Toxic Shock Syndrome

A severe, rapidly progressive, toxin mediated multisystem illness caused by exotoxin producing strains of Staphylococcus aureus or Streptococcus pyogenes, characterised by fever, hypotension, a diffuse erythematous rash and multi organ involvement.

It was historically associated with tampon use in menstruating women, though it is now recognised across a broader range of clinical contexts including surgical wound infection, skin and soft tissue infection, and postpartum infection.

It is a medical emergency requiring immediate aggressive resuscitation alongside source control and specific antimicrobial therapy.

Pathophysiology

• Staphylococcal toxic shock syndrome is mediated predominantly by toxic shock syndrome toxin 1, and streptococcal toxic shock syndrome by pyrogenic exotoxins. Both act as superantigens that bypass conventional antigen specific T cell activation.
• They directly cross link major histocompatibility complex class II molecules on antigen presenting cells with T cell receptors on a very large proportion of circulating T cells. This triggers massive, non specific polyclonal T cell activation and an overwhelming cytokine storm.
• The cytokine storm underlies the profound capillary leak, vasodilation and multi organ dysfunction characteristic of this syndrome.
• Streptococcal toxic shock syndrome is more frequently associated with an identifiable, often severe, invasive soft tissue infection (including necrotising fasciitis) as the source, and carries a higher associated mortality than the staphylococcal form.

• Abrupt onset of high fever, hypotension and a diffuse, macular, erythematous, sunburn like rash characterises the core presentation, with the rash typically desquamating, particularly on the palms and soles, one to two weeks after the acute illness, a delayed and diagnostically useful retrospective feature.
• Multi organ involvement is required for formal diagnostic criteria and reflects the severity of this condition, including gastrointestinal involvement (vomiting, diarrhoea), renal impairment, hepatic dysfunction, coagulopathy, and altered mental status, with the specific combination and severity of organ involvement contributing to overall illness severity assessment.
• Myalgia, headache and conjunctival hyperaemia frequently accompany the core features, and profound, rapidly progressive hypotension with evidence of poor peripheral perfusion reflects the severity of the underlying capillary leak and vasodilatory shock physiology.
• A specific identifiable source (retained tampon, surgical wound infection, skin or soft tissue infection, postpartum or post abortion infection) should be actively sought, though in a proportion of staphylococcal cases no clear focus is ever identified despite thorough evaluation.

• Diagnosis is predominantly clinical, based on established criteria requiring fever, hypotension, the characteristic rash with subsequent desquamation, and involvement of a defined minimum number of organ systems.
• Blood cultures are typically negative in staphylococcal toxic shock syndrome (reflecting the localised nature of toxin producing infection rather than bacteraemic spread).
• In streptococcal toxic shock syndrome, blood cultures are frequently positive given the more commonly invasive, bacteraemic nature of the underlying infection in this form.
• Culture of any identified potential source site (vaginal swab, wound swab, or other relevant specimen) supports identification of the causative organism and strain. Full blood count, renal and liver function, coagulation studies and creatine kinase support assessment of the extent of multi organ involvement and overall severity.
• A thorough search for and, where identified, prompt removal of any retained foreign material (tampon, nasal packing, other retained device) forms an essential and specific part of the initial assessment given its direct relevance to source control.

• Immediate, aggressive intravenous fluid resuscitation is the first priority, given the profound capillary leak and vasodilatory shock physiology characteristic of this condition. Large volumes are frequently required, guided by standard haemodynamic monitoring and response, and vasopressor support (noradrenaline as first line) is added for shock refractory to adequate fluid resuscitation.
• Source control is essential and should be pursued urgently alongside resuscitation. It includes immediate removal of any retained tampon or other foreign material, thorough drainage of any abscess or collection, and, where a severe underlying soft tissue infection such as necrotising fasciitis is the source, emergency surgical debridement without delay.
• Empirical combination antibiotic therapy should cover both Staphylococcus aureus (including methicillin resistant strains where locally prevalent) and Streptococcus pyogenes.
• A typical regimen comprises vancomycin (loaded then dosed to target trough) or flucloxacillin, combined with clindamycin 900 mg intravenously every eight hours.
• Clindamycin is specifically included given its mechanism of action inhibiting bacterial protein synthesis, which directly suppresses ongoing toxin production.
• This is an important adjunctive effect distinct from and additional to its conventional bactericidal or bacteriostatic activity against the organism itself. Clindamycin is considered a critical component of the antibiotic regimen in this specific toxin mediated condition regardless of the primary agent selected for bactericidal cover.
• Intravenous immunoglobulin, at a dose of 1 to 2 g per kg given as a single dose or divided over two to three days, is used as an adjunctive therapy, particularly for streptococcal toxic shock syndrome and for severe or refractory staphylococcal disease.
• There is evidence and biological plausibility that intravenous immunoglobulin neutralises circulating superantigen toxin. The quality of supporting evidence varies, and its use is generally guided by specialist infectious disease and intensive care input.
• Intensive supportive care, including management of acute kidney injury, respiratory support where required, and correction of coagulopathy, is provided within an intensive care setting given the severity and multi organ nature of this condition. Close monitoring for and management of the specific pattern of organ dysfunction present in the individual patient is needed.
• Given the historical association with tampon use, education regarding appropriate tampon use (avoiding prolonged wear, using the lowest absorbency appropriate to flow, and alternating with sanitary pads) forms part of preventive counselling, alongside prompt medical attention for any symptoms suggestive of this condition in a menstruating tampon user.
• It should be emphasised that toxic shock syndrome can arise from numerous other sources, and this specific association represents only one of several recognised clinical contexts for this condition.