Aetiology

Streptococcal toxic shock syndrome (TSS) is defined as an invasive infection secondary to group A streptococcus (Streptococcus pyogenes) associated with shock and multi-organ system failure occurring early in the course of the disease.[1][2]​​​​ Invasive streptococcal infections include bacteraemia, cellulitis, meningitis, pneumonia, empyema, peritonitis, septic arthritis, puerperal sepsis, burn wound sepsis, necrotising fasciitis, or gangrenous myositis.[9] The most common sites of entry of bacteria include the skin, vagina, and pharynx. In many cases of streptococcal TSS, no site of entry is found.[41] The organism is spread through direct contact with mucosa from the nose or throat of infected patients or through contact with infected wounds.

Staphylococcal TSS is an invasive infection secondary to either methicillin-sensitive (MSSA) or methicillin-resistant (MRSA) Staphylococcus aureus and is associated with tampon use and postpartum infections but is not restricted to these cases.

  • Menstrual TSS occurs in women during menstruation with extended use of a single tampon or, historically, with highly absorbant tampons.

  • Non-menstrual TSS can result from a variety of staphylococcal postpartum vaginal and caesarean wound infections, including mastitis, therapeutical abortions, episiotomy infections, endometritis, and infected abdominal wounds. Sinusitis, septorhinoplasty, osteomyelitis, arthritis, burns, cutaneous infections, soft-tissue infections, enterocolitis, endovascular infections, visceral abscesses, and post-influenza respiratory infections have also been implicated.[4]​​[5][6][7][8]

TSS with necrotising fasciitis, caused by Streptococcus agalactiae, has also been reported infrequently.[42]​ Other organisms infrequently associated with TSS include Streptococcus viridans, group C Streptococcus, group G Streptococcus, and Clostridium sordellii.[30]

Pathophysiology

Streptococcal TSS is mediated by streptococcal pyrogenic exotoxins (superantigens) and virulence factors (M strains with M proteins 1 and 3) that activate the immune system to release inflammatory cytokines.[43][44]​ The cytokines (TNF-alpha, interleukin [IL]-1, and IL-6) result in shock and multi-organ failure.[45] Streptococcal pyrogenic exotoxins A (SPEA) and B (SPEB) are found in most severe invasive group A streptococcal infections. Streptococcal superantigen (SSA) is associated with TSS.[46][47]​ Patients with invasive group A streptococcal infections have significantly lower levels of protective antibodies against M-protein and superantigens, suggesting that lack of humoral immunity against the group A streptococcal virulence factors contributes to susceptibility to invasive infection.[48][49][50][51]​ Several studies have shown that protective humoral immunity to group A streptococcal virulence factors is important in preventing disease.​[48][49][50][51][52]​[53][54]

Group A streptococcal infections with diverse emm genotypes have been isolated from patients with streptococcal infections. More recently, the emm-49 genotype has been associated with more severe invasive streptococcal infections. CsrS gene mutations in severe invasive group A streptococcal infections have been demonstrated.[55]

Staphylococcal TSS from MSSA or MRSA strains is caused by the TSS toxin-1 (TSST-1). This exotoxin is implicated in 90% to 100% of strains associated with menstrual TSS and in 40% to 60% of non-menstrual cases.[56][57][58] Community-acquired MSSA and MRSA strains are more likely to produce enterotoxin B or C.[59] Enterotoxins C, D, E, H have been implicated less frequently.[60] Antibodies to TSST-1 develop in 90% to 95% of the population by the fourth decade.[13] Patients with the clinical TSS lack the antibody to TSST-1 and other staphylococcal enterotoxins and usually do not develop the antibody in the convalescent stage.[61]

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