Discuss the diagnosis and early management of necrotising fasciitis associated with Group A
Streptococcal (GAS) infection.

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College answer

The management of necrotizing fasciitis associated with Group A Streptococcal infection consists of 

  • Diagnosis, 
  • Antibiotic therapy, 
  • Supportive therapy for associated shock, and 
  • Prompt surgical intervention. 

Diagnosis History

  • Necrotising infections are likely to have pain far in excess of superficial appearance
  • May have history of recent trauma, cuts, wounds or IVDU
  • Predisposition: diabetes, peripheral vascular disease, immunosuppression, steroid use
  • May have history of systemic symptoms; fever, chills, nausea, myalgia, headache

Examination Local 

  • Red, swollen, tender, area, dark discoloration of the skin
  • Bullous formation and areas of necrosis are late signs

Systemic

  • Signs of systemic toxicity and organ failure may be present (renal impairment, coagulopathy, liver abnormalities, acute respiratory distress, erythematous rash)

Investigations

  • Culture of swabs, tissue in selective media
  • PCR
  • Frozen section biopsy at time of surgery
  • Blood culture
  • CT or MRI may show extent of infection
  • Routine investigations: ABG, FBC, Coags and fibrinogen, LFTs, EUC, lactate
  • Streptozyme test – need antibody production. Better at detecting post-streptococcal disease like PSGN, rheumatic fever o
    • Anti-streptolysin (ASO) 
    • Anti-hyaluronidase (AHase) 
    • Anti-streptokinase (ASKase) 
    • Anti-nicotinamide-adenine dinucleotidase (anti-NAD) 
    • Anti-DNAse B antibodies
  • Rapid Antigen Detection test – more useful for diagnosis of pharyngitis

Antibiotic therapy

  • Group A Strep. remain susceptible to beta-lactam antibiotics.  
  • Penicillin is still drug of choice
  • Clindamycin should be added to the regimen as clindamycin may be more effective in invasive infections. The efficacy of clindamycin is unaffected by the size of the inoculum and the stage of bacterial growth. Clindamycin also inhibits the production of toxin by streptococci. 
  • In a patient where the initial microbiology is uncertain a broad spectrum antibiotic – such as meropenem should be considered.

Supportive management

  • Often requires monitoring in an intensive care unit with insertion of arterial and central lines, aggressive fluid resuscitation, inotropic support, invasive respiratory support and not infrequently renal replacement therapy. 
  • IVIG is of benefit in TSS to help limit spread of disease and improve mortality. 
  • Hyperbaric oxygen therapy may be considered but is adjunctive and other therapy should not be delayed.  

Prompt Surgery

  • Early and extensive surgical intervention is key with remove all affected tissue. 
  • Daily returns to operating theatres until there is no longer further evidence of spread are often necessary

Additional Examiners‟ Comments:

Many candidates‟ answer contained lists of facts with very little clinical perspective. Although the pass rate overall was good, much better marks would have been possible if candidates actually read the question and discussed the diagnosis and early management rather than just reciting textbook facts. 

Discussion

This question closely resembles the generic mass of necrotising fasciitis questions, such as  Question 25 from the first paper of 2016, Question 24 from the first paper of 2011 and Question 1 from the first paper of 2001. The unique features are the question about diagnosis and the reference to Group A Streptococci specifically. Moreover, the question and college answer seem to jump back and forth between the American and the British spelling of "necrotising", suggesting that at least some of the college answer was cut and pasted from somewhere. This brings into question the seriousness of the comment about mindlessly reciting textbook facts. In any case, the pass rate was 94%, which means the marking criteria did not contain anything which might have tested "clinical perspective".

The diagnosis can be discussed in terms of history, examination, biochemistry, microbiology, imaging and anatomical pathology. The definitive resource for this is probably Wong et al (2005). However, much of the summary below actually comes from the 1995 article by McHenry et al, and represents the historical and clinical features found in a retrospective case series of necrotising fasciitis patients.

Features of history

  • Rapidly develping symptoms
  • Reasonably young patients
  • Previously healthy
  • History of minor trauma, eg. scratch, bruise
  • Initial injury is frequently trivial and blunt rather than penetrating
  • Intense pain and tenderness over the involved skin and underlying muscle
  • Pain is out of proportion to physical findings
  • Risk factors may be apparent: diabetes, alcoholism, obesity, steroid use.

Features of physical examination

  • At the earliest stages, necrotising facsiitis is indistinguishable from severe cellulitis.
  • Severe pain on palpation is an early feature
  • The affected tissue is oedematous and has a "wooden, hardened feel"
  • Erythema is present early.
  • Skin "blebs", i.e. bullae with clear fluid develop as skin ischaemia progresses, and these become haemorrhagic in a late presentation
  • Crepitus on palpation is another late sign
  • Decreased sensation of the overlying skin develops late in the course, and the skin may appear clearly gangrenous

Biochemical features

  • Acute renal failure
  • Coagulopathy; DIC
  • Raised inflammatory markers (WCC, CRP)
  • Hypocalcemia
  • Metabolic (lactic) acidosis
  • Rapid antigen detection test for Group A Strep: this is mainly for pharyngitis (Gerber et al, 2004), but has been used to achieve a rapid diagnosis of lifethreatening GAS soft tissue infection (Ault et al, 1996)
  • "Streptozyme" tests; which, according to a 2009 book chapter by Gould and Reeves are "generally not helpful except as paired acute and convalescent titres", which means the patient will be long dead if you wait for these to become diagnostic of necrotising fasciitis. Oh well, here'es a list of theem anyway, directly from Question 2 from the second paper of 2016​
    • Anti-streptolysin (ASO) 
    • Anti-hyaluronidase (AHase) 
    • Anti-streptokinase (ASKase) 
    • Anti-nicotinamide-adenine dinucleotidase (anti-NAD) 
    • Anti-DNAse B antibodies

Radiological appearance

  • CT findings:
    • Deep fascial thickening
    • Contrast enhancement
    • Fluid and gas in the soft tissue planes in and around the superficial fascia
  • Ultrasound findings:
    • Thickening and distortion of the deep fascia
    • Fluid collections along the deep fascia
  • MRI findings
    • Deep fascial thickening
    • Deep fascial fluid collections
    • Hyperintense T2W signal within the muscles

Surgical findings

  • The presence of grayish necrotic fascia
  • A lack of resistance to blunt dissection: i.e. the normally firmly adherent superficial fascia just sort of falls apart under gentle traction your hands.
  • Lack of bleeding of the fascia during dissection
  • The presence of foul smelling ‘dishwater’ pus.

Histopathology

  • The histologic criteria for diagnosis as described by Stamenkovic and Lew (1984) were as follows:
    • Necrosis of the superficial fascia
    • Polymorphonuclear infiltration of the dermis and fascia
    • Fibrinous thrombi of arteries and veins coursing through the fascia
    • Angiitis with fibrinoid necrosis of arterial and venous walls
    • Presence of microorganisms within the destroyed fascia and dermis
    • An absence of muscle involvement.

Microbiology

  • S.pyogenes is frequently the organism found on tissue culture
  • Blood cultures are also frequently positive

As for the management: the key points to remember are:

  • Source control
  • Clindamycin
  • IV immunoglobulin
  • Hyperbaric oxygen

That's the specific management. The supportive management is boring and algorithmic. The suitably boring and algorithmic answer to Question 25 from the first paper of 2016 is reproduced below. The candidates were offered a necrotising fasciitis in a diabetic leg, and were invited to "describe the management priorities in the first 24 hours".

  • Attention to the ABCS, with management of life-threatening problems simultanous with a rapid focused examination and a brief history.
  • Airway
    • Assess the need for intubation in the context of a potentially decreased level of consciousness
  • Breathing/ventilation
    • Assess efficacy of spontaneous breathing, and the need for mechanical ventilation.
    • Administer supplemental oxygen at a high flow- it may not be particularly helpful at atmospheric pressure, but hyperoxia does seem to retard the growth of anaerobic organisms.
  • Circulatory support
    • Administer a 20-30ml/kg fluid bolus
    • Secure central venous access and commence vasopressors- start with noradrenaline
    • Aim for a MAP over 65mmHg
  • Specific investigations
    • A full panel of blood tests including blood cultures, CK and an ABG
    • A CT scan of the lower limbs and pelvis, as a prelude to surgical intervention
  • Supportive management
    • Continue fluid resuscitation and vasopressors in pursuit of haemodynamic goals
    • Ensure normoglycaemia and normoxia
    • Correct acid base balance
    • Attend to organ system failure - consider early dialysis if there is rhabdomyolysis
  • Monitoring
    • Admit to ICU
    • Commence continuous blood pressure monitoring via arterial line
    • Assess for ketosis/ketoacidosis - this is a Type 1 diabetic, and this is exactly the sort of trigger that would produce a DKA.
  • Specific management
    • Commence broad spectrum antibiotics. In this case, the choice is clindamycin plus anycillin or anypenem. The addition of clindamycin is well supported - particularly with Group A streptococci, where it inhibits the bacterial synthesis of endotoxin.
    • Immediately contact surgical services for source control - debridement is the single most useful management strategy; everything else is fairly cosmetic in terms of decreasing mortality.
    • Consider IV immunoglobulin (i.e. if this is a streptococcal toxic shock syndrome - which manifests as massive cardiovascular collapse and organ system failure very early in the infective process). The use of IVIG in this setting has been well studied, and though those European investigators didn't reach statistical significance in their primary endpoit (mortality), they did note a significant decrease in organ failure scores in the IVIG group.
    • Consider an early referral to a specialist centre where hyperbaric oxygen therapy can be carried out. This management strategy historically did not seem to reduce either mortality or the number of debridements. However, recent data suggests that they were doing it wrong in the 1990s, and modern hyperbaric oxygen therapy seems to be associated with a 50% reduction in mortality (from 9.4% to 4.5%).

References

Chelsom, J., et al. "Necrotising fasciitis due to group A streptococci in western Norway: incidence and clinical features." The Lancet 344.8930 (1994): 1111-1115.

McHenry, Christopher R., et al. "Determinants of mortality for necrotizing soft-tissue infections." Annals of surgery 221.5 (1995): 558.

Wong, Chin-Ho, and Yi-Shi Wang. "The diagnosis of necrotizing fasciitis." Current opinion in infectious diseases 18.2 (2005): 101-106.

Ault, Mark J., Joel Geiderman, and Richard Sokolov. "Rapid identification of group A streptococcus as the cause of necrotizing fasciitis." Annals of emergency medicine 28.2 (1996): 227-230.

Gerber, Michael A., and Stanford T. Shulman. "Rapid diagnosis of pharyngitis caused by group A streptococci." Clinical microbiology reviews17.3 (2004): 571-580.

Gould, Kate, and David Reeves, eds. Managing skin and soft tissue infections: expert panel recommendations on key decision points. Oxford University Press, 2003.