Histological Aspects and Pathophysiology of Vasculitides in the Skin

Abstract

　The histopathological aspects of vasculitides in the skin are classified into leukocytoclastic vasculitis and polyarteritis nodosa (PAN) -type necrotizing arteritis. Leukocytoclastic vasculitis includes cutaneous leukocytoclastic vasculitis, IgA vasculitis, anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis, and drug-induced or cancer-associated vasculitis. Necrotizing arteritis includes cutaneous arteritis specific to the skin and cutaneous lesions of the systemic PAN. Immune complexes and ANCA are involved in the pathogenesis of leukocytoclastic vasculitis. ANCA cooperates with pro-inflammatory cytokines to activate neutrophils and injure small vessels. This ANCA-cytokine sequence has been regarded as a pivotal theory for understanding the pathogenesis of ANCA-associated vasculitis. Recent studies have revealed that neutrophil extracellular traps (NETs) are also implicated in the vascular endothelial cell injury. In addition, NETs are implicated in the mechanism of ANCA production. These findings suggest that the vicious cycle of NETs-ANCA is involved in the pathogenesis of ANCA-associated vasculitis. On the contrary, the pathogenesis of PAN-type necrotizing arteritis remains unknown.