Pathophysiology
Regardless of the underlying cause of purpura fulminans, 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 purpura fulminans, 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.
Purpura fulminans may also lead to severe large vessel venous thrombosis if untreated in its early stages.Purpura fulminans secondary to severe infection is self-limiting. In cases of homozygous protein C deficiency, episodes of purpura fulminans and other thrombotic events are recurrent. Moreover, infant survival due to maintenance replacement therapy is often associated with intellectual disability or visual impairment. For post-infection purpura fulminans, new lesions will occur while neutralising autoantibodies are present (1–2 weeks after presentation).A multi-disciplinary care team is usually required for rehabilitation after purpura fulminans. Epidemiology
Purpura fulminans is rare and most commonly occurs in babies and small children but can also be a rare manifestation in adults when it is associated with severe infections. For example, Meningococcal septicaemia is complicated by purpura fulminans in 10–20% of cases among children. Purpura fulminans associated with congenital (inherited) protein C deficiency occurs in 1:500,000–1,000,000 live births. Research
Due to the rarity of purpura fulminans and its occurrence in vulnerable patient groups like children research on the condition is very limited and evidence based knowledge is scarce. History
Purpura fulminans was first described by Guelliot in 1884. References
External links
Medscape: Purpura Fulminans