SPARC Is Highly Expressed in Young Skin and Promotes Extracellular Matrix Integrity in Fibroblasts via the TGF-ß Signaling Pathway.

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-ß) 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-ß 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.

Complete and transparent reporting of primary end points of randomized trials in the dermatology literature: A comparison of registered and published primary end points.

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.

Effects of reflection and immediate feedback to improve clinical reasoning of medical students in the assessment of dermatologic conditions: a randomised controlled trial.

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.

Natural course of new-onset urticaria: Results of a 10-year follow-up, nationwide, population-based study.

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.

Imiquimod-applied Interleukin-10 deficient mice better reflects severe and persistent psoriasis with systemic inflammatory state.

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.

Misclassification of study designs in the dermatology literature.

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.

Serum amyloid A1 secreted from UV-irradiated keratinocytes induces matrix metalloproteinase-1 in fibroblasts through toll-like receptor 4.

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.

Cocoa Flavanol Supplementation Influences Skin Conditions of Photo-Aged Women: A 24-Week Double-Blind, Randomized, Controlled Trial.

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.

Pulsed intravenous immunoglobulin therapy in refractory ulcerated livedoid vasculopathy: seven cases and a literature review.

Livedoid vasculopathy (LV) is a thrombotic vasculopathy of the skin of unknown origin. No treatment has been validated in this indication, but case reports demonstrated successful use of intravenous immunoglobulins (IVIg) in LV. We assessed the efficacy and tolerability of 2 g/kg IVIg therapy every month for 2∼3 cycles in patients with refractory LV. We analyzed the efficacy, side effects and recurrence after long-term follow-up (51.9 ± 14.0 months) in seven patients with LV treated with 2 g/kg of IVIg. Mean clinical score of sum of erythema, ulceration and pain index (each: 0-3) was 5.7 ± 0.9 before the therapy and significantly lower after therapy (1.1 ± 0.5) (p = 0.001). Even after just one cycle of IVIg, the score decreased significantly from 5.7 ± 0.9 to 3.7 ± 0.9 (p = 0.002), especially the pain score. In one patient, LV has not recurred for over 7 years; six patients experienced recurrence after a mean of 12.7 ± 2.8 months. Out of the six patients, two patients were re-administered IVIg whereas the others were well controlled by conventional therapy. We propose that IVIg is a rapid, effective, and safe therapeutic option in LV refractory to other treatment modalities.

Maternal and Perinatal Factors of Importance for Occurrence and Severity of Infantile Haemangioma.

To determine which patient and maternal factors are associated with the occurrence and the severity of infantile haemangioma (IH), a single-centre retrospective observational study was conducted with 96 haemangioma patients and 143 age-matched control babies, born in the same hospital between March 2012 and March 2013. The IH patients were selected according to diagnosis from dermatologists, either consulted from the department of paediatrics or in outpatient setting. Unplanned female children whose mothers smoked and/or consumed alcohol when pregnant was more likely to have IH (p < 0.0.05). The higher the birth weight, the more superficial the haemangioma (p = 0.023), and localised lesions were more common in singleton babies (p = 0.023) and babies conceived by normal fertilisation (p = 0.002). The occurrence and severity of IH is not only influenced by patient factors but also by maternal factors especially care during pregnancy period. By controlling these factors, the incidence and severity of IH may be lowered.

CCL28 Cannot Replace IgE for Severity by Objective SCORAD Index in Atopic Dermatitis in Children.

BACKGROUND: Recently, CC chemokine ligand28 (CCL28) has been reported as a severity marker in atopic dermatitis. We studied the association between objectively observed lesions and the level of CCL28 in children patients. METHODS: A total of 105 children patients were grouped by the objective Scoring Atopic Dermatitis index (SCORAD). Total IgE, specific IgE, complete blood count, and serum level of CCL28 were evaluated. RESULTS: The mean age of the subjects was 5.3 (range, 0 - 12 years). The median SCORAD was 21.4 and consisted of mild 70%, moderate 25%, and severe 6% disease. There were no statistical differences among severity groups for CCL28 or for total IgE. Total IgE showed positive correlation with eosinophil count (r = 0.429, p < 0.01), and SCORAD (r = 0.210, p < 0.05). CONCLUSIONS: The disease severity of atopic dermatitis in children is not correlated to the level of CCL28, but rather related to that of total IgE.

Long-term topical oestrogen treatment of sun-exposed facial skin in post-menopausal women does not improve facial wrinkles or skin elasticity, but induces matrix metalloproteinase-1 expression.

It is controversial whether treatment with oestrogen stimulates collagen production or accumulation in sun-exposed skin. The aim of this study was to determine the effect of long-term treatment with topical oestrogen on photoaged facial skin, with regard to wrinkle severity, and expression of procollagen and matrix metalloproteinase-1 enzyme. Two groups of 40 post-menopausal women applied either 1 g of 1% oestrone or vehicle cream once daily to the face for 24 weeks. Visiometer R1-R5 values (skin wrinkles) and Cutometer values (skin elasticity) were not significantly improved in the oestrone group after 24 weeks of treatment. Type I procollagen immunostaining did not increase in the oestrone group compared with the control group. However, levels of matrix metalloproteinase-1 mRNA increased robustly (10.3 times) in oestrone-treated skin compared with vehicle-treated skin. Thus, treatment with topical oestrogen may be deleterious in ultraviolet-induced skin ageing, at least in part, through induction of matrix metalloproteinase-1 (MMP-1) expression in human skin.

Impact of residual skin lesions and previous biologic treatment failure on patient-reported outcomes in patients with psoriasis receiving biologic treatment.

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.

Quick and easy correction of a symptomatic pincer nail using a shape memory alloy device.

BACKGROUND: Pincer nails are characterized by the transverse curvature increasing from the proximal to the distal aspect along the longitudinal axis. A novel treatment technique using a shape memory alloy device was recently introduced. OBJECTIVE: To determine the treatment outcomes and safety of a shape memory alloy device. METHODS AND MATERIALS: This was a retrospective analysis of 21 cases of pincer nail of the great toe in 14 patients. Subjective indices (pain, inconvenience, global assessment scores) and objective parameters (transverse angle, width index) on days 0 (D0) and 1 (D1) and weeks 2 (W2) and 12 (W12) were investigated. RESULTS: All parameters started to show significant improvement on D1. From D0 to D1, pain score fell from 3.6 ± 1.0 to 1.5 ± 0.7, inconvenience score fell from 3.3 ± 1.0 to 1.5 ± 0.7, global assessment score increased from 1.5 ± 0.7 to 2.5 ± 0.7, transverse angle improved from 86.4 ± 27.7° to 114.7 ± 21.6°, and width index improved from 67.6 ± 13.1% to 89.0 ± 9.7%. These effects were consistent during 12 weeks of follow-up. Two cases (9.5%) recurred, but symptoms were less severe than before. No complication was identified. CONCLUSION: A shape memory alloy device was an effective and safe way to rapidly correct symptomatic pincer nail deformity.

Evaluation of scientific programs at a large-scale academic congress: lessons from the 22nd World Congress of Dermatology.

BACKGROUND: The organization of a scientific program and the arrangement of the speakers require a considerable amount of time and effort. However, little is known about how to reinforce the participants' satisfaction with scientific programs at a large-scale academic congress with multiple parallel sessions. OBJECTIVES: This study had three main purposes: (1) to create a reference for future congresses, (2) to determine session popularity and participation rate, and (3) to identify which characteristics of sessions can affect the perception of the audience. METHODS: A total of 216 scientific sessions during the 22nd World Congress of Dermatology were evaluated using printed evaluation surveys. RESULTS: The average scores for all sessions and speakers were relatively high. There were significant differences in the numbers of total session scores, collected surveys and speakers for each session category. The number of speakers at each session was not related to the session results. It was found that among the three different session grades (excellent, fair and poor), the proportion of speakers of each grade especially contributed to the perceived quality of the poor-grade sessions. CONCLUSIONS: This survey will help to organize scientific sessions and improve the quality of academic congresses.

A nationwide study of acne treatment patterns in Korea: analysis of patient preconceived notions and dermatologist suggestion for treatment.

Patients often have preconceived notions about acne treatments before visiting dermatologists. The aim of this study was to explore the association between patients' beliefs regarding acne and physicians' suggestion for treatment modality in dermatology clinics. A cross-sectional, nationwide multicentre study was conducted. A total of 1,370 patients completed questionnaires about beliefs about acne treatment before seeking medical care, and 101 dermatologists assessed their acne severity and proposed treatment methods. We found that patients had preconceptions in understanding disease characteristics, assessing subjective acne severity and preferring specific treatment modalities. Dermatologists' determination of topical agents as first-line treatment was affected by disease severity and patients' preferences. They were also more likely to prescribe isotretinoin even in moderate acne compared to oral antibiotics and topical agents. Selections of physical treatments and light-based therapies were affected by patients' preferences, subjective self-evaluation and dermatologists' assessments. Thus, we suggest that acne treatment strategies should incorporate both patients' subjective perceptions and objective clinical practices into a management paradigm.

Association Between Short-Term PASI90 Achievement and Drug Survival of Biologics in Patients with Psoriasis.

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