What is leukocytoclastic vasculitis?

What is Leukocytoclastic Vasculitis

Leukocytoclastic vasculitis (LCV) is a histopathologic pattern of small-vessel vasculitis characterized by neutrophilic inflammation with fibrinoid necrosis and nuclear fragmentation ("leukocytoclasia") affecting dermal capillaries and post-capillary venules, typically presenting as palpable purpura. 1

Pathophysiology

• LCV results from immune-complex-mediated deposition on endothelial cells of small blood vessels in the skin 2
• The inflammatory infiltrate consists of neutrophils with fibrinoid necrosis and disintegration of nuclei into fragments, which defines the term "leukocytoclasia" 1
• This represents a histopathologic description rather than a specific disease entity, and can be found in various types of vasculitis affecting skin and internal organs 1

Clinical Presentation

• Palpable purpura is the hallmark and most specific clinical finding, typically appearing on dependent areas like the lower extremities 3, 1
• Lesions are often painful or itchy, and may be accompanied by erythema 4
• The rash can progress to ulceration in severe cases 4
• Skin involvement may be isolated or represent manifestation of systemic vasculitis 1

Etiology and Associated Conditions

Common triggers include:

• Medications (most common): Penicillins, cephalosporins, sulfonamides, phenytoin, allopurinol, daptomycin, amiodarone, and warfarin 2, 5, 1, 6
• Infections: Group A Streptococcus, hepatitis B and C viruses 5, 1
• Systemic vasculitides: ANCA-associated vasculitis, IgA vasculitis (Henoch-Schönlein purpura), cryoglobulinemic vasculitis, hypocomplementemic urticarial vasculitis 7, 1
• Autoimmune disorders: Connective tissue diseases, systemic lupus erythematosus 1
• Malignancies 1
• Idiopathic (when no cause identified) 5

Diagnostic Approach

Diagnosis requires skin biopsy for histopathologic confirmation - this is the only definitive way to diagnose LCV 1, 4

Essential workup to determine extent and etiology:

• Complete blood count with differential (evaluate for leukocytosis, thrombocytosis) 5
• Renal function tests and urinalysis to assess for systemic involvement 1
• Inflammatory markers (ESR, CRP) - typically elevated 5
• ANCA testing (MPO and PR3) to evaluate for ANCA-associated vasculitis 1
• Complement levels (C3, C4) - low in certain systemic vasculitides 7, 1
• Hepatitis B and C serology 1
• Antinuclear antibodies (ANA) 1
• IgA staining on biopsy specimens to evaluate for IgA vasculitis 1

Histopathologic features:

• Neutrophilic infiltration of vessel walls 1
• Fibrinoid necrosis 8
• Nuclear fragmentation (leukocytoclasia) 1
• Red blood cell extravasation 7
• Endothelial cell damage 7

Critical pitfall: Shave biopsies may be inadequate - formal incisional biopsies provide better tissue for definitive diagnosis, especially when excluding malignancy 4

Treatment Strategy

For skin-limited disease:

• Rest (avoiding prolonged standing or walking) 1
• Low-dose corticosteroids 1
• Colchicine as alternative therapy 1
• Discontinue culprit medication if drug-induced - this is usually resolutive with favorable prognosis 1

For systemic vasculitis with LCV:

• Higher-dose corticosteroids are required 1
• Immunosuppressive agents according to severity of organ involvement and underlying disease 1
• Treatment should target the specific underlying systemic vasculitis (e.g., rituximab or cyclophosphamide for ANCA-associated vasculitis) 8

Prognosis

• Skin-limited LCV is typically self-limiting with good overall prognosis 4
• Drug-induced LCV resolves after discontinuation of the offending agent 1
• A minority of patients follow a protracted course requiring systemic treatment 4
• When associated with systemic vasculitis, prognosis depends on extent of organ involvement and underlying disease 1