eMedicine Specialties > Dermatology > Bacterial Infections

Staphylococcal Scalded Skin Syndrome

Author: Jessica H Kim, MD, Clinical Assistant Professor, Division of Dermatology, University of Washington School of Medicine; Dermatology Consultant, Cascade Eye & Skin Centers
Coauthor(s): Paul Benson, MD, Chief, Program Director, Dermatology Service, Walter Reed Army Medical Center; Associate Professor, Department of Dermatology, Uniformed Services University of the Health Sciences at Bethesda
Contributor Information and Disclosures

Updated: Apr 29, 2009

Introduction

Background

Staphylococcal scalded skin syndrome (SSSS) is a toxin-mediated type of exfoliative dermatitis. Toxin-mediated staphylococcal syndromes comprise a group of blistering skin diseases, ranging in severity from localized bullous impetigo to staphylococcal scalded skin syndrome, in which superficial blistering and exfoliation follow widespread painful erythema.

Pathophysiology

Staphylococcal scalded skin syndrome (SSSS)is caused by toxigenic strains of Staphylococcus aureus, usually belonging to phage group 2 (types 3A, 3B, 3C, 55, or 71). Two exotoxins (ETs), epidermolytic toxin A (ET-A) and epidermolytic toxin B (ET-B), are responsible for the pathologic changes seen in staphylococcal scalded skin syndrome.¹ These toxins cause intraepidermal splitting through the granular layer by specific cleavage of desmoglein 1 (also the target protein in the autoimmune blistering dermatosis, pemphigus foliaceus), a desmosomal cadherin protein that mediates cell-to-cell adhesion of keratinocytes in the granular layer.^2,3,4

Specific targeting of desmoglein 1 by ETs allows S aureus to proliferate and spread beneath the barrier of the skin. Crystal structures and amino acid sequences indicate that these toxins act as serine proteases and cleave desmoglein 1 after glutamic acid residue 381 between extracellular domains 3 and 4. The ET-A and ET-B amino acid sequences are approximately 40% identical with each other.

Researchers have found an additional ET family member, ET-D, by screening the genomes of S aureus isolated from patients with skin infections. They demonstrated that ET-D specifically digested desmoglein 1. However, only ET-A and ET-B have been firmly linked to human staphylococcal scalded skin syndrome. The ET-D gene was detected mainly in isolates from patients with skin and soft-tissue infections, such as furuncles, abscesses and finger pulp infections.^5,6

It has been suggested that ET-B is more frequently isolated than ET-A in children with staphylococcal scalded skin syndrome. This link between ET-B and generalized staphylococcal scalded skin syndrome might be due to increased virulence of ET-B or to more abundant ET-B release. Because ET-A is chromosome borne and ET-B is plasmid borne, multiple copies of the ET-B gene could possibly lead to higher ET-B production. However, levels of ET-A and ET-B are quite similar in vitro. The link between ET-B and generalized staphylococcal scalded skin syndrome may be explained, at least in part, by lower levels of anti-ETB antibodies than anti-ETA antibodies in the general population.

An asymptomatic adult carrier introduces the causative bacteria into the nursery. Asymptomatic nasal carriage of S aureus occurs in 20-40% of healthy individuals, with the organism being isolated from the hands, the perineum, and the axillae in a smaller proportion of the general population.

Frequency

United States

Staphylococcal scalded skin syndrome most commonly occurs in infants and in young children, and it tends to occur in outbreaks in neonatal nurseries or in day care nurseries. Large outbreaks of staphylococcal scalded skin syndrome in neonatal nurseries have been described, but the occurrence of staphylococcal scalded skin syndrome in adults as a nosocomial infection appears to be exceptional; epidemics have never been observed.

Epidemiologic data on strains of S aureus that produce ET are scarce. In a prospective clinical and bacteriologic study, 5.1% of 944 isolates of S aureus were identified as ET producers. Staphylococcal scalded skin syndrome in adults is an exceedingly rare disorder, with only 50 reported cases.

International

A retrospective study at the Lagos University Teaching Hospital in Nigeria over a 12-year period (January 1995 to December 2006) reviewed the presentation, etiology, and prognosis of nonburn epidermal loss. Only 2 (9%) of 19 patients had confirmed staphylococcal scalded skin syndrome. The first patient was an 18-day-old boy and the other was a 26-day-old girl admitted with a left lateral thigh abscess. Cultures in both cases yielded the growth of S aureus, which responded well to antibiotic treatment and dressings.⁷

In another retrospective study in England, hospital admissions were reviewed to identify trends in community-onset disease that were likely to be caused by pathogenic staphylococci. Hospital admission rates for staphylococcal septicemia, staphylococcal pneumonia, staphylococcal scalded skin syndrome, and impetigo increased greater than 5-fold from 1989 through 2004. Staphylococcal scalded skin syndrome was seen primarily in individuals older than 16 years. This reflects the real increases in pathogenic community-onset staphylococcal disease over the past 15 years.⁸

Mortality/Morbidity

Children generally do well and are not as ill as their dramatic eruptions might suggest. Staphylococcal scalded skin syndrome is usually associated with a trivial infective focus in the conjunctivae or the skin; however, severe infections, such as sepsis, do contribute to a low but appreciable fatality rate (4%).

• Morbidity in the occasional child who develops cellulitis, sepsis, and pneumonia can be significant.
• In children, the foci of staphylococcal infections are usually the nasopharynx or localized skin infections.

Adults with staphylococcal scalded skin syndrome often have blood cultures positive for toxigenic S aureus, and mortality rates can be high (>60%). The predisposing conditions are renal failure and immunocompromise. In older patients, underlying consumptive infectious diseases contribute to the high mortality rates.⁹

Staphylococcal scalded skin syndrome has been reported as a complication of septic arthritis after an elective right knee arthroscopy and lupus nephritis associated with chronic immunosuppressant therapy.¹⁰

A single report describes concurrent staphylococcal scalded skin syndrome and toxic shock syndrome (TSS), an acute life-threatening illness caused by TSS toxin also produced by S aureus, in a 43-year-old man associated with a abscess from previous dental work. This patient had normal renal function, but the amount of toxin produced from the abscess may have overwhelmed the kidneys' capacity to remove it. Although colonization with a strain of S aureus capable of producing TSS toxin and ET-Aor ET-B is possible, the clinical presentation of both staphylococcal scalded skin syndrome and TSS is extremely uncommon.¹¹ Only one other such case has been reported.¹²

Race

Black children are less prone to staphylococcal scalded skin syndrome than white children.

Sex

A male-to-female predominance exists (2:1 in sporadic cases, 4:1 in epidemics).

Age

• The disease most commonly affects children younger than 5 years, particularly neonates. A decreased ability to achieve renal clearance of toxins and a lack of specific immunity (antibody) to the toxins make neonates the group at highest risk.
• Older children and adults may also develop the disease. In such cases, renal insufficiency or immunodeficiency (eg, HIV infection, advanced stage of cancer) appears to explain the susceptibility to the syndrome. This happens because for the development of staphylococcal scalded skin syndrome, a massive production of toxins or deficiency in their elimination must be present. Adults who are affected range in age from 19-91 years, with one half of the cases occurring in adults older than 60 years.^13,14,15,16

Clinical

History

• Staphylococcal scalded skin syndrome (SSSS) originates from a focus of infection that may be a purulent conjunctivitis, otitis media, or occult nasopharyngeal infection. A case of staphylococcal scalded skin syndrome from a nasal septal abscess, presumably arising from a traumatic hematoma (a tsunami survivor), has been reported.¹⁷ In premature infants, a previous amniocentesis procedure and intrauterine infection have been reported as triggers for staphylococcal scalded skin syndrome.^18,19
• Staphylococcal scalded skin syndrome usually begins with fever, irritability, and a generalized, faint, orange-red, macular erythema with cutaneous tenderness.
• Periorificial and flexural accentuation may be observed. A positive Nikolsky sign (slippage of the superficial layer of the epithelium on gentle pressure) can often be elicited at this stage.

Physical

• Within 24-48 hours, the rash progresses from a scarlatiniform to a blistering eruption.

• Characteristic tissue paper–like wrinkling of the epidermis is followed by the appearance of large, flaccid bullae in the axillae, in the groin, and around the body orifices.

• Subsequent generalized involvement occurs elsewhere on the body, but infection spares the mucous membranes.
• As sheets of epidermis are shed, a moist erythematous base is revealed.
• Despite the dramatic clinical picture, the entire process usually subsides with superficial desquamation, and healing is usually complete within 5-7 days.
• In adults, it is frequently followed by bacteremia and pneumonia, favoring a poor prognosis.
• Cultures obtained from intact bullae are usually sterile; this finding is consistent with hematogenous dissemination of a toxin produced at a distant focus of staphylococcal infection.
• An abortive form of staphylococcal scalded skin syndrome, known as the scarlatiniform variant, shows the early erythrodermic and final desquamative stages seen in staphylococcal scalded skin syndrome, but the bullous stage does not occur.
• Other intermediate forms of scalded skin syndrome begin as localized bullous impetigo, but they evolve to produce regionally limited bullae and denuded areas that may or may not harbor staphylococci.

Causes

See Pathophysiology.

• ET-A and ET-B are serine proteases that specifically target desmoglein-1. They are also sources of superantigenic activity and activate macrophages to produce proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin 6. ET-A with an active site mutation was shown to possess a similar inflammatory activity, indicating that the inflammatory activity of ET-A was separate from its epidermolytic activity.²⁰ Systemic symptoms, particularly the characteristic rash, are very likely a direct result of the toxin.
• A small number of patients with SSSS develop low titers of immunoglobulin G antibodies specific for desmoglein-1 after binding and systemic digestion of desmoglein-1 by staphylococcal exfoliative toxins. The relevance of this finding to the onset of autoimmune diseases remains to be proven. Other genetic or environmental factors may be needed to extend the immune response to encompass pathogenic antibodies and to produce overt clinical pemphigus foliaceus.²¹

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