Generalized staphylococcal scalded skin syndrome

Etiology

• Staphylococcal scalded skin syndrome (SSSS) is a potentially lethal dermatologic condition.
  • It is caused by strains of Staphylococcus aureus that produce exfoliative exotoxins A and B (ETA and ETB).
    • These exotoxins act as serine proteases that cleave desmoglein 1 (a desmosomal protein); cleavage leads to loss of keratinocyte-keratinocyte adhesion in the stratum granulosum, which compromises skin architecture.
    • Rates of SSSS due to Methicillin-Resistant S. Aureus (MRSA) vary by location but are relatively low.
• There are two forms of SSSS:
  • Localized disease (known as bullous impetigo), which rarely affects the periocular region.
  • Generalized disease, which almost always affects the periocular region.
• This review will focus on the generalized form of SSSS, which occurs when the exotoxin spreads hematogenously, causing widespread damage to the epidermis.   

Epidemiology

• Estimated incidence is between 0.09 and 0.56 cases per million (Handler, 2014).
• Primarily a disease of immunocompetent children
  • Disease most commonly occurs from the neonatal period (as early as 48 hours after birth) to 5 years of age.
    • Antibodies against the staphylococcal exotoxins are typically acquired in childhood, which accounts for the relative rarity of disease in older children and adults.
    • Infants are especially vulnerable due to immature renal function, leading to reduced clearance of exotoxins. 
  • Approximately one-third of healthy individuals are colonized with S. Aureus and can serve as a vector of disease (Sakr, 2018).
  • Outbreaks are commonly seen in schools and day care facilities. 
• SSSS is rare in adults; about 60 cases have been documented.
  • Renal impairment is a major risk factor as it leads to impaired excretion of circulating exotoxins. However, multiple cases have been reported in immunocompetent adults without renal dysfunction (Patel, 2000). 

Clinical features

• History
  • Prodrome of fever, agitation and irritability (particularly in young children), sore throat, anorexia, and conjunctivitis.
• After a non-specific prodromal period, erythroderma develops. This is followed by superficial desquamation with some areas of skin sparing. This gives the skin a wrinkled appearance and skin may slough off with gentle pressure (Nikolsky sign). After this, fragile vesicles and bullae form that then burst to reveal an erythematous base.
  • Periocular crusting often occurs after lesions burst.
  • Disease is confined to the epidermis which differentiates SSSS from Toxic epidermal necrolysis (TEN), a common mimic characterized by dermal involvement.
• Disease classically begins on the head or face (Figure 1).
• In neonates, lesions are typically also present around the umbilical stump and in the diaper area.
• Absence of mucous membrane involvement helps differentiate SSSS from similar blistering conditions including TEN and Stevens-Johnson syndrome.
• Systemic features including fever, malaise, and signs of significant dehydration such as poor skin turgor and delayed capillary refill time are usually present.

Other diagnostic tests (required)

• Typical clinical pattern (see clinical features)
• Skin biopsy and histopathologic evaluation demonstrating:
• Detachment of the superficial epidermis beginning at the stratum granulosum.
• Lack of notable inflammation.  
• Isolation of S. Aureus producing ETA or ETB
• Skin cultures with nasal swab
• Blood cultures
• Culture of the umbilical stump in neonates

Other diagnostic studies

• Tzanck smear
  • May be combined with negative direct immunofluorescence to increase specificity.
• Gram stain (demonstrating clusters of gram-positive cocci) may be used in a resource limited setting.
  • In conjunction with typical clinical features, suggestive findings on gram stain is justification to start empiric therapy.
  • Testing is relatively rapid; thus, it may shorten time between presentation and treatment.
  • As disease is toxin mediated, samples cannot be taken from bullae or vesicles as they will not contain bacteria.
• Dermatoscopy demonstrates erosions with peripheral epidermal remnants and can help support the diagnosis.  

• Toxic epidermal necrolysis
• Stevens-Johnson Syndrome
• Epidermolysis bullosa
• Pemphigus foliaceous
• Drug reaction with eosinophilia and systemic symptoms (DRESS)
• Staphylococcal toxic shock syndrome

• Medical therapy: treatment is multidisciplinary and often requires a burn unit or intensive care unit.        
• Early treatment with intravenous anti-staphylococcal antibiotics (i.e. beta-lactamase resistant penicillin) is critical in decreasing morbidity and mortality.
• Flucloxacillin is a commonly used for adults and children.
• Topical mupirocin may be used to eradicate nasal colonization of S. Aureus and topical antibiotics can be added for concurrent conjunctivitis.
• Clarithromycin or cefuroxime can be used in penicillin allergy.
• Adjuvant clindamycin, vancomycin or linezolid may be used if MRSA is suspected.
• MRSA coverage is generally added empirically in areas of high MRSA prevalence or if patients fail to improve with standard therapy.
• However, compared to Staphylococcal infections overall, those associated with SSSS are less likely to be methicillin-resistant and more likely to be clindamycin-resistant.
• The combination of clindamycin with melittin (a drug with broad spectrum antibacterial, antiviral, antifungal, antiprotozoal and anti-inflammatory effects) has been recently demonstrated to have synergistic activity against Staphylococcal exfoliative exotoxin A and B (Mahmoudi, 2020).
• Fresh frozen plasma (FFP) was demonstrated in a case series to effectively neutralize antibodies against exotoxin A in the pediatric population (Tenendbaum, 2007).
• Use of intravenous immunoglobulin (IVIG) can be attempted in children who have failed other treatments, although its use may be associated with prolonged hospitalization (Li, 2013 & Handler, 2014).
• A recent case report demonstrated the efficacy of IVIG as part of a multimodal treatment regimen in an adult with SSSS (Urata, 2018).
• Analgesics (i.e. acetaminophen, fentanyl)
• Intravenous fluid resuscitation
• Nasogastric feeding
• Wound dressings
• Surgical therapy: not applicable
• Natural history and prognosis:
• Disease progresses from erythroderma to desquamation and blister formation within 48 hours of onset.
• Bullae will burst and heal without scarring.
• Reepithelization of skin usually occurs within 1-2 weeks.
• Mortality rates with appropriate treatment are approximately 4-11% in children and 40-63% in adults (Patel, 2003).

• Sepsis
• Pneumonia
• Thermal dysregulation
• Dehydration and electrolyte abnormalities
• Secondary infection of denuded skin


Photograph courtesy of D@nderm.

Figure 1. Early stages of staphylococcal scalded skin syndrome with diffuse facial erythema and exfoliation. 

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