Natural Moisturizing Factor Levels Research Articles

Reduced Skin Microbiome Diversity in Infancy Is Associated with Increased Risk of Atopic Dermatitis in High-Risk Children

It is currently unknown whether alterations in the skin microbiome exist prior to development of atopic dermatitis (AD). In this prospective Danish birth cohort of 300 children, we examined whether skin microbiome alterations during the first 2 months of life were associated with an increased risk of AD in the first 2 years, and its severity, following adjustment for environmental factors and selected skin chemokine and natural moisturizing factor levels. We found no overall association between the skin microbiome at birth and 2 months of age and AD during the first 2 years of life. However, when restricting the analysis to children with at least one parent with atopy, a lower alpha diversity at 2 months of age was associated with an increased risk of AD (adjusted hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.1-2.6). We observed a stronger association in children where both parents had atopy (HR 4.4 [1.1-18.2]). The putative pathogenic role of changes in the skin microbiome on AD risk remains uncertain but may play a role in those with an atopic predisposition.

Moisturizing at a molecular level - The basis of Corneocare.

This review covers the last 20 years of research we and our collaborators have conducted on ethnic differences in facial skin moisturization placed in historical context with previous research. We have focussed particularly on the biochemical and cellular gradients of the stratum corneum (SC) with the aim of discovering new skin moisturization and SC maturation mechanisms, identifying new technologies and/or providing conceptual innovations for ingredients that will improve our understanding and treatment of dry skin. Specifically, we discuss gradients for corneodesmosomes and proteases, corneocyte phenotype-inducing enzymes, filaggrin and natural moisturizing factor (NMF), and barrier lipids. These gradients are interdependent and influence greatly corneocyte maturation. The interrelationship between corneodesmolysis and the covalent attachment of ω-hydroxy ceramides and ω-hydroxy fatty acids to the corneocyte protein envelope forming the corneocyte lipid envelope is especially relevant in our new understanding of mechanisms leading to dry skin. This process is initiated by a linoleoyl-ω-acyl ceramide transforming enzyme cascade including 12R lipoxygenase (12R-LOX), epidermal lipoxygenase-3 (eLOX3), epoxide hydrolase 3 (EPHX3), short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7), ceramidase and transglutaminase 1. Our research has opened the opportunity of using novel treatment systems for dry skin based on lipids, humectants, niacinamide and inhibitors of the plasminogen system. It is clear that skin moisturization is a more complex mechanism than simple skin hydration.

Performance and Tolerance of a Protocol for Idiopathic Chronic Greasy Seborrhea in 18 Dogs Using a Shampoo and Mousse Containing Plant Extracts

The study aimed to evaluate the tolerance, performance and effect on hair lipids and skin hydration of a protocol combining applications of one shampoo and subsequent mousses containing plant extracts (Ophytrium and Seboliance) in dogs with an undiagnosed chronic greasy keratinisation disorder. Six dogs were washed with plain water on day (D)0. Twelve dogs were shampooed on D0 and received eight mousse applications at 48-72 h intervals from D2 to D18. Clinical score (CS), Natural Moisturizing Factors (NMF) and hair lipids (HL) were evaluated on D0, D0 + 4 h, D7, D14 and D24. At baseline, no significant differences were observed in CS, NMF and HL between groups. In the control group, CS and HL remained stable throughout the study while a slight decrease in NMF was observed at D0 + 4 h. CS was significantly reduced in the test group between D0 and D7 (-53%) which reached 91% at D24 (p < 0.05), with no side effects. NMF levels decreased in the test group at D0 + 4 h (-73%, p < 0.0001) and returned to baseline from D14. In conclusion, one shampoo and subsequent mousse applications rapidly and safely improved coat quality in dogs with an undiagnosed keratinisation disorder without affecting NMF and HL contents over the study period.

A comprehensive comparison of facial skin hydration based on capacitance and conductance measurements in Chinese women.

The aim of this study was to compare the data of conductance and capacitance measurements of facial skin hydration and to evaluate and discuss the advantages and disadvantages of the different approaches. We measured skin capacitance (Corneometer® CM 825) and skin conductance (Skicon-200EX®) on 30 pre-defined facial sites of 125 Chinese women, resulting in 3750 readings per device. The data were analysed and compared, and continuous colour maps were generated on a 3D avatar for capacitance, conductance, relative difference (Δ%) and correlation (R-value) by interpolating between the individual readings and converting the values to colours. This visualization allows a better interpretation of the results. The complexity of facial skin hydration is revealed by this approach. The similarities and discrepancies in the facial hydration maps are clearly apparent. Due to the superiority of the Skicon in measuring high hydration levels, differences in skin hydration were evident on the forehead compared with the Corneometer maps, which may be related to the more superficial measurement of the Skicon within the stratum corneum. Conversely, a greater understanding of the complexity of facial skin hydration in the nasolabial fold was obvious when using the Corneometer. The best congruence between the instruments was found at two specific but separated facial areas, one around the inner eye region and the other one on a line between the nasolabial sulcus and the oblique, lateral jaw. Interestingly, the data were not normally distributed for both instruments and they had opposite skews. All facial clusters were statistically different from each other (p< 0.001), except the cheek and jaw for the Skicon. Larger than expected percentage coefficients of variance were found for the Corneometer on some facial sites that might be explainable by differences in stratum corneum physiology and biochemistry. Corneometer values of 48 AU and Skicon values of 132 μS were taken as the cutoff for normally hydrated facial skin. Both devices have their advantages and disadvantages suggesting that bio-instrumental measurement of skin hydration is actually more complicated than commonly thought and that the different facial zones and the use of multiple instrumentation have not been adequately considered.

Why Does Facial Eczema Differ From Body Eczema?

The pathophysiology of atopic dermatitis (AD) is multifactorial, influenced by genetics, skin barrier dysfunction, and environmental stressors. There is a lack of research comparing the etiologies and pathologic mechanisms accounting for differences in facial vs body eczema. To explore reasons why facial eczema may differ from body eczema. There are key differences in the environments of the face and body that may lead to AD exacerbation. These include differences in the skin microbiome, sebaceous glands concentration, and levels of natural moisturizing factor. The face is exposed to more environmental stress compared with the rest of the body. These stresses include aeroallergens, ultraviolet radiation, and cosmetic products. Management of facial eczema also differs from that of body eczema due to the avoidance of high potency topical steroids on the face. Topical steroids increase microbiome diversity, and lack of topical steroid use on the face can lead to decreased microbiome diversity and increased AD severity. Facial and body eczema differ due to differences seen in anatomical structure and environmental exposures. These differences should be further researched and used in the management of facial vs body eczema and can also be used in the development of new AD treatments. J Drugs Dermatol. 2022;21(10): 1119-1123. doi:10.36849/JDD.6354.

Biomarkers in asthma in the context of atopic dermatitis in young children.

BackgroundDiverse pathways stemming from a history of atopic dermatitis (AD) might modulate different biomarkers associated with the development of asthma. Biomarkers associated with AD and asthma separately have been investigated, but none have characterized a combined AD+asthma phenotype. We investigated the clinical and molecular characteristics associated with an AD+asthma phenotype compared with AD, asthma and controls.MethodsFrom a prospective birth cohort and the outpatient allergy clinic, we included four groups of 6–12‐year‐old children: (1) healthy controls (2) previous, current, or present AD without asthma, (3) previous, current, or present AD and current asthma and (4) current asthma without AD. We performed clinical examinations and interviews and measured serum IgE, natural moisturizing factors (NMF), and plasma cytokine levels.ResultsWe found an increased number of IgE sensitizations in AD+asthma, prominent after stratifying for food allergens (p < .05). Pro‐Th2 cytokines CCL18, TSLP, and Eotaxin‐3 were elevated in AD+asthma, though not significantly higher than asthma, and elevated in asthma compared with controls. NMF levels were decreased in AD compared with asthma and control groups (p = .019, p < .001, respectively). NMF levels correlated negatively to sensitization (p = .026), though nonsignificant with only the patient groups.ConclusionOur results indicate that Th2 cytokines and increased number of sensitizations are associated with AD + asthma phenotypes compared with AD alone and that skin barrier impairment as well as decreased airway epithelial integrity may play a role in sensitization and immune modulation. Our findings suggest candidate biomarkers that should be further explored for their functional roles and prognostic potential.

Natural moisturizing factors in children with and without eczema: Associations with lifestyle and genetic factors.

Filaggrin-derived natural moisturizing factors (NMF) play an important role in skin barrier function and in atopic dermatitis (AD). Its deficiency is associated with dry skin and increased surface pH. Studies on childhood environmental exposures and associations with NMF levels are scarce. To investigate previous exposures and genetic factors and their associations with NMF levels in young children. In a case-control study nested in a prospective birth cohort (Odense Child Cohort), 169 healthy controls (HC) and 99 children with AD were included consecutively at the age of 7 years based on previous responses from questionnaires administered at 18 months, 3 years and 5 years, pertaining to past medical history, including allergy-specific questions. NMF levels were measured via a stratum corneum tape-stripping technique, genotyping for filaggrin (FLG) gene variants was performed and data on external exposures, including usage of moisturizer and topical steroids, antibiotics and early pet exposures, were obtained from questionnaires. Natural moisturizing factors levels were significantly lower in AD participants compared to HC (P < 0.001). This significance persisted after stratifying for AD subgroups of present AD, current AD during the last year and previous AD (P < 0.001, P = 0.039, P = 0.009 respectively). There was a significant association between NMF and FLG genotype (P = 0.016, P = 0.002 for HC, AD respectively). NMF levels were negatively correlated with early age moisturizer use (<18 months, P = 0.001) in HC but not significant in AD. We found decreased levels of NMF with early moisturizer use and a genetic influence of the FLG variant on these levels. NMF was decreased in the AD subgroup with previous AD compared with HC, which could suggest the persistence of a Th2 cytokine milieu suppressing these levels.

Assessment of biomarkers in pediatric atopic dermatitis by tape strips and skin biopsies.

The cytokine profile of atopic dermatitis (AD) depends on age, ethnicity, and disease severity. This study examined biomarkers in children with AD collected by tape strips and skin biopsies, and examined whether the levels differed with filaggrin genotype, disease severity, and food allergy. Twenty-five children aged 2-14years with AD were clinically examined. Skin biopsies were collected from lesional skin and tape strips were collected from lesional and non-lesional skin. We analyzed natural moisturizing factor (NMF) and 17 immune markers represented by mRNA levels in skin biopsies and protein levels in tape strips. Common filaggrin gene mutations were examined in all children. The cytokine profile in lesional skin was dominated by a T helper (Th) 2 response in skin biopsies, and by a general increase in innate inflammation markers (interleukin (IL)-1α, IL-1β, IL-8, IL-18) along with TARC and CTACK in tape strips. The levels of TARC, CTACK, IL-8, IL-18showed significant correlation with AD severity in both lesional and non-lesional tape stripped skin, while no significant correlations were observed in skin biopsy data. In tape strips from lesional and non-lesional skin, the levels of NMF and selected cytokines differed significantly between children with and without FLG mutations and food allergy. Sampling of the stratum corneum with non-invasive tape strips can be used to identify biomarkers that are associated with disease severity, food allergy and FLG mutations. Skin biopsies showed robust Th2signature but was inferior for association analysis regarding severity.

Stratum corneum markers of innate and T helper cell-related immunity and their relation to the disease severity in Croatian patients with atopic dermatitis.

Atopic dermatitis (AD) presents with the wide spectrum of clinical phenotypes within and between various populations. Recent study showed low frequency of filaggrin loss-of-function (FLG LOF) mutations in Croatian AD patients. At present, there are no data on biomarkers of immune response in Croatian AD patients that might be useful in the selection and monitoring of novel immune therapies. To investigate levels of cytokines of various signature in the stratum corneum (SC) collected from lesional and non-lesional skin of AD patients and healthy controls and to evaluate their relationship with the severity of disease and skin barrier function. SC samples were collected from 100 adult patients with moderate-to-severe AD and 50 healthy controls. The levels of 21 cytokines were measured by multiplex immunoassay. We conducted machine learning analysis to assess whether a small number of cytokine measurements can discriminate between healthy controls and AD patients and can predict AD severity (SCORAD). The SC levels of thirteen cytokines representing innate immunity, Th-1, Th-2 and Th-17/22 immune response showed significant differences between healthy and AD skin. Our analysis demonstrated that as few as three cytokines measured in lesional skin can discriminate healthy controls and AD with an accuracy of 99% and that the predictive models for SCORAD did not achieve a high accuracy. Cytokine levels were highly correlated with the levels of filaggrin degradation products and skin barrier function. Stratum corneum analysis revealed aberrant levels of cytokines representing innate immunity, Th-1-, Th-2- and Th-17/22-mediated immune response in Croatian AD patients. Increased Th-2 cytokines and their strong association with natural moisturizing factor (NMF) can explain low NMF levels despite of low frequency of FLG LOF mutations in Croatian population. Predictive models for SCORAD identified cytokines associated with SCORAD but warrants further investigation.

Staphylococcus aureus binds to the N-terminal region of corneodesmosin to adhere to the stratum corneum in atopic dermatitis

Staphylococcus aureus colonizes the skin of the majority of patients with atopic dermatitis (AD), and its presence increases disease severity. Adhesion of S. aureus to corneocytes in the stratum corneum is a key initial event in colonization, but the bacterial and host factors contributing to this process have not been defined. Here, we show that S. aureus interacts with the host protein corneodesmosin. Corneodesmosin is aberrantly displayed on the tips of villus-like projections that occur on the surface of AD corneocytes as a result of low levels of skin humectants known as natural moisturizing factor (NMF). An S. aureus mutant deficient in fibronectin binding protein B (FnBPB) and clumping factor B (ClfB) did not bind to corneodesmosin in vitro. Using surface plasmon resonance, we found that FnBPB and ClfB proteins bound with similar affinities. The S. aureus binding site was localized to the N-terminal glycine-serine-rich region of corneodesmosin. Atomic force microscopy showed that the N-terminal region was present on corneocytes containing low levels of NMF and that blocking it with an antibody inhibited binding of individual S. aureus cells to corneocytes. Finally, we found that S. aureus mutants deficient in FnBPB or ClfB have a reduced ability to adhere to low-NMF corneocytes from patients. In summary, we show that FnBPB and ClfB interact with the accessible N-terminal region of corneodesmosin on AD corneocytes, allowing S. aureus to take advantage of the aberrant display of corneodesmosin that accompanies low NMF in AD. This interaction facilitates the characteristic strong binding of S. aureus to AD corneocytes.

Stratum corneum levels of inflammatory mediators and natural moisturizing factor in patch test reactions to thiurams and fragrances and their possible role in discrimination between irritant and allergic reactions to hapten mixtures.

Patch test (PT) reactions to thiuram mix (TM) and fragrance mix (FM) I or II without concomitant reactions to their single constituents are potentially caused by the irritant properties of the mixes. Comparing inflammatory profiles of PT reactions to TM, FM I, FM II, and their constituents and assessing their potential in discrimination of irritant and allergic reactions. Levels of 14 cytokines and natural moisturizing factor (NMF) were determined in stratum corneum samples collected from PT reactions to TM, FM I or II, their constituents, and petrolatum (pet.) control sites in 36 individuals. Levels of interleukin (IL)-16, chemokine (CXC motif) ligand (CXCL) 8, CXCL10, chemokine (CC motif) ligand (CCL) 17, and CCL22 were significantly increased in reactions (+, ++) to thiurams and fragrances compared to their petrolatum. controls, except for PT reactions to FM I/II with negative breakdown testing in which, however, decreased levels of NMF were observed. In doubtful reactions to FM I/II with negative breakdown testing, NMF was significantly lower than in petrolatum controls. PT reactions to thiurams and fragrances indicate a Th2-skewed inflammation. The inflammatory profiles suggest that weak or doubtful FM I/II reactions without accompanying reaction to a constituent were irritant. IL-16 might be suitable to distinguish irritant from allergic reaction.

Barrier damaging effects of n-propanol in occlusion-modified tandem repeated irritation test: Modulation by exposure factors and atopic skin disease.

Recent studies provide evidence for significant and previously underestimated barrier damaging effects of repeated exposure to 60% n-propanol in healthy skin in vivo. To investigate further the cumulative effects of a range of n-propanol concentrations relevant at the workplace in healthy and atopic dermatitis (AD) individuals, and study the modulation of the outcomes by co-exposure and host-related factors. Healthy adult and AD volunteers were exposed to n-propanol concentrations from 30% to 75% in occlusion-modified tandem repeated irritation test with measurements of erythema, transepidermal water loss, capacitance, and the natural moisturizing factor (NMF) levels at baseline and after 96 hours. n-Propanol exerted significant barrier damaging effects even at the lowest concentration in both groups. Exposure to all n-propanol concentrations significantly reduced the NMF levels. Preceding low-grade trauma by occlusion/water exposure reduced the skin irritation threshold in both groups. The differences in the severity of the barrier function impairment after exposure to the same concentrations under the same conditions between the AD and control groups were significant. The negative effects of cumulative exposure to n-propanol in healthy and atopic skin shown in the study suggest the need for critical re-evaluation of its irritant properties in vivo.

Filaggrin Expression and Processing Deficiencies Impair Corneocyte Surface Texture and Stiffness in Mice

Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models with genetic deficiencies in the synthesis or degradation of filaggrin monomers for NMFs, cell stiffness (elastic modulus) and corneocyte surface protrusion density (dermal texture index). Five neonatal and adult mouse models carrying inactivating mutations of SASPase (Sasp-/-), filaggrin (Flgft/ft and Flg-/-), filaggrin-hornerin (FlgHrnr-/-), and bleomycin hydrolase (Blmh-/-) were investigated. Sasp-/- and Flg-/- were on the hairless mouse background. Atomic force microscopy was used to determine elastic modulus and dermal texture index. Corneocytes of each neonatal as well as hairless adult knockout mouse exhibited an increased number of protrusions and decreased elastic modulus. In these mice, NMFs were reduced except for Sasp-/-. Dermal texture index was inversely correlated with NMFs and elastic modulus. Our findings demonstrate that any filaggrin-NMF axis deficiency can affect corneocyte mechanical properties in mice and likely in humans. Differences in NMFs and corneocyte surface texture between neonatal and adult as well as hairless and hairy mice emphasize the need for carefully selecting the most appropriate animal models for studies.

A minimally invasive tool to study immune response and skin barrier in children with atopic dermatitis

Atopic dermatitis (AD) affects children of all skin types. Most research has focused on light skin types. Studies investigating biomarkers in people with AD with dark skin types are lacking. To explore skin barrier and immune response biomarkers in stratum corneum (SC) tape strips from children with AD with different skin types. Tape strips were collected from lesional and nonlesional forearm skin of 53 children with AD and 50 controls. We analysed 28 immunomodulatory mediators, and natural moisturizing factors (NMF) and corneocyte morphology. Interleukin (IL)-1β, IL-18, C-X-C motif chemokine (CXCL) 8 (CXCL8), C-C motif chemokine ligand (CCL) 22 (CCL22), CCL17, CXCL10 and CCL2 were significantly higher (P<0·05) in lesional AD skin compared with nonlesional AD skin; the opposite trend was seen for IL-1α. CXCL8, CCL2 and CCL17 showed an association with objective SCORing Atopic Dermatitis score. NMF levels showed a gradual decrease from healthy skin to nonlesional and lesional AD skin. This gradual decreasing pattern was observed in skin type II but not in skin type VI. Skin type VI showed higher NMF levels in both nonlesional and lesional AD skin than skin type II. Corneocyte morphology was significantly different in lesional AD skin compared with nonlesional AD and healthy skin. Minimally invasive tape-stripping is suitable for the determination of many inflammatory mediators and skin barrier biomarkers in children with AD. This study shows differences between children with AD with skin type II and skin type VI in NMF levels, suggesting that some aspects of pathophysiological mechanisms may differ in AD children with light versus dark skin types.

Adhesion of Staphylococcus aureus to Corneocytes from Atopic Dermatitis Patients Is Controlled by Natural Moisturizing Factor Levels.

ABSTRACTThe bacterial pathogen Staphylococcus aureus plays an important role in atopic dermatitis (AD), a chronic disorder that mostly affects children. Colonization of the skin of AD patients by S. aureus exacerbates the disease, but the molecular determinants of the bacterium-skin adhesive interactions are poorly understood. Specifically, reduced levels of natural moisturizing factor (NMF) in the stratum corneum have been shown to be associated with more severe AD symptoms, but whether this is directly related to S. aureus adhesion is still an open question. Here, we demonstrate a novel relationship between NMF expression in AD skin and strength of bacterial adhesion. Low-NMF corneocytes, unlike high-NMF ones, are covered by a dense layer of nanoscale villus protrusions. S. aureus bacteria isolated from AD skin bind much more strongly to corneocytes when the NMF level is reduced. Strong binding forces originate from a specific interaction between the bacterial adhesion clumping factor B (ClfB) and skin ligands. Remarkably, mechanical tension dramatically strengthens ClfB-mediated adhesion, as observed with catch bonds, demonstrating that physical stress plays a role in promoting colonization of AD skin by S. aureus. Collectively, our findings demonstrate that patient NMF levels regulate the strength of S. aureus-corneocyte adhesion, the first step in skin colonization, and suggest that the ClfB binding mechanism could represent a potential target for new therapeutic treatments.

Early-life regional and temporal variation in filaggrin-derived natural moisturizing factor, filaggrin-processing enzyme activity, corneocyte phenotypes and plasmin activity: implications for atopic dermatitis.

SummaryBackgroundFilaggrin is central to the pathogenesis of atopic dermatitis (AD). The cheeks are a common initiation site of infantile AD. Regional and temporal expression of levels of filaggrin degradation products [natural moisturizing factors (NMFs)], activities of filaggrin‐processing enzymes [bleomycin hydrolase (BH) and calpain‐1 (C‐1)] and plasmin, and corneocyte envelope (CE) maturity in early life are largely unknown.ObjectivesWe conducted a cross‐sectional, observational study investigating regional and age‐dependent variations in NMF levels, activity of proteases and CE maturity in stratum corneum (SC) from infants to determine whether these factors could explain the observed predilection sites for AD in early life.MethodsWe measured NMF using a tape‐stripping method at seven sites in the SC of 129 children (aged < 12 months to 72 months) and in three sites in 56 neonates and infants (< 48 h to 3 months). In 37 of these neonates and infants, corneocyte size, maturity, BH, C‐1 and plasmin activities were determined.Results NMF levels are low at birth and increase with age. Cheek SC, compared with elbow flexure and nasal tip, has the lowest NMF in the first year of life and is the slowest to reach stable levels. Cheek corneocytes remain immature. Plasmin, BH and C‐1 activities are all elevated by 1 month of age in exposed cheek skin, but not in elbow skin.ConclusionsRegional and temporal differences in NMF levels, CE maturity and protease activities may explain the predilection for AD to affect the cheeks initially and are supportive of this site as key for allergen priming in early childhood. These observations will help design early intervention and treatment strategies for AD.

Effect of atopic skin stressors on natural moisturizing factors and cytokines in healthy adult epidermis.

Epidermal deficiency of filaggrin, and the derived natural moisturizing factors (NMFs), is associated with increased risk of atopic dermatitis (AD). While filaggrin gene mutations cause filaggrin deficiency, there is limited insight into the causative environmental factors. To explore the effect of selected exogenous skin stressors on NMF and skin cytokine levels in healthy adult epidermis. Forty healthy volunteers (aged 18-49 years) were exposed to hard, soft and chlorinated water, 0·5% sodium lauryl sulfate, house dust mite, cat allergen, staphylococcal enterotoxin B (SEB), cooling and histamine. Participants were tape-stripped and biophysiological measurements performed. NMF was determined after 24 and 48 h, whereas skin cytokines were measured after 24 h for selected exposures. At 24 h, a significant decrease in NMFs was observed for soft (0·51 ± 0·19 g m-2 h-1 ) and hard water (0·61 ± 0·32 g m-2 h-1 ) compared with occlusion alone (0·71 ± 0·18 g m-2 h-1 ). Hard water led to increased levels of interleukin (IL)-4, interferon (IFN)-γ and IL-10. Exposure to house dust mite and SEB led to a significant decrease in NMFs after 24 h (0·77 ± 0·28 and 0·80 ± 0·28 g m-2 h-1 , respectively) compared with occlusion alone (1·00 ± 0·42 g m-2 h-1 ). House dust mite led to an increase in IFN-γ, IL-2 and IL-4 vs. the nonoccluded control site. Based on experimental exposure to selected atopic skin stressors, we conclude that NMFs levels are decreased along with increased secretion of various skin cytokines in healthy individuals. Our data highlight environmental factors that might play a role in AD pathophysiology.

Specific barrier response profiles after experimentally induced skin irritation in vivo.

BackgroundRecently, natural moisturizing factors (NMFs) and corneocyte surface topography were suggested as biomarkers for irritant dermatitis.ObjectivesTo investigate how exposure to different irritants influences corneocyte surface topography, NMF levels and the barrier function of human skin in vivo.MethodsEight healthy adult volunteers were exposed to aqueous solutions of 60% n‐propanol, 0.5% sodium lauryl sulfate (SLS), 0.15% sodium hydroxide, and 2.0% acetic acid, and distilled water, in a repeated irritation test over a period of 96 hours. Erythema, transepidermal water loss (TEWL), skin hydration, the dermal texture index (DTI) and NMF levels were measured at baseline, and after 24 and 96 hours.ResultsSLS and sodium hydroxide had the most pronounced effects on erythema and TEWL. Although n‐propanol caused only slight changes in TEWL and erythema, it showed pronounced effects on skin hydration, NMF levels, and the DTI. NMF was the only parameter that was significantly altered by all investigated irritants. The changes in the DTI were inversely associated with NMF levels and skin hydration.ConclusionSkin barrier impairment and the inflammatory response are irritant‐specific, emphasizing the need for a multiparametric approach to the study of skin irritation. NMF levels seem to be the most sensitive parameter in detecting irritant‐induced skin barrier alterations.

Changes in filaggrin degradation products and corneocyte surface texture by season.

During the winter in northern countries, the risk of dermatitis is increased due to low temperature and humidity. Dermatitis is particularly common on weather-exposed skin such as the cheeks and hands. Recently, increased numbers of unidentified nanosized protrusions on the corneocyte surface were associated with dermatitis and deficiency of natural moisturizing factor (NMF). To investigate the effect of season on NMF levels and corneocyte surface texture in cheek and hand skin of healthy adults. Eighty healthy volunteers (40 male and 40 female) were recruited: 40 aged 18-40years and 40 aged ≥70years. Cheek and dorsal hand skin was tape stripped in the winter and summer. Analysis for NMF and corneocyte surface texture was done (Dermal Texture Index, DTI). Potential confounders were registered and adjusted for. In cheek skin, NMF levels were reduced and DTI elevated during the winter compared with the summer. Older participants had higher NMF levels than younger participants. In the summer, DTI level was dependent on self-reported ultraviolet exposure. In hand skin, NMF levels were higher during the winter than in the summer, and female participants had higher NMF levels than male participants. Seasonal effects on NMF and DTI on the cheeks and hands were found, suggesting an influence of climatic factors at the biochemical and ultrastructural levels. Significant variations were also observed regarding age and sex, making it difficult to draw firm conclusions. Our study adds new pieces to the puzzle of seasonal differences in xerosis and dermatitis.

Concentration of filaggrin monomers, its metabolites and corneocyte surface texture in individuals with a history of atopic dermatitis and controls.

Atopic dermatitis (AD) is characterized by skin barrier dysfunction. Notably, a high number of nano-scale protrusions on the surface of corneocytes, which can be expressed by the Dermal Texture Index (DTI), were recently associated with paediatric AD, loss-of-function mutations in filaggrin gene (FLG) and reduced levels of natural moisturizing factors (NMF). No study has so far examined the association between these parameters and monomeric filaggrin levels in adults. To determine DTI, monomeric filaggrin and NMF in healthy controls and a group of patients with controlled dermatitis. A total of 67 adults (20 healthy controls and 47 dermatitis patients) were included. In the patient population, a personal history of AD was diagnosed by the U.K. Working Party's Diagnostic Criteria. All participants were tested for FLG mutations (R501X, 2282del4, R2447X). Transepidermal water loss, monomeric filaggrin, DTI and NMF were measured. In the patient population, 78.7% (37/47) had a history of AD and 59.5% (28/47) had FLG mutations. Patients had significantly higher levels of DTI and significantly lower levels of monomeric filaggrin and NMF compared to the 20 healthy controls. Among patients, reduced level of monomeric filaggrin and NMF correlated with the presence of FLG mutations and clinical phenotypes such as xerosis, palmar hyperlinearity and AD. Among healthy controls, DTI was significantly higher in the oldest age group compared to the two younger age groups. A significant difference in DTI, monomeric filaggrin and NMF levels was found when comparing dermatitis patients with healthy controls. These findings suggest that even mild dermatitis or non-visible inflammation has a significant and negative effect on the skin barrier as inflammation is known to reduce filaggrin levels. DTI was significantly increased in aged individuals in the healthy control group, suggesting a gradual change in corneocyte morphology with age.