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Purpura Fulminans

Acquired purpura fulminans

Purpura fulminans is a life-threatening, massive infarction of the skin, which occurs due to severe impairment of the coagulation system, and manifests as extensive purpuric skin lesions. This disorder is most commonly seen in patients who develop disseminated intravascular coagulation due to various causes.


Presentation

Clinical presentation of purpura fulminans is characterized by a sudden onset of initially erythematous macules and petechiae which progress within hours into massive ecchymoses with irregular and sharp borders, distributed on various parts of the body. In addition to skin lesions, symptoms that may appear include fever, hypotension, and often shock, if purpura fulminans is a complication of an acute infection. Neonatal purpura fulminans develops within the first 72 hours after birth, with a similar clinical presentation, and in all patients, because of massive infarction of the skin and organs, major organ dysfunction may occur, presenting with symptoms related to the target organ. In severe cases that accompany DIC, vascular thrombosis and pulmonary embolism may occur, and persistent bleeding from wounds and puncture sites is also observed. In severe cases, gangrene and necrosis of extremities may be observed, requiring amputation of fingers and even limbs.

Easy Bruising
  • There is evidence of bleeding under the skin, with easy bruising and the development of petechiae. In the acute form there may be bleeding from any of the body orifices, such as hematuria, nosebleed, vaginal bleeding, and bleeding gums.[medical-dictionary.thefreedictionary.com]
Fever
  • PF though common with rocky mountain spotted fever (RMSF) is rarely seen in association with Indian tick typhus, the usual cause of spotted fever in India.[ncbi.nlm.nih.gov]
  • The case is presented to sensitize the physicians to keep malaria as a differential in cases of fever with purpura fulminans.[ncbi.nlm.nih.gov]
  • A previously healthy man presented with fever for 2 days and rapidly progressive purpuric rash for 1 day.[ncbi.nlm.nih.gov]
  • We report on the case of a 42-year-old man without any co-morbidities who presented with fever and purpura fulminans and later developed metastatic endophthalmitis. He was treated with intravenous and intravitreal vancomycin.[ncbi.nlm.nih.gov]
  • We report a series of 5 case-patients who had Israeli spotted fever, of whom 2 had purpura fulminans and died.[ncbi.nlm.nih.gov]
Hypotension
  • He progressed into hypotension, disseminated intravascular coagulation and refractory shock despite resuscitation and early antibiotic commencement.[ncbi.nlm.nih.gov]
  • On day 2, after initial improvement, a recurrence of hypotension led to the diagnosis of acute meningococcal myocarditis, which evolved favourably within a week.[ncbi.nlm.nih.gov]
  • Patients present with high-grade fever, petechial or purpuric rash and rapid progression to purpura fulminans and hypotension [ 1 ].[clinmedjournals.org]
  • , fever, and disseminated intravascular coagulation, usually following an infectious illness. purpura fulminans A life-threatening condition of acute onset occurring in infants, which is characterised by cutaneous haemorrhage and necrosis, hypotension[medical-dictionary.thefreedictionary.com]
  • A 52-year-old woman with rheumatoid arthritis treated with prednisone and etanercept presented with fevers, headaches, and hypotension. The patient was admitted to the medical intensive care unit with presumed septic shock.[jamanetwork.com]
Vascular Disease
  • Cutaneous vascular diseases. In: James WD, Berger TG, Elston DM, editors. Andrew’s diseases of the skin: clinical dermatology. 10th ed. Philadelphia, Pa: Saunders; 2006. 2. Rintala E, Kauppila M.[westjem.com]
Muscular Atrophy
  • Further investigation revealed that he is heterozygous for a duplication of a thymine nucleoside in his SMN1 gene at position 91 in codon 31, which causes a frame shift mutation and is consistent with spinal muscular atrophy.[jmedicalcasereports.biomedcentral.com]
Purpura
  • […] this form of purpura fulminans.[emedicine.medscape.com]
  • 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[en.wikipedia.org]
  • It is often fatal. purpura gangrenosa fibrinolytic purpura edit English purpura fulminans A purpura characterized blood spots, bruising and discolouration of the skin resulting from coagulation in small blood vessels within the skin and rapidly leads[wikidata.org]
  • Treating purpura fulminans is achieved through elimination of the underlying cause, since purpura itself cannot be treated by any means.[symptoma.com]
  • Streptococcus pyogenes is an uncommon pathogen of purpura fulminans, and the pathogenesis of S. pyogenes-purpura fulminans remains unclear because of paucity of cases.[ncbi.nlm.nih.gov]
Petechiae
  • The patient's condition aggravated, with need for invasive mechanical ventilation and intermittent haemodialysis, and evolution from a petechiae-like rash to purpura and gangrene, culminating in bilateral lower limb amputation.[ncbi.nlm.nih.gov]
  • […] purpura [ per pu-rah ] a hemorrhagic disease characterized by extravasation of blood into the tissues, under the skin, and through the mucous membranes, and producing spontaneous bruises, ecchymoses, and petechiae (small hemorrhagic spots) on the skin[medical-dictionary.thefreedictionary.com]
  • Cutaneous examination revealed multiple erythematous, petechiae and ecchymotic patches over upper and lower extremities [Figure 1] and trunk.[ijpd.in]
  • Often there is pain followed by petechiae. Ecchymoses develop and evolve into painful indurated, well-demarcated purple papules with erythematous borders (as you can see in the image this lesions are coalescent).[unboundedmedicine.com]
  • The clinical presentation is the sudden and abrupt appearance of initially small petechiae, accompanied by cutaneous pain.[symptoma.com]
Hemorrhagic Bullae
  • Extensive purpuric, reticulated plaques with central necrosis and hemorrhagic bullae on the abdomen (A) and lower left leg extending onto the thigh (B).[mdedge.com]
  • Several days later there were geographic plaques of noninflammatory purpura and ecchymoses with hemorrhagic bullae. There was a sharp demarcation between involved and uninvolved skin (B).[mdedge.com]
  • bullae - black necrotic lesions and gangrene May involve heart, kidneys, and lungs Treatment Neonatal Purpura Fulminans Fresh Frozen Plasma (FFP) (see Fresh Frozen Plasma, [[Fresh Frozen Plasma]]): to replace protein C Low Molecular Weight Heparin/Coumadin[mdnxs.com]
  • She had extensive purpura with hemorrhagic bullae on her left leg. The patient was very ill-appearing with hypotension, tachycardia, tachypnea, and oliguria. There was no other bleeding.[westjem.com]
  • Later in the course, hemorrhagic bullae may form which contribute to the classic hard eschars characteristic of purpura fulminans.[ncbi.nlm.nih.gov]
Skin Discoloration
  • He then developed dusky skin discoloration and systemic flaccid bullae with desquamation. Biopsy was consistent with purpura fulminans and the patient eventually developed symmetric peripheral gangrene, requiring amputations of all four extremities.[ncbi.nlm.nih.gov]
Anger
  • ., Département de Reanimation Médicale et de Medicine Hyperbare, CHU Angers, Rue Larrey, 49933 Angers, France. E-mail: [email protected] Supported by a grant from the Société de Réanimation de Langue Française; S.[doi.org]
Altered Mental Status
  • An African American man in his fortiespresented with altered mental status and was noted to have evidence of disseminated intravascular coagulation according to his lab data.[ncbi.nlm.nih.gov]

Workup

After suspicion towards purpura fulminans arises, workup should involve a complete blood count (CBC), particularly focusing on the evaluation of platelet count. In addition to blood count, a coagulation panel including prothrombin time (PT) and activated partial thromboplastin time (aPTT) should be obtained, alongside values of fibrinogen and D-dimers. This is required in order to gain a full view of the coagulation cascade, and try to determine the cause [14]. 

Vital information can be obtained from patient history, which may reveal that the patient suffers from enzyme deficiencies, or had signs of infection prior to the development of purpura fulminans, which may indicate meningococcal infection. Physical examination should be performed, and together with laboratory findings, the cause of this condition will be identified. Idiopathic cases have been observed and are considered to have been caused by a latent viral or bacterial infection [15].

Normocytic Anemia
  • She had normocytic anemia, platelet clumps, and monocytosis as well as a deranged clotting profile.[ncbi.nlm.nih.gov]
Plasmodium Falciparum
  • Rickettsial infection Plasmodium falciparum malaria Non-infective DIC from any cause LITFL list snake bite as an important cause MAHA (microangiopathic haemolytic anaemia) TTP (thrombotic thrombocytopenic purpura) Vasopressor excess Warfarin-induced skin[derangedphysiology.com]
  • On further workup, the patient was diagnosed to have Plasmodium falciparum malaria on peripheral smear and antigen testing. The fever responded to intravenous artesunate and oral doxycycline.[bjid.org.br]
  • 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[en.wikipedia.org]
Eikenella
  • We herein describe the first case of septic shock due to a Gemella bergeri coinfection with Eikenella corrodens.[ncbi.nlm.nih.gov]
Fibrinoid Necrosis
  • A skin biopsy showed fibrinoid necrosis in the vessel wall with microthrombi and red-cell extravasation. A diagnosis of purpura fulminans was made.[ncbi.nlm.nih.gov]
Pleural Exudate
  • Autopsy examination revealed purulent pleural exudate, which grew toxic shock syndrome toxin-1-producing S. aureus.[ncbi.nlm.nih.gov]

Treatment

Treating purpura fulminans is achieved through elimination of the underlying cause, since purpura itself cannot be treated by any means. 

While the cause is being investigated, replacement therapy must be initiated, including:

  • Platelet transfusion, due to a potentially excessive rapid loss of thrombocytes.
  • Cryoprecipitate transfusion for replacement of fibrinogen and factor VIII
  • Fresh frozen plasma, which increases levels of natural anticoagulants and other clotting factors, including antithrombin, and proteins C and S
  • Heparin can be sometimes useful, but under specific indications, because it is not advised to give patient with purpura fulminans that have excessive bleeding. However, for patients with prothrombotic symptoms such as venous thrombosis, may benefit from heparin.

If the cause is suspected to be an infection, broad-spectrum intravenous antibiotic therapy is absolutely necessary, and should primarily target Neisseria meningitidis, for which ceftriaxone is the primary choice, usually as 2gr q12h for at least 7 days. Other cause-related therapies include administration of intravenous immunoglobulins, while amputations may also be necessary in the case of severe gangrene.

Prognosis

Prognosis of purpura fulminans solely depends on the underlying cause, but the conditions accompanied by it are usually extremely severe. Neonatal forms of purpura fulminans are 100% fatal without replacement of deficient clotting factors, while meningococcal sepsis can still be a fatal condition, even despite therapy. Improvements in supportive therapy have been made within the last few decades and have improved patient outcomes, including prevention of secondary infections, and transfusion of necessary blood products.

Etiology

Disorders of the coagulation system and purpuric lesions may occur due to various causes, but purpura fulminans implies a major coagulation disorder and has been observed in the following conditions:

  • Disseminated intravascular coagulation (DIC) - Abnormal and excessive generation of prothrombotic factors in the circulation can occur because of various reasons, including infections, surgical complications, malignant diseases, and enzyme deficiencies. Depending on the rate and severity of DIC, it may either cause venous thrombosis, pulmonary embolism, with low rates of bleeding (slowly evolving), or it may cause thrombocytopenia and depletion of clotting factors (rapidly evolving), leading to bleeding and multiorgan failure. Regardless of the type, purpura fulminans can arise as a manifestation of this disorder. 
  • Infection - Meningococcal infection [6] and the development of sepsis caused by Neisseria meningitidis is a life-threatening infection that is most commonly encountered in children [7], and is characterized by very high fever and constitutional symptoms. In 15-25% of the cases, abrupt development of disseminated purpuric lesions is observed. Despite all treatment strategies, this infection can still be fatal, due to its abrupt onset and severe damage to blood vessels and coagulation system [8].
  • Neonatal purpura fulminans (congenital deficiency of protein C or S) - Although it is very rare [9], neonates who are born with a deficiency of either protein C or S develop extensive purpuric lesions on their first day of life, and the condition may be life-threatening if not supplemented with appropriate enzymes [10]. 
  • Drug-induced  - Purpura fulminans can be caused by medications. Several drugs, including sulfonamides, penicillins, and phenytoin have been mentioned as potential causes of this disorder, through mechanisms still not fully understood [11].
  • Thrombocytopenia - Any disease which accelerates platelet consumption, or decreases platelet production can predispose patients to purpura fulminans [12], including idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), and malignant diseases which deplete platelets.
  • Clotting factor deficiencies - Purpura can often be a manifestation of clotting factor deficiencies, and purpura fulminans can be observed in severer cases. Examples include von Willebrand disease, hemophilia A and B, antithrombin III deficiency, and other clotting factor deficiencies.

Epidemiology

Purpura fulminans can be observed among patients of any age and gender, depending on the cause. This disorder is observed in neonates, young children, and adults of any age, because the conditions in which this disorder appears, may occur at any point in life.

Sex distribution
Age distribution

Pathophysiology

Purpuric lesions on the skin occur due to extravasation of blood from blood vessels into the surrounding environment. This "pooling" of blood under the skin can occur either due to uncontrolled activation of the coagulation cascade, and subsequent depletion of platelets leading to massive bleeding, or due to slow and excessive activation of prothrombotic factors, leading to thrombosis and vascular infarctions, which cause blood vessel rupture and release of blood from the vessels.

In the case of clotting factor deficiency, the coagulation pathway cannot perform its regular functions, leading to a decreased capacity of blood for coagulation, resulting in bleeding. In cases of malignancies, such as lymphomas, or after chemotherapy, thrombocytes may be depleted, thus leading to purpura fulminans through a similar mechanism.

Infections, particularly meningococcal sepsis, cause rapid and possibly lethal damage to the vascular system. Proinflammatory cytokines, including tumor necrosis factor alpha (TNF)–α, and interleukin 1 (IL-1), rapidly consume clotting factors, and the effects of bacterial endotoxins lead to the development of microemboli in the circulation and widespread disruption of the endothelial barrier [13]. 

It is important to mention that purpura fulminans can occur only if the coagulation cascade is severely impaired, and should not be confused with the development of purpura and purpuric lesions that are commonly seen in some other disorders, such as Henoch-Schonlein purpura, autoimmune vasculitis, and some other diseases.

Prevention

In order to prevent the development of purpura fulminans, early signs of this disorder must be identified, so that complications may be prevented. However, it is difficult to establish the diagnosis early because of the sudden onset of the purpuric rash. Nevertheless, in all patients who have predisposing conditions, such as clotting factor deficiencies, or disease-related thrombocytopenias, regular checkups should be performed in order to evaluate the status of the coagulation system. Proper management of existing conditions, such as ITP and TTP, may reduce the risk of this potentially fatal disorder.

Summary

Purpura fulminans arises due to severe damage of the coagulation system [1], and is one of the clinical manifestations of disseminated intravascular coagulation (DIC) [2], which develops as a result of various conditions, such as infections, autoimmune diseases and congenital enzyme deficiencies affecting the coagulation cascade. The pathogenesis comprises severe imbalance of coagulation factors and platelets, leading to extravasation of blood from the vessels, and cutaneous hemorrhage. In the case of massive vascular thrombosis, gangrenous tissue necrosis develops [3] and extensive damage to the skin and the surrounding tissues may occur.  Depending on the cause, purpura fulminans may be observed in patients of all ages, including neonates, children, and adults [4]. The clinical presentation is the sudden and abrupt appearance of initially small petechiae, accompanied by cutaneous pain. As the disease progresses, extensive and massive ecchymoses (purpura) with sharp and irregular borders are exhibited, either deep purple or blue in color. Symptoms such as fever and hypotension may be observed, as well as shock and gangrenous necrosis of extremities. Laboratory tests should include a full blood count (with an emphasis on platelet count), biochemical parameters including fibrinogen, D-dimer, as well as PT and PTT, to determine the status of the coagulation system. Patient history, as well as physical examination, may point to the underlying cause, and immediate treatment is absolutely necessary in order to achieve a good prognosis, which depends on the cause. Treatment also includes replacement therapy of necessary blood products, including platelets, coagulation factors and activated protein [5], which may be life-saving. 

Patient Information

Purpura fulminans is a form of skin rash which occurs in diseases which profoundly damage the coagulation system, and if this condition is observed on physical examination, it should be treated as a medical emergency. Purpura fulminans manifests as a deep purple to blue rash that develops on numerous locations on the body within hours and is usually accompanied by pain. This rash occurs because of the imbalance between the factors which are responsible for normal blood coagulation, resulting in leakage of blood from blood vessels. This blood concentrates under the skin, and bleeding into the external environment may occur.

This disorder may be seen in neonates and children who are suffering from deficiencies of some of the factors in the coagulation system, in patients suffering from meningococcal infection, or in those that are suffering from conditions that impair the number of thrombocytes or platelets. Diseases that cause this condition may be fatal, which is why a prompt diagnosis is necessary. Through patient history, physical examination, as well as certain laboratory tests, suspicion towards this disorder arises and immediate treatment must be initiated. Treatment should be directed at the underlying cause, but it also aims at replenishing blood products that are depleted, such as platelets and coagulation factors. Because of the rapid and abrupt course of this disease, prevention is not really possible, but patients with disorders known to cause purpura fulminans should manage their illnesses adequately, in order to prevent potentially life-threatening consequences. 

References

Article

  1. D'Cruz D, Cervera R, Olcay Aydintug A, Ahmed T, Font J, Hughes GR. Systemic lupus erythematosus evolving into systemic vasculitis: a report of five cases. Br J Rheumatol. 1993;Feb 32(2):154-7.
  2. Kondaveeti S, Hibberd ML, Booy R, Nadel S, Levin M. Effect of the Factor V Leiden mutation on the severity of meningococcal disease. Pediatr Infect Dis J. 1999; Oct 18(10):893-6.
  3. Wheeler JS, Anderson BJ, De Chalain TM. Surgical interventions in children with meningococcal purpura fulminans--a review of 117 procedures in 21 children. J Pediatr Surg 2003; 38:597.
  4. Andreasen TJ, Green SD, Childers BJ. Massive infectious soft-tissue injury: diagnosis and management of necrotizing fasciitis and purpura fulminans. Plast Reconstr Surg. 2001; Apr 1:107(4):1025-35.
  5. de Kleijn ED, de Groot R, Hack CE, et al. Activation of protein C following infusion of protein C concentrate in children with severe meningococcal sepsis and purpura fulminans: a randomized, double-blinded, placebo-controlled, dose-finding study. Crit Care Med 2003; 31:1839.
  6. Darmstadt GL. Acute infectious purpura fulminans: pathogenesis and medical management. Pediatr Dermatol 1998; 15:169.
  7. Wong, VK, Hitchcock, W, Mason, WH. Meningococcal infections in children: a review of 100 cases, Ped Infect Dis J 1989; 8:224.
  8. Algren JT, Lal S, Cutliff SA, Richman BJ. Predictors of outcome in acute meningococcal infection in children. Crit Care Med 1993; 21:447.
  9. Sen K, Roy A. Management of neonatal purpura fulminans with severe protein C deficiency. Indian Pediatr. 2006;Jun 43(6):542-5.
  10. Gladson CL, Groncy P, Griffin JH. Coumarin necrosis, neonatal purpura fulminans, and protein C deficiency.Arch Dermatol. 1987; Dec 123(12):1701a-1706a.
  11. ten Holder SM, Joy MS, Falk RJ. Cutaneous and systemic manifestations of drug-induced vasculitis. Ann Pharmacother 2002; 36:130.
  12. Leung AK, Chan KW. Evaluating the child with purpura. Am Fam Physician 2001; 64:419.
  13. Madden RM, Gill JC, Marlar RA. Protein C and protein S levels in two patients with acquired purpura fulminans. Br J Haematol. 1990;May 75(1):112-7.
  14. Khair K, Liesner R. Bruising and bleeding in infants and children--a practical approach. Br J Haematol 2006; 133:221.
  15. Brown DL, Greenhalgh DG, Warden GD. Purpura fulminans: a disease best managed in a burn center. J Burn Care Rehabil. 1998; Mar-Apr 19(2):119-23.

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Last updated: 2019-07-11 21:30