Streptococcal toxic shock syndrome (StrepTSS) is a severe, invasive group A streptococcal (GAS) infection associated with the sudden onset of shock, acute respiratory distress syndrome, renal failure, bacteremia, and death. Fifty percent of StrepTSS patients develop necrotising fasciitis or myonecrosis which progresses rapidly and requires emergent amputation or extensive surgical debridement to ensure survival.

Necrotising Fasciitis/myonecrosis is characterised by excruciating pain at the site of infection, the onset of which occurs well before shock or organ failure is manifest. The overlying skin becomes erythematous with purple, hemorrhagic bullae - clinical clues indicating that destruction of the deeper tissues is occurring. Histologically, there are large numbers of organisms, massive tissue necrosis and a notable absence of inflammatory cells.

The mechanisms responsible for the early onset of severe pain and the rapid regional destruction of tissues in this infection have not been elucidated. We hypothesized that toxin - induced ischemia contributes to both pain and tissue necrosis. Using Doppler flowmetry. local blood flow at the site of intramuscular injection of exotxins from an invasive M-type 1 GAS was evaluated in a rat model.

GAS exotoxins caused a rapid, dose-dependent decrease in perfusion that was irreversi at the highest toxin concentration tested. Videomicroscopy revealed that blood flow was impeded by occlusive intravascular cellular aggregates. Flow cytometry confirmed that GAS toxins induced the co-aggregation of platlets and neutrophils, that this activity was attributable to streptolysin O (SLO), and that platelet/neutrophil complex formation was largely mediated by platlet P-selectin (CD62P).

Immunotherapeutic stratergies targeting platelet adherence molecules may prevent vascular occlusion, maintain tissue viability, and reduce the need for amputation in necrotising GAS infections.

With kind permission from Dennis L Stevens. Speaker at the strepEURO meeting in Lund. 23rd May 06.