Necrotising fasciitis

Synonyms: necrotising soft tissue infection, Fournier's gangrene (necrotising fasciitis of scrotum or vulva), Ludwig's angina (necrotising fasciitis of submandibular space)

What is necrotising fasciitis?

Necrotising fasciitis (NF) or flesh-eating disease is an uncommon but life-threatening infection.¹ It is defined as necrotising infection involving any layer of the deep soft tissue compartment (dermis, subcutaneous tissue, fascia or muscle).

Organisms spread from the subcutaneous tissue along the superficial and deep fascial planes. Muscle is usually spared; however, myonecrosis can occur due to compartment syndrome. Types of bacteria which may be involved in necrotising infections have been classified into:

• Type 1 - polymicrobial infection with aerobic and anaerobic bacteria: usually in patients with immunocompromise or chronic disease.

• Type 2 - Group A streptococcus (GAS): occurs in any age group and in otherwise healthy people; occasionally accompanied by staphylococcal infection.

• Type 3 - Gram-negative monomicrobial infection:

  • This includes marine organisms such as Vibrio spp. and Aeromonas hydrophila, which can occur following seawater contamination of wounds, injuries involving fish fins or stings, and raw seafood consumption - particularly in patients with chronic liver disease.

  • These marine infections are particularly virulent and can be fatal within 48 hours.

• Type 4 - marine and fungal infection:

  • Zygomycetes after traumatic wounds or burns.

  • Candidal infection in immunocompromised patients.

  • Can be rapidly progressive with high mortality.

• Necrotising fasciitis is uncommon but carries high mortality and complication rates. Many doctors will encounter at least one case during their career but are unlikely to be familiar with the condition.

• The estimated incidence in the western world is about 0.24–0.4/100,000 people per year.³ However, in some areas of the world, NF is more common and more than one case in every 100,000 people is reported.

• The median age is around 60 years, and the majority of cases are men.⁴

• The incidence of necrotising fasciitis in the UK is estimated at 500 new cases each year.

Risk factors for necrotising fasciitis³

These include:

• Skin injury including insect bite, trauma and open wounds.

• Underlying conditions including alcohol abuse, intravenous drug abuse, chronic liver or renal disease, diabetes, malignancy, immunosuppression and possibly, tuberculosis.

• Necrotising fasciitis in children may follow varicella-zoster infection.

Note that necrotising fasciitis can occur in previously healthy people with no underlying disease, particularly where Group A streptococci are involved.

General points

• Have a high index of suspicion for NF - for example, with unexplained limb pain.

• Patients are systemically ill with disproportionately severe pain; there are only minor skin changes in the early phases.

• Necrotising fasciitis can affect any part of the body but usually involves the extremities, perineum or trunk.

• Ask about recent injury or illness, sea water exposure or fish sting and underlying conditions including intravenous drug abuse.

Necrotising fasciitis symptoms⁶

Necrotising fasciitis typically develops over a few days but can progress much more rapidly in some cases - for example, with infection with Vibrio spp. and A. hydrophila where it may be fatal within 48 hours. The typical development of symptoms and signs is:

Days 1-2 approximately:

• Local pain, swelling and erythema. This mimics cellulitis or erysipelas: the necrotising infection is deep in the skin and not visible.

• Severe, constant pain, out of proportion to the physical signs, is a notable feature.

• The margins of infection are poorly defined, with tenderness extending beyond the apparent area of involvement (unlike cellulitis).

• There is no response to antibiotics (unlike cellulitis).

• Lymphangitis is rarely seen (unlike cellulitis).

• Systemic illness - malaise, tachycardia ± fever and dehydration. One review suggests that patients often 'feel worse than they have ever felt and don't know why'.

Days 2-4 approximately:

• The affected area develops tense oedema, extending beyond the margin of erythema.

• There may be bullae, indicating skin ischaemia (unlike cellulitis). These may become haemorrhagic.

• Skin becomes discoloured, progressing to grey necrosed skin which breaks down.

• The subcutaneous tissues have a wooden-hard feel (unlike cellulitis or erysipelas). Fascial planes and muscle groups are not palpable.

• There may be crepitus due to subcutaneous gas.

• Pain sensation may progress from intense tenderness to anaesthesia as the nerves are destroyed.

• There may be a broad erythematous tract in the skin along the route of the infection as it advances cephalad.

• If there is an open wound, probing the edges with a blunt instrument produces easy dissection of the superficial fascial planes well beyond the wound margins.

Days 4-5 approximately:

• Hypotension and septic shock develop.

• Patients become confused and apathetic.

Fournier's gangrene is a rapidly progressive form of infective necrotising fasciitis of the perineal, genital or perianal regions, leading to thrombosis of the small subcutaneous vessels and necrosis of the overlying skin.⁷

• Cellulitis or erysipelas.

• Pyoderma gangrenosum.

• Limb ischaemia, compartment syndrome.

• Deep vein thrombosis or thrombophlebitis.

• Osteomyelitis with soft tissue involvement.

The diagnosis is clinical - if there is strong clinical suspicion of NF, exploratory surgery is required regardless of test results.

A high index of suspicion is needed when a patient presents with cutaneous infection causing swelling, pain and erythema, particularly if the patient also has diabetes, malignancy, alcohol abuse, or chronic liver or kidney disease. The presence of bullae or gas on plain X-ray can be diagnostic. Early surgical exploration is advised when there is any uncertainty.⁹

The LRINEC (Laboratory Risk Indicator for Necrotising Fasciitis) score is based on six biochemical blood test analytes (CRP, leukocytes, haemoglobin, sodium, creatinine and glucose) and is intended to distinguish NF from non-necrotising skin and soft tissue infections.⁵ The score has shown good sensitivity in several studies.¹⁰¹¹

During surgery, the diagnosis of NF is made on its macroscopic features, which include: grey necrotic tissue, lack of bleeding, thrombosed vessels, 'dishwater pus', lack of resistance to finger dissection and non-contracting muscle.

The following tests may help to identify possible necrotising infection where the clinical picture is uncertain. However, note that exploratory surgery and tissue biopsy are the gold standard for diagnosis of NF.

• Blood tests - Appropriate initial investigations are as for all patients presenting with sepsis – FBC, U+Es, LFTs, coagulation screen, CRP, lactate, ABG/VBG and blood cultures.¹²

  • Bloods may show leucocytosis, acidosis, altered coagulation profile, hypoalbuminaemia and abnormal renal function

  • White cell count >15.4 x 10⁹/L.

  • Serum sodium less than 135 mmol/L.

  • Raised CRP ( >16 mg/dL).

  • Raised CK level (>600 U/L).

  • Urea >18 mg/dL.

• Bedside finger test:

  • This is carried out under local anaesthesia, with an incision of 2 cm down to the deep fascia. Gentle probing with the index finger is performed at the level of the deep fascia.

  • Signs of NF are lack of bleeding, malodorous 'dishwater pus' and lack of normal tissue resistance to blunt finger dissection.

  • An alternative is bedside incisional biopsy to the fascia, with immediate frozen section, culture and Gram stain.

• Microbiology:

  • Blood cultures.

  • Wound swab.

  • Gram stain and culture of affected tissues (from surgery or biopsy).

  • Fungal culture is important in the immunocompromised and in trauma patients.

• Radiology - note this cannot rule out NF, as there are many false negatives:

  • CT, US and MRI have all been used to image necrotising soft tissue infection, however no imaging modality is considered definitive and it is vital to ensure that if imaging is performed, it must not unduly delay surgical intervention.¹²

• Other tests:

  • Tissue oxygen saturation measured by near-infrared spectroscopy, as a bedside test.

The essential treatment is early and aggressive debridement of the involved tissue. Resuscitation, antibiotics and medical care are also important.

Resuscitation and medical care

• Patients may be shocked or haemodynamically unstable; resuscitation and intravenous fluids may be needed.

• An intensive care unit is often appropriate.

Surgery

• The initial surgery is the most important determinant for survival. The debridement must be extensive, with adequate margins so that no infected tissue remains.

• Following initial debridement, the wound must be observed closely. Surgical debridement is repeated daily until the infection is controlled.

• When the infection is controlled, daily dressings are required under sedation.

• Closure of the wound is by secondary suturing ± skin grafts. Vacuum-assisted wound closing devices may assist healing.

Antibiotics

Immediately start a broad-spectrum, intravenous antibiotic at a high dose. These should cover streptococci, staphylococci, Gram-negative rods and anaerobes.

Non-surgical treatment¹⁴

• Non-surgical measures include close monitoring and general supportive treatment in an intensive care setting with antimicrobial treatment.

• Nutritional support is required from day one, owing to the high protein and fluid loss from the wound (similar to major burns). In severe cases, patients may need twice their basal calorie requirements. Nasogastric feeding may be helpful.

• NF carries a significant mortality rate, particularly if marine organisms (see 'classification and aetiology', above) are involved.

• Septic or toxic shock (the latter due to streptococcal endotoxin production).

• The deep tissue infection may lead to vascular occlusion, ischaemia and tissue necrosis. There may be nerve damage and muscle necrosis.

• Large areas of tissue loss may require skin grafting, reconstructive surgery or amputation.

• Necrotising fasciitis is a serious surgical emergency with mortality as high as 32–50%.

• Mortality in NF is usually caused by pronounced sepsis with secondary multiorgan failure.

• Poor prognosis has been linked to advanced age, type of organism, uncontrolled diabetes, state of immunosuppression and delay in aggressive surgical intervention.

• Even people who survive may require prolonged recovery due to significant functional deficits as a result of amputations and scarring.

UK guidelines advise that antibiotic prophylaxis is given to eligible close contacts of a single confirmed case of invasive Group A Streptococcus and should commence as soon as possible (within 24 hours, and preferably the same day) but not to commence beyond 10 days of iGAS diagnosis in the index case.¹⁵

Eligible individuals include:

• Pregnant women from ≥37 weeks gestation

• Neonates and women within the first 28 days of delivery regardless of whether either
  were the index case.

• Older household contacts (≥75 years).

• Individuals who develop chickenpox with active lesions within the time period of 7
  days prior to diagnosis of iGAS infection in the index case or within 48 hours after
  commencing antibiotics by the iGAS case, if exposure ongoing.

Phenoxymethylpenicillin (penicillin V) is the drug of choice for adults and children with no history
of penicillin allergy. Macrolides remain the option of choice and where susceptibilities are available. Due to its long half-life, a 5-day course of once daily azithromycin achieves equivalent total drug exposure to 10 days of shorter acting agents.