Atopic dermatitis: Role of the skin barrier, environment, microbiome, and therapeutic agents.

Atopic dermatitis (AD) is a chronic, inflammatory skin disorder characterized by eczematous and pruritic skin lesions. In recent decades, the prevalence of AD has increased worldwide, most notably in developing countries. The enormous progress in our understanding of the complex composition and functions of the epidermal barrier allows for a deeper appreciation of the active role that the skin barrier plays in the initiation and maintenance of skin inflammation. The epidermis forms a physical, chemical, immunological, neuro-sensory, and microbial barrier between the internal and external environment. Not only lesional, but also non-lesional areas of AD skin display many morphological, biochemical and functional differences compared with healthy skin. Supporting this notion, genetic defects affecting structural proteins of the skin barrier, including filaggrin, contribute to an increased risk of AD. There is evidence to suggest that natural environmental allergens and man-made pollutants are associated with an increased likelihood of developing AD. A compromised epidermal barrier predisposes the skin to increased permeability of these compounds. Numerous topical and systemic therapies for AD are currently available or in development; while anti-inflammatory therapy is central to the treatment of AD, some existing and novel therapies also appear to exert beneficial effects on skin barrier function. Further research on the skin barrier, particularly addressing epidermal differentiation and inflammation, lipid metabolism, and the role of bacterial communities for skin barrier function, will likely expand our understanding of the complex etiology of AD and lead to identification of novel targets and the development of new therapies.

Eczematous Drug Eruptions.

Eczematous drug eruptions are a heterogenous group of skin reactions that resemble eczema both clinically and histologically. We reviewed the literature and cataloged the systemically administered medications that cause these eruptions, along with their characteristic clinical presentations. We identified three primary pathophysiologic etiologies: (1) cutaneous immunomodulation, (2) skin dehydration, and (3) delayed hypersensitivity. Notably, eczematous eruptions caused by altered immunity in the skin may be increasing in incidence as some responsible drugs, in particular biologic therapies (such as tumor necrosis factor-α and interleukin-17 inhibitors) and targeted cancer treatments (including immune checkpoint inhibitors and epidermal growth factor receptor inhibitors), become more commonly employed in clinical practice. Other notable causes of eczematous eruptions include antiviral agents for hepatitis C virus and cardiovascular medications in elderly individuals, and notable subtypes of eczematous reactions include systemic contact dermatitis and photoallergic reactions, which are also discussed. The diagnostic gold standard is drug rechallenge and most reactions may be treated effectively with emollients, topical corticosteroids, and oral antihistamines.

Clinical Evaluation of a Nature-Based Bakuchiol Anti-Aging Moisturizer for Sensitive Skin.

BACKGROUND: Patients with sensitive skin find topical retinoid use for anti-aging purposes challenging due to irritation. Bakuchiol, a meroterpene from the Psoralea corylifolia seed, has retinol functionality through retinol-like regulation of gene expression. OBJECTIVE: This research examined the tolerability, efficacy, and barrier effects of a nature-based bakuchiol-containing cleanser and moisturizer in subjects with sensitive skin. METHODS: 60 female subjects Fitzpatrick skin types I–V age 40–65 years with sensitive mild to moderate photodamaged skin were enrolled in this 4 week study. A sensitive skin panel was constructed: 1/3 eczema/atopic dermatitis, 1/3 rosacea, 1/3 cosmetic intolerance syndrome. Subjects used a nature-based cleanser and moisturizer twice daily and underwent transepidermal water loss (TEWL), corneometry, tolerability assessments, and efficacy assessments at baseline, 5–10 minutes post-application, and week 4. RESULTS: The skin care products were well tolerated and efficacious (P<0.001) in terms of investigator assessed improvement in visual smoothness, tactile smoothness, clarity, radiance, overall appearance, and global anti-aging. Cheek corneometry measurements demonstrated a statistically significant 16% increase in skin moisture content (P<0.001). CONCLUSION: A bakuchiol nature-based anti-aging moisturizer is well tolerated and effective in individuals with sensitive skin.J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5522.

Atopic Dermatitis and the Role of the Skin Microbiome in Choosing Prevention, Treatment, and Maintenance Options.

BACKGROUND: Atopic dermatitis (AD) is a common skin condition characterized by disturbed barrier function, skin inflammation, and cutaneous dysbiosis. Clinically, it manifests as chronic-recurrent xerosis, pruritus, and erythematous lesions. Its pathophysiology is complex, making the selection of appropriate treatment options a task. AIM: To share insights gained from a literature review and discussions with experts in dermatology on key factors related to the prevention, treatment, and management of AD in relation to the skin microbiome. METHODS: Results from an expert panel were summarized and discussed to provide updated recommendations for the treatment and maintenance of AD. RESULTS: Evidence supports a strategy for managing inflammatory skin diseases with a selenium-rich post-biotic thermal water and biomass containing moisturizer. The moisturizer helps to restore homeostasis of the skin, re-populate a diverse microbiome, encourage the growth of commensal bacteria, and improve barrier function and symptoms of AD. CONCLUSIONS: Normalization of skin microbiome diversity using a topical moisturizer containing post-biotic aqua and biomass may offer a valuable option for the treatment and maintenance of inflammatory skin diseases. Clinicians should discuss the benefits of this treatment in the context of a full AD management program that covers prevention, active treatment, and maintenance. J Drugs Dermatol. 2020;19(10):935-940. doi:10.36849/JDD.2020.5393.

Efficacy of Nonprescription Moisturizers for Atopic Dermatitis: An Updated Review of Clinical Evidence.

Twice-daily moisturization is recommended by international guidelines as the bedrock of the management of atopic dermatitis (AD). Moisturizers should be selected based on proven clinical effectiveness in improving the skin barrier and improving the symptoms of AD. We searched the PubMed database for clinical trials assessing daily moisturization for the treatment of AD published between 2006 and 2019. Studies had to assess the efficacy of commercially available moisturizers using objective measures of corneometry, transepidermal water loss, or incidence of flare as endpoints, and treatments had to be currently available to patients. Clinical studies showed that moisturization (typically twice daily) significantly improved the skin barrier in adults and children with AD. Longer-term flare studies showed that daily moisturization reduced the incidence of flares and extended the time between flares. Proactive moisturization of infants at high risk of developing AD may reduce its manifestation. Therapeutic moisturizers for AD are specifically formulated with ingredients that target symptoms of AD, such as itch, inflammation, or compromised skin barrier. The US FDA requires that any moisturizer available in the USA and claiming to treat AD must contain colloidal oatmeal. Healthcare providers can maximize compliance and outcomes by educating patients on the benefits of liberally applying a therapeutic moisturizer twice daily to support the skin barrier and help reduce the incidence of flares. Specific recommendations should be for clinically tested moisturizers evaluated using objective, validated skin assessments.

Air Particulate Matter Induces Skin Barrier Dysfunction and Water Transport Alteration on a Reconstructed Human Epidermis Model.

Knowing the damage that particulate matter (PM) can cause in skin is important for tightly controlling the release of air pollutants and preventing more serious diseases. This study investigates if such alterations are present in reconstructed human epidermis exposed to coarse air PM. Exposure of reconstructed human epidermis to increasing concentrations (2.2, 8.9, and 17.9 µg/cm2) of standard urban PM over time led to decreased cell viability at 48 hours. The barrier function was shown to be compromised by 24 hours of exposure to high doses (17.9 µg/cm2). Morphological alterations included cytoplasm vacuolization and partial loss of epidermal stratification. Cytokeratin 10, involucrin, loricrin, and filaggrin protein levels were significantly decreased. We confirmed an inflammatory process by IL-1α release and found a significant increase in AQP3 expression. We also demonstrated changes in NOTCH1 and AhR expression of epidermis treated with coarse air PM. The use of hydrogen peroxide altered AQP3 and NOTCH1 expression, and the use of N-acetyl-L-cysteine altered NOTCH1 expression, suggesting that this is a redox-dependent process. These results demonstrate that coarse air PM induces dose-dependent inflammatory response and alterations in protein markers of differentiation and water transport in the epidermis that could ultimately compromise the structural integrity of the skin, promoting or exacerbating various skin diseases.

Handheld confocal Raman spectroscopy (CRS) for objective assessment of skin barrier function and stratification of severity in atopic dermatitis (AD) patients.

BACKGROUND: We developed the first-of-its-kind handheld confocal Raman spectroscopy (CRS) system to quantify the concentration of natural moisturizing factors in the skin. OBJECTIVE: To evaluate the feasibility of our handheld CRS system and propose a novel quantitative index to measure skin barrier function. METHODS: This prospective study included 30 atopic dermatitis (AD) patients and 14 healthy volunteers. All AD participants were assessed using the Scoring Atopic Dermatitis (SCORAD) severity instrument, a vapometer for trans-epidermal water loss and a moisture meter for skin surface moisture. A handheld CRS operating at 785 nm laser was used to measure the biochemical constituents of the skin up to a depth of ∼100 µm. We trained a linear kernel-based support vector machine (SVM) model for eczema classification based on the water, ceramide and urocanic acid content. A novel Eczema Biochemical Index (EBI) was then formulated using the skin constituents measured from the AD participants to stage disease severity. RESULTS: The SVM model used to classify healthy participants and AD patients obtained high cross-validated area under the curve of 0.857 and accuracy of 0.841, with high sensitivity and specificity values of 0.857 and 0.833 respectively. EBI can be used to stratify AD patients of varying severity, based on the biochemical constituents in the skin. CONCLUSION: As compared to the standard CRS system, the handheld CRS offers higher portability and provides Raman measurements at various body regions with similar sensitivity. This suggests that a handheld CRS device could be a valuable point-of-care resource in both research and clinical use.

Skin of atopic dermatitis patients shows disturbed ß-glucocerebrosidase and acid sphingomyelinase activity that relates to changes in stratum corneum lipid composition.

Patients with Atopic Dermatitis (AD) suffer from inflamed skin and skin barrier defects. Proper formation of the outermost part of the skin, the stratum corneum (SC), is crucial for the skin barrier function. In this study we analyzed the localization and activity of lipid enzymes ß-glucocerebrosidase (GBA) and acid sphingomyelinase (ASM) in the skin of AD patients and controls. Localization of both the expression and activity of GBA and ASM in the epidermis of AD patients was altered, particularly at lesional skin sites. These changes aligned with the altered SC lipid composition. More specifically, abnormal localization of GBA and ASM related to an increase in specific ceramide subclasses [AS] and [NS]. Moreover we related the localization of the enzymes to the amounts of SC ceramide subclasses and free fatty acids (FFAs). We report a correlation between altered localization of active GBA and ASM and a disturbed SC lipid composition. Localization of antimicrobial peptide beta-defensin-3 (HBD-3) and AD biomarker Thymus and Activation Regulated Chemokine (TARC) also appeared to be diverging in AD skin compared to control. This research highlights the relation between correct localization of expressed and active lipid enzymes and a normal SC lipid composition for a proper skin barrier.

Claudin-1 decrease impacts epidermal barrier function in atopic dermatitis lesions dose-dependently.

The transmembrane protein claudin-1 is a major component of epidermal tight junctions (TJs), which create a dynamic paracellular barrier in the epidermis. Claudin-1 downregulation has been linked to atopic dermatitis (AD) pathogenesis but variable levels of claudin-1 have also been observed in healthy skin. To elucidate the impact of different levels of claudin-1 in healthy and diseased skin we determined claudin-1 levels in AD patients and controls and correlated them to TJ and skin barrier function. We observed a strikingly broad range of claudin-1 levels with stable TJ and overall skin barrier function in healthy and non-lesional skin. However, a significant decrease in TJ barrier function was detected in lesional AD skin where claudin-1 levels were further reduced. Investigations on reconstructed human epidermis expressing different levels of claudin-1 revealed that claudin-1 levels correlated with inside-out and outside-in barrier function, with a higher coherence for smaller molecular tracers. Claudin-1 decrease induced keratinocyte-autonomous IL-1ß expression and fostered inflammatory epidermal responses to non-pathogenic Staphylococci. In conclusion, claudin-1 decrease beyond a threshold level results in TJ and epidermal barrier function impairment and induces inflammation in human epidermis. Increasing claudin-1 levels might improve barrier function and decrease inflammation and therefore be a target for AD treatment.

Increased regulatory T cells and eosinophils characterize atopic dermatitis-like graft-versus-host disease compared with lichen planus-like graft-versus-host disease.

BACKGROUND: Graft-versus-host disease (GVHD) has various cutaneous manifestations. Little is known about the mechanisms of cutaneous GVHD with different clinical features. OBJECTIVE: To characterize the immunologic features and skin barrier functions of cutaneous GVHD. METHODS: The study included 19 patients with atopic dermatitis (AD)-like GVHD, 8 with lichen planus (LP)-like GVHD, 24 with AD, and 15 healthy controls. The subpopulation of T cells in peripheral blood and skin lesions was measured by flow cytometry and immunofluorescence, respectively. Filaggrin expression in skin lesions was measured by Western blot and immunohistochemistry. Transepidermal water loss was also measured using Tewameter TM 300 (Courage & Khazaka Electronic GmbH, Köln, Germany). RESULTS: The number of peripheral blood eosinophils in AD-like GVHD was significantly higher than that in LP-like GVHD. Type 2 helper T cells in peripheral blood and skin lesions were increased in AD-like GVHD and LP-like GVHD. Regulatory T cells in peripheral blood and skin lesions were increased in AD-like GVHD. Filaggrin expression and transepidermal water loss were increased in skin lesions of AD-like GVHD and LP-like GVHD. LIMITATIONS: The number of patients is limited. CONCLUSION: Although AD-like GVHD and LP-like GVHD both had elevated type 2 helper T cells and impaired skin barrier, increased eosinophils and regulatory T cells were found only in AD-like GVHD.

Skin barrier immunity and ageing.

The skin is the outermost layer of the body with an extensive surface area of approximately 1·8 m2 , and is the first line of defence against a multitude of external pathogens and environmental insults. The skin also has important homeostatic functions such as reducing water loss and contributing to thermoregulation of the body. The structure of the skin and its cellular composition work in harmony to prevent infections and to deal with physical and chemical challenges from the outside world. In this review, we discuss how the structural cells such as keratinocytes, fibroblasts and adipocytes contribute to barrier immunity. We also discuss specialized immune cells that are resident in steady-state skin including mononuclear phagocytes, such as Langerhans cells, dermal macrophages and dermal dendritic cells in addition to the resident memory T cells. Ageing results in an increased incidence of cancer and skin infections. As we age, the skin structure changes with thinning of the epidermis and dermis, increased water loss, and fragmentation of collagen and elastin. In addition, the skin immune composition is altered with reduced Langerhans cells, decreased antigen-specific immunity and increased regulatory populations such as Foxp3+ regulatory T cells. Together, these alterations result in decreased barrier immunity in the elderly, explaining in part their increased susceptiblity to cancer and infections.

The role of ceramides in skin homeostasis and inflammatory skin diseases.

Ceramides, members of sphingolipid family, are not only the building blocks of epidermal barrier structure, but also bioactive metabolites involved in epidermal self-renewal and immune regulation. Hence, abnormal ceramide expression profile is recognized to defect extracellular lipid organization, disturb epidermal self-renewal, exacerbate skin immune response and actively participate in progression of several inflammatory dermatoses, exemplifying by psoriasis and atopic dermatitis. Here, we discuss recent advances in understanding skin ceramides and their regulatory roles in skin homeostasis and pathogenic roles of altered ceramide metabolism in inflammatory skin diseases. These insights provide new opportunities for therapeutic intervention in inflammatory dermatoses.

Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis.

Importance: Molecular profiling of skin biopsies is the criterion standard for evaluating the cutaneous atopic dermatitis (AD) phenotype. However, skin biopsies are not always feasible in children. A reproducible minimally invasive approach that can track cutaneous disease in pediatric longitudinal studies or clinical trials is lacking. Objective: To assess a minimally invasive approach using tape strips to identify skin biomarkers that may serve as a surrogate to biomarkers identified using whole-tissue biopsies. Design, Setting, and Participants: This cross-sectional study of 51 children younger than 5 years recruited children with moderate to severe AD and children without AD from the dermatology outpatient clinics at a children's hospital. Sixteen tape strips were serially collected from the nonlesional and lesional skin of 21 children who had AD and were less than 6 months from disease initiation and from the normal skin of 30 children who did not have AD between January 22, 2016, and April 20, 2018. Main Outcomes and Measures: Gene and protein expression were evaluated using quantitative real-time polymerase chain reaction and immunohistochemistry. Results: A total of 51 children younger than 5 years were included in the study; 21 children had moderate to severe AD with less than 6 months of disease duration, and 30 children did not have AD. Of the 21 children with AD, the mean (SD) age was 1.7 (1.7) years, and most were male (15 [71.4%] and white (15 [71.4%]). Of the 30 children without AD, the mean (SD) age was 1.8 (2.0) years, and most were female (20 [66.7%]) and white (22 [73.3%]). Seventy-seven of 79 evaluated immune and barrier gene products were detected (gene detection rate, 97%) in 70 of 71 tape strips (sample detection rate, 99%), with 53 of 79 markers differentiating between children with lesional and/or nonlesional AD from children without AD. Many cellular markers of T cells (CD3), AD-related dendritic cells (Fc ε RI and OX40 ligand receptors), and key inflammatory (matrix metallopeptidase 12), innate (interleukin 8 [IL-8] and IL-6), helper T cell 2 (TH2; IL-4, IL-13, and chemokines CCL17 and CCL26), and TH17/TH22 (IL-19, IL-36G, and S100A proteins) genes were significantly increased in lesional and nonlesional AD compared with tape strips from normal skin. For example, IL-4 mean (SE) for lesional was -15.2 (0.91) and normal was -19.5 (0.48); P < .001. Parallel decreases occurred in epidermal barrier gene products (FLG, CLDN23, and FA2H) and negative immune regulators (IL-34 and IL-37). For example, the decrease for FLG lesional was mean (SE) -2.9 (0.42) and for normal was 2.2 (0.45); P < .001. Associations were found between disease severity or transepidermal water loss and TH2 (IL-33 and IL-4R) and TH17/TH22 (IL-36G and S100As) products in lesional and nonlesional AD skin (evaluated using the SCORing Atopic Dermatitis, Eczema Area and Severity Index, and Pruritus Atopic Dermatitis Quickscore tools). Conclusions and Relevance: In this study, tape strips provide a minimally invasive alternative for serially evaluating AD-associated cutaneous biomarkers and may prove useful for tracking pediatric AD therapeutic response and predicting future course and comorbidities.

Systemic and stratum corneum biomarkers of severity in infant atopic dermatitis include markers of innate and T helper cell-related immunity and angiogenesis.

BACKGROUND: Biomarkers of atopic dermatitis (AD) are largely lacking, especially in infant AD. Those that have been examined to date have focused mostly on serum cytokines, with few on noninvasive biomarkers in the skin. OBJECTIVES: We aimed to explore biomarkers obtainable from noninvasive sampling of infant skin. We compared these with plasma biomarkers and structural and functional measures of the skin barrier. METHODS: We recruited 100 infants at first presentation with AD, who were treatment naive to topical or systemic anti-inflammatory therapies, and 20 healthy children. We sampled clinically unaffected skin by tape stripping the stratum corneum (SC). Multiple cytokines and chemokines and natural moisturizing factor were measured in the SC and plasma. We recorded disease severity and skin barrier function. RESULTS: Nineteen SC and 12 plasma biomarkers showed significant differences between healthy and AD skin. Some biomarkers were common to both the SC and plasma, and others were compartment specific. Identified biomarkers of AD severity included T helper 2-skewed markers [interleukin (IL)-13, CCL17, CCL22, IL-5]; markers of innate activation (IL-18, IL-1α, IL1ß, CXCL8) and angiogenesis (Flt-1, vascular endothelial growth factor); and others (soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, IL-16, IL-17A). CONCLUSIONS: We identified clinically relevant biomarkers of AD, including novel markers, easily sampled and typed in infants. These markers may provide objective assessment of disease severity and suggest new therapeutic targets, or response measurement targets for AD. Future studies will be required to determine whether these biomarkers, seen in very early AD, can predict disease outcomes or comorbidities.

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

BACKGROUND: 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. OBJECTIVES: To explore the effect of selected exogenous skin stressors on NMF and skin cytokine levels in healthy adult epidermis. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Epidermal Overexpression of Xenobiotic Receptor PXR Impairs the Epidermal Barrier and Triggers Th2 Immune Response.

The skin is in daily contact with environmental pollutants, but the long-term effects of such exposure remain underinvestigated. Many of these toxins bind and activate the pregnane X receptor (PXR), a ligand-activated transcription factor that regulates genes central to xenobiotic metabolism. The objective of this work was to investigate the effect of constitutive activation of PXR in the basal layer of the skin to mimic repeated skin exposure to noxious molecules. We designed a transgenic mouse model that overexpresses the human PXR gene linked to the herpes simplex VP16 domain under the control of the keratin 14 promoter. We show that transgenic mice display increased transepidermal water loss and elevated skin pH, abnormal stratum corneum lipids, focal epidermal hyperplasia, activated keratinocytes expressing more thymic stromal lymphopoietin, a T helper type 2/T helper type 17 skin immune response, and increased serum IgE. Furthermore, the cutaneous barrier dysfunction precedes development of the T helper type 2/T helper type 17 inflammation in transgenic mice, thereby mirroring the time course of atopic dermatitis development in humans. Moreover, further experiments suggest increased PXR signaling in the skin of patients with atopic dermatitis when compared with healthy skin. Thus, PXR activation by environmental pollutants may compromise epidermal barrier function and favor an immune response resembling atopic dermatitis.

SERPINB3/B4 contributes to early inflammation and barrier dysfunction in an experimental murine model of atopic dermatitis.

Serine proteases are critical for epidermal barrier homeostasis, and their aberrant expression and/or activity is associated with chronic skin diseases. Elevated levels of the serine protease inhibitors SERPINB3 and SERPINB4 are seen in patients with atopic dermatitis and psoriasis. However, their mechanistic role in the skin is unknown. To evaluate the contribution of Serpinb3a (mouse homolog of SERPINB3 and SERPINB4) in atopic dermatitis, we examined the effect of topical Aspergillus fumigatus extract exposure in wild-type and Serpinb3a-null mice on transepidermal water loss (TEWL), sensitization, and inflammation. Allergen exposure induced Serpinb3a expression in the skin, along with increased TEWL, epidermal thickness, and skin inflammation, all of which were attenuated in the absence of Serpinb3a. Attenuated TEWL correlated with decreased expression of the pro-inflammatory marker S100A8. Silencing of SERPINB3/B4 in human keratinocytes decreased S100A8 expression, supporting a role for SERPINB3/B4 in the initiation of the acute inflammatory response. RNA-seq analysis following allergen exposure identified a network of pro-inflammatory genes induced in wild-type mice that was absent in Serpinb3a-null mice. In conclusion, Serpinb3a deficiency attenuates barrier dysfunction and the early inflammatory response following cutaneous allergen exposure, supporting a role for Serpinb3a (mice) and SERPINB3/B4 (humans) early in atopic dermatitis.

Immunological and molecular targets of atopic dermatitis treatment.

Atopic dermatitis (AD) is a common, chronic inflammatory skin disease with a highly variable clinical phenotype and heterogeneous pathophysiology. Its pathogenesis is associated with alterations to both the skin barrier and the immune system, which may in turn be influenced by genetic mutations and the patient's environment. Basic and translational research, as well as clinical trials, have helped broaden our knowledge of the molecular mechanisms underlying the development of AD and to identify potential treatment targets and approaches. These include new ways of reducing transepidermal water loss and the shedding of corneocytes, new ways of interacting with established molecular targets (such as histamine receptors and interleukins and other T-cell cytokines), and the identification of new molecular targets (such as toll-like receptors and tight junction proteins). Well-established treatment options such as emollients, corticosteroids and topical calcineurin inhibitors will clearly continue to have a role in treating AD. Among the new agents that could be joining them in the near future are sphinganin (a precursor of ceramides 1 and 3), cannabinoids, highly targeted monoclonal antibodies and subcutaneous immunotherapy.

Correlation between serum thymus and activation-regulated chemokine levels and stratum corneum barrier function in healthy individuals and patients with mild atopic dermatitis.

BACKGROUND: Serum thymus and activation-regulated chemokine (TARC) levels closely reflect the disease activity of atopic dermatitis (AD). AD is characterized by impaired epidermal barrier function and atopic dry skin. However, dry skin is also a very common problem in healthy individuals. OBJECTIVE: To investigate the relationship between serum TARC levels and epidermal barrier function in healthy subjects and patients with mild AD. METHODS: This study included 2 groups, 121 healthy subjects (healthy group) and 66 patients with mild AD (mild AD group). Barrier function was assessed by transepidermal water loss (TEWL) and stratum corneum hydration (SCH). RESULTS: Significantly elevated serum TARC levels and TEWL values and significantly decreased SCH values were detected in the mild AD group compared to those in the healthy group. In the mild AD group, serum TARC levels were significantly correlated with TEWL values and were inversely correlated with SCH values. Importantly, serum TARC levels were also inversely correlated with SCH values in the healthy controls. TEWL values in the healthy group tended to be correlated with TARC levels but did not reach statistical significance. CONCLUSION: Together with TEWL and SCH, serum TARC level is a useful biomarker, reflecting impairment of epidermal function in AD patients as well as healthy subjects.