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Synonyms: streptococcal toxic shock-like syndrome, 'toxic strep'
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. 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 in the UK and several European countries.
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.
In the early 1990s there were roughly 40 cases per year in the UK, with 2-3 deaths per year. This has since declined due to change in tampon manufacture, and increased awareness.
- The incidence of both TSS and STSS appeared to increase through the 1980s and 1990s but has now stabilised. Incidence ranges currently estimated between 0·03 to 0·50 cases per 100,000 people, with overall mortality around 8%.
- Infections not associated with menstruation have become more common as menstrual cases have declined. The incidence in children is lower than that in adults.
- Both conditions are relatively rare; worldwide background prevalence of TSS is approximately 3/100,000 people.
Possible risk factors
- S. aureus cellulitis: case reports of TSS after mosquito bites.
- 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 - eg, nasal.
- Recreational intravenous drug use.
- Allergic contact dermatitis.
- Varicella spp.
- Influenza A virus.
- There is debate around an association with non-steroidal anti-inflammatory drug use.
Presentation is usually nonspecific and patients generally present with flu-like symptoms and can develop a life-threatening TSS in just a few hours. Features may include:
- Fever: this is usually high at approximately 39ºC.
- Rash: this is usually diffuse, macular and erythrodermic (intense widespread reddening of skin). A scarlatiniform eruption, ie 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.
- Any patient with a fever and a rash.
- 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 disease.
- Viral infection and exanthem.
- Typhus/other rickettsial infections.
- Cardiogenic shock.
- Listeria monocytogenes infection.
- Blood cultures are positive in 5-15% of cases of TSS and in approximately 50% of STSS.
- FBC often shows leukocytosis 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.
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.
- Antibiotics should include a penicillinase-resistant penicillin, cephalosporin, or vancomycin (in methicillin-resistant S. aureus-prevalent areas) along with either clindamycin or linezolid.
- Steroids may play a role in improving survival. Research has shown that a long course of low-dose corticosteroids reduces 28-day all-cause mortality, and intensive care unit and hospital mortality.
- There is no evidence for the use of activated protein C for treating patients with severe sepsis or septic shock. Activated protein C was therefore withdrawn in 2011.
- Mortality rate for TSS is around 5-15%.
- A fatality rate of up to 64% has been noted in cases of STSS in the UK.
- Recurrence of TSS is found in 30-40% of cases.
Further reading and references
Korman TM, Boers A, Gooding TM, et al; Fatal case of toxic shock-like syndrome due to group C streptococcus associated with superantigen exotoxin. J Clin Microbiol. 2004 Jun42(6):2866-9.
Hagiya H, Okita S, Kuroe Y, et al; A fatal case of streptococcal toxic shock syndrome due to Streptococcus dysgalactiae subsp. equisimilis possibly caused by an intramuscular injection. Intern Med. 201352(3):397-402. Epub 2013 Feb 1.
Berger S, Kunerl A, Wasmuth S, et al; Menstrual toxic shock syndrome: case report and systematic review of the literature. Lancet Infect Dis. 2019 Sep19(9):e313-e321. doi: 10.1016/S1473-3099(19)30041-6. Epub 2019 May 28.
Chuang YY, Huang YC, Lin TY; Toxic shock syndrome in children: epidemiology, pathogenesis, and management. Paediatr Drugs. 20057(1):11-25.
Annane D, Clair B, Salomon J; Managing toxic shock syndrome with antibiotics. Expert Opin Pharmacother. 2004 Aug5(8):1701-10.
Inokuchi R, Ueda Y, Sonoo T, et al; Toxic shock syndrome. BMJ Case Rep. 2015 Apr 152015. pii: bcr-2015-209635. doi: 10.1136/bcr-2015-209635.
Tilanus AM, de Geus HR, Rijnders BJ, et al; Severe group A streptococcal toxic shock syndrome presenting as primary peritonitis: a case report and brief review of the literature. Int J Infect Dis. 2010 Sep14 Suppl 3:e208-12. doi: 10.1016/j.ijid.2009.07.014. Epub 2009 Nov 13.
Marik PE, Lipman J; The definition of septic shock: implications for treatment. Crit Care Resusc. 2007 Mar9(1):101-3.
McKinnon HD Jr, Howard T; Evaluating the febrile patient with a rash. Am Fam Physician. 2000 Aug 1562(4):804-16.
Patel GP, Gurka DP, Balk RA; New treatment strategies for severe sepsis and septic shock. Curr Opin Crit Care. 2003 Oct9(5):390-6.
Gottlieb M, Long B, Koyfman A; The Evaluation and Management of Toxic Shock Syndrome in the Emergency Department: A Review of the Literature. J Emerg Med. 2018 Jun54(6):807-814. doi: 10.1016/j.jemermed.2017.12.048. Epub 2018 Jan 20.
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 Jul48(1):28-54. Epub 2006 May 2.
Annane D, Bellissant E, Bollaert PE, et al; Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. BMJ. 2004 Aug 28329(7464):480. Epub 2004 Aug 2.
Martí-Carvajal AJ et al; Human recombinant activated protein C for severe sepsis and septic shock in adult and paediatric patients, Cochrane Library, Dec 2012
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 Mar8(3):174-81.