Clinical, Microbial, and Biochemical Aspects of the Exfoliative Toxins Causing Staphylococcal Scalded-Skin Syndrome

Abstract

SUMMARY The exfoliative (epidermolytic) toxins of Staphylococcus aureus are the causative agents of the staphylococcal scalded-skin syndrome (SSSS), a blistering skin disorder that predominantly affects children. Clinical features of SSSS vary along a spectrum, ranging from a few localized blisters to generalized exfoliation covering almost the entire body. The toxins act specifically at the zona granulosa of the epidermis to produce the characteristic exfoliation, although the mechanism by which this is achieved is still poorly understood. Despite the availability of antibiotics, SSSS carries a significant mortality rate, particularly among neonates with secondary complications of epidermal loss and among adults with underlying diseases. The aim of this article is to provide a comprehensive review of the literature spanning more than a century and to cover all aspects of the disease. The epidemiology, clinical features, potential complications, risk factors, susceptibility, diagnosis, differential diagnoses, investigations currently available, treatment options, and preventive measures are all discussed in detail. Recent crystallographic data on the toxins has provided us with a clearer and more defined approach to studying the disease. Understanding their mode of action has important implications in future treatment and prevention of SSSS and other diseases, and knowledge of their specific site of action may provide a useful tool for physiologists, dermatologists, and pharmacologists.

Molluscum contagiosum prevents progression of staphylococcal scalded skin syndrome

“…Because antibiotics target the offending organism, exfoliation will continue for one to two days after antibiotic administration, indicating the importance of other specific therapeutic molecules [4]. The phenomenon observed in our patient suggests that development of drugs based on the structures of the toxin and inflammatory cytokines including IL-18 may be invaluable for halting the progression of severe cases, particularly in neonates or adults, in whom mortality rates are still high [1,3,4].…”

“…The phenomenon observed in our patient suggests that development of drugs based on the structures of the toxin and inflammatory cytokines including IL-18 may be invaluable for halting the progression of severe cases, particularly in neonates or adults, in whom mortality rates are still high [1,3,4]. …”

“…Experimental injection of the ETA to an infant mouse resulted in typical blisters just below the stratum corneum which forms the epidermal barrier. ETA is also the source of superantigenic activity and ETA activates macrophages to produce proinflammatory cytokines such as TNF-alpha and IL-6 [4]. ETA with an active site mutation, ETA(Ser195Cys), was shown to posses a similar inflammatory activity, indicating that the inflammatory activity of ETA was separate from its epidemiolytic activity [4].…”

“…ETA is a serine protease that specifically targets desmoglein-1, a desmosomal cadherin, but not another related protein, desmoglein-3 [2,4]. Experimental injection of the ETA to an infant mouse resulted in typical blisters just below the stratum corneum which forms the epidermal barrier.…”

“…ETA is also the source of superantigenic activity and ETA activates macrophages to produce proinflammatory cytokines such as TNF-alpha and IL-6 [4]. ETA with an active site mutation, ETA(Ser195Cys), was shown to posses a similar inflammatory activity, indicating that the inflammatory activity of ETA was separate from its epidemiolytic activity [4]. Since S. aureus in SSSS produces ETA at a site distant from the exfoliation, it is very likely that these systemic symptoms, particularly the characteristic rash, are a direct result of the toxin [4].…”