The Role and Benefits of Dermocosmetics in Acne Management in Japan.

In Japan, as in other countries around the world, acne vulgaris is a common disease and a frequent reason for patients to consult dermatologists. For optimal management of acne, it is important to understand how available products to support skin health can be used both with and without prescription products. Dermocosmetics can be defined as skincare agents with dermatologically active ingredients that directly support or care for the symptoms of various skin conditions (distinct from vehicle effects). There are products with active ingredients-including familiar ones such as niacinamide, retinol derivatives, and salicylic acid-that target important aspects of acne pathophysiology. Others, including ceramides, glyercin, thermal spring water, and panthenols, may have positive effects on skin barrier function that are useful in managing acne. This publication will discuss the roles of dermocosmetics in acne either as monotherapy to manage the milder forms of acne and help prevent relapses, or as adjuncts to prescription therapy to increase efficacy or adherence and assist in prevention of local adverse effects. Dermocosmetics may also have active ingredients that positively impact the skin microbiome.

Characterization of acne patients carrying clindamycin-resistant Cutibacterium acnes: A Japanese multicenter study.

Use of antimicrobials for acne treatment is correlated with an increased occurrence of antimicrobial-resistant Cutibacterium acnes. To clarify the role of antimicrobial use on the resistance and to investigate the characteristics of resistant strains, we conducted a multicenter study in dermatological clinics frequently visited by new patients with acne vulgaris. We collected specimens in 264 acne patients and tested 164 C. acnes strains isolated from 164 patients visiting 13 dermatological clinics. Antimicrobial susceptibility testing showed that the rates of resistance for tetracyclines, macrolides and clindamycin were significantly higher in C. acnes strains isolated from patients using antimicrobials for acne treatment than patients not using them. In particular, clindamycin-resistant strains were frequently isolated from patients with older median age (≥24 years) and severe/moderate acne. After investigating the resistance mechanism of 15 high-level clindamycin-resistant strains, the transposable clindamycin resistance genes, erm(X) or erm(50), were detected in 14 strains. Using single-locus sequence typing for C. acnes, the strains with erm(X) or multidrug resistance plasmid pTZC1 coding erm(50) and tetracycline resistance gene tet(W) were classified into clade F, which were specifically isolated from Japanese patients with acne, except for one strain. Our data showed that patients' information, such as antimicrobial use, age and acne severity, are valuable in estimating whether a patient carries antimicrobial-resistant C. acnes. Additionally, our results suggest that the clade F strains have a high risk of acquiring multidrug resistance.

Lower Incidence of In-Hospital Falls in Patients Hospitalized in Window Beds Than Nonwindow Beds.

OBJECTIVES: Comparing the incidence rate of in-hospital falls between patients hospitalized in window beds and nonwindow beds. DESIGN: Retrospective cohort study. SETTING: A general hospital in Mie, Japan. PARTICIPANTS: A total of 2767 patients (mean age, 68.4 years) hospitalized in four-bedded rooms between January 2014 and December 2016. MEASURES: We identified patients' bed status (window/nonwindow) and the incidence of in-hospital falls using data on medical records and incidence reports, respectively. RESULTS: During an observation period of 25,450 person-days, 57 patients had in-hospital falls (incidence rate, 2.24/1000 person-days). Incidence rate for in-hospital falls was significantly lower in the window-bed group (n = 1273) than in the nonwindow-bed group (n = 1494) [incidence rate ratio (IRR) 0.49, 95% confidence interval (CI), 0.29, 0.84]. In the multivariable analysis adjusted for age, gender, BMI, smoking and drinking habit, surgical operation during hospitalization, and independence in daily living, the window-bed group exhibited significantly lower incidence rate for in-hospital falls than the nonwindow-bed group (IRR 0.54, 95% CI 0.32, 0.93). Sensitivity analysis excluding patients aged <60 years suggested a consistent result: incidence rate for in-hospital falls was significantly lower in the window-bed group (n = 1123) than in the nonwindow-bed group (n = 925) (IRR 0.55, 95% CI 0.31, 0.95). CONCLUSIONS AND IMPLICATIONS: The incidence rate of in-hospital falls was significantly lower among patients hospitalized in window beds than nonwindow beds. Hospitalization in window beds might be a novel, simple preventive option for in-hospital falls. Further large-scale, prospective, multicenter research is required.

Japanese Dermatological Association Guidelines: Guidelines for the treatment of acne vulgaris 2017.

The Guidelines for the Treatment of Acne Vulgaris of the Japanese Dermatological Association was first published in Japanese in 2008 and revised in 2016 and 2017. These guidelines (GL) indicate the standard acne treatments in Japan and address pharmaceutical drugs and treatments applicable or in use in Japan. In these GL, the strength of the recommendation is based on clinical evidences as well as availability in Japanese medical institutions. In the 2016 and 2017 GL, some of the clinical questions were revised, and other questions were added in accordance with approval of topical medicines containing benzoyl peroxide (BPO). Rather than monotherapies of antibiotics, the 2017 GL more strongly recommend combination therapies, especially fixed-dose combination gels including BPO in the aspects of pharmacological actions and compliance in the acute inflammatory phase to achieve earlier and better improvements. The 2017 GL also indicate to limit the antimicrobial treatments for the acute inflammatory phase up to approximately 3 months and recommend BPO, adapalene, and a fixed-dose combination gel of 0.1% adapalene and 2.5% BPO for the maintenance phase to avoid the emergence of antimicrobial-resistant Propionibacterium acnes. The 2017 GL also discuss rosacea, which requires discrimination from acne and a different treatment plan.

Decreased daytime light intensity at nonwindow hospital beds: Comparisons with light intensity at window hospital beds and light exposure in nonhospitalized elderly individuals.

Light is crucial for the synchronization of internal biological rhythms with environmental rhythms. Hospitalization causes a range of unfavorable medical conditions, including delirium, sleep disturbances, depressed mood, and increased fall, especially in elderly people. The hospital room environment contributes significantly to patients' circadian physiology and behavior; however, few studies have evaluated light intensity in hospital settings. In this study, bedside light intensity during the daytime (6:00-21:00) was measured at 1-min intervals using a light meter on 4869 bed-days at the Inabe General Hospital in Mie, Japan (latitude 35°N), for approximately 1 month in each season. Daytime light exposure in home settings was measured in nonhospitalized elderly individuals (n = 1113) for two consecutive days at 1-min intervals using a wrist light meter. Median daytime light intensities at window and nonwindow hospital beds were 327.9 lux [interquartile range (IQR), 261.5-378.4] and 118.4 lux (IQR, 100.6-142.9), respectively, and daytime light intensity measured in nonhospitalized elderly individuals was 337.3 lux (IQR, 165.5-722.7). Compared with data in nonhospitalized elderly individuals, nonwindow beds were exposed to significantly lower daytime light intensity (p < 0.001), whereas window beds were exposed to similar daytime light intensity to that of home settings (p = 1.00). These results were consistent regardless of seasons (spring, summer, fall, and winter) or room directions (north vs. south facing). The lowest median daytime light intensity was observed at nonwindow beds in north-facing rooms during the winter (84.8 lux; IQR, 76.0-95.8). Further studies evaluating the incidence of in-hospital outcomes between patients hospitalized in window and nonwindow beds are needed.

Risk Factors for Pressure Ulcers at the Ala of Nose in Oral Surgery.

A quality review revealed pressure ulcers at the ala of nose in 16 cases (2.2%) over 3 years. We therefore retrospectively investigated the risk factors for alar pressure ulcers from nasal tubes. Male gender was the highest risk factor (odds ratio = 9.1411; 95% confidence interval = 1.680-170.58), and the second highest risk factor was duration of anesthesia (odds ratio = 1.0048/min of anesthesia; 95% confidence interval = 1.0034-1.0065). Male gender and duration of anesthesia appear to be risk factors for nasal tube pressure ulcers at the ala of nose in patients.

Physiological and microbiological verification of the benefit of hair washing in patients with skin conditions of the scalp.

BACKGROUND: It is unclear whether hair washing is effective against scalp eruption and pruritus caused by seborrheic dermatitis or psoriasis vulgaris. AIMS: To assess whether a proper hair-washing regimen, including the use of antibacterial shampoo, can ameliorate scalp eruption symptoms and alter the composition of the scalp microflora. METHODS: Eighteen patients with seborrheic dermatitis or psoriasis vulgaris scalp eruptions were instructed in proper techniques of daily hair washing, rinsing, and shampooing, which they underwent for 12 weeks. They used control shampoo in weeks 1-4 and 9-12, and an antibacterial shampoo during weeks 5-8. At the start of the test period and at weeks 4, 8, and 12, we assessed scalp symptoms (erythema, scaling/desquamation, dryness, itchiness, and scratching scars); microbial DNA levels from lesion and nonlesion areas; and levels of interleukin (IL)-1α, IL-1ra, and total protein in the scalp's horny layer. RESULTS: Compared to baseline values, scaling/desquamation and itchiness improved significantly at weeks 8 and 12. Other observed skin symptoms also improved over time. Malassezia colonization levels in lesion and nonlesion areas decreased gradually; the decrease was significant at week 8 in lesion areas and at weeks 4 and 8 in nonlesion areas. Bacterial colonization levels also decreased gradually, achieving significance in lesion areas at week 4. Gradual decreases in IL-1ra/IL-1α level showed statistical significance at weeks 4 and 12, while the protein quantity significantly decreased at week 12. CONCLUSION: Proper hair washing improved scalp condition symptoms, and possibly the underlying etiology.

Adherence to oral and topical medication in 445 patients with tinea pedis as assessed by the Morisky Medication Adherence Scale-8.

BACKGROUND: Adherence is defined as the extent to which a person's behavior corresponds with recommendations from health care providers. Adherence to treatment is an important factor for a good therapeutic outcome. OBJECTIVES: This study aimed to examine the adherence of patients with tinea pedis and to clarify the factors related to it. MATERIALS AND METHODS: We assessed medication adherence for oral and topical drugs using a translated version of the Morisky Medication Adherence Scale-8 (MMAS-8) together with other background factors in 445 Japanese patients with tinea pedis, using a questionnaire in a web-based monitoring system. RESULTS: Overall, high, medium and low adherence rates as assessed by MMAS-8 were 8.7%, 31.7% and 59.6% for oral medication, and 8.6%, 17.4% and 74.0% for topical medication, respectively. The adherence level was significantly higher for oral medication than for topical medication. Subgroup analyses showed that the adherence level for topical medication was significantly higher when topical and oral medications were used in combination than when topical medication was used alone. A low adherence level was shown in employed patients, those for whom their oral medication had not been effective and those with topical medication who had visited their hospital less often than once every six months. CONCLUSION: Patient adherence to therapy can be effectively improved by selecting highly effective medication while considering the prescription of topical and oral antifungal medications concomitantly, by carefully selecting a therapy plan for employed patients and by encouraging patients to visit their doctor regularly.

Characterization of socioeconomic status of Japanese patients with atopic dermatitis showing poor medical adherence and reasons for drug discontinuation.

BACKGROUND: Patients' high adherence to medication is indispensable for the management of skin diseases including atopic dermatitis. We previously showed poor medication adherence in Japanese dermatological patients. OBJECTIVE: This study was conducted to determine the level of adherence to oral or topical medication in Japanese patients with atopic dermatitis, attempting to characterize the socioeconomic status of those patients with poor adherence. METHODS: A web questionnaire survey on demographic data as well as adherence level was conducted on patients registered in the monitoring system. Adherence level was assessed with Morisky Medication Adherence Scale-8 (MMAS-8). Among a total of 3096 respondents with dermatological disorders, data of 1327 subjects with atopic dermatitis were extracted and analyzed. RESULTS: More than 80% of subjects felt that both oral and topical medications were safe and efficacious, while less than 60% of them were satisfied with their treatment. Levels of adherence to oral and topical treatments were evaluated with MMAS-8, giving scores of 4.6 and 4.2, respectively. Demographic factors such as gender, marital status, state of employment, alcohol consumption, frequency of hospital visits, and experience of drug effectiveness had a significant impact on the degree of adherence to treatment. CONCLUSION: Medication adherence level in Japanese subjects with atopic dermatitis was relatively low compared with that of other chronic diseases. Our survey has characterized patients with poor adherence, who are good targets for interventions to maximize potentially limited healthcare resources.

Transient improvement of urticaria induces poor adherence as assessed by Morisky Medication Adherence Scale-8.

Poor adherence to medication is a major public health challenge. Here, we aimed to determine the adherence to oral and topical medications and to analyze underlying associated factors using the translated Japanese version of Morisky Medication Adherence Scale-8 regarding urticaria treatment. Web-based questionnaires were performed for 3096 registered dermatological patients, along with a subanalysis of 751 registered urticaria patients in this study. The adherence to oral medication was significantly associated with the frequency of hospital visits. Variables that affected the adherence to topical medication included age and experience of drug effectiveness. The rate of responses that "It felt like the symptoms had improved" varied significantly among the dermatological diseases treated with oral medications. Dermatologists should be aware that adherence to the treatment of urticaria is quite low. Regular visits and active education for patients with urticaria are mandatory in order to achieve a good therapeutic outcome by increasing the adherence.

Poor adherence to medication as assessed by the Morisky Medication Adherence Scale-8 and low satisfaction with treatment in 237 psoriasis patients.

Previously we assessed the medication adherence for oral and topical remedies by a translated Japanese version of the Morisky Medication Adherence Scale-8 (MMAS-8) together with socioeconomic backgrounds in 3096 Japanese dermatological patients, and found the medication adherence, especially to topical drugs, was poor in these patients. In order to elucidate the disease-specific sociomedical factors, we further sub-analyzed the medication adherence in 237 psoriasis patients and compared it with that in other dermatological diseases such as atopic dermatitis, urticaria or tinea. This study was conducted among patients registered in monitoring system and 3096 eligible patients were enrolled. Our web-based questionnaire included the following items such as age, sex, annual income, main health-care institution, experience of effectiveness by oral or topical medication, overall satisfaction with treatment, and MMAS-8 for oral or topical medication. Mean adherence score by MMAS-8 was 5.2 for oral and 4.3 for topical medication. More patients with psoriasis used a university hospital and fewer used a private clinic compared with those with the other skin disease patients. Experience of drug effectiveness by oral medication and overall satisfaction with treatment was lower in psoriasis patients than in other patients. In oral medication, significantly better adherence was observed in those of higher age and with higher annual income. The adherence to medication, especially to topical drugs, was poor in 237 psoriasis patients. We speculated that some severe psoriasis patients were not sufficiently treated systemically and were resistant to topical therapy, leading to poor adherence.

Post-mastectomy benign lymphangioendothelioma of the skin following chronic lymphedema for breast carcinoma: a teaching case mimicking low-grade angiosarcoma and masquerading as Stewart-Treves syndrome.

Benign lymphangioendothelioma (BL) represents a very rare lymphatic vascular proliferation. Our aim is to be aware that owing to its characteristic features, pathologists can easily misinterpret it as cutaneous low-grade angiosarcoma when examining only small specimens. In the present case, multiple small and yellowish to reddish soft nodules were noticed in the edematous left arm of a 54-year-old Japanese female 4 years after the radical mastectomy with axillary lymph nodes dissection and following radiotherapy to the chest for the left breast carcinoma. The biopsy specimen showed an ill-defined lesion composed of a proliferation of irregular and sometimes anastomosing vascular structures in the dermis, lined by endothelial cells having mildly hyperchromatic and pleomorphic nuclei, but no mitotic figures. As the lesion grew within deeper dermis, these proliferating vessels dissected dermal collagenous bands, occasionally arranged in low-papillary projections and/or characteristic hobnail cytomorphology. We first interpreted it as low-grade angiosarcoma following chronic lymphedema due to the operation, i.e., the so-called Stewart-Treves syndrome. Although additional treatments were performed for 7 years, she had neither local invasion nor metastases of these tumors, respectively, and was alive and well. Retrospective immunohistochemical findings demonstrated that these mildly atypical endothelial cells were strongly positive for lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 as well, and MIB-1 labeling index was less than 1%. Therefore, we finally made a diagnosis of BL of the skin. MIB-1 labeling index might be useful and adjunctive aids for reaching the correct diagnosis of cutaneous BL, especially in case of small or inadequate specimens.Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_197.

D1-like dopamine receptors antagonist inhibits cutaneous immune reactions mediated by Th2 and mast cells.

BACKGROUND: Dopamine transduces signals via five subtypes of G protein-coupled receptors. Among these subtypes, the D1 and D5 receptors belong to the D1-like group. Although dopamine is known to mediate immune responses, its involvement in cutaneous immunity remains unclear. OBJECTIVE: The aim of this study is to determine the role of dopamine and its D1-like receptors in cutaneous immune responses. METHODS: By using the D1-like receptor antagonist SCH 23390, we examined the role of D1-like receptors in murine models of Th1-type contact hypersensitivity and Th2-type atopic dermatitis in vivo, and in mast cells and Th2 cell differentiation in vitro. RESULTS: Administration of SCH 23390 did not affect Th1-type contact hypersensitivity but suppressed the immediate-type reaction (ITR) and the late phase reaction (LPR) in the atopic dermatitis model. In addition, SCH 23390-treated mice showed higher IFN-γ and lower IL-4 mRNA levels in the ear skin of challenged mice than did non-treated mice as analyzed by real-time RT PCR. Consistently, the passive cutaneous anaphylaxis reaction was significantly reduced in SCH 23390-treated mice. Moreover, dopamine enhanced mast cell degranulation and Th2 cell differentiation, and both activities were abrogated by SCH 23390. CONCLUSION: These findings suggest that the D1-like receptors mediate immediate and late phase skin reactions by promoting Th2 induction and mast cell degranulation.

Acicular, but not globular, titanium dioxide nanoparticles stimulate keratinocytes to produce pro-inflammatory cytokines.

Titanium dioxide (TiO2 ) nanoparticles, widely used for daily products, are believed to be biologically inert, but they may cause adverse effects on cells, presumably depending on the particle size and shape. One of the critical targets of TiO2 particles is epidermal keratinocytes, and their initial response to TiO2 may be production of pro-inflammatory cytokines. We therefore investigated the effects of four types of TiO2 particles on cytokine expression/production by real-time reverse transcription polymerase chain reaction and enzyme-linked immunoassay. The TiO2 particles included three acicular types, FTL-100 (length, 1.68 µm; diameter, 130 nm), FTL-200 (2.86, 210) and FTL-300 (5.15, 270), and one globular type, PT-301 (diameter, 270 nm). Normal human epidermal keratinocytes (NHEK) were cultured with each of the TiO2 particles. During cultivation, the acicular forms of TiO2 were seen by scanning electron microscopy to be internalized by NHEK. The three acicular particles increased the mRNA expressions and supernatant productions of interleukin (IL)-1α, IL-1ß, IL-6, tumor necrosis factor-α and IL-8 in particle number-dependent manners, whereas globular PT-301 had very weak activity. Thus, TiO2 particles may induce skin inflammation depending on the size and shape, providing knowledge on their health usage.

Combination of skin-directed therapy and oral etoposide for smoldering adult T-cell leukemia/lymphoma with skin involvement.

Approximately 50% of patients with adult T-cell leukemia/lymphoma (ATLL) have skin involvement, and the smoldering, skin lesion-bearing cases are often treated with various skin-directed therapies, such as phototherapy and radiation therapy. Daily oral administration of etoposide plus prednisolone (EP) is also used for smoldering-type ATLL. However, it remains unclear whether these therapies improve patients' survival. We retrospectively analyzed the prognosis of patients with smoldering, skin lesion-bearing ATLL (n = 62), who were treated, as first therapy, with one skin-directed therapy (n = 29), oral EP alone (n = 14) or a combination of skin-directed therapy and oral EP (n = 19). Multivariate analysis revealed that the hazard ratios (HRs) for the overall survival (OS) and progression-free survival (PFS) with the combination therapy were significantly lower than those with the skin-directed therapy (HR 0.1, p = 0.001; HR 0.2, p = 0.002, respectively). These results suggest that the combination of skin-directed therapy and oral EP improves the clinical outcome of patients with smoldering, skin lesion-bearing ATLL.

Defective epidermal innate immunity and resultant superficial dermatophytosis in adult T-cell leukemia/lymphoma.

PURPOSE: Superficial dermatophytosis is quite commonly seen in patients with adult T-cell leukemia/lymphoma (ATLL), as approximately 50% of the patients develop cutaneous mycotic infections. Because superficially infected fungi in the stratum corneum of the epidermis cannot directly contact with T cells infiltrating in the upper dermis, some perturbation of epidermal innate immunity has been postulated. Interleukin (IL)-17-producing helper T cells (Th17) can induce the keratinocyte production of antimicrobial peptides such as human ß defensin (HBD)-2 and LL-37, which play an essential role in cutaneous innate immunity. EXPERIMENTAL DESIGN: We investigated the frequency of circulating Th17 cells, serum levels of cytokines, and epidermal expression of HBD-1, 2, 3, and LL-37 in ATLL patients with or without superficial dermatophytosis. RESULTS: The frequency of peripheral Th17 cells and the serum level of IL-17 was significantly decreased in ATLL patients, whereas the serum IL-10 and TGF-ß1 levels were increased as compared with healthy controls. Furthermore, ATLL patients with dermatophytosis had higher IL-10 and TGF-ß1 levels and lower IL-17 levels than did those without dermatophytosis. Immunohistochemical study revealed that the epidermal expression of both HBD-2 and LL-37 were significantly lower in ATLL patients with dermatophytosis than in non-ATLL patients with dermatophytosis. CONCLUSIONS: Taken together, these results suggest that the keratinocyte production of antimicrobial peptides promoted by Th17 cells is reduced in ATLL patients, leading to the perturbed innate immunity and the frequent occurrence of superficial dermatophytosis.

A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: possible immunological state of the intrinsic type.

BACKGROUND: Atopic dermatitis (AD) can be classified into the major extrinsic type with high serum IgE levels and impaired barrier, and the minor intrinsic type with normal IgE levels and unimpaired barrier. OBJECTIVE: To characterize the intrinsic type of Japanese AD patients in the T helper cell polarization in relation to the barrier condition. METHODS: Enrolled in this study were 21 AD patients with IgE<200kU/L (IgE-low group; 82.5±59.6kU/L) having unimpaired barrier, and 48 AD patients with IgE>500kU/L (IgE-high group; 8.050±10.400kU/L). We investigated filaggrin gene (FLG) mutations evaluated in the eight loci common to Japanese patients, circulating Th1, Th2 and Th17 cells by intracellular cytokine staining and flow cytometry, and blood levels of CCL17/TARC, IL-18, and substance P by ELISA. RESULTS: The incidence of FLG mutations was significantly lower in the IgE-low group (10.5%) than the IgE-high group (44.4%) (normal individuals, 3.7%). The percentage of IFN-γ-producing Th1, but not Th2 or Th17, was significantly higher in the IgE-low than IgE-high group. Accordingly, Th2-attracting chemokine CCL17/TARC, was significantly lower in the IgE-low than the IgE-high group. There were no differences between them in serum IL-18 levels, or the plasma substance P levels or its correlation with pruritus. CONCLUSION: The IgE-low group differed from the IgE-high group in that it had much less FLG mutations, increased frequency of Th1 cells, and lower levels of CCL17. In the intrinsic type, non-protein antigens capable of penetrating the unimpaired barrier may induce a Th1 eczematous response.