What is leucocytoclastic vasculitis in adults with a history of autoimmune disorders or exposure to certain medications?

What is Leucocytoclastic Vasculitis?

Leucocytoclastic vasculitis (LCV) is a small-vessel vasculitis characterized histopathologically by neutrophilic infiltration with nuclear fragmentation (leukocytoclasia), fibrinoid necrosis of vessel walls, and endothelial damage, most commonly presenting as palpable purpura on the lower extremities. 1

Pathophysiology and Mechanism

LCV is primarily mediated by immune complex deposition in small vessel walls, which triggers neutrophil recruitment and subsequent vascular endothelial damage with red blood cell extravasation 1, 2. The inflammatory infiltrate consists predominantly of neutrophils with characteristic nuclear debris ("leukocytoclasia"), fibrinoid necrosis, and perivascular fibrin deposition, though no single histologic feature is pathognomonic 3.

In the context of autoimmune disorders, LCV represents cutaneous manifestations of systemic vasculitides including:

• ANCA-associated vasculitides (Wegener's granulomatosis, microscopic polyangiitis) 1
• Mixed cryoglobulinemia syndrome (particularly HCV-associated), where circulating immune complexes cause vasculitic manifestations 3
• Connective tissue diseases (systemic lupus erythematosus, rheumatoid arthritis) 1
• IgA vasculitis (Henoch-Schönlein purpura) 1

Clinical Presentation

Primary Cutaneous Features

• Palpable purpura is the hallmark presentation, most commonly affecting the lower extremities 1, 2
• Lesions may also present as petechiae, target lesions, or rarely annular configurations 4, 5
• Individual lesions typically persist for days in urticarial vasculitis, contrasting with ordinary urticaria where weals resolve within 2-24 hours 3

Systemic Manifestations

When LCV extends beyond skin-limited disease, patients may develop:

• Constitutional symptoms: fever, myalgia, fatigue, arthralgias 4, 2
• Renal involvement: glomerulonephritis with hematuria and proteinuria 1, 2
• Gastrointestinal: abdominal pain 2
• Neurologic: sensory neuropathy or mononeuritis multiplex indicating severe vasculitic involvement 4

Etiologic Considerations in Adults with Autoimmune History

Drug-Induced LCV

In patients with medication exposure, certain drugs induce ANCA formation leading to neutrophil activation and vascular inflammation, with propylthiouracil and TNF inhibitors being notable culprits. 6 Levamisole-induced vasculitis characteristically presents with neutropenia, retiform purpuric rash, and dual MPO/PR3 ANCA positivity 7. Discontinuation of the offending medication is often sufficient for resolution in most drug-induced cases. 6

Autoimmune-Associated LCV

• Mixed cryoglobulinemia (especially HCV-related) presents with the classic triad of purpura, weakness, and arthralgias, along with low C4 complement and cutaneous leucocytoclastic vasculitis 3
• ANCA-associated vasculitides require distinction between organ-threatening disease versus isolated cutaneous involvement 3, 8
• Atypical c-ANCA patterns may represent non-vasculitic conditions (inflammatory bowel disease, primary sclerosing cholangitis, rheumatoid arthritis) rather than true ANCA-associated vasculitis 8

Diagnostic Approach

Essential Initial Workup

When LCV is suspected, perform a comprehensive evaluation to distinguish skin-limited disease from systemic vasculitis: 1, 2

• Skin biopsy from lesional tissue is essential for histopathologic confirmation showing leucocytoclasia, endothelial damage, perivascular fibrin deposition, and red cell extravasation 3, 1
• Complete blood count with differential to detect eosinophilia, leukopenia, or neutropenia 6, 2
• Urinalysis with microscopy specifically examining for dysmorphic RBCs and red cell casts indicating glomerulonephritis 8, 2
• Renal function assessment and proteinuria quantification 8, 2

Serologic Testing

• ANCA testing: Confirm antigen specificity using ELISA for MPO-ANCA and PR3-ANCA to distinguish true AAV from atypical non-vasculitic ANCA 8
• Complement levels: C3 and C4 to identify hypocomplementemic disease (worse prognosis in urticarial vasculitis) 3
• Cryoglobulins: Repeated testing may be necessary as levels fluctuate and false-negatives occur 3
• Hepatitis B and C serology 1, 2
• Antinuclear antibodies and rheumatoid factor 2
• Serum protein electrophoresis 2

Critical Pitfall

Do not rely on immunofluorescence ANCA patterns alone—always confirm with antigen-specific testing, as atypical c-ANCA has entirely different disease associations than true vasculitis. 8

Prognosis and Disease Severity

The prognosis of LCV depends critically on the underlying etiology and extent of organ involvement, not the cutaneous findings themselves. 2 A patient with cutaneous LCV and moderate nephritis as part of Henoch-Schönlein purpura has substantially better prognosis than identical findings in Wegener's granulomatosis 2. Drug-induced LCV generally has favorable prognosis with discontinuation of the culprit agent 1, 2.

Treatment Principles

Skin-Limited Disease

For isolated cutaneous LCV without systemic involvement 1:

• Rest with leg elevation (avoiding prolonged standing/walking)
• Low-dose corticosteroids
• Colchicine as alternative therapy
• Cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) 3

Drug-Induced LCV

Immediate discontinuation of the suspected offending medication is critical and often sufficient for resolution. 6, 1

Systemic Vasculitis-Associated LCV

When LCV represents systemic vasculitis with organ-threatening disease, initiate remission induction therapy with rituximab or cyclophosphamide plus high-dose glucocorticoids. 8 Plasma exchange should be considered in severe acute kidney injury or dialysis-requiring patients 8. Treatment intensity must match the underlying systemic disease severity, not the cutaneous manifestations 3, 1.

Specific Scenarios

• Mixed cryoglobulinemia: Treat underlying HCV infection; systemic corticosteroids for severe manifestations 3
• Atypical c-ANCA without true vasculitis: Treat the underlying condition (IBD, PSC, RA) rather than initiating vasculitis-directed immunosuppression 8
• Refractory cases with neuropathy: Intravenous immunoglobulins may be effective after failure of conventional systemic treatments 4