Necrotizing soft-tissue skin infections (NSTIs) encompass progressive, rapidly spreading, inflammatory infections located in the deep subcutaneous tissues and adjacent fascia. Other names include gas gangrene or Fournier gangrene when involving the perineum.
While mortality varies, most studies report the estimated mortality to be 15-20%, which is largely unchanged over the last 30 years.[1, 2, 3, 4] The rapid clinical course is assumed to be related to microbial virulence, and many recent studies show that the majority of cases are polymicrobial as opposed to being due to a single organism such as group A ?-hemolytic Streptococcus or Streptococcus pyogenes.
NSTI is a rare diagnosis with a wide spectrum of presentations to the emergency department (ED) contributing to the difficulty of arriving at an early diagnosis. Definitive treatment remains early and aggressive surgical intervention, and delay often results in increased morbidity and mortality.[4, 5]
Necrotizing fasciitis moves along the deep fascial planes with a paucity of early examination findings, which often results in delayed diagnosis. Cutaneous findings appear later in the disease course as a result of vasculitis and thrombosis of perforating vessels leading to tissue ischemia and infarction. Vascular compromise necessitates surgical management because delivery of antibiotics is ineffective.
Clinical features of pain out of proportion to examination findings or significant pain extending past what appears to be the border of the infection should raise the concern for a necrotizing soft-tissue skin infection (NSTI). Exotoxin release by clostridia, staphylococci, and streptococci can enhance virulence and result in release of cytokines, leading to systemic inflammatory response progressing to sepsis.
Epidemiology and Microbiology
The incidence of necrotizing soft-tissue skin infections (NSTIs) is approximately 500-1500 cases per year, with a recent increase thought to be related to increased microbial virulence and antibiotic resistance.
NSTIs characteristically begin with external trauma as minor as an injection or insect bite, but can also occur spontaneously, with only 10-40% of patients able to give history of preceding skin break.[6, 7]
Chronic edema resulting in venous stasis or peripheral vascular disease, as well as preexisting diabetic foot wounds, are associated with NSTIs. NSTIs occur more commonly in patients with comorbidities such as diabetes mellitus, chronic alcoholism, chronic renal disease, HIV disease, liver disease, and underlying malignancy.[7, 8]
Rarely necrotizing infections can occur in the retroperitoneum and manifest cutaneously on the abdominal wall as a complication of intra-abdominal infectious processes, perforated viscous, or severe pancreatitis complicated by abscess.[9, 10, 11]
NSTI can be classified based on microbial etiology. Type I infections are the most common and are polymicrobial.[1, 6] Type II NSTI is monomicrobial in etiology and is associated with streptococci, staphylococci, and clostridia. Staphylococcal NSTI is increasing in prevalence owing to more cases of methicillin-resistant Staphylococcus aureus (MRSA) and association with intravenous drug use, particularly the use of black tar heroin. Type III NSTI is caused by Vibrio vulnificus classically associated with salt-water exposure in patients with underlying cirrhosis.
Classification of NSTIs is as follows:
- Type I – Polymicrobial etiology (most common)
- Type II – Monomicrobial etiology (Streptococcus, Staphylococcus, Clostridium)
- Type III -V vulnificus (associated with seawater exposure)
Presentation and Diagnosis
Necrotizing soft-tissue skin infections (NSTIs) can be difficult to diagnose early in the disease course as initial signs and symptoms can be typical of cellulitis.[7, 8] As mentioned previously, the classic examination finding of pain out of proportion to examination or pain extending beyond the border of infection are both concerning for NSTI. Hemorrhagic bullae, ecchymosis, and crepitus are later findings.
It is common for patients with NSTI to present with signs of systemic toxicity due to a systemic inflammatory response from cytokine release. However, some patients with underlying chronic illness may be relatively immunosuppressed and demonstrate a less dramatic presentation.
Some patients present with “la belle indifference” and despite a severely infected extremity seem inappropriately unbothered, which may be a result of local ischemia causing the skin to become insensate.
See the images below.
[/i]Left upper extremity shows necrotizing fasciitis in an individual who used illicit drugs. Cultures grew Streptococcus milleri and anaerobes (Prevotella species). Patient would grease, or lick, the needle before injection.
[/i]Necrotizing fasciitis at a possible site of insulin injection in the left upper part of the thigh in a 50-year-old obese woman with diabetes.
[/i]Photomicrograph of Fournier gangrene (necrotizing fasciitis), oil immersion at 1000× magnification. Note the acute inflammatory cells in the necrotic tissue. Bacteria are located in the haziness of their cytoplasm. Courtesy of Billie Fife, MD, and Thomas A. Santora, MD. When evaluating a patient for possible NSTI, the border of erythema should always be marked upon initial evaluation to assess for rapid advancement.
Radiographic studies can demonstrate subcutaneous emphysema, but this is late finding and should not be used to rule out NSTI; however, if present, it is associated with severe disease.[12, 13] Advanced imaging modalities such as CT and MRI can reveal fascial thickening, irregularities of or fluid along the fascial planes, edema, or even necrosis of the underlying muscle, but they may not be appropriate for patients who are unstable or if it would delay surgical intervention. Emergency ultrasonography can also be used to aid in the diagnosis by revealing similar findings of thickened or irregular fascia or fluid along the fascial planes.[14, 15] See the image below.
[/i]Ultrasound image demonstrating thickened, irregular fascial plane with edema within underlying muscle representing myonecrosis in patient with confirmed necrotizing fasciitis. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score can be used to increase suspicion for a necrotizing skin infection. The LRINEC score includes 6 variables associated with NSTI and are used to calculate a score correlating to the risk of NSTI (see tables 1 and 2 below). Patients with an LRINEC score of 6 or higher are at highest risk for the presence of a necrotizing infection. However, an LRINEC score of 6 or less cannot be used to rule out the diagnosis completely. Patients still need a thorough evaluation to rule out the disease. Not included in the LRINEC score is a serum lactate level, which, if elevated, should also increase concern for NSTI. Patients with concern for NSTI can rapidly deteriorate and should be reevaluated frequently.
Table 1. LRINEC Score Parameters
|Laboratory Parameter||LRINEC Points|
|C-reactive protein (mg/L)|
|Risk Category||LRINEC Score||Points||Probability of NSTI||%|
Emergency Department Management
Patients with suspected necrotizing fasciitis must be promptly and aggressively treated to reduce morbidity and mortality. Immediate surgical consultation is indicated when a diagnosis of necrotizing soft-tissue skin infection (NSTI) is suspected. Obtain intravenous access in the unaffected extremity. Administer intravenous broad-spectrum antibiotics and begin fluid resuscitation with normal saline or lactated Ringer solution. Consider central venous access for measurement of central venous pressure and central venous oxygen saturation to initiate early goal-directed therapy for patients presenting with sepsis. Consider supplemental oxygen and intubation if hypoxia or altered mental status exist. Prompt surgery consultation should be made for definitive management. Tetanus status should be assessed and updated if indicated.
Broad-spectrum intravenous antibiotics should be initiated upon suspicion for possible NSTI. Antibiotic selection should cover gram-positive, gram-negative, and anaerobic organisms. Penicillin is recommended for the coverage of streptococcal and clostridial organisms. Clindamycin has the added benefit in cases with streptococcal or clostridial involvement. Vancomycin, linezolid, or daptomycin should be included in the regimen for coverage of methicillin-resistant S aureus (MRSA). Since most are polymicrobial infections, broad-spectrum coverage is recommended until bacterial etiology is defined.
Based on current recommendations, the authors suggest an initial regimen of vancomycin 25-30 mg/kg IV q12h, clindamycin 600-900 mg IV q8h plus meropenem 500 mg-1 g IV q8h or piperacillin/tazobactam 4.5 g IV q6h.[18, 19, 20] Ciprofloxacin or ceftazidime can be added for freshwater exposure to cover V vulnificus. Antibiotics should be renally dosed. For hypersensitivity to penicillins or cephalosporins, an alternate regimen with an aminoglycoside plus metronidazole 500 mg IV q8h can be considered.
Intravenous immunoglobulin (IVIG) is an experimental treatment for necrotizing fasciitis and is postulated to bind exotoxin produced by streptococcal and staphylococcal species, potentially delaying the onset of the systemic inflammatory response and sepsis and should be considered on a case-by-case basis.
Hyperbaric Oxygen Therapy
Hyperbaric oxygen therapy (HBO) involves the use of oxygen at 2-3 times atmospheric pressure with proposed benefits of bacteriocidal effects, improved polymorphonuclear lymphocyte function, and enhanced wound healing. There are few controlled clinical studies with conflicting results. HBO should be considered as a treatment adjunct and does not replace surgical debridement.
Debridement and Definitive Surgical Management
Aggressive surgical debridement of all necrotic tissue is the definitive treatment of necrotizing fasciitis. Antibiotic treatment alone without surgical intervention leads to progressive sepsis. Debridement is best accomplished by early and extensive incision of skin and subcutaneous tissue wide into healthy tissue, followed by excision of all necrotic fascia and nonviable skin and subcutaneous tissue.
Consultations and Transfer
Obtain early surgical consultation for aggressive debridement in cases of suspected necrotizing soft-tissue skin infection (NSTI) without delay for results of laboratory or radiology studies. Consider surgical subspecialty consultation for necrotizing fasciitis involving specific anatomic areas such as urology in cases of Fournier gangrene. Consultation with an infectious diseases specialist may help guide initial empiric antibiotic therapy.If the current facility is not capable of handling the aggressive care, monitoring, and serial surgical debridement that these patients require, then arrangements for transfer should be made. Transfer to a hyperbaric center may be necessary after initial debridement; however, patients should not be considered for transfer until they remain hemodynamically stable.