Neutrophil Extracellular Traps are Present in Immune-complex-mediated Cutaneous Small Vessel Vasculitis and Correlate with the Production of Reactive Oxygen Species and the Severity of Vessel Damage

Formation of neutrophil extracellular traps has been implicated in autoimmunity. However, the presence and clinical relevance of neutrophil extracellular traps in immune-complex-mediated cutaneous small and medium vessel vasculitides has not been investigated. This study retrospectively analysed 72 patients with histology-proven hypersensitivity vasculitis (n = 21), IgA vasculitis (n = 22), urticarial vasculitis (n = 22), erythema elevatum diutinum (n = 3) and polyarteritis nodosa (n = 4). Neutrophil extracellular traps were detected in hypersensitivity vasculitis, IgA vasculitis, urticarial vasculitis and erythema elevatum diutinum, but not in polyarteritis nodosa lesions. Neutrophil extracellular traps were found around inflamed vessels, and their formation was highest early after the onset of vasculitis and decreased progressively thereafter. Neutrophil extracellular traps were strongly correlated with the histological severity of vasculitis and the production of reactive oxygen species. Both hypersensitivity vasculitis and IgA vasculitis showed significantly more neutrophil extracellular traps than did urticarial vasculitis, independent of the histological severity and duration of vasculitis. These results provide evidence on the implication of neutrophil extracellular traps in the early phases of immune-complex-mediated small vessel vasculitis.