Early skin inflammatory biomarker is predictive of development and persistence of atopic dermatitis in infants.

BACKGROUND: The Short-Term Topical Application for Prevention of Atopic Dermatitis (STOP AD) study, a randomized, open-label trial evaluating the effect of short-term (from the first 4 postnatal days to age 8 weeks) skin barrier protection using Aveeno Dermexa Fast & Long-Lasting Balm (Johnson & Johnson, New Brunswick, NJ) in infants with a parent with allergic disease, demonstrated decreased cumulative incidence and decreased prevalence of atopic dermatitis (AD) at age 12 months. OBJECTIVE: In the STOP AD study, we aimed to identify skin biomarkers that are associated with risk of development of AD. METHODS: Skin swabs were collected from the cheek and antecubital fossa (AF) at baseline, age 8 weeks, and age 12 months from subsets of study participants from the intervention arm (n = 43 of 119) and control arm (n = 43 of 138) and were analyzed for specific cytokines (CCL27, CXCL2, human ß-defensin-1 [hBD-1], IL-18, IL-8, IL-1α, IL-1 receptor antagonist [IL-1RA], IL-1ß, S100A8/9, and IL-36γ) by ELISA. RESULTS: Higher titers of S100A8/9 at the AF at age 8 weeks in infants with the filaggrin wild-type genotype (FLGwt), but not in those with filaggrin loss-of-function mutation (FLGmut), predicted (1) development of AD in the first year of life (P = .033), (2) presence of AD at ages 6 or 12 months (P = .009 and .035, respectively), (3) persistence of AD between ages 6 and 12 months (P < .001), and (4) development of AD with the emollient intervention. CONCLUSION: Increased titers of S100A8/9 from skin swabs of the AF in high-risk infants at age 8 weeks with FLGwt were predictive of AD development in the first year of life and other AD features. These findings suggest that there are different molecular pathways leading to AD in individuals with FLGmut and in individuals with FLGwt. Early identification of infants who are likely to develop AD will allow more targeted interventions.

Skin surface biomarkers are associated with future development of atopic dermatitis in children with family history of allergic disease.

BACKGROUND: Atopic dermatitis (AD) is a common childhood chronic inflammatory skin disorder that can significantly impact quality of life and has been linked to the subsequent development of food allergy, asthma, and allergic rhinitis, an association known as the "atopic march." OBJECTIVE: The aim of this study was to identify biomarkers collected non-invasively from the skin surface in order to predict AD before diagnosis across a broad age range of children. METHODS: Non-invasive skin surface measures and biomarkers were collected from 160 children (3-48 months of age) of three groups: (A) healthy with no family history of allergic disease, (B) healthy with family history of allergic disease, and (C) diagnosed AD. RESULTS: Eleven of 101 children in group B reported AD diagnosis in the subsequent 12 months following the measurements. The children who developed AD had increased skin immune markers before disease onset, compared to those who did not develop AD in the same group and to the control group. In those enrolled with AD, lesional skin was characterized by increased concentrations of certain immune markers and transepidermal water loss, and decreased skin surface hydration. CONCLUSIONS: Defining risk susceptibility before onset of AD through non-invasive methods may help identify children who may benefit from early preventative interventions.

Skin maturation from birth to 10 years of age: Structure, function, composition and microbiome.

Infant and adult skin physiology differ in many ways; however, limited data exist for older children. To further investigate the maturation processes of healthy skin during childhood. Skin parameters were recorded in 80 participants of four age groups: babies (0-2 years), young children (3-6 years), older children (7-<10 years) and adults (25-40 years). Overall, skin barrier function continues to mature, reaching adult levels of transepidermal water loss (TEWL), lipid compactness, stratum corneum (SC) thickness and corneocyte size by the age of about 6 years. Higher levels of lactic acid and lower levels of total amino acids in the SC of babies and young children further indicate higher cell turnover rates. In all age groups, TEWL and skin surface hydration values remain higher on the face compared with the arm. Skin becomes darker and contains higher levels of melanin with increasing age. The composition of skin microbiome of the dorsal forearm in all children groups is distinct from that in adults, with Firmicutes predominating in the former and Proteobacteria in the latter. Skin physiology, along with the skin microbiome, continues to mature during early childhood in a site-specific manner.

Age-dependent changes in epidermal architecture explored using an automated image analysis algorithm on in vivo reflectance confocal microscopy images.

BACKGROUND: Reflectance confocal microscopy (RCM) allows for real-time in vivo visualization of the epidermis at the cellular level noninvasively. Parameters relating to tissue architecture can be extracted from RCM images, however, analysis of such images requires manual identification of cells to derive these parameters, which can be time-consuming and subject to human error, highlighting the need for an automated cell identification method. METHODS: First, the region-of-interest (ROI) containing cells needs to be identified, followed by the identification of individual cells within the ROI. To perform this task, we use successive applications of Sato and Gabor filters. The final step is post-processing improvement of cell detection and removal of size outliers. The proposed algorithm is evaluated on manually annotated real data. It is then applied to 5345 images to study the evolution of epidermal architecture in children and adults. The images were acquired on the volar forearm of healthy children (3 months to 10 years) and women (25-80 years), and on the volar forearm and cheek of women (40-80 years). Following the identification of cell locations, parameters such as cell area, cell perimeter, and cell density are calculated, as well as the probability distribution of the number of nearest neighbors per cell. The thicknesses of the Stratum Corneum and supra-papillary epidermis are also calculated using a hybrid deep-learning method. RESULTS: Epidermal keratinocytes are significantly larger (area and perimeter) in the granular layer than in the spinous layer and they get progressively larger with a child's age. Skin continues to mature dynamically during adulthood, as keratinocyte size continues to increase with age on both the cheeks and volar forearm, but the topology and cell aspect ratio remain unchanged across different epidermal layers, body sites, and age. Stratum Corneum and supra-papillary epidermis thicknesses increase with age, at a faster rate in children than in adults. CONCLUSIONS: The proposed methodology can be applied to large datasets to automate image analysis and the calculation of parameters relevant to skin physiology. These data validate the dynamic nature of skin maturation during childhood and skin aging in adulthood.

Directional assessment of the skin barrier function in vivo.

INTRODUCTION: The fundamental function of the epidermis is to provide an inside-out barrier to water loss and an outside-in barrier to penetration of external irritants. Transepidermal water loss (TEWL) has been extensively used as a method of estimating the skin barrier quality, typically without any consideration of directionality. The validity of TEWL as an estimate of skin permeability to external substances has been controversial in vitro and in vivo. The aim of this work was to assess the relationship between TEWL and the penetration of a topically applied external marker (caffeine) in healthy skin in vivo before and following a challenge to the barrier. METHODS: The skin barrier was challenged by application of aqueous solutions of mild cleanser products under occlusion for 3 h on the forearms of nine human participants. Skin barrier quality was evaluated before and after the challenge by measuring the TEWL rate and the permeated amount of topically applied caffeine using in vivo confocal Raman microspectroscopy. RESULTS: No skin irritation was observed following the skin barrier challenge. TEWL rates and the caffeine penetrated amount in the stratum corneum after the challenge were not correlated. A weak correlation was observed when the changes were corrected to water-only treatment. TEWL values can be influenced by environmental conditions as well as the skin temperature and water content. CONCLUSIONS: Measuring TEWL rates is not always representative of the outside-in barrier. TEWL may be useful in differentiating large changes in skin barrier function (e.g., between healthy and compromised skin) but is less sensitive to small variations following topical application of mild cleansers.

Automatic granular and spinous epidermal cell identification and analysis on in vivo reflectance confocal microscopy images using cell morphological features.

Significance: Reflectance confocal microscopy (RCM) allows for real-time in vivo visualization of the skin at the cellular level. The study of RCM images provides information on the structural properties of the epidermis. These may change in each layer of the epidermis, depending on the subject's age and the presence of certain dermatological conditions. Studying RCM images requires manual identification of cells to derive these properties, which is time consuming and subject to human error, highlighting the need for an automated cell identification method. Aim: We aim to design an automated pipeline for the analysis of the structure of the epidermis from RCM images of the Stratum granulosum and Stratum spinosum. Approach: We identified the region of interest containing the epidermal cells and the individual cells in the segmented tissue area using tubeness filters to highlight membranes. We used prior biological knowledge on cell size to process the resulting detected cells, removing cells that were too small and reapplying the used filters locally on detected regions that were too big to be considered a single cell. The proposed full image analysis pipeline (FIAP) was compared with machine learning-based approaches (cell cutter, different U-Net configurations, and loss functions). Results: All methods were evaluated both on simulated data (four images) and on manually annotated RCM data (seven images). Accuracy was measured using recall and precision metrics. Both accuracy metrics were higher in the proposed FIAP for both real ( precision = 0.720 ± 0.068 , recall = 0.850 ± 0.11 ) and synthetic images ( precision = 0.835 ± 0.067 , recall = 0.925 ± 0.012 ). The tested machine learning methods failed to identify and segment keratinocytes on RCM images with a satisfactory accuracy. Conclusions: We showed that automatic cell segmentation can be achieved using a pipeline based on membrane detection, with an accuracy that matches expert manual cell identification. To our knowledge, this is the first method based on membrane detection to study healthy skin using RCM images evaluated against manually identified cell positions.

Computational modelling predicts impaired barrier function and higher sensitivity to skin inflammation following pH elevation.

Skin surface pH has been identified as a key regulator of the epidermal homeostasis through its action on serine protease activity. These enzymes, like kallikreins (KLK), are responsible for the degradation of corneodesmosomes, the protein structures linking together corneocytes, and are regulated by Lympho-Epithelial Kazal-Type-related Inhibitor (LEKTI). KLK activity increases at pH levels higher than physiological. An increase in skin surface pH has been observed in patients suffering from skin diseases characterized by impaired barrier function, like atopic dermatitis. In this work, we introduce an agent-based model of the epidermis to study the impact of a change in skin surface pH on the structural and physiological properties of the epidermis, through the LEKTI-KLK mechanism. We demonstrate that a less acidic pH, compared to the slightly acidic pH observed in healthy skin, is sufficient to significantly affect the water loss at the surface and the amount of irritant permeating through the epidermis. This weakening of the skin barrier function eventually results in a more intense skin inflammation following exposure to an external irritant. This work provides additional evidence that skin surface pH and serine proteases can be therapeutic targets to improve skin barrier integrity.

Automating reflectance confocal microscopy image analysis for dermatological research: a review.

SIGNIFICANCE: Reflectance confocal microscopy (RCM) is a noninvasive, in vivo technology that offers near histopathological resolution at the cellular level. It is useful in the study of phenomena for which obtaining a biopsy is impractical or would cause unnecessary tissue damage and trauma to the patient. AIM: This review covers the use of RCM in the study of skin and the use of machine learning to automate information extraction. It has two goals: (1) an overview of information provided by RCM on skin structure and how it changes over time in response to stimuli and in disease and (2) an overview of machine learning approaches developed to automate the extraction of key morphological features from RCM images. APPROACH: A PubMed search was conducted with additional literature obtained from references lists. RESULTS: The application of RCM as an in vivo tool in dermatological research and the biologically relevant information derived from it are presented. Algorithms for image classification to epidermal layers, delineation of the dermal-epidermal junction, classification of skin lesions, and demarcation of individual cells within an image, all important factors in the makeup of the skin barrier, were reviewed. Application of image analysis methods in RCM is hindered by low image quality due to noise and/or poor contrast. Use of supervised machine learning is limited by time-consuming manual labeling of RCM images. CONCLUSIONS: RCM has great potential in the study of skin structures. The use of artificial intelligence could enable an easier, more reproducible, precise, and rigorous study of RCM images for the understanding of skin structures, skin barrier, and skin inflammation and lesions. Although several attempts have been made, further work is still needed to provide a definite gold standard and overcome issues related to image quality, limited labeled datasets, and lack of phenotype variability in available databases.

Epidermal barrier function in human immunodeficiency virus-infected South African infants compared with uninfected.

BACKGROUND AND OBJECTIVE: Infant human immunodeficiency virus (HIV) infection remains a problem in different parts of the world. Early signs of disease manifestation often involve infant skin. This study compared the skin barrier properties of HIV infected with uninfected infants. METHODS: A cross-sectional descriptive study was undertaken with HIV positive and HIV negative unexposed African infants (6 weeks-12 months). Both had normal birth weight for age, no pre-existing dermatoses or co-infections, and received all their vaccinations timeously. The HIV positive infants were on antiretroviral (ARV) therapy. The skin barrier quality was assessed by measuring the transepidermal water loss (TEWL) and skin surface hydration (SSH) on the dorsal arm (1) and the inner forearm (2). RESULTS: Eighty-six HIV negative and 43 HIV positive African children were recruited. There were significant differences between the two groups based on the presence of HIV infection. In both sites, measured TEWL rates were significantly higher for the HIV positive children. There was a nonsignificant difference between the SSH values for site 1 and a marginally significant difference for site 2, with the average values higher in the HIV positive group. In both groups, TEWL rates and SSH values were significantly lower on site 1 compared to site 2. CONCLUSION: Differences in skin barrier properties of HIV infected and uninfected children may exist. The altered skin barrier in infected children may be one of the factors that predisposes them to various inflammatory and infectious dermatoses. Improving the skin barrier may assist in preventing these conditions.

Deciphering the Role of Skin Surface Microbiome in Skin Health: An Integrative Multiomics Approach Reveals Three Distinct Metabolite‒Microbe Clusters.

The advent of 16S RNA profiling and shotgun metagenomics has enabled a holistic approach to the study of the skin microbiome composition. Despite the interesting findings in this rapidly developing scientific area, the big question remains: What role does the microbiome play in skin physiology? To begin answering this question, we employed an integrative methodology for microbiome and metabolome analysis of skin surface samples collected from the volar forearm of healthy infants aged 3-6-months. Whereas the infant skin metabolome was dominated by amino acids, lipids, and xenobiotics, the primary phyla of the microbiome were Firmicutes, Actinobacteria, and Proteobacteria. Zooming in on the species level revealed a large contribution of commensals belonging to the Cutibacterium and Staphylococcus genera, including Cutibacterium acnes, Staphylococcus epidermidis, and S. aureus. This heterogeneity was further highlighted when combining the microbiome with metabolome data. Integrative analyses delineated the coexistence of three distinct metabolite‒microbe clusters: one dominated by Cutibacterium linked to hydrophobic elements of the skin barrier, one associating Staphylococcus genus with amino acids relevant to the water holding capacity and pH regulation of the skin surface, and one characterized by Streptococcus and independent of any particular metabolomic profile.

An integrative multi-omic analysis reveals a major metabolic rewiring between baby foreskin keratinocytes and adult female abdominal keratinocytes.

Even though its development starts early in utero, neonatal skin is still immature at birth relative to adult and undergoes a maturation process extending to the first years of life. It is now established that the stratum corneum is thinner and dryer and that skin contains less natural moisturizing factors and lipids in newborns compared to children and adults. Moreover, it has been shown that skin surface area expansion is not linear throughout life and is peaking perinatally, suggesting that baby skin has a higher epidermal cellular turnover. Despite growing resources showing differences between adult and infant skin physiology, molecular and metabolic specificities of baby skin are still poorly understood. To address this critical knowledge gap, we performed an integrative transcriptomic and metabolomic study comparing human primary foreskin and abdominal keratinocytes from male babies and female adults, respectively. Based on state-of-the-art integrative frameworks, our analyses revealed a major shift in the global energetic metabolism in baby foreskin keratinocytes compared to adult abdominal keratinocytes, highlighting increased amino acid metabolism and mitochondrial oxidative phosphorylation in baby cells to fuel the citric acid cycle, while showing glycolysis as the major cell energy source in adult cells.

Unlocking the Mechanisms of Cutaneous Adverse Drug Reactions: Activation of the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway by EGFR Inhibitors Triggers Keratinocyte Differentiation and Polarization of Epidermal Immune Responses.

EGFR inhibitors used in oncology therapy modify the keratinocyte differentiation processes, impairing proper skin barrier formation and leading to cutaneous adverse drug reactions. To uncover the molecular signatures associated with cutaneous adverse drug reactions, we applied phosphoproteomic and transcriptomic assays on reconstructed human epidermis tissues exposed to a therapeutically relevant concentration of afatinib, a second-generation EGFR inhibitor. After drug exposure, we observed activation of the phosphatidylinositol 3-kinase/protein kinase B pathway associated with an increased expression of gene families involved in keratinocyte differentiation, senescence, oxidative stress, and alterations in the epidermal immune-related markers. Furthermore, our results show that afatinib may interfere with vitamin D3 metabolism, acting via CYP27A1 and CYP24A1 to regulate calcium concentration through the phosphatidylinositol 3-kinase/protein kinase B pathway. Consequently, basal layer keratinocytes switch from a pro-proliferating to a prodifferentiative program, characterized by upregulation of biomarkers associated with increased keratinization, cornification, T helper type 2 response, and decreased innate immunity. Such effects may increase skin susceptibility to cutaneous penetration of irritants and pathogens. Taken together, these findings demonstrate a molecular mechanism of EGFR inhibitor-induced cutaneous adverse drug reactions.

A Predictive Self-Organizing Multicellular Computational Model of Infant Skin Permeability to Topically Applied Substances.

Computational models of skin permeability are typically based on assumptions of fixed geometry and homogeneity of the whole epidermis or of epidermal strata and are often limited to adult skin. Infant skin differs quantitatively from that of the adult in its structure and its functional properties, including its barrier function to permeation. To address this problem, we developed a self-organizing multicellular epidermis model of barrier formation with realistic cell morphology. By modulating the parameters relating to cell turnover reflecting those in adult or infant epidermis, we were able to generate accordingly two distinct models. Emerging properties of these models reflect the corresponding experimentally measured values of epidermal and stratum corneum thickness. Diffusion of an externally applied substance (e.g., caffeine) was simulated by a molecular exchange between the model agents, defined by the individual cells and their surrounding extracellular space. By adjusting the surface concentration and the intercellular exchange rate, the model can recapitulate experimental permeability data after topical exposure. By applying these parameters to an infant model, we were able to predict the caffeine concentration profile in infant skin, closely matching experimental results. This work paves the way for a better understanding of skin physiology and function during the first years of life.

The stratum corneum water content and natural moisturization factor composition evolve with age and depend on body site.

BACKGROUND: The study objective was to examine if age and chronic environmental exposure affect the water content and the composition of the natural moisturizing factors (NMFs) of the stratum corneum (SC). METHODS: Forty healthy Caucasian women 18-70 years of age were recruited. Measurements were done on the cheek and on two skin sites on the arm (one relatively protected and one exposed to environmental factors). SC water content and NMF composition were measured by Raman confocal microspectroscopy. RESULTS: The SC water content was gradually reduced with age, reaching statistically significant levels only on the exposed arm site. The SC water content remained higher on the face than on the two arm sites throughout the ages tested. The age-dependent concentration changes of various amino acids were species-specific, potentially indicating different protein sources. Interestingly, on the arm sites, the sum of decreasing amino acid concentrations is compensated by the sum of those increasing, resulting in constant total amino acid content. However, on the face, the total amino acid content statistically increased with age potentially relating to the declining cell turnover rates. The lactate content was higher on the face for all ages and statistically decreased on both arm sites. CONCLUSION: Both chronological aging and chronic exposure to environmental factors mildly affect SC hydration, while they have variable effects in the concentrations of NMF components. The dynamics of NMF composition may at least partially explain the age-related changes in SC hydration.

EGFR inhibitors switch keratinocytes from a proliferative to a differentiative phenotype affecting epidermal development and barrier function.

BACKGROUND: Cutaneous adverse drug reactions (CADR) associated with oncology therapy involve 45-100% of patients receiving kinase inhibitors. Such adverse reactions may include skin inflammation, infection, pruritus and dryness, symptoms that can significantly affect the patient's quality of life. To prevent severe skin damages dose adjustment or drug discontinuation is often required, interfering with the prescribed oncology treatment protocol. This is particularly the case of Epidermal Growth Factor Receptor inhibitors (EGFRi) targeting carcinomas. Since the EGFR pathway is pivotal for epidermal keratinocytes, it is reasonable to hypothesize that EGFRi also affect these cells and therefore interfere with the epidermal structure formation and skin barrier function. METHODS: To test this hypothesis, the effects of EGFRi and Vascular Endothelial Growth Factor Receptor inhibitors (VEGFRi) at therapeutically relevant concentrations (3, 10, 30, 100 nM) were assessed on proliferation and differentiation markers of human keratinocytes in a novel 3D micro-epidermis tissue culture model. RESULTS: EGFRi directly affect basal keratinocyte growth, leading to tissue size reduction and switching keratinocytes from a proliferative to a differentiative phenotype, as evidenced by decreased Ki67 staining and increased filaggrin, desmoglein-1 and involucrin expression compared to control. These effects lead to skin barrier impairment, which can be observed in a reconstructed human epidermis model showing a decrease in trans-epidermal water loss rates. On the other hand, pan-kinase inhibitors mainly targeting VEGFR barely affect keratinocyte differentiation and rather promote a proliferative phenotype. CONCLUSIONS: This study contributes to the mechanistic understanding of the clinically observed CADR during therapy with EGFRi. These in vitro results suggest a specific mode of action of EGFRi by directly affecting keratinocyte growth and barrier function.

Biomarker Mapping on Skin Tape Strips Using MALDI Mass Spectrometry Imaging.

Keratinocyte organization and biochemistry are important in forming the skin's protective barrier. Intrinsic and extrinsic factors can affect skin barrier function at the cellular and molecular levels. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometric imaging, a technique which combines both molecular aspects and histological details, has proven to be a valuable method in various disciplines including pharmacology, dermatology and cosmetology. It typically requires ex vivo samples, prepared following frozen tissue sectioning. This paper demonstrates the feasibility of performing MALDI analysis on tape strips collected non-invasively on skin. The aim is to obtain molecular imaging of corneocytes on tapes towards novel biological insights. Tapes were collected from two skin sites (volar forearm and cheek) of human volunteers. Ten molecules relating to skin barrier function were detected with a single mode of acquisition at high spatial resolution with a 7 T MALDI-Fourier transform ion cyclotron resonance (FTICR) instrument. The method sensitivity was adequate to create molecular maps which could be overlaid on transmission microscopy images of the same area of the tape. Analysis of the molecular distributions from tapes at the two skin sites was consistent with the known skin properties of the two sites, confirming the validity of the observations. Hierarchical clustering analysis was used to differentiate corneocyte populations based on their molecular profiles. Furthermore, morphological analysis provided a new way of considering statistical populations of corneocytes on the same tape, rather than measuring a single averaged value, providing additional useful information relating to their structure-function relationship.

Variation of cultured skin microbiota in mothers and their infants during the first year postpartum.

BACKGROUND/OBJECTIVES: The establishment of newborn skin flora depends on the ongoing skin maturation and the existence of potential microbial colonizers within the environment of the infant during a period of intense mother-infant physical interaction. This longitudinal study assessed culturable skin bacteria in the mother-infant dyad during the first year of life. METHODS: A total of 17 mother-infant dyads were swabbed within 24 hours postpartum and at 3, 6, 9, and 12 months. Skin swabbing was performed on two anatomical areas per individual (mothers: chest-abdomen; infants: forehead-buttocks) and were incubated in five different solid culture media to optimize yield. Isolated bacterial species were identified to genus or species level using the API system (BioMeriéux, Marcy l'Etoile, France). RESULTS: A total of 444 microbial strains were isolated belonging to 22 genera: 6 "frequent" (isolated from > 5% samples: S aureus, Proteus, Klebsiella, Pseudomonas, Enterobacter, and Enterococcus) and 16 "infrequent." Isolated genera per individual peaked at 6 months postpartum for mothers and infants (P < 0.05). Enterobacter, Enterococcus, Klebsiella, and Pseudomonas isolation rates varied significantly as a function of sampling time contrary to the rather constant isolation rates of Proteus and S aureus. The rates of concordant isolation of the same microbial species within the mother-infant dyad tended to drop from birth to the end of the first year postpartum. CONCLUSIONS: Distinct variations in the isolation rates of skin commensals from specific anatomical sites of the mother-infant dyad indicate bidirectional microbial transmission. Increasing skin flora individuality of the growing infant was recorded, manifested by declining rates of concordant isolation of the same microbial species from mother and her infant.

Epidermal barrier function in healthy black South African infants compared with adults.

A cross-sectional observational study of 43 infants and 60 adult women was performed in South Africa to assess skin barrier (SB) function through noninvasive quantification of transepidermal water loss (TEWL) and skin surface hydration (SSH). TEWL and SSH improved with age and in anatomic locations with chronic environmental exposure in keeping with reported trends in other ethnicities.

Infant Skin Barrier, Structure, and Enzymatic Activity Differ from Those of Adult in an East Asian Cohort.

Skin physiology is dynamically changing over the first years of postnatal life; however, ethnic variations are still unclear. The aim of this study was to characterize infant skin barrier function, epidermal structure, and desquamation-related enzymatic activity as compared to that of adult skin in an East Asian population. The skin properties of 52 infants (3-24 months) and 27 adults (20-40 years) were assessed by noninvasive methods at the dorsal forearm and upper inner arm. Transepidermal water loss and skin surface conductance values were higher and more dispersed for infants compared to adults. Infant skin surface pH was slightly lower than adult on the dorsal forearm. The infant SC and viable epidermis were thinner compared to adults with differences that were site-specific. Although the chymotrypsin-like activity for infant skin was comparable to adult level, the caseinolytic specific activity was significantly higher for the infant cohort. These observations indicate a differently controlled pattern of corneocyte desquamation in infants. In conclusion, structural and functional differences exist between infant and adult skin in the East Asian population pointing to dynamic maturation of the epidermal barrier early in life.