Necrotizing Fasciitis

Necrotising fasciitis is a rapidly progressive, life-threatening soft tissue infection in which the fascia and subcutaneous tissue necrose while the overlying skin (at first) and the underlying muscle are relatively spared. It is a surgical emergency, and early recognition and aggressive debridement are the only interventions that improve survival. [1]

What it is. A necrotising soft tissue infection (NSTI) of the fascial planes. The infection spreads along the relatively avascular fascia, thrombosing the perforating vessels as it goes, and the skin necrosis is secondary. Unlike cellulitis, it travels in the deep fascial planes, which is why the surface examination is misleadingly benign. [2]

How common. Incidence is 0.4-0.9 per 100,000 per year [3] and has risen 2-4 fold over the past 20 years. Men outnumber women 2-3:1, and the age distribution is bimodal, peaking in neonates and in adults over 50. Overall mortality is 20-40%; the figures by timing of treatment and by organism are in the Prognosis section.

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Who gets it. Most cases occur in diabetics and the immunocompromised, though Type II GAS disease can occur in healthy adults:

• Diabetes mellitus - the major risk factor: impaired immunity and vascular disease
• Immunocompromise - HIV, chemotherapy, steroids, transplantation
• Alcohol excess - liver disease, malnutrition, poor wound care
• Breaks in the skin - surgical wounds, injection sites, trauma
• Extremes of age - the very young and the elderly
• Tissue ischaemia - peripheral vascular disease, vasculitis, pressure sores
• Intravenous drug use - contaminated needles, injection-site infection
• Chronic illness - renal failure, malignancy, malnutrition

History. Joseph Jones, a Confederate surgeon, first described the disease in 1871 during the American Civil War, and Wilson coined the term "necrotising fasciitis" in 1952. It was previously known as "hospital gangrene" and "streptococcal gangrene", and it remains associated with military trauma, natural disasters and epidemics of intravenous drug use.

Why it spreads along the fascia. The fascia is relatively avascular, so few immune cells reach the infection. Bacterial enzymes (hyaluronidase, lipases, collagenases) digest the connective tissue, and thrombosis of the perforating vessels starves the skin above, which is the ischaemia behind pain out of proportion to what is visible. Toxin production drives the systemic toxicity and shock. Because necrosis advances along the plane so quickly, a deceptively small area of involvement at presentation may become extensive within hours if it is not debrided.

Type I, polymicrobial. Aerobes and anaerobes infect synergistically: the aerobes consume oxygen, the anaerobes thrive in the hypoxia that results and produce gas (crepitus), and enzymes from several organisms accelerate the destruction. It typically arises in compromised tissue: diabetes, peripheral vascular disease, a surgical wound.

Type II, monomicrobial group A Streptococcus. GAS carries several virulence factors:

• Streptolysin O and S - pore-forming toxins that lyse cells
• Streptococcal pyrogenic exotoxins (SPE-A, B, C) - superantigens that trigger massive cytokine release
• M-protein - antiphagocytic, promotes adherence
• Streptokinase - activates plasminogen and promotes spread

Streptococcal toxic shock syndrome (STSS). A superantigen activates 20-30% of T-cells, against 0.01% in a normal antigen response, and the cytokine storm that follows is STSS.

Type III, clostridial gas gangrene. Clostridium perfringens produces alpha-toxin, a lecithinase that lyses cell membranes and causes massive tissue necrosis. Gas (CO2, H2) forms rapidly and gives the crepitus, and the course is so fast that it can be fatal within hours.

Vibrio vulnificus. A Gram-negative rod of warm seawater that enters through minor wounds while handling seafood or swimming, and produces cytolysins and proteases. It is particularly severe in patients with liver disease or haemochromatosis, iron overload feeding bacterial growth, and septicaemic infection carries a mortality of 50-60%.

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The two common types differ in who they affect, how they present and how they are treated:

Early necrotising fasciitis mimics cellulitis. The diagnosis lies in the discordance between what the patient reports, which is severe, and what you can see, which is relatively little.

History

Pain out of proportion is the cardinal feature. The pain seems excessive for the appearance, extends beyond the visible erythema and responds poorly to analgesia. It may paradoxically improve as the nerves themselves necrose, which is an ominous sign rather than a reassuring one.

Rapid progression. "It wasn't like this four hours ago": erythema spreading despite antibiotics, blisters appearing over hours.

Systemic symptoms. Fever, rigors and sweating; nausea, vomiting and diarrhoea; confusion or altered consciousness; and the patient who tells you they feel they are going to die.

Precipitants. Ask about:

• Minor trauma - a scratch, insect bite or abrasion
• Recent surgery - abdominal, perineal or orthopaedic
• Injection - intravenous drug use or an intramuscular injection
• Perianal abscess or pilonidal disease
• Childbirth or episiotomy
• Varicella in children
• NSAID use, which may mask the early symptoms (below)

Physical Examination

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Hard signs are 100% specific. Any one of them mandates immediate surgery:

• Crepitus - gas in the tissues, felt as a crackling, best at the periphery of the infection; may be absent in Type II (GAS)
• Skin necrosis - dusky, purplish, non-blanching skin, with loss of sensation as the cutaneous nerves die
• Bullae - haemorrhagic bullae are the more ominous, serous ones still concerning; both mean the dermis has separated from the epidermis through vascular thrombosis
• Dishwater discharge - thin, grey, foul-smelling fluid, "washing-up water", seen where the skin breaks down spontaneously or on aspiration
• Visible fascial necrosis - grey, non-viable fascia seen through a break in the skin

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Soft signs demand high clinical suspicion, and several together should prompt surgical exploration:

• Pain out of proportion, as in the history, with pain extending beyond the erythema
• Rapidly spreading erythema - mark the border with a pen and look again in 1-2 hours; spread despite intravenous antibiotics
• Systemic toxicity - heart rate above 100, systolic pressure below 90, temperature above 38.5°C or below 36°C, altered mental state
• Failure to respond to antibiotics - no improvement, or worsening, after 24-48 hours of appropriate intravenous antibiotics; this should prompt urgent surgical review
• Skin changes beyond cellulitis - woody induration, oedema beyond the erythema, vesicles (early bullae)

Where it strikes. The common sites, and what each brings with it:

• Lower limb - the most common site overall, often in diabetics with foot ulcers; can track to the pelvis along the fascial planes
• Upper limb - often after intravenous drug use or minor trauma; can spread rapidly to the chest wall and may present as compartment syndrome
• Perineum (Fournier's gangrene) - male predominance 10:1; from a perianal abscess, urethral instrumentation or a scrotal abscess; can spread to the abdominal wall and thighs; mortality 40-50%
• Abdominal wall - after surgery (especially bowel surgery) or trauma; may track into the retroperitoneum
• Head and neck (cervical NF) - from dental infection (progression of Ludwig's angina) or a pharyngeal abscess; airway compromise is the primary threat, and it can spread to the mediastinum

Differential Diagnosis

Laboratory Investigations

LRINEC. The Laboratory Risk Indicator for NECrotizing fasciitis scores six routine blood results:

The total is read in three bands:

• Below 6 - low risk (positive predictive value below 50%)
• 6-7 - intermediate risk; keep clinical vigilance high
• 8 or more - high risk (positive predictive value 75% or more); strongly consider surgery

The limitation. LRINEC was developed retrospectively and its sensitivity is only 60-80%, so a normal score does not exclude necrotising fasciitis. Clinical judgement remains paramount. [4]

Other blood tests. Each answers a different question:

• Blood cultures - positive in 20-50%, and identify the organism
• Lactate - raised lactate means tissue hypoperfusion and a worse prognosis
• Creatine kinase - raised if there is myonecrosis, which carries a worse prognosis
• Procalcitonin - may help separate bacterial infection from other causes
• Coagulation - PT/INR, APTT, fibrinogen and D-dimer, because DIC is common
• Arterial blood gas - a metabolic acidosis indicates severe sepsis

Imaging

Plain radiograph. A quick screen for gas. Gas tracking along the fascial planes is pathognomonic but present in only 25-50%: more often in Type I (polymicrobial) and Type III (clostridial), and it may be absent in Type II (GAS). Sensitivity is low, and the absence of gas does not exclude the diagnosis.

CT. The most useful modality if time permits. It is quick to acquire, shows the extent of disease for surgical planning, and picks up gas that a radiograph misses. The findings:

• Gas tracking along the fascial planes (specific, but not always present)
• Fascial thickening and enhancement
• Fluid collections along the fascia
• Non-enhancement of the fascia, which indicates necrosis
• The extent of soft tissue involvement

A normal CT does not exclude necrotising fasciitis.

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MRI. The most sensitive modality, and rarely indicated acutely. It takes 30-60 minutes, may not be available after hours, and is reserved for the equivocal case where there is time. The findings:

• T2 hyperintensity along the fascia (oedema)
• Fascial thickening greater than 3mm
• Non-enhancement with gadolinium (necrosis)
• Fluid tracking along the fascial planes

Ultrasound. A bedside tool of limited use: available at the bedside, no radiation, and it can guide aspiration, but it is operator dependent, of limited sensitivity, and cannot assess the deep fascial planes. The findings:

• Subcutaneous thickening
• Fascial thickening greater than 4mm
• Fluid along the fascial planes
• Hyperechoic foci with dirty shadowing (gas)

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The Finger Test (Bedside Diagnosis)

When. Clinical suspicion is high but the diagnosis is uncertain. It is done under local anaesthesia at the bedside or in theatre.

How. Make a 2cm incision through skin and subcutaneous tissue down to the fascia, and look for:

1. Lack of bleeding, because the vessels are thrombosed
2. "Dishwater" grey pus, which is pathognomonic
3. Necrotic fascia - grey and stringy, separating easily on finger dissection
4. A positive finger test - the finger passes along the fascial plane with no resistance

If positive, proceed immediately to extensive debridement.

Algorithm

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Three pillars, run at once. Resuscitation (fluids, vasopressors, intensive care), debridement (early, extensive and repeated) and antibiotics (empirical and broad-spectrum, with clindamycin for toxin inhibition). None waits for the others.

Surgery is both diagnostic and therapeutic, and it is the definitive treatment: the infection cannot be controlled with antibiotics alone, and no amount of them substitutes for adequate debridement of necrotic tissue.

Debridement TechniqueSecond-Look SurgeryAmputationWound Reconstruction

Timing. Operate as soon as the patient is resuscitated enough for anaesthesia, within hours rather than days, and do not wait for imaging when the clinical diagnosis is clear. Delay to debridement is the strongest modifiable predictor of death: in McHenry's series the mean time from admission to surgery was 90 hours in non-survivors against 25 hours in survivors, and Kobayashi found that delay beyond 12 hours markedly increased the number of debridements, septic shock and acute kidney injury.

Principles. The debridement is aggressive and extensive: all necrotic tissue is removed, and since healthy tissue bleeds, you debride until you see bleeding edges. Add fasciotomies if compartment syndrome is suspected.

Step by step.

1. Incise longitudinally over the area of maximal involvement, extending beyond the visible erythema into healthy tissue
2. Assess the fascia with the finger test: necrotic fascia is grey and stringy and separates from the underlying muscle with finger dissection, while healthy fascia is glistening white and adherent
3. Debride the fascia, excising everything that offers no resistance until it bleeds and is adherent, extending the incisions to follow the necrosis
4. Assess the muscle: healthy muscle is pink, contracts to stimulation and bleeds when cut; necrotic muscle is dull, non-contractile and does not bleed, and is debrided (myonecrosis means a worse prognosis)
5. Assess the skin: skin that is viable now may necrose over the next 24-48 hours, so preserve what is viable (it can be excised at the re-look) and excise only what is overtly dead
6. Leave the wound open, under saline-soaked dressings or NPWT, and plan the return to theatre

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When. Return to theatre at 24-48 hours, or earlier if the patient deteriorates.

Why. To check that the first debridement was adequate, to excise any tissue that has demarcated since, to reassess the viability of muscle and skin, and to repeat until all necrosis has been excised and the patient is improving.

When to stop. No further necrotic tissue, a healthy bleeding wound bed, viable granulation tissue forming, and a patient who is improving systemically.

How many. Most patients need 2-4 debridements, and some need more, especially in Fournier's gangrene. Underestimating the need for a re-look is a common error.

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Indications for primary amputation.

• Life-threatening sepsis refractory to debridement
• Extensive circumferential involvement of the limb
• Associated vascular injury that precludes limb salvage
• Myonecrosis involving entire compartments of the limb

The decision. It may take several debridements before the picture is clear, so involve senior colleagues early and raise the possibility with the patient and family early if amputation looks likely.

The level. Proximal to all necrotic tissue, with healthy bleeding muscle at the amputation site. Leave the stump open for monitoring; it may need revision if infection persists.

Amputation Decision

Amputation is a life-saving procedure in fulminant NF. Delay in amputation to "try to save the limb" can result in patient death. The principle is "life over limb". Early discussion with family about this possibility is essential.

When. Only once the infection is controlled: all necrotic tissue removed, a healthy granulating bed, and a systemically stable patient.

Options.

• Secondary intention - for small wounds, with NPWT to promote granulation
• Split-thickness skin graft - the most common closure, once healthy granulation is present; meshed for large defects
• Dermal substitutes (Integra, Matriderm) - for large defects with exposed critical structures, as a two-stage procedure with a split-thickness graft
• Flaps - local, regional or free, for defects with exposed bone, tendon or vessels; these need plastic surgery input
• Perineal reconstruction - Fournier's gangrene often needs complex reconstruction: scrotal or penile skin grafts, testicular transposition, gracilis flaps for perineal defects

Complications

Early. The complications of the acute illness:

• Septic shock - multi-organ failure, DIC, death
• ARDS
• Acute kidney injury - from sepsis and rhabdomyolysis
• Limb loss - amputation is required in 15-20%
• Exsanguinating haemorrhage - from eroded vessels
• Toxic shock syndrome - especially in Type II (GAS)

Late. The survivor is left with:

• Chronic wounds - prolonged healing, skin grafts
• Scarring and contractures - which may limit function
• Chronic pain - phantom limb pain after amputation
• Psychological morbidity - PTSD, depression, body image
• Functional impairment - particularly after amputation

Prognostic Factors

Survival Outcomes

Mortality. In the pre-antibiotic era it was 70-80%. With modern treatment it is 20-40% overall, falling to 10-25% with early recognition and aggressive surgery, and 50-70% when treatment is delayed.

What improves survival.

• Recognition within 24 hours of the onset of symptoms
• Surgery within 6-8 hours of presentation
• Adequate debridement, with multiple re-looks
• Intensive care with multi-organ support
• Clindamycin in the antibiotic regimen
• IVIG in streptococcal toxic shock

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Global Epidemiology

Necrotising fasciitis is uncommon but its incidence appears to be rising worldwide. Reported population incidence is approximately 0.4-1.0 per 100,000 per year in high-income countries, with overall mortality of 20-40% even in modern series. The McHenry single-centre series reported 29% mortality and identified delay to debridement as the dominant determinant of death PMID 7748037, while the Stevens & Bryant NEJM review summarises the global microbiology and management of necrotising soft-tissue infections PMID 29211672.

Guideline Comparison

There is broad international consensus on the core principles - early surgical debridement, broad-spectrum antibiotics with clindamycin for toxin suppression, and aggressive resuscitation - although no high-quality randomised data exist for the surgical strategy itself.

Access, Equity & Wound-Healing Considerations

Globally, determinants of NF outcome extend beyond the pathogen and the operating theatre:

• Rural and remote access: In many countries patients first present to facilities without on-site ICU or surgical capability and require urgent transfer to a definitive centre; transfer time is itself a contributor to debridement delay and mortality.
• Disadvantaged and Indigenous populations: Worldwide, groups with higher rates of diabetes, chronic kidney disease and skin infection (including Indigenous populations) carry elevated NF risk; renal dosing of antibiotics, family involvement and culturally safe wound care should inform management.
• Smoking cessation: Smoking impairs graft take and wound healing, so supporting cessation (behavioural support plus nicotine replacement therapy) is important for reconstructive success in survivors.

1. Sartelli M, Guirao X, Hardcastle TC, et al. 2018 WSES/SIS-E consensus conference: recommendations for the management of skin and soft-tissue infections. World J Emerg Surg. 2018;13:58. doi:10.1186/s13017-018-0219-9

2. Stevens DL, Bryant AE. Necrotizing Soft-Tissue Infections. N Engl J Med. 2017;377(23):2253-2265. doi:10.1056/NEJMra1600673

3. Arif N, Yousfi S, Vinnard C. Deaths from necrotizing fasciitis in the United States, 2003-2013. Epidemiol Infect. 2016;144(6):1338-1344. doi:10.1017/S0950268815002745

4. 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. doi:10.1097/01.ccm.0000129486.35458.7d

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8. Kobayashi L, Konstantinidis A, Shackelford S, et al. Necrotizing soft tissue infections: delayed surgical treatment is associated with increased number of surgical debridements and morbidity. J Trauma. 2011;71(5):1400-1405. doi:10.1097/TA.0b013e31820db8fd

9. Mascini EM, Jansze M, Schouls LM, Verhoef J, Van Dijk H. Penicillin and clindamycin differentially inhibit the production of pyrogenic exotoxins A and B by group A streptococci. Int J Antimicrob Agents. 2001;18(4):395-398. doi:10.1016/s0924-8579(01)00413-7

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