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

Abstract

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.

Keywords: ceramides; lipid; sensitive skin.

FIGURE 1

Skin hypersensitivity and physiological properties of individuals with and without sensitive skin (SS). (a–e) Scores of 1% lactic acid stinging test (LAST) (a), skin hydration values (b), a* values (c), erythema index (EI) (d), and trans‐epidermal water loss (TEWL) values (e) of individuals without SS (non‐SS) (n = 18) and those with SS (n = 48). Values are expressed as mean ± SD (standard deviation). Statistical significances were assessed using Mann–Whitney U test for (a) or Student's t test for (b–e). ***p < 0.001. N.S., not significant. A.U., arbitrary unit.

FIGURE 2

Intercellular lipids (ICLs) in the stratum corneum (SC) of individuals with and without SS. (a–d) Levels of total ICLs (a), total ceramides (CERs) (b), total free fatty acids (FFAs) (c), free cholesterol (CHOL) (d), and CHOL sulfate (e) in tape‐stripped SC from individuals without SS (non‐SS) (n = 18) and those with SS (n = 48). (f) Levels of CER[NDS], [NS], [NH], [NP], [ADS], [AS], [AH], [AP], [EOS], [EOH], and [EOP] in the tape‐stripped SC. (g) Levels of CER[NS] containing 32–54 total carbon atoms in the tape‐stripped SC. Values are expressed as mean ± SD (standard deviation). Statistical significances were assessed using Student's t test. *p < 0.05. N.S., not significant.

FIGURE 3

CER[NP]/[NS] and Pk2.7/Pk2.4 ratios in the SC of individuals with and without SS, and correlation between them. (a–b) CER[NP]/[NS] ratio (a) and orthorhombic‐hexagonal lateral packing ratio of intercellular lipids (Pk2.7/Pk2.4 ratio) (b) in tape‐stripped SC from individuals without SS (non‐SS) (n = 18) and those with SS (n = 48). Values are expressed as mean ± SD (standard deviation). Statistical significances were assessed using Student's t test. **p < 0.01; *p < 0.05. (c) The representative electron diffraction pattern of corneocytes collected from the cheek. The black arrow and white arrowhead indicate positions of Pk2.4 and Pk2.7, respectively. (d) Correlation between CER[NP]/[NS] and Pk2.7/Pk2.4 ratios in all participants of the two groups (n = 66). Open and closed circles indicate non‐SS and SS, respectively. Correlation was examined using Pearson's correlation analysis. r _p , Pearson's correlation coefficient. **p < 0.01.

FIGURE 4

Corneocyte size in the SC of individuals with and without SS, and correlation between interleukin‐1 receptor antagonist (IL‐1ra)/IL‐1α and CER[NP]/[NS] ratios. (a) Corneocyte size in tape‐stripped SC from individuals without SS (non‐SS) (n = 18) and those with SS (n = 48). Values are expressed as mean ± SD (standard deviation). Statistical significance was assessed using Student's t test. ***p < 0.001. (b–c) Correlations between corneocyte size and CER[NP]/[NS] (b) and Pk2.7/Pk2.4 (c) ratios in all participants of the two groups (n = 66). (d) Correlation between IL‐1ra/IL‐1α and CER[NP]/[NS] ratios in tape‐stripped SC from participants of the two groups (n = 57). Open and closed circles indicate non‐SS and SS, respectively. Correlations were examined using Pearson's correlation analysis. r _p , Pearson's correlation coefficient. ***p < 0.001; **p < 0.01; *p < 0.05.