• Bullous impetigo;
  • exfoliative toxin;
  • France;
  • generalized exfoliative syndrome;
  • incidence;
  • staphylococcal scalded skin syndrome;
  • Staphylococcus aureus ;
  • typing


  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information

Clin Microbiol Infect


Epidemiological data on staphylococcal scalded skin syndromes (SSSS), including bullous impetigo (BI) and generalized exfoliative syndrome (GES), are scarce. To better characterize SSSS and associated Staphylococcus aureus strains, we conducted a retrospective study of 349 cases collected in France between 1997 and 2007 by the National Reference Centre of Staphylococci. Our results showed a stationary evolution of SSSS cases, with a heterogeneous distribution of cases in France. Although notification was not exhaustive, we estimated an incidence of 0.56 cases/year/million inhabitants, in accordance with previous studies conducted in France and Europe, with a median age of 2 years old and sex ratios of 1. A seasonal effect was observed, with a higher GES/BI ratio in autumn compared with other seasons, which could be explained by the impact of viral co-infection. Genetic analysis of S. aureus strains showed that accessory gene regulator (agr) 4, exfoliative toxin A (eta) and B (etb) genes, staphylococcal and enterotoxin-like O (selo) gene and agr4 etb selo profiles were predominantly associated with GES, whereas agr2 eta and agr4 eta selo were more frequently observed with BI. Only one methicillin-resistant strain was found. Protein A (spa) typing identified two main genotypes: spa clonal complex (CC) 159/sequence-type (ST) 121 (75%) and spaCC346/ST15 (18%). spaCC159 was mainly associated with agr4 eta etb selo, agr4 eta selo and agr4 etb selo, and spaCC346 was mainly associated with agr2 eta, suggesting that French SSSS cases are caused by these two main lineages. However, in a multivariate analysis, only etb was independently associated with GES.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information

Staphylococcal scalded skin syndrome (SSSS) is a generic term referring to a group of rare blistering diseases ranging from generalized diseases (generalized exfoliative syndrome (GES), Ritter’s disease in newborns) to localized bullous impetigo (BI) caused by Staphylococcus aureus producing exfoliative (or epidermolytic) toxin (ET). To date, four variants of the toxin have been described: exfoliative toxins A, B, C and D (ETA–ETD) [1–3]. ETA, ETB and ETD belong to the serine protease family, whereas there are still doubts concerning ETC because the sequence published in GenBank (BAA99412) corresponds to an adenylosuccinate lyase [2]. The ETs induce epidermal blistering through the cleavage of the cell–cell adhesion molecule desmoglein-1, which is only expressed by keratinocytes in the granular cell layer [4]. ET activity is host specific and among ETs only ETA and ETB exhibit human specificity as the result of a strong cleavage activity of human desmoglein-1, which explains why only ETA-producing and ETB-producing strains are epidemiologically associated with SSSS, and not ETD [4–6].

Only 5% of S. aureus human isolates produce ETA or ETB, with differences in their prevalence between countries [7]. Previous studies have suggested that ET-producing strains are mainly associated with a few S. aureus genetic backgrounds, as defined by phage type, accessory gene regulator (agr) groups or amplified fragment length polymorphism analysis, but these genetic backgrounds have not been extensively defined by ‘protein A (spa) typing’ or multilocus sequence typing [8,9]. From an epidemiological point of view, data on SSSS are scarce in the absence of active survey of the diseases.

The aim of this work was to examine the epidemiology of SSSS and the microbiological characteristics of ET-producing strains isolated in France during the last 10 years.

Material and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information


All cases of SSSS referred to the National Reference Centre of staphylococci (CNR-Staph) between 1 January 1997 and 31 December 2007, from different hospitals in France were considered in the study. The included cases were identified primarily by review of the medical records. GES was diagnosed in patients with erythroderma progressing within 1–2 days to spontaneous exfoliation with a positive Nikolsky’s sign and fever; BI was diagnosed in patients with localized bullous lesions and exfoliation who were afebrile [7]. A total of 349 cases fulfilling the definition of SSSS were included in this study, comprising 212 GES cases and 137 BI cases. Data including age, sex, date of SSSS diagnosis, geographic localization, source of the clinical sample where the strain was isolated and clinical associate diagnosis were collected for each case.

S. aureus isolates

Staphylococcus aureus was isolated from patients with GES by swab culture of the skin surface or distant sites, such as the throat, nose, eyes and ears, and blood culture. Isolates from patients with BI were generally cultured from bullous lesions. A single isolate was studied when multiple identical isolates were recovered from the same patient. The S. aureus was identified as previously described [8].

Strain characterization

A total of 283 strains, corresponding to 167 GES and 116 BI cases, were selected among 349 strains including 3, 1, 9, 28, 38, 33, 36, 50, 52 and 33 strains isolated in 1997, 1998 and 2000 to 2007, respectively. They comprised a subset of strains isolated between 1997 and 1999 from Jarraud’s collection (a random selection of strain isolated between 1985 and 1999) [8] and all SSSS strains received by the CNR-Staph between 2000 and 2007. Genomic DNA was extracted with a standard procedure. A PCR was used to detect sequences specific for agr and the following toxin genes as previously described [8,10,11]: tst, sea, seb, sec, sed, seh, selo, eta, etb, etd, pvl and mecA encoding toxic shock syndrome toxin-1, staphylococcal enterotoxins A–D and H, staphylococcal enterotoxin-like O, exfoliative toxins A, B and D, Panton–Valentine leukocidin and methicillin resistance, respectively. Staphylococcal Cassette Chromosome mec cassette type was determined by DNA microarray (StaphyType kit; Alere Technologies GmBH, Jena, Germany) as previously described [12]. Typing of spa was also performed as previously described [13]; spa types were determined using Ridom Staph Type® software (Ridom GmbH, Münster, Germany, [13], and spa types were clustered into clonal complexes (spaCCs) with the integrated Based Upon Repeat Patterns (BURP) algorithm [14]. User-definable parameters were set as follows: ‘cluster spa types into spaCC if cost distances are ≤4’ and ‘exclude spa types shorter than five repeats’. Sequence type (ST) was inferred from certain spa-types as suggested by Ridom Staph Type® software [13].

Statistical analysis

Incidence per million inhabitants was calculated per year on the average population of the cover area. The average yearly population corresponding to the period 1997–2007 was obtained from the French ‘Institut national de la statistique et des études économiques’ (INSEE; The number of observed cases per year was considered a sample over the time to estimate 95% CI for the number of expected new cases per year. Taking into account that the occurrence of SSSS is extremely rare, the 95% CI were calculated assuming a Poisson distribution as previously performed [15]. Chi-square tests were used to compare proportions. Genetic determinants (toxin gene, agr type, spaCC) with unequal distribution between GES and BI were included in a binary multivariate logistic regression analysis to determine the most influential explanatory variables for the clinical presentation. All of the analyses were performed using SPSS® software (SPSS Inc., Chicago, IL, USA).


  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information

Number and distribution of SSSS cases in France

Between January 1997 and December 2007, we collected 349 cases, including 212 cases of GES and 137 cases of BI. The number of cases varied from 10 to 53 per year, with a non-significant increase in the number of cases during these 10 years (Fig. 1). The mean incidence of SSSS in France was estimated to be 0.56 cases/year/million inhabitants (95% CI 0.37–0.74; Table 1) with extreme values going to 0.17 (95% CI 0.01–0.27) cases/year/million inhabitants in 1997 to 0.84 (95% CI 0.63–1.1) cases/year/million inhabitants in 2006. However, high variation between administrative regions was observed (1–118 cases), suggesting a non-exhaustive sample (Table 1). The highest notification was in the Rhône area (75 cases in 10 years for 1 700 000 inhabitants, that is c.4.4 (95% CI 1.3–7.6) cases/year/million inhabitants), where CNR-Staph is located. At the regional level, we observed a homogeneous distribution of SSSS cases per year, except for the Ile de France region from 2003 to 2005 and the Aquitaine region in 2005 (see Supplementary material, Fig. S1).


Figure 1.  Distribution of the number of cases of staphylococcal scalded skin syndrome (SSSS), generalized exfoliative syndrome (GES) and localized bullous impetigo (BI) per year and per year estimated incidence of SSSS cases according to the French National Reference Centre of staphylococci notifications from 1997 to 2007. Annual estimated incidences of SSSS cases (dotted curve and secondary scale in grey) were calculated with the French population data provided by the French ‘Institut National des Statistiques et des Etudes Economiques’ and available from

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Table 1.   Estimated incidence of staphylococcal scalded skin syndrome (SSSS) cases in France according to the French National Reference Centre of staphylococci notifications from 1997 to 2007
Name of French regionNumber of SSSS cases between 1997 and 2007Number of inhabitantsaCalculated incidence of SSSS cases
  1. aNumber of inhabitants in 2008, as provided by the French Institut National des Statistiques et des Etudes Economiques, available from

Alsace61 837 0870.33
Aquitaine293 177 6250.91
Auvergne91 341 8630.67
Brittany73 149 7010.22
Burgundy171 638 5881.04
Centre32 531 5880.12
Champagne-Ardennes41 338 0040.30
Corse0302 9660
Franche-Comté31 163 9310.26
Ile de France4311 659 2600.37
Languedoc-Roussillon42 581 7180.15
Limousin10740 7431.35
Lorraine122 346 3610.51
Lower Normandy61 467 4250.41
Midi-Pyrénées92 838 2280.32
Nord Pas de Calais214 024 4900.52
Pays de Loire63 510 1700.17
Picardy51 906 6010.26
Poitou-Charentes61 752 7080.34
Provence Alpes Côte d’Azur204 882 9130.41
Rhône-Alpes1186 117 2291.93
Upper Normandy61 825 6670.33
Overseas regions52 013 4450.25
Total34964 148 3110.54

Characteristics of patients suffering from SSSS

The vast majority of the cases occurred in young patients, with a median age of 1.8 years for GES (newborn to 81.3 years) and 2.3 years for BI (newborn to 72.3 years). Only five (2.4%) cases of GES and ten (7.3%) cases of BI were from patients older than 18 years. Sex ratios were roughly similar: 0.81 for GES and 1.19 for BI. Of note, 19 (5.4%) cases of SSSS occurred after varicella: nine (4.2%) GES and ten (7.3%) BI.

Effect of seasons on SSSS occurrence

We observed variations in the number of notified cases of SSSS between seasons. The number of SSSS cases increased during the summer for both GES and BI. However, the GES/BI ratio was significantly higher in autumn compared with other seasons (p 0.021; Fig. 2).


Figure 2.  Distribution of staphylococcal scalded skin syndrome presentations over the seasons. BI, localized bullous impetigo; GES, generalized exfoliative syndrome. p calculated using a chi-square test.

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Isolation sites of SSSS strains

Of the 212 cases of GES, eta- and/or etb-positive strains were isolated from skin lesions in 119 (56.1%) cases; the throat, nose, eyes or ears in 75 (35.4%) cases; and the stool in two (0.9%) cases. In 13 (6.1%) cases, toxigenic strains were isolated from deep sites, such as blood cultures (eight cases, 3.8%) and peritoneal fluid. The sampling site was not indicated for three (1.4%) patients. In the 137 BI cases, eta- and/or etb-positive strains were isolated from skin lesions in 113 (82.5%) cases and the throat, nose, eyes or ears in 23 (20.4%) cases. Only one (0.7%) sampling site was not known.

Toxin profiles of French SSSS strains

The toxin gene profile was determined in a subset of 283 strains. These strains were all positive for the production of at least one exfoliative toxin: 36% of strains carried eta alone, 10% carried etb alone and 54% carried both eta and etb. No strain carried the etd gene (Table 2). Allelic determination of agr showed that 76% of strains were agr4, 22% were agr2, 2% were agr3 and one strain was agr1. Among genes encoding superantigenic toxins, 80% of isolates were positive for selo and 4% were positive for seb, whereas sea and sed were detected only once, no strain contained tst or sec, and pvl was detected in two isolates. The most frequent gene associations were agr4 eta etb selo (50%), followed by agr2 eta (17%), agr4 eta selo (12%) and agr4 etb selo (10%).

Table 2.   Distribution of toxin and spa clusters among Staphylococcus aureus isolates from generalized exfoliative syndromes (GES) and bullous impetigo (BI)
Genes/gene associationGES (n = 167)BI (n = 116)pa
  1. spa type using Ridom Staph Type® software and spaCC were determined using the integrated Based Upon Repeat Patterns (BURP) algorithm as described in Material and methods. Sequences specific for agr1–4 and the toxin genes tst, sea, seb, sec, sed, seh, selo, eta, etb, and lukS-PV-lukF-PV were detected by polymerase chain reaction. Percentages were calculated in comparison to total numbers of GES and BI respectively. Data given in parentheses are expressed as percentage.

  2. Nd, not determined.

  3. aChi-square test.

  4. beta, etb and etd: genes encoding exfoliative toxins A, B and D.

  5. cetd detection was performed on only 278 isolates.

  6. dsea–d, genes encoding staphylococcal enterotoxin A–D.

  7. eselo, genes encoding staphylococcal enterotoxin-like O.

  8. fpvl, gene encoding Panton–Valentine leukocidin.

  9. gmecA, gene encoding resistance to methicillin.

  10. hagr, allele of accessory gene regulator.

  11. jspaCC, clonal complexes determined by spa typing.

 etab 142 (85)112 (97)0.001
 etbb 127 (76)54 (47)<0.001
 etdb 0c0cnd
 sead 1 (0.6)0nd
 sebd 7 (4)4 (3.4)nd
 sedd 1 (0.6)0nd
 seloe 146 (87)82 (71)0.001
 pvlf 2 (1.1)0nd
 agr1h 01 (0.9)nd
 agr2h 24 (14)38 (33)<0.001
 agr3h 3 (1.8)2 (1.7)nd
 agr4h 140 (83)75 (65)<0.001
 spaCC159 141 (84.4)71 (61.2)<0.001
 spaCC346 16 (9.6)34 (29.3)<0.001
 spa209/4812 3 (1.8)6 (5.2)nd
 spa186/692 3 (1.8)2 (1.7)nd
 spa2166/8692 1 (0.6)1 (0.9)nd

Spa types of French SSSS strains and their sequence type assignments

Spa typing was successfully performed on 280 of the 283 S. aureus isolates and led to the classification of 277 strains with 40 different spa types distributed in five main spaCC clusters plus singletons (Tables 2 and 3). The number of isolates associated with each spaCC cluster ranged from 2 to 212 isolates. Among them, 75% belonged to spaCC159 (ST121), and 18% belonged to spaCC346 (ST15). For the other spaCCs, no founder was identified. The distribution of spaCCs remained stable during the 10 years of the survey.

Table 3.  Spa type, agr type and toxin gene profile of Staphylococcus aureus isolates from staphylococcal scalded skin syndrome
Cluster (spaCCa) spa type agrb Genes encoding toxinsTotalGES (n = 167)BI (n = 116)
  1. spa type and spaCC were determined using the integrated Based Upon Repeat Patterns (BURP) algorithm as described in Material and methods. Sequences specific for agr1–4 and the toxin genes tst, sea, seb, sec, sed, seh, selo, eta, etb, and lukS-PV-lukF-PV were detected by PCR.

  2. GES, generalized exfoliative syndrome; BI, bullous impetigo; ND, not described; NC, not clustered; NT, not typeable.

  3. aspaCC, clonal complexes determined by spa typing.

  4. bagr, allele type of accessory gene regulator.

  5. ceta, etb, genes encoding exfoliative toxins A and B.

  6. dseb, gene encoding staphylococcal enterotoxin B.

  7. eselo, gene encoding staphylococcal enterotoxin-like O.

  8. gpvl, gene encoding Panton–Valentine leukocidin.

1 (spaCC159)1594 etac, etbc, sebd, seloe211
eta, etb, selo824933
eta, selo1596
etb, seb, selo110
etb, selo17152
2 eta, etb, selo110
eta, etb110
eta, selo101
eta 211
1624 eta, etb, selo101
eta, selo110
1714 eta, etb, selo17125
eta, selo312
etb, selo110
2694 eta, etb, selo220
eta, selo202
2 eta 110
2724 eta, etb, selo330
eta, seb, selo110
eta, selo202
2844 eta, etb, selo321
4084 eta, etb, selo431
6052 eta 110
6454 eta, etb, selo10100
eta, seb, selo101
eta, selo202
etb, selo431
6594 eta, etb, selo330
eta, selo110
2 eta 101
9404 etb, selo, pvlf110
10774 etb, selo110
12604 eta, etb, selo101
2 eta, selo110
14254 eta, etb, selo330
20194 eta, selo101
20864 eta, selo110
21554 eta, etb, seb, selo642
eta, etb, selo110
32414 eta, selo101
41514 etb, selo110
43904 eta, etb, selo110
81944 eta, etb, selo101
etb, selo101
86394 eta, etb, selo101
86884 etb, selo110
87624 eta, etb, selo110
88224 eta, etb, selo220
2 (spaCC346)844 eta, etb, selo312
eta, selo110
2 eta, selo101
eta 291217
972 eta 101
2542 eta 514
3464 eta 101
2 eta, selo 101
eta 303
1 eta, selo 101
3602 eta 101
18752 eta 101
18772 eta 211
3 (spaCC ND)2094 eta, selo101
2 eta, selo624
eta 101
48122 eta, selo110
4 (spaCC ND)1864 eta, etb, selo110
3 eta 220
6923 eta 202
5 (spaCC ND)21664 eta, etb, selo110
86924 eta, etb, selo101
NC671 eta, selo110
36233 eta, sea, selo, pvl110
NT4 eta, selo202
NT4 etb, selo110

Methicillin resistance of French SSSS strains

Only one strain isolated from a post-varicella GES and characterized by a genetic profile of agr3 eta spa t186 (ST88) was mecA positive, showing an IV-SSCmec cassette type (Table 2).

Analysis of potential associations between SSSS clinical presentation, toxin gene contents, and spa type

When we compared the distribution of genes between isolates from patients with GES and BI, the distribution of eta, etb, selo, agr2 and agr4 differed significantly (Table 2). Briefly, etb, selo and agr4 were more frequent in isolates from GES than BI; however, the opposite was found for eta and agr2. When we compared associations between gene profiles and the type of diseases, we observed similar results: agr4 eta etb selo and agr4 etb selo gene profiles were predominantly associated with GES, whereas for BI, the predominant gene profiles were agr2 eta and agr4 eta selo. Clinical presentation also depended of the spa type: spaCC159 was more frequent in isolates from GES than BI, whereas it was the opposite for spaCC349. Gene profiles of the strains were also linked to the spa type. Genotypes agr4 eta etb selo, agr4 etb selo, and agr4 eta selo were mainly associated with spaCC159, whereas genotype agr2 eta was predominantly associated with spaCC346. However, in binary logistic regression analysis including spaCC groups, agr alleles, eta, etb and selo, only etb was independently associated with GES (p 0.01).


  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information

We have retrospectively examined the epidemiology of 349 cases of SSSS, corresponding to 212 cases of GES and 137 cases of BI, that were reported to CNR-Staph from 1997 to 2007 by medical laboratories distributed throughout France. The number of cases remained stable during these 10 years, except for the Ile de France region from 2003 to 2005 and the Aquitaine region in 2005, which corresponded to two outbreaks in maternity wards, as previously reported [16,17]. Although SSSS is not a notifiable disease in France, our results allowed us to establish a mean incidence of SSSS cases based on spontaneous reporting by French microbiological laboratories of 0.56 (95% CI 0.37–0.74) cases/year/million, in accordance with previous estimates (0.30 and 0.35 during 1994–1997 and 1998–2000, respectively) and an estimation of 0.13 in Germany [15,18,19]. However, a large discrepancy in the notification between French regions is observed, suggesting many under-declarations of cases to CNR-Staph. Incidence estimation in the Rhône area, where declarations are the highest, was 4.4 cases/year/million. This value is closer to the incidence recently described in the Czech Republic from a 15-year survey, with an average incidence of 25.11 cases/million/year in children under 1 year old, which corresponds to 2.53 cases per million inhabitants per year [20]. However, SSSS, notably GES, can be difficult to diagnose on clinical signs with the lack of adapted microbiological samples and strain isolation. In accordance to similar SSSS surveys based on S. aureus strain isolations, our study is not exhaustive suggesting a higher incidence of SSSS cases in France than measured. Prospective surveys, including mild SSSS forms and based on clinical and histological data, should be performed. When we examined variations in the GES/BI ratio between seasons, most of the SSSS cases were observed during the summer. However, we observed a significantly higher ratio of GES/BI in autumn than other seasons (Fig. 2). Autumn shows a high incidence of viral upper respiratory tract infections in France caused by rhinovirus, parainfluenza virus, enterovirus, respiratory syncytial virus and influenza virus [21]. Because GES is usually accompanied by non-specific virus-like prodromal signs and symptoms in the upper respiratory tract, such as coryza, viral infections could contribute to the development of GES in young patients colonized by S. aureus ET-producing strains. We hypothesize that in ET-producing strain carriers, a virus infecting the upper respiratory tract of a young patient alters the epithelium and stimulates S. aureus proliferation, triggering ET production and diffusion in the body. Cooperation between influenza and parainfluenza viruses, and S. aureus has been previously described in pneumonia [22–24]. Moreover, we previously conducted a retrospective survey on S. aureus superinfections during varicella [25]. Exfoliative toxin genes were the second major toxinic factor detected in S. aureus isolates, suggesting that a specific survey should be performed to confirm the involvement of a virus in the pathophysiology of SSSS.

Regarding patient data linked to strains, the most cases occurred in young children. Only five GES and ten BI cases were observed in adult patients without renal dysfunction or immunosuppression, two main factors classically reported to be associated with SSSS in adults [26]. The vast majority of GES cases occurred in patients with only nasal colonization by S. aureus ET-producing strains and no focal infection; the exceptions were SSSS cases after superinfection of varicella, peritoneal infection and endocarditis.

In contrast to Japan, Switzerland and Taiwan [27–29], we did not observe the emergence of methicillin-resistant S. aureus (MRSA) -associated exfoliative toxin genes, with only one MRSA strain being agr3 spa t186 (ST88) with an IV-SSCmec cassette type. Although epidemiological data on MRSA isolated from SSSS were scarce, ST88, ST89 and ST91 have recently been linked to MRSA associated with BI in Japan [29,30]. Our strain belongs to one of these main MRSA clones and could be an imported Japan strain; however, no clinical data sustain this hypothesis. For decades, the majority of S. aureus strains responsible for SSSS in Europe have belonged to phage group II, particularly types 71 and 55/71 [26], agr4 or agr2 and the specific amplified fragment length polymorphism phylogenetic groups AF1 agr4 or AF2 agr2 [8,9]. Our results showed that 75% of S. aureus strains isolated from SSSS were agr4 spaCC159 (ST121), and 18% were agr2 spaCC346 (ST15). These strains correspond to AF1 agr4 and AF2 agr2, respectively. Because we did not perform phage typing, we do not know to which phage type they belonged. ST121 clones have previously been associated with skin and soft tissue infections involving Panton–Valentine leukocidin-positive methicillin-susceptible S. aureus (MSSA) strains in Europe and China [31]. Sporadic ST121 strains with exfoliative genes, MSSA and, more recently, MRSA have been described in paediatric patients in Portugal [32]. However, a recent multicentre Japanese study on MRSA strains responsible for BI noted that ST121 seemed to be the most common ST for exfoliative-positive MSSA [30]. Moreover, data describing ST15 strains are scarce. MRSA ST15 strains have been found in Italy, and ST15 MSSA strains with spa type t084 from spaCC346 have been similarly observed in China and Africa, but no data regarding exfoliative toxins or associations with specific clinical signs are available [33,34]. Only the previous Japanese study found three isolates of ST15 MSSA in addition to an ST8 MRSA in BI lesions [30]. Hence, our work is the first study that clearly associates, on a large collection of strains, spaCC159 (ST121) and spaCC346 (ST15) with SSSS and, more precisely, spaCC159 (ST121) with GES and spaCC346 (ST15) with BI. In fact, the genetic background of S. aureus is not enough to explain the occurrence of SSSS because ETA and/or ETB are necessary to induce SSSS. Because eta and etb are carried by mobile genetic elements [26,35], it is possible that the spaCC159 (ST121) and spaCC346 (ST15) backgrounds are favourable for their acquisition or expression. Moreover, we previously showed that eta was associated with BI, whereas etb was associated with GES [36]. The strength of this association was confirmed in our multivariate analysis, which demonstrated that only etb was independently associated with GES. Finally, we confirmed the lack of association between SSSS and ETD, with no etd-positive strain, as previously described in 2006 and confirmed by Japanese and Czech studies [5,6,37]. However, the possibility of overlooking an SSSS-like disease caused by an etd-positive strain could not be excluded because the clinical symptoms induced by these isolates may be milder than those caused by eta-positive or etb-positive strains and not notified to CNR-Staph.

In conclusion, during the last 10 years, we observed the stability of epidemiological parameters of SSSS and S. aureus lineages involved in these diseases, including spaCC159 (ST121) and spaCC346 (ST15) carrying eta or etb. We confirmed that the generalized form of SSSS is linked to the presence of etb, whereas the relative increase in GES in autumn suggests that autumnal upper respiratory tract infections by a viral agent may trigger ET effects in S. aureus ET-producing carriers.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information

We thank our biologist colleagues and specialists in laboratory medicine who sent us French Staphylococcus aureus isolates. We are also grateful to Christine Courtier, Christine Gardon, Céline Spinelli, Caroline Bouveyron, Virginie Dumoulin, Annie Martra and Martine Rougier for their technical help.

Transparency Declaration

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information

This study was supported by Institut Français de Veille Sanitaire (InVS), Institut National de la Santé et de la Recherche Médicale (INSERM) and Hospices Civils de Lyon. The authors declare that they have no conflicting interests in relation to this work.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information
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Supporting Information

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information

Figure S1. Distribution of the number of cases of staphylococcal scalded skin syndrome per year among French administrative regions between 1997 and 2007.

clm12053_sm_FigS1.pdf180KSupporting info item

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