Background
Staphylococcal scalded skin syndrome (SSSS), also known as Ritter von Ritterschein disease (in newborns), Ritter disease, and staphylococcal epidermal necrolysis, encompasses a spectrum of superficial blistering skin disorders caused by the exfoliative toxins of some strains of Staphylococcus aureus. [1]
It is a syndrome of acute exfoliation of the skin typically following an erythematous cellulitis. Severity of staphylococcal scalded skin syndrome varies from a few blisters localized to the site of infection to a severe exfoliation affecting almost the entire body. A mild form of the illness involving desquamation of just the skin folds following impetigo has been described. [1, 2]
Pathophysiology
Staphylococcal scalded skin syndrome (SSSS) is caused by an exfoliative toxin produced by roughly 5% of Staphylococcus aureus. As the syndrome evolves, an initial infection occurs, commonly at a site such as the oral or nasal cavities, throat, or umbilicus. [3] Epidermolytic toxins are produced by the infecting Staphylococcus species; these toxins act at a remote site leading to a red rash and separation of the epidermis beneath the granular cell layer. Bullae form, and diffuse sheetlike desquamation occurs. Two types of staphylococcal scalded skin syndrome are thought to exist: a localized form, in which there is only patchy involvement of the epidermis, and a generalized form, in which significant areas are involved, remote from the initial site of infection. [1]
Two exfoliative toxins (ETA and ETB) have been isolated and characterized, but the exact mechanism by which they cause exfoliation had until recently been uncertain. The toxins likely act as proteases that target the protein desmoglein-1 (DG-1), an important keratinocyte cell-to-cell attachment protein found only in the superficial epidermis. [4, 5, 6] The relative quantity of DG-1 in the skin differs with age and may partially explain the increased frequency of staphylococcal scalded skin syndrome in children younger than 5 years. It is theorized that immature renal function in this age group may contribute to impaired clearance of circulating exotoxins, contributing to more extensive disease. Another theory suggests that the exfoliative toxins may possess a superantigenic activity.
The decrease in frequency of staphylococcal scalded skin syndrome (SSSS) in adults is thought to be explained by the presence of antibodies specific for exotoxins and also improved renal clearance of toxins that are produced.
Initial studies suggested that phage lytic group II S aureus (subtypes 3A, 3B, 3C, 55 and 71) were solely responsible for exfoliative toxin production, but it is now known that all phage groups are able to produce exfoliative toxin and cause staphylococcal scalded skin syndrome.
Staphylococcal scalded skin syndrome differs from bullous impetigo. Both are blistering skin diseases caused by staphylococcal exfoliative toxin. However, in bullous impetigo, the exfoliative toxins are restricted to the area of infection, and bacteria can be cultured from the blister contents. In staphylococcal scalded skin syndrome, the exfoliative toxins are spread hematogenously from a localized source potentially causing epidermal damage at distant sites. Therefore, cultures of the bullous material are sterile. [1]
Staphylococcal scalded skin syndrome differs from the more severe toxic epidermal necrolysis (TEN), in that the cleavage site in staphylococcal scalded skin syndrome is intraepidermal, as opposed to TEN, which involves necrosis of the full epidermal layer (at the level of the basement membrane).
Epidemiology
Frequency
United States
Staphylococcal scalded skin syndrome (SSSS) is most common in children and neonates. Staphylococcal scalded skin syndrome is rarer in adults, but it has been described in adults with renal failure, immunologic deficiency, and other chronic illness. [7, 8] . The mean annual incidence of SSSS can be approximated as 7.67 (range 1.83-11.88) per million US Children, with 45.1 cases per million in US infants aged < 2 years. [9]
International
Internationally, predominance is in children as well. Overall incidence is higher in developing countries and wherever the incidence of staphylococcal infections is higher. Additionally, some geographic difference exists in the incidence of staphylococcal strains and the types of exotoxins produced. [10] Some recent reports show an increase in hospitalizations and prescriptions for staphylococcal disease, including SSSS, [11, 9]
Mortality/Morbidity
The mortality rate from staphylococcal scalded skin syndrome (SSSS) in children is very low (0.33-5%), unless associated sepsis or an underlying serious medical condition exists. The mortality rate in adults is higher (as high as 50-60%), although this may be a reflection of the underlying disorder, which increased susceptibility to SSSS, and not SSSS itself. [12, 13, 14, 9] Significant morbidity can result from hematologic or local spread of infection. [15] Complications are usually the result of sepsis, superinfection, and dehydration or electrolyte imbalance due to denuded skin.
Sex
SSSS is associated with female sex with adjusted odds ratio of 1.12 (1.00-1.25). [9]
Age
Staphylococcal scalded skin syndrome (SSSS) primarily is a disease of children.
Children are more at risk because of lack of immunity and immature renal clearance capability (exfoliative toxins are renally excreted). Maternal antibodies transferred to infants in breastmilk are thought to be partially protective, but neonatal disease can still occur possibly as a result of inadequate immunity or immature renal clearance of exotoxin. [16, 17, 18, 19] There is at least one report of recurrent SSSS in a neonate. [20]
SSSS can occur individually or as outbreaks in nurseries. Outbreaks are usually due to asymptomatic carriers who spread the disease to susceptible individuals. [21]
Most children are younger than 2 years, and almost all are younger than 6 years. [9]
SSSS is rare in adults, with fewer than 50 cases formally reported in the literature. Adults with SSSS are most often chronically ill, are immunocompromised, or have renal failure. SSSS can also appear in adults in cases with a high burden of staphylococcal infection where the quantity of exotoxin is significant. There is also a case report of SSSS in an adult after tooth extraction. [22]
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Staphylococcal scalded skin syndrome. Photograph by David Effron, MD, FACEP.
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Staphylococcal scalded skin syndrome. Photograph by David Effron, MD, FACEP.
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Staphylococcal scalded skin syndrome. Photograph by David Effron, MD, FACEP.
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Staphylococcal scalded skin syndrome. Photograph by David Effron, MD, FACEP.
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Staphylococcal scalded skin syndrome. Photograph by David Effron, MD, FACEP.
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Staphylococcal scalded skin syndrome. Photograph by David Effron, MD, FACEP.
