Maintenance of an Acidic Skin Surface with a Novel Zinc Lactobionate Emollient Preparation Improves Skin Barrier Function in Patients with Atopic Dermatitis

Abstract

Introduction: The skin of patients with atopic dermatitis (AD) is characterised by elevated pH. As a central homeostatic regulator, an increased pH accelerates desquamation and suppresses lipid processing, resulting in diminished skin barrier function. The aim of this study was to determine whether a novel zinc lactobionate emollient cream can strengthen the skin barrier by lowering skin surface pH.

Methods: A double-blind, forearm-controlled cohort study was undertaken in patients with AD. Participants applied the test cream to one forearm and a vehicle cream to the other (randomised allocation) twice daily for 56 days. Skin surface pH and barrier function (primary outcomes) were assessed at baseline and after 28 days and 56 days of treatment, amongst other tests.

Results: A total of 23 adults with AD completed the study. During and after treatment, a sustained difference in skin surface pH was observed between areas treated with the test cream and vehicle (4.50 ± 0.38 versus 5.25 ± 0.54, respectively, p < 0.0001). This was associated with significantly reduced transepidermal water loss (TEWL) on the test cream treated areas compared with control (9.71 ± 2.47 versus 11.20 ± 3.62 g/m²/h, p = 0.0005). Improvements in skin barrier integrity, skin sensitivity to sodium lauryl sulphate, skin hydration, and chymotrypsin-like protease activity were all observed at sites treated with the test cream compared with the control.

Conclusion: Maintenance of an acidic skin surface pH and delivery of physiologic lipids are beneficial for skin health and may help improve AD control by reducing sensitivity to irritants and allergens.

Keywords: Acid mantle; Atopic dermatitis; Eczema; Emollient; Protease; Skin barrier; pH.

Fig. 1

The effect of a single application of the study products on pH_SS. a pH_SS up to 12 h post-application. The mean is shown with error bars indicating SEM. b pH_SS 3 h, c 6 h and d 12 h post-treatment. One-way ANOVA revealed a significant difference between treatments at all post-application timepoints (p < 0.0001). Significance values show the results of Dunnet’s post-test for pairwise comparisons between treatments and the untreated control. Boxes represent the interquartile range, whiskers show the range, median is indicated as a horizontal line, ‘+’ denotes the mean. ns not significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. The dotted line indicates the baseline mean for all measurements. NTC no treatment control, pHss skin surface pH, SEM standard error of the mean, ANOVA analysis of variance

Fig. 2

Biophysical properties of the skin surface are modified by use of the study products. pH_SS (a) TEWL (c) and hydration(e) at baseline, after 4 weeks and after 8 weeks of study treatment, 12 h post-application. A significant interaction between treatment and time was established in a two-way ANOVA (n = 21); a, p < 0.0001; c, p = 0.0025; e, p = 0.005. Significance values show the results of Šídák’s post-test for pairwise comparisons between treatments at each timepoint. pH_SS (b) and hydration (f) after 4 weeks of treatment, 6 h post application. Significance values show the result of a paired t-test, n = 10. d Pre-treatment correlation between pH_SS and TEWL, r indicates Pearson correlation coefficient. Boxes represent the interquartile range, whiskers show the range, median is indicated as a horizontal line, ‘+’ denotes the mean. ns not significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. The dotted line indicates the baseline mean for all measurements. wks weeks, AU arbitrary units, pHss skin surface pH, TEWL transepidermal water loss; ANOVA analysis of variance

Fig. 3

After 8 weeks of treatment with the study products, skin sensitivity, skin barrier integrity and skin barrier cohesion differ depending on treatment. Following 24 h exposure to SLS, differences between treatment sites were observed in a TEWL (g/m²/h), n = 42, b visual redness score (subjective score from 0 to 3), n = 42 and c Erythema Index (AU), n = 40. STS reveals treatment site differences in d TEWL₂₀ (barrier integrity), n = 42. e Cumulative amount of protein removed, mean ± SEM, n = 42. f Total amount of protein removed (skin barrier cohesion), n = 41. Significance values show the results of a paired t-test (panels a, c, d, and f) or Wilcoxon signed rank test (panel b). Boxes represent the interquartile range, whiskers show the range, median is indicated as a horizontal line, ‘+’ denotes the mean. ns not significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. The dotted line indicates the pre-test mean for all measurements. AU arbitrary unit, TEWL transepidermal water loss, SLS sodium lauryl sulphate; STS skin tape stripping, TEWL_20, TEWL after 20 consecutive tape strips, SEM standard error of the mean

Fig. 4

Protease activity after 8 weeks of treatment. a Caseinolytic protease activity at three depths through the stratum corneum. Sampling depth (p < 0.0001) but not treatment (p = 0.25) was a significant factor in a two-way ANOVA (n = 21), the interaction between treatment and sampling depth was not significant (p = 0.84). No pairwise comparisons were made. b Chymotrypsin-like activity at three depths through the stratum corneum. Treatment (p = 0.031) and sampling depth (p = 0.02) were significant factors in a two-way ANOVA (n = 21), the interaction between treatment and sampling depth was not significant (p = 0.3). Significance values show the results of Šídák’s post-test for pairwise comparisons between treatments at each sampling depth. Boxes represent the interquartile range, whiskers show the range, median is indicated as a horizontal line, ‘+’ denotes the mean. ns not significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. ANOVA analysis of variance