Measuring the effects of topical moisturizers on changes in stratum corneum thickness, water gradients and hydration in vivo

Background Moisturizers are the most commonly used topically applied product for the treatment of dry skin conditions. They affect many properties and functions of the stratum corneum but some moisturizers have been reported to be detrimental to barrier function. Stratum corneum barrier function is a composite of its total structure and thickness but few studies have taken this into account. As a biosensor, the stratum corneum (SC) will change its structure in response to treatment and a swelling effect has been clearly demonstrated by skin hydration. Recently several moisturizing agents have been shown to have an effect on SC swelling behaviour with conflicting results. However, there is a paucity of data reported for measuring the effects of long‐term usage of moisturizers on SC thickness in vivo as, until recently, traditional techniques did not have the resolution to measure the effects of moisturizers on nonpalmoplantar body sites. The development of confocal Raman spectroscopy for use in human subjects provides noninvasive, real‐time, in vivo measurement of SC water concentration profiles and we have also used this state of the art equipment to measure the effect of the long‐term use of moisturizers on SC thickness for the first time. Objectives To validate the use of confocal Raman spectroscopy (CRS) to measure SC thickness and then use it to investigate the short‐ and long‐term effects of moisturizers (one of which is known to improve SC barrier function) on SC thickness, water gradients and hydration. Methods Two studies were conducted: (i) to validate the use of CRS for measuring SC thickness through comparison with optical coherence tomography (OCT); and (ii) once validated to use CRS to measure the long‐term effects of three commercially available moisturizers (A, B, C) on SC thickness and water gradients, together with total hydration, over a 3‐week period (2 weeks of treatment and 1 week regression) and compare the spectroscopy‐derived hydration value with instrumentally derived capacitance hydration values. Results (i) A strong, positive correlation in SC thickness was obtained between CRS and OCT (OCT‐derived thickness = 0·96 × CRS‐derived thickness, r² = 0·93; P <0·0001). OCT was shown, however, to have a lower resolution than CRS in distinguishing SC thickness on thinner nonpalmoplantar body sites. Using the CRS method, differences in SC thickness were readily apparent on different body sites (cheek 12·8 ± 0·9 μm, volar forearm 18·0 ± 3·9 μm, leg 22·0 ± 6·9 μm). (ii) Examining the effects of moisturizers in a blinded, randomized 3‐week study in human volunteers (n = 14) demonstrated that only one commercially available formulation (A) changed SC water gradients, thickness and hydration as measured by CRS. These hydration data did not directly correlate with capacitance hydration values. Conclusions (i) In vivo CRS was validated as a technique to measure SC thickness on both palmoplantar and, particularly, on nonpalmoplantar skin sites. (ii) Moisturizers improve skin moisturization but in this study only formulation A improved SC thickness, water gradients and hydration as measured by CRS. We hypothesize that this was due to compositional differences between the products. We believe that niacinamide (nicotinamide, vitamin B₃) is probably contributing significantly to this effect, as it has been proven to increase epidermal lipogenesis and SC barrier function in other studies. These results show that by using CRS, we were able for the first time to determine the effect of moisturizer on multiple SC barrier endpoints including SC thickness, and water content as a function of depth and total SC water content.     

Sodium lauryl sulfate (SLS) induced irritant contact dermatitis: a correlation study between ceramides and in vivo parameters of irritation

Sodium lauryl sulfate (SLS), a surfactant frequently used in the induction of experimental irritant contact dermatitis in animals and in humans, characterstically induces a dose-related increase in TEWL (transepidermal water loss). Ceramides are considered to be important in the regulation of the skin barrier. We therefore examined the relationship between initial ceramide content of stratum corneum and induced changes in skin color (erythema) and barrier function, after SLS application under occlusion (1% and 3% in water) to the forearm of 14 volunteers. Stratum corneum sheets were removed, stratum corneum lipids extracted, and ceramide composition determined from chromatograms (TLC) using densitometry. After determining baseline skin color and TEWL at each area. 2 samples of stratum corneum were obtained from each volunteer. Clinical and instrumental controls of the SLS-induced irritation were performed at 24, 48, 72 and 96 h. Erythema was evaluated by colorimetry; barrier impairment by changes in TEWL. We found inverse correlations between baseline ceramide 61 (weight) and the 24 h erythema score for SLS: between ceramide I and 24 h TEWL, and between ceramide 611 and 72 h TEWL for SLS 3%. Our findings suggest that low levels of these ceramides may determine a proclivity to SLS-induced irritant contact dermatitis.     

Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis

BACKGROUND: Gadolinium (Gd)-based magnetic resonance contrast agents (GBMCA), including gadodiamide, have been identified as the probable causative agents of the serious disease, nephrogenic systemic fibrosis (NSF). OBJECTIVES: To investigate retained Gd-containing deposits in skin biopsies from patients with NSF and to determine their relative concentrations over time from administration of GBMCA. METHODS: An investigator-blinded retrospective study, analysing 43 skin biopsies from 20 patients with gadodiamide-related NSF and one NSF-negative gadodiamide-exposed dialysis patient, ranging from 16 days to 1991 days after Gd contrast dose. Utilizing automated quantitative scanning electron microscopy/energy-dispersive X-ray spectroscopy we determined the concentration of Gd and associated elements present as insoluble deposits in situ in the tissues. RESULTS: We detected Gd in skin lesions of all 20 patients with NSF, whereas Gd was undetectable in the NSF-negative patient. Gd concentration increased over time in 60% of patients with multiple sequential biopsies (n=10), decreasing only when the initial sampling time was >23 months after first gadodiamide dose. All Gd-containing deposits contained phosphorus, calcium and sodium. The ratio of Gd to calcium in tissue deposits correlated positively with the gadodiamide dose and with serum ionized calcium at the time of Gd exposure. CONCLUSIONS: These findings demonstrate the in vivo release (through transmetallation) of the toxic free Gd3+ from gadodiamide, and its retention in apatite-like deposits. We suggest that Gd may be mobilized over time from bone stores, explaining variably delayed onset of NSF and increasing skin concentration over time in patients with NSF.     

Evaluation of carotenoids and reactive oxygen species in human skin after UV irradiation: a critical comparison between in vivo and ex vivo investigations

UV irradiation is one of the most harmful exogenous factors for the human skin. In addition to the development of erythema, free radicals, that is reactive oxygen species (ROS), are induced under its influence and promote the development of oxidative stress in the skin. Several techniques are available for determining the effect of UV irradiation. Resonance Raman spectroscopy (RRS) measures the reduction of the carotenoid concentration, while electron paramagnetic resonance (EPR) spectroscopy enables the analysis of the production of free radicals. Depending on the method, the skin parameters are analysed in vivo or ex vivo. This study provides a critical comparison between in vivo and ex vivo investigations on the ROS formation and carotenoid depletion caused by UV irradiation in human skin. The oxygen content of tissue was also determined. It was shown that the antioxidant status measured in the skin samples in vivo and ex vivo was different. The depletion in the carotenoid concentration in vivo exceeded the value determined ex vivo by a factor of about 1.5, and the radical formation after UV irradiation was significantly greater in vivo by a factor of 3.5 than that measured in excised human skin, which can be explained by the lack of oxygen ex vivo.     

Importance of intercellular lipids in water-retention properties of the stratum corneum: induction and recovery study of surfactant dry skin

Summary In order to further clarify the role of intercellular lipids in the water-retention properties of the stratum corneum, forearm skin of six healthy male volunteers was treated with 5% sodium dodecyl sulfate (SDS) for 1, 10, and 30 min. All treatment periods induced chapping and scaling of the stratum corneum without any inflammatory reaction, accompanied by a significant decrease in its water-retention function. Electron-microscopic analysis of SDS-treated stratum corneum revealed selective depletion of the lipids from the intercellular spaces, accompanied by marked disruption of multiple lamellae structures. Lipid analysis also showed a considerable and selective loss of intercellular lipids such as cholesterol, cholesterol ester, free fatty acid, and sphingolipids. To evaluate the recovery potential for intercellular lipids, lipids which were separated as sebaceous-rich lipids (SLs) and stratum corneum lipids (SCLs) wer applied daily on SDS-treated forearm skin. Two daily applications of the SCLs which were emulsified at 10% concentration in W/O (water in oil) cream caused a significant increase in conductance, accompanied by a definite improvement in the level of scaling over no application or W/O emulsion base only, whereas SLs in the W/O emulsion base led to no significant recovery in either conductance value or scaling. When two daily topical applications of four chromatographically separated lipid fractions (cholesterol ester, free fatty acid, cholesterol, and sphingolipid) from the SCL were carried out at 1% concentration in the same system, the cholesterol ester and sphingolipid fractions were found to induce a significant increase in the conductance value over no application. In contrast, the free fatty acid and cholesterol fractions showed no significant increase in conductance value. Similarly, the scaling which occurred after SDS treatment had a tendency to decrease after the two daily applications with the fractions of cholesterol ester, sphingolipids, and free fatty acid as compared with that of the base emulsion. These findings strongly suggest that sphingolipids, possibly in combination with other neutral lipids, play an essential role in the establishment or maintenance of water-retention capacity in the stratum corneum.     

Whole-body autoradiography after systemic and topical administration of methyl acrylate in the guinea pig

Summary Whole-body autoradiography was performed in the guinea pig with methyl (2,3-¹⁴C)-acrylate. Radioactive material quickly disappeared from the body after oral and, somewhat slower, after i. p. administration for the greater part.After administration in a closed cup on the skin a slow penetration in the dermis occurred preceded by the toxic effect, mainly a strong edema. In the first 16 h metabolism was primarily restricted to the skin, internal organs showed a slow rise in radioactivity. A large part of the labeled material was retained in the dermis.The detoxification was screened by estimating the urinary thioether content and respiratory carbon dioxide. This showed that in addition to oxidation to carbon dioxide the binding to SH-groups was the principal way of metabolism.This investigation was supported by Praeventiefonds grant 28-483     

Biophysical characteristics of skin in diabetes: a controlled study

Background  Cutaneous complications are common in diabetes. Previous assays suggest that hyperglycemia and decreased insulin signal are involved in the impairment of skin function. The aim of this study was to evaluate the biophysical characteristics of skin in patients with diabetes mellitus and compares them with healthy non-diabetic controls.
Objective  To measure biophysical characteristic of skin including transepidermal water loss (TEWL), water content, sebum and skin elasticity in patients with diabetes mellitus and compare them with healthy non-diabetic controls.
Methods  This case-control study was conducted on 38 patients with diabetes and 40 age- and sex-matched healthy people. The biophysical properties of skin including stratum corneum (SC) hydration, sebum content, TEWL and skin elasticity were measured and compared between the two groups at three different locations of the body.
Results  The measurement of SC hydration and TEWL showed no significant difference between diabetics and controls. The skin surface lipids on the forehead but not other sites were significantly lower in the diabetics than in the controls. Acoustic wave propagation speed, a measurement related to skin elasticity, was significantly lower in forearm and forehead of diabetics.
Conclusion  Diabetes affects some functional properties of epidermis and dermis that may responsible for many cutaneous manifestations of diabetes. These results suggest that patients with diabetes mellitus tend to show a normal hydration state of the SC together with decreased sebaceous gland activity and impaired skin elasticity, without any impairment of the SC barrier function.

Conflicts of interest

None declared     

Comparison of structure and organization of cutaneous lipids in a reconstructed skin model and human skin: spectroscopic imaging and chromatographic profiling

The use of animals for scientific research is increasingly restricted by legislation, increasing the demand for human skin models. These constructs present comparable bulk lipid content to human skin. However, their permeability is significantly higher, limiting their applicability as models of barrier function, although the molecular origins of this reduced barrier function remain unclear. This study analyses the stratum corneum (SC) of one such commercially available reconstructed skin model (RSM) compared with human SC by spectroscopic imaging and chromatographic profiling. Total lipid composition was compared by chromatographic analysis (HPLC). Raman spectroscopy was used to evaluate the conformational order, lateral packing and distribution of lipids in the surface and skin/RSM sections. Although HPLC indicates that all SC lipid classes are present, significant differences are observed in ceramide profiles. Raman imaging demonstrated that the RSM lipids are distributed in a non‐continuous matrix, providing a better understanding of the limited barrier function.     

Peak blistering point: influence on fluid levels of 5-MOP in human skin in vivo after systemic administration

Summary The concentration of 5-methoxypsoralen (5-MOP) in suction blister fluid (SBF) after oral intake was determined in relation to the peak blistering point. Interstitial fluid was obtained from nine healthy male volunteers by applying mild suction (300–350 mmHg) to the skin of the volar aspect of the forearm. Blisters were raised at three different times: 18 h prior to drug administration (group I); 2 h prior to drug administration (group II); and during drug ingestion (group III). SBF levels of 5-MOP were determined in each group of blisters 2 h after oral administration of 1.2 mg/kg micronized 5-MOP. The results showed a statistically significant difference in the concentrations of 5-MOP between each group of blisters. The highest concentration of 5-MOP in the SBF was found in group III and the lowest in group II blisters. These findings suggest that the point of peak blistering in relation to drug administration needs to be known in each pharmacological study using suction blisters.     

Well being,psychopathology and coping strategies in psoriasis compared with atopic dermatitis: a controlled study

Background There is a vast literature describing the association between psoriasis, atopic dermatitis (AD) and psychological distress. Some of these studies were uncontrolled and others used non‐dermatological diseases as control, but only a few used chronic skin diseases as controls. Objective To compare well being, psychopathology and coping strategies of psoriatic, AD and healthy controls in a prospective case‐control study. Methods Thirty‐seven psoriatic patients and 31 AD patients were recruited from the Hadassah Ein Karem Hospital, Jerusalem, Israel, outpatient and inward clinic. The participants in the control group were 31 healthy workers and volunteers with no dermatological diseases from Kaplan Hospital, Rehovot, Israel. We used self‐report questionnaires [Mental Health Inventory (MHI) and Adjustment to Chronic Skin Diseases Questionnaire (ACSD)], a projective technique (Hand Test) and assessment tools (Clinical Global Impression). Results Psoriatic patients experienced reduced well being (P = 0.007) and more anxiety and depression (P = 0.018) than normal controls. Psoriatic patients also displayed more severe psychopathology (P = 0.039) a more passive attitude towards life, and loss of meaning in life (P = 0.001) as measured by the projective technique compared with AD patients and normal controls. Conclusions We propose two explanations, derived from the psychological and the psycho‐neuro‐immunological domains. First, greater mental distress in psoriasis is because of the greater stigma it bears compared with AD. Alternatively, we hypothesize that the psoriatic inflammatory process may possibly have a direct central nervous system effect.     

Skin hydration and transepidermal water loss in patients with a history of sulfur mustard contact: a case–control study

Background   Skin lesions are among the most common complications of contact with sulfur mustard.
Objective   This study was aimed to measure skin water content and transepidermal water loss (TEWL) in patients with a history of sulfur mustard contact.
Methods   Three hundred ten male participants were included in this study: 87 (28.1%) sulfur mustard–exposed patients with current skin lesions (group 1), 71 (22.9%) sulfur mustard–exposed patients without skin lesions (group 2), 78 (25.2%) patients with dermatitis (group 3) and 74 (23.8%) normal controls (group 4) The water content and TEWL of skin was measured at four different locations of the body: forehead, suprasternal, palm and dorsum of hand. Nonparametric statistical tests (Kruskal–Wallis) were used to compare the four groups, and P  < 0.05 was considered statistically significant.
Results   The mean age of participants were 44.0 ± 6.7, 41.9 ± 5.9, 43.8 ± 9.3 and 44.8 ± 8.9 years in groups 1 to 4, respectively ( P  = 0.146). Xerosis, post-lesional hyperpigmentation and lichenification were significantly more common in either sulfur mustard–exposed participants or non-exposed participants with dermatitis ( P  < 0.05). Skin hydration was higher in subjects with sulfur mustard contact than in non-injured participants ( P  < 0.05) in the dorsum and palm of hands and forehead. TEWL was significantly higher in participants only in suprasternal area and dorsum of hand.
Conclusion   Contact with sulfur mustard agent can alter biophysical properties of the skin-especially the function of stratum corneum as a barrier to water loss-several years after exposure.

Conflicts of interest

None declared.