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PubMed2006

Distribution of the exfoliative toxin D gene in clinical Staphylococcus aureus isolates in France.

Exfoliative toxin D (ETD) was identified recently as a new exfoliative toxin serotype. Like other exfoliative toxins, ETD induces intra-epidermal cleavage through the granular layer of the epidermis of neonatal mice. The distribution of ETD production was investigated in Staphylococcus aureus isolates from infected and colonised patients in France. The etd gene was found in 55 (10.5%) of 522 isolates tested. Isolates responsible for bullous impetigo and generalised staphylococcal scalded skin syndrome did not harbour etd, but etd was significantly more frequent in isolates causing cutaneous abscesses and furuncles. Most etd- and Panton-Valentine leukocidin-positive strains belonged to the clone of community-acquired methicillin-resistant S. aureus spreading currently throughout France.

DNA Primers↗
PubMed2000

Staphylococcal exfoliative toxins cleave alpha- and beta-melanocyte-stimulating hormones.

The staphylococcal exfoliative toxins (ETs) A and B (ETA and ETB) are 27-kDa exotoxins produced by certain strains of Staphylococcus aureus and are the causative agents of staphylococcal scalded-skin syndrome. The crystal structures of the ETs strongly indicate that the proteins are members of the serine protease family of enzymes, although protease activity until now has not yet been conclusively demonstrated. Here, we show that the peptide beta-melanocyte-stimulating hormone (beta-MSH) is cleaved by ETA and that both ETA and ETB are capable of cleaving alpha-MSH. Both toxins exhibit cleavage at specific glutamic acid residues in MSH peptides. Moreover, biologically inactive mutants of ETA were incapable of cleaving beta-MSH.

Amino Acid Sequence↗
PubMed2000

Recombinant Staphylococcus aureus exfoliative toxins are not bacterial superantigens.

Staphylococcal scalded-skin syndrome is an exfoliative dermatitis characterized by the separation of the epidermis at the stratum granulosum. This disruption is mediated by one of two Staphylococcus aureus exotoxins, exfoliative toxins A and B (ETA and ETB). Both ETA and ETB have been reported to be bacterial superantigens. A controversy exists, however, as other data indicate that these exotoxins are not superantigens. Here we demonstrate that recombinant exfoliative toxins produced in Escherichia coli do not act as T-cell mitogens and thus are not bacterial superantigens. These data fit the clinical profile of the disease, which is not associated with the classic symptoms of a superantigen-mediated syndrome.

Animals↗
PubMed1997

Producibility of exfoliative toxin and staphylococcal coagulase types of Staphylococcus aureus strains isolated from skin infections and atopic dermatitis.

BACKGROUND: Strains of Staphylococcus aureus which cause staphylococcal scalded skin syndrome (SSSS) and bullous impetigo secrete exfoliative toxin (ET). Two antigenically distinct serotypes of ET, ETA and ETB, have been reported. MATERIALS AND METHODS: Two hundred eighty-three strains of S. aureus isolated from impetigo, SSSS, furuncles (including furunculosis) and atopic dermatitis were examined in terms of the producibility of ET, ET serotypes and coagulase types. We examined ET production and ET serotypes using the polymerase chain reaction with the oligonucleotide primers for eta and etb. RESULTS: The incidence of ET producers was 69.4% (100/144) in impetigo, 100% (6/6) in SSSS, 2.8% (3/112) in atopic dermatitis and 0% (0/21) in furuncles. ETA alone was produced by 57 strains from impetigo and by 3 strains from atopic dermatitis. ETB alone was produced by 36 strains from impetigo and by all 6 strains from SSSS. Seven strains from impetigo produced both ETA and ETB. Most ETA producers belonged to coagulase type V and most ETB producers to coagulase type I. Impetigo strains mostly belonged to type I or V. All strains from SSSS were classified as type I. Type IV was most frequent among S. aureus isolates from furuncles. CONCLUSION: These results add to the epidemiological information as to ET producibility and ET serotypes of S. aureus strains isolated from impetigo, SSSS, furunculosis and atopic dermatitis. We have found that there is a relationship between the ET serotypes and the coagulase types of ET-producing strains.

Coagulase↗
PubMed2005

Current options for the treatment of impetigo in children.

Impetigo contagiosa is a common, superficial, bacterial infection of the skin characterised by an inflamed and infected epidermis caused by Staphylococcus aureus, Streptococcus pyogenes or both. The less common bullous impetigo is characterised by fragile fluid-filled vesicles and flaccid blisters, and is invariably caused by pathogenic strains of S. aureus. In bullous impetigo, exfoliative toxins are produced, although these are restricted to the area of infection and bacteria can be cultured from the blister contents. In the rare variant, staphylococcal scalded skin syndrome, the exfoliative toxins are spread haematogenously from a localised source causing widespread epidermal damage at distant sites.

Anti-Bacterial Agents↗
PubMed2006

[Desmoglein, the target molecule in autoimmunity and infection].

To form the human body and maintain the integrity of its complex tissues, individual cells need to hold tightly to each other. The desmosome is the major type of intercellular adhesive junction, and has desmoglein (Dsg), a cadherin type cell-cell adhesion molecule, as a transmembrane component. Dsg is now known to be targeted in autoimmune diseases, infectious diseases, as well as inherited diseases. Patients with pemphigus, an autoimmune blistering disease of the skin and mucous membrane, have IgG autoantibodies directed against Dsg1 and Dsg3. A subset of patients with pemphigus have Dsg1/Dsg4 crossreacting IgG autoantibodies. Exfoliative toxins produced by Staphylococcal aureus, which causes Staphylococcal Scalded Skin Syndrome (SSSS) and bullous impetigo, specifically digest Dsg1. A subset of patients with SSSS develop a low titer of anti-Dsg1 IgG autoantibodies. A mutation in DSG1 gene causes striate palmoplantar keratoderma and a mutation in DSG4 gene causes inherited hypotrichosis. It is not clear why so many diseases are clustered in desmogleins, but there must be a reason for this. Studies on desmogleins will provide an important framework to understand the mysteries between autoimmunity and infection.

Animals↗
PubMed2000

Mutational analysis of the superantigen staphylococcal exfoliative toxin A (ETA).

Exfoliative toxin A (ETA) is known to be a causative agent of staphylococcal scalded skin syndrome (SSSS). Although relatively little is known about exactly how the exfoliative toxins (ETs) cause SSSS, much has been discovered recently that may help elucidate the mechanism(s) by which ETA exhibits activities such as lymphocyte mitogenicity and epidermolytic activity. Here, we have shown that highly purified ETA does have T lymphocyte mitogenic activity in that wild-type ETA induced T cell proliferation whereas several single amino acid mutants lacked significant activity. Neither wild-type ETA nor any single amino acid mutants were proteolytic for a casein substrate, yet esterase activity was detected in wild-type ETA and several mutants, but eliminated in other mutants. A mutation in aa 164 (Asp to Ala) showed a 9-fold increase in esterase activity as well. Finally, we correlated esterase activity with epidermolytic activity. All mutants that lost esterase activity also lost epidermolytic activity. Conversely, mutants that retained esterase activity also retained exfoliative activity, implicating serine protease or serine protease-like activity in the causation of SSSS. Moreover, the mutants that displayed markedly reduced T cell superantigenic activity retained their epidermolytic activity (although some of these mutants required higher doses of toxin to cause disease), which suggests an ancillary role for this activity in SSSS causation.

Amino Acid Substitution↗
PubMed1999

[Neonatal staphylococcal epidermolysis due to maternal-fetal transmission].

INTRODUCTION: The staphylococcal scalded skin syndrome (SSSS) is due to exfoliative toxins A or B excreted by some strains of Staphylococcus aureus. This syndrome is exceptional in the first hours of life. We report a case of SSSS due to materno-fetal infection. CASE REPORT: At 31 weeks of pregnancy a 40-year-old mother was febrile (39 degrees C) and a premature rupture of the amniotic sac occurred the following day. SSSS was diagnosed at 6 hours of life in the newborn, a 1760 g female. Staphylococcus aureus grew on the blood and vaginal bacterial cultures of the mother, as well as, from cultures of skin, nose, throat, and umbilical catheter in the newborn. The strains of Staphylococcus aureus isolated in the mother and the child had identical characteristic antibiotype and genotype by Random-PCR. The genes for both exfoliations A and B were present. Epidermization was rapidly obtained and no septicemia or septic complication was noted. DISCUSSION: Staphylococcus aureus is usually responsible for nosocomial infections which occur in the early newborn period. In most cases, the infection is transmitted by a carrier who manipulates the child (family, visitors, nurse or medical staff). In our case, onset of SSSS early after birth suggested a perinatal transmission, due to lower genital tract infection in the mother. The presence of SSSS in the child and not in the mother may be explained by a massive perinatal infection and low elimination of the toxin in the newborn resulting in higher concentrations of exfoliative toxins in the blood.

Adult↗
PubMed2000

Non-thermic skin affections.

The Centre for Burns can help by its means (material, technical and personal) in the treatment of burns with extensive and deep losses of the skin cover and other tissue structures and in some affections with a different etiology (non-thermic affections). Indicated for admission are, in particular, extensive exfoliative affections--Stevens-Johnson's syndrome (SJS), Lyell's syndrome--toxic epidermal necrolysis (TEN) and staphylococcal scalded skin syndrome (SSSS), deep skin and tissue affections associated with fulminant purpura (PF), possibly other affections (epidermolysis bullosa, posttraumatic avulsions etc.). The similarity with burn injuries with loss of the skin cover grade II is typical, in particular in exfoliative affections with a need for adequate fluid replacement in the acute stage and aseptic surgical treatment of the affected area from the onset of the disease. In conditions leading to full thickness skin loss, in addition to general treatment rapid plastic surgical interventions dominate.

Child↗
PubMed2002

Differential pathomechanisms of epidermal necrolytic blistering diseases.

Staphylococcal scalded skin syndrome (SSSS) results from the effect of exfoliative-toxins produced by staphylococcal strains. The disease affects predominantly children, and is rare in adults. We report two cases of the adult type of SSSS. Corticotherapy, chronic alcohol abuse and epilepsy-related immune changes might have been predisposing factors in these patients. The immunopathological characteristics of the inflammatory cell infiltrate in adults SSSS have not been thoroughly explored so far in the literature. Biopsies from 2 patients with bullous SSSS skin were studied by means of immunochemistry using a panel of 10 antibodies directed to FXIIIa, CD15, CD31, CD45R0, CD50, CD54, CD62E, CD95, CD106, and L1-protein, respectively. Cutaneous biopsies from related blistering diseases were compared. They included drug-induced toxic epidermal necrolysis (TEN), bullous impetigo and superficial pemphigus. A dense cell infiltrate composed of granulocytes (CD15+), macrophages (L1 protein+) and memory T cells (CD45R0+) and a strong expression of ICAM-3 (CD50) were present in the epidermis. CD95+ keratinocytes were lining the intraepidermal blisters. Type I dermal dendrocytes (Factor XIIIa+) were numerous and plump in the dermis. Bullous impetigo exhibited the same pattern of inflammatory cells, but with a lower density in type I dermal dendrocytes. TEN differed from SSSS by both the absence of CD15+ granulocytes and a stronger expression of the pro-apoptotic CD95 antigen in the epidermis. In superficial pemphigus, CD95 antigen was not expressed, and CD15+ granulocytes, CD45R0+ lymphocytes and L1 protein+ monocytes were much less numerous. It is concluded that the specific binding of SSSS-induced exotoxins to the desmosomes alters the keratinocyte metabolism leading to an inflammatory reaction followed by focal apoptosis. Our findings are in line with the concept that SSSS exotoxins might be superantigens. A common pathomechanism leading to epidermal destruction is likely operative in SSSS and bullous impetigo. The inflammatory cell composition in TEN and superficial pemphigus markedly differs from that in SSSS.

Female↗
PubMed1992

[Clinical studies on panipenem/betamipron in pediatrics].

Panipenem/betamipron (PAPM/BP) was given by 30 minutes drip infusion to 15 children with acute bacterial infections including 11 with acute pneumonia, 2 each with staphylococcal scalded skin syndrome and urinary tract infections. Good to excellent clinical responses were obtained in all of the 15 patients and bacterial eradications were obtained for all 12 strains identified in these cases. Urticaria considered to be drug related was observed in 1 patient. Slight elevations of GOT and GPT and eosinophilia were observed in 1 case each. From the above clinical results, it appears that PAPM/BP is a useful antibiotic for treatment of pediatric patients with various bacterial infections.

Acute Disease↗
PubMed1992

Staphylococcal toxin-mediated syndromes in childhood.

Staphylococcal toxic shock syndrome (TSS) and staphylococcal scalded skin syndrome (SSSS) are two distinct toxin-mediated syndromes with prominent cutaneous features. The exanthematous presentation of these syndromes places them in the broad category of childhood exanthems, and the ability to recognize these potentially devastating illnesses is essential for pediatricians and dermatologists who may encounter children with fever and rash. Recent advances in the understanding of the pathogenesis of these entities has helped to explain the distinctive clinical presentations of TSS and SSSS. Toxic shock syndrome toxin-1 (TSST-1) and enterotoxins are the secretory products of Staphylococcus aureus that lead to TSS. Many of the clinical features of TSS (fever, shock, multiple organ dysfunction) can be explained by the effects of cytokines (especially interleukin-1 and tumor necrosis factor) induced by TSST-1. TSS is not an exclusively menstrual event associated with tampon use. Nonmenstrual pediatric TSS may be associated with a wide variety of staphylococcal infections. Infected burn wounds in hospitalized children and bacterial tracheitis (in some cases following influenza B infection) are relatively high-risk settings for pediatric TSS. The epidermolytic toxins (A and B) directly produce subgranular epidermolysis leading to SSSS. SSSS encompasses a clinical spectrum from bullous impetigo to the widespread exfoliation of the Ritter disease variant of SSSS. This entity usually occurs in children under 5 years of age, and is primarily explained by lack of immunity to the toxins as well as renal immaturity leading to poor clearance of toxin. The newborn nursery is an important setting where epidemics of SSSS have occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1989

[The SSS syndrome. Description of a case and review of the literature].

A 1-month-old infant with an extensive dermatitis with flaccid bullae, without mucous membrane involvement is described. Staphylococcus aureus was recovered from blood, conjunctiva, skin and nasopharynx. A classification of Staphylococcal Scalded Skin Syndrome (SSSS), as well as etiology and therapeutic modalities, is briefly discussed.

Diagnosis, Differential↗
PubMed1989

[Clinical studies on cefpodoxime proxetil in the pediatric fields].

Cefpodoxime proxetil (CPDX-PR, CS-807) was given orally to 18 children with acute bacterial infections including 10 with acute tonsillitis, 3 with acute bronchitis, 1 with pneumonia, 3 with staphylococcal scalded skin syndrome and 1 with infectious impetigo. Daily dosages per kg bodyweight ranging from 7.5 to 18 mg were given in 2 or 3 divided doses per day for 5 to 15 days. Clinical responses were excellent in 3 (16.7%), good in 11 (61.1%), fair in 4 (22.2%) and poor in 0 (0%), with an overall efficacy rate of 77.8%. Good bacteriological responses were obtained in 6 out of the 7 cases from which pathogens were identified. No side effect was observed. The above results suggest that CPDX-PR is a useful new oral cephalosporin derivative for the treatment of bacterial infections in children.

Acute Disease↗
PubMed1988

[Clinical studies of rokitamycin dry syrup on skin and soft tissue infections in the pediatric fields].

Rokitamycin (RKM) dry syrup, a newly developed macrolide antibiotic, was administered to children with ages between 6 months and 15 years and 10 months suffering from skin and soft tissue infections including 41 cases of impetigo, one case of staphylococcal scalded skin syndrome (SSSS) and 2 cases of subcutaneous abscess totalling 44 cases. The average daily dose level used was 31.3 mg/kg divided into 3 or 4 doses, for an average of 6 days of treatment. MICs of 4 different macrolide antibiotics including RKM, erythromycin (EM), josamycin (JM) and midecamycin acetate (MDM acetate) were determined against 32 bacterial strains isolated from these cases including 30 strains of Staphylococcus aureus and 2 strains of Streptococcus pyogenes. The inoculum level used was 10(6) cells/ml. Among these strains of bacteria, 20 strains of S. aureus and 1 strain of S. pyogenes were also used, at the same inoculum size, for the determination of MICs of 4 beta-lactam antibiotics including 3 different penicillins such as ampicillin (ABPC), methicillin (DMPPC) and cloxacillin (MCIPC) and cefaclor (CCL), a cephem antibiotic. RKM was then evaluated through the above treatment for its clinical efficacy, bacteriological effects, side effects and effects on laboratory test values. Obtained results are summarized as follows. 1. Activities of drugs tested were compared to each other. MIC90 of RKM against S. aureus averaged 0.39 microgram/ml, and against no strains of S. aureus showed MIC values of higher than 25 micrograms/ml, thus, the antibacterial activity of RKM against S. aureus was the highest among the 8 drugs tested. The activity of MCIPC was next highest followed by that of DMPPC, MIC determination was done on only 2 strains, or, for some drugs, only one strain, of S. pyogenes, and RKM showed activities somewhat lower than ABPC and EM, and similar to JM and CCL within the limited testing. 2. Clinical efficacies of RKM determined by doctors in charge were 97.6% in the 41 cases of impetigo, with good or excellent efficacies were observed, 100% in the single case of SSSS and the 2 cases of subcutaneous abscess. Thus an overall efficacy on the 44 cases was rated very high, at 97.7%. 3. Clinical efficacy rating according to accumulated scores was determinable in 37 cases including all the 3 diseases on the third day of treatment with an efficacy rate of 89.2%. Ratings were determinable on the fifth and the seventh days of treatment in 24 and 21 cases, respectively, with all the cases judged good or excellent.(ABSTRACT TRUNCATED AT 400 WORDS)

Abscess↗
PubMed1988

[Use of cultured epidermis of human origin for demonstrating the acantholytic action of staphylococcal exfoliatin A].

Cultured human epithelia obtained from epidermal cells in vitro were used to assay the activity of staphylococcal epidermolytic toxin and develop an in vitro experimental model for the staphylococcal scalded skin syndrome. Human epidermal cells were grown from single epidermal cell suspensions obtained through trypsinization of adult normal skin into multilayered epithelia (with a basal cell layer, several intermediate and one or two upper layers) on mouse 3T3 feeder cells. First passage cultures were incubated with exfoliative toxin A from phage Group II staphylococci at various concentrations in DMEM. They were examined at various time intervals by direct microscopic and histological examination of respectively the culture plates or the epidermal sheets after their detachment from the plates with dispase grad II. A total exfoliation could be obtained at 24 hour at concentrations of Img and 500 micrograms/ml, only local areas of epidermolysis noted at 100 micrograms/ml. The intraepithelial separation was noted to occur between the basal layer and the lowest intermediate layer. No exfoliation could be observed at lower concentrations. Up to 4-5 hours few changes were evident, but at this time small areas of epidermolysis developed. With exfoliatin 100 micrograms/ml, intraepidermal blisters were clearly visible, occurring either between the basal cells and the lowest intermediate layer or between the first two intermediate cell layers. At the ultrastructural level, desmosomes were sparse and altered, with enlargement of the intercellular spaces and condensation of tonofilaments. These data indicate that human epidermal cell cultures, although their differentiation in culture only mimics what occurs in vivo, can be used as an in vitro model of the staphylococcal TEN to further investigate the site of action of such a toxin and the cellular mechanism responsible for the syndrome.

Adult↗
PubMed1993

Bullous dermatoses associated with systemic disease.

The bullous diseases that are neither immune-mediated nor inherited form a heterogeneous group that may be classified according to their major histopathologic characteristics. Such a classification allows clear distinctions to be made between entities that may have clinical similarities such as staphylococcal scalded skin syndrome, toxic shock syndrome, erythema multiforme/toxic epidermal necrolysis, and acute graft-versus-host disease. Proper differentiation of these entities is critical for their study and for appropriate management.

Amyloidosis↗
PubMed1993

[Clinical studies on flomoxef in neonates].

Clinical studies on flomoxef (FMOX) were performed in neonates and the results obtained are summarized as follows. Treatment with FMOX was made in 4 cases of neonatal bacterial infections; 2 cases of sepsis (suspected) and 1 case each of infection of umbilicus and staphylococcal scalded skin syndrome. Results obtained were excellent in 1 case, good in 3 cases. No significant side effects due to the drug were observed in any cases.

Cephalosporins↗