Regardless of the underlying cause of<unk> , the mechanism of disease is similar with deficiency in protein C concentration or decrease in protein C activity which promotes blood clotting (thrombosis). In cases of severe sepsis, there is widespread activation of the acute systemic inflammatory response, including activation of the coagulation and complement pathways, as well as endothelial dysfunction. Activated protein C helps regulate the systemic inflammatory response. During sepsis, signalling by the inflammatory cytokines, interleukin-1 and tumour necrosis factor, mediate altered protein transcription in the systemic inflammatory response, resulting in decreased synthesis of the regulatory proteins antithrombin, protein C and protein S, with increased synthesis of prothrombotic proteins Factor VIII, von Willebrand factor, and fibrinogen. Activated protein C binds to endothelial protein C receptor and subsequently cleaves the endothelial cell protease activated receptor-1, not only altering coagulation profiles but down-regulating pro-inflammatory and pro-apoptotic mediators, up-regulation of anti-inflammatory and anti-apoptotic pathways and stabilization of the endothelial cell barrier functions. Systemic coagulation activation may lead to depletion of circulating coagulation factors and platelets, which subsequently lead to bleeding. In early<unk> , lesion progression correlates with the histological appearance of blockage of small skin blood vessels with blood clots causing capillary dilation and congestion with red blood cells. In later stage lesions, there is irreversible endothelial ischaemic injury with extravasation of blood cells into the dermis and gangrenous necrosis, sometimes with secondary infection. The depletion of anticoagulant and anti-inflammatory proteins, in particular, protein C and its co-factor, protein S, may also promote thrombus formation, inhibit fibrinolysis and lead to further activation of the inflammatory pathways.
Purpura fulminans
Acne fulminans
Pyoderma gangrenosum
Leukemia cutis
Visceral larva migrans
Dandruff
Erythema multiforme minor
Ecthyma gangrenosum