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• Nearly all care dependent nursing home residents have mild forms of skin dryness. • Skin care dependent nursing home residents receive moisturizers more frequently. • Skin care provided by nurses might be more helpful than skin care performed independently. To identify possible factors associated with different severities of xerosis cutis and to describe possible associations between (skin) care dependency and application of moisturizers. Cross-sectional study using baseline data from a cluster-randomized controlled trial. Demographic and health characteristics, skin physiological measurements, functional abilities and application of moisturizers were compared between the participants with mild and severe dry skin. Frequency of moisturization were also compared based on the participants' skin care dependency. The more distal the body area, the more severe xerosis were observed. There were no or minor differences between the groups, except for the stratum corneum hydration and skin surface pH. Participants with severe xerosis received moisturizers less often. Skin care dependent residents received moisturizers frequently. There is under-application regarding xerosis cutis treatment in long-term care. Skin care provided by nurses, in adequate frequencies, might be helpful compared to skin care performed by the residents themselves. [ABSTRACT FROM AUTHOR]

Pathological dry skin is a disturbing and intractable healthcare burden, characterized by epithelial hyperplasia and severe itch. Atopic dermatitis (AD) and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing (scRNA-seq). However, scRNA-seq analysis of the dry skin mouse model (acetone/ether/water (AEW)-treated model) is still lacking. Here, we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell (PBC) state that exclusively expresses transcription factor CUT-like homeobox 1 (Cux1). Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases (CDKs) and cyclins. Clinically, Cux1 + PBCs were increased in patients with psoriasis, suggesting that Cux1 + PBCs play an important part in epidermal hyperplasia. This study presents a systematic knowledge of the transcriptomic changes in a chronic dry skin mouse model, as well as a potential therapeutic target against dry skin-related dermatoses. [Display omitted] • Single-cell transcriptome profiling reveals keratinocytes heterogeneity in chronic dry skin mouse model. • The elevated transcriptional factor Cux1 induces basal cell hyperproliferation. • Cux1-positive basal cells contribute to epidermal hyperplasia of the psoriasis patient. • Enhancement of cell-type-specific inflammatory cytokines changed the communication network during skin dryness. [ABSTRACT FROM AUTHOR]

Dry skin induced chronic pruritus is an increasingly common and debilitating problem, especially in the elderly. Although keratinocytes play important roles in innate and adaptive immunity and keratinocyte proliferation is a key feature of dry skin induced chronic pruritus, the exact contribution of keratinocytes to the pathogenesis of dry skin induced chronic pruritus is poorly understood. In this study, we generated the acetone-ether-water induced dry skin model in mice and found that epidermal hyperplasia induced by this model is partly dependent on the β-catenin signaling pathway. XAV939, an antagonist of β-catenin signaling pathway, inhibited epidermal hyperplasia in dry skin model mice. Importantly, dry skin induced chronic pruritus also dramatically reduced in XAV939 treated mice. Moreover, acetone-ether-water treatment-induced epidermal hyperplasia and chronic itch were decreased in Trpv4 −/− mice. In vitro, XAV939 inhibited hypo-osmotic stress induced proliferation of HaCaT cells, and hypo-osmotic stress induced proliferation of in HaCaT cells and primary cultured keratinocytes were also significantly reduced by blocking TRPV4 function. Finally, thymic stromal lymphopoietin release was examined both in vivo and in vitro, which was significantly inhibited by XAV939 treatment and Trpv4 deficiency, and anti-TSLP antibody treatment significantly decreased AEW-induced scratching behavior. Overall, our study revealed a unique ability of TRPV4 expressing keratinocytes in the skin, which critically mediated dry skin induced epidermal hyperplasia and chronic pruritus, thus provided novel insights into the development of therapies for chronic pruritus in the elderly. [Display omitted] • Dry skin induced epidermal hyperplasia and pruritus dependent on β-catenin signaling pathway. • Dry skin induced epidermal hyperplasia and pruritus partly dependent on TRPV4. • Hypo-osmotic stress induced keratinocytes proliferation and TSLP release dependent on β-catenin signaling pathway. • Hypo-osmotic stress induced cytosol-nucleus transportation of β-catenin dependent on TRPV4. [ABSTRACT FROM AUTHOR]

[Display omitted] • The 400 µm long DMNs penetrate the skin to a depth of ≈200 µm for dry skin and ≈200–290 µm for the barrier-disrupted skin. • The dissolved polymer expands more expansively in barrier-disrupted skin than in intact skin, with the smallest expansion observed in dry skin. • The DMNs-induced microchannel areas are significantly more pronounced in barrier-disrupted and dry skin than in intact skin. • To optimize DMN-induced drug delivery, it is essential to select a suitable skin model, considering the skin conditions and the dissolvability of needle materials. Dissolvable microneedles (DMNs), fabricated from biocompatible materials that dissolve in both water and skin have gained popularity in dermatology. However, limited research exists on their application in compromised skin conditions. This study compares the hyaluronic acid-based DMNs penetration, formation of microchannels, dissolution, and diffusion kinetics in intact, barrier-disrupted (tape stripped), and dry (acetone-treated) porcine ear skin ex vivo. After DMNs application, comprehensive investigations including dermoscopy, stereomicroscope, skin hydration, transepidermal water loss (TEWL), optical coherence tomography (OCT), reflectance confocal laser scanning microscopy (RCLSM), confocal Raman micro-spectroscopy (CRM), two-photon tomography combined with fluorescence lifetime imaging (TPT-FLIM), histology, and scanning electron microscopy (SEM) were conducted. The 400 µm long DMNs successfully penetrated the skin to depths of ≈200 µm for dry skin and ≈200–290 µm for barrier-disrupted skin. Although DMNs fully inserted into all skin conditions, their dissolution rates were high in barrier-disrupted and low in dry skin, as observed through stereomicroscopy and TPT-FLIM. The dissolved polymer exhibited a more significant expansion in barrier-disrupted skin compared to intact skin, with the smallest increase observed in dry skin. Elevated TEWL and reduced skin hydration levels were evident in barrier-disrupted and dry skins compared to intact skin. OCT and RCLSM revealed noticeable skin indentation and pronounced microchannel areas, particularly in barrier-disrupted and dry skin. Additional confirmation of DMN effects on the skin and substance dissolution was obtained through histology, SEM, and CRM techniques. This study highlights the impact of skin condition on DMN effectiveness, emphasizing the importance of considering dissolvability and dissolution rates of needle materials, primarily composed of hyaluronic acid, for optimizing DMN-based drug delivery. [ABSTRACT FROM AUTHOR]

Xerosis cutis of the feet is one of the most common skin conditions among type 2 diabetics. Whether skin dryness among diabetic patients is different from 'general' skin dryness is unclear. The overall aim was to compare the structure, function and molecular markers of dry and cracked foot skin between diabetics and non-diabetics. The foot skin of 40 diabetics and 20 non-diabetics was evaluated. A clinical assessment of skin dryness was performed and transepidermal water loss, stratum corneum hydration, skin surface pH, epidermal thickness, skin roughness, elasticity and structural stiffness were measured. Ceramides, natural moisturizing factors, histamines, proteins and molecular markers of oxidative stress were analyzed based on a non-invasive sampling method for collection of surface biomarkers. The mean number of superficial fissures in the diabetic group was nearly three times higher than in the non-diabetic group (11.0 (SD 6.2) vs. 3.9 (SD 4.2)). The skin stiffness was higher in the diabetic group and the values of almost all molecular markers showed considerably higher values compared to non-diabetics. Malondialdehyde and glutathione were lower in the diabetic sample. The high number of superficial fissures may be based on an increased stiffness of dry diabetic foot skin combined with different concentrations of molecular markers in the stratum corneum compared to dry foot skin of non-diabetics. • The mean number of superficial fissures in the diabetic group was nearly three times higher than in the non-diabetic group. • In diabetics stiffness was generally higher at all skin areas. • The dorsal skin of diabetics showed higher roughness, was thinner and less hydrated, clinically possibly leading to higher fragility. [ABSTRACT FROM AUTHOR]

Older nursing home residents are prone to develop different skin conditions at the same time, including xerosis cutis, skin tears, pressure ulcers, incontinence-associated dermatitis or intertrigo. Guidelines and recommendations mainly address these skin conditions separately. The overall aim of this study was to measure the effects of the implementation of a skincare and prevention package. A two-arm cluster-randomised controlled trial was conducted. In nursing homes being assigned to the intervention group, an evidence-based and structured skincare and prevention programme was implemented for six months. Nursing home residents in the control group received standard care as usual. Blinded dermatologists conducted head-to-toe skin assessments, and the researchers assessed skin barrier parameters including stratum corneum hydration and transepidermal water loss at the upper and lower extremities after three and six months. Outcomes included the cumulative incidence of incontinence-associated dermatitis, skin tears, pressure ulcers and intertrigo, and were presented as intention-to-treat and per protocol analysis. Skin dryness and resident-reported outcomes (pain, itch, quality of life) were assessed. A random sample of 17 nursing homes in the federal state of Berlin, Germany, was drawn and randomised in intervention (n = 9) and control groups (n = 8). In total, 165 participants were allocated to the intervention, and 149 participants were allocated to the control group. The cumulative incidence of skin tears (19.2 %, 95 % CI 12.8–27.8), pressure ulcers (13.6 %, 95 % CI 8.1–21.9) and intertrigo (27.0 %, 95 % CI 18.4–37.7) was lower in the intervention compared to the control group, with cumulative incidences of 27.2 % (95 % CI 19.3–36.9) for skin tears, 16.9 % (95 % CI 10.6–25.9) for pressure ulcer, and 37.8 % (95 % CI 27.5–49.4) for intertrigo. The incidence of incontinence-associated dermatitis was higher in the intervention group (26.3 %, 95 % CI 17.9–36.8) compared to the control group (23.1 %; 95 % CI 14.6–34.5). Mean skin dryness was lower in the intervention group but showed variation. The impact on pain, itch, and quality of life was trivial. The present study results indicate that the implementation of tailored and evidence-based nursing routines improves skin health and safety in residential long-term care. Evidence suggests that multiple adverse skin conditions can be prevented by regular skin assessments and individually tailored skincare routines. Positive effects on skin dryness were observed, but skin physiology parameters did not indicate changes of the skin barrier function. This study is registered at the German Clinical Trials Register (registration number: DRKS00015680; date of registration: January 29th, 2019) and ClinicalTrials.gov (NCT03824886 ; date of registration: January 31st, 2019). [ABSTRACT FROM AUTHOR]

Background: Pruritus is one of the common problems in hemodialysis patients that involves more than 45% of Iranian patients. Its exact pathogenesis is unclear. Meanwhile, violet is an old plant with anti-scratching effects, which is extensively used to treat diseases in the Persian medicine. This study aimed to evaluate the effect of massaging the body with and without violet oil in the treatment of uremic pruritus.Methods: In this study 57 hemodialysis patients who had uremic pruritus were categorized randomly into two groups. The treatment involved massage with and without topical 5 ml violet oil for 7 min during six sessions (two weeks) on the healthy hand which did not have fistula pruritus score questionnaire were completed before and after the intervention.Results: There was no difference between the two groups before the intervention; however, after the intervention, a significant difference was observed within each group and between the groups in terms of skin dryness score, severity, location, and frequency of pruritus, which were recovered significantly in both groups.Conclusion: The results of this study indicated that massage with violet oil is more effective than massage alone and is recommended as a complementary treatment for patients with uremic pruritis. [ABSTRACT FROM AUTHOR]

• Very wet skin reduces the variability in precision grip task than dry skin condition. • Moisture on fingertips to be considered for using precision grip as a diagnostic tool for patients with hand dysfunction. • Extent of moisture decides the strategy of grip force to be applied during object manipulation in precision grip task. Several extrinsic factors affect precision grip task variability. Presence of moisture in glabrous skin can regulate the impact of extrinsic factors. Consequently, wetness may influence the precision grip task variability per se by regulating its force, rate and time parameters. This study aims to examine the influence of age, coefficient of skin friction (CF) and object weight (extrinsic factors) on precision grip task variability in dry skin condition (DSC) and very wet skin conditions (VWSC). Eighty healthy subjects performed precision grip task with four different weights (1.3N, 1.4N, 1.5N, and 1.7N) sequentially in DSC and VWSC. Simple and multiple linear regression analysis were performed to estimate the independent and combined effect of extrinsic factors on precision grip parameters. Our results show that the extent of variability caused by the extrinsic factors on precision grip task significantly reduced when objects were held with VWSC than DSC. Wetting of the skin also decreased standard deviation and coefficient of variation of friction. The frictional range of individuals was widespread in DSC (0.62–3.42) while VWSC brought it to a closer range (0.77–1.64). Our findings suggest that wetness of skin reduces precision grip task variability, and further knowledge on this may help in designing precision grip as a quantitative screening tool for patients with hand dysfunction. [ABSTRACT FROM AUTHOR]

Chronic skin diseases with itch and dry skin show increased peripheral nerve fiber elongation into the epidermis. However, the characteristics of the elongated nerve fibers remain unclear. Therefore, we investigated the characteristics of the elongated nerve fibers using a dry skin mouse model with itch. In this mouse model, prepared via repetitive treatments with an acetone/ether mixture and water, the stratum corneum water content was decreased, whereas spontaneous scratching and epidermal hyperplasia were increased. In addition, the number of substance P (SP)- and calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers (C-fibers) was increased in the epidermis of treated mice compared to that in non-treated control mice. However, neurofilament 200-immunoreactive nerve fibers (A-fibers) were not detected in the epidermis of treated mice. These results suggest that the elongated epidermal peripheral nerve fibers comprise SP/CGRP-containing C-fibers but not A-fibers. Thus, these fibers may be involved in the induction of dry skin pruritus. [ABSTRACT FROM AUTHOR]

Background Pressure ulcers are a serious health problem in medical and nursing care. Therefore, effective prevention is crucial. Major pressure ulcer risk factors have been identified but the particular role of dry skin (xerosis cutis) is unclear. Objectives To investigate possible associations between dry skin and pressure ulcers focusing on the sacrum/trochanter and at heel/ankle skin areas. Design Two multicenter cross-sectional studies. Settings/participants In 2014 and 2015 thirty nursing homes and thirteen hospitals in Germany participated. In total 3837 participants were included. Mean age was 76.1 (SD 15.5) years. Methods Skin assessments and data collection were performed by trained nurses based on a standardized data collection form. Descriptive comparisons and multilevel logistic regressions predicting pressure ulcers at sacrum/trochanter and ankle/heel were conducted. Results The prevalence of skin dryness at the trunk was significantly higher for subjects with pressure ulcers category 2+ at the sacral area compared to without (39.0% vs. 24.4%, p = 0.010). Adjusted to demographic variables, mobility and type of institution dry skin at the trunk was no longer associated with pressure ulceration (OR 1.11 (95% CI 0.62–2.00)). 71.9% of patients with heel/ankle pressure ulcers category 2+ were affected by dry skin at legs or feet, compared to 42.8% of subjects without pressure ulcers (p < 0.001). In the adjusted analysis the OR was 1.85 (95% CI 0.83–4.14). Conclusions Study results indicate that dry skin at the feet may be considered as a risk factor for heel pressure ulcer development. Skin dryness may be less important for sacral pressure ulcers. Therefore, the variable skin status should be better defined in future studies and pressure ulcer risk models. Results further support differences in pressure ulcer aetiologies between anatomical locations. [ABSTRACT FROM AUTHOR]

Glucosylceramide (GlcCer) has various effects such as skin moisturizing, improvement of atopic dermatitis, and enhancement of skin barrier function. However, the mechanism of GlcCer on skin barrier function remains unclear. In this study, the effect of GlcCer from pineapples (P-GlcCer) on dry skin protection and intestinal immunity was investigated using HR-1 hairless mice fed on a special diet and an in vitro co-culture model consisting of intestinal epithelial Caco-2 and macrophage RAW264.7. The oral administration of P-GlcCer showed an improvement in skin barrier function and enhancement of interleukin-23p19 mRNA ( Il23a ) expression in the small intestine. Il23a expression in LPS-stimulated RAW264.7 cells was enhanced by the purified GlcCer in P-GlcCer. Furthermore, pretreatment of Caco-2 with a β-glucocerebrosidase or a ceramidase inhibitor suppressed the enhancement of Il23a expression, but a sphingosine kinase inhibitor did not. It was demonstrated that not P-GlcCer itself but the intestinal metabolite 4,8-sphingadienine ameliorated dry skin symptoms. [ABSTRACT FROM AUTHOR]

Background Dry skin (xerosis cutis) is increasingly recognized as a relevant health problem in daily life and in health and nursing care. The use of bath additives such as oils is common to reduce dry skin, but empirical evidence supporting this practice is limited. Objectives The aim of this study was to investigate the effectiveness of using a bath oil additive in improving skin barrier function and ameliorating dry skin in comparison to non-oil containing skin cleansers for bathing or showering. Design Single centre randomized observer blind pragmatic parallel group trial. Settings Outpatient/community care. Participants Volunteers showing clinically mild to moderate dry skin recruited from the city of Berlin. Methods Healthy children and adults were randomly assigned to use either a commercially available bath oil or to continue using their regular non-oil containing skin cleansers every other day over a study period of 28 days. Skin barrier parameters and the severity of dry skin were assessed at baseline and at two follow-up visits at the study centre. Transepidermal water loss was the primary outcome. Results All sixty participants randomized completed the trial. Median age was 32.5 (IQR 8.3 to 69) years. At the end of study the mean transepidermal water loss in the intervention group was statistically significant lower compared to the control group (mean difference −1.9 (95% CI −3.1 to −0.8) g/m 2 /h). Stratum corneum hydration was statistically significantly higher in the intervention group at the end of the study. Skin surface pH and roughness were comparable in both groups and remained unchanged, while both groups showed a trend to improvement in dry skin symptoms Conclusions This pragmatic trial provides empirical evidence that the regular use of the investigated bath oil is effective in improving the skin barrier function in children and adults with mild dry skin when used in routine skin care and supports its use as a basic element for the management of a broad spectrum of dry skin conditions. Trial registration ClinicalTrials.gov Identifier NCT02557698 . [ABSTRACT FROM AUTHOR]

Dry skin is a common skin problem in older persons. Aim of this study was to determine the prevalence, associated factors of dry skin in older inpatients. A multicenter cross-sectional study was designed and conducted. On 31 March and 29 May in 2021 two days, fifty hospitals and two nursing homes in China participated in the study. In total, 33,769 participants were included. The mean age was 73.2 (SD 8.9) years. A whole-body skin examination and associated data collection were performed by 1067 trained nurses based on a standardized data form and methods. Descriptive and univariable analyses and multivariable logistic regressions were conducted. In total, 11,602 participants had dry skin with a prevalence of 34.4%, mainly located on the upper and lower limbs with very severe skin dryness, 21.2% of the participants reported that their dry skin had pruritus, and 12.5% complained that sleep was affected by dry skin. The stronger predictor for dry skin was nursing homes (OR 5.07, 95% CI 3.99–6.45). Other predictors for dry skin were age, male sex, nutrition, lower activity level, skincare dependence, renal and pulmonary impairment, diabetes mellitus, varicose veins, cardiovascular diseases and Parkinsonism, diuretics, statins and antibiotics. The predictive model of area under ROC curve was 0.628(95% CI 0.622–0.634). The prevalence of dry skin among Chinese older patients was at high level and was associated with multiple factors. Persons with skin dryness have a higher proportion of skin itching and poor sleep. It has been registered in the Chinese Clinical Trial Registry (ChiCTR2100042893). [ABSTRACT FROM AUTHOR]

Background Maintaining and improving skin health of patients and long-term care receivers is a widely agreed upon goal in health and nursing care. Care dependent and aged persons have a high predisposition to develop dry skin conditions. Objectives The aim of this study was to estimate the prevalence and severity of skin dryness in hospitals and nursing homes and to identify person- and health-related variables associated with this skin condition. Design The study was part of a bigger annual multicentre descriptive cross-sectional prevalence study of health problems. Settings/participants Fourteen nursing homes and six hospitals in Germany participated in this study in 2014. A total of 1710 subjects ( n = 1091 long-term care residents and n = 619 in-patients) were included. Methods Skin assessments were conducted and skin dryness was measured using the Overall Dry Skin Score. Mobility was measured using the respective item of the Care Dependency Scale. Demographic, functional and physiological parameters were compared between subjects with and without dry skin. A logistic regression model predicting skin dryness was created. Results The prevalence of skin dryness was 48.8% (95% CI 46.5–51.2). Nursing home residents were most often affected (52.6%; 95% CI 49.6–55.6) compared to in-patients (42.2%; 95% CI 38.3–46.1). The skin of feet and legs were most often affected by skin dryness (42.9%) compared to other skin areas. Being older (OR 1.01; 95% CI 1.01–1.02), having pruritus (OR 14.21; 95% CI 8.00–22.95), oncological (OR 1.95; 95% CI 1.30–2.91), musculoskeletal diseases (OR 1.31; 95% CI 1.04–1.64), being skin care independent (OR 0.48; 95% CI 0.32–0.70) were the strongest covariates for the presence of dry skin in the multivariate model. Conclusions Based on a large sample results indicate that approximately every second nursing home resident and hospital in-patient are affected by dry skin. Severe forms occur more often in hospital in-patients compared to nursing home residents. Skin care interventions to tackle dry skin are recommended particularly for hospital patients and nursing home residents who are affected by pruritus or oncological diseases, who are in need of washing/bathing assistance, and who have musculoskeletal diseases. [ABSTRACT FROM AUTHOR]

Background Pruritus and discomfort are often present in patients with xerosis and atopic dermatitis. Several studies suggest an important role of diet in skin pathophysiology. Objective This study evaluated the effect of dietary fatty acids in the skin physiology via an itch-related animal model with and without supplementation with fish oil (FO), a source of polyunsaturated fatty acids (PUFA), especially omega 3 ( n -3). Methods Male Wistar rats were divided into two groups—non-supplemented (control) and supplemented with FO (3 g/kg/day) by gavage for 90 days. Every 30 days, scratching and skin parameters (transepidermal water loss (TEWL), hydration, and local blood flow) were evaluated before and after dorsal skin exposure to acetone to induce the itch-related dry skin. At the end of the study, animals were sacrificed, and skin samples collected for fatty acids composition analysis by GC–FID. Results FO supplementation reduced the TEWL and increased the skin hydration, with significant changes from day 60 on, while skin microcirculation registered no changes. It also alleviated the acetone induced skin barrier alteration, revealed by a faster resolution of TEWL and hydration, and elimination of itch-related scratching induced by dry skin. These changes were associated with the shift in the skin fatty acids incorporation pattern (richer in n -3 with n -6/ n -3 < 5) resulting from the FO supplementation. Conclusion Skin barrier dynamics seem to be influenced by FO n -3 PUFA, with suppressive effects on the scratching behaviour induced by dry skin. Hence, long-term supplementation with n -3 PUFA rich nutrients might reinforce and restore cutaneous integrity and function. [ABSTRACT FROM AUTHOR]

Background Many targeted therapies used in the treatment of cancer can lead to the development of xerosis, but the incidence and relative risk of xerosis have not been ascertained. Objective We conducted a systematic review and metaanalysis of clinical trials, to ascertain the incidence and risk of developing xerosis after taking anticancer drugs. Methods The PubMed (1966-October 2013), Web of Science (January 1998-October 2013), and American Society of Clinical Oncology abstracts (2004-2013) databases were searched for clinical trials of 58 targeted agents. Results were calculated using random or fixed effects models. Results The incidences of all- and high-grade xerosis were 17.9% (95% confidence interval [CI]: 15.6-20.4%) and 1.0% (95% CI: 0.9-1.5%), respectively. The risk of developing all-grade xerosis was 2.99 (95% CI: 2.0-4.3), and it varied across different drugs ( P < .001). Limitations The reporting of xerosis may vary among clinicians and institutions, and the incidence may be affected by age, concomitant medications, comorbidities, and underlying malignancies or skin conditions. Conclusion Patients receiving targeted therapies have a significant risk of developing xerosis. Patients should be counseled and treated early for this symptom to prevent suboptimal dosing and quality of life impairment. [ABSTRACT FROM AUTHOR]

There has been a rapid emergence of numerous targeted agents in the oncology community in the last decade. This exciting paradigm shift in drug development lends promise for the future of individualized medicine. Given the pace of development and clinical deployment of targeted agents with novel mechanisms of action, dermatology providers may not be familiar with the full spectrum of associated skin-related toxicities. Cutaneous adverse effects are among the most frequently observed toxicities with many targeted agents, and their intensity can be dose-limiting or lead to therapy discontinuation. In light of the often life-saving nature of emerging oncotherapeutics, it is critical that dermatologists both understand the mechanisms and recognize clinical signs and symptoms of such toxicities in order to provide effective clinical management. Part I of this continuing medical education article will review in detail the potential skin-related adverse sequelae, the frequency of occurrence, and the implications associated with on- and off-target cutaneous toxicities of inhibitors acting at the cell membrane level, chiefly inhibitors of epidermal growth factor receptor, KIT, and BCR-ABL, angiogenesis, and multikinase inhibitors. [ABSTRACT FROM AUTHOR]

Chronic pruritus, or itch, is common and debilitating, but the neuroimmune mechanisms that drive chronic itch are only starting to be elucidated. Recent studies demonstrate that the IL-33 receptor (IL-33R) is expressed by sensory neurons. However, whether sensory neuron–restricted activity of IL-33 is necessary for chronic itch remains poorly understood. We sought to determine if IL-33 signaling in sensory neurons is critical for the development of chronic itch in 2 divergent pruritic disease models. Plasma levels of IL-33 were assessed in patients with atopic dermatitis (AD) and chronic pruritus of unknown origin (CPUO). Mice were generated to conditionally delete IL-33R from sensory neurons. The contribution of neuronal IL-33R signaling to chronic itch development was tested in mouse models that recapitulate key pathologic features of AD and CPUO, respectively. IL-33 was elevated in both AD and CPUO as well as their respective mouse models. While neuron-restricted IL-33R signaling was dispensable for itch in AD-like disease, it was required for the development of dry skin itch in a mouse model that mirrors key aspects of CPUO pathology. These data highlight how IL-33 may be a predominant mediator of itch in certain contexts, depending on the tissue microenvironment. Further, this study provides insight into future therapeutic strategies targeting the IL-33 pathway for chronic itch. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Background: Dry skin causes pruritus and discomfort in patients with xerosis and atopic dermatitis. General treatment for skin dryness involves the topical application of an emollient. However, more effective, simpler therapies are desired. Collagen tripeptide (CTP) is a highly purified, non-antigenic, low-allergenic collagen fraction that is known to have various biological effects. Objective: To clarify the therapeutic effects of CTP for dry skin using acetone-induced dry skin model mice. Methods: ICR mice were treated with acetone followed by oral administration of CTP (80 or 500mg/kg/day) for 3 days. Hyaluronic acid production induced by CTP was assessed using human dermal fibroblasts in vitro and in an acetone-induced dry skin model mice in vivo. Transepidermal water loss (TEWL) and scratching behavior were evaluated. Furthermore, the effects of CTP on intraepidermal nerve fibers and expression of semaphorin 3A (Sema3A) and nerve growth factor (NGF) were examined by immunohistochemistry and quantitative RT-PCR. Results: CTP enhanced hyaluronic acid production in human dermal fibroblasts in vitro and in murine skin in vivo. Oral administration of CTP in acetone-induced dry skin model mice significantly decreased TEWL and suppressed scratching behavior. Intraepidermal nerve growth was dramatically inhibited in CTP-treated mice. Quantitative PCR analysis and immunohistochemical study revealed that CTP abolished the increased NGF and decreased Sema3A levels induced by acetone treatment. Conclusion: Oral administration of CTP improves dry skin and normalizes axon-guidance factors in the epidermis in addition to reducing pruritus. CTP may be used in a new therapeutic strategy against dry skin and pruritus. [Copyright &y& Elsevier]

Abstract: Background: UV-based therapy has anti-pruritic effects in inflammatory skin diseases, such as atopic dermatitis and psoriasis. These anti-pruritic effects may be partly due to inhibition of intraepidermal nerve growth, but they have not been fully characterized. Objective: This study was performed to characterize the anti-nerve growth effects of UV-based therapies in acetone-treated mice as an acute dry skin model. Methods: Nerve fibers penetrate into the epidermis 24h after acetone treatment in mice, and nerve growth peaks 48h after acetone treatment. To investigate the effects of UV-based therapies on the epidermal nerve fibers, including combination treatment with corticosteroid ointment, the mice were treated with psoralen ultraviolet A (PUVA), PUVA and betamethasone valerate ointment (PUVA+BV), narrowband ultraviolet B (NB-UVB), or an excimer lamp. Each therapy was provided 24h after acetone treatment, and skin samples were taken 48h later. Nerve fiber densities and expression levels of nerve growth factor (NGF) and semaphorin 3A (Sema3A) in the epidermis were examined by immunohistochemistry. Results: Penetration of nerve fibers into the epidermis was observed in the acetone-treated mice, concomitant with increased NGF and decreased Sema3A levels in the epidermis. The acetone-induced intraepidermal nerve growth was significantly decreased by PUVA, PUVA+BV, NB-UVB, and excimer lamp treatments compared with controls. In addition, PUVA+BV and NB-UVB normalized the abnormal expression of NGF and Sema3A in the epidermis, but no such normalization was observed with excimer lamp treatment. Conclusion: UV-based therapies, especially NB-UVB and excimer lamp treatments, may be effective therapeutic methods for pruritus involving epidermal hyperinnervation. [Copyright &y& Elsevier]

Abstract: Lipophilic moisturizers are widely used to treat dry skin. However, their interaction with the lipids in the upper layer of the skin, the stratum corneum (SC), is largely unknown. In the present study this interaction of three moisturizers, isostearyl isostearate (ISIS), isopropyl isostearate (IPIS) and glycerol monoisostearate (GMIS), has been elucidated using lipid mixtures containing isolated ceramides (CER), cholesterol (CHOL) and free fatty acids (FFA), mimicking the lipid composition and organization in SC. The conformational ordering and the lateral packing of the lipid mixtures were examined by Fourier transformed infrared spectroscopy. Equimolar CER:CHOL:FFA mixtures show an orthorhombic to hexagonal phase transition between 22 and 30 °C and an ordered–disordered phase transition between 46 and 64 °C. Addition of 20% m/m ISIS or IPIS increased the thermotropic stability of the orthorhombic lateral packing, while GMIS had no influence. Furthermore, small amounts of all three moisturizers are incorporated into the CER:CHOL:FFA lattice, while the majority of the moisturizer exists in separate domains. Especially the thermotropic stabilization of the orthorhombic lateral packing, which might reduce water loss from the skin, is considered to contribute to the moisturizing effect of IPIS and ISIS in stratum corneum. [Copyright &y& Elsevier]

Summary: Background: Skin dryness is apparent in several pruritic skin diseases, such as xerosis and atopic dermatitis. Our previous study has demonstrated an increase of nerve fibers in the epidermis of patients with xerosis, suggesting the contribution of nerve fibers to itching. Objective: This study was conducted to reveal a direct linkage between dry skin and intraepidermal nerve growth. Methods: ICR mice treated with acetone were used as a dry skin model. Time-dependent measurement of transepidermal water loss (TEWL) and stratum corneum (SC) hydration was performed on the treated areas. Moreover, both the distribution of intraepidermal nerve fibers and the expression of epidermal nerve growth factor (NGF) and amphiregulin (AR) were examined sequentially with immunohistochemistry and quantitative RT-PCR. The same experiments were carried out in control mice treated with sterile water. Results: Enhanced TEWL and decreased SC hydration were observed in the acetone-treated skins during the first hour after the treatment. These parameters gradually returned to the normal range within 48h. In the acetone-treated mice, we found that there were many nerve fibers in the epidermis between 16 and 48h after the treatment. No changes of the parameters for barrier disruption and intraepidermal nerve growth were observed in the control skins. Moreover, the expression of epidermal NGF and AR at the protein and mRNA levels was increased before the penetration of nerve fibers into the epidermis. Conclusions: These results suggest that increases of epidermal NGF and AR levels are associated with intraepidermal nerve growth in acetone-treated mice. [Copyright &y& Elsevier]

Abstract: Kukui nut (Aleurites moluccana) oil is starting to become a source of ingredients for cosmetics preparation. Fatty acid profiles are considered to be important for quality assessment. As part of an effort to grow the kukui nut oil industry, information was needed to determine whether fatty acid profiles of kukui nut oils made 10 years ago have changed over time. Commercial chemical preparation procedures and laboratory analytical methods have been modified. In addition, it was desirable to know whether oils from nuts from different parts of the world and oils subjected to deodorization procedures had similar fatty acid profiles. All kukui nut oils from Polynesian sources (Hawaii, Tonga) had identical fatty acid profiles over a 10-year period. This finding suggests that production practices for obtaining the oil and analytical procedures had not changed significantly over time. One Polynesian oil had a profile that was similar to the kukui nut oils obtained from Indonesia and East Timor. Like deodorized kukui nut oils obtained by steam distillation, these were also different from most of the Polynesian oils in that their linolenic acid (18:3cΔ9,12,15) values were significantly lower. [Copyright &y& Elsevier]

As a model of dry skin pruritus in mice, one hind paw was treated twice daily with a mixture of acetone/diethylether/water (AEW); controls received water only. A protective collar prevented the animals from accessing the treatment area. At 16 days, the collar was removed and AEW-treated mice exhibited marked biting of the treated paw; the number and cumulative duration of bites was significantly greater than in controls. After 3 additional treatment days (collars intact), animals were perfused for c-fos immunohistochemistry. There was significantly more fos-like immunoreactivity in the ipsilateral lumbar spinal cord of AEW-treated animals, with the majority in superficial laminae. It is proposed that biting of the dry skin reflects pruritus, and that neurons predominantly in superficial laminae of the dorsal horn may signal itch sensation. [Copyright &y& Elsevier]

The microinflammatory model of skin aging is described. This model accounts for the loss of elasticity, resiliene and flexibility of the dermis, as well as for the appearance of wrinkles and for the thinning of the epidermis which are associated with aging. The lack of appropriate apparatuses for the correct measurements of skin hydration does not allow one to test this model for its predictive capability of the appearance of dry skin with age. The micro-inflammatory model of skin aging fails to predict the appearance of age spots on the surface of the skin. [Copyright &y& Elsevier]

Epidermal keratinocytes are exposed to a low water concentration at the stratum corneum-stratum granulosum interface. When epithelial tissues are osmotically perturbed, cellular protection and cell volume regulation is mediated by accumulation of organic osmolytes such as taurine. Previous studies reported the presence of taurine in the epidermis of several animal species. Therefore, we analyzed human skin for the presence of the taurine transporter (TAUT) and studied the accumulation of taurine as one potential mechanism protecting epidermal keratinocytes from dehydration. According to our results, TAUT is expressed as a 69 kDa protein in human epidermis but not in the dermis. For the epidermis a gradient was evident with maximal levels of TAUT in the outermost granular keratinocyte layer and lower levels in the stratum spinosum. No TAUT was found in the basal layer or in the stratum corneum. Keratinocyte accumulation of taurine was induced by experimental induction of skin dryness via application of silica gel to human skin. Cultured human keratinocytes accumulated taurine in a concentration- and osmolarity-dependent manner. TAUT mRNA levels were increased after exposure of human keratinocytes to hyperosmotic culture medium, indicating osmosensitive TAUT mRNA expression as part of the adaptation of keratinocytes to hyperosmotic stress. Keratinocyte uptake of taurine was inhibited by β-alanine but not by other osmolytes such as betaine, inositol, or sorbitol. Accumulation of taurine protected cultured human keratinocytes from both osmotically induced and ultraviolet-induced apoptosis. Our data indicate that taurine is an important epidermal osmolyte required to maintain keratinocyte hydration in a dry environment. [ABSTRACT FROM AUTHOR]

Background: Some extragenital symptoms have been suggested to be associated with the menopause and thus to be affected by estrogen status. In such case extragenital symptoms may be more frequent in postmenopausal women without hormone replacement therapy (HRT) than in premenopausal women or women using HRT.Objective: To assess if the prevalence of a number of extragenital symptoms is higher in postmenopausal women without than with HRT, or in premenopausal women of the same age.Material and Methods: All women aged 53 and 54 years in the community of Linköping (n=1760) were sent a validated questionnaire about use of HRT, time since last menstruation and about different extragenital symptoms.Results: 1298 (73.8%) women answered the questionnaire and answers from 1180 (67%) women were possible to analyze. Postmenopausal women woke up significantly more often during night than premenopausal, and those without HRT often due to hot flushes and sweating. Women with HRT reported more muscular pain than the others. We found no other significant difference in prevalence of extragenital symptoms between the three groups of women.Conclusions: Sleeping disorders, arthralgia, xerophthalmia, xerostomia and dry skin are not more prevalent in 53 and 54 years old postmenopausal women without HRT than in women with HRT or in premenopausal women of the same age. It may still be that some of these symptoms are related to estrogen deficiency, but do not develop until some years after menopause. It may also be that women with the most severe symptoms decided to use HRT and thereby decreased symptoms to the same level as in non-users. [ABSTRACT FROM AUTHOR]

Background: Seasonal changes affect the condition of skin and may trigger various cutaneous disorders. Objective: To clarify the effects of the environmental humidity on the skin pathology, we studied the effects of the humidity on a water-holding function of the stratum corneum. Methods: We evaluated the skin surface conductance, amino acid in the stratum corneum, and immunoreactivity of filaggrin of the epidermis of hairless mice kept in different environmental humidity. Results: Skin surface conductance in the stratum corneum of hairless mice 3–7 days after transfer from a humid environment (>80% relative humidity) to a dry (<10% relative humidity) environment, was significantly lower than that of the mice transferred from a normal environment (relative humidity=40–70%) to a dry environment. The free amino acid content in the stratum corneum significantly decreased 24 h after we transferred the mice from a normal to a dry condition, then it recovered to the original level within 3 days, while the mice transferred from a humid to a dry condition showed a significantly lower amino acid content even 7 days after the transfer. No obvious change was observed in the relative composition of the major components of the free amino acids during the experiments. Immunoreactivity of filaggrin, which is the main precursor of free amino acids in the stratum corneum, also became faint in the epidermis of the mice transferred from a humid or normal to a dry environment. Conclusion: These results suggested that a drastic decrease in the environmental humidity reduced the total free amino acid generation and consequently induced skin surface dryness in the stratum corneum. [Copyright &y& Elsevier]

Previous reports demonstrated that long-term exposure to extremes in humidity influence permeability barrier homeostasis. Here the effects of a sudden shift from a high humidity to a dry environment were studied. Mice were initially maintained in either a humid (> 80% relative humidity) or normal environment (relative humidity = 40–70%), and then transferred to a dry environment (< 10% relative humidity). Within 2 d of transfer from a humid to a dry environment a 6–7-fold increase in transepidermal water loss occurred that returned to normal within 7 d. No increase in transepidermal water loss occurred in response to a switch from a normal to a dry environment. At a time when barrier function was abnormal, both stratum corneum hydration and pH were normal, indicating that the mechanisms that regulate these functions differ. Following transfer from a humid to dry environment, electron microscopy revealed a marked decrease in: (i) lamellar bodies in the outermost stratum granulosum; (ii) deposition of lamellar body contents at the stratum granulosum–stratum corneum interface; and (iii) the quantity of intercellular lamellae in the stratum corneum, which together could account for the barrier abnormality. Transfer of mice from a normal to a dry environment rapidly stimulated epidermal proliferation, whereas animals switched from a humid to a dry environment displayed a delayed increase in proliferation that might also contribute to the barrier abnormality. The present study demonstrates that sudden changes from a high to a low humidity environment results in abnormal barrier function, which could adversely influence the incidence and/or severity of skin disorders. [ABSTRACT FROM AUTHOR]

Summary The stratum corneum requires ceramides, cholesterol, and fatty acids to provide the cutaneous permeability barrier. The lipids are organized in intercellular membranes exhibiting short- and long-periodicity lamellar phases. In recent years, the phase behavior of barrier lipid mixtures has been studied in vitro. The relationship of human stratum corneum lipid composition to membrane organization in vivo, however, has not been clearly established. Furthermore, the special function of the different ceramide species in the stratum corneum is largely unknown. We examined lipid organization and composition of stratum corneum sheets from different subtypes of healthy human skin (normal, dry, and aged skin). Lipid organization was investigated using X-ray diffraction and demonstrated that the 4.4 nm peak attributed to the long periodicity phase was frequently missing for skin with a low Cer(EOS)/Certotal ratio, indicating an important part for Cer(EOS), which contains ω-hydroxy fatty acid (O) ester-linked to linoleic acid (E) and amide-linked to sphingosine (S). A deficiency in the 4.4 nm peak was predominantly observed in young dry skin. In one case of aged skin, however, and less often in young normal skin this peak was also missing. Furthermore, the ceramide composition of samples without the 4.4 nm peak showed a deficiency of Cer(EOH), which contains 6-hydroxy-4-sphingenine (H), and an increase in Cer(NS) and Cer(AS), which contain nonhydroxy (N) or α-hydroxy fatty acids (A). In addition, a 3.4 nm peak attributed to crystalline cholesterol occurred in most cases of aged and dry skin, but was not observed in young normal skin. Our results do not indicate a definite pattern of correlation between lipid organization and types of human skin. They demonstrate, however, that Cer(EOS) and Cer(EOH) are key elements for the molecular organization of the long periodicity lamellar phase in the human stratum corneum. [ABSTRACT FROM AUTHOR]

Abstract: In common dermatoses, such as atopic dermatitis (AD), a decline in skin barrier function often accompanies an increased severity of clinical symptomatology, including pruritus . Skin barrier disruption alters epidermal innervation and increases nerve density in the skin . These findings are indicative of increases in sensory receptors responsive to exogenous trigger factors, suggesting that hyperinnervation is partly responsible for intense itch sensations . Therefore, the abnormal innervation associated with skin barrier dysfunction such as dry skin has been considered as a target of antipruritic therapy. Moreover, recent studies have demonstrated that epidermal innervation is probably regulated by a fine balance of nerve elongation factors (e.g., nerve growth factor (NGF), amphiregulin, gelatinase) and nerve repulsion factors (e.g., semaphorin 3A (Sema3A), anosmin-1) . Although many people use emollients daily to alleviate symptoms of clinically and subjectively dry skin , the effects of emollients on nerve fiber density and nerve growth activity in dry skin remain unclear. We therefore examined the anti-nerve growth effects of petrolatum and heparinoid cream in the epidermis of acetone-treated mice, an animal model of acute dry skin . [Copyright &y& Elsevier]

Using a dry skin model in rats, we assessed spontaneous itch-related scratching behavior and associated c-fos expression in the superficial dorsal horn of the spinal cord. The number of spontaneous bouts of hind limb scratching directed toward the nape of the neck was significantly higher after 5 days of topical application of acetone–diethylether–water (AEW) compared to pre-treatment levels or to control animals treated with water only. In AEW-treated animals, neurons expressing Fos-like immunoreactivity (FLI) were observed in superficial laminae of the dorsal horn at C3–C5 levels. There was a significant, positive correlation between the number of neurons in lamina I expressing FLI and the number and cumulative duration of spontaneous scratching bouts. These results suggest that this model may be useful to assess mechanisms of dry skin pruritus, and that lamina I neurons are activated as a consequence of itching and/or scratching in this model. [Copyright &y& Elsevier]

Background In administration of anti-EGFR antibody preparation, acne-like rash, hand foot skin reaction, and skin dryness occur frequently. Patient adherence of external moisturizing agent used for prevention of dermatopathy seems to be poor. We prepared information prescription booklet for cancer patients receiving chemotherapy (information prescription booklets) and video material based on this. Pharmacist conducted patient instruction using these tools. We evaluated the change in adherence by using such information prescription booklet and video material. Method The subjects were patients with panitumumab and cetuximab at the Shizuoka Cancer Center. The index of adherence is the daily usage amount of external moisturizing agent. Adherence was observed in three periods. Period 1; before distribution of information prescription booklet (before March 2017), Period 2; after distribution of information prescription booklet (March 2017 - May 2018), Period 3; after distribution of information prescription booklet and video material (after May 2018). Result Number of patients in periods 1, 2 and 3 were 45, 70, and 30, respectively. The number of administrations of the anti-EGFR antibody preparation during the observation period was 9 to 11 times (median). The amount of external preparation used per day(mean(SD)) was 5.0(3.3) g/day in Period 1. In contrast, the amount were increased to 7.3(6.2) g/day and 9.1(5.0) g/day in the period 2 and the period 3 after distribution of the information prescription booklet and information prescription bookleti wth video material respectively (p = 0.026, p = 0.001). Discussion Patient instruction using the information prescription booklet and video material was thought to be effective in improving supportive therapy adherence by positively affecting the preventive behavior of the patient. [ABSTRACT FROM AUTHOR]

Background: Determinants and the extent of dry skin in healthy middle-aged and elderly populations have not been well established.Objective: We aimed to identify the prevalence and determinants for generalized dry skin (GDS) and localized dry skin (LDS) within a large prospective population-based cohort of middle-aged and elderly individuals of the Rotterdam Study.Methods: Dry skin was physician-graded as none, localized, or generalized. For GDS and LDS, separate multivariable logistic regression analyses were performed to search for association with participant characteristics, lifestyle factors, environmental factors, several comorbidities, and drug exposure.Results: Among the 5547 eligible participants, 60% had dry skin, of whom a fifth had GDS. Age, female sex, skin color, body mass index, outside temperature, eczema, and chemotherapy in the past were significant determinants for both GDS and LDS. Smoking, the use of statins and diuretics, poorer self-perceived health, and several dermatologic conditions increased the likelihood of having GDS only. Daily cream use was associated with less LDS.Limitations: Interobserver variability and residual confounding could have influenced our results. Because of our cross-sectional design, we could not infer causality.Conclusion: We identified factors significantly associated with dry skin in a general middle-aged and elderly population, with health parameters more strongly associated with GDS. [ABSTRACT FROM AUTHOR]