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Recent advances in biologic treatments have made clear skin a realistic treatment goal for psoriasis. However, clear skin may not uniformly translate to an absence of impact on patients' quality of life. This retrospective observational study aimed to elucidate the factors influencing patient-reported outcomes in patients with psoriasis who have demonstrated successful clinician-reported outcomes on using biologics. A total of 96 patients who have achieved a ≥75% improvement in Psoriasis Area and Severity Index (PASI) scores with ≥6 months of biologic treatment were included. Their median PASI score was 0.4, with 37.5% having achieved PASI 100 (clear skin). Furthermore, 47.9% reported no impact of psoriasis on their quality of life (Dermatology Life Quality Index [DLQI] score 0 or 1), while 52.1% reported a negative impact (DLQI score ≥2). Notably, 28.1% of the participants had a history of biologic treatment failure, defined as the inability to achieve or sustain a 75% PASI improvement with the previously used biologic agent. Multivariable logistic regression analysis revealed a positive association between achieving PASI 100 and reporting no impact of psoriasis on quality of life (adjusted odds ratio [aOR] 3.88, 95% confidence interval [CI] 1.49-10.91, P = 0.007). Conversely, prior biologic treatment failure was negatively associated with reporting no impact of psoriasis on quality of life (aOR 0.13, 95% CI 0.02-0.65, P = 0.023). Furthermore, among patients with clear skin, those with experience of previous biologic treatment failure reported significantly lower quality of life than those without such experience (P = 0.033). In conclusion, minimal residual skin lesions and prior biologic treatment failure were associated with poorer patient-reported outcomes in patients with psoriasis. Opting for a biologic agent with the highest predicted efficacy, rather than pursuing a "step-up" approach with a higher possibility of treatment failure, may be a more suitable strategy in the biologic treatment of psoriasis., (© 2024 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Competing Interests: Conflicts of interest None disclosed.

Competing Interests: The authors have nothing to disclose.

The matricellular secreted protein acidic and rich in cysteine (SPARC; also known as osteonectin), is involved in the regulation of extracellular matrix (ECM) synthesis, cell-ECM interactions, and bone mineralization. We found decreased SPARC expression in aged skin. Incubating foreskin fibroblasts with recombinant human SPARC led to increased type I collagen production and decreased matrix metalloproteinase-1 (MMP-1) secretion at the protein and mRNA levels. In a three-dimensional culture of foreskin fibroblasts mimicking the dermis, SPARC significantly increased the synthesis of type I collagen and decreased its degradation. In addition, SPARC also induced receptor-regulated SMAD (R-SMAD) phosphorylation. An inhibitor of transforming growth factor-beta (TGF-β) receptor type 1 reversed the SPARC-induced increase in type I collagen and decrease in MMP-1, and decreased SPARC-induced R-SMAD phosphorylation. Transcriptome analysis revealed that SPARC modulated expression of genes involved in ECM synthesis and regulation in fibroblasts. RT-qPCR confirmed that a subset of differentially expressed genes is induced by SPARC. These results indicated that SPARC enhanced ECM integrity by activating the TGF-β signaling pathway in fibroblasts. We inferred that the decline in SPARC expression in aged skin contributes to process of skin aging by negatively affecting ECM integrity in fibroblasts.

Background: Factors other than efficacy and safety could influence the survival of biologics in patients with psoriasis. Little is known about whether different disease groups affect drug survival of biologics or not., Objective: This study aimed to investigate whether the availability of alternative biologics and disease groups could influence drug survival of biologics approved for psoriasis and psoriasis arthritis (PsA)., Methods: A nationwide population-based retrospective cohort study was conducted using the Health Insurance and Review Assessment data in Korea between January 2009 and August 2019., Results: The drug survival analysis included 5,634 biologic episodes. Ustekinumab was the most frequently prescribed drug (n=2,488, 44.2%). Multivariable time-dependent Cox regression analysis showed that higher age, female sex, no comorbidity, concomitant cyclosporine or acitretin use, biologic-experienced and use of tumor necrosis factor (TNF)-α inhibitors were predictors of drug discontinuation. PsA was a predictor of drug persistence, particularly for TNF-α inhibitors. Ustekinumab and adalimumab discontinuation significantly increased after introducing secukinumab and ustekinumab, respectively., Conclusion: The availability of alternative biologics and disease groups affect biologic drug survival in patients with psoriasis and PsA., Competing Interests: The authors have nothing to disclose., (Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Background: With accumulating evidence that achieving a 90% improvement in the Psoriasis Area and Severity Index score (PASI90) has better correlation with improved health-related quality of life as compared to PASI75 achievement, there has been demand for establishing new treatment goals for psoriasis. We investigated whether the short-term PASI90 achievement would predict longer drug survival as compared to PASI75 achievement., Objective: We investigated whether the short-term PASI90 achievement would predict longer drug survival as compared to PASI75 achievement., Methods: This single-center retrospective cohort study reviewed 180 treatment series in 128 patients with plaque psoriasis, who were treated with tumor necrosis factor-alpha inhibitors (n=12), ustekinumab (n=88), secukinumab (n=23), guselkumab (n=45), and ixekizumab (n=12). The first effectiveness assessment, usually performed within 12 to 20 weeks, was considered a short-term treatment response to biologics., Results: After adjustment for covariates, time-dependent Cox proportional hazards regression analysis showed that moderate responders (short-term achievement of ≥PASI75 but

Background: In psoriasis treatment, not all body regions improve simultaneously after clinical interventions., Objective: This study was aimed at evaluating clinical responses across body regions, which may differentially influence patient treatment plans., Methods: This prospective, observational, and multi-center study was conducted in Koreans who adhered to ustekinumab treatment based on criteria per local label and reimbursement guidelines. A total of 581 were included in this analysis., Results: The mean (±standard deviation) psoriasis area severity index (PASI) score at baseline, age, disease duration, and body surface area (%) were 18.9±9.69, 44.2±13.29 years, 11.3±9.65 years, and 27.8±17.83, respectively. Across the head and neck, upper extremities, trunk, and lower extremities, the correlation between the PASI sub-scores for the upper and lower extremities was the highest (r=0.680). The mean PASI sub-score for the lower extremities was the highest at baseline. PASI90 and PASI100 scores were the highest for the head and neck region, indicating the highest response rates, while those for the lower extremities were consistently low at all visits., Conclusion: We found differences in regional ustekinumab responses, with the lower extremities being the most difficult to treat. These findings should be considered in psoriasis treatment., Competing Interests: CONFLICTS OF INTEREST: Dr. Sang Wook Son has no conflict of interest to declare. Dae Young Yu, Youngdoe Kim, and Dr. YoungJa Lee are employees of Janssen Korea Ltd. Dr. Hyo Hyun Ahn performed phase II clinical trial sponsored by Regeneron, and phase III trial by Novartis, Pfizer, and Galderma. Dr. Yong Hyun Jang served as a speaker or consultant for AbbVie, Eli Lilly, GlaxoSmithKline, LEO Pharma, Janssen, Sanofi Genzyme, and Novartis also performed phase III clinical trials sponsored by Pfizer and Eli Lilly. Dr. Joo Young Roh served as a adviser or investigator for clinical trials for Novratis, Eli-Lilly, Janssen, Abbvie, BMS and Regeneron and Sanofi. Dr. Young Bok Lee served as a speaker for AbbVie, Janssen, Novartis and has engaged or been working as a principal investigator or sub-investigator in number of clinical trials sponsored by Janssen, Novartis, and Sanofi. Dr. Ji Yeoun Lee served as a speaker for Novartis. Dr. Myung Hwa Kim served as a speaker for Novartis and has engaged or been working as a principal investigator or sub-investigator in number of clinical trials sponsored by Eli-Lilly, Janssen, LEO Pharma, Novartis, Abbvie, and Sanofi. Dr. Gyeong-Hun Park and Dr. Hyun-Sun Yoon have no conflict of interest to declare. Dr. Sang Woong Youn served as a speaker for AbbVie, Eli Lilly, Janssen, and Novartis and also performed phase III clinical trials sponsored by AbbVie, BMS, Eli Lilly, Janssen, Novartis and UCB., (Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Background: Appropriate primary end points in randomized controlled trials (RCTs) improve the quality of the measurement and enable comparison of the findings with those of other trials., Objective: To assess the quality of reporting primary end points in RCTs recently published in dermatology journals., Methods: We identified 134 primary reports of RCTs among original articles in 4 dermatology journals published from January 2016 to December 2018. Details were extracted from articles, supplements, and trial registries. A multivariable logistic regression analysis was conducted to identify factors associated with adequate primary end point reporting., Results: Adequate primary end point reporting was conducted in 76 of 134 RCTs (56.7%). Nine missed the definition of primary end points, and 13 did not define the timing of primary end points in the publications. Among 113 RCTs reporting primary end points explicitly in the articles, 16 showed discrepancies between registration and publication, and 21 were not able to valuate prespecification of primary end points. Multicenter studies and sponsor-initiated trials were significantly associated with adequate reporting quality after adjusting for covariates., Limitations: Prespecification was evaluated based on a comparison of the article and registry., Conclusions: The quality of primary end point reporting, particularly in prespecification, has remained unsatisfactory in the recent dermatology literature., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background There is emerging evidence that rosacea, a chronic cutaneous inflammatory disease, is associated with various systemic diseases. However, its association with cardiovascular disease (CVD) remains controversial. We aimed to investigate whether patients with rosacea are at increased risk of developing CVD. Methods and Results This retrospective cohort study from the Korean National Health Insurance Service-Health Screening Cohort included patients with newly diagnosed rosacea (n=2681) and age-, sex-, and index year-matched reference populations without rosacea (n=26 810) between 2003 and 2014. The primary outcome was subsequent CVD including coronary heart disease and stroke. Multivariable Cox regression analyses were used to evaluate adjusted hazard ratios for subsequent CVD adjusted for major risk factors of CVD. Compared with the reference population (13 410 women; mean [SD] age, 57.7 [9.2] years), patients with rosacea (1341 women; mean [SD] age, 57.7 [9.2] years) displayed an increased risk for CVD (adjusted hazard ratios, 1.20; 95% CI, 1.03-1.40) and coronary heart disease (adjusted hazard ratios, 1.29; 95% CI, 1.05-1.60). The risk for stroke was not significantly elevated (adjusted hazard ratios, 1.12; 95% CI, 0.91-1.37). Conclusions This study suggests that patients with rosacea are more likely to develop subsequent CVD. Proper education for patients with rosacea to manage other modifiable risk factors of CVD along with rosacea is needed.

Background: Misclassification of study designs of journals can hinder the readers from assessing the strengths and weaknesses of the study and evaluating the applicability of the study in the real-world setting. However, it seems that it is common for authors to neglect to classify the study design., Objective: We aimed to evaluate the accuracy of the classification of study designs and examine the common errors., Methods: This descriptive study analyzed four Asian dermatology journals listed in the science citation index expanded from January 2018 to December 2018. We investigated discrepancies between author-reported and actual study designs. Design Algorithm for Medical Literature on Intervention (DAMI) was used to determine the actual study design., Results: Of the 177 papers analyzed, only 72 articles (40.7%) revealed their study design and among them, 23 articles (32.0%) showed discrepancies between the author-reported and the actual study designs. Case-control studies were the most commonly misclassified study designs by authors., Conclusion: There were considerable differences between the author-reported study design and the actual study design in Asian dermatology journals. Proper classification of study designs by the authors is essential to strengthen evidencebased medicine., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (Copyright © 2020 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Background: There are few studies that directly compared different interventions to improve medical students' clinical reasoning for dermatologic conditions., Objective: To investigate the effectiveness of adding practice with reflection and immediate feedback on traditional dermatology electives in improving medical students' ability in evaluating skin lesions., Methods: The participants were fourth-year medical students of Seoul National University College of Medicine, Korea, who were enrolled to take a 2-week dermatology elective course (n = 87). Students were assigned to one of the three educational interventions: 2-h training involving 10 written clinical cases (experimental); 1-h lecture and 1-h outpatient clinic (lecture); and 2-h outpatient clinic (no intervention). Before and at the end of rotation, diagnostic accuracy was estimated using 20 written clinical cases with photographs (10 novel cases presented in diagnostic training [training set], 10 cases with diagnoses not included in training [control set])., Results: There was a significant interaction effect of intervention×set×time. A post hoc analysis indicated that the students in the experimental group outperformed students in the other two groups only in the training set of the final tests; after completing the 2-week rotation, for the training set, the mean score was higher in the experimental group (7.5 ± 1.3) than in the lecture (5.7 ± 1.6) and no intervention (5.6 ± 1.3) groups, producing an effect size of 1.2 standard deviation (SD) and 1.5 SD, respectively., Conclusion: Practicing written clinical cases with reflection and feedback is superior to a lecture-based approach and yields additional benefits to a dermatology elective, thereby enhancing medical students' ability to accurately diagnose skin lesions., Trial Registration: ClinicalTrials.gov, NCT03472001. Registered 21 March 2018.

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Background: Previous studies have demonstrated efficacy and safety of oral alitretinoin in hand eczema (HE) whereas in palmoplantar pustulosis (PPP), which can be difficult to distinguish from HE, efficacy of alitretinoin is still controversial., Objective: This study aimed to investigate the efficacy and safety of oral alitretinoin in HE and PPP and factors that affect the response of these disorders to alitretinoin., Methods: We retrospectively analyzed Korean adult patients with moderate-to-severe HE and PPP treated with oral alitretinoin, 46 patients for efficacy assessment and 55 patients for safety assessment., Results: Among 46 patients who were treated with alitretinoin for at least 1 month, 29 patients (61.1% in HE and 40.0% in PPP) showed response to alitretinoin in the median 14 weeks after treatment. Hyperkeratotic HE showed higher response rate than either vesicular HE or PPP ( p =0.026 and p =0.026, respectively). However, PPP with hyperkeratotic features showed as much response as hyperkeratotic HE ( p =0.554). When responders and non-responders in total patients were compared, morphology, not diagnosis or initial severity, was the only significantly different factor between the two groups. After alitretinoin discontinuation in responders, relapse rate was 63.6% (7/11) and median time to relapse was 150 days (range, 76~730 days). Adverse events occurred in 47.3% (26/55); however, there were no serious adverse events., Conclusion: In HE or PPP, lesions with hyperkeratotic morphology can be predicted to respond well to alitretinoin regardless of diagnosis., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (Copyright © 2019 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Background: Previous epidemiologic studies of the natural course of urticaria mainly focused on chronic spontaneous urticaria and were conducted at hospitals. The natural course of new-onset urticaria in the general population is unknown., Methods: Patients with new-onset urticaria were identified from the National Health Insurance Service-National Sample Cohort data. Patients who had at least one visit for urticaria in 2002 and 2003 were excluded and the study cohort consisted of 1,027,620 subjects with no history of urticaria. We analyzed cumulative incidences of urticaria, chronic urticaria, and chronic urticaria remission using the life table estimation method from 2004 to 2013. Their association with related factors was analyzed using the Cox proportional hazards analysis., Results: From 2004 to 2013, a total of 49,129 patients with new-onset urticaria were identified. The 10-year cumulative incidence rate of urticaria for the general population was 4.9% and that of chronic urticaria among patients with new-onset urticaria was 7.8%. Remission rates of chronic urticaria were 52.6% at 1 year and 88.9% at 5 years. Age, sex, residential area, and autoimmune thyroid disease were significantly associated with urticaria or chronic urticaria, but not with chronic urticaria remission, after adjusting for covariates. Female individuals were more likely to have new-onset urticaria but less likely to develop chronic urticaria compared with male individuals., Conclusions: During the 10-year follow-up period, only a small proportion of patients with new-onset urticaria developed chronic urticaria. Remission was achieved in the majority of patients with chronic urticaria regardless of demographic characteristics or accompanying thyroid disease., (Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: A few anecdotal case reports demonstrated that tofacitinib improved nail changes associated with AA., Objective: To investigate nail changes in patients with AA treated with tofacitinib and evaluate the relationship between nail and hair responses to tofacitinib., Methods: This is a retrospective study of 33 adult patients with moderate-to-severe AA treated with oral tofacitinib monotherapy for at least 4 months., Results: Fifteen patients had nail involvement and demonstrated more severe hair loss than those without nail involvement (p = .040). However, there was no significant difference in hair regrowth between two groups. Of 15 patients with nail involvement, 11 (73.3%) showed improvement regardless of type of nail change; the first improvement was observed at a median of 5 months (range, 1-11) after administration. Nail improvement was associated with neither initial severity of hair loss nor hair response to tofacitinib. Nail improvement tended to occur later than hair regrowth., Conclusions: Oral tofacitinib monotherapy improves nail involvement associated with AA. Nail involvement is not a poor prognosis factor in hair regrowth with tofacitinib treatment and there is no evident relationship between nail and hair responses.

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Gasdermin (GSDM)‑C is a member of the GSDM gene family and is expressed in the epithelial cells of various tissue types, including skin. GSDMC expression is induced by ultraviolet (UV) irradiation and contributes to UV‑induced matrix metalloproteinase 1 expression in human skin keratinocytes. However, how UV irradiation induces GSDMC expression remains unclear. The present study aimed to investigate the role of transient receptor potential cation channel subfamily V member 1 (TRPV1) and a calcium/calcineurin‑signaling pathway in UV‑induced GSDMC expression in human skin keratinocytes. Suppression of TRPV1 activity by treatment with the TRPV1 antagonists capsazepine and ruthenium red significantly reduced UV‑induced GSDMC expression, whereas direct activation of TRPV1 by capsaicin, a TRPV1 agonist, increased GSDMC expression. The results demonstrated that extracellular calcium and calcineurin activity may be necessary for UV‑induced GSDMC expression in HaCaT cells. In addition, UV‑induced GSDMC expression was either decreased or increased following knockdown or overexpression of nuclear factor of activated T‑cells, cytoplasmic 1 (NFATc1), respectively. These data suggested that TRPV1 may serve an important role in the induction of GSDMC expression by UV and that UV‑induced GSDMC expression may be mediated via a calcium/calcineurin/NFATc1 pathway.

Background: The appropriate classification of study designs is important for review and assessment of the relevant scientific literature as a basis for decision making; however, little is known about whether study designs have been appropriately reported in the dermatology literature., Objective: We aimed to validate the study designs in the dermatology literature and investigate discrepancies between author-reported and actual study designs., Methods: We reviewed all issues of 3 major dermatology journals from January to December 2016. A total of 295 original articles investigating associations between exposures and health outcomes were included for analysis. We used a validated algorithm to classify the study designs., Results: Among the 295 articles, 174 (59.0%) clearly mentioned the study design in the text. All interventional studies were correctly classified on the basis of study design (n = 42); however, 35 of 132 observational studies (26.5%) showed discrepancies between the author-reported and actual study design. When the author-reported design was a prospective cohort, retrospective cohort, or case-control study (n = 61), approximately half of the studies were misclassified by the authors (n = 30)., Limitations: We analyzed only 3 journals in the dermatology field., Conclusions: Our findings revealed substantial discrepancies between author-reported and actual study designs in the dermatologic literature, particularly among observational studies., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Background: Ultraviolet (UV) radiation plays important roles in various skin diseases including premature aging and cancer. UV has been shown to regulate the expressions of many genes including matrix metalloproteinases (MMPs). Gasdermin C (GSDMC) belongs to Gasdermin family and is known to be expressed in the epithelial cells of many tissues including the skin. However, the functions of GSDMC remain poorly understood., Objective: We aimed to investigate the role of GSDMC in UV-induced MMP-1, MMP-3, and MMP-9 expressions in human skin keratinocytes., Methods: Primary human skin keratinocytes and an immortalized human skin keratinocyte cell line (HaCaT cells) were irradiated with UV. Knockdown and overexpression of GSDMC were performed to study the effect of GSDMC. The mRNA and protein levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively., Results: We found that GSDMC expression is increased by UV irradiation in human skin keratinocytes. Further studies showed that GSDMC expression is increased at relatively late time points after UV irradiation and that this GSDMC induction plays important roles in the expressions of MMP-1, but not of MMP-3 and MMP-9, and the activations of ERK and JNK induced by UV. In addition, we found that overexpression of GSDMC increases the MMP-1 expression and the activities of ERK and JNK and that GSDMC-induced MMP-1 expression is suppressed by inhibition of ERK or JNK activities., Conclusions: Our results suggest that GSDMC is increased by UV radiation and contributes to UV-induced MMP-1 expression through the activation of ERK and JNK pathways., (Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Background: Bacterial skin infections occur secondarily in conditions involving a vulnerable skin barrier such as atopic eczema, as well as primarily such as impetigo. They are mainly caused by Staphylococcus aureus and Streptococci . Recently, the prevalence of methicillin-resistant S. aureus has been increasing., Objective: To determine the characteristics of community-acquired bacterial skin infections, to observe their antibiotic susceptibility patterns, and to evaluate factors contributing to the treatment response., Methods: We retrospectively reviewed outpatients under 30 years old from 2010 to 2015, from whom we had taken skin swabs for antibiotic susceptibility testing. We collected clinical and microbiological characteristics from the medical records., Results: We evaluated the culture results of 197 patients and reviewed their medical records. Overall, 86.3% (n=170) of the patients responded to the initial treatment regimen. S. aureus was the most commonly isolated pathogen (52.6%) and showed a high resistance rate to penicillin (90.9%) and oxacillin (36.3%). In the multivariable logistic regression analysis, resistance to 3 or more antibiotics ( p =0.044), culture amounts described as "many" ( p =0.040), and non-systemic antibiotic use ( p <0.001) were significantly associated with lower treatment response. However, methicillin resistance was not associated with lower treatment response both in univariable and multivariable analyses., Conclusion: Among young patients, S. aureus was the most predominant pathogen present in bacterial skin infections. Resistance to high numbers of antibiotics and the use of non-systemic antibiotics were associated with lower treatment response. First-generation cephalosporins may be the most effective first-line empirical regimen for bacterial skin infections treated in outpatient settings, regardless of methicillin resistance., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Previous studies have shown that imiquimod-induced psoriasis-like skin inflammation in mice resembles phenotypic changes and cytokine profiles of human psoriasis. However, a psoriasis animal model reflecting the chronic inflammatory course and comorbidities has not yet been established. We aimed to evaluate the imiquimod-applied interleukin (IL)-10 deficient mouse model in comparison with previous models. IL-10 deficient and wild-type (WT) mice received either imiquimod or vehicle cream for 12 days and were sacrificed on day 15. For earlier time point data, either imiquimod or vehicle cream was applied for 2 days, and the mice were sacrificed on day 3. Imiquimod-applied IL-10 deficient mice showed more persistent psoriasis-like inflammation and higher severity index than did WT between day 8 and 15. Histopathologically, they demonstrated significantly thicker epidermis and larger number of CD45+, myeloperoxidase+ and IL-17+ cell counts on day 15. Quantitative reverse transcription-polymerase chain reaction with skin tissue revealed significantly higher imiquimod-induced IL-23p19 expression in imiquimod-applied IL-10 deficient mice on day 15. IL-10 deficient mice also showed significantly higher serum levels of imiquimod-induced IL-17A and tumor necrosis factor-α by enzyme-linked immunosorbent assay on day 15. Furthermore, IL-10 deficient mice showed more prominent increase of spleen weight and decrease of body weight in response to imiquimod application on day 3 and 15. In conclusion, IL-10 deficient mice model with imiquimod application may better reflect severe and persistent psoriasis with systemic inflammatory state., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Allergens tend to sensitize simultaneously. Etiology of this phenomenon has been suggested to be allergen cross-reactivity or concurrent exposure. However, little is known about specific allergen sensitization patterns., Objective: To investigate the allergen sensitization characteristics according to gender., Methods: Multiple allergen simultaneous test (MAST) is widely used as a screening tool for detecting allergen sensitization in dermatologic clinics. We retrospectively reviewed the medical records of patients with MAST results between 2008 and 2014 in our Department of Dermatology. A cluster analysis was performed to elucidate the allergen-specific immunoglobulin (Ig)E cluster pattern., Results: The results of MAST (39 allergen-specific IgEs) from 4,360 cases were analyzed. By cluster analysis, 39items were grouped into 8 clusters. Each cluster had characteristic features. When compared with female, the male group tended to be sensitized more frequently to all tested allergens, except for fungus allergens cluster., Conclusion: The cluster and comparative analysis results demonstrate that the allergen sensitization is clustered, manifesting allergen similarity or co-exposure. Only the fungus cluster allergens tend to sensitize female group more frequently than male group., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Background: Delivery of pathology reports to the patient is a key step in the biopsy pathway, which is important for patient safety in dermatology. Automated systems for facilitating such medical process began in 2010 in our hospital, sending short message service to scheduled patients., Objective: The purpose of this study was to evaluate the delivery of pathology reports to patients and investigate factors that influence this process and annual trends., Methods: We retrospectively reviewed the medical records of all outpatients (n=2,452) who underwent skin biopsy at our department of dermatology in 2009 and 2014. In each year group, we analyzed the proportion of revisiting patients in terms of year, sex, age, season, biopsy method and diagnosis., Results: In 2009, a smaller proportion of patients (205; 91.5%) who had undergone shave or excisional biopsy than of those who had undergone punch biopsy returned (781; 98.0%; p <0.001). This trend was not significant in 2014. Whereas there was no significant difference of return visit ratio between men and women in 2009, a higher proportion of women (754; 98.0%) than men (633; 95.6%) re-visited after skin biopsy to confirm their diagnosis in 2014 ( p =0.008). Three patients with either a malignant tumor or suspected malignant lesion that required complete excision did not return to our clinic., Conclusion: Pathology report delivery rates were fairly satisfactory, regardless of year, age, season, and diagnosis. Sex and biopsy method influenced the return visit ratio. More organized follow-up protocols are required to strengthen patient safety and prevent critical patient drop-out., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Background: Periostin is a novel matricellular protein expressed in many tissues, including bone, periodontal ligament, and skin. Although its expression is prominent in various fibrotic conditions, studies of periostin in localized scleroderma are rare., Objective: To investigate the expression of periostin and other molecules in localized scleroderma., Methods: A retrospective study of 14 patients with confirmed mature stage localized scleroderma was undertaken. Fourteen age-matched and biopsy site-matched subjects with normal skin were included as controls. Collagen fiber deposition, periostin, procollagen, transforming growth factor-β, and matrix metalloproteinase (MMP)-1 expression were assessed and compared between the two groups. Co-localization of α-smooth muscle actin and periostin was evaluated using confocal microscopy., Results: Periostin was predominantly expressed along the dermo-epidermal junction in the controls. Conversely, patients with localized scleroderma demonstrated increased collagen fiber deposition and periostin expression that was more widely distributed along the entire dermis. MMP-1 staining showed increased expression in the epidermis and dermis of patients compared to scanty expression in the controls. A semi-quantitative evaluation showed a higher proportion of excessive collagen bundle deposition (57.1% vs. 7.1%, p =0.013), diffuse periostin positivity (42.9% vs. 0%, p =0.016), and moderate MMP-1 positivity (71.4% vs. 7.1%, p =0.001) in patients than in the controls., Conclusion: Compared to the controls, patients with localized scleroderma had enhanced periostin expression corresponding to increased collagen fiber deposition and unexpected overexpression of MMP-1. The results of this human in vivo study may implicate the pathogenesis of localized scleroderma., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Ultraviolet (UV) irradiation on skin triggers photoageing-related phenotypes such as formation of wrinkles. UV ray upregulates matrix metalloproteinase-1 (MMP-1), which in turn degrades extracellular matrix proteins, mostly collagens. Serum amyloid A1 (SAA1) is an acute-phase protein of which plasma concentration increases in response to inflammation. Although the expression of SAA1 in the skin was reported, its function in the skin is yet to be studied. In this research, we found that the expression of SAA1 was increased in acute UV-irradiated buttock skin and photoaged forearm skin in vivo. UV irradiation also increased SAA1 in normal human epidermal keratinocytes (NHEK), and treatment of recombinant human SAA1 (rhSAA1) induced MMP-1 in normal human dermal fibroblasts (NHDF) but not in NHEK. Next, we demonstrated that NHDF treated with UV-irradiated keratinocyte-conditioned media showed the increased MMP-1 expression; however, this increase of MMP-1 in NHDF was inhibited by knockdown of SAA1 in NHEK. In addition, knockdown of Toll-like receptor 4 (TLR4) inhibited rhSAA1-induced MMP-1 expression in NHDF. Taken together, our data showed that UV-induced SAA1 production in NHEK, and this secreted SAA1 induced MMP-1 expression in NHDF in a paracrine manner through TLR4 signalling pathway. Therefore, our results suggest that SAA1 can be a potential mediator for UV-induced MMP-1 expression in human skin., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cacao beans contain various bioactive phytochemicals that could modify the pathogeneses of certain diseases. Here, we report that oral administration of cacao powder (CP) attenuates UVB-induced skin wrinkling by the regulation of genes involved in dermal matrix production and maintenance. Transcriptome analysis revealed that 788 genes are down- or upregulated in the CP supplemented group, compared with the UVB-irradiated mouse skin controls. Among the differentially expressed genes, cathepsin G and serpin B6c play important roles in UVB-induced skin wrinkle formation. Gene regulatory network analysis also identified several candidate regulators responsible for the protective effects of CP supplementation against UVB-induced skin damage. CP also elicited antiwrinkle effects via inhibition of UVB-induced matrix metalloproteinases-1 expression in both the human skin equivalent model and human dermal fibroblasts. Inhibition of UVB-induced activator protein-1 via CP supplementation is likely to affect the expression of matrix metalloproteinases-1. CP supplementation also downregulates the expression of cathepsin G in human dermal fibroblasts. 5-(3',4'-Dihydroxyphenyl)-γ-valerolactone, a major in vivo metabolite of CP, showed effects similar to CP supplementation. These results suggest that cacao extract may offer a protective effect against photoaging by inhibiting the breakdown of dermal matrix, which leads to an overall reduction in wrinkle formation., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The consumption of dietary antioxidants is considered to be a good strategy against photo-aging. However, the results of previous clinical trials that investigated the effects of oral consumption of high-flavanol cocoa products on skin photo-aging have been contradictory., Objective: The aim of this study was to investigate whether high-flavanol cocoa supplementation would improve the moderately photo-aged facial skin of female participants, by assessing skin wrinkles and elasticity., Methods: We performed a 24-wk, randomized, double-blind, placebo-controlled study to evaluate the effects of oral supplementation of cocoa flavanols on cutaneous photo-aging. All participants were moderately photo-aged Korean women with visible facial wrinkles (age range: 43-86 y). Participants were randomly assigned to receive a placebo beverage or cocoa beverage that contained 320 mg total cocoa flavanols/d. We measured wrinkles, skin elasticity, and hydration at baseline and at 12 and 24 wk. The primary endpoint was the mean percentage change in the average roughness value (Rz) at 24 wk., Results: At 24 wk, the mean percentage change in Rz (primary endpoint) was significantly lower in the cocoa group than in the placebo group (-8.7 percentage points; 95% CI: -16.1, -1.3 percentage points; P = 0.023). The mean percentage changes in gross elasticity, as determined by a cutometer, also differed between the groups at 12 wk (9.1 percentage points; 95% CI: 1.5, 16.7 percentage points; P = 0.020) and 24 wk (8.6 percentage points; 95% CI: 1.0, 16.2 percentage points; P = 0.027). However, there were no significant differences in skin hydration and barrier integrity between the 2 groups., Conclusions: In moderately photo-aged women, regular cocoa flavanol consumption had positive effects on facial wrinkles and elasticity. Cocoa flavanol supplementation may contribute to the prevention of the progression of photo-aging. This trial was registered at clinicaltrials.gov as NCT02060097., (© 2016 American Society for Nutrition.)

Background: Ultrasonography (US) has recently proved to be useful in diagnostic dermatology. It is convenient to use, completely safe, and provides valuable information., Objective: This study was performed to compare the diagnostic accuracy of US with that of clinical diagnosis in patients with benign subcutaneous lesions., Methods: We retrospectively examined data for 100 patients with benign subcutaneous lesions who were diagnosed with US and either biopsy or surgery at Seoul National University Boramae Hospital between January 2010 and May 2013., Results: Ultrasonography significantly increased the diagnostic yield of benign subcuta-neous lesions (after physical examination [PE], 52.0%; after US, 82.0%; P < 0.005). Rates of sensitivity and specificity for the diagnosis of lipoma were 61.5 and 92.0%, respectively, after PE, and 100 and 100%, respectively, after US. Rates of sensitivity and specificity for the diagnosis of epidermal cysts were 69.4 and 78.4%, respectively, after PE, and 91.8 and 92.2%, respectively, after US. Additionally, rates of sensitivity and specificity for pilomatrixoma were 12.5 and 98.9%, respectively, after PE, and 75.0 and 100%, respectively, after US. Although the accuracy of diagnosis of vascular anomalies and nerve sheath tumors was increased after US, the difference was not significant (vascular anomalies: 40.0% after PE and 80.0% after US; nerve sheath tumors: 28.6% after PE and 42.9% after US)., Conclusions: This study suggests that US is a simple and reliable tool that can aid the diagnosis of benign subcutaneous lesions., (© 2015 The International Society of Dermatology.)