Toxic Shock Syndrome

Synonyms: TSS, Streptococcal toxic shock-like syndrome (STSS), Toxic strep.

Toxic Shock Syndrome (TSS) is a multisystem inflammatory response to the presence of bacterial exotoxins. It was first described amongst children by Todd in 1978¹ where the toxins were secreted by Staphylococcus aureus. Subsequently it was found to be associated with tampon use in menstruating women and Group A streptococcal infections (the streptococcal toxic shock-like syndrome - STSS). It is now recognised as a consequence of a range of infections associated with toxin-secreting Staphylococci and Streptococci.

The infecting staphylococcal or streptococcal exotoxin acts as a superantigen, setting off a reactive inflammatory cascade mediated predominantly by Tumour Necrosis Factor-Alpha and Interleukin-1.

Roughly 40 cases per year in UK, with 2-3 deaths per year.²

• The incidence of both TSS and STSS appeared to increase through the 1980s and '90s but has now stabilised. A UK series showed an incidence of streptococcal-TSS increasing from 1 to 9.5 per million population per year in the 1990s.³
• Infections not associated with menstruation have become commoner as menstrual cases have declined. The incidence in children is lower than that in adults.⁴
• Both conditions are relatively rare; worldwide background prevalence of TSS is approximately 3/100,000 people.⁵

Possible risk factors

• S. aureus cellulitis
• Wounds including burns
• Tampon use (now less relevant since changes in manufacture/patterns of use) or gynaecological infection
• Puerperal sepsis
• Postoperative infections (classical signs of infection may be absent in wound)
• Packed wounds e.g. nasal
• Sinusitis
• Tracheitis
• Recreational intravenous drug use
• HIV
• Allergic contact dermatitis
• Varicella spp.
• Influenza A
• There is debate around an association with NSAID use⁴

The hallmark features are:

• Fever; this is usually high at approx. 39ºC
• Rash; this is usually diffuse, macular and erythrodermic (intense widespread reddening of skin). A scarlatiniform eruption i.e. widespread fine, red, papular - 'sandpaper-like' with flexural accentuation, may also be seen.
• Hypotension; this may be profound and is due to suppression of myocardial contractility by the toxin.
• Multiorgan dysfunction
• Desquamation of palms and soles of feet 1-2 weeks after onset
• Palms, soles of feet, mucous membranes and tongue may be bright red.
• Nausea, vomiting and diarrhoea are relatively frequent presenting features.
• Myalgia and muscle weakness are common.
• Confusion and disorientation may indicate encephalopathy.

Examination should seek evidence of the source of the infection by:

• Close examination of skin
• Checking for tampons; gynaecological examination
• Respiratory examination

• Cellulitis
• Meningococcal disease
• Gram-negative septic shock
• Erythema multiforme/Stevens-Johnson syndrome/Toxic epidermal necrolysis (as drug reaction)
• Heat-related illness
• Infectious mononucleosis
• Infective endocarditis
• Kawasaki's disease
• Viral infection and exanthem
• Leptospirosis
• Typhus/other rickettsial infections
• Cardiogenic shock
• Listeria monocytogenes infection
• Typhoid
• Dengue Fever

• Blood cultures are positive in 5-15% of cases of TSS and approximately 50% of STSS.⁶
• FBC often shows leucocytosis and low platelets.
• U&Es may show raised urea and creatinine, electrolyte disturbance and hypocalcaemia.
• CK and LFTs may be elevated.
• Urinalysis may show microscopic haematuria/myoglobinuria.
• Any wounds should be swabbed for culture.
• Throat swab/others as per clinical suspicion of focus of infection.
• CXR may be useful if suspected pneumonic focus.

Early diagnosis and rapid intervention are the key to arresting the cascade of inflammation that leads to rapid deterioration:

• Any persisting focus of infection such as abscess, wound pack, wound slough or tampon should be immediately removed, with surgical assistance if necessary.
• Aggressive haemodynamic resuscitation, preferably with central fluid volume monitoring and regular electrolyte testing is crucial.
• Vasopressor agents may be used to manage shock, under expert guidance.
• Any abnormality of glucose levels should be closely managed and normalised.⁷
• Antibiotics should be given early and in sufficient doses:
  • Choice of agent depends on suspected pathogen and local patterns of prevalence and resistance. Cephalosporins and clindamycin provide broad cover that should be effective against relevant organisms.⁵
• Steroids may play a role in improving survival, along with activated protein C and intravenous immunoglobulin.⁸ Long course of low dose corticosteroids reduced 28-day all-cause mortality, and intensive care unit and hospital mortality.⁹

• Mortality rate for TSS is around 5-15%.⁶
• A fatality rate of up to 64% has been noted in cases of streptococcal-TSS in the UK.³
• Recurrence of TSS is found in 30-40% of cases.

• Recurrence
• Cardiomyopathy
• Rhabdomyolysis
• Acute renal failure
• Encephalopathy and cerebral oedema
• Acute respiratory distress syndrome
• Hepatic necrosis
• Thrombocytopenia and marrow suppression
• Disseminated Intravascular Coagulopathy
• Metabolic acidosis, electrolyte disturbance