The relationship between MMP-2 and TIMP-2 gene polymorphisms and skin barrier function, inflammatory cytokine levels in acne patients

Evaluation of skin barrier function based on skin dermoscopic features in patients with rosacea.

<p dir="ltr">Objective: The NIDDK Diabetic Foot Consortium tested the hypothesis that compromised restoration of skin barrier function of closed diabetic foot ulcers (DFU), as measured by high trans-epidermal water loss (TEWL), is associated with an increased risk of DFU recurrence. </p><p dir="ltr">Research Design and Methods. This is a multi-center, non-interventional study measuring TEWL in 418 adult participants with diabetes and a recently healed DFU. TEWL was measured at the center of the closed wound and at an anatomically similar reference area on the contralateral foot within 2 weeks of wound closure (visit 1) and were repeated at a wound closure confirmation visit 2 weeks later (visit 2). Participants were followed for up to 16 weeks to assess for wound recurrence. Participant self-reported and clinician assessment of DFU wound recurrence were recorded.</p><p dir="ltr">Results. DFU recurrence by week 16 occurred in 21.5% of participants. Mean TEWL at the center of the healed DFU at visit 1 was higher for those with recurrence compared to those without (p=0.006). Among participants with high TEWL (>30.05 g.m-2.h-1), 35% reported wound recurrence by 16 weeks versus 17% (low TEWL). The odds ratio for recurrence for participants with high TEWL was 2.66 (p<0.001). Self-reported wound recurrence was highly concordant with clinician assessment of wound recurrence. </p><p dir="ltr">Conclusion. Compromised wound healing mechanisms culminating in wound closure associated with defective skin barrier function is associated with increased risk of DFU recurrence. Measurement of TEWL has value as a predictor of functional wound healing and may impact clinical practice, leading to better outcomes. </p>

<p dir="ltr">Objective: The NIDDK Diabetic Foot Consortium tested the hypothesis that compromised restoration of skin barrier function of closed diabetic foot ulcers (DFU), as measured by high trans-epidermal water loss (TEWL), is associated with an increased risk of DFU recurrence. </p><p dir="ltr">Research Design and Methods. This is a multi-center, non-interventional study measuring TEWL in 418 adult participants with diabetes and a recently healed DFU. TEWL was measured at the center of the closed wound and at an anatomically similar reference area on the contralateral foot within 2 weeks of wound closure (visit 1) and were repeated at a wound closure confirmation visit 2 weeks later (visit 2). Participants were followed for up to 16 weeks to assess for wound recurrence. Participant self-reported and clinician assessment of DFU wound recurrence were recorded.</p><p dir="ltr">Results. DFU recurrence by week 16 occurred in 21.5% of participants. Mean TEWL at the center of the healed DFU at visit 1 was higher for those with recurrence compared to those without (p=0.006). Among participants with high TEWL (>30.05 g.m-2.h-1), 35% reported wound recurrence by 16 weeks versus 17% (low TEWL). The odds ratio for recurrence for participants with high TEWL was 2.66 (p<0.001). Self-reported wound recurrence was highly concordant with clinician assessment of wound recurrence. </p><p dir="ltr">Conclusion. Compromised wound healing mechanisms culminating in wound closure associated with defective skin barrier function is associated with increased risk of DFU recurrence. Measurement of TEWL has value as a predictor of functional wound healing and may impact clinical practice, leading to better outcomes. </p>

OBJECTIVEThe National Institute of Diabetes and Digestive and Kidney Diseases Diabetic Foot Consortium tested the hypothesis that compromised restoration of the skin barrier function of closed diabetic foot ulcers (DFUs), as measured by high transepidermal water loss (TEWL), is associated with an increased risk of DFU recurrence.RESEARCH DESIGN AND METHODSThis was a multicenter noninterventional study measuring TEWL in 418 adult participants with diabetes and a recently healed DFU. TEWL was measured at the center of the closed wound and at an anatomically similar reference area on the contralateral foot within 2 weeks of wound closure (visit 1); measurements were repeated at a wound closure confirmation visit 2 weeks later (visit 2). Participants were observed for up to 16 weeks to assess for wound recurrence. Participant self-reported and clinician assessments of DFU wound recurrence were recorded.RESULTSDFU recurrence by week 16 occurred in 21.5% of participants. Mean TEWL at the center of the healed DFU at visit 1 was higher for those with recurrence compared with those without (P = 0.006). Among participants with high TEWL (>30.05 g · m−2 · h−1), 35% reported wound recurrence by 16 weeks versus 17% of those with low TEWL. The odds ratio for recurrence for participants with high TEWL was 2.66 (P < 0.001). Self-reported wound recurrence was highly concordant with clinician assessment of wound recurrence.CONCLUSIONSCompromised wound healing mechanisms culminating in wound closure associated with defective skin barrier function is associated with increased risk of DFU recurrence. Measurement of TEWL has value as a predictor of functional wound healing and could affect clinical practice, leading to better outcomes.

The protection against water loss and the prevention of substances and bacteria penetrating into the body rank as the most important functions of the skin. This so-called 'skin barrier function' is the natural frontier between the inner organism and the environment, and is primarily formed by the epidermis. An impairment of the skin barrier function is often found in diseased and damaged skin. An influence of ageing on skin barrier function is widely accepted, but has not been conclusively evaluated yet. Therefore, the aim of this clinical study was to assess the potential influence of ageing on skin barrier function, including transepidermal water loss (TEWL), stratum corneum hydration, sebum content and pH value. One hundred and fifty healthy women aged 18-80, divided into five age groups with 30 subjects each, were evaluated in this study. TEWL, hydration level, sebum secretion and pH value of hydro-lipid acid film were measured with worldwide acknowledged biophysical measuring methods at cheek, neck, décolleté, volar forearm and dorsum of hand. Whereas TEWL and stratum corneum hydration showed only very low correlation with subject's age, the sebum production decreased significantly with age, resulting in the lowest skin surface lipids levels measured in subjects older than 70 years. The highest skin surface pH was measured in subjects between 50 and 60 years, whereas the eldest age group had the lowest mean pH. The dorsum of the hand was the location with the highest TEWL and lowest stratum corneum hydration in all age groups. The results show that only some parameters related to skin barrier function are influenced by ageing. Whereas sebum production decreases significantly over lifetime and skin surface pH is significantly increased in menopausal woman, TEWL and stratum corneum hydration show only minor variations with ageing.

Sebum composition may be more important than amount for acne lesions, and current research on skin surface lipids (SSLs) focuses on determining their relative content. The objective of this study was to analyze the changes in the absolute content of SSLs in acne patients and their relationship with skin barrier function. To evaluate skin barrier function, transepidermal water loss (TEWL), skin moisture, sebum content, skin elasticity, and whiteness were measured, while SSL changes were investigated using LC-MS/MS. The results indicated that adult acne patients have reduced skin barrier function, as demonstrated by changes in skin moisture, sebum content, skin flexibility, and whitening. Notably, AGlcSiE, Cer, CL, Co, LPC, PA, PC, PE, PI, SM, So, SQDG, and TG were considerably enhanced in acne patients' SSLs, whereas CerG1, DG, DGDG, MGDG, PG, and phSM were decreased. Furthermore, side chain analysis showed that the ratio of linoleic acid to linolenic acid in acne patients' skin surface lipids was higher than in healthy controls, and the caprylic acid/capric acid ratio was likewise greater. The correlation study of SSLs and skin barrier function demonstrated that increasing LPC and decreasing PG are associated with skin barrier function deterioration. In conclusion, acne patients have compromised skin barrier function and altered SSL absolute content, and certain SSL species identified in this study could serve as potential targets for research into acne pathogenesis.

Filaggrin loss-of-function (FLG) mutations are associated with eczema and skin barrier impairment, but it is unclear whether skin barrier impairment precedes phenotypic eczema in FLG mutation carriers. To study the association between FLG mutations, skin barrier impairment and clinical eczema at 3 months of age. A total of 88 infants were examined for eczema. Disease severity was determined by the SCORAD eczema severity score. Transepidermal water loss (TEWL) was measured on unaffected forearm skin. Venous blood samples were screened for the four most common FLG mutations found in the U.K. white population (R501X, 2282del4, R2447X and S3247X). Median SCORAD and TEWL measurements in children with and without eczema and FLG mutations were compared. Thirty-three per cent (29/88) of children had clinical eczema. Median SCORAD was 10·6 (range 3·5-31·0). TEWL (g m⁻² h⁻¹) was higher in children with eczema compared with unaffected infants (median TEWL 14·24 vs. 11·24, P < 0·001). Higher TEWL was associated with more severe disease (r = 0·59, P < 0·001, median TEWL, SCORAD < 15, 13·1 vs. 29·6, SCORAD ≥ 15, P = 0·029). Clinically dry skin was associated with higher TEWL, even in the absence of eczema (median TEWL 17·55 vs. 11·08, P = 0·008). Seventeen per cent (15/88) of children carried at least one FLG mutation. FLG mutation carriers were significantly more likely to have clinically dry skin, even in the absence of eczema [odds ratio (OR) 8·50, 95% confidence interval (CI) 1·09-66·58, P = 0·042]. FLG mutation carriers were also more likely to have eczema by 3 months of age (OR 4·26, 95% CI 1·34-13·57, P = 0·014). FLG mutations were significantly associated with higher median TEWL (all children, FLG 'yes' 21·59 vs. FLG 'no' 11·24, P < 0·001), even without clinical eczema (FLG 'yes' 15·99 vs. FLG 'no' 10·82, P = 0·01). By the age of 3 months, FLG mutations are associated with an eczema phenotype, dry skin and TEWL. The observation that TEWL is elevated in unaffected FLG mutation carriers suggests that skin barrier impairment precedes clinical eczema.

Localized scleroderma (LS) is a disease characterized by fibrotic changes in the dermis. Connective tissue growth factor and transforming growth factor β2 are the main mediators of fibrogenesis; this, along with excessive connective tissue production, affects epidermal keratinocytes, and thereby contributes to the changed quality of skin barrier. The objective of this article was to study the objective measurement of the skin barrier quality in LS with transepidermal water loss (TEWL) meter. The measurements of TEWL were performed on LS plaques in all three stages of various body locations. Control measurements were made on the contralateral side of healthy skin. The difference between TEWL in LS area and the contralateral side of the healthy skin was evaluated. A higher average TEWL 7.86 g/m(2) /h (SD 5.29) was observed on LS plaques compared with the control measurements on healthy skin 6.39 g/m(2) /h (SD 2.77). TEWL average values decreased from the inflammatory stage, through the sclerotic and to the atrophic stage. The mean difference 1.301 g/m(2) /h (SD 5.16) was found between TEWL on LS plaques and on the contralateral healthy skin in 82 measurements, i.e., a higher TEWL was observed in LS. The difference was statistically significant with p = 0.0250. Although fibrogenesis in scleroderma is localized in dermis, the skin barrier changes can be detected.

Measurement of transepidermal water loss (TEWL) is widely used to evaluate skin barrier function. This study compared two devices-the DermaLab (DL) TEWL probe and the VapoMeter (VM) - from data collected across three studies to measure TEWL in scarred and normal skin. Each site was measured three times per device, alternating devices to allow vapor clearance. Inter-device reliability was assessed from 1,617 paired locations, each averaged from the three readings. Intra-observer reliability was able to be determined from a dataset of 1,628 DL and 1,635 VM measurements. Data were stratified into low, medium, and high TEWL ranges based on measurement distribution and observations. Overall inter-device reliability was 'good' but varied by range: 'poor' in low, 'excellent' in medium, and 'moderate' in high TEWL ranges. In the medium range, the VM reported nearly twice the TEWL values compared to the DL, while in the high range, it read approximately 34% higher. Both devices showed excellent intra-observer reliability overall. However, in the low TEWL range, the DL exhibited 'moderate' reliability, whereas the VM showed slightly better, 'good' reliability. Differences in chamber architecture-semiopen for the DermaLab and closed for the VM-appear to drive the observed variability in measurement reliability across TEWL ranges. Analysis of this large dataset indicates that the VM likely approaches saturation at the categorized 'high' TEWL values, constraining its accuracy, whereas the DermaLab exhibits reduced measurement stability at low TEWL levels, limiting its applicability under those conditions. Targeted methodological work is needed to refine DL performance in the lowTEWL regime and to more precisely define the upper operational limit of the VM.

Background: The relationship between the skin barrier- and lung function in infancy is largely unexplored. We aimed to explore if reduced skin barrier function by high transepidermal water loss (TEWL), or manifestations of eczema or Filaggrin (FLG) mutations, were associated with lower lung function in three-month-old infants. Methods: From the population-based PreventADALL cohort, 899 infants with lung function measurements and information on either TEWL, eczema at three months of age and/or FLG mutations were included. Lower lung function by tidal flow-volume loops was defined as a ratio of time to peak tidal expiratory flow to expiratory time (tPTEF/tE) <0.25 and a tPTEF <0.17 s (<25th percentile). A high TEWL >8.83 g/m2/h (>75th percentile) denoted reduced skin barrier function, and DNA was genotyped for FLG mutations (R501X, 2282del4 and R2447X). Results: Neither a high TEWL, nor eczema or FLG mutations, were associated with a lower tPTEF/tE. While a high TEWL was associated with a lower tPTEF; adjusted OR (95% CI) 1.61 (1.08, 2.42), the presence of eczema or FLG mutations were not. Conclusions: Overall, a high TEWL, eczema or FLG mutations were not associated with lower lung function in healthy three-month-old infants. However, an inverse association between high TEWL and tPTEF was observed, indicating a possible link between the skin barrier- and lung function in early infancy.

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. To investigate skin barrier response to occlusion on intact and damaged skin. 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. 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). 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.

Canine atopic dermatitis (cAD) is a genetically inherited clinical syndrome that encompasses a diversity of mechanisms and can have a variety of triggers. Development of clinical disease is the result of genetic factors and environmental conditions, which shape the resulting immunological response. Clinical disease becomes evident once a threshold of inflammatory response is achieved. Skin barrier impairment plays a role in promoting cutaneous dysbiosis and increased allergen penetration. Keratinocytes shape the response of dendritic cells and subsequent lymphocytic response. Thymic stromal lymphopoietin is one of the links between the damaged skin barrier and the modulation of a T-helper (Th)2 response. It is still unclear whether mutations in skin barrier genes exist in atopic dogs, as they do in humans, or whether the observed alterations are purely secondary to inflammation. A dysregulated immune response with increased Th2, Th17 and CD4+ CD25+ regulatory T cells has been reported. A variety of cytokines [interleukin(IL)-31, IL-34, Macrophage migration inhibitory factor] are proposed as potential biomarkers and treatment targets because they are increased in the serum of atopic dogs when compared to controls, although a correlation between serum levels of these factors and severity of disease is not always present. The main issue with many published studies is that atopic dogs are always only compared to normal controls. Thus, it is unclear whether the changes that we find are truly a signature of cAD or merely a manifestation of nonspecific broad inflammatory responses. Studies considering comparison with other inflammatory diseases different from cAD are urgently needed to correctly identify what is specific to this complicated syndrome.

Data of objective skin barrier parameters in acne patients with and without therapy compared with normal controls are limited. This information could provide more insight into the pathogenesis of acne vulgaris and optimal acne treatment. To measure and compare skin barrier parameters in a large cohort of acne patients with and without therapy compared with normal controls. This cross-sectional analytic study was conducted on healthy Thai volunteers. After completing a questionnaire on their general information and skincare routine, volunteers received a full skin examination and were divided into subjects with and without acne. Skin barrier parameters, including the transepidermal water loss (TEWL), skin hydration and sebum production were measured and compared between the two groups. Factors that may affect each parameter were analysed and adjusted for in a multivariate regression analysis. In addition, data from acne patients with and without treatment were evaluated. The study included 316 volunteers (164 acne patients, 152 controls), mostly female (79% acne, 78% controls). The mean age of the acne group was considerably lower than that of the control group (34 vs 48.6 years (p < 0.001)). Acne patients showed significantly higher TEWL (13.16 vs 10.63 g/m²/day, p < 0.001), sebum production (median 3 vs 0 A.U, p = 0.002), and skin hydration (244.60 vs 222.60 uS, p = 0.001). These differences remained significant after adjusting for confounding factors. Additionally, significant differences were observed between controls, acne. Patients receiving and not receiving acne medications. The highest TEWL was observed in acne patients receiving treatment, followed by untreated acne patients and normal controls (p = 0.0003). Skin hydration exhibited a comparable pattern (p = 0.03). There were significantly higher TEWL, sebum production and hydration in acne patients. Acne treatment further impaired the skin barrier. These findings support the possible benefits of moisturisers with barrier-enhancing properties in patients receiving acne medications.

Atopic eczema (AE) is associated with Staphylococcus aureus (S. aureus) colonization and skin barrier dysfunction, often measured by increased transepidermal water loss (TEWL). In the present study, the primary aim was to see whether S. aureus colonization in the vestibulum nasi and/or fauces was associated with increased TEWL in infants with healthy skin and infants with eczema. Secondarily, we aimed to investigate whether TEWL measurements on non-lesional skin on the lateral upper arm is equivalent to volar forearm in infants. In 167 of 240 infants, recruited from the general population, TEWL measurements on the lateral upper arm and volar forearm, using a DermaLab USB, fulfilled our environmental requirements. The mean of three TEWL measurements from each site was used for analysis. The infants were diagnosed with no eczema (n = 110), possible AE (n = 28) or AE (n = 29). DNA samples were analysed for mutations in the filaggrin gene (FLG). Bacterial cultures were reported positive with the identification of at least one culture with S. aureus from vestibulum nasi and/or fauces. S. aureus colonization, found in 89 infants (53%), was not associated with increased TEWL (i.e. TEWL in the upper quartile), neither on the lateral upper arm or volar forearm (p = 0.08 and p = 0.98, respectively), nor with AE (p = 0.10) or FLG mutation (p = 0.17). TEWL was significantly higher on both measuring sites in infants with AE compared to infants with possible AE and no eczema. FLG mutation was significantly associated with increased TEWL, with a 47% difference in TEWL. We conclude that S. aureus in vestibulum nasi and/or fauces was not associated with TEWL, whereas TEWL measurements on the lateral upper arm and volar forearm appear equally appropriate in infants.

Barrier Function, Epidermal Differentiation, and Human β-Defensin 2 Expression in Tinea Corporis