 1

Initial Disease Stratification

The critical first step is distinguishing isolated cutaneous disease from systemic vasculitis with skin involvement, as treatment algorithms differ fundamentally 1, 2:

• Isolated cutaneous vasculitis presents with palpable purpura (the hallmark finding) typically on dependent areas like lower extremities, without life- or organ-threatening manifestations 3, 1
• Systemic vasculitis includes gangrene, digital necrosis, severe organ involvement, or features suggesting ANCA-associated vasculitis, requiring immediate aggressive immunosuppression 1, 4

Diagnostic Workup

Before initiating treatment, obtain:

• Skin biopsy extending to subcutis from the most tender, reddish or purpuric lesion, examined with both light microscopy (showing fibrinoid necrosis, red blood cell extravasation, endothelial damage) and direct immunofluorescence (distinguishing IgA vasculitis from IgG/IgM patterns) 3, 2, 4
• Laboratory assessment for systemic involvement: complete blood count, ESR/CRP, kidney function, urinalysis, complement levels (C3/C4), ANCA testing (MPO and PR3), cryoglobulins 5, 3, 2
• History focusing on recent medications (most common trigger at 52%), preceding infections (34%), and autoimmune conditions 2, 6

Treatment Algorithm for Isolated Cutaneous Disease

Self-Limited or Single Episode

For patients with an identified trigger and no systemic involvement 2, 6:

• Remove the inciting factor (discontinue offending drug, treat underlying infection) 2, 6
• Conservative measures: leg elevation, avoid prolonged standing, warming 4, 7
• Symptomatic relief: NSAIDs for pain and inflammation 2, 7, 8
• Antihistamines for associated pruritus 7

Most cases resolve spontaneously with this approach, with complete recovery observed in all patients after median 4-month follow-up 6

Chronic or Recurrent Disease

For persistent or recurrent cutaneous vasculitis without systemic involvement 2, 7:

First-line agents (use singly or in combination):

• Colchicine as initial therapy 2, 4, 7
• Dapsone as alternative or combination with colchicine 2, 4, 7

Second-line options for refractory cases:

• Azathioprine 1-2 mg/kg/day 1, 2, 8
• Mycophenolate mofetil 2 g/day 1, 7, 8
• Methotrexate 2, 4, 8

Treatment Algorithm for Systemic Vasculitis with Cutaneous Involvement

Severe or Organ-Threatening Disease

Immediate induction therapy (do not delay for biopsy if clinical presentation and positive ANCA support diagnosis) 5, 1:

• High-dose glucocorticoids: prednisone 1 mg/kg/day 1, 9
• Plus cyclophosphamide as first-line combination 1, 4
• Or rituximab 375 mg/m² weekly for 4 weeks (91% remission rate, particularly effective for refractory ANCA-associated vasculitis) 1, 4

Continue high-dose glucocorticoids for minimum 1 month before gradual taper 1

Maintenance Therapy

After achieving remission 1:

• Azathioprine 1-2 mg/kg/day for at least 18 months in complete remission 1
• Continue maintenance immunosuppression to prevent relapse 5, 1

Mandatory Prophylaxis

For all patients receiving intensive immunosuppression 1:

• Pneumocystis prophylaxis: trimethoprim-sulfamethoxazole for patients on cyclophosphamide 1
• Bone protection: calcium, vitamin D, and bisphosphonates for all patients on glucocorticoids 1, 9

Refractory Disease Options

When standard therapy fails 1, 4:

• Intravenous immunoglobulin (IVIG) 2 g/kg over 5 days 1, 4, 7
• Plasmapheresis/plasma exchange for severe refractory cases 4, 7
• Rituximab if not already used (highly effective with 91% remission in refractory cases) 1

Special Considerations

ANCA-Negative Patients

Approximately 10% of patients with clinical small-vessel vasculitis are persistently ANCA-negative but are treated identically to ANCA-positive patients 5. However, carefully exclude vasculitis mimics including systemic lupus erythematosus, infections, malignancies, and thrombotic disorders like antiphospholipid syndrome 5, 4

Autoimmune Context

Patients with checkpoint inhibitor therapy may develop vasculitis with atypical features: autoantibodies (ANA, ANCA, RF) are often absent despite clinical vasculitis 5. Prompt rheumatology consultation is essential, with median time to evaluation ideally under 7-10 days 5

Common Pitfalls

• Never delay treatment in rapidly deteriorating patients with positive MPO/PR3-ANCA and compatible clinical presentation while waiting for biopsy results 5
• Don't undertreat systemic disease: isolated cutaneous vasculitis and systemic vasculitis with skin involvement require fundamentally different treatment intensities 1
• Avoid premature steroid taper: maintain high-dose glucocorticoids for minimum 1 month before gradual reduction 1
• Don't forget prophylaxis: infection risk is substantial with cyclophosphamide, and bone loss occurs rapidly with high-dose glucocorticoids 1

Prognosis

Isolated cutaneous vasculitis is generally benign with complete recovery expected, though 8% experience relapses 6. Systemic vasculitis requires long-term maintenance therapy with careful monitoring for relapse, defined as return of disease activity after remission 5, 1