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Diagnosis and Management of Necrotizing Fasciitis

Jason W. Stoneback, MD; David J. Hak, MD, MBA

Abstract

Necrotizing fasciitis is a rare, life-threatening soft tissue infection. It can be caused by many different organisms that spread rapidly along the fascial planes. Rapid assessment, emergent surgical debridement, and multidisciplinary support are required. Orthopedic surgeons are often called to evaluate, diagnose, and treat patients with soft tissue infections of the extremities. Although uncommon, it is critical to promptly identify a suspected case of necrotizing fasciitis from less serious soft tissue infections such as cellulitis or abscesses.

The incidence of necrotizing fasciitis has been reported to be between 500 and 1500 cases per year in the United States.1 A previous insurance claim database study cited an incidence of 0.04 per 1000 person-years.2 Mortality rates have been reported to range from 8% to 65%, averaging 21.9%.3

Trauma, diabetes, intravenous drug abuse, immunodeficiency, chronic disease, minor abrasions, lacerations, insect bites, chronic ulcers, burns, and surgical wound infections have all been implicated as risk factors in the development of necrotizing fasciitis.4-6 The development of necrotizing fasciitis is typically associated with an injury to the involved area. Trauma, either penetrating or blunt, has been shown to be a risk factor for the development of necrotizing fasciitis. While a traumatic mechanism is often present, the inciting event can be innocuous or remote.

Necrotizing fasciitis typically begins as an area of inflamed skin with or without history of skin trauma. In the early stages it can be difficult, but extremely important, to differentiate more common skin infections such as cellulitis or soft tissue abscess from the more severe diagnosis of necrotizing fasciitis. The initial presentation may appear innocuous, with stable vital signs and benign skin manifestations. The patient’s condition may then rapidly deteriorate. The benign skin findings are replaced with a rapidly progressing area of skin induration and advancing erythema, followed by the development of overlying blisters and skin necrosis. This is accompanied by a rapid change in the patient’s vital signs, with fever, tachycardia, hypotension, and signs of multiple organ failure, often requiring admission to the intensive care unit.

Wang et al7 proposed 3 stages of progressive skin examination findings that occur with necrotizing fasciitis. Stage 1 (early) begins with tenderness to palpation (extending beyond the apparent area of skin involvement), erythema, swelling, and warmth to palpation. The transition to stage 2 (intermediate) is marked by serous-filled blister or bullae formation along with skin fluctuance and induration. Stage 3 (late) is heralded by hemorrhagic bullae, skin anesthesia, crepitus, and skin necrosis with dusky discoloration progressing to gangrene.

The superficial fascia is the principal site of the pathologic process (Figure 1). Bacteria inoculate this normally sterile location either through penetrating injury or by hematogenous spread. Bacteria then rapidly replicate, synthesizing enzymes and toxins that facilitate their spread through the superficial fascial planes. In conjunction with the rapid microbial proliferation, angiothrombotic microbial invasion and liquifactive necrosis of the superficial fascia occurs. Destruction of the superficial fascial layer along with the adjacent nutrient vessels to the skin leads to progressive overlying skin ischemia and ultimately full-thickness skin loss.

Numerous bacteria have been implicated in necrotizing fasciitis. A recent systematic review reported that the 3 most commonly cultured organisms in necrotizing fasciitis were Staphylococcus aureus, group A Streptococcus, and Streptococcus viridans.3 A wide range of other organisms, including fungal species, have been cultured from the wounds of patients with necrotizing fasciitis (Table 1).3 While most necrotizing fasciitis infections are polymicrobial, invasive group A Streptococcus is one of the most prevalent organisms. According to a 2008 Centers for Disease Control report, approximately 9000 to 11,500 cases of invasive group A Streptococcus disease occur each year in the United States, resulting…

Early diagnosis combined with emergent surgical debridement, appropriate broad-spectrum empiric antibiotic treatment, and a multidisciplinary team approach is essential for successful treatment of necrotizing fasciitis.
Cover illustration © Lisa Clark
Cover illustration © Lisa Clark

Necrotizing fasciitis is a rare, life-threatening soft tissue infection. It can be caused by many different organisms that spread rapidly along the fascial planes. Rapid assessment, emergent surgical debridement, and multidisciplinary support are required. Orthopedic surgeons are often called to evaluate, diagnose, and treat patients with soft tissue infections of the extremities. Although uncommon, it is critical to promptly identify a suspected case of necrotizing fasciitis from less serious soft tissue infections such as cellulitis or abscesses.

Epidemiology and Risk Factors

The incidence of necrotizing fasciitis has been reported to be between 500 and 1500 cases per year in the United States.1 A previous insurance claim database study cited an incidence of 0.04 per 1000 person-years.2 Mortality rates have been reported to range from 8% to 65%, averaging 21.9%.3

Trauma, diabetes, intravenous drug abuse, immunodeficiency, chronic disease, minor abrasions, lacerations, insect bites, chronic ulcers, burns, and surgical wound infections have all been implicated as risk factors in the development of necrotizing fasciitis.4-6 The development of necrotizing fasciitis is typically associated with an injury to the involved area. Trauma, either penetrating or blunt, has been shown to be a risk factor for the development of necrotizing fasciitis. While a traumatic mechanism is often present, the inciting event can be innocuous or remote.

Clinical Presentation and Pathophysiology

Necrotizing fasciitis typically begins as an area of inflamed skin with or without history of skin trauma. In the early stages it can be difficult, but extremely important, to differentiate more common skin infections such as cellulitis or soft tissue abscess from the more severe diagnosis of necrotizing fasciitis. The initial presentation may appear innocuous, with stable vital signs and benign skin manifestations. The patient’s condition may then rapidly deteriorate. The benign skin findings are replaced with a rapidly progressing area of skin induration and advancing erythema, followed by the development of overlying blisters and skin necrosis. This is accompanied by a rapid change in the patient’s vital signs, with fever, tachycardia, hypotension, and signs of multiple organ failure, often requiring admission to the intensive care unit.

Wang et al7 proposed 3 stages of progressive skin examination findings that occur with necrotizing fasciitis. Stage 1 (early) begins with tenderness to palpation (extending beyond the apparent area of skin involvement), erythema, swelling, and warmth to palpation. The transition to stage 2 (intermediate) is marked by serous-filled blister or bullae formation along with skin fluctuance and induration. Stage 3 (late) is heralded by hemorrhagic bullae, skin anesthesia, crepitus, and skin necrosis with dusky discoloration progressing to gangrene.

The superficial fascia is the principal site of the pathologic process (Figure 1). Bacteria inoculate this normally sterile location either through penetrating injury or by hematogenous spread. Bacteria then rapidly replicate, synthesizing enzymes and toxins that facilitate their spread through the superficial fascial planes. In conjunction with the rapid microbial proliferation, angiothrombotic microbial invasion and liquifactive necrosis of the superficial fascia occurs. Destruction of the superficial fascial layer along with the adjacent nutrient vessels to the skin leads to progressive overlying skin ischemia and ultimately full-thickness skin loss.

Figure 1: Schematic representation of necrotizing fasciitis location within the soft tissues
Figure 1: Schematic representation of necrotizing fasciitis location within the soft tissues. Rapid bacterial replication along superficial and deep fascial planes leads to liquifactive necrosis and ultimately full-thickness skin loss.

Microbiology

Numerous bacteria have been implicated in necrotizing fasciitis. A recent systematic review reported that the 3 most commonly cultured organisms in necrotizing fasciitis were Staphylococcus aureus, group A Streptococcus, and Streptococcus viridans.3 A wide range of other organisms, including fungal species, have been cultured from the wounds of patients with necrotizing fasciitis (Table 1).3 While most necrotizing fasciitis infections are polymicrobial, invasive group A Streptococcus is one of the most prevalent organisms. According to a 2008 Centers for Disease Control report, approximately 9000 to 11,500 cases of invasive group A Streptococcus disease occur each year in the United States, resulting in 1000 to 1800 deaths annually.8 Necrotizing fasciitis comprises approximately 6% to 7% of these invasive cases.

Table 1: Cultured  Microorganisms in Necrotizing Fasciitis Cases

Nuwayhid et al6 found group A Streptococcus necrotizing fasciitis cases were approximately 6 times more likely to have a recent history of blunt trauma than adjusted controls. This study highlights the importance of the evaluating physician having a high level of suspicion for necrotizing fasciitis even in the absence of an obvious site of entry for bacteria.

Diagnostic Tests

The diagnosis of necrotizing fasciitis is primarily a clinical one. However, plain radiographs, computed tomography (CT), magnetic resonance imaging (MRI), and laboratory data can provide useful supplemental information and raise the suspicion for necrotizing fasciitis when the diagnosis is uncertain. These adjunctive diagnostic tests can also provide prognostic information. Because of the need for prompt initiation of treatment, adjunctive diagnostic tests should not impede the timing of surgical exploration and debridement. Necrotizing fasciitis is a clinical diagnosis where only emergent surgical debridement and appropriate antibiotic treatment can prevent progression and death.

Plain Radiography

A common misconception exists that subcutaneous gas is a common plain radiographic finding in necrotizing fasciitis. However, this finding is relatively infrequent, with subcutaneous gas present in only 13% of necrotizing fasciitis cases.3 Additionally, subcutaneous gas may not be present in earlier stages of the disease process and only become manifest as the patient’s condition deteriorates. While plain radiographs are not mandatory for the treatment of soft tissue infections, they can provide useful information such as retained foreign bodies like broken hypodermic needles that the surgeon may encounter during debridement of the infected wound.

Computed Tomography

Computed tomography has a higher sensitivity than plain radiography in identifying early soft tissue changes characteristic of necrotizing fasciitis.9,10 Findings of necrotizing fasciitis found on CT are fat stranding, along with fluid and gas collections that dissect along fascial planes. Additionally, fascial thickening and nonenhancing fascia on contrast CT suggests fascial necrosis.10 While CT has a higher sensitivity than plain radiographs in detecting soft tissue manifestations of necrotizing fasciitis, it takes valuable time and should not impede emergent surgical debridement. Furthermore, gas formation is not found in all cases of necrotizing fasciitis, and its absence on CT does not exclude the diagnosis of necrotizing fasciitis.11 While CT may play a role in planning surgical debridement in craniofacial areas, its routine use is not recommended for the diagnosis of necrotizing fasciitis of the extremities.12

Magnetic Resonance Imaging

Magnetic resonance imaging is the imaging modality of choice for soft tissue conditions. Magnetic resonance imaging can differentiate cases of severe cellulitis and pyomyositis from necrotizing fasciitis and identify underlying pathology such as abscess that can be the root cause of the soft tissue infection.13,14 Subcutaneous tissue low-signal intensity on T1-weighted images combined with high-signal intensity of the subcutaneous tissues and involvement of the deep fascia on T2-weighted images confirm the diagnosis of necrotizing fasciitis. Schmid et al13 found MRI to be 100% sensitive and 86% specific and have a diagnostic accuracy of 94% for necrotizing fasciitis when correlated with intraoperative findings. However, the authors noted that surgical findings found MRI overestimated the extent of infection.13 Again, it should be emphasized that MRI or other adjunctive tests should not delay emergent surgical exploration and debridement in cases of suspected necrotizing fasciitis.

Ultrasound

Recently there has been increasing interest by emergency department physicians in the diagnostic use of ultrasound. Ultrasound can be rapidly preformed to help differentiate simple cellulitis from cases of underlying abscess and has shown some usefulness in the diagnosis of necrotizing fasciitis.15 In a prospective observational study of 62 patients with clinically suspected necrotizing fasciitis, ultrasound revealed a sensitivity of 88.2%, specificity of 93.3%, positive predictive value of 95.4%, negative predictive value of 95.4%, and diagnostic accuracy of 91.9%.15 The authors used the findings of diffuse subcutaneous thickening accompanied with fluid accumulation of >4 mm in depth along the deep fascial layer to confirm the diagnosis of necrotizing fasciitis.15 While ultrasound may have some diagnostic usefulness in the emergency department, its use requires further study and a highly skilled operator limiting its practical use.

Laboratory Analysis

In the early stages, patients can have normal vital signs and a relatively benign clinical examination. Ancillary diagnostic imaging such as CT and MRI can cause significant time delays and are not always accessible. In an effort to provide readily accessible ancillary diagnostic information in patients with suspected necrotizing fasciitis, Wong et al16 analyzed several laboratory parameters in patients with documented necrotizing fasciitis. From this data, the authors developed the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) Score. The LRINEC Score uses basic laboratory parameters found in routine serum blood analysis. The LRINEC Score is based on serum C-reactive protein, total white blood cell count, hemoglobin, sodium, creatinine, and glucose levels. Cutoff values for each parameter allow a total score to be calculated (Table 2).16 A LRINEC Score of >6 was found to have a positive predictive value of 92% and a negative predictive value of 96%.16 While the score has been validated by the authors with an external cohort, others have questioned the scores reliability and clinical usefulness.17,18

Table 2: The Laboratory Risk Indicator for Necrotizing Fasciitis Scoring System

Frozen Section

Fascial biopsy with frozen section has been shown to identify patients with necrotizing fasciitis accurately and quickly.19,20 Early diagnosis by fascial biopsy frozen section can be performed at the bedside under local anesthetic using 1% lidocaine.20 After obtaining local analgesia, a full thickness 2×1-cm elliptical biopsy of the skin, deep soft tissue, and fascia are taken from the suspected area of infection as well as from the leading edge of any erythema, induration, or necrosis.20 Tissue biopsies are then immediately evaluated by frozen section pathologic analysis, gram stain, and culture.

Authors that advocate the use of frozen tissue biopsy cite that early detection of necrotizing fasciitis decreases morbidity and mortality rates by facilitating early diagnosis, leading to earlier surgical intervention and appropriate antibiotic treatment.19,20

Treatment

Emergent surgical exploration and debridement is the critical element in necrotizing fasciitis treatment, followed by appropriate antibiotic and supportive therapy. Additionally, a multidisciplinary team approach with coordination between the surgeon, intensivist, dietician, infectious disease specialist, and plastic surgeon is integral to decreasing morbidity and mortality. Other therapies such as intravenous immune globulin and hyperbaric oxygen therapy may have some usefulness as adjunctive treatment in patients with necrotizing fasciitis but remain controversial.

Surgical Debridement

Multiple authors have shown that early and thorough surgical debridement decreases mortality in patients with necrotizing fasciitis.21,22 Bilton et al21 found patients who had early surgical debridement had decreased mortality rates when compared to patients with delayed debridement. Wong et al22 found a nine-fold increase in mortality rate with a delay in surgical debridement >24 hours from hospital admission.

Surgical debridement requires a meticulous technique and must be aggressive to halt progression of infection. Wong et al23 advocated 4 steps in their approach to surgical debridement of patients with necrotizing fasciitis, which include confirming the diagnosis and isolation of the causative organism, defining the extent of fasciitis, surgical excision of involved fascia, and postexcision wound care. Diagnosis is confirmed on surgical exploration by the presence of grayish necrotic deep fascia and abnormally nonadherent subcutaneous tissue that easily dissects from the deep fascia with blunt finger traction coupled with foul-smelling “dishwater” purulence.22,23 Frozen section histological analysis may also be used if the diagnosis is in question but is not required. Cultures should be obtained during the initial surgical debridement to tailor specific antibiotic management.

In the awake and alert patient, the extent of fasciitis can initially be clinically determined by the extent of tenderness to palpation, and then substantiated through surgical dissection until normal tissue is encountered.23 To halt the spread of the infection, complete surgical excision requires removal of all infected and necrotic tissue including a 5- to 10-mm margin of healthy fascia (Figure 2).23 Postexcision wound care starts with meticulous hemostasis, as many of these patients are coagulopathic.23 Nonadherent compressive dressings should then be applied, followed by repeat wound inspection in <24 hours.23

Figure 2: Necrotizing fasciitis
Figure 2: Intraoperative photograph of a patient with necrotizing fasciitis after initial debridement. Gray “dishwater pus” and liquifactive necrosis tracking along fascial planes was encountered. After multiple serial debridements and wound vacuum placement, partial delayed primary closure and split-thickness skin grafting was needed for wound closure.

In the immediate postoperative period, the patient should be closely monitored for signs of continuing advancement of infection. The patient should be scheduled to return to the operating room in 24 hours for an initial second look, with multiple surgical debridements being the norm rather than the exception. Angoules et al3 reported that patients required an average of 3 surgical debridements, with 22.3% of patients requiring amputation for failure of multiple surgical debridements to control the infection. After adequate serial surgical debridement, 48.4% required a skin graft and 4.5% required rotational flap coverage.3

Supportive Care

Necrotizing fasciitis patients often become hemodynamically unstable and coagulopathic and require ventilator support, making early involvement of intensivists central to patient management. One study reported an average intensive care unit stay of 10.6 days.24 The average inpatient hospitalization is 24.9 days.3 Sepsis, serial surgical debridement, and frequent massive surgical wounds that require extensive reconstruction make nutritional support of paramount importance. One study found 94% of necrotizing fasciitis patients required total enteral nutrition and/or total parenteral nutrition for an average of 24 days.25

Antibiotic Therapy

While surgical debridement is the cornerstone of necrotizing fasciitis management, appropriate antibiotic selection can treat sepsis and halt further bacterial spread. Once the diagnosis of necrotizing fasciitis is suspected, proper empiric antibiotic treatment should be started immediately, followed by culture-specific tailoring of antibiotics with infectious disease specialist involvement.

Broad-spectrum antibiotic coverage should initially be selected to provide treatment for gram-positive, gram-negative, and anaerobic organisms. There is increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA),26 and appropriate empiric coverage should be initiated until MRSA has been ruled out. An acceptable empiric antibiotic regimen includes linezolid, which covers MRSA with the additional benefit of inhibiting invasive group A Streptococcus virulence proteins similar to clindamycin.27 In addition to linezolid, piperacillin/tazobcatam or meropenem should be administered for gram-positive/negative and anaerobic coverage until culture-specific results and sensitivities are available.

No general consensus exists on the necessary duration of antibiotic therapy. Some authors have recommended continuing antibiotic therapy until no additional surgical debridements are required and the patient no longer exhibits signs of systemic inflammation.28

Antibiotic therapy alone has been shown to have high mortality rates due to reduced antibiotic delivery in poorly vascularized/necrotic tissue at the infection site. Surgical debridement is required to decrease necrotic tissue load and provide a viable tissue bed amenable to the delivery of antibiotics.

Adjunctive Therapy

Hyperbaric oxygen therapy has been studied as an adjunctive treatment modality for patients with necrotizing fasciitis. The increased partial pressure of oxygen may enhance leukocyte-killing activity, suppress bacterial growth, enhance antibiotic effects, and improve tissue repair.29 Some studies have found hyperbaric oxygen therapy to be beneficial in reducing mortality and amputation rate in patients with necrotizing fasciitis.30 While some retrospective studies have found benefit, others have not, and multicenter prospective randomized trials are needed.31,32

Intravenous immunoglobulin is a concentrated pooled product derived from human donors primarily containing immunoglobulin G isotopes. Recommendation for its use is based on its binding of several staphylococcal superantigens, thereby preventing peripheral blood T-cell stimulation.33 Clinical studies have been limited, and there is currently insufficient evidence to recommend for or against the adjunctive use of intravenous immunoglobulin in patients with necrotizing fasciitis.34

Conclusion

Necrotizing fasciitis is an uncommon but potentially lethal condition associated with high rates of morbidity and mortality. Immunodeficiency, multiple medical comorbidities, and intravenous drug abuse have been implicated as risk factors. A high index of suspicion is required since a patient’s initially benign clinical condition can rapidly deteriorate with the development of sepsis, multiple organ failure, and death. Early diagnosis coupled with emergent surgical debridement, appropriate broad-spectrum empiric antibiotic treatment, and a multidisciplinary team approach is essential for successful treatment.

References

  1. Anaya DA, Dellinger EP. Necrotizing soft-tissue infection: diagnosis and management [published online ahead of print January 22, 2007]. Clin Infect Dis. 2007; 44(5):705-710.
  2. Ellis Simonsen SM, van Orman ER, Hatch BE, et al. Cellulitis incidence in a defined population. Epidemiol Infect. 2006; 134(2):293-299.
  3. Angoules AG, Kontakis G, Drakoulakis E, Vrentzos G, Granick MS, Giannoudis PV. Necrotising fasciitis of upper and lower limb: a systematic review [published online ahead of print November 28, 2007]. Injury. 2007; (38 Suppl 5):S19-26.
  4. Chen JL, Fullerton KE, Flynn NM. Necrotizing fasciitis associated with injection drug use [published online ahead of print May 23, 2001]. Clin Infect Dis. 2001; 33(1):6-15.
  5. Miller AT, Saadai P, Greenstein A, Divino CM. Postprocedural necrotizing fasciitis: a 10-year retrospective review. Am Surg. 2008; 74(5):405-409.
  6. Nuwayhid ZB, Aronoff DM, Mulla ZD. Blunt trauma as a risk factor for group A streptococcal necrotizing fasciitis [published online ahead of print August 13, 2007]. Ann Epidemiol. 2007; 17(11):878-881.
  7. Wang YS, Wong CH, Tay YK. Staging of necrotizing fasciitis based on the evolving cutaneous features. Int J Dermatol. 2007; 46(10):1036-1041.
  8. Group A Streptococcal (GAS) Disease (strep throat, necrotizing fasciitis, impetigo). Centers for Disease Control and Prevention Web site. http://www.cdc.gov/ncidod/dbmd/diseaseinfo/groupastreptococcal_g.htm. Published April 3, 2008. Accessed December 15, 2010.
  9. Walshaw CF, Deans H. CT findings in necrotising fasciitis—a report of four cases. Clin Radiol. 1996; 51(6):429-432.
  10. Fayad LM, Carrino JA, Fishman EK. Musculoskeletal infection: role of CT in the emergency department. Radiographics. 2007; 27(6):1723-1736.
  11. Wysoki MG, Santora TA, Shah RM, Friedman AC. Necrotizing fasciitis: CT characteristics. Radiology. 1997; 203(3):859-863.
  12. Saldana M, Gupta D, Khandwala M, Weir R, Beigi B. Periorbital necrotizing fasciitis: outcomes using a CT-guided surgical debridement approach. Eur J Ophthalmol. 2010; 20(1):209-214.
  13. Schmid MR, Kossmann T, Duewell S. Differentiation of necrotizing fasciitis and cellulitis using MR imaging. AJR Am J Roentgenol. 1998; 170(3):615-620.
  14. Seok JH, Jee WH, Chun KA, et al. Necrotizing fasciitis versus pyomyositis: discrimination with using MR imaging [published online ahead of print March 3, 2009]. Korean J Radiol. 2009; 10(2):121-128.
  15. Yen ZS, Wang HP, Ma HM, Chen SC, Chen WJ. Ultrasonographic screening of clinically-suspected necrotizing fasciitis. Acad Emerg Med. 2002; 9(12):1448-1451.
  16. Wong CH, Khin LW, Heng KS, Tan KC, Low CO. The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections. Crit Care Med. 2004; 32(7):1535-1541.
  17. Tsai YH, Hsu RW, Huang KC, Huang TJ. Laboratory indicators for early detection and surgical treatment of vibrio necrotizing fasciitis [published online ahead of print March 16, 2010]. Clin Orthop Relat Res. 2010; 468(8):2230-2237.
  18. Holland MJ. Application of the Laboratory Risk Indicator in Necrotising Fasciitis (LRINEC) score to patients in a tropical tertiary referral centre. Anaesth Intensive Care. 2009; 37(4):588-592.
  19. Stamenkovic I, Lew PD. Early recognition of potentially fatal necrotizing fasciitis. The use of frozen-section biopsy. N Engl J Med. 1984; 310(26):1689-1693.
  20. Majeski J, Majeski E. Necrotizing fasciitis: improved survival with early recognition by tissue biopsy and aggressive surgical treatment. South Med J. 1997; 90(11):1065-1068.
  21. Bilton BD, Zibari GB, McMillan RW, Aultman DF, Dunn G, McDonald JC. Aggressive surgical management of necrotizing fasciitis serves to decrease mortality: a retrospective study. Am Surg. 1998; 64(5):397-400.
  22. Wong CH, Chang HC, Pasupathy S, Khin LW, Tan JL, Low CO. Necrotizing fasciitis: clinical presentation, microbiology, and determinants of mortality. J Bone Joint Surg Am. 2003; 85(8):1454-1460.
  23. Wong CH, Yam AK, Tan AB, Song C. Approach to debridement in necrotizing fasciitis [published online ahead of print July 9, 2008]. Am J Surg. 2008; 196(3):e19-24.
  24. 24. Zahar JR, Goveia J, Lesprit P, Brun-Buisson C. Severe soft tissue infections of the extremities in patients admitted to an intensive care unit. Clin Microbiol Infect. 2005; 11(1):79-82.
  25. Graves C, Saffle J, Morris S, Stauffer T, Edelman L. Caloric requirements in patients with necrotizing fasciitis. Burns. 2005; 31(1):55-59.
  26. King MD, Humphrey BJ, Wang YF, Kourbatova EV, Ray SM, Blumberg HM. Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections. Ann Intern Med. 2006; 144(5):309-317.
  27. Coyle EA, Cha R, Rybak MJ. Influences of linezolid, penicillin, and clindamycin, alone and in combination, on streptococcal pyrogenic exotoxin a release. Antimicrob Agents Chemother. 2003; 47(5):1752-1755.
  28. Sarani B, Strong M, Pascual J, Schwab CW. Necrotizing fasciitis: current concepts and review of the literature [published online ahead of print December 12, 2008]. J Am Coll Surg. 2009; 208(2):279-288.
  29. Kaide CG, Khandelwal S. Hyperbaric oxygen: applications in infectious disease. Emerg Med Clin North Am. 2008; 26(2):571-595.
  30. Escobar SJ, Slade JB Jr, Hunt TK, Cianci P. Adjuvant hyperbaric oxygen therapy (HBO2) for treatment of necrotizing fasciitis reduces mortality and amputation rate. Undersea Hyperb Med. 2005; 32(6):437-443.
  31. Jallali N, Withey S, Butler PE. Hyperbaric oxygen as adjuvant therapy in the management of necrotizing fasciitis. Am J Surg. 2005; 189(4):462-466.
  32. Hassan Z, Mullins RF, Friedman BC, et al. Treating necrotizing fasciitis with or without hyperbaric oxygen therapy. Undersea Hyperb Med. 2010; 37(2):115-123.
  33. Takei S, Arora YK, Walker SM. Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens [see comment]. J Clin Invest. 1993; 91(2):602-607.
  34. Darabi K, Abdel-Wahab O, Dzik WH. Current usage of intravenous immune globulin and the rationale behind it: the Massachusetts General Hospital data and a review of the literature. Transfusion. 2006; 46(5):741-753.

Authors

Drs Stoneback and Hak are from Denver Health, University of Colorado, Denver, Colorado.

Drs Stoneback and Hak have no relevant financial relationships to disclose.

Correspondence should be addressed to: David J. Hak, MD, MBA, Denver Health, University of Colorado, 777 Bannock St, MC 0188, Denver, CO 80204 (david.hak@dhha.org).

doi: 10.3928/01477447-20110124-20

10.3928/01477447-20110124-20

Necrotizing fasciitis is a rare, life-threatening soft tissue infection. It can be caused by many different organisms that spread rapidly along the fascial planes. Rapid assessment, emergent surgical debridement, and multidisciplinary support are required. Orthopedic surgeons are often called to evaluate, diagnose, and treat patients with soft tissue infections of the extremities. Although uncommon, it is critical to promptly identify a suspected case of necrotizing fasciitis from less serious soft tissue infections such as cellulitis or abscesses.

The incidence of necrotizing fasciitis has been reported to be between 500 and 1500 cases per year in the United States.1 A previous insurance claim database study cited an incidence of 0.04 per 1000 person-years.2 Mortality rates have been reported to range from 8% to 65%, averaging 21.9%.3

Trauma, diabetes, intravenous drug abuse, immunodeficiency, chronic disease, minor abrasions, lacerations, insect bites, chronic ulcers, burns, and surgical wound infections have all been implicated as risk factors in the development of necrotizing fasciitis.4-6 The development of necrotizing fasciitis is typically associated with an injury to the involved area. Trauma, either penetrating or blunt, has been shown to be a risk factor for the development of necrotizing fasciitis. While a traumatic mechanism is often present, the inciting event can be innocuous or remote.

Necrotizing fasciitis typically begins as an area of inflamed skin with or without history of skin trauma. In the early stages it can be difficult, but extremely important, to differentiate more common skin infections such as cellulitis or soft tissue abscess from the more severe diagnosis of necrotizing fasciitis. The initial presentation may appear innocuous, with stable vital signs and benign skin manifestations. The patient’s condition may then rapidly deteriorate. The benign skin findings are replaced with a rapidly progressing area of skin induration and advancing erythema, followed by the development of overlying blisters and skin necrosis. This is accompanied by a rapid change in the patient’s vital signs, with fever, tachycardia, hypotension, and signs of multiple organ failure, often requiring admission to the intensive care unit.

Wang et al7 proposed 3 stages of progressive skin examination findings that occur with necrotizing fasciitis. Stage 1 (early) begins with tenderness to palpation (extending beyond the apparent area of skin involvement), erythema, swelling, and warmth to palpation. The transition to stage 2 (intermediate) is marked by serous-filled blister or bullae formation along with skin fluctuance and induration. Stage 3 (late) is heralded by hemorrhagic bullae, skin anesthesia, crepitus, and skin necrosis with dusky discoloration progressing to gangrene.

The superficial fascia is the principal site of the pathologic process (Figure 1). Bacteria inoculate this normally sterile location either through penetrating injury or by hematogenous spread. Bacteria then rapidly replicate, synthesizing enzymes and toxins that facilitate their spread through the superficial fascial planes. In conjunction with the rapid microbial proliferation, angiothrombotic microbial invasion and liquifactive necrosis of the superficial fascia occurs. Destruction of the superficial fascial layer along with the adjacent nutrient vessels to the skin leads to progressive overlying skin ischemia and ultimately full-thickness skin loss.

Numerous bacteria have been implicated in necrotizing fasciitis. A recent systematic review reported that the 3 most commonly cultured organisms in necrotizing fasciitis were Staphylococcus aureus, group A Streptococcus, and Streptococcus viridans.3 A wide range of other organisms, including fungal species, have been cultured from the wounds of patients with necrotizing fasciitis (Table 1).3 While most necrotizing fasciitis infections are polymicrobial, invasive group A Streptococcus is one of the most prevalent organisms. According to a 2008 Centers for Disease Control report, approximately 9000 to 11,500 cases of invasive group A Streptococcus disease occur each year in the United States, resulting…

Early diagnosis combined with emergent surgical debridement, appropriate broad-spectrum empiric antibiotic treatment, and a multidisciplinary team approach is essential for successful treatment of necrotizing fasciitis.
Cover illustration © Lisa Clark
Cover illustration © Lisa Clark

Necrotizing fasciitis is a rare, life-threatening soft tissue infection. It can be caused by many different organisms that spread rapidly along the fascial planes. Rapid assessment, emergent surgical debridement, and multidisciplinary support are required. Orthopedic surgeons are often called to evaluate, diagnose, and treat patients with soft tissue infections of the extremities. Although uncommon, it is critical to promptly identify a suspected case of necrotizing fasciitis from less serious soft tissue infections such as cellulitis or abscesses.

Epidemiology and Risk Factors

The incidence of necrotizing fasciitis has been reported to be between 500 and 1500 cases per year in the United States.1 A previous insurance claim database study cited an incidence of 0.04 per 1000 person-years.2 Mortality rates have been reported to range from 8% to 65%, averaging 21.9%.3

Trauma, diabetes, intravenous drug abuse, immunodeficiency, chronic disease, minor abrasions, lacerations, insect bites, chronic ulcers, burns, and surgical wound infections have all been implicated as risk factors in the development of necrotizing fasciitis.4-6 The development of necrotizing fasciitis is typically associated with an injury to the involved area. Trauma, either penetrating or blunt, has been shown to be a risk factor for the development of necrotizing fasciitis. While a traumatic mechanism is often present, the inciting event can be innocuous or remote.

Clinical Presentation and Pathophysiology

Necrotizing fasciitis typically begins as an area of inflamed skin with or without history of skin trauma. In the early stages it can be difficult, but extremely important, to differentiate more common skin infections such as cellulitis or soft tissue abscess from the more severe diagnosis of necrotizing fasciitis. The initial presentation may appear innocuous, with stable vital signs and benign skin manifestations. The patient’s condition may then rapidly deteriorate. The benign skin findings are replaced with a rapidly progressing area of skin induration and advancing erythema, followed by the development of overlying blisters and skin necrosis. This is accompanied by a rapid change in the patient’s vital signs, with fever, tachycardia, hypotension, and signs of multiple organ failure, often requiring admission to the intensive care unit.

Wang et al7 proposed 3 stages of progressive skin examination findings that occur with necrotizing fasciitis. Stage 1 (early) begins with tenderness to palpation (extending beyond the apparent area of skin involvement), erythema, swelling, and warmth to palpation. The transition to stage 2 (intermediate) is marked by serous-filled blister or bullae formation along with skin fluctuance and induration. Stage 3 (late) is heralded by hemorrhagic bullae, skin anesthesia, crepitus, and skin necrosis with dusky discoloration progressing to gangrene.

The superficial fascia is the principal site of the pathologic process (Figure 1). Bacteria inoculate this normally sterile location either through penetrating injury or by hematogenous spread. Bacteria then rapidly replicate, synthesizing enzymes and toxins that facilitate their spread through the superficial fascial planes. In conjunction with the rapid microbial proliferation, angiothrombotic microbial invasion and liquifactive necrosis of the superficial fascia occurs. Destruction of the superficial fascial layer along with the adjacent nutrient vessels to the skin leads to progressive overlying skin ischemia and ultimately full-thickness skin loss.

Figure 1: Schematic representation of necrotizing fasciitis location within the soft tissues
Figure 1: Schematic representation of necrotizing fasciitis location within the soft tissues. Rapid bacterial replication along superficial and deep fascial planes leads to liquifactive necrosis and ultimately full-thickness skin loss.

Microbiology

Numerous bacteria have been implicated in necrotizing fasciitis. A recent systematic review reported that the 3 most commonly cultured organisms in necrotizing fasciitis were Staphylococcus aureus, group A Streptococcus, and Streptococcus viridans.3 A wide range of other organisms, including fungal species, have been cultured from the wounds of patients with necrotizing fasciitis (Table 1).3 While most necrotizing fasciitis infections are polymicrobial, invasive group A Streptococcus is one of the most prevalent organisms. According to a 2008 Centers for Disease Control report, approximately 9000 to 11,500 cases of invasive group A Streptococcus disease occur each year in the United States, resulting in 1000 to 1800 deaths annually.8 Necrotizing fasciitis comprises approximately 6% to 7% of these invasive cases.

Table 1: Cultured  Microorganisms in Necrotizing Fasciitis Cases

Nuwayhid et al6 found group A Streptococcus necrotizing fasciitis cases were approximately 6 times more likely to have a recent history of blunt trauma than adjusted controls. This study highlights the importance of the evaluating physician having a high level of suspicion for necrotizing fasciitis even in the absence of an obvious site of entry for bacteria.

Diagnostic Tests

The diagnosis of necrotizing fasciitis is primarily a clinical one. However, plain radiographs, computed tomography (CT), magnetic resonance imaging (MRI), and laboratory data can provide useful supplemental information and raise the suspicion for necrotizing fasciitis when the diagnosis is uncertain. These adjunctive diagnostic tests can also provide prognostic information. Because of the need for prompt initiation of treatment, adjunctive diagnostic tests should not impede the timing of surgical exploration and debridement. Necrotizing fasciitis is a clinical diagnosis where only emergent surgical debridement and appropriate antibiotic treatment can prevent progression and death.

Plain Radiography

A common misconception exists that subcutaneous gas is a common plain radiographic finding in necrotizing fasciitis. However, this finding is relatively infrequent, with subcutaneous gas present in only 13% of necrotizing fasciitis cases.3 Additionally, subcutaneous gas may not be present in earlier stages of the disease process and only become manifest as the patient’s condition deteriorates. While plain radiographs are not mandatory for the treatment of soft tissue infections, they can provide useful information such as retained foreign bodies like broken hypodermic needles that the surgeon may encounter during debridement of the infected wound.

Computed Tomography

Computed tomography has a higher sensitivity than plain radiography in identifying early soft tissue changes characteristic of necrotizing fasciitis.9,10 Findings of necrotizing fasciitis found on CT are fat stranding, along with fluid and gas collections that dissect along fascial planes. Additionally, fascial thickening and nonenhancing fascia on contrast CT suggests fascial necrosis.10 While CT has a higher sensitivity than plain radiographs in detecting soft tissue manifestations of necrotizing fasciitis, it takes valuable time and should not impede emergent surgical debridement. Furthermore, gas formation is not found in all cases of necrotizing fasciitis, and its absence on CT does not exclude the diagnosis of necrotizing fasciitis.11 While CT may play a role in planning surgical debridement in craniofacial areas, its routine use is not recommended for the diagnosis of necrotizing fasciitis of the extremities.12

Magnetic Resonance Imaging

Magnetic resonance imaging is the imaging modality of choice for soft tissue conditions. Magnetic resonance imaging can differentiate cases of severe cellulitis and pyomyositis from necrotizing fasciitis and identify underlying pathology such as abscess that can be the root cause of the soft tissue infection.13,14 Subcutaneous tissue low-signal intensity on T1-weighted images combined with high-signal intensity of the subcutaneous tissues and involvement of the deep fascia on T2-weighted images confirm the diagnosis of necrotizing fasciitis. Schmid et al13 found MRI to be 100% sensitive and 86% specific and have a diagnostic accuracy of 94% for necrotizing fasciitis when correlated with intraoperative findings. However, the authors noted that surgical findings found MRI overestimated the extent of infection.13 Again, it should be emphasized that MRI or other adjunctive tests should not delay emergent surgical exploration and debridement in cases of suspected necrotizing fasciitis.

Ultrasound

Recently there has been increasing interest by emergency department physicians in the diagnostic use of ultrasound. Ultrasound can be rapidly preformed to help differentiate simple cellulitis from cases of underlying abscess and has shown some usefulness in the diagnosis of necrotizing fasciitis.15 In a prospective observational study of 62 patients with clinically suspected necrotizing fasciitis, ultrasound revealed a sensitivity of 88.2%, specificity of 93.3%, positive predictive value of 95.4%, negative predictive value of 95.4%, and diagnostic accuracy of 91.9%.15 The authors used the findings of diffuse subcutaneous thickening accompanied with fluid accumulation of >4 mm in depth along the deep fascial layer to confirm the diagnosis of necrotizing fasciitis.15 While ultrasound may have some diagnostic usefulness in the emergency department, its use requires further study and a highly skilled operator limiting its practical use.

Laboratory Analysis

In the early stages, patients can have normal vital signs and a relatively benign clinical examination. Ancillary diagnostic imaging such as CT and MRI can cause significant time delays and are not always accessible. In an effort to provide readily accessible ancillary diagnostic information in patients with suspected necrotizing fasciitis, Wong et al16 analyzed several laboratory parameters in patients with documented necrotizing fasciitis. From this data, the authors developed the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) Score. The LRINEC Score uses basic laboratory parameters found in routine serum blood analysis. The LRINEC Score is based on serum C-reactive protein, total white blood cell count, hemoglobin, sodium, creatinine, and glucose levels. Cutoff values for each parameter allow a total score to be calculated (Table 2).16 A LRINEC Score of >6 was found to have a positive predictive value of 92% and a negative predictive value of 96%.16 While the score has been validated by the authors with an external cohort, others have questioned the scores reliability and clinical usefulness.17,18

Table 2: The Laboratory Risk Indicator for Necrotizing Fasciitis Scoring System

Frozen Section

Fascial biopsy with frozen section has been shown to identify patients with necrotizing fasciitis accurately and quickly.19,20 Early diagnosis by fascial biopsy frozen section can be performed at the bedside under local anesthetic using 1% lidocaine.20 After obtaining local analgesia, a full thickness 2×1-cm elliptical biopsy of the skin, deep soft tissue, and fascia are taken from the suspected area of infection as well as from the leading edge of any erythema, induration, or necrosis.20 Tissue biopsies are then immediately evaluated by frozen section pathologic analysis, gram stain, and culture.

Authors that advocate the use of frozen tissue biopsy cite that early detection of necrotizing fasciitis decreases morbidity and mortality rates by facilitating early diagnosis, leading to earlier surgical intervention and appropriate antibiotic treatment.19,20

Treatment

Emergent surgical exploration and debridement is the critical element in necrotizing fasciitis treatment, followed by appropriate antibiotic and supportive therapy. Additionally, a multidisciplinary team approach with coordination between the surgeon, intensivist, dietician, infectious disease specialist, and plastic surgeon is integral to decreasing morbidity and mortality. Other therapies such as intravenous immune globulin and hyperbaric oxygen therapy may have some usefulness as adjunctive treatment in patients with necrotizing fasciitis but remain controversial.

Surgical Debridement

Multiple authors have shown that early and thorough surgical debridement decreases mortality in patients with necrotizing fasciitis.21,22 Bilton et al21 found patients who had early surgical debridement had decreased mortality rates when compared to patients with delayed debridement. Wong et al22 found a nine-fold increase in mortality rate with a delay in surgical debridement >24 hours from hospital admission.

Surgical debridement requires a meticulous technique and must be aggressive to halt progression of infection. Wong et al23 advocated 4 steps in their approach to surgical debridement of patients with necrotizing fasciitis, which include confirming the diagnosis and isolation of the causative organism, defining the extent of fasciitis, surgical excision of involved fascia, and postexcision wound care. Diagnosis is confirmed on surgical exploration by the presence of grayish necrotic deep fascia and abnormally nonadherent subcutaneous tissue that easily dissects from the deep fascia with blunt finger traction coupled with foul-smelling “dishwater” purulence.22,23 Frozen section histological analysis may also be used if the diagnosis is in question but is not required. Cultures should be obtained during the initial surgical debridement to tailor specific antibiotic management.

In the awake and alert patient, the extent of fasciitis can initially be clinically determined by the extent of tenderness to palpation, and then substantiated through surgical dissection until normal tissue is encountered.23 To halt the spread of the infection, complete surgical excision requires removal of all infected and necrotic tissue including a 5- to 10-mm margin of healthy fascia (Figure 2).23 Postexcision wound care starts with meticulous hemostasis, as many of these patients are coagulopathic.23 Nonadherent compressive dressings should then be applied, followed by repeat wound inspection in <24 hours.23

Figure 2: Necrotizing fasciitis
Figure 2: Intraoperative photograph of a patient with necrotizing fasciitis after initial debridement. Gray “dishwater pus” and liquifactive necrosis tracking along fascial planes was encountered. After multiple serial debridements and wound vacuum placement, partial delayed primary closure and split-thickness skin grafting was needed for wound closure.

In the immediate postoperative period, the patient should be closely monitored for signs of continuing advancement of infection. The patient should be scheduled to return to the operating room in 24 hours for an initial second look, with multiple surgical debridements being the norm rather than the exception. Angoules et al3 reported that patients required an average of 3 surgical debridements, with 22.3% of patients requiring amputation for failure of multiple surgical debridements to control the infection. After adequate serial surgical debridement, 48.4% required a skin graft and 4.5% required rotational flap coverage.3

Supportive Care

Necrotizing fasciitis patients often become hemodynamically unstable and coagulopathic and require ventilator support, making early involvement of intensivists central to patient management. One study reported an average intensive care unit stay of 10.6 days.24 The average inpatient hospitalization is 24.9 days.3 Sepsis, serial surgical debridement, and frequent massive surgical wounds that require extensive reconstruction make nutritional support of paramount importance. One study found 94% of necrotizing fasciitis patients required total enteral nutrition and/or total parenteral nutrition for an average of 24 days.25

Antibiotic Therapy

While surgical debridement is the cornerstone of necrotizing fasciitis management, appropriate antibiotic selection can treat sepsis and halt further bacterial spread. Once the diagnosis of necrotizing fasciitis is suspected, proper empiric antibiotic treatment should be started immediately, followed by culture-specific tailoring of antibiotics with infectious disease specialist involvement.

Broad-spectrum antibiotic coverage should initially be selected to provide treatment for gram-positive, gram-negative, and anaerobic organisms. There is increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA),26 and appropriate empiric coverage should be initiated until MRSA has been ruled out. An acceptable empiric antibiotic regimen includes linezolid, which covers MRSA with the additional benefit of inhibiting invasive group A Streptococcus virulence proteins similar to clindamycin.27 In addition to linezolid, piperacillin/tazobcatam or meropenem should be administered for gram-positive/negative and anaerobic coverage until culture-specific results and sensitivities are available.

No general consensus exists on the necessary duration of antibiotic therapy. Some authors have recommended continuing antibiotic therapy until no additional surgical debridements are required and the patient no longer exhibits signs of systemic inflammation.28

Antibiotic therapy alone has been shown to have high mortality rates due to reduced antibiotic delivery in poorly vascularized/necrotic tissue at the infection site. Surgical debridement is required to decrease necrotic tissue load and provide a viable tissue bed amenable to the delivery of antibiotics.

Adjunctive Therapy

Hyperbaric oxygen therapy has been studied as an adjunctive treatment modality for patients with necrotizing fasciitis. The increased partial pressure of oxygen may enhance leukocyte-killing activity, suppress bacterial growth, enhance antibiotic effects, and improve tissue repair.29 Some studies have found hyperbaric oxygen therapy to be beneficial in reducing mortality and amputation rate in patients with necrotizing fasciitis.30 While some retrospective studies have found benefit, others have not, and multicenter prospective randomized trials are needed.31,32

Intravenous immunoglobulin is a concentrated pooled product derived from human donors primarily containing immunoglobulin G isotopes. Recommendation for its use is based on its binding of several staphylococcal superantigens, thereby preventing peripheral blood T-cell stimulation.33 Clinical studies have been limited, and there is currently insufficient evidence to recommend for or against the adjunctive use of intravenous immunoglobulin in patients with necrotizing fasciitis.34

Conclusion

Necrotizing fasciitis is an uncommon but potentially lethal condition associated with high rates of morbidity and mortality. Immunodeficiency, multiple medical comorbidities, and intravenous drug abuse have been implicated as risk factors. A high index of suspicion is required since a patient’s initially benign clinical condition can rapidly deteriorate with the development of sepsis, multiple organ failure, and death. Early diagnosis coupled with emergent surgical debridement, appropriate broad-spectrum empiric antibiotic treatment, and a multidisciplinary team approach is essential for successful treatment.

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Authors

Drs Stoneback and Hak are from Denver Health, University of Colorado, Denver, Colorado.

Drs Stoneback and Hak have no relevant financial relationships to disclose.

Correspondence should be addressed to: David J. Hak, MD, MBA, Denver Health, University of Colorado, 777 Bannock St, MC 0188, Denver, CO 80204 (david.hak@dhha.org).

doi: 10.3928/01477447-20110124-20

This Article