[Staphylococcal scalded skin syndrome associated with long-term catherter related infection in an adult].

Staphylococcal scalded skin syndrome (SSSS) is an extensive desquamative erythmatous condition caused by the Staphylococcus aureus exfoliative toxin. Although adult cases of SSSS are rare, the mortality rate is high. We report herein on a case of SSSS due to long-term catheter-related bloodstream infection caused by exfoliative toxin B, which produced methicillin-resistant Staphylococcus aureus. A 64-year-old man was admitted to our hospital with a high fever and generalized exfoliative dermatitis. He had an implanted port vascular access device in his left arm. The port was removed because it was thought to be the focus of infection. A Gram stain of the pus from the incision site revealed Gram positive coccus in clusters, and we administered intravenous vancomycin. MRSA was isolated from blood cultures and the pus, and histiology of a skin biopsy specimen from the exfoliation dermatitis showed epidermal detachment in the uppermost layer, which was consistent with SSSS. Although the patient developed infective endocarditis and septic embolisms, he eventually recovered. PCR of the MRSA was positive for exfoliative toxin B, and we finally diagnosed an adult case of SSSS due to exfoliative toxin B producing MRSA.

Plakoglobin rescues adhesive defects induced by ectodomain truncation of the desmosomal cadherin desmoglein 1: implications for exfoliative toxin-mediated skin blistering.

Desmoglein 1 (Dsg1) is a desmosomal cadherin that is essential to epidermal integrity. In the blistering diseases bullous impetigo and staphylococcal scalded-skin syndrome, pathogenesis depends on cleavage of Dsg1 by a bacterial protease, exfoliative toxin A, which removes residues 1 to 381 of the Dsg1 ectodomain. However, the cellular responses to Dsg1 cleavage that precipitate keratinocyte separation to induce blister formation are unknown. Here, we show that ectodomain-deleted Dsg1 (Δ381-Dsg1) mimics the toxin-cleaved cadherin, disrupts desmosomes, and reduces the mechanical integrity of keratinocyte sheets. In addition, we demonstrate that truncated Dsg1 remains associated with its catenin partner, plakoglobin, and causes a reduction in the levels of endogenous desmosomal cadherins in a dose-dependent manner, leading us to hypothesize that plakoglobin sequestration by truncated Dsg1 destabilizes other cadherins. Accordingly, a triple-point mutant of the ectodomain-deleted cadherin, which is uncoupled from plakoglobin, does not impair adhesion, indicating that this interaction is essential to the pathogenic potential of truncated Dsg1. Moreover, we demonstrate that increasing plakoglobin levels rescues cadherin expression, desmosome organization, and functional adhesion in cells expressing Δ381-Dsg1 or treated with exfoliative toxin A. Finally, we report that histone deacetylase inhibition up-regulates desmosomal cadherins and prevents the loss of adhesion induced by Dsg1 truncation. These findings further our understanding of the mechanism of exfoliative toxin-induced pathology and suggest novel strategies to suppress blistering in bulbous impetigo and staphylococcal scalded-skin syndrome.

Cleavage isn't everything: potential novel mechanisms of exfoliative toxin-mediated blistering.

This Commentary describes breakthroughs in understanding the interactions between desmoglein 1 and plakogloben in staphylococcal-mediated blistering skin diseases.

Mechanisms of blister formation by staphylococcal toxins.

Many children suffer from the bacterial skin diseases bullous impetigo and staphylococcal scalded skin syndrome (SSSS). Staphylococcus aureus, which produces exfoliative toxins (ETs), causes these diseases. Recently, it was proven that ETs cleave the cell adhesion molecule desmoglein (Dsg) 1, which plays an important role in maintaining the proper structure and barrier function of the epidermis. Surprisingly, Dsg1 is also the antibody target in the autoimmune disease pemphigus foliaceus. Skin biopsies from pemphigus foliaceus patients show the same pathology as those from bullous impetigo and SSSS patients. The crystal structure of ET suggests that it is a serine protease with an inactive catalytic site, which may become activated when ET binds a specific receptor. This receptor binding is thought to cause a change in conformation that exposes the catalytic site. It has recently been shown that Dsg1 specifically binds and activates ET, which in turn cleaves the bound Dsg1 at only one peptide bond. This process is absolutely dependent on the calcium-dependent conformation of Dsg1. These data suggest that ETs have a very high specificity for human Dsg1, and that S. aureus uses ETs to disrupt the barrier of the human epidermis in order to survive and proliferate on the human body.

Clinical syndromes caused by staphylococcal epidermolytic toxin.

Coagulase-positive staphylococci of phage group II produce an epidermolytic toxin that results in a spectrum of diseases that include localized bullous impetigo, generalized scarlatiniform syndrome without exfoliation, and staphylococcal scalded-skin syndrome (SSSS). The mechanism of action of the toxin occurs at the level of the lower stratum granulosum, resulting in intraepidermal cleavage. Generalized exfoliative dermatitis, or SSSS, is one of the most severe infections characterized by generalized epidermolysis with desquamation. Generalized scarlatiniform syndrome is an erythematous rash without exfoliation. A localized infection that results in a bulla larger than 5 mm in diameter is bullous impetigo.