Altered Ceramide Profile of Facial Sensitive Skin: Disordered Intercellular Lipid Structure Is Linked to Skin Hypersensitivity.

BACKGROUND: Although sensitive skin (SS) is a syndrome characterized by cutaneous hypersensitivity to environmental factors, its pathophysiology remains elusive. AIMS: We aimed to explore the characteristics of ceramides (CERs) and intercellular lipid (ICL) structures of individuals with and without facial SS and their relationship with skin hypersensitivity. PATIENTS/METHODS: Healthy Japanese females were divided into SS or non-SS groups based on self-perception and lactic acid stinging test (LAST). Stratum corneum (SC) lipids were analyzed using a liquid chromatograph-mass spectrometer, and the orthorhombic-hexagonal lateral packing structure of ICLs was assessed using electron diffraction. RESULTS: According to the mean LAST score, individuals with SS (n = 48) had mild-to-moderate skin hypersensitivity. SS exhibited not significantly but slightly impaired skin barrier function (p = 0.072) and lower levels of CER[NH], [NP], [EOS], [EOH] (all p < 0.05), and [EOP] (p = 0.073) in the SC compared with non-SS (n = 18). Notably, the CER[NP]/[NS] ratio, a marker of skin barrier function, was positively correlated with the orthorhombic-hexagonal lateral packing ratio of ICLs (p = 0.002), whereas it was negatively correlated with the LAST score (p = 0.015) and the interleukin (IL)-1 receptor antagonist/IL-1α ratio (p = 0.003) in the SC, an indicator of chronic inflammation. Moreover, corneocyte size was reduced in SS (p < 0.001), suggesting inferior SC maturation, and was positively correlated with the CER[NP]/[NS] (p < 0.001) and the orthorhombic-hexagonal ratios (p = 0.011). CONCLUSIONS: Individuals with SS showed an abnormal CER profile, particularly the altered CER[NP]/[NS] ratio, which was in turn associated with disordered ICL structure and skin hypersensitivity. Abnormal epidermal turnover may be an underlying mechanism of the abnormalities.