Don't be caught out by necrotising fasciitis
Dr Marina Morgan explains why a quick diagnosis of necrotising fasciitis can mean the difference between life and death
GPs will encounter two types of necrotising fasciitis, (NF). Most (80 per cent) are 'synergistic', a mix of coliforms and anaerobes, usually in elderly nursing home patients with widespread carcinoma or intra-abdominal sepsis. The other, devastating, headline-grabbing 'flesh-eating killer bug ate my face' type, is due to Group A beta haemolytic streptococci (GAS), producing fulminant tissue destruction, unapparent until late in the infection, with a far higher mortality and morbidity than meningococcal septicaemia.
The incidence of invasive GAS infection is similar to that of bacterial meningitis, but is increasing. GAS NF occurs in 0.4 per 100,000, mortality increasing with age to 63 per cent over the age of 60. Until recently, the lowest mortality achieved was 23 per cent, but in Exeter, the rate is now less than 8 per cent.
Inoculation through damaged skin or bacteraemic 'seeding' of tissues already inflamed by minor trauma is often reported. Hence there may be a preceding sore throat, flu-like illness or watery vaginal discharge (pus is rare in GAS infections, leukocidin destroys polymorphs producing a watery, sero-sanguineous discharge). Haemoglobinuria due to lysis of red cells by haemolysins contributes to renal failure.
Hyaluronidase, streptokinase, and collagenases aid the spread of the GAS through tissue planes, and 'super-antigens' hyperstimulate T lymphocytes, causing a massive release of intermediary inflammatory agents and cytokines, augmenting septic shock.
Clinical diagnosis of GAS NF
Its protean manifestations make diagnosis in general practice difficult; misdiagnoses include venous thromboses, pulmonary emboli, sprains and arthritis. Even in hospital, with investigations readily accessible, roughly 30 per cent are initially misdiagnosed as influenza, gastroenteritis or thromboses.
Ultimately, diagnosis hinges on clinical intuition, realising the patient is far sicker than appears, and particularly, noting the agonising pain out of proportion to physical signs.
Tangential questioning may suggest the diagnosis. Two post mortems of young women who had been treated with NSAIDs for severe acute hip pain, and a third treated for flu with NSAIDs (her only other symptom being a watery vaginal discharge) all yielded GAS from the genital tract and peritoneum.
Under-diagnosed in life and missed at post mortems because cultures are rarely taken, a fulminant infection producing little pus, with little inflammatory infiltrate on histology, GAS remains a challenge.
Confusion, gastroenteritis, hypotension, and inflammation should suggest streptococcal toxic shock syndrome (STSS). An initially unimpressive area of pain, swelling and erythema, often suggestive of sprain or uncomplicated cellulitis, progresses, becoming tensely swollen, shiny and indurated.
Lymphadenitis is rare, due to blockage of the lymph channels. Eventually, disproportionate pain and violaceous skin discoloration easily mistaken for a bruise supervenes, and the diagnosis becomes obvious as cutaneous necrosis develops. In a recent case of postpartum mammary GAS NF, the bruising was initially mistaken for a dilated vein.
Even in hospital, differentiating severe cellulitis from early myositis or necrotising fasciitis is difficult without C-reactive protein and creatine kinase levels. Compartment syndrome is easily missed in a cellulitic limb if sensation testing and intracompartmental pressure monitoring is omitted. Surgery and histology confirms the diagnosis. Surgery should not be delayed for MRI, CT scans or frozen sections.
A patient with classic late NF, will have complained of agonising, disproportionate pain, and is now hypotensive, paradoxically apathetic, detached from their surroundings with incipient skin necrosis and cutaneous anaesthesia. Necrosis and bullae really do develop as one watches, reminiscent of fulminant meningococcal septicaemia.
Role of NSAIDs in NF
NSAIDs impair the killing of GAS, by lessening the 'respiratory burst' of polymorphs, and diagnosis may be delayed due to the masking of pain and temperature.
Having now managed more than 35 cases of GAS necrotising fasciitis (nearly all of whom were taking NSAIDs) we use other agents when severe streptococcal infection is a possibility.
GP role in NF
Thinking of the diagnosis early before the fulminant stage, with referral to hospital is the key to survival. Supportive fluid administration and, as in meningococcaemia, penicillin could be usefully given. However, the antibiotic of choice, intravenous clindamycin, is rarely available in general practice.
Liz Saunders, who recently admitted a case, found the information sheets sent to GPs 'really helpful, particularly the symptom progression, the severe pain becoming anaesthetic. When I saw the patient the diagnosis was obvious, but in retrospect, the clues had been present for some time. A rare disease, I hope never to see another one.'
Hospital management of NF
Aggressive education of junior doctors and admission ward staff about GAS, and a fax cascade to remind GPs of what to look for, has led to earlier diagnosis and therapy.
Working with plastic surgeons and intensivists, together with massive doses
(40-70g) of intravenous immunoglobulin and antibiotics, rapid surgical debridement and haemofiltration in theatre, has decreased our mortality rate from 30 per cent to less than 8 per cent in the past five years.
Clindamycin, the drug of choice, directly switches off the exotoxin protein assembly inside the cells. Penicillin, active against the rapidly dividing streptococci in uncomplicated low-grade infections is ineffective in NF where streptococci are in their non-dividing 'stationary' phase (the 'eagle effect').
Guidelines recommend clindamycin doses of up to 1.2g iv qds, plus iv benzyl penicillin in high doses. In practice the dilution effect of the fluid replacement makes under-dosing likely, so we initially use clindamycin at 2.4g qds iv for the first 24 hours.
Finally, we routinely screen close contacts with throat swabs, there being a 200 times increased risk of invasive GAS infection, (approximately half the risk of meningococcal contacts), and give 10 days penicillin or erythromycin to carriers, and anyone performing mouth to mouth resuscitation on the index case.
GAS NF affects previously healthy, young and fit people,
as well as those with a history of:
· Non-steroidal anti-inflammatory drugs (NSAIDs)
· HIV infection
· IV drug usage (up to 62 per cent, especially if skin popping)
· Cancer (in up to 12 per cent of necrotising fasciitis)
Clues to diagnosis of streptococcal infection
· History of sore throat, contact with or recent minor streptococcal infection
· Flu-like illness
· Trauma: knocking a limb, minor surgery, childbirth
· Wound or vaginal discharge
· Toxic shock syndrome-related symptoms: diarrhoea and vomiting, confusion, rigors, widespread rash
Clues suggestive of GAS NF
Flu-like illness followed by severe pain that is:
· Early: exquisite, agonising pain, out of proportion to external signs and symptoms, necessitating potent analgesics
· Late: anaesthesia (perineural blood vessels thrombosed) and cutaneous necrosis with the vertical spread of infection
Blood test findings in GAS NF
· Hb: low (haemolysis)
· WBC: often very low
· CRP: usually extremely high (>300g/l)
· Creatinine kinase: usually high except in pure fat necrosis
(eg breast tissue)
· Blood culture
· Biochemistry usually indices of renal failure
The 'Lee Spark' NF Foundation: Severe Streptococcal Infections and Necrotising Fasciitis Support has been an invaluable source of information for our patients: not only a peer support group, but enabling patients to compare their progress during rehabilitation. I highly recommend this group, which is a charity, and happily provides information for health care workers too.
Web address: www.nfsuk.org.uk Telephone: 01254 878701