What clinical features should I look for to differentiate Staphylococcal Scalded Skin Syndrome (SSSS) from other blistering skin conditions?

Guideline-aligned answer with reasoning, red flags and references. Clinically reviewed by Dr Kola Tytler MBBS CertHE MBA MRCGP.

Posted: 22 August 2025Updated: 22 August 2025 Guideline-Aligned (High Confidence) Clinically Reviewed
Dr Kola Tytler MBBS CertHE MBA MRCGPClinical Lead • iatroX

To differentiate Staphylococcal Scalded Skin Syndrome (SSSS) from other blistering skin conditions, several key clinical features should be considered. SSSS is characterised by widespread erythema (redness) and the formation of flaccid blisters [Liy-Wong et al., 2021]. A crucial differentiating sign is a positive Nikolsky's sign, where the superficial epidermis peels away with gentle lateral pressure [Liy-Wong et al., 2021].

A significant feature that helps distinguish SSSS from other severe blistering conditions, such as Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis, is the absence of mucosal involvement [Liy-Wong et al., 2021]. In SSSS, the mucous membranes of the mouth, eyes, and genitals are typically spared [Liy-Wong et al., 2021]. The condition often begins with a localised staphylococcal infection, such as conjunctivitis, otitis media, or impetigo, before progressing to widespread skin exfoliation [Liy-Wong et al., 2021]. SSSS is caused by exfoliative toxins produced by Staphylococcus aureus [Ladhani et al., 1999; Liy-Wong et al., 2021] and predominantly affects neonates and young children [Liy-Wong et al., 2021].

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