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Atopic dermatitis (AD) is a common eczematous skin disorder characterized by skin inflammation, barrier disruption, chronic pruritus and marked scratching. Th2 cytokines, especially IL-13, play a pathogenic role in AD. IL-13 signals via a heterodimeric receptor composed of IL-4Rα and IL-13 Rα1. A second receptor, IL-13 Rα2, binds to IL-13 with high affinity, but it works as a decoy receptor. IL-13 Rα2 is overexpressed in the lesional skin of AD. Notably, mechanical scratching, as well as IL-13 itself, also upregulates IL-13 Rα2 expression. The scratch-induced IL-13 Rα2 upregulation may attenuate the IL-13-mediated epidermal barrier dysfunction and dermal fibrosis. Recent studies stress an importance of another IL-13 Rα2 ligand, chitinase 3-like 1 or YKL-40 in Th2 differentiation. However, the implications of increased IL-13 Rα2 levels remain elusive in AD. In this review, we summarize the recent topics on IL-13 Rα2 in atopic skin inflammation. [ABSTRACT FROM AUTHOR]

These results indicate that the natural antioxidants cinnamaldehyde and GFF are capable of inhibiting protein expression of the senescence marker CDKN2A in a NRF2-dependent manner. 1 Cinnamaldehyde (A, C E) and GFF (B, F H) reduce the CDKN2A protein expression and upregulate the protein levels of antioxidative GPX2 and NQO1 enzymes. [Extracted from the article]

Psoriasis is an (auto)immune-mediated disease that manifests as widespread desquamative erythema. The TNF-α/IL-23/IL-17A axis is crucial to its pathogenesis, which is demonstrated by its excellent therapeutic response to biologics that target this axis. There is a strong association between HLA-C*0602 and psoriasis, and researchers have identified autoantigens that are restricted to this major histocompatibility class I molecule. These auto-Ags include LL-37, A disintegrin and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5), and keratin 17. IL-17A-producing T cells have been identified in T cell populations that are reactive to these auto-Ags. In addition, lipid Ags have surfaced as candidate auto-Ags that activate IL-17A-producing T cells in a CD1a-restricted manner. In this article, we review the candidate auto-Ags that may contribute to the activation of the IL-17A-deviated immune response in psoriasis. [ABSTRACT FROM AUTHOR]

Both seborrheic keratosis and basal cell carcinoma are common skin tumors in daily clinical practice. However, the coexistence of seborrheic keratosis and basal cell carcinoma is rare. In this report, we present a case of occult microscopic basal cell carcinoma arising in a lesion of seborrheic keratosis. This case indicates that the basal cell carcinoma could arise from seborrheic keratosis and might help to clarify the origin of basal cell carcinoma. [ABSTRACT FROM AUTHOR]

Abstract: T helper type 2 (Th2)‐derived cytokines, such as IL‐4, IL‐13, and IL‐31, play a fundamental role in the development and progression of atopic dermatitis (AD). In addition to gene mutations of filaggrin (FLG), the Th2‐deviated microenvironment downregulates FLG expression and disrupts barrier function, resulting in Staphylococcus aureus colonization and increased penetration of external allergens. From lesional AD skin, the Th2 milieu helps to release Th2‐related chemokines such as CCL17, CCL22, and CCL26, which augment recruitment of Th2 cells and eosinophils. IL‐4 and IL‐13 stimulate B cells to produce IgE that links AD to other atopic comorbidities. IL‐31 is the major pruritogenic cytokine in AD. Notably, the anti–IL‐4 receptor α antibody dupilumab and the anti–IL‐31 receptor A antibody nemolizumab have proven to be effective for treatment of AD. In the present review, Th2 signatures in AD are examined and overviewed. [ABSTRACT FROM AUTHOR]

Background: Comorbidities of cardiovascular diseases (CVDs), metabolic syndrome and autoimmune diseases with systemic inflammation are recent topics in medicine. Inflammatory skin diseases such as atopic dermatitis and psoriasis are an active source of diverse proinflammatory cytokines and chemokines, which are readily detectable in the circulation and are likely to be involved in developing comorbidities. Evidence: Both atopic dermatitis and psoriasis are frequently comorbid with CVD, metabolic syndrome and autoimmune diseases, the consequence of which is called 'inflammatory skin march', 'psoriatic march' or 'march of psoriasis'. Conclusion: In this review, we summarize the epidemiological evidence and pathogenetic concepts regarding inflammatory skin march in atopic dermatitis and psoriasis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic or chronically relapsing, eczematous, severely pruritic skin disorder mostly associated with IgE elevation and skin barrier dysfunction due to decreased filaggrin expression. The lesional skin of AD exhibits Th2- and Th22-deviated immune reactions that are progressive during disease chronicity. Th2 and Th22 cytokines further deteriorate the skin barrier by inhibiting filaggrin expression. Some IgEs are reactive to self-antigens. The IgE autoreactivity may precipitate the chronicity of AD. Upon activation of the ORAI1 calcium channel, atopic epidermis releases large amounts of thymic stromal lymphopoietin (TSLP), which initiates the Th2 and Th22 immune response. Th2-derived interleukin-31 and TSLP induce an itch sensation. Taken together, TSLP/Th2/Th22 pathway is a promising target for developing new therapeutics for AD. Enhancing filaggrin expression using ligands for the aryl hydrocarbon receptor may also be an adjunctive measure to restore the disrupted barrier function specifically for AD. [ABSTRACT FROM AUTHOR]

Nonsegmental vitiligo is an acquired leukoderma characterized by the destruction of melanocytes. Autoimmunity is the most widely accepted hypothesis to explain the pathogenesis of nonsegmental vitiligo. Increased oxidative stress and decreased expression of E-cadherin may facilitate the loss of melanocytes. Because vitiligo preferentially affects cosmetically sensitive regions such as the face, hands, and genital area, it imposes significant psychological and social burdens. In this review, we discuss recent topics in the epidemiology, pathogenesis, genetic background, and therapeutic advances of nonsegmental vitiligo. [ABSTRACT FROM AUTHOR]

Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that binds to structurally diverse chemicals including dioxins, coal tar, flavonoids and tryptophan photoproducts. Upon ligation, cytoplasmic AHR translocates to the nucleus, heterodimerizes with aryl hydrocarbon receptor nuclear translocator and mediates numerous biological effects by inducing the transcription of various AHR-responsive genes such as epidermal barrier proteins. The activation of AHR usually generates oxidative stress. However, AHR also mediates antioxidant signaling by a plethora of ligands via nuclear factor-erythroid 2-related factor-2. Both oxidative and antioxidant ligands upregulate the expression of the filaggrin gene. We review the role of AHR signaling in the gene regulation of epidermal barrier proteins. [ABSTRACT FROM AUTHOR]

The article focuses on porokeratosis which is a skin disorder of abnormal keratinization, that manifests as patches with peripheral keratotic ridge that corresponds to cornoid lamella. It mentions that overexpression of S100 calcium-binding protein A7 (S100A7) protein is an integral part of abnormal epidermal differentiation in cornoid lamella of porokeratosis. It states that S100A protein is a binding proteins encoded by genes in epidermal differentiation complex and regulates cell structure.

Autoantibodies to the desmosomal proteins desmoglein 1 and 3 cause pemphigus foliaceus and pemphigus vulgaris, which are characterised by keratinocyte dissociation (acantholysis) and intraepidermal blister formation. The passive transfer of pathogenic anti-desmoglein antibodies induces blisters in mice in vivo and the loss of keratinocyte adhesion in vitro. The pathogenetic mechanisms of acantholysis due to anti-desmoglein autoantibodies are not fully understood. However, recent studies have revealed that signalling-dependent and signalling-independent pathways are operative in the loss of cell adhesion. In this review, we focus on the pathomechanism of acantholysis due to autoantibodies to desmogleins and recent therapeutic approaches. [ABSTRACT FROM AUTHOR]

Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that binds to structurally diverse synthetic and naturally occurring chemicals including dioxins, flavonoids, tryptophan photoproducts, and Malassezia metabolites. Upon binding to its ligands, cytoplasmic AhR translocates to the nucleus, heterodimerizes with aryl hydrocarbon receptor nuclear translocator (ARNT), and mediates numerous biological and toxicological effects by inducing the transcription of various AhR-responsive genes. AhR ligation controls oxidation/antioxidation, epidermal barrier function, photo-induced response, melanogenesis, and innate immunity. This review summarizes recent advances in the understanding of the regulatory mechanisms of skin homeostasis mediated by the AhR/ARNT system. [ABSTRACT FROM AUTHOR]

The recent therapeutic success of specific biologics points a crucial role of IL-13/IL-4 and IL-22 in atopic dermatitis and of TNF- , IL-23, and IL-17A in psoriasis. The IL-13/IL-4 axis plays a major and pathogenic role in atopic dermatitis because its overdrive downregulates the expression of barrier-related molecules such as filaggrin. Atopic dermatitis and psoriasis are common inflammatory skin diseases that enormously deteriorate the psycho-physical and socio-economic condition of the patients who are afflicted with these conditions. [Extracted from the article]

All patients completed GQ (range 0-4), POEM (range 0-28), NRS (range, 0-10), and VRS (range, 0-4) to evaluate itch intensity. In this study, 39 of 219 patients had a POEM score of >=25, but only 10 of 219 patients had a GQ score of 4 (very severe). The minimal clinically important difference (MCID) for POEM has been reported to be 3.4.5 The POEM bandings for Mongolian AD patients in the present study were all within the MCID, which indicates that POEM is a clinically acceptable tool. [Extracted from the article]

Abstract: 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. [Copyright &y& Elsevier]

DESIGN is a seven-item (depth, exudates, size, inflammation/infection, granulation, necrosis, and pocket) monitoring scale for pressure ulcers developed in 2002 by the scientific education committee of the Japanese Society of Pressure Ulcers. DESIGN is a very useful tool for chronological monitoring of each pressure ulcer, but a key limitation of this tool is its inability to compare the wound-healing process among different pressure ulcers in different patients due to a lack of statistical item weighting. Our aim was to weight DESIGN items by statistical analysis and develop a new validated tool to overcome this limitation. Subjects comprised 3,601 patients with pressure ulcers. Patients were followed every week during the study period. To establish the weighting of each item and grade, we estimated the probabilities of wound healing at 12-month follow-up using multivariable Cox's regression analysis. Weighting (−β value) for each item in order of the highest rank was: pocket, 2.289; size, 1.573; inflammation/infection, 0.778; granulation tissue, 0.682; exudate, 0.543; and necrotic tissue, 0.529. Based on these findings, a new, validated 'DESIGN-Rating tool' for monitoring the progression of pressure ulcer healing was developed, implying the development of an absolute evaluation tool and clinical indicator to assess the quality of medical care. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) play key rolls in various aspects of immunity. The functions of DC depend on the subsets as well as their location or activation status. Understanding developmental lineages, precursors and inducing factors for various DC subsets would help their clinical application, but despite extensive efforts, the precise ontogeny of various DC, remain unclear and complex. Because of their many functional similarities to macrophages, DC were originally thought to be of myeloid-lineage, an idea supported by many in vitro studies where monocytes or GM-CSF (a key myeloid growth factor) has been extensively used for generating DC. However, there has been considerable evidence which suggests the existence of lymphoid-lineage DC. After the confusion of myeloid-/lymphoid-DC concept regarding DC surface markers, we have now reached a consensus that each DC subset can differentiate through both myeloid- and lymphoid-lineages. The identification of committed populations (such as common myeloid- and lymphoid progenitors) as precursors for every DC subsets and findings from various knockout (KO) mice that have selected lymphoid- or myeloid-lineage deficiency appear to indicate flexibility of DC development rather than their lineage restriction. Why is DC development so flexible unlike other hematopoitic cells? It might be because there is developmental redundancy to maintain such important populations in any occasions, or such developmental flexibility would be advantageous for DC to be able to differentiate from any "available" precursorsin situ irrespective of their lineages. This review will cover ontogeny of conventional (CD8+/- DC) DC, plasmacytoid DC and skin Langerhans cells, and recently-identified many Pre-DC (immediate DC precursor) populations, in addition to monocytes and plasmacytoid DC, will also be discussed. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common, chronic, relapsing, severely pruritic, eczematous skin disease. Topical steroids are the mainstay of treatment. However, the adverse effects of steroids on hormonal function are the major obstacle for their use as long-term topical therapy. Topical calcineurin inhibitors, such as tacrolimus, not only complement existing treatment options but also overcome some of the drawbacks of topical steroid therapy and fulfill the long-term needs of patients in preventing disease progression. Short- and long-term efficacy and safety of topical tacrolimus has been widely recognized and it is also accepted as a first-line treatment for the inflammation of AD. In order to reduce the possible long-term adverse effects, it is important to monitor the clinical dose in daily clinics. [ABSTRACT FROM AUTHOR]

We summarized the Therapeutic Guidelines for Atopic Dermatitis 2002, and outlined important points with reference to medical care and management of atopic dermatitis. [ABSTRACT FROM AUTHOR]

OX40 is one of the co-stimulatory molecules expressed on T cells, and it is engaged by OX40L, primarily expressed on professional antigen-presenting cells such as dendritic cells. The OX40L–OX40 axis is involved in the sustained activation and expansion of effector T and effector memory T cells, but it is not active in naïve and resting memory T cells. Ligation of OX40 by OX40L accelerates both T helper 1 (Th1) and T helper 2 (Th2) effector cell differentiation. Recent therapeutic success in clinical trials highlights the importance of the OX40L–OX40 axis as a promising target for the treatment of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Skin inflammation often evokes pruritus, which is the major subjective symptom in many inflammatory skin diseases such as atopic dermatitis and prurigo nodularis. Pruritus or itch is a specific sensation found only in the skin. Recent studies have stressed the pivotal role played by interleukin-31 (IL-31) in the sensation of pruritus. IL-31 is produced by various cells including T helper 2 cells, macrophages, dendritic cells and eosinophils. IL-31 signals via a heterodimeric receptor composed of IL-31 receptor A (IL-31RA) and oncostatin M receptor β. Recent clinical trials have shown that the anti-IL-31RA antibody nemolizumab can successfully decrease pruritus in patients with atopic dermatitis and prurigo nodularis. The IL-31 pathway and pruritic skin are highlighted in this review article. [ABSTRACT FROM AUTHOR]

Azelastine hydrochloride (AZE) is an anti-allergic drug that inhibits the release of various chemical mediators from mast cells. We compared the immunosuppressive effects of AZE and FD-506 in vivo and in vitro. Topical application of AZE strongly inhibited the efferent phase of contact hypersensitivity, as did application of FK-506. In in vitro experiments, we found that 1) the suppression by AZE on interleukin (IL)-2 production from splenic T cells was partial and considerably large amounts of IL-2 were still produced, even in the presence of 10-5 M of AZE, which was in sharp contrast to the observed marked inhibition of [³H]-TdR incorporation; 2) AZE significantly inhibited the phorbol myristate acetate-induced IL-2 responsiveness; 3) AZE did not inhibit the IL-2 receptor α expression of activated T cells; and 4) the significant inhibitory action was still observed even when AZE was added at 48 h after the initiation of culture. In regard of FD-506, we found that 1) FD-506 completely blocked the production of IL-2; 2) exogeneous IL-2 consistently restored the FK-506-induced inhibition; 3) FK-506 affected the phorbol myristate acetate - induced IL-2 responsiveness very little, if any; and 4) the significant suppression was observed only when FK-506 was added within 24 h after the initiation of culture. Thus, AZE exerts its in vitro immunosuppressive activity preferentially by interfering with the IL-2 responsiveness. with partial inhibition of IL-2 production. Conversely, FK-506 acts as a strong inhibitor of IL-2 production without a prominent effect on IL-2 responsiveness. The immunosuppressive activity of AZE shown in vitro may also be operative in vivo and may be applicable for topical use. [ABSTRACT FROM AUTHOR]

CD1 antigens are classified into at least three groups, CDla, CDlb, and CDlc. In order to delineate the localization of epitopes of CD1 antigens in human skin, we examined the irnrnunoreactivity of fourteen different CD1 antibodies (seven CDla, five CDlb, and two CDlc antibodies). The epitopes for CDla, CDlb, and CDlc are differentially localized on epidermal Langerhans cells, dermal dendritic cells, keratinocytes, the luminal portion of eccrine gland ducts, and the basement membrane zone in normal human skin. [ABSTRACT FROM AUTHOR]

Although the pathogenesis of atopic dermatitis (AD) is unknown, many immunologic abnormalities such as high levels of serum IgE and increase of IgE Fc receptor-positive lymphocytes have been demonstrated. Recently, interleukin 4 (IL-4) has been shown to induce enormously the production of IgE and to enhance the expression of IgE Fc receptor by B cells, suggesting the possible involvement of IL-4 in the pathogenesis of AD. We examined IL-4 responsiveness or interleukin 2 (IL-2) responsiveness of peripheral blood mono- nuclear cells of 31 patients with AD, 19 healthy individuals, and seven patients with other skin diseases. We found that IL-4 responsiveness of AD was higher than that of non-AD control, although IL-2 responsiveness of AD showed no significant change. However, the value of the IL-4 responsiveness did not significantly correlate with the clinical severity, personal history of respiratory allergy, serum IgE level, or clinical course of patients with AD. The hyperresponsiveness to IL-4 detected in AD was not likely to be due to the effects of steroids or anti-mast cell drugs because the value of IL-4 responsiveness was significantly low, compared to AD, in patients with other skin diseases who were treated similarly. Because the T-cell - enriched population, but not the B-cell - enriched population, showed significant proliferation in response to exogeneous IL-4 or IL-2, T cells were the main population that reacted in our proliferation assay. These results indicate that IL-4 - driven proliferative response may be efficiently operative in T cells in patients with AD. [ABSTRACT FROM AUTHOR]

To determine the direct effects of glucocorticosteroids on epidermal Langerhans cells (LC), we treated isolated LC with dexarnethasone (DEX) in vitro, and investigated Ia expression by LC using immunofluorescence microscopy and FACS analysis. We found that DEX directly decreased the number of Ia+ LC in a dose-and time-dependent manner. Pulse incubation with DEX also inhibited the immunostimulatory function of LC in vitro. FACS analysis demonstrated that LC detected in DEX-treated culture expressed a similar amount of Ia antigen and Fc receptor on the cell surface as LC cultured with the solvent control, suggesting that LC may be composed of a heterogeneous population in terms of sensitivity to DEX, and DEX may completely abolish the expression of surface molecules on a subpopulation of LC or may be cytolytic to this sensitive population. [ABSTRACT FROM AUTHOR]

Cylcosporin A (CSA) is a potent immunosuppressive drug that inhibits the proliferation of activated T cells by blocking the production of interleukin 2. Recent studies have demonstrated that CSA also inhibits the proliferation of neoplastic cells of hematopoietic and nonhematopoietic origin. CSA has also been reported to be effective in the treatment of psoriasis, which is characterized by epidermal hyperproliferation. As so many of the therapeutically effective agents in psoriasis are antiproliferative, we sought to determine whether CSA affects the proliferation of keratinocytes. We studied the effect of CSA on the proliferation of normal and transformed keratinocytes and demonstrated that CSA inhibits DNA synthesis and proliferation of keratinocytes. CSA also inhibits DNA synthesis of other neoplastic cells of hematopoietic and nonhematopoietic origin. These findings indicate the CSA inhibits the proliferation of various cell types. [ABSTRACT FROM AUTHOR]

Although both fluorescein isothiocyanate (FITC) and trinitrophenyl (TNP) covalently couple primarily to the ∊-amino group of lysine residues of surface glycoprotein, FITC is structurally different from TNP. In this paper, we investigated the immune regulatory mechanisms in contact sensitivity (CS) to FITC by the administration of FITC and FITC-conjugated epidermal cells (FITCEC) via various routes. Mice injected with FITC via i.p. or i.v. route did not induce CS but induced hyporesponsiveness to the following sensitization with FITC painting. Mice injected with FITC via s.c. route induced neither CS nor hyporesponsiveness to the following FITC painting. Administration of FITC via i.v. route was demonstrated to induce hapten-specific suppressor T cells. Inoculation of FITC-EC via s.c. or J.p. route induced CS, whereas injection of FITC-EC via i.v. route did not induce CS but induced hyporesponsiveness to the following FITC painting. The results are compared with the previous data obtained by trinitrobenzene sulfonate and trinitrophenylconjugated epidermal cells. [ABSTRACT FROM AUTHOR]

Recent studies suggest that skin graft rejection and delayed-type hypersensitivity (DTH) are different manifestations of the same mechanism. In order to investigate the alloantigenicity of epidermal cells and epidermal Langerhans cells (LC), we used epidermal cell suspensions; experiments were performed to try to induce DTH to alloantigens by the subcutaneous administration of epidermal cells. Our study establishes the precise conditions for the induction of DTH response to alloantigens using epidermal cells. Transfer experiments have shown that effector cells were Thy-1+, Lyt-1+, and Lyt-2- cells. Furthermore, the experiments using congenic strains of mice and grafted skin revealed the contribution of gene products coded by MHC and non-MHC, and also the epidermal LC in the induction of DTH response. [ABSTRACT FROM AUTHOR]

Poisoning by high concentrations of dioxin and its related compounds manifests variable toxic symptoms such as general malaise, chloracne, hyperpigmentation, sputum and cough, paresthesia or numbness of the extremities, hypertriglyceridemia, perinatal abnormalities, and elevated risks of cancer-related mortality. Such health hazards are observed in patients with Yusho (oil disease in Japanese) who had consumed rice bran oil highly contaminated with 2,3,4,7,8-pentachlorodibenzofuran, polychlorinated biphenyls, and polychlorinated quaterphenyls in 1968. The blood concentrations of these congeners in patients with Yusho remain extremely elevated 50 years after onset. Dioxins exert their toxicity via aryl hydrocarbon receptor (AHR) through the generation of reactive oxygen species (ROS). In this review article, we discuss the pathogenic implication of AHR in dioxin-induced health hazards. We also mention the potential therapeutic use of herbal drugs targeting AHR and ROS in patients with Yusho. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction, and chronic pruritus. As the anti-interleukin-4 (IL-4) receptor α antibody dupilumab improves all three cardinal features of AD, the type 2 cytokines IL-4 and especially IL-13 have been indicated to have pathogenic significance in AD. Accumulating evidence has shown that the skin barrier function is regulated via competition between the aryl hydrocarbon receptor (AHR) axis (up-regulation of barrier) and the IL-13/IL-4‒JAK‒STAT6/STAT3 axis (down-regulation of barrier). This latter axis also induces oxidative stress, which exacerbates inflammation. Conventional and recently developed agents for treating AD such as steroid, calcineurin inhibitors, cyclosporine, dupilumab, and JAK inhibitors inhibit the IL-13/IL-4‒JAK‒STAT6/STAT3 axis, while older remedies such as coal tar and glyteer are antioxidative AHR agonists. In this article, I summarize the pathogenic and therapeutic implications of the IL-13/IL-4‒JAK‒STAT6/STAT3 axis and the AHR axis in AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is an eczematous, pruritic skin disorder with extensive barrier dysfunction and elevated interleukin (IL)-4 and IL-13 signatures. The barrier dysfunction correlates with the downregulation of barrier-related molecules such as filaggrin (FLG), loricrin (LOR), and involucrin (IVL). IL-4 and IL-13 potently inhibit the expression of these molecules by activating signal transducer and activator of transcription (STAT)6 and STAT3. In addition to IL-4 and IL-13, IL-22 and IL-17A are probably involved in the barrier dysfunction by inhibiting the expression of these barrier-related molecules. In contrast, natural or medicinal ligands for aryl hydrocarbon receptor (AHR) are potent upregulators of FLG, LOR, and IVL expression. As IL-4, IL-13, IL-22, and IL-17A are all capable of inducing oxidative stress, antioxidative AHR agonists such as coal tar, glyteer, and tapinarof exert particular therapeutic efficacy for AD. These antioxidative AHR ligands are known to activate an antioxidative transcription factor, nuclear factor E2-related factor 2 (NRF2). This article focuses on the mechanisms by which FLG, LOR, and IVL expression is regulated by IL-4, IL-13, IL-22, and IL-17A. The author also summarizes how AHR and NRF2 dual activators exert their beneficial effects in the treatment of AD. [ABSTRACT FROM AUTHOR]

The excellent clinical efficacy of anti-interleukin 17A (IL-17A) biologics on psoriasis indicates a crucial pathogenic role of IL-17A in this autoinflammatory skin disease. IL-17A accelerates the proliferation of epidermal keratinocytes. Keratinocytes produce a myriad of antimicrobial peptides and chemokines, such as CXCL1, CXCL2, CXCL8, and CCL20. Antimicrobial peptides enhance skin inflammation. IL-17A is capable of upregulating the production of these chemokines and antimicrobial peptides in keratinocytes. CXCL1, CXCL2, and CXCL8 recruit neutrophils and CCL20 chemoattracts IL-17A-producing CCR6+ immune cells, which further contributes to forming an IL-17A-rich milieu. This feed-forward pathogenic process results in characteristic histopathological features, such as epidermal hyperproliferation, intraepidermal neutrophilic microabscess, and dermal CCR6+ cell infiltration. In this review, we focus on IL-17A and keratinocyte interaction regarding psoriasis pathogenesis. [ABSTRACT FROM AUTHOR]

The aryl hydrocarbon receptor (AHR)/AHR-nuclear translocator (ARNT) system is a sensitive sensor for small molecular, xenobiotic chemicals of exogenous and endogenous origin, including dioxins, phytochemicals, microbial bioproducts, and tryptophan photoproducts. AHR/ARNT are abundantly expressed in the skin. Once activated, the AHR/ARNT axis strengthens skin barrier functions and accelerates epidermal terminal differentiation by upregulating filaggrin expression. In addition, AHR activation induces oxidative stress. However, some AHR ligands simultaneously activate the nuclear factor-erythroid 2-related factor-2 (NRF2) transcription factor, which is a master switch of antioxidative enzymes that neutralizes oxidative stress. The immunoregulatory system governing T-helper 17/22 (Th17/22) and T regulatory cells (Treg) is also regulated by the AHR system. Notably, AHR agonists, such as tapinarof, are currently used as therapeutic agents in psoriasis and atopic dermatitis. In this review, we summarize recent topics on AHR related to atopic dermatitis and psoriasis. [ABSTRACT FROM AUTHOR]

Background: Daily skin care is important for treatment of skin diseases, but few studies have reported on appropriate washing methods. Aim: This study aimed to provide guidance on washing techniques and examine changes in skin condition after using the recommended washing technique and foaming‐type skin cleanser in patients with atopic or asteatotic dermatitis. Methods: An internet‐based questionnaire survey on skin symptoms and cleaning methods was conducted. Further, a left–right comparative, nonrandomized trial was performed in 19 patients with asteatotic or atopic dermatitis and xerosis. Participants were instructed to wash with a cotton towel and their normal cleanser during Weeks 1–4 and with bare hands or a cotton towel and the recommended foaming‐type cleanser during Weeks 5–8. Results: The survey revealed that the degree of lathering differed depending on the cleaning tool. In the trial, scores for erythema, desquamation, and xerosis in the lower legs were significantly reduced after 4 weeks compared with scores at the start. Between Weeks 4 and 8, scores for erythema, xerosis, and pruritus in the inner forearm on the side washed with bare hands and scores for xerosis, pruritus, and excoriation on the side washed with a cotton towel were significantly reduced. A significant increase was noted in stratum corneum ceramide content on both left and right inner forearms, whereas a significant decrease was noted in stratum corneum thymus and activation‐regulated chemokine level ratios in the lower legs on both sides. Conclusions: Xerotic skin disease symptoms can be improved using appropriate body washing methods. [ABSTRACT FROM AUTHOR]

The coexistence of epidermal cysts and lipomas at the same site is extremely rare, although epidermal cysts and lipomas are both common benign skin tumors. We present a rare case of an epidermal cyst with underlying lipoma on the back. This case report may simply be a result of coincidence, but the possibility of underlying subcutaneous tumors should be considered before epidermal cyst surgery. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-24 is a member of the IL-20 family of cytokines and is produced by various types of cells, such as CD4+ T cells, NK cells, mast cells, keratinocytes, bronchial epithelial cells, and myofibroblasts. Previous studies suggest that IL-24 plays an essential role in the pathogenesis of pro-inflammatory autoimmune disorders such as psoriasis, arthritis, and inflammatory bowel diseases. However, the role of IL-24 in the pathogenesis of allergic diseases has been elusive. It has already been reported that IL-24 is involved in the pathogenesis of allergic lung and skin diseases. Moreover, we have recently revealed for the first time the pivotal functions of IL-24 in IL-13–mediated skin barrier dysfunction in atopic dermatitis (AD), which is known to be a characteristic of AD caused by Th2 cytokines such as IL-4 or IL-13. In this review, we show recent advances in the basic characteristics of IL-24 and its novel functions in the pathogenesis of allergic skin inflammation, focusing on AD. A better understanding of the role of IL-24 in allergic diseases can lead to the development of new therapeutic options. [ABSTRACT FROM AUTHOR]

• Cinnamaldehyde inhibits UVB-induced ROS production and DNA damage in keratinocytes. • Cinnamaldehyde attenuates UVB-induced oxidative stress in vivo. • Cinnamaldehyde attenuates collagenolysis by modifying Col1a1 and Mmp13 expression. • Cinnamaldehyde may protect against UVB-induced photoaging. Ultraviolet (UV) irradiation disrupts skin through several deleterious actions, such as induction of reactive oxygen species (ROS), DNA damage, and collagen degradation. Cinnamaldehyde (CIN) is a major constituent of the cinnamon and it possesses potent antioxidative activity; however, it is unclear whether CIN is capable of inhibiting the adverse effects of UVB. To investigate protective effects of CIN against UVB-induced photodamage. HaCaT keratinocytes were pretreated with CIN, irradiated with UVB, and assessed for the ROS production by flow cytometry and for the DNA damage by ELISA. As in vivo mouse model, Hos:HR-1 hairless mice were treated with ointments containing DMSO or CIN and irradiated multiple times with UVB. After 10 weeks of irradiation, wrinkle formation, epidermal thickness, infiltrating cell number, malondialdehyde amount, collagen amount, MAP kinase signaling, and related gene expressions (Hmox1 , Col1a1 , Mmp1a , and Mmp13) were analyzed. CIN significantly reduced the ROS production and accelerated the repair of DNA damage pyrimidine(6-4)pyrimidone photoproducts in UVB-irradiated human keratinocytes in vitro. In the mouse model, topical application of CIN significantly inhibited wrinkle formation, epidermal hyperplasia, and dermal inflammatory cell infiltration. The antioxidative process was significantly promoted in the CIN-applied site, as evidenced by upregulation of the antioxidative enzyme Hmox1 as well as the reduced accumulation of malondialdehyde. In addition, topical application of CIN normalized the UVB-induced collagen/ Col1a1 downregulation and the UVB-induced Mmp13 upregulation, implying the prevention of UVB-induced collagen degradation. CIN and CIN-containing herbal agents may exert potent protective effects against UVB exposure on skin. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 70-year-old man diagnosed with scrotal angiokeratomas and treated using small-spot narrow-band intense pulsed light (IPL). It notes the effectiveness and safety of IPL in treating the disease. It also observes the rapid postoperative recovery of the patient as the treatment was only completed in roughly two months.

The authors propose the consolidation of the verbalizations of extremes of the visual analogue scale (VAS) for itch intensity and sleep disturbance or nocturnal itch in pruritus. The use of VAS to assess pruritus severity is considered. Core items for evaluating pruritus in clinical settings discussed by members of the Japanese Society for Dermatoallergology and Contact Dermatitis are described. The necessity of clarifying the verbal expression of the ten-point end in VAS is also addressed.

Highlights • An accelerated TNF/IL23/IL17 axis causes psoriasis and psoriatic arthritis. • Efficacies of anti-TNF/IL23/IL17 biologics are different. • Anti-IL23/IL17 agents are superior than anti-TNF agents in psoriasis. • Anti-TNF agents are superior than anti-IL23/IL17 agents in psoriatic arthritis. Abstract Psoriasis and psoriatic arthritis cause significant physical and psychological burdens for afflicted individuals. An accelerated TNF-α/IL-23/IL-17 axis is their major pathomechanism; therefore, anti-TNF-α/IL-23/IL-17 biologics are very effective for the treatment of skin and joint lesions in psoriasis and psoriatic arthritis. Given that the IL-17 signature is more upregulated in the skin than in synovium in psoriatic arthritis, anti-IL-23/IL-17 agents seem to be superior to anti-TNF-α remedies in the treatment of skin lesions. In this review, we focus on the differential efficacy of anti-TNF-α/IL-23/IL-17 biologics in psoriasis and psoriatic arthritis. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 64-year-old high-school language teacher who noted the itching of his scalp and posterior neck region after he started using color shampoo two to three times a week from one year. Topics discussed include the presence of erythema on the scalp, the importance of distinguishing post-inflammatory depigmentation from vitiligo, rhododenol-induced leukoderma, and BB75 patch test site.

Facial skin aging is an important psychophysical and social concern, especially in women. We compared facial parameters reflecting aging of the skin in 1999 and 2010 in 86 female volunteers. Then, all subjects applied three Galactomyces ferment filtrate-containing skin care products (G3 products; SK-II Facial Treatment Essence, SK-II Cellumination Essence, and SK-II Skin Signature Cream) twice daily for 12 months (M), with the skin parameters being measured at 2 M, 8 M, and 12 M during this period. Facial skin aging parameters such as wrinkles, hyperpigmented spots, and roughness significantly deteriorated during the 11-year interval. This 11-year aging process was associated with reduced hydration and increased transepidermal water loss (TEWL). Notably, treatment with G3 products significantly and cumulatively increased skin hydration with a correlated reduction of TEWL during the 12 M treatment period. Such treatment also significantly and cumulatively reversed the 11-year facial skin aging in the three parameters of wrinkles, spots, and roughness. These results suggest that facial skin retains the potential to recover from the aging process when it is applied with appropriate cosmetic agents. [ABSTRACT FROM AUTHOR]

Background: Interleukin-31 may play a role in the pathobiologic mechanism of atopic dermatitis and pruritus. We wanted to assess the efficacy and safety of nemolizumab (CIM331), a humanized antibody against interleukin-31 receptor A, in the treatment of atopic dermatitis.Methods: In this phase 2, randomized, double-blind, placebo-controlled, 12-week trial, we assigned adults with moderate-to-severe atopic dermatitis that was inadequately controlled by topical treatments to receive subcutaneous nemolizumab (at a dose of 0.1 mg, 0.5 mg, or 2.0 mg per kilogram of body weight) or placebo every 4 weeks or an exploratory dose of 2.0 mg of nemolizumab per kilogram every 8 weeks. The primary end point was the percentage improvement from baseline in the score on the pruritus visual-analogue scale (on which a negative change indicates improvement) at week 12. Secondary end points included changes in the score on the Eczema Area and Severity Index (EASI, on which a negative change indicates improvement), and body-surface area of atopic dermatitis.Results: Of 264 patients who underwent randomization, 216 (82%) completed the study. At week 12, among the patients who received nemolizumab every 4 weeks, changes on the pruritus visual-analogue scale were -43.7% in the 0.1-mg group, -59.8% in the 0.5-mg group, and -63.1% in the 2.0-mg group, versus -20.9% in the placebo group (P<0.01 for all comparisons). Changes on the EASI were -23.0%, -42.3%, and -40.9%, respectively, in the nemolizumab groups, versus -26.6% in the placebo group. Respective changes in body-surface area affected by atopic dermatitis were -7.5%, -20.0%, and -19.4% with nemolizumab, versus -15.7% with placebo. Among the patients receiving nemolizumab every 4 weeks, treatment discontinuations occurred in 9 of 53 patients (17%) in the 0.1-mg group, in 9 of 54 (17%) in the 0.5-mg group, and in 7 of 52 (13%) in the 2.0-mg group, versus in 9 of 53 (17%) in the placebo group.Conclusions: In this phase 2 trial, nemolizumab at all monthly doses significantly improved pruritus in patients with moderate-to-severe atopic dermatitis, which showed the efficacy of targeting interleukin-31 receptor A. The limited size and length of the trial preclude conclusions regarding adverse events. (Funded by Chugai Pharmaceutical; XCIMA ClinicalTrials.gov number, NCT01986933 .). [ABSTRACT FROM AUTHOR]

OX40 is crucial for T-cell differentiation and memory induction. The anti-OX40 antibody, rocatinlimab inhibits the OX40 pathway. We evaluated the efficacy and safety of rocatinlimab in adults with moderate-to-severe atopic dermatitis. This multicentre, double-blind, placebo-controlled phase 2b study was done at 65 secondary and tertiary sites in the USA, Canada, Japan, and Germany. Eligible patients were adults (aged 18 years or older) with confirmed atopic dermatitis (American Academy of Dermatology Consensus Criteria or local diagnostic criteria) with moderate-to-severe disease activity, as defined by an Eczema Area and Severity Index (EASI) score of 16 or more, validated Investigator's Global Assessment for Atopic Dermatitis score of 3 (moderate) or 4 (severe), and affected body surface area 10% or higher at both screening and baseline, with documented history (within 1 year) of inadequate response to topical medications or if topical treatments were medically inadvisable. Patients were randomly assigned (1:1:1:1:1) to receive subcutaneous rocatinlimab every 4 weeks (150 mg or 600 mg) or every 2 weeks (300 mg or 600 mg) or subcutaneous placebo up to week 18, with an 18-week active-treatment extension and 20-week follow-up. Percentage change from baseline in EASI score was assessed as the primary endpoint at week 16 and during the active extension and follow-up in all randomly assigned patients exposed to study drug with a post-baseline EASI score at week 16 or earlier according to the group they were randomly assigned to. Safety was assessed in all randomly assigned patients exposed to study drug; patients were analysed according to the group they were randomly assigned to. The study is registered with ClinicalTrials.gov , NCT03703102. Between Oct 22, 2018, and Oct 21, 2019, 274 patients (114 [42%] women, 160 [58%] men; mean age 38·0 years [SD 14·5]) were randomly assigned to one of the rocatinlimab groups (217 [79%] patients) or to the placebo group (57 [21%] patients). Compared with placebo (−15·0 [95% CI −28·6 to −1·4]), significant least-squares mean percent reductions in EASI score at week 16 were observed in all rocatinlimab groups (rocatinlimab 150 mg every 4 weeks −48·3 [−62·2 to −34·0], p=0·0003; rocatinlimab 600 mg every 4 weeks −49·7 [−64·3 to −35·2], p=0·0002; rocatinlimab 300 mg every 2 weeks −61·1 [−75·2 to −47·0], p<0·0001; and rocatinlimab 600 mg every 2 weeks −57·4 [−71·3 to −43·4], p<0·0001). The most common adverse events during the double-blind period in patients receiving rocatinlimab (adverse events ≥5% of patients in the total rocatinlimab group and more common than the placebo group) were pyrexia (36 [17%] patients), nasopharyngitis (30 [14%] patients), chills (24 [11%] patients), headache (19 [9%] patients), aphthous ulcer (15 [7%] patients), and nausea (13 [6%] patients). There were no deaths. Patients treated with rocatinlimab had progressive improvements in atopic dermatitis, which was maintained in most patients after treatment discontinuation. Treatment was well tolerated. Kyowa Kirin. [ABSTRACT FROM AUTHOR]

Sleep shortage is a major concern in modern life and induces various psycho-physical disorders, including skin problems. In cosmeceutics, females are aware that sleep deprivation worsens their facial skin tone. Here, we measured the effects of sleep deprivation on facial skin yellowness and examined yellow chromophores, such as bilirubin and carotenoids, in blood serum as potential causes of yellowness. Total sleep deprivation (0 h sleep overnight, N = 28) and repeated partial sleep deprivation (4 h sleep for 5 consecutive days, N = 10) induced significant increases in facial skin yellowness. The higher yellowness was sustained even after both sleep deprivation types stopped. However, circulating levels of yellow chromophores were unchanged in the total sleep deprivation study. Neither circulating interleukin-6 nor urinary biopyrrin levels were affected by total sleep deprivation, suggesting that apparent oxidative stress in the body was not detected in the present total deprivation protocol. Facial redness was affected by neither total nor repeated partial sleep deprivation. Therefore, blood circulation may play a limited role in elevated yellowness. In conclusion, facial skin yellowness was indeed increased by sleep deprivation in our clinical studies. Local in situ skin-derived factors, rather than systemic chromophore change, may contribute to the sleep deprivation-induced elevation of facial skin yellowness. [ABSTRACT FROM AUTHOR]

Itching due to atopic dermatitis causes sleep disorders in children, but its pathology is unknown. The aim of this study is to investigate nocturnal scratching as an indirect index of itching during sleep and its relationship with depth of sleep in children with atopic dermatitis. Nocturnal scratching was measured in a total of 20 children with atopic dermatitis, using a smartwatch installed with the application Itch Tracker. Depth of sleep was analysed using polysomnography. The severity of atopic dermatitis was scored using Eczema Area and Severity Index (EASI) and Patient-Oriented Eczema Measure (POEM). The number and time of nocturnal scratching measured by Itch Tracker had a significantly positive correlation with EASI scores, whereas POEM scores were not correlated with EASI scores. Mean sleep efficiency was 90.0% and scratching episodes (n=67) started mainly during the awake stage or light sleep stages. In the scratching episodes that started during sleep stages (n=34), the sleep stage changed to a lighter one or to the awake stage in 35.5% of episodes. Itch Tracker is applicable to measure nocturnal scratching in children. Nocturnal scratching can deteriorate quality of sleep by changing the sleep stage to a lighter one or to the awake stage. [ABSTRACT FROM AUTHOR]