Toxic shock syndrome

Synonyms: streptococcal toxic shock-like syndrome, '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. 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.

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. This has since declined due to change in tampon manufacture, and increased awareness.

Group C and Group G streptococci have been reported to cause invasive disease similar to that classically associated with group A streptococcus¹².

• 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%³.

• Infections not associated with menstruation have become more common as menstrual cases have declined. The incidence in children is lower than that in adults⁴.

• Both conditions are relatively rare; worldwide background prevalence of TSS is approximately 3/100,000 people⁵.

Possible risk factors

• S. aureus cellulitis: case reports of TSS after mosquito bites⁶.

• 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.

• 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 use⁴.

Presentation

Presentation is usually nonspecific and patients generally present with flu-like symptoms and can develop a life-threatening TSS in just a few hours⁷. 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 toxin⁸.

• 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.

• Any patient with a fever and a rash⁹.

• 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.

• Leptospirosis.

• Typhus/other rickettsial infections.

• Cardiogenic shock.

• Listeria monocytogenes infection.

• Typhoid.

• Dengue.

Investigations

• 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.

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 normalised¹⁰.

• Antibiotics should include a penicillinase-resistant penicillin, cephalosporin, or vancomycin (in methicillin-resistant S. aureus-prevalent areas) along with either clindamycin or linezolid¹¹.

• Steroids may play a role in improving survival¹². Research has shown that a long course of low-dose corticosteroids reduces 28-day all-cause mortality, and intensive care unit and hospital mortality¹³.

• 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 2011¹⁴.

Prognosis

• Mortality rate for TSS is around 5-15%.

• A fatality rate of up to 64% has been noted in cases of STSS in the UK¹⁵.

• Recurrence of TSS is found in 30-40% of cases.

Complications

• Recurrence.

• Cardiomyopathy.

• Rhabdomyolysis.

• Acute kidney injury.

• Encephalopathy and cerebral oedema.

• Acute respiratory distress syndrome.

• Hepatic necrosis.

• Thrombocytopenia and marrow suppression.

• Disseminated intravascular coagulopathy (DIC).

• Metabolic acidosis, electrolyte disturbance.