Synonyms: TSS, streptococcal toxic shock-like syndrome (STSS), 'toxic strep'

Definition

Toxic shock syndrome (TSS) is a multisystem inflammatory response to the presence of bacterial exotoxins.

Todd first described it amongst children in 1978; the toxins were secreted by Staphylococcus aureus.¹ 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. Enhanced surveillance of the rate of Group A infections is undertaken by microbiologists (on behalf of the Health Protection Agency) in the UK and several European countries.

Pathogenesis

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.

Epidemiology

In the early 1990s there were roughly 40 cases per year in the UK, with 2-3 deaths per year.² This has since declined due to change in tampon manufacture, and increased awareness. However the current level of group A (Streptococcus pyogenes) streptococcal infections remains above that seen in recent years, despite seasonal declines that have been noted during 2009.³

• The incidence of both toxic shock syndrome (TSS) and streptococcal toxic shock-like syndrome (STSS) appeared to increase through the 1980s and 1990s but has now stabilised. A UK series showed an incidence of STSS increasing from 1 to 9.5 per million population per year in the 1990s.⁴
• Infections not associated with menstruation have become more common as menstrual cases have declined. The incidence in children is lower than that in adults.⁵
• Both conditions are relatively rare; worldwide background prevalence of TSS is approximately 3/100,000 people.⁶

Possible risk factors

• S. aureus cellulitis
• Wounds (including burns)
• Tampon use (now less relevant) 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 virus
• There is debate around an association with non-steroidal anti-inflammatory drug use⁵

Presentation

The hallmark features are:

• Fever - this is usually high at approximately 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 the skin
• Checking for tampons; gynaecological examination
• Respiratory examination

Differential diagnosis

• 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

Investigations

• Blood cultures are positive in 5-15% of cases of toxic shock syndrome (TSS) and in approximately 50% of streptococcal toxic shock-like syndrome (STSS).⁷
• 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 there is suspected pneumonic focus.

Management

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 removed immediately, 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.⁸
• 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.⁶
• Steroids may play a role in improving survival, along with activated protein C and intravenous immunoglobulin.⁹ Research has shown that a long course of low-dose corticosteroids reduces 28-day all-cause mortality, and intensive care unit and hospital mortality.¹⁰

Prognosis

• Mortality rate for toxic shock syndrome (TSS) is around 5-15%.⁷
• A fatality rate of up to 64% has been noted in cases of streptococcal toxic shock syndrome (STSS) in the UK.⁴
• Recurrence of TSS is found in 30-40% of cases.

Complications

• Recurrence
• Cardiomyopathy
• Rhabdomyolysis
• Acute renal failure
• Encephalopathy and cerebral oedema
• Acute respiratory distress syndrome
• Hepatic necrosis
• Thrombocytopenia and marrow suppression
• Disseminated intravascular coagulopathy (DIC)
• Metabolic acidosis, electrolyte disturbance

Document references

1. Todd J, Fishaut M, Kapral F, et al; Toxic-shock syndrome associated with phage-group-I Staphylococci. Lancet. 1978 Nov 25;2(8100):1116-8. [abstract]
2. Health Protection Agency; Communicable Disease Report. Toxic shock syndrome and related conditions in the United Kingdom: 1992 and 1993
3. Richman KM, Rickman LS; The potential for transmission of human immunodeficiency virus through human bites. J Acquir Immune Defic Syndr. 1993 Apr;6(4):402-6. [abstract]
4. Barnham MR, Weightman NC, Anderson AW, et al; Streptococcal toxic shock syndrome: a description of 14 cases from North Yorkshire, UK. Clin Microbiol Infect. 2002 Mar;8(3):174-81. [abstract]
5. Chuang YY, Huang YC, Lin TY; Toxic shock syndrome in children: epidemiology, pathogenesis, and management. Paediatr Drugs. 2005;7(1):11-25. [abstract]
6. Annane D, Clair B, Salomon J; Managing toxic shock syndrome with antibiotics. Expert Opin Pharmacother. 2004 Aug;5(8):1701-10. [abstract]
7. Sharma S, Harding G; Toxic Shock Syndrome, eMedicine, May 2009.; Good images of skin signs.
8. Patel GP, Gurka DP, Balk RA; New treatment strategies for severe sepsis and septic shock. Curr Opin Crit Care. 2003 Oct;9(5):390-6. [abstract]
9. Nguyen HB, Rivers EP, Abrahamian FM, et al; Severe sepsis and septic shock: review of the literature and emergency department management guidelines. Ann Emerg Med. 2006 Jul;48(1):28-54. Epub 2006 May 2. [abstract]
10. Annane D, Bellissant E, Bollaert PE, et al; Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. BMJ. 2004 Aug 28;329(7464):480. Epub 2004 Aug 2. [abstract]

Internet and further reading

• Marik PE, Lipman J; The definition of septic shock: implications for treatment. Crit Care Resusc. 2007 Mar;9(1):101-3. [abstract]
• McKinnon HD Jr, Howard T; Evaluating the febrile patient with a rash. Am Fam Physician. 2000 Aug 15;62(4):804-16. [abstract]
• Toxic Shock Syndrome Information Service

Acknowledgements