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Necrotizing Fasciitis and Purpura Fulminans
Updated: Mar 13, 2009
Introduction
Necrotizing fasciitis and purpura fulminans are destructive infections that involve both skin and soft tissues. These life-threatening infections have different presentations and pathophysiology. This article outlines the clinical presentations of these infections, reviews the bacteriology of each infection, and notes the treatment strategies for managing these massive soft-tissue infections.
Necrotizing Fasciitis
Necrotizing fasciitis is a potentially fatal infection involving rapidly progressive, widespread necrosis of the superficial fascia. Necrotizing fasciitis was first described by a Confederate Army surgeon, Joseph Jones, during the US Civil War.1 In 1883, Fournier documented necrotizing fasciitis in the perineal and genital region.2 Meleney later reported 20 patients he encountered in China in whom necrotizing fasciitis was caused by hemolytic streptococcus.3 Wilson used the term necrotizing fasciitis without assigning a specific pathologic bacterium that caused the disease.4
Smith et al first classified soft tissue infections as either local or spreading.5 Lewis later further classified soft tissue infections into either necrotizing or non-necrotizing.6 He further subdivides these infections into either focal or diffuse.
Pathophysiology
Necrotizing fasciitis is characterized by widespread necrosis of the subcutaneous tissue and the fascia. It was once considered an uncommon clinical entity. In the 1990s, the media popularized the idea that this infection was caused by "flesh-eating bacteria." Although the pathogenesis of necrotizing fasciitis is still open to speculation, the rapid and destructive clinical course of necrotizing fasciitis is thought to be due to multibacterial symbiosis and synergy.1 Historically, group A β-hemolytic streptococcus (GABS) has been identified as a major cause of this infection. This monomicrobial infection is usually associated with an underlying cause, such as diabetes, atherosclerotic vascular disease, or venous insufficiency with edema. GABS usually affects the extremities; approximately two thirds of the GABS infections are located in the lower extremities.7During the last 2 decades, scientists have found that the pathogenesis of necrotizing fasciitis was usually polymicrobial rather than monomicrobial. In 1982, Rouse et al reported 28 cases of necrotizing fasciitis.8 They pointed out that all but 4 of these infections were polymicrobial. The overall mortality rate was 73% (20 of 27 patients). They indicated that prompt recognition and treatment of necrotizing fasciitis was essential. Of 12 patients whose treatment was delayed for more than 12 hours, 11 patients died.
In 1995, McHenry et al reported findings very similar to those of Rouse et al.9 McHenry et al reported on the determinants of mortality for recognizing soft tissue infections. Necrotizing soft tissue infections were determined to be polymicrobial in 45 of the patients studied (69%). The average time from admission to operation was 90 hours in nonsurvivors; in survivors, this average time was 25 hours. Early debridement of the infection was obviously associated with a significant decrease in mortality. In a series of 163 consecutive patients reported by Andreasen et al, 71% of the patients with necrotizing fasciitis had a polymicrobial infection.10
In many cases of necrotizing fasciitis, an identifiable antecedent trauma is evident. Surprisingly, the initial lesion is often trivial, such as an insect bite, minor abrasion, boil, or injection site. Olafsson et al indicate that the hallmark symptom of necrotizing fasciitis is intense pain and tenderness over the involved skin and underlying muscle.11 The intensity of the pain often causes suspicion of a torn or ruptured muscle. This severe pain is frequently present before the patient develops fever, malaise, and myalgias.
Other indicative findings include edema extending beyond the area of erythema, skin vesicles, and crepitus. McHenry et al and others have noted that the subcutaneous tissue demonstrates a wooden, hardened feel in cases of necrotizing fasciitis. The fascial planes and muscle groups cannot be detected by palpation. Laboratory evaluation should include complete blood counts, blood chemistries, arterial blood gases, and tissue and blood cultures. Radiographic studies must be undertaken to detect air in soft tissues. Fugitt el al point out that, when the patient is seriously ill, necrotizing fasciitis is a surgical emergency with high mortality; therefore, imaging studies should not delay surgical intervention.12
Diagnostic Studies
The authors have reported appropriate radiological studies that allow early diagnosis of necrotizing infections.13 In addition, these studies permit visualization of the location of the rapidly spreading infection. Plain radiographs, often obtained to detect soft tissue gas that is sometimes present in polymicrobial or clostridial necrotizing fasciitis, are of no value in the diagnosis of necrotizing infections.14 Indeed, nondiagnostic plain radiographs may even hinder the diagnosis of necrotizing infection.13 In their study of 29 patients with necrotizing soft tissue infections, Lille et al reported that nondiagnostic radiographs correlate with a delay in operative intervention and consequent increased morbidity and mortality.15Most fluid collections in the tissue, especially in the musculoskeletal system, can be localized and aspirated under ultrasonographic guidance. However, the appearance of ultrasounds cannot determine whether fluid is infected; laboratory analysis is required. Craig notes that the combined use of magnetic resonance imaging (MRI) and aspiration under ultrasonographic guidance is very useful in complicated infections (eg, septic arthritis and osteomyelitis).16 Its role in the diagnosis of necrotizing fasciitis should be considered.16 Early muscle necrosis may be apparent.
Parenti et al retrospectively reviewed the ultrasonographic appearances of 32 pathologically proven cases of necrotizing fasciitis.17 Ultrasonography revealed changes in the subcutaneous fat (28 of 32 patients), investing fascia (18 of 32 patients), and muscle (15 of 32 patients), which correlated well with histological findings. However, in some cases, ultrasonography missed histologically apparent inflammation in the subcutaneous tissues (3 of 32 patients) or muscle (8 of 32 patients).17 Ultrasound-guided aspiration of perifascial fluid can help isolate the pathogen.18 Successful treatment requires early recognition, aggressive antibiotic therapy, and adequate surgical debridement.
While no published, well-controlled, clinical trial has compared the efficacy of various diagnostic imaging modalities in the diagnosis of necrotizing infections, MRI is the preferred technique to detect soft tissue infection because of its unsurpassed soft tissue contrast and sensitivity in detecting soft tissue fluid, its spatial resolution, and its multiplanar capabilities.19,20 In a study of 13 patients with thoracic and abdominal wall infections, Sharif et al reported that computed tomography (CT) and MRI were superior to sonography, scintigraphy, and plain radiography in providing useful information about the nature and extent of infections.21 Furthermore, they suggested that while CT compares favorably with MRI in accurate diagnosis of soft tissue infection, multiplanar MRI images can be obtained without ionizing radiation and the use of intravenous contrast agents.
The usefulness of MRI in the diagnosis of necrotizing fasciitis has been supported in a study by Rahmouni et al, who were able to differentiate in 36 patients between nonnecrotizing cellulitis that would respond to medical treatment and severe necrotizing infections that required rapid life-saving surgery.22 In the authors’ reported case of necrotizing fasciitis, MRI provided dramatic evidence of an inflammatory process infiltrating the fascial planes.13
Uman et al recommended percutaneous needle aspiration followed by prompt Gram staining and culture for a rapid bacteriologic diagnosis in soft tissue infections.23 A needle aspirate should be taken on the advancing edge of the infection, where GABS is plentiful.24 A Gram stain of the tissue aspirate can be used to differentiate erysipelas from necrotizing infections. Cocci are plentiful in the aspirate from necrotizing infection, while they are rarely identified in the aspirate in patients with erysipelas.24 The results of the microbiological aspirate should be complemented by blood cultures.
The finger test and rapid frozen section biopsy examinations should also be used in the diagnosis of patients who present with necrotizing fasciitis.25,26 The area of suspected involvement is first infiltrated with local anesthesia. A 2-cm incision is made in the skin down to the deep fascia. Lack of bleeding is a sign of necrotizing fasciitis. On some occasions, a dishwater-colored fluid is noticed seeping from the wound. A gentle, probing maneuver with the index finger covered by a sterile powder-free surgical double glove is then performed at the level of the deep fascia. If the tissues dissect with minimal resistance, the finger test is positive.
Tissue biopsies are then sent for frozen section analysis. The characteristic histologic findings are obliterative vasculitis of the subcutaneous vessels, acute inflammation, and subcutaneous tissue necrosis. If either the finger test or rapid frozen section analysis is positive, or if the patient has progressive clinical findings consistent with necrotizing fascia, immediate operative treatment must be initiated.
Treatment
Because necrotizing fasciitis is a surgical emergency, the patient must be admitted immediately into a hospital setting, like a regional burn center or trauma center in which the surgical staff is skilled in performing extensive debridement and reconstructive surgery. Such regional burn centers are ideal for the care of these patients because they also have hyperbaric oxygen facilities. Whenever possible, aggressive resuscitation must be initiated immediately to maintain hemod ynamic stability.
A polymicrobial synergistic infection has been recently found to be the most common cause of necrotizing fasciitis.9 Polymicrobial infections are often associated with previous surgical procedures, pressure ulcers, penetrating trauma, perianal abscesses, and intravenous drug use. In the study by Andreasen et al, 71% of their patients had polymicrobial infections.10
Antibiotic therapy is a key consideration for these polymicrobial infections. The surgeon may use a combination of penicillin G and an aminoglycoside (if renal function permits), as well as clindamycin (to cover streptococci, staphylococci, gram-negative bacilli, and anaerobes).
Clindamycin remains the antibiotic of choice for necrotizing infections.14 First, unlike penicillin, the efficacy of clindamycin is not affected by the inoculum size or stage of bacterial growth.27,28 Second, clindamycin is a potent suppressor of bacterial toxin synthesis.29,30 Third, subinhibitory concentrations of clindamycin facilitate the phagocytosis of GABS.13 Fourth, clindamycin reduces the synthesis of penicillin-binding protein, which, in addition to being a target for penicillin, is also an enzyme involved in cell wall synthesis and degradation.28 Fifth, clindamycin has a longer postantibiotic effect than β-lactins such as penicillin.30 Finally, Stevens, Bryant, and Hackett demonstrated that clindamycin causes suppression of lipopolysaccharide-induced mononuclear synthesis of tumor necrosis factor-α (TNF-α).31 Consequently, the success of clindamycin also may be related to its ability to modulate the immuneresponse.32
Initial antimicrobial therapy should be broad-based to cover aerobic gram-positive and gram-negative organisms and anaerobes. The authors recommend penicillin G, 24 million units per day IV, divided into doses administered every 4-6 hours; clindamycin, 900 mg IV every 8 hours; and gentamicin, 1 mg/kg IV every 8 hours. A more specifically targeted antibiotic regimen may be begun after the results of initial gram-stained smear, culture, and sensitivities are available. Although some necrotizing infections may still be susceptible to penicillin, clindamycin is the treatment of choice for necrotizing infections because it is a potent suppressor of bacterial toxin synthesis and because the inoculum size or stage of bacterial growth does not affect its efficacy. If staphylococci or gram-negative rods are involved, vancomycin and other antibiotics to treat gram-negative orgamisms other than aminoglycosides may be required.
Surgery is the primary treatment for necrotizing fasciitis. During surgery, all operating room personnel should be wearing a powder-free double-glove hole indication system that protects the staff as well as the patient from exposure to deadly blood-borne viral infections.33 The US Food and Drug Administration (FDA) only requires that glove manufacturers must produce sterile surgical gloves whose leakage rate does not exceed 2.5%. This high frequency of glove holes is an invitation to the spread of deadly blood-borne infections between operating room personnel and the patient. The double-glove system is also powder-free, thereby reducing the potentially serious complications of cornstarch. Cornstarch in wounds has been well documented to potentiate the development of infection. In addition, the cornstarch on latex gloves can carry the latex antigen and precipitate anaphylactic reactions in individuals who are allergic to latex.34
Surgeons must be consulted early in the care of these patients. Early surgical debridement of necrotic tissue is a life-saving treatment. Meleney was the first to recognize the importance of early surgical fasciotomy and debridement.3 The importance of early diagnosis is underscored by many studies that document the significant benefit to prognosis and outcome associated with early and aggressive debridement of necrotizing soft tissue infections.15,35,36,37 In addition, early surgical treatment may minimize tissue loss, eliminating the need for amputation of the infected extremity.38,39
The authors recommend wide, extensive debridement of all tissues that can be easily elevated off of the fascia with gentle pressure. Wide debridement of all necrotic and poorly perfused tissues is associated with more rapid clinical improvement. Controversy exists regarding how much tissue should be initially excised because the skin may often appear normal. Andreasen et al examined the normal-appearing tissues microscopically and reported that the tissues had extensive early vascular thrombosis as well as vasculitis.10 Their findings indicate that these tissues, though they have a normal appearance, have a high potential for full-thickness loss.
After the initial debridement, the wound must be carefully examined. Hemodynamic instability is usually present after surgery, and it may cause progressive skin necrosis. After debridement, the patient may return as often as necessary for further surgical debridement. The anesthesiologist is an important member of the operative team because continued resuscitative efforts are undertaken during the operative procedure.
Following each debridement of the necrotic tissue, daily antibiotic dressings are recommended.40 Silver sulfadiazine (Silvadene) remains the most popular antimicrobial cream. This agent has broad-spectrum antibacterial activity and is associated with relatively few complications in these wounds. The current formulation of silver sulfadiazine contains a lipid-soluble carrier, polypropylene glycol, which has certain disadvantages, including pseudoeschar formation. When this antibacterial agent is formulated with poloxamer 188, the silver sulfadiazine can be washed easily from the wound because of its water solubility, making dressing changes considerably more comfortable. If the patient is allergic to sulfa, alternative agents include Polysporin, Bacitracin, and Bactroban. While these agents are relatively inexpensive, they may induce allergies.Mafenide is an alternate agent that penetrates eschar more effectively than silver sulfadiazine. Consequently, it is frequently used on infected wounds that do not respond to silver sulfadiazine. Use mafenide with caution because it can induce metabolic acidosis.
Acticoat has the beneficial antimicrobial properties of the silver ion by coating the dressing material with a thin, soluble silver film. This dressing appears to maintain antibacterial levels of silver ions in the wound for up to 5 days. Because Acticoat remains on the wound for up to 5 days, the patient is spared the pain and expense associated with the dressing changes. Additional studies are now underway to determine the ultimate benefit of this product.
Once all of the affected tissues have been debrided, soft tissue reconstruction can be considered. In the authors’ experience, this may take at least 2 debridements. When the debridement involves relatively small (<25%) body surface areas (BSA), skin grafts and flaps can provide coverage. When donor-site availability is limited, alternatives to standard skin graft construction must be considered, including Integra artificial skin (Integra Life Sciences, Plainsboro, NJ) and AlloDerm (LifeCell Corporation, Blanchburg, NJ).41,42
Because of persistent hypotension and diffuse capillary leak, massive amounts of intravenous fluids may be necessary after the patient is admitted to the hospital. Nutritional support is also an integral part of treatment for patients with necrotizing fasciitis. This supplementation should be initiated as soon as hemodynamic stability is achieved. Enteral feeding should be established as soon as possible to offset the catabolism associated with large open wounds. Successful use of intravenous immunoglobulin (IVIG) has been reported in the treatment of streptococcal toxic shock syndrome (STSS).43,44 A 5-day course of immunoglobulin was used in that authors’ reported patient.13
Recently, the efficacy and safety of high-dose polyspecific IVIG as adjunctive therapy in STSS were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial.45 The trial was stopped prematurely because of slow patient recruitment. The results were determined from 21 enrolled patients, 10 of whom received IVIG and 11 of whom received placebo. The primary end point was mortality at 28 days. The placebo group demonstrated a 3.6-fold higher mortality rate. Sarani et al indicate that this therapy has not been approved by the FDA for the treatment of necrotizing fasciitis.46
The use of adjunctive therapies, such as hyperbaric oxygen therapy (HBOT), for necrotizing fasciitis infection continues to receive much attention.13 Well-controlled, randomized, clinical trials demonstrating a statistically significant benefit of HBOT are lacking. Consequently, the use of HBOT as an adjunctive therapy for necrotizing fasciitis infections continues to be controversial.47,48,49 However, in hospitals where it is available, HBOT is recognized for its potential benefit in patients with these severe life-threatening infections.14,50 The beneficial effects of HBOT have recently been confirmed by another nonrandomized study reported in 1994.51 While the literature seems to support the use of HBOT as an adjunctive treatment measure in patients with necrotizing fasciitis, transfer to a hospital equipped with HBOT should not delay emergency surgical intervention.
Purpura Fulminans
Disease Classification
Purpura fulminans is a rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin that is rapidly progressive and is accompanied by vascular collapse and disseminated intravascular coagulation.52 It usually occurs in children, but this syndrome has also been noted in adults.10 It was first discovered by Guelliot in 1884.53 The 3 forms of this disease are classified by the triggering mechanisms.Neonatal purpura fulminans
Neonatal purpura fulminans is associated with a hereditary deficiency of the natural anticoagulants protein C and protein S, as well as antithrombin III (ATIII). Protein C is synthesized in the liver as a polypeptide. Purified plasma protein C concentrate has been successfully used to treat patients with thrombotic episodes in neonatal purpura fulminans. Hereditary protein C deficiency is caused by homozygous as well as heterozygous mutations that result in severe coagulopathies.
Protein S was first purified from plasma by DiScipio and colleagues, who named protein S in honor of the city of its discovery, Seattle.54 Hereditary protein S deficiency associated with thrombosis is caused by homozygous and heterozygous mutations. It is synthesized by hepatocytes, neuroblastoma cells, kidney cells, testis, megakaryocytes, and endothelial cells and is found in platelet granules.
ATIII is a protein made in the liver. It inhibits coagulation and limits the formation of blood clots. A shortage of ATIII affects the normal process of coagulation and can lead to excessive blood clotting. This protein plays a major role in the regulation of hemostasis by inhibiting thrombin. ATIII deficiency predisposes patients to venous thromboembolism events by impairing the clearance of anticoagulation factors.
ATIII deficiency is usually inherited and affects males and females equally. ATIII deficiency is found in approximately one in 2,000-5,000 individuals. All family members should be tested if the family has a history of the disease.
ATIII deficiencies fall into 3 categories. Patients with Type I deficiency have reduced amounts of ATIII protein and functional activity. Patients with Type II and III deficiency have normal levels of ATIII, but some of the proteins do not function properly.
Patients with ATIII deficiency have thromboembolic problems that usually begin in early adulthood. Clots forming in the legs may cause pain and swelling. Pulmonary embolism (PE) is also encountered. Homozygote-deficient newborns may, however, have a purpura fulminans type of presentation with embolic lesions in the skin. ATIII concentrate has been available commercially since 1974. These vitamin K–dependent ATIII cofactors are profibrinolytic and inactivate clotting factors V and VIII.55
Presentation of intense venous thrombosis of the skin and other organs occurs within the first days of life in a patient with neonatal purpura fulminans. These infants with severe genetic protein deficiency develop recurrent episodes of purpura fulminans, despite therapy with long-term high-intensity anticoagulation.
Idiopathic purpura fulminans
The second type of purpura fulminans is idiopathic or chronic purpura fulminans, which follows a bacterial or viral illness and occurs after a variable latent period.56 The idiopathic type of purpura fulminans was first recognized as entity in 1964. It usually follows an initiating febrile illness that manifests with rapidly progressive purpura, which may lead to skin necrosis, gangrene of limbs or digits, and major organ dysfunction. Deficiency of protein S is considered to be central to the pathogenesis of idiopathic purpura fulminans, and disseminated intravascular coagulation is considered to be the major pathophysiological mechanism responsible for peripheral gangrene.
Acute infectious purpura fulminans
The most common form of purpura fulminans occurs superimposed on a bacterial infection and has been called acute infectious purpura fulminans. In this illness, the balance of anticoagulant and procoagulant endothelial cell activity is disturbed. This disturbance is precipitated by bacterial endotoxin and mediated by various factors that include the inflammatory cytokines interleukin (IL)-12, interferon-γ, tumor necrosis factor-α (TNF-α), and IL-1, which consume ATIII as well as proteins C and S.57 Microemboli and direct bacterial damage to vessels have also been linked with this process. The 2 most common causes of acute infectious purpura fulminans are meningococcus and varicella. Gram-negative bacilli, staphylococci, Rickettsia species, streptococci, and measles have also been found to be associated with this form of purpura fulminans.
Clinical Presentation
Neonatal purpura fulminansWithin the first 72 hours after birth, a neonate with neonatal purpura fulminans exhibits purpuric lesions over many different skin sites, including the perineal region, the flexor surface of the thighs, and abdominal skin. Homozygosity or compound heterozygosity for protein C mutations result in an absolute deficiency of protein C. Fortunately, absolute deficiency of protein C is exceedingly rare in neonates.58 The complete lack of plasma protein C activity causes neonatal purpura fulminans, a devastating thrombotic disorder of the neonate. It is characterized by sudden onset of widespread purpuric lesions that progress to gangrenous necrosis and is associated with disseminated intravascular coagulation.
The acquired form of neonatal purpura fulminans, usually recognized in older infants, is a postmeningococcal sepsis syndrome that results in decreased levels in activity of protein C. In addition, neonates may be born with an inherited deficiency in either protein S or ATIII that may lead to neonatal purpura fulminans.
Idiopathic purpura fulminans
Idiopathic purpura fulminans usually follows the initiating infectious manifestation with rapidly progressing purpura that may lead to skin necrosis, gangrene of the limbs or digits, and major organ dysfunction.59 The disease usually begins 7-10 days after the onset of the precipitating infection. It then progresses rapidly to purpura, leading to extensive areas of skin necrosis. The illness is often complicated by impaired perfusion of limbs and digits as well as major organ dysfunction caused by thromboembolic phenomena involving the lungs, the heart, or the kidneys. Protein C, protein S, and ATIII levels are often virtually undetectable at the time of admission.
Acute infectious purpura fulminans
Over time, the term purpura fulminans has been applied to cases of purpura fulminans that occur in the face of overwhelming sepsis (ie, sepsis-associated fulminans). The 4 primary features of this syndrome are large purpuric skin lesions, fever, hypotension, and disseminated intravascular coagulation. Meningococcemia is generally more predisposed than other bacteria to cause a dysfunction of the activated protein C pathway. More recently, Staphylococcus aureus has been associated with purpura fulminans with accompanying toxic shock syndrome.60
Diagnosis and Treatment
Neonatal purpura fulminansNeonatal purpura fulminans occurs usually in patients with a deficiency of protein C. Protein C deficiency is usually inherited in an autosomal dominant manner, with heterozygous carriers often remaining asymptomatic until later in life, when they become very susceptible to venous thromboembolism. Autosomal recessive protein C deficiency, which is caused by homozygous or compound heterozygous mutations in protein C, is less common and usually leads to a more severe form of the disease, with onset of thrombotic manifestations at birth.
Within the first 72 hours after birth, purpuric lesions usually appear on the surface of the skin. The skin lesions soon enlarge and become vesiculated, producing hemorrhagic bullae with subsequent necrosis and black eschar formation. The margins of the lesions become erythematous and indurated. Thrombocytopenia is often evident. The patient may later develop signs of a urinary tract infection (UTI). (For more information on the diagnosis and treatment of UTIs, visit eMedicine articles Urinary Tract Infection, Females; and Urinary Tract Infection, Males.)
Immediate treatment with platelet concentrate is recommended to reverse the thrombocytopenia and the bleeding manifestations. The neonate often develops disseminated intravascular coagulation. In the absence of signs of generalized septicemia, deficiencies of the anticoagulant factors protein C, protein S, and ATIII remain important considerations. Consequently, the endogenous activity of these anticoagulant factors must be assessed using a chromogenic assay.
With a provisional diagnosis of purpura fulminans due to protein C deficiency, fresh frozen plasma transfusion must be started. The fresh frozen plasma can later be replaced by low molecular weight heparin. Subsequently, oral anticoagulation with warfarin must be instituted. The debridement of the dead tissue is mandatory. The protein C, protein S, and ATIII genes must be analyzed in the patient and his or her parents. These patients require long-term oral anticoagulation, which, if well-tolerated, can be adequate for them to remain free of coagulopathy throughout life.61 If these assays reveal a genetic defect in the protein C or ATIII genes, the protein C or ATIII concentrates can be used to correct this coagulation disorder.
Idiopathic purpura fulminans
In 1995, Sheridan et al described a management strategy in idiopathic purpura fulminans with multiple organ failure in children. In these patients, the necrosis of soft tissue was associated with meningococcal sepsis.62 Purpura fulminans was rarely a cause of meningococcal sepsis. The predominant presentation of meningococcal sepsis is bacterial meningitis.
In 3 cases reported by Sheridan et al, the purpura fulminans involved a large percentage of the patients' body surface areas. The 15-year-old boy had skin lesions on 55% of his body surface area. The 11-month-old girl was affected on 25% of her body surface area. The 2-year-old boy had evidence of purpura fulminans on 55% of his body surface area. The pathogenesis of purpura fulminans was not known, but probably involved acute transient decreases in protein C, protein S, or ATIII. The successful management of meningococcal sepsis was obviously facilitated by early diagnosis and aggressive antibiotic therapy. The management of these cases of purpura fulminans was extremely challenging because the children had evidence of multiple organ failure.
To better understand the current management of idiopathic purpura fulminans, 7 burn centers performed a 10-year retrospective chart review of patients who were diagnosed with idiopathic purpura fulminans.63 A total of 70 patients were identified, with a mean patient age of 13 years. Neisseria meningitidis was the most common pathogen identified in infants and adolescents. Streptococcus species commonly affected the adult population. Acute management consisted of antibiotic treatment, volume resuscitation, and ventilatory and inotropic support. Protein C replacement was performed in only 9% of the cases. One fourth of the patients required amputation of all of the extremities. When performed early, fasciotomies may reduce the depth of soft tissue involvement and the extent of amputation. Although the overall mortality in this study was only 13%, the surgeons believedthis number to be inaccurately low because it does not reflect the number of patients who succumbed to sepsis in facilities outside of the multicenter study group.
Idiopathic purpura fulminans often follows the initiating febrile illness and manifests with rapidly progressive purpura that may lead to skin necrosis, gangrene of limbs or digits, and major organ dysfunction. In general, the authors recommend a conservative approach that includes excising gangrenous areas after they have been demarcated from purpuric and indeterminate zones. However, in the presence of infection, early aggressive surgical debridement is essential to prevent invasive wound sepsis. When compartment syndrome is suspected in patients with tense limbs and distal ischemia, early fasciotomy is recommended. If established gangrene is present, conservative amputation is warranted.
Idiopathic purpura fulminans begins suddenly with the development of progressively enlarging, well-demarcated purplish areas of hemorrhagic cutaneous necrosis with deranged coagulation factors. Most cases occur in children. More than 90% are preceded by infection, commonly varicella or streptococcal infection. The idiopathic purpura fulminans usually begins 7-10 days after the onset of the infection. Lesions begin as erythematous macules that progress within hours to sharply defined areas of purpura. Critically impaired circulation to skin and lower limbs may develop within a few hours. In some cases, patients have undetectable levels of free protein S at the time of admission. Procoagulate and anticoagulate factors, including protein C, protein S, and ATIII, must be measured by functional assays.
Manco-Johnson and Knapp-Clevenger described the use of activated protein C in a 14-year-old girl with protein C deficiency due to idiopathic purpura fulminans.64 At the end of the activated protein C infusions, all skin lesions of purpura fulminans were resolved. The patient experienced no adverse reactions to protein C. The authors concluded that activated protein C is safe and effective for the treatment of purpura fulminans with severe genetic protein C deficiency. Recognition of the pathophysiologic mechanism of idiopathic purpura fulminans provides a rational basis for treatment with immediate heparinization and infusions of fresh frozen plasma.59 In some cases complicated by major vessel thrombosis, the use of tissue-type plasminogen activated may reduce thromboembolic complications.59
Acute infectious purpura fulminans
Over time, purpura fulminans has been applied to cases of acute infectious purpura fulminans that occur in the face of overwhelming sepsis. The authors must reiterate that the 4 primary features of this syndrome are large purpuric skin lesions, fever, hypotension, and disseminated intravascular coagulation. Meningococcemia and infection due to S aureus both lead to acute infectious purpura fulminans. Patients with these infections have remarkably reduced levels of activated protein C as a result of dysfunction of the endothelial protein C activation pathway. Activated protein C is not only an anticoagulant but also serves as an important modulator of the inflammatory response.
On the basis of extensive experience, the authors believe that patients who present with acute infectious purpura fulminans should receive antibiotic therapy not only against Neisseria meningitidis and streptococci, but also against methicillin-resistant S aureus. Consideration should also be given to the early administration of activated protein C concentrates to minimize purpura skin injury and to reduce the inflammatory cascade before irreparable tissue injury occurs.65 Finally, because toxic shock syndrome is mediated by strong antigens, intravenous immunoglobulin (IVIG) therapy should be implemented because these preparations contain significant antibodies against the causative exotoxins.66 Hyperbaric oxygen therapy (HBOT) has been rarely used in the treatment of purpura fulminans and has not been considered an important part of its therapy.
Keywords
necrotizing fasciitis, superficial fascia, group A β-hemolytic streptococcus, polymicrobial, antecedent trauma, ultrasound, magnetic resonance imaging, finger-test, penicillin G, aminoglycoside, clindamycin, powder-free double-glove hole indication system, Food and Drug Administration, FDA, debridement, immunoglobulin, hyperbaric oxygen, Integra, AlloDerm, purpura fulminans, protein C, protein S, antithrombin III, ATIII, antithrombin 3, AT3, neonatal purpura fulminans, idiopathic purpura fulminans, acute infectious purpura fulminans, antithrombin III concentrate, purified plasma protein C concentrate, meningococcus, varicella
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Further Reading
Keywords
necrotizing fasciitis, superficial fascia, group A β-hemolytic streptococcus, polymicrobial, antecedent trauma, ultrasound, magnetic resonance imaging, finger-test, penicillin G, aminoglycoside, clindamycin, powder-free double-glove hole indication system, Food and Drug Administration, FDA, debridement, immunoglobulin, hyperbaric oxygen, Integra, AlloDerm, purpura fulminans, protein C, protein S, antithrombin III, ATIII, antithrombin 3, AT3, neonatal purpura fulminans, idiopathic purpura fulminans, acute infectious purpura fulminans, antithrombin III concentrate, purified plasma protein C concentrate, meningococcus, varicella
