Purpura fulminans is an acute, often fatal, thrombotic disorder which manifests as blood spots, bruising and discolouration of the skin resulting from coagulation in small blood vessels within the skin and rapidly leads to skin necrosis and disseminated intravascular coagulation. Causes
Purpura fulminans is caused by defects in the protein C anticoagulant pathway. Identification of the cause of purpura fulminans often depends on the patients age and circumstances of presentation. Congenital protein C deficiency
Congenital (inherited) defects in protein C activity are autosomal dominant and may be partial or severe loss of function. Hundreds of natural mutations of the protein C gene (PROC) have been identified. Acquired protein C deficiency
Acquired protein C deficiency is caused by either depletion of available protein C in plasma or decreased protein C synthesis (caused by administration of vitamin K antagonists, severe liver failure or complications of prematurity). Severe acute sepsis
Purpura fulminans is a presenting feature of severe acute sepsis, such as Neisseria meningitidis, Streptococcus pneumoniae, Group A and B Streptococci, and less commonly with Haemophilus influenzae, Staphylococcus aureus, or Plasmodium falciparum (malaria) infections, particularly in individuals with asplenia. Combination of sepsis and partial congenital defect
In some cases, a combination of sepsis and a partial congenital defect in the protein C anticoagulant pathway initiates purpura fulminans. Unknown
In rare instances, purpura fulminans is an autoimmune manifestation against protein C or protein S after normally benign infections, such as chicken pox. Sometimes purpura fulminans has unknown cause.
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. Diagnosis
Early purpura fulminans lesions look similar to traumatic skin bleeds or purpuric rashes, such as immune thrombocytopenic purpura or thrombotic thrombocytopenic purpura; however, purpura fulminans will rapidly progress to necrosis whereas other purpuric rashes do not. In most cases, differential diagnoses may be distinguished from purpura fulminans by other clinical and laboratory findings.The initial appearance of purpura fulminans lesions is of well-demarcated erythaamatous lesions which progress rapidly to develop irregular central areas of blue-black haemorrhagic necrosis. Advancing areas of necrosis are often surrounded by a thin border of erythaema that fades into adjacent unaffected skin. Haemorrhage into the necrotic skin causes purpura fulminans lesions to become painful, dark and raised, sometimes with vesicle or blister (bulla) formation.The distribution of purpura fulminans lesions may be different according to the underlying pathogenesis. Purpura fulminans in severe sepsis typically develops in the distal extremities and progresses proximally or appears as a generalised or diffuse rash affecting the whole body surface. In cases of severe inheritable protein C deficiency, purpura fulminans with disseminated intravascular coagulation manifests within a few hours or days after birth.