Dermatologic Manifestations of Staphylococcal Scalded Skin Syndrome

Updated: Apr 25, 2017
  • Author: Elizabeth J Usedom, MSc; Chief Editor: Dirk M Elston, MD  more...
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Overview

Background

Staphylococcal scalded skin syndrome (SSSS) is a toxin-mediated exfoliative dermatitis. Toxin-mediated staphylococcal syndromes comprise a group of blistering skin diseases, ranging in severity from localized bullous impetigo to SSSS. SSSS is a systemic toxigenic process producing constitutional symptoms and widespread superficial blistering and exfoliation of the skin following generalized painful erythema.

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Pathophysiology

Staphylococcal scalded skin syndrome (SSSS) is caused by toxigenic strains of Staphylococcus aureus, a gram-positive, catalase-positive bacterium. Only 5% of all S aureus strains produce the epidermolytic toxins responsible for SSSS. The specific toxigenic strains usually belong 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 SSSS. [1] These toxins cause intraepidermal splitting through the granular layer of the epidermis, or stratum granulosum, by specific cleavage of desmoglein 1 (Dsg-1) (also the target protein in the autoimmune blistering dermatosis, pemphigus foliaceus). DSG1 is a desmosomal cadherin protein that mediates cell-to-cell adhesion of keratinocytes in all layers of the epidermis, including the skin and mucosa, but is in greatest abundance within the stratum granulosa. Desmoglein 3 (Dsg-3) (the target protein in the autoimmune blistering dermatosis, pemphigus vulgaris) is also present in the epidermis; it is expressed in the deeper layers of the skin and present in all layers of the mucosa. The distribution of desmogleins in the epidermis explains the preferential blistering of SSSS in the superficial skin and lack of blistering in mucous membranes. Despite cleavage of Dsg-1 by ET-A and ET-B, Dsg-3 maintains the integrity of the deeper layers of the skin, beginning with the stratum spinosum, and all layers of the mucosa. [2, 3, 4]

Specific targeting of Dsg-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 are calcium-dependent, atypical serine proteases and exhibit substrate specificity for glutamic acid. Therefore, these toxins cleave Dsg-1 at the N-terminus of 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. ET-A is expressed in more than 80% of toxigenic strains of S aureus and represents the more prevalent ET seen in SSSS. ET-B was found to be the more prevalent toxin in toxigenic strains only in Japan. [5]

An additional ET family member, ET-D, has been identified by screening the genomes of S aureus isolated from patients with skin infections. Studies demonstrated that ET-D specifically digests Dsg-1. However, ET-D is less common in S aureus isolated from SSSS cases and only ET-A and ET-B have been firmly linked to human SSSS. The ET-D gene was detected mainly in isolates from patients with skin and soft-tissue infections, namely furuncles, abscesses, and finger pulp infections. [6, 7]

In addition to the cleavage of Dsg-1, ET-A is correlated with a blunted inflammatory response within the affected superficial skin. While no direct effect by ET-A on white blood cells (WBCs) has been shown, it is hypothesized that Dsg-1 cleavage somehow triggers inhibition of the WBC infiltration of the local environment. Interleukin 6 (IL-6) production and subsequent release by keratinocytes is increased without similar increases in acute, proinflammatory cytokines following Dsg-1 cleavage. Both phenomena contribute to the local modulation of the immune response in SSSS. [8]

It has been suggested that ET-B is more frequently isolated than ET-A in children with SSSS. This link between ET-B and generalized SSSS 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 intracellular copies of ET-B may exist, which would 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 SSSS may be explained, at least in part, by lower levels of anti–ET-B antibodies compared with anti–ET-A antibodies in the general population.

The mechanism of neonatal infection is through an asymptomatic adult carrier introducing the causative bacteria into nurseries. Nursery attendants have been identified as the source more commonly than infant mothers. Asymptomatic nasal carriage of S aureus occurs in 20-40% of healthy individuals. The bacterium is also commonly isolated from the hands, perineum, and axillae in a smaller portion of the general population. Common foci of infection in the affected patient include the conjunctivae, periumbilical and perioral regions, nares, and perineum. These sites should be targeted for isolation of S aureus in affected patients.

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Epidemiology

Frequency

United States

Staphylococcal scalded skin syndrome (SSSS) most commonly occurs in infants and in young children, and it tends to occur in outbreaks in neonatal nurseries or in daycare nurseries. [9, 10, 11] Large outbreaks of SSSS in neonatal nurseries have been described, but the occurrence of SSSS in adults as a nosocomial infection appears to be exceptional; epidemics have never been observed. Adult infection and disease development are seen in specific instances involving either predisposition to SSSS development, such as HIV infection or chronic kidney disease, or a procedure or trauma that creates a potential nidus for S aureus infection.

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. SSSS in adults is an exceedingly rare disorder; however, more than 50 cases have been documented.

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 SSSS. 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. [12]

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, SSSS, and impetigo increased greater than 5-fold from 1989 through 2004. SSSS 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. [13] An outbreak in a maternity unit in England from December 2012 to March 2013 reinforced the importance of the role of healthcare workers in the nosocomial transmission of the syndrome. [14] A similar outbreak in a maternity unit in Italy from November 2014 to December 2014 identified 3 (4.5%) of 66 infants with SSSS. The infection was traced to methicillin-resistant S aureus (MRSA) colonization of three nurses and one mother. Overall, carriage of S aureus in the nares among the healthcare workers in the maternity unit was 24.1%. This report further supports the prevalence of asymptomatic carriers and their impact in neonatal outbreaks. [15]

Race

Black children are less prone to staphylococcal scalded skin syndrome (SSSS) than white children. This finding could be explained by the greater percentage of white individuals colonized with S aureus within the nasal mucosa compared with all other races. It has been well documented that carriage of S aureus is associated with increased risk of infection. The greater percentage of carriage in the white population may be correlated with the larger number of documented cases of SSSS within this population. [16]

Sex

Staphylococcal scalded skin syndrome occurs equally in both males and females in children. However, a slight male-to-female predominance of 2:1 exists in adults.

Age

Three significant factors determine the age distribution of staphylococcal scalded skin syndrome (SSSS): (1) antibody-mediated immunity to the epidermolytic toxins, (2) renal clearance of the toxins, and (3) general immune status of an individual. Antibodies to ET-A and ET-B develop over time and are seen in older children and adult sera. A lack of specific toxin immunity (antibodies) in neonates is one factor that puts this group at highest risk. Both ET-A and ET-B are cleared by the kidneys; therefore, a decreased ability to achieve renal clearance of toxins puts both neonates and all individuals with chronic kidney disease at a greater risk. Immunodeficiency in adults due to HIV infection, advanced stage of cancer, or numerous comorbid conditions, also increases the risk of SSSS. The immature immune system of the neonate and child also contributes to the prevalence of disease in this population.

Owing to these factors, SSSS most commonly affects children younger than 5 years, particularly neonates. Older children and adults also may develop the disease. Although most cases can be explained by renal insufficiency or immunodeficiency, not all adults have an underlying condition. Infection in healthy adults usually occurs from a massive production of toxins as opposed to the mode of disease in the previously mentioned groups, which occurs through deficiency in toxin elimination. Affected adults range in age from 19-91 years, with half the cases occurring in adults older than 60 years. [17, 18, 19, 20]

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Prognosis

The prognosis of the disease in children is favorable, as the mortality rate is less than 5% with appropriate treatment. In adult cases of staphylococcal scalded skin syndrome (SSSS), the mortality rate is high, reaching 60% in some studies, despite appropriate antibiotic therapy. [5]

Children generally do well and are not as ill as their dramatic eruptions might suggest. SSSS 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 (<10%). [21] 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 SSSS often have blood cultures positive for toxigenic S aureus, and mortality rates can be high (40-63%). [21] The predisposing conditions are renal failure and an immunocompromised state. In older patients, underlying consumptive infectious diseases contribute to the high mortality rates. [22]

SSSS in the adult population has been reported as a complication of septic arthritis after an elective right knee arthroscopy, diffuse large B-cell lymphoma following a right groin biopsy, and lupus nephritis associated with chronic immunosuppressant therapy and renal impairment. [23, 24]

A single report describes concurrent SSSS 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 an 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-A or ET-B is possible, the clinical presentation of both SSSS and TSS is extremely uncommon. [25] Only one other such case has been reported. [26]

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