Purpura Fulminans - Causes, Types, and Pathophysiology

Introduction

Purpura fulminant is a rare emergency dermatological situation characterized by acute purpuric rash, which causes coagulation of the microvasculature; this can lead to purpuric lesions and skin necrosis. It progresses rapidly and is associated with fever, hemorrhage in multiple sites, hypotension, disseminated intravascular coagulation (a condition that causes blood clots throughout the blood vessels), and circulatory collapse. This condition can occur in newborns, children, and adults. Management of this condition includes supportive care, targeted treatments, and the management of secondary complications. In severe cases, it can result in amputation.

What Is Purpura Fulminans?

Purpura fulminans is an acute purpuric rash in which there is the coagulation of the microvasculature, and it leads to purpuric lesions and skin necrosis. This condition can occur in newborns, children, and adults.

What Are the Causes of Purpura Fulminans?

The causes are:

1. Neonatal purpura fulminans occur due to inherited deficiency in protein S, protein C, and antithrombin III.

2. Idiopathic purpura fulminans occur due to decreased levels of protein S in the plasma concentration, which occurs after seven to ten days of infectious, autoimmune disorders.

3. Acute infectious purpura fulminans occur due to acquired deficiency in proteins C, protein S and antithrombin III, which is triggered by endotoxin (a component that is present on the outer membrane of bacteria).

What Are the Types of Purpura Fulminans?

There are three types of purpura fulminans, which are:

• Neonatal Purpura Fulminans: It is a rare condition that is due to acquired or congenital deficiencies of C, S protein, and antithrombin III. This condition needs quick diagnosis and management by replacement therapy using protein C concentrate and fresh frozen plasma and maintaining using warfarin or low molecular weight heparin to avoid coagulation (blood clot).

• Idiopathic Purpura Fulminans: It is a severe prothrombotic coagulation disorder that occurs after infectious, autoimmune disorders such as chickenpox or human herpesvirus 6 (HHV-6) infection. This causes a decreased level of protein S in the plasma concentration.

• Acute Infectious Purpura Fulminans: It is characterized by acute onset of progressive hemorrhage and disseminated intravascular necrosis. This condition manifests as a finding in most severe septic patients, such as necrotizing fasciitis (a type of bacterial infection that destroys the skin and can lead to severe complications if not treated), meningococcemia (a bacterial infection that is caused by Neisseria meningitides).

What Is The Pathophysiology Of Purpura Fulminans?

It is an acute condition characterized by progressive rapid hemorrhage and necrosis. The pathophysiology of Purpura fulminans includes:

• The neonatal purpura fulminans are associated with hereditary deficiencies of C and S protein and antithrombin III. These proteins are pro-fibrinolytic (prevents blood clots), and protein C is a major inhibitor of the blood clot system and inhibits factors Va and VIIIa (blood clotting factors); therefore, protein C down-regulates thrombin synthesis. In case of these deficiencies, it can lead to blood clots. In neonates, there is massive venous and arterial thrombosis, including other organs, within a week of birth.

• In the case of idiopathic purpura fulminans, which causes the development of anti-protein S antibodies, these antibodies bind to the protein S causing its destruction, and this leads to hypo-activation of the protein C pathway. Therefore all these cause blood clots in the system.

• Acute infectious purpura fulminans occur due to an acquired deficiency of protein C, which is involved in coagulation. The bacterial endotoxins cause disruption in the protein S, protein C, and antithrombin III, which causes blood clots in dermal vessels throughout the body.

What Are The Clinical Features Of Purpura Fulminans?

The clinical features of purpura fulminans are:

• In the early stages, petechial rashes, which are small pinpoint rashes that are less than two millimeters, are seen.

• Later stages can show hemorrhagic bullae, which are larger and filled with blood.

• An erythematous area that contains centrally blue-black hemorrhagic necrosis areas.

• Formation of vesicles and bullae.

• Affected skin is painful and indurated (hardness on the skin).

• Loss of sensation in the affected skin.

• Secondary infections, such as the formation of gangrene (tissue death due to loss of blood supply), can occur.

• Necrosis of the skin can extend deeper into the tissues.

What Is The Diagnosis Of Purpura Fulminans?

The diagnosis should involve a thorough examination of the skin, and in the case of neonates, petechial rash or bruising should trigger the consideration of purpura fulminans. The diagnosis should involve the following:

• Testing the levels of protein C, protein S and antithrombin III in the plasma.

• In case of infections, culture and lab testing should be done.

• White blood cell (WBC) count, and a sodium level is done to rule out necrotizing fasciitis.

• Platelet count, coagulation factors, d-dimer assay, and fibrinogen level are checked to evaluate thrombocytopenia.

What Are The Complications Of Purpura Fulminans?

The complications of purpura fulminans include:

• Bleeding from multiple sites.

• Severe septic shock.

• Hematuria (blood in urine).

• Oliguria (urine output less than 400 milliliters per day).

• Respiratory distress.

• Multiple end organ damage.

• Necrosis.

What Is The Treatment Of Purpura Fulminans?

The treatment is mainly supportive and involves adequate hydration. The treatment includes:

• Anticoagulation therapy to prevent the formation of necrosis.

• Transfusion of blood, coagulation factors, and platelets.

• Early surgical removal of necrotized tissues.

• Protein C and S levels are assessed, and lower levels are managed by transfusion of fresh frozen plasma.

• Anticoagulant factors such as heparin and warfarin are also used in a transfusion.

• In the case of idiopathic purpura fulminans, along with transfusion of blood. Coagulation factors and platelets, and immunomodulation with corticosteroids are done.

• In case of acute infections, broad-spectrum antibiotics should be given.

• Activated protein C is used to reduce inflammation and restore the balance of coagulation.

What Is The Differential Diagnosis Of Purpura Fulminans?

The differential diagnosis of purpura fulminans includes:

• Necrotizing fasciitis (a type of bacterial infection that destroys the skin and can lead to severe complications if not treated).

• Meningococcemia (a bacterial infection that is caused by Neisseria meningitidis).

• Toxic shock syndrome (a severe life-threatening condition caused due to bacteria).

• Vasculitis (blood vessel inflammation).

• Coumadin necrosis (unpredictable reaction to anti-coagulation therapy).

• Thrombotic thrombocytopenic purpura (a type of blood disorder, which results in blood clots throughout the body).

• Thrombophlebitis (blood clots in the vein causing inflammation).

• Calciphylaxis (painful ulcers and blood clots in the vessels which occur due to accumulation of calcium).

Conclusion

Purpura fulminans is a rare disorder that requires emergency treatment and involves mainly supportive care and adequate hydration. Management should include transfusion of blood, coagulation factors, platelets, and debridement of necrotized tissues.