Non‐invasive assessment of tryptophan fluorescence and confocal microscopy provide information on skin barrier repair dynamics beyond TEWL

The stratum corneum (SC) serves a primary function of skin barrier and understanding the kinetics of SC formation may provide great insight for skin diagnosis and evaluation of therapies. Besides trans‐epidermal water loss (TEWL), few methods have been characterized to assess skin barrier non‐invasively in vivo, particularly for dynamic measurements on the same specimen over time. The objective of this study was to characterize alternative non‐invasive methods to evaluate the dynamic processes involved in the recovery of normal human SC after total removal. TEWL, tryptophan fluorescence and reflectance confocal microscopy (RCM) were used to determine skin barrier function, cell turnover and epidermal morphology over a period of 10 days after total removal of the SC by tape stripping. The results show a biphasic recovery of TEWL over time, which contrasted with a linear increase of 2.3 μm/day in SC thickness. Tryptophan assessment of cell turnover also demonstrated a biphasic pattern attaining a maximum three to four times the levels of the control site 3 days after injury that slowly returned to baseline and displayed great correlation (R² > 0.95) to viable epidermis thickness that also achieved a maximum about 3 days after injury with an approximate increase of 55%. When plotting the change of TEWL versus SC thickness, a single exponential function is observed [Δ‐TEWL = 55 exp (?0.157×)] which contrasts with other proposed models. These methods were able to present rates for SC recovery processes beyond skin barrier (TEWL) that may provide new insights on kinetics of barrier formation for evaluation of skin conditions and treatments.     

Barrier function of intact and impaired skin: percutaneous penetration of caffeine and salicylic acid

Background Normally, percutaneous absorption tests are carried out using skin biopsies for an apparent and acceptable physiological condition. However, under different pathological conditions, the stratum corneum (SC) barrier function is impaired. Methods The barrier function of the SC was assessed by correlation between the number of repeated applications of tape strips on the skin and its transepidermal water loss (TEWL), as well as by in vitro percutaneous absorption studies of different compounds, using Franz diffusion cells and porcine skin previously stripped. Results A progressive diminution of the skin barrier function has been detected by TEWL both in vitro and in vivo as the number of skin tape strips increases. On the other hand, the percutaneous absorption of the compounds tested increases in a different way as the number of strips increases. Salicylic acid increases linearly depending on the barrier disturbance. However, percutaneous absorption of caffeine exponentially increased with barrier disturbance. Our results indicate that the barrier impairment of skin always increases the penetration behavior of a given compound; however, the hydrophilic–lipophilic balance of the compounds or formulations used could greatly modify its penetration profile, especially when a modified skin is used. Conclusions This in vitro protocol may be useful to simulate the percutaneous absorption profile of some drugs applied onto skin with an impaired SC barrier function and could be used to avoid, to some extent, the use of in vivo experimental animal models in the dermopharmaceutical field.     

Patterns of aluminum hydroxychloride deposition onto the skin

Background: Aluminum hydroxychloride (AlCl₃) is an antiperspirant. Aim: To revisit the AlCl₃ deposition in vivo and in vitro on glass slides and stratum corneum (SC) harvested by cyanoacrylate skin surface strippings (CSSS). Methods: Transepidermal water loss (TEWL) was assessed following application of 5% AlCl₃ on the forearms. The AlCl₃‐coated skin, glass slides and CSSS were observed using two ultraviolet light‐emitting CCD cameras in order to record changes in specular reflectance related to AlCl₃ deposition. In addition, the corneoxenometry bioassay was performed in order to predict AlCl₃ irritation. Results: AlCl₃ deposited on glass slides looked as linear threads and rings of similar sizes. AlCl₃ deposits on skin were almost restricted inside the microrelief lines and as annular deposits at their crossings where acrosyringia are opening. After daily AlCl₃ applications, deposits extended on the CSSS plateaus. At rest in absence of sweating, TEWL was decreased following AlCl₃ applications. During physical exercise, the TEWL increase was limited on the AlCl₃ areas. CSSS appeared unreactive to AlCl₃ at the corneoxenometry bioassay. Conclusion: The similar aspect of AlCl₃ deposits on human SC and on glass slides suggested a physical property of AlCl₃. Repetitive applications of AlCl₃ increased both the deposit area and the barrier function.     

Distinct barrier integrity phenotypes in filaggrin-related atopic eczema following sequential tape stripping and lipid profiling

Background Filaggrin gene (FLG) loss‐of‐function mutations have been shown to represent the strongest so far known genetic risk factor for atopic dermatitis (AD). Whereas the barrier characteristics in FLG mutation carriers under baseline conditions have been investigated, there are only limited data on the permeability barrier function in filaggrin‐AD under compromised conditions. Aim We investigated: (i) stratum corneum (SC) integrity/cohesion; (ii) barrier recovery after controlled mechanical and irritant‐induced barrier abrogation; and (iii) the lipid composition of the non‐lesional and lesional skin of AD patients harbouring the European R501X, 2282del4, 3702delG, R2447X or S3247X FLG variants. Methods Thirty‐seven AD patients (14 FLG mutation carriers and 23 non‐carriers) and 20 healthy controls participated in the study. Stratum corneum integrity/cohesion was assessed by measurement of transepidermal water loss (TEWL) and amount of removed protein following sequential tape stripping. Barrier recovery was monitored by repeated measurements of TEWL and erythema up to 96 h after barrier abrogation. Samples for lipid analysis were obtained from non‐lesional and lesional skin using the cyanoacrylate method. Results Tape stripping revealed distinct genotype‐related impairment of the SC integrity/cohesion. No differences in the rate of barrier recovery among the groups were found. The SC lipid analysis revealed significant differences regarding the percentage amount of cholesterol, ceramide/cholesterol ratio and triglycerides in the uninvolved skin as well as the amounts of free fatty acids, CER[EOH] and triglycerides in the skin lesions of the AD FLG mutation carriers. Conclusions Our results provide evidence for discernible FLG‐related barrier integrity phenotypes in atopic eczema.     

Effects of CO<Subscript>2</Subscript>-enriched water on barrier recovery

The objective of the present study was to evaluate the impact of CO₂-enriched water on barrier recovery of detergent-damaged skin compared to tap water employing bioengineering methods and thin-layer chromatography (TLC) analysis of stratum corneum (SC) lipids. Irritation of the skin was elicited on the forearms of 20 volunteers using 1% sodium lauryl sulphate (SLS). The degree of skin irritation was followed over 10 days in terms of skin colour reflectance (L*a*b*), transepidermal water loss (TEWL), and skin capacitance expressed as median values. For TLC analysis, SC lipids were extracted prior to and during the observation period. Clinical examination showed the efficacy of CO₂-enriched water on barrier recovery. Compared to unenriched tap water, CO₂-enriched water produced a significant (P<0.01) increase in total SC lipids and in particular in the ceramide fraction. Furthermore, TEWL was significantly (P<0.01) lower in skin treated with CO₂-enriched water than in skin treated with unenriched water. These findings may indicate that rinsing with CO₂-enriched water enhances (1) clinical regeneration of detergent-damaged skin, (2) epidermal lipid synthesis, and (3) barrier repair after detergent-induced perturbation.     

The importance of free fatty acid chain length for the skin barrier function in atopic eczema patients

An important feature of atopic eczema (AE) is a decreased skin barrier function. The stratum corneum (SC) lipids – comprised of ceramides (CERs), free fatty acids (FFAs) and cholesterol – fulfil a predominant role in the skin barrier function. In this clinical study, the carbon chain length distribution of SC lipids (FFAs and CERs) and their importance for the lipid organization and skin barrier function were examined in AE patients and compared with control subjects. A reduction in FFA chain length and an increase in unsaturated FFAs are observed in non‐lesional and lesional SC of AE patients. The reduction in FFA chain length associates with a reduced CER chain length, suggesting a common synthetic pathway. The lipid chain length reduction correlates with a less dense lipid organization and a decreased skin barrier function. All changes are more pronounced in lesional SC compared with non‐lesional skin. No association was observed between lipid properties and filaggrin mutations, an important predisposing factor for developing AE. The results of this study demonstrate an altered SC lipid composition and signify the importance of these changes (specifically regarding the CER and FFA chain lengths) for the impaired skin barrier function in AE. This provides insights into epidermal lipid metabolism as well as new opportunities for skin barrier repair.     

Dirt‐binding particles consisting of hydrogenated castor oil beads constitute a nonirritating alternative for abrasive cleaning of recalcitrant oily skin contamination in a three‐step programme of occupational skin protection

Background In occupational fields with exposure to grease, oil, metal particles, coal, black lead or soot, cleansing formulations containing abrasive bodies (e.g. refined walnut shell, corn, wood, plastic or pumice) are used. These may constitute an irritant per se. As an alternative, hydrogenated castor oil (also known as castor wax) beads have been developed as dirt‐binding particles. A polar surface contributes to their mechanical cleaning effects in removal of oily grime. Objectives Standardized examination of the in vivo effects upon the skin barrier of castor wax beads in comparison with abrasive bodies and pure detergent. Methods Three cleansing preparations – (i) detergent, (ii) detergent containing castor wax beads, (iii) detergent containing walnut shell powder – were each repetitively applied in vivo (four times daily for 3 weeks), mimicking workplace conditions, in 30 healthy volunteers (15 with and 15 without an atopic skin diathesis) and compared vs. (iv) no treatment. The treatment effects upon the skin barrier were monitored by repeated measurements of functional parameters [transepidermal water loss (TEWL), redness] and surface topography. Results After a 3‐week treatment, a significant global treatment effect (P < 0·0001) was found in the atopic group concerning TEWL as indicator for barrier function. A significantly higher TEWL and increasing erythema in the area treated with detergent containing walnut shell powder reflected its irritant effect compared with castor wax beads dispensed in the identical detergent. Cleaning properties of the two formulas were comparably superior to detergent alone. Conclusions Castor wax beads constitute a novel nonirritating alternative for abrasive cleaning of recalcitrant oily skin contamination appropriate for individuals with an atopic skin diathesis in a three‐step programme of occupational skin protection. As the skin barrier may additionally be influenced by the composition of dirt and use of skin protection and skin care measures under real workplace conditions, this component may now be used and examined further in different occupations.     

An ex vivo human skin model for studying skin barrier repair

In the studies described in this study, we introduce a novel ex vivo human skin barrier repair model. To develop this, we removed the upper layer of the skin, the stratum corneum (SC) by a reproducible cyanoacrylate stripping technique. After stripping the explants, they were cultured in vitro to allow the regeneration of the SC. We selected two culture temperatures 32°C and 37°C and a period of either 4 or 8 days. After 8 days of culture, the explant generated SC at a similar thickness compared to native human SC. At 37°C, the early and late epidermal differentiation programmes were executed comparably to native human skin with the exception of the barrier protein involucrin. At 32°C, early differentiation was delayed, but the terminal differentiation proteins were expressed as in stripped explants cultured at 37°C. Regarding the barrier properties, the SC lateral lipid organization was mainly hexagonal in the regenerated SC, whereas the lipids in native human SC adopt a more dense orthorhombic organization. In addition, the ceramide levels were higher in the cultured explants at 32°C and 37°C than in native human SC. In conclusion, we selected the stripped ex vivo skin model cultured at 37°C as a candidate model to study skin barrier repair because epidermal and SC characteristics mimic more closely the native human skin than the ex vivo skin model cultured at 32°C. Potentially, this model can be used for testing formulations for skin barrier repair.     

Improved barrier function observed in cultured skin substitutes developed under anchored conditions

Background/purpose: The current method of producing cultured skin substitutes (CSS) is focused on providing treatments for severe skin wounds/burns. We have developed a modified growth method to make them more suitable for in vitro product‐testing/toxicity‐testing purposes. Method: CSS grown in Petri dishes were either transferred to Franz diffusion cells on day 5 (modified method) or left in the Petri dish (standard method) and maintained in these environments for the remainder of the growth phase. Mitochondrial metabolism (MTT assay) was measured on days 5, 10 and 14 and histology was studied on days 5, 10 and 14. Barrier function for all tissues was evaluated by transferring them to Franz cells (standard method) and measuring transepidermal water loss (TEWL), ³H₂O penetration and ¹⁴C‐niacinamide permeability on days 7, 14 and 21. Results: CSS grown by the standard and modified methods showed comparable cell viability and tissue morphology. Barrier function, however, was markedly improved in CSS grown by the modified method. The average improvement at days 7 and 14 was 1.3‐fold for TEWL, 2.1‐fold for ³H₂O penetration and 6.4‐fold for ¹⁴C‐niacinamide permeability. The barrier function of CSS grown by the modified method was still significantly lower than that of human cadaver skin tested by the same methods. Conclusions: CSS developed using the anchored multi‐cell system showed similar cell viability and morphology and improved barrier function compared with CSS produced by the standard Petri dish method, thereby improving its potential as an in vitro skin permeability and toxicity model.     

Effect of Aqueous Cream BP on human stratum corneum in vivo

Background Aqueous Cream BP is widely prescribed to patients with eczema to relieve skin dryness. The formulation contains sodium lauryl sulphate (SLS), a chemical that is a known skin irritant and a commonly used excipient in personal care and household products. The chronic effects of Aqueous Cream BP application on skin barrier function have not been determined. Objectives To characterize and assess skin barrier function of healthy skin after application of Aqueous Cream BP and to study the physical effects of the formulation on the stratum corneum (SC). Methods The left and right volar forearms of six human volunteers were each separated into treated and control sides. The treated sides of each forearm were subjected to twice daily applications of Aqueous Cream BP for 4 weeks at the end of which concomitant tape stripping and transepidermal water loss (TEWL) measurements were made. The untreated sides of the forearms were not exposed to any products containing SLS during the study period. Results Changes in SC thickness, baseline TEWL and rate of increase in TEWL during tape stripping were observed in skin treated with Aqueous Cream BP. The mean decrease in SC thickness was 1·1 μm (12%) (P = 0·0015) and the mean increase in baseline TEWL was 2·5 g m^?2 h^?1 (20%) (P < 0·0001). Reduced SC thickness and an increase in baseline TEWL, as well as a faster rate of increase in TEWL during tape stripping, were observed in 16 out of 27 treated skin sites. Conclusions The application of Aqueous Cream BP, containing ～1% SLS, reduced the SC thickness of healthy skin and increased its permeability to water loss. These observations call into question the continued use of this emollient on the already compromised barrier of eczematous skin.     

Ability to estimate relative percutaneous penetration via a surrogate maker – trans epidermal water loss?

Aims: This study measures the dynamic change of the trans‐epidermal water loss (TEWL) rate and in vitro skin permeation data of tritiated water and [¹⁴C]‐clonidine HCl in order to refine our knowledge in the relationship between percutaneous penetration and TEWL. Measures: TEWL values were measured before and during the experimental period. Single application of tritiated water and [¹⁴C]‐clonidine HCl were dosed at the same time on dermatomed human skin samples collected from 12 donors in a flow through diffusion cell system. Radioactivity of absorbed dose: stratum corneum, epidermis, dermis, receptor fluid collected every 4 hours, as well as removable dose residue was counted to determine accountability, percent dose, μg equivalent, and flux rate. These data were further combined with TEWL values to analyze their possible relationship. Results: Results showed that baseline TEWL values correlated with the thickness of dermatomed skin (r=?0.44, P=0.007), and with tritiated water fluxes (r=0.34, P=0.04) and [¹⁴C]‐clonidine HCl (r=0.36; P=0.03). The fluxes of tritiated water and [¹⁴C]‐clonidine HCl were correlated (r=0.67, P<0.001). When TEWL and permeation data were compared, the pattern of tritiated water expressed as a percent dose permeated in receptor fluid resembled the TEWL pattern. Conclusion: The methodology described provides evidences of the correlation of TEWL and skin integrity and skin permeation and further demonstrates to be a rapid alternative to tritiated water permeation for measuring skin barrier functions in vitro. To develop TEWL measurement as a possible predictive model to assess in vitro percutaneous absorption, however more chemicals with various physical‐chemical properties need to be examined, and the relationships to TEWL and tritiated water flux better defined.     

Skin barrier response to occlusion of healthy and irritated skin: Differences in trans‐epidermal water loss,erythema and stratum corneum lipids

Background. Occlusion of the skin is a risk factor for development of irritant contact dermatitis. Occlusion may, however, have a positive effect on skin healing. No consensus on the effect of occlusion has been reached. Objectives. To investigate skin barrier response to occlusion on intact and damaged skin. Methods. In study A, the response to occlusion (nitrile glove material) for either 8 hr daily for 7 days or for 72 consecutive hours, respectively, was determined and compared with that of non‐occluded skin. In study B, the response to occlusion of for 72 consecutive hours of skin that had been damaged by either sodium lauryl sulfate (SLS) or tape stripping, respectively, was determined and compared with that of to non‐occluded pre‐damaged skin. Skin barrier function was assessed by measurements of trans‐epidermal water loss (TEWL) and erythema. In study A, stratum corneum lipids were analysed. Results. Occlusion of healthy skin did not significantly influence skin barrier function, ceramide profile or the ceramide/cholesterol ratio. Occlusion of the skin after SLS irritation resulted in higher TEWL than in the control (P = 0.049). Occlusion of the skin after tape stripping resulted in lower TEWL than in control skin (P = 0.007). Conclusions. A week of occlusion did not significantly affect healthy skin, but was found to decrease healing of SLS‐damaged skin, and to improve healing of tape‐stripped skin.     

Stratum corneum integrity as a predictor for peristomal skin problems in ostomates

Background Peristomal skin problems are common, most often the result is disruption of the skin barrier and this may account for more than one in three visits to ostomy nurses. Therefore a specific assessment of individual risk factors relating to the skin barrier function would be of great interest. Methods Skin barrier integrity in ostomy patients with peristomal skin problems (PSP) was compared with that of ostomy patients with normal skin (controls) using transepidermal water loss (TEWL). Mechanical barrier disruption was determined by a tape stripping test and chemical barrier disruption [sodium lauryl sulphate (SLS) 0·25%]. Results Patients and controls had a highly significant increase in TEWL value in the peristomal area compared with nonperistomal contralateral abdominal skin (P < 0·0001 for both groups). The skin barrier of normal‐looking contralateral skin of ostomates was found to be borderline impaired in patients with PSP compared with those without. A linear association was seen between the number of tape strips removed and TEWL for both cases and controls. Tape stripping suggested that patients with PSP had less resilient skin (P = 0·002). A significant difference in TEWL value between cases and controls was also seen for the SLS patch test on the dorsal skin (P = 0·02). Conclusion Successive tape stripping, a situation analogous to the normal use of a pouching system, caused a higher degree of barrier damage more rapidly in patients with PSP, indicating an impaired mechanical quality of the barrier. The SLS exposure test suggested a generally increased susceptibility to irritant dermatitis as assessed by TEWL. Our findings suggest tape stripping and SLS testing may have a role as predictive tests to identify patients at risk of PSP.     

Topical application of a linoleic acid‐ceramide containing moisturizer exhibit therapeutic and preventive benefits for psoriasis vulgaris: a randomized controlled trial

Psoriasis is a chronic skin inflammatory disorder with frequent relapse. Ceramides and their key enzymes are deficient in the lesions, resulting in impaired epidermal permeability barrier, which correlates with disease severity. We evaluated the efficacy of linoleic acid‐ceramide moisturizer (LA‐Cer) as an adjunctive and preventive therapy for psoriasis vulgaris. 106 patients were randomized into two groups. The control group (C₁) received Mometasone Furoate 0.1% Cream (MF) while the treatment group (T₁) was given 0.1% MF in combination with LA‐Cer moisturizer. Psoriasis Area and Severity Index (PASI), pruritus, capacitance (CAP), and transepidermal water loss (TEWL) of normal skin and lesion were evaluated at Week 0, 2, 4, 8. Subsequently, T₁ patients were randomized for another 1 year. LA‐Cer‐group (T₂) maintained the use of moisturizer while control group (C₂) discontinued. CAPs, TEWLs, PASI were assessed after 1 year. Primary endpoints (PASI‐50 at Week 8) revealed superiority of LA‐Cer‐MF versus MF, less relapse, and rebound in LA‐Cer‐group than control (C₂) at Year 1. There were time‐by‐therapy interaction effect on CAPs, lesional TEWL, and PASI. LA‐Cer‐MF induced higher CAP, an earlier reduction of lesional TEWL and PASI than control (C₁). CAPs, lesional TEWL, and PASI remained stable in LA‐Cer‐group. CAPs, lesional TEWL, and PASI were comparable to the baseline levels in control group (C₂). Topical LA‐Cer moisturizer can alleviate psoriasis, and could be a valuable approach for the treatment and prevention of psoriasis.     

Depletion of stratum corneum intercellular lipid lamellae and barrier function abnormalities after long-term topical corticosteroids

The intercellular lipid lamellae of the stratum corneum (SC) is believed to provide the permeability barrier of the epidermis. Previous functional studies have demonstrated an increase in the transepidermal water loss (TEWL) after long-term use of topical corticosteroids (TCS); however, direct morphological confirmation of this barrier abnormality is still lacking. The aim of this study was to determine whether any abnormality could be detected in the structure of the SC intercellular lipid lamellae in patients after long-term TCS. Atrophic skin and untreated normal skin of 10 patients after long-term TCS were examined by transmission electron microscopy using ruthenium tetroxide- fixed tissue for the multilamellar lipid sheets of SC, and oil red O stain for neutral lipids of the SC. Layers of the SC were evaluated by 0·1% methylene blue stain after alkaline expansion, and TEWL was measured by Evaporimeter EPI. The TCS-treated atrophic skin had fewer layers of horny cells, mean 9–4 layers, than the normal control skin, 18 layers (P<0·001) and increased TEWL of 21·3g/m² compared with the control skin TEWL of 6·7 g/m²(P<0·01). The mean neutral lipid content of the SC was also significantly lower (P<0·001). Moreover, ultrastructural studies revealed a marked decrease in both the numbers of intercellular lipid lamellae of SC and membrane-coating granules of stratum granulosum in the atrophic skin. These results suggest that the diminution in the SC intercellular lipid lamellae and SC cell layers play an important part in the pathogenesis of barrier dysfunction after long-term use of TCS.     

Variation in barrier impairment and inflammation of human skin as determined by sodium lauryl sulphate penetration rate

BACKGROUND: Skin irritability after a brief exposure to the model skin irritant, sodium lauryl sulphate (SLS), is known to vary considerably between individuals. A difference in the skin barrier to SLS may contribute to this variation. To date, no human in vivo data have been available on SLS penetration into the skin. OBJECTIVES: We studied whether the SLS penetration rate into the stratum corneum (SC) is related to impairment of the water barrier function and inflammation of the skin. METHODS: The penetration of SLS into the SC was assessed using a noninvasive tape-stripping procedure in 20 volunteers after a 4-h exposure to 1% SLS. Additionally, the effect of a 24-h exposure to 1% SLS on the skin water barrier function was assessed by measuring the transepidermal water loss (TEWL). The accompanying inflammation was quantified by measuring erythema. RESULTS: The mean +/- SD diffusivity of SLS (D) and the SLS permeability coefficient (Kp) were 1.4 +/- 0.6 x 10(-8) cm2 h(-1) and 1.5 +/- 0.7 x 10(-3) cm h(-1), respectively. A multiple regression analysis showed that the baseline TEWL, SC thickness and SLS penetration parameters K (SC/water partition coefficient) and D clearly influenced the increase in TEWL after the 24-h irritation test (explained variance: r2 = 0.80). Change in erythema was mainly influenced by SC thickness. CONCLUSIONS: We found that variation in the barrier impairment and inflammation of human skin depends on the SLS penetration rate, which was mainly determined by SC thickness.     

Cold plasma is well‐tolerated and does not disturb skin barrier or reduce skin moisture

Background: Cold plasma, a new treatment principle in dermatology based on ionic discharge delivering reactive molecular species and UV‐light, exhibits strong antimicrobial efficacy in vitro and in vivo. Before implementing plasma as new medical treatment tool, its safety must be proven, as well as assessing skin tolerance and patient acceptance. Patients and Methods: We investigated the plasma effects of three different plasma sources (pulsed, non‐pulsed atmospheric pressure plasma jet (APPJ) and a dielectric barrier discharge (DBD)) on the transepidermal water loss (TEWL) and skin moisture after treating the fingertips of four healthy male volunteers. Results: TEWL values were reduced by pulsed APPJ and DBD by about 20% but increased after non‐pulsed APPJ by 5–20%. TEWL values normalized 30 min after all forms of plasma treatment. Skin moisture was increased immediately and 30 min after treatment with pulsed APPJ but was not affected by non‐pulsed APPJ and DBD. Conclusions: All plasma treatments were well‐tolerated and did not damage the skin barrier nor cause skin dryness. Cold plasma fulfils basic recommendations for safe use on human skin and as future option may serve as the first physical skin antiseptic.     

Transepidermal water loss in the orphan forms of ichthyosis

As a surrogate measure of skin barrier dysfunction, we sought to determine differences in transepidermal water loss (TEWL) among ichthyosis subtypes and correlate TEWL with clinical severity. Subjects with Netherton syndrome had the highest TEWL values (increased water loss), while TEWL values were lowest in subjects with epidermolytic ichthyosis. TEWL correlated with severity only in lamellar ichthyosis and age was inversely correlated with TEWL (r_s = −.213, P = .02). TEWL is an objective measure that complements disease severity in ichthyosis and may be used as an adjuvant to monitor treatment response.     

Topically applied fatty acids are elongated before incorporation in the stratum corneum lipid matrix in compromised skin

In several skin diseases, both the lipid composition and organization in the stratum corneum (SC) are altered which contributes to the impaired skin barrier function in patients. One of the approaches for skin barrier repair is treatment with topical formulations to normalize SC lipid composition and organization. Vernix caseosa (VC), a white cheesy cream on the skin during gestational delivery, has shown to enhance skin barrier repair. In this study, we examined how a fatty acid (FA) containing formulation mimicking the lipid composition of VC interacts with the lipid matrix in the SC. The formulation was applied on ex vivo human skin after SC removal. Subsequently, the ex vivo human skin generated SC during culture. The effect of FA containing formulations on the lipid organization and composition in the regenerated SC was analysed by Fourier transform infrared (FTIR) spectroscopy and liquid chromatography mass spectroscopy (LC/MS), respectively. FTIR results demonstrate that the FAs are intercalated in the lipid matrix of the regenerated SC and partition in the same lattice with the endogenous SC lipids, thereby enhancing the fraction of lipids forming an orthorhombic (very dense) packing in the SC. LC/MS data show that the topically applied FAs are elongated before intercalation in the lipid matrix and are thus involved in the lipid biosynthesis in the skin.     

Functional analysis of the stratum corneum of scalp skin: studies in patients with alopecia areata and androgenetic alopecia

Abstract Because of the presence of thick long hairs on the scalp, little information is available concerning the functional characteristics of the stratum corneum (SC) of scalp skin. We therefore conducted a functional study of the SC of lesional scalp skin of patients with alopecia areata and of patients with androgenetic alopecia. We compared the scalp with the cheek and the flexor surface of the forearm (volar forearm). The water barrier function of the scalp SC of both patient groups, in terms of transepidermal water loss (TEWL), was almost comparable to that of the volar forearm, and was far better than that of facial skin. However, hydration of the scalp skin surface, as evaluated by measurement of high-frequency conductance, was markedly higher than that of facial skin, and showed significantly higher values than the volar forearm. These characteristics seem to be dependent, at least to some extent, on the amount of sebum-derived skin surface lipids because these were abundant on the scalp skin. Moreover, removal of skin surface lipids led to a significant decrease in skin surface hydration. The superficial corneocytes, the size of which reflects the proliferative activity of the epidermis, were substantially smaller on the scalp than on the volar forearm but significantly larger than on the cheek. These findings suggest that the rate of turnover of the scalp epidermis is intermediate between that of the facial and volar forearm epidermis. We conclude that the SC of the scalp skin in humans is functionally distinct from that of the face and extremities. Received: 6 January 2000 / Revised: 11 August 2000 / Accepted: 25 September 2000