Enhancement of stratum corneum lipid structure improves skin barrier function and protects against irritation in adults with dry, eczema-prone skin

Abstract

Background: The skin of patients with atopic dermatitis is characterized by abnormal stratum corneum lipid levels. Consequently, the lamellar matrices are disrupted and skin barrier function is diminished, increasing skin sensitivity to irritants and allergens.

Objectives: To determine whether a cream containing ceramides, triglycerides and cholesterol in a multivesicular emulsion can reinforce the skin barrier and protect against skin irritation.

Methods: A randomized observer-blind intrapatient-controlled study in 34 adults with dry, eczema-prone skin was conducted. Each participant underwent 4 weeks of treatment with the test cream on one forearm and lower leg and a reference emollient cream on the other. Skin properties were determined before and after treatment. Lipid structure was assessed by Fourier-transform infrared spectroscopy using a novel interface.

Results: Skin barrier integrity was greater at sites treated with the test cream [effect size for area under the transepidermal water loss curve -162, 95% confidence interval (CI) -206 to -118]. Skin sensitivity to sodium lauryl sulfate was reduced (-0·5 points visual redness, 97·57% CI -1·00 to -0·25), as was transepidermal water loss (-15·3 g m^-2 h^-1 , 95% CI -20·3 to -10·4) compared with the reference. Sites treated with the test cream displayed enhanced lipid chain ordering, which was significantly associated with skin barrier integrity (r = 0·61). Compared with the reference, treatment with the test cream increased hydration (8·61 capacitance units, 95% CI 6·61-10·6) and decreased signs of dryness.

Conclusions: The test cream facilitates skin barrier restoration and protects the skin from dryness and irritation. Compared with a commonly prescribed emollient in the UK, the test cream is highly suited to the management of dry, sensitive skin.

Figure 1

Study flow diagram.

Figure 2

Skin barrier (SB) primary outcomes assessed at forearm sites. (a–c) Skin sensitivity to sodium lauryl sulfate (SLS) following 28 days of treatment measured as the change (day 31, 24 h after patch removal, minus day 29, before patch application): (a) visual redness/erythema, (b) objective redness (arbitrary units, AU) and (c) transepidermal water loss (TEWL). (d) SB function measured as (resting) TEWL before, during (day 15) and after treatment (day 29). (e) TEWL in response to skin tape stripping (STS) (standardized physical skin challenge). (f) SB integrity determined as the area under the TEWL curve (AUC) in response to STS: higher TEWL AUC indicates weaker SB integrity. (g) The cumulative amount of protein removed by STS. (h) The total amount of protein removed by STS. (i) The relationship between TEWL AUC and skin sensitivity to SLS. Boxes indicate the median and 25th and 75th percentiles, with ‘+’ for the mean and whiskers showing 1·5 × interquartile range. Asterisks indicate the results of pairwise testing: ns, not significant; *P < 0·05; **P < 0·01; ***P < 0·001; ****P < 0·0001.

Figure 3

Skin moisturization outcomes measured at the lower legs. Skin hydration measured as electrical capacitance (a) and skin‐surface dryness assessed visually (c) before, during (day 15) and after treatment (day 29). Boxes indicate the median and 25th and 75th percentiles, with ‘+’ for the mean and whiskers showing 1·5 × interquartile range. Asterisks indicate the results of pairwise testing: ns, not significant; **P < 0·01; ***P < 0·001; ****P < 0·0001. (b, d) Representative colour images (16 × 12 mm) of the treatment sites, acquired before (day 1) and after (day 29) treatment: (b) images taken from a 75‐year‐old male participant; (d) images taken from a 37‐year‐old female participant. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 4

Study outcomes following stratification by age. (a–c) Skin sensitivity to SLS following 28 days of treatment measured as the change in (a) visual redness, (b) objective redness and (c) transepidermal water loss (TEWL). (d–h) Resting TEWL (day 29 – day 1 change, d), SB integrity post‐treatment (day 28, e), total amount of protein removed by STS (day 28, f), skin hydration (day 29 – day 1 change, g) and skin dryness (day 29 – day 1 change, h) in response to treatment for 28 days. Boxes indicate the median and 25th and 75th percentiles, with ‘+’ for the mean and whiskers showing 1·5 × interquartile range. Asterisks indicate the results of pairwise testing: ns, not significant; *P < 0·05; **P < 0·01; ***P < 0·001; ****P < 0·0001.

Figure 5

Average Fourier‐transform infrared spectrum of (a) the test products and (b) the skin sites post‐treatment (after five tape strips and normalized to the amide II peak at ~1550 cm⁻¹). The letters indicate the peaks associated with water (W), lipids (L), triglycerides (T) and glycerol (G). (c) Focus on the lipid peak at ~2850 cm⁻¹ following baseline correction. The centre of gravity (COG) of this peak is associated with stratum corneum lipid. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 6

Molecular properties of the stratum corneum (SC) determined by Fourier‐transform infrared spectroscopy. (a) Total lipid, (b) lipid ester, (c) glycerol and (e) water levels relative to amide II and lipid peak centre of gravity (COG, d) by SC depth (inset graphs display mean SC or skin‐surface levels). Asterisks indicate the results of pairwise testing: **P < 0·01, ****P < 0·0001. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 7

Mean lipid peak centre of gravity (COG) and water levels across the first 5‐μm depth of the stratum corneum (SC) for the whole cohort (a, c) and stratified by age group (b, d). Asterisks indicate the results of pairwise testing: **P < 0·01, ***P < 0·001, ****P < 0·0001.

Figure 8

(a) Correlation between lipid peak centre of gravity (COG) and transepidermal water loss (TEWL) area under the curve (AUC) showing that low lipid peak COG is associated with low TEWL AUC (an indicator of high barrier integrity). (b) Association between relative water levels and stratum corneum (SC) hydration.