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Toxic shock syndrome

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5-year-old Damon scalded his chest after reaching up to grab a rather appealing hot chocolate. His Mum performed appropriate first aid and the injury was dressed and treated at their local minor injury unit. Unfortunately, Damon has been picking at the wound (a very bad habit). His Mum brings him to the emergency department two days later. He has a rash around the burn, fever, rigors and seems lethargic.

Why worry about toxic shock with burns?

Burns are common. Children are particularly vulnerable in the home. Children may be scalded (the most frequent cause), sustain a contact burn, or a flame burn. Undertake a detailed assessment and consider non-accidental injury.

Burns range in severity. They may be relatively minor and superficial, with no lasting signs or complications, or they may be deep or large and can be both physically and psychologically damaging. Even small burns can cause significant morbidity and mortality if toxic shock develops.

What is Toxic Shock Syndrome?

Toxic Shock Syndrome (TSS) is a rare but life-threatening complication of burn injuries. It occurs in genetically susceptible children due to infection with a toxin-producing bacterium. This is most frequently a toxin-producing strain of Staphylococcus aureus, but has also been seen with Streptococcus pyogenes, Pseudomonas, and Klebsiella.

These toxins are powerful superantigens that cause an exaggerated immune response. The overwhelming immune response may lead to multi-organ failure and death.

Antibodies to the toxin are protective and develop with age. This may explain why TSS is rarely seen in adults.

Why does this occur in burn injuries?

TSS occurs in burns when the injury is colonised by toxin-producing bacteria. A number of factors lead to the creation of a favourable environment where toxin production occurs at an exponential rate. This is mainly due to the loss of the protective skin barrier. The serum in the interstitial space is an ideal growth medium for toxins. The aerobic environment, neutral pH, and higher temperatures which naturally occur following a burn injury also favours toxin production.

What about other causes of toxic shock?

Although rare, TSS is most commonly seen in children with minor burns and scalds. Other causes relate to local infections by Staphylococcus aureus or Streptococcus pyogenes. These include surgical wounds, retained products of conception, deep abscesses, or lacerations. Tampon use causing TSS is a favourite for exams, though the incidence is decreasing as manufacturing practices change.

Invasive Group A Streptococcus (iGAS) is of particular importance given the current scarlet fever outbreak with a recent systematic review and meta-analysis demonstrating a substantial burden of iGAS amongst young children.

How can we recognise toxic shock syndrome?

TSS is characterised by an acute onset of shock, fever, rash, and systemic upset that occurs between one and seven days after the burn injury. The burn itself may not always look infected. There may be prodromal symptoms like nausea and vomiting couple with nonspecific symptoms such as myalgia, lethargy, and headache. Symptoms may develop quickly, and children are at risk of rapid deterioration. Unfortunately, initial non-specific symptoms can be dismissed if TSS is not actively considered.

The diagnosis is made clinically and as toxic shock syndrome progresses hypotension and multiorgan failure occur. The Center for Disease Control (CDC) provides detailed diagnostic criteria. There are also abbreviated criteria for children (fever >/=39oc, rash, diarrhoea and vomiting, irritability, lymphopenia).

Lymphopenia and hyponatraemia are often seen on lab tests. Additional lab tests may also help look for signs of multisystem organ involvement.

What is the management of toxic shock?

TSS has a mortality of up to 50%. As such, early and aggressive management is crucial. This consists of four main principles: resuscitation and stabilisation, wound cleaning and debridement, intravenous antibiotics, and providing passive immunity against the toxin with fresh frozen plasma (FFP) or intravenous immunoglobulin (IVIG). The seven Rs of management are another useful way of approaching management.

A multicentre study published by the British Paediatric Surveillance Unit looked at 49 TSS cases over one year from paediatric and burns specialist centres. Although limited by the small sample size, this is reasonable for an observational study for a rare disease process. The majority (78%) of these children were managed in PICU with 68% requiring ventilatory support, 67% inotropic support, and 12% haemofiltration. Additionally, FFP was given in 40% of cases, and IVIG in 20%. This study highlights that the early management of children with suspected TSS should take place in a high dependency setting.

What about antibiotics?

Antibiotics treat the underlying cause of sepsis and shock. Early antibiotics for children with sepsis is associated with reduced mortality in a number of retrospective observational studies. The time cut-off is not clear though studies show an incremental risk of harm beyond 3 hours. However, for the septic shock associated with TSS consensus opinion is that antibiotics should be given as soon as possible, and ideally within 1 hour.

Broad-spectrum antibiotics mat include vancomycin or linezolid due to the prevalence of MRSA. Clindamycin has also been shown to suppress toxin production and enhance bacterial clearance, but since it is bacteriostatic rather than bactericidal it should be added to antibiotic regimes. Ideally, they should be started after blood cultures and cultures from the burn wound have been taken but this should not delay treatment.

What about inotropes?

Adrenaline and noradrenaline have both vasopressor and inotropic effects. These are used widely and are effective in treating children with fluid-resistant shock. These vasoactive agents should be considered after 40-60ml/kg of fluid resuscitation (or sooner if there is evidence of fluid overload). There are no studies directly comparing these agents in children. Either can be used first line.

Adrenaline and noradrenaline should be administered centrally. However, if central venous access is not available and it is an emergency, consensus opinion is that they may be diluted and administered peripherally (intravenous) or given undiluted via the intraosseous route until more definitive central venous access is obtained.

What about intravenous immunoglobulins?

Children who develop TSS often lack neutralising antibodies against the toxins and other virulence factors. IVIG acts to boost passive immunity and inhibit the inflammatory response in TSS.

The utility of IVIG has previously been questioned due to batch-to-batch variability and a lack of high-quality studies in children. Small observational studies have shown conflicting results in sepsis. Although there have been no randomised control trials supporting its use in TSS, observational studies suggest a reduction in mortality compared to patients receiving antibiotics only.

Take home points

Have a high index of suspicion

Consider the diagnosis in any child with a fever of 39oC, rash, or sudden change in clinical condition after a burn injury

The early use of clindamycin is vital to suppress toxin production

Early diagnosis and aggressive treatment reduce morbidity and mortality

Damon is admitted and receives fluid resuscitation, IV antibiotics and later fresh frozen plasma. After a few days of rather aggressive treatment, he has improved significantly and is looking forward to going home.

References

Adalat S, Dawson T, Hackett SJ, Clark JE; In association with the British Paediatric Surveillance Unit. Toxic shock syndrome surveillance in UK children. Arch Dis Child. 2014;99(12):1078-1082.

Edwards-Jones V. Toxic shock syndrome: causes in people with burn wounds. Wounds. 2006;2(4):66-73

Gill P, Falder S. Early management of paediatric burn injuries. Paediatr Child Health. 2017;27(9):406-414

Gutzler L, Schiestl C, Meuli M, Oliveira C. Toxic shock syndrome in paediatric thermal injuries: A case series and systematic literature review. Burns. 2018;44(1):e1-e12.

Hodille E, Badiou C, Bouveyron C, et al. Clindamycin suppresses virulence expression in inducible clindamycin-resistant Staphylococcus aureus strains. Ann Clin Microbiol Antimicrob. 2018;17(1):38. 

Khajuria A, Nadama HH, Gallagher M, Jones I, Atkins J. Pediatric Toxic Shock Syndrome After a 7% Burn: A Case Study and Systematic Literature Review. Ann Plast Surg. 2020;84(1):35-42.

Lappin E, Ferguson AJ. Gram-positive toxic shock syndromes. Lancet Infect Dis. 2009;9(5):281-290.

Parks T, Wilson C, Curtis N, Norrby-Teglund A, Sriskandan S. Polyspecific Intravenous Immunoglobulin in Clindamycin-treated Patients With Streptococcal Toxic Shock Syndrome: A Systematic Review and Meta-analysis. Clin Infect Dis. 2018;67(9):1434-1436. 

Pomeroy S, Young AE, Williams P. Burns (Paediatric): Toxic Shock Syndrome and Sepsis. Bristol Royal Hospital for Children Clinical Guideline. 2021. Accessed online at https://foi.avon.nhs.uk/Download.aspx?r=1&did=17054&f=Burns%20Paediatric%20Toxic%20Shock%20Syndrome%20And%20Sepsis-2.pdf

Ross A, Shoff HW. Toxic Shock Syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing; November 17, 2021.

Shah SS, Hall M, Srivastava R, Subramony A, Levin JE. Intravenous immunoglobulin in children with streptococcal toxic shock syndrome. Clin Infect Dis. 2009;49(9):1369-1376.

Sherwood E, Vergnano S, Kakuchi I, et al. Invasive group A streptococcal disease in pregnant women and young children: a systematic review and meta-analysis. Lancet Infect Dis. 2022;22(7):1076-1088. 

Thielemans E, Oliver J, McMinn A, et al. Clinical Description and Outcomes of Australian Children With Invasive Group A Streptococcal Disease. Pediatr Infect Dis J. 2020;39(5):379-384. 

Weiss SL, Peters MJ, Alhazzani W, et al. Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Intensive Care Med. 2020;46(Suppl 1):10-67. 

Wilkins AL, Steer AC, Smeesters PR, Curtis N. Toxic shock syndrome – the seven Rs of management and treatment. J Infect. 2017;74 Suppl 1:S147-S152. doi:10.1016/S0163-4453(17)30206-2

Young AE, Thornton KL. Toxic shock syndrome in burns: diagnosis and management. Arch Dis Child Educ Pract Ed. 2007;92(4):ep97-ep100.

Authors

  • Owen Hibberd is an Emergency Medicine Trainee in Cambridge, currently studying on the QMUL PEM MSc. Interested in Paediatric Emergency Medicine, Pre-Hospital Emergency Medicine and Medical Education. He/him.

  • Costas Kanaris is a Paediatric Intensive Care Consultant in Cambridge and an Associate Editor of the Journal of Child Health Care. He has a PhD in Medical Ethics and Law and is an Honorary Senior Lecturer at Queen Mary University of London.

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