Cellulitis and necrotizing soft tissue infection (NSTI) are infections spreading along skin and soft tissue. Both conditions have β-hemolytic streptococci as major causes, mainly Streptococcus pyogenes (GAS) and Streptococcus dygalactiae (SD). But cellulitis and NSTI are two manifestations of streptococcal disease in different ends of the spectrum with respect to severity and urgent need for multidisciplinary medical resources. Even so, they may be hard to discern in early phases. More insight is needed into the pathogenetic and clinical differences in order to improve diagnostics and identify new therapeutic targets.
In studies based on the Scandinavian INFECT cohort, we have characterized and compared the two entities with respect to risk factors, clinical features and inflammatory mediators in plasma. We confirmed streptococcal NSTI to be associated with blunt trauma. Septic shock is rare in cellulitis but was common in NSTI caused by SD and even more frequent in GAS NSTI. Factors associated with mortality in GAS NSTI included age, septic shock and no administration of IVIG. Studying 37 different plasma mediators, we found profound differences in mediator levels between NSTIs and cellulitis cases, with AUC values above 0.90 for several mediators. We also observed major differences in inflammatory profiles between cases with septic shock and those without, and we identified candidate markers for prediction of a severe outcome. The findings point at major pathogenetic differences along the spectrum of streptococcal disease and also at potential diagnostic, prognostic and therapeutic targets, particularly for NSTIs. Biomarkers for diagnosis and treatment guidance in streptococcal NSTIs should be further explored.