TSS is a rare acute febrile disease characterized by fever, diffuse erythroderma (that later desquamates), vomiting, abdominal pain, diarrhea, myalgia, and nonspecific neurologic abnormalities.¹ It can progress rapidly to hypotension, multiorgan failure, and death.²

It was first described in 1978 in seven children with S. aureus infections.³ An epidemic was noted in menstruating women associated with continuous tampon use in 1980. With the withdrawal of superabsorbent tampons from the market and other public health interventions, the incidence of menstrual TSS decreased from 13.7 per 100,000 persons in 1980 to 0.3 per 100,000 in 1986.^4,5 Nonmenstrual TSS has been described in both children and adults in various clinical scenarios.^6,7 Since 1987, a toxic shock-like syndrome similar to that attributable to staphylococcus has been reported due to highly invasive streptococcal infections. Several studies have reported that invasive STSS is more common in adults than children.^8–10 The Centers for Disease Control and Prevention (CDC) use “STSS” to distinguish streptococcal from TSS caused by staphylococcal infection in their case definition.¹¹

Because TSS and STSS are syndromes, the diagnosis is made when several clinical signs are found together (Tables 61-1 and 61-2 for CDC case definitions).^11,12 The rarity of such cases and the difficulty meeting the strict definition are reasons for the paucity of medical literature, specifically prospective studies on TSS. In addition, since 1986, there has not been ongoing population-based active surveillance to assess the incidence or disease burden of TSS.

The pathogenesis of TSS is thought to be related to the production of toxins, referred to as TSS toxin-1 (TSST-1) and to staphylococcal enterotoxins (SE).⁷ It is likely that more than one toxin may be involved. These toxins are thought to be superantigens, which are a group of proteins that can overactivate the immune system bypassing certain steps in the usual antigen-mediated immune response sequence.¹³ This causes massive T-cell stimulation and an overwhelming immune cascade with cytokines that is destructive to all end organs. The conventional antigen presentation activates around 0.01% of the host T-cell population whereas the superantigen binding activates up to 20% to 30% of host T-cells.¹⁴ The majority of cases of TSS are caused by coagulase-positive S. aureus, although recently, coagulase-negative strains have been isolated. It often develops from a site of colonization rather than infection.¹ There have been reports of TSST-1 in association with methicillin-resistant S. aureus (MRSA); therefore, it is important to consider TSS in patients with MRSA and shock.¹⁵

STSS is caused by invasive GAS which are thought to produce the streptococcal enterotoxin. It occurs most commonly following varicella in previously healthy children and/or during the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Sites of infection in STSS are much deeper than in staphylococcal TSS, such as infection following blunt trauma.¹ The interactions between the host immune system and the pathogen play a major role in determining which patients colonized or infected with toxin-producing S. aureus or Streptococcus pyogenes go on to develop TSS.¹⁶

When superantigens come in contact with cells, they react with various consequences: activation of blood vessel muscle cells leads to vasodilation and hypotension, activation of skin cells leads to rash, activation of gut cells leads to diarrhea, and activation of muscle cells leads to pain and cramps.¹ The most impressive aspect of the pathophysiology of TSS is the massive vasodilatation and rapid movement of serum proteins and fluid from the intravascular to the extravascular space causing oliguria, hypotension, edema, and low central venous pressure. The multisystem collapse seen in TSS may be either a reflection of the rapid onset of shock or may be from the direct effects of toxin(s) on the parenchymal cells of the involved organs.

The CDC has reported a decrease in the annual incidence of TSS, presumably from the increased awareness of risk associated with tampon use. In addition, aggressive supportive care such as early goal-directed fluid resuscitation likely prevents severe manifestation of TSS, decreasing the number of cases that fulfill all the CDC diagnostic criteria. Approximately half of the cases of TSS are associated with tampon use, while the other half occurs in children, men, and nonmenstruating women.¹⁷ Nonmenstrual cases occur in a variety of clinical settings, but are chiefly associated with postpartum or cutaneous/subcutaneous S. aureus infections. Predisposing factors include relatively small body surface area burns, abrasions, abscesses, nasal packing, and infected surgical wounds.

In the United Kingdom, it was estimated that 3% to 13% of children admitted to a burn unit developed TSS.¹⁸ TSS is more common in children with burns of relatively low body surface area. Although children have a higher incidence of minor S. aureus infection than adults, the incidence and mortality of TSS in children are lower. Patients with TSS do not develop a significant antibody response to TSST-1. Therefore, there is a significant recurrence rate for TSS (30%). Secondary cases are milder and occur within 3 months of the original episode; the overall mortality rate is 5%.⁴ The incidence of STSS corresponds to the incidence of invasive GAS disease, which varies according to geographic location and occurs in clusters.