Clinical Features and Awareness of Hand Eczema in Korea.

BACKGROUND: Hand eczema is one of the most common skin disorders and negatively affects quality of life. However, a large-scale multicenter study investigating the clinical features of patients with hand eczema has not yet been conducted in Korea. OBJECTIVE: To identify the prevalence of various hand diseases, which is defined as all cutaneous disease occurring in hands, and to investigate the clinical features of patients with hand eczema and the awareness about hand eczema in the general population and to compare the prevalence of hand eczema between health care providers and non-health care providers. METHODS: To estimate the prevalence of hand diseases, we analyzed the medical records of patients from 24 medical centers. Patients were assessed by online and offline questionnaires. A 1,000 from general population and 913 hand eczema patients answered the questionnaire, for a total of 1,913 subjects. RESULTS: The most common hand disease was irritant contact dermatitis. In an online survey, the lifetime prevalence of hand eczema was 31.2%. Hand eczema was more likely to occur in females (66.0%) and younger (20~39 years, 53.9%). Health care providers and housewives were the occupations most frequently associated with hand eczema. Winter (33.6%) was the most common season which people experienced aggravation. The 63.0% and 67.0% answered that hand eczema hinders their personal relationship and negatively affects daily living activities, respectively. CONCLUSION: Hand eczema is a very common disease and hinders the quality of life. The appropriate identification of hand eczema is necessary to implement effective and efficient treatment.

Role of Arachidonic Acid in Promoting Hair Growth.

BACKGROUND: Arachidonic acid (AA) is an omega-6 polyunsaturated fatty acid present in all mammalian cell membranes, and involved in the regulation of many cellular processes, including cell survival, angiogenesis, and mitogenesis. The dermal papilla, composed of specialized fibroblasts located in the bulb of the hair follicle, contributes to the control of hair growth and the hair cycle. OBJECTIVE: This study investigated the effect of AA on hair growth by using in vivo and in vitro models. METHODS: The effect of AA on human dermal papilla cells (hDPCs) and hair shaft elongation was evaluated by MTT assay and hair follicle organ culture, respectively. The expression of various growth and survival factors in hDPCs were investigated by western blot or immunohistochemistry. The ability of AA to induce and prolong anagen phase in C57BL/6 mice was analyzed. RESULTS: AA was found to enhance the viability of hDPCs and promote the expression of several factors responsible for hair growth, including fibroblast growth factor-7 (FGF-7) and FGF-10. Western blotting identified the role of AA in the phosphorylation of various transcription factors (ERK, CREB, and AKT) and increased expression of Bcl-2 in hDPCs. In addition, AA significantly promoted hair shaft elongation, with increased proliferation of matrix keratinocytes, during ex vivo hair follicle culture. It was also found to promote hair growth by induction and prolongation of anagen phase in telogen-stage C57BL/6 mice. CONCLUSION: This study concludes that AA plays a role in promoting hair growth by increasing the expression of growth factors in hDPCs and enhancing follicle proliferation and survival.

Long pulsed 1064 nm Nd:YAG laser treatment for wrinkle reduction and skin laxity: evaluation of new parameters.

INTRODUCTION: Among non-ablative devices for wrinkle reduction and skin laxity, long pulsed 1064 nm Nd:YAG laser (LPND) has considerable effectiveness. It can penetrate to deep dermis due to its longer wavelength. This study assesses the efficacy and safety of LPND applying new parameters for skin rejuvenation in Korean subjects. METHODS: A prospective randomized split-faced study was done (n = 20). Half of the face was treated with three passes of LPND at a spot size of 12 mm, 20-24 J/cm(2) fluence, 12 ms width, and frequency of 2 Hz, for three sessions, every four weeks. Outcomes were measured by wrinkle evaluation of blinded investigators, subjects' self-assessment, objective measurements of elasticity, and skin biopsy. RESULTS: Four weeks after the final treatment sessions, the average wrinkle grades of the treated side were reduced by 45.1%. Skin elasticity was significantly increased. The increment of collagen and elastic fiber in papillary dermis was confirmed histologically. No adverse reaction was reported. Pain on the treated side was mild without needing anesthesia. DISCUSSION: The authors studied new parameters for LPND for improvement of wrinkles and skin laxity with fewer treatment sessions without serious complications. Histologic findings corresponded to clinical improvement. CONCLUSION: New parameters of LPND can achieve wrinkle improvement with few side effects.

Decreased ATP synthesis and lower pH may lead to abnormal muscle contraction and skin sensitivity in human skin.

BACKGROUND: Sensitive skin represents hyperactive sensory symptoms showing exaggerated reactions in response to internal stimulants or external irritants. Although sensitive skin is a very common condition affecting an estimated 50% of the population, its pathophysiology remains largely elusive, particularly with regard to its metabolic aspects. OBJECTIVE: The objective of our study was to investigate the pathogenesis of sensitive skin. METHODS: We recruited healthy participants with 'sensitive' or 'non-sensitive' skin based on standardized questionnaires and 10% lactic acid stinging test, and obtained skin samples for microarray analysis and subsequent experiments. RESULTS: Microarray transcriptome profiling revealed that genes involved in muscle contraction, carbohydrate and lipid metabolism, and ion transport and balance were significantly decreased in sensitive skin. These altered genes could account for the abnormal muscle contraction, decreased ATP amount in sensitive skin. In addition, pain-related transcripts such as TRPV1, ASIC3 and CGRP were significantly up-regulated in sensitive skin, compared with non-sensitive skin. CONCLUSIONS: Our findings suggest that sensitive skin is closely associated with the dysfunction of muscle contraction and metabolic homeostasis.

Long-term utility and durability of the therapeutic effects of bimatoprost 0.03% for eyelash augmentation in healthy Asian subjects.

BACKGROUND: Eyelashes of Asians differ from those of Caucasians in morphology and growth characteristics. Ethnic differences also exist for the tolerability profile of prostaglandin analogues. OBJECTIVE: To evaluate the long-term utility and durability of bimatoprost 0.03% in eyelash augmentation in Asian females. METHODS: One cohort received bimatoprost 0.03% for 36 weeks and another for 20 weeks, with the latter cohort followed for 16 weeks after treatment cessation. The primary endpoint was the percent change in eyelash length at week 20. Secondary measures included percent change in eyelash thickness and darkness, physician's Global Eyelash Assessment and patient satisfaction. RESULTS: At week 20, eyelash length was enhanced in a time-dependent manner, with maximum improvement achieved (19.3%; p < 0.0001). Significant improvements in thickness and darkness were also achieved (22.9%, 6.0%; p < 0.0001). 77.8% of subjects improved by ≥1 grade on Global Eyelash Assessment, with 83.1% satisfied/very satisfied. Improvements were maintained with ongoing treatment to 36 weeks, while these effects were progressively lost with discontinuation. CONCLUSION: Bimatoprost 0.03% safely enhanced eyelashes in Asian females, maintained with ongoing treatment. Cessation of treatment was associated with progressive loss of effects.

Valproic acid promotes human hair growth in in vitro culture model.

BACKGROUND: ß-Catenin, the transducer of Wnt signaling, is critical for the development and growth of hair follicles. In the absence of Wnt signals, cytoplasmic ß-catenin is phosphorylated by glycogen synthase kinase (GSK)-3 and then degraded. Therefore, inhibition of GSK-3 may enhance hair growth via ß-catenin stabilization. Valproic acid is an anticonvulsant and a mood-stabilizing drug that has been used for decades. Recently, valproic acid was reported to inhibit GSK-3ß in neuronal cells, but its effect on human hair follicles remains unknown. OBJECTIVES: To determine the effect of VPA on human hair growth. METHODS: We investigated the effect of VPA on cultured human dermal papilla cells and outer root sheath cells and on an in vitro culture of human hair follicles, which were obtained from scalp skin samples of healthy volunteers. Anagen induction by valproic acid was evaluated using C57BL/6 mice model. RESULTS: Valproic acid not only enhanced the viability of human dermal papilla cells and outer root sheath cells but also promoted elongation of the hair shaft and reduced catagen transition of human hair follicles in organ culture model. Valproic acid treatment of human dermal papilla cells led to increased ß-catenin levels and nuclear accumulation and inhibition of GSK-3ß by phosphorylation. In addition, valproic acid treatment accelerated the induction of anagen hair in 7-week-old female C57BL/6 mice. CONCLUSIONS: Valproic acid enhanced human hair growth by increasing ß-catenin and therefore may serve as an alternative therapeutic option for alopecia.

Exomic sequencing of immune-related genes reveals novel candidate variants associated with alopecia universalis.

Alopecia areata (AA) is a common autoimmune disorder mostly presented as round patches of hair loss and subclassified into alopecia totalis/alopecia universalis (AT/AU) based on the area of alopecia. Although AA is relatively common, only 5% of AA patients progress to AT/AU, which affect the whole scalp and whole body respectively. To determine genetic determinants of this orphan disease, we undertook whole-exome sequencing of 6 samples from AU patients, and 26 variants in immune-related genes were selected as candidates. When an additional 14 AU samples were genotyped for these candidates, 6 of them remained at the level of significance in comparison with 155 Asian controls (p<1.92×10(-3)). Linkage disequilibrium was observed between some of the most significant SNPs, including rs41559420 of HLA-DRB5 (p<0.001, OR 44.57) and rs28362679 of BTNL2 (p<0.001, OR 30.21). While BTNL2 was reported as a general susceptibility gene of AA previously, HLA-DRB5 has not been implicated in AA. In addition, we found several genetic variants in novel genes (HLA-DMB, TLR1, and PMS2) and discovered an additional locus on HLA-A, a known susceptibility gene of AA. This study provides further evidence for the association of previously reported genes with AA and novel findings such as HLA-DRB5, which might represent a hidden culprit gene for AU.

Clinical characteristics and prognostic factors in early-onset alopecia totalis and alopecia universalis.

Alopecia totalis (AT) and alopecia universalis (AU), severe forms of alopecia areata (AA), show distinguishable clinical characteristics from those of patch AA. In this study, we investigated the clinical characteristics of AT/AU according to the onset age. Based on the onset age around adolescence (< or ≥ 13 yr), 108 patients were classified in an early-onset group and the other 179 patients in a late-onset group. We found that more patients in the early-onset group had a family history of AA, nail dystrophy, and history of atopic dermatitis than those in the late-onset group. These clinical differences were more prominent in patients with AU than in those with AT. In addition, significantly more patients with concomitant medical disorders, especially allergic diseases were found in the early-onset group (45.8%) than in the late-onset group (31.2%). All treatment modalities failed to show any association with the present hair condition of patients. In the early-onset group, patients with AU or a family history of AA showed worse prognosis, whereas this trend was not observed in the late-onset group. Systemic evaluations might be needed in early-onset patients due to the higher incidence of comorbid diseases. It is suggested that patients with AU or family history of AA make worse progress in the early-onset group than in the late-onset group.

Comparative secretome analysis of human follicular dermal papilla cells and fibroblasts using shotgun proteomics.

The dermal papilla cells (DPCs) of hair follicles are known to secrete paracrine factors for follicular cells. Shotgun proteomic analysis was performed to compare the expression profiles of the secretomes of human DPCs and dermal fibroblasts (DFs). In this study, the proteins secreted by DPCs and matched DFs were analyzed by 1DE/LTQ FTICR MS/MS, semi-quantitatively determined using emPAI mole percent values and then characterized using protein interaction network analysis. Among the 1,271 and 1,188 proteins identified in DFs and DPCs, respectively, 1,529 were further analyzed using the Ingenuity Pathway Analysis tool. We identified 28 DPC-specific extracellular matrix proteins including transporters (ECM1, A2M), enzymes (LOX, PON2), and peptidases (C3, C1R). The biochemically- validated DPC-specific proteins included thrombospondin 1 (THBS1), an insulin-like growth factor binding protein3 (IGFBP3), and, of particular interest, an integrin beta1 subunit (ITGB1) as a key network core protein. Using the shotgun proteomic technique and network analysis, we selected ITGB1, IGFBP3, and THBS1 as being possible hair-growth modulating protein biomarkers.

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.

Lipid ingredients in moisturizers can modulate skin responses to UV in barrier-disrupted human skin in vivo.

BACKGROUND: Chemicals with a molecular weight <500 and adequate lipid solubility can penetrate the intact human skin. As many lipid ingredients in moisturizers have molecular weights <500, the lipid ingredients may penetrate into the skin and affect skin responses to UV; however, little is known about this phenomenon. OBJECTIVE: To evaluate the effects of major lipid ingredients in moisturizers on skin responses to UV in tape-stripped human skin in vivo. METHODS: We evaluated the effects of three major lipid ingredients in moisturizers (cholesterol, linoleic acid, and a synthetic ceramide, N-oleoyl-phytosphingosine) on skin responses to UV in the tape-stripped skin of healthy volunteers. After 2 days of lipid-application, the areas were irradiated with UV, and skin samples were obtained 24h after irradiation. Histologic features and the expression of the markers of collagen metabolism and inflammatory mediators were evaluated. RESULTS: Compared to vehicle, topical cholesterol significantly decreased the degree of dermal inflammatory infiltrates and exocytosis, and also decreased the expression of MMP-1, IL-6, and IL-1ß mRNA. In contrast, topical linoleic acid increased the induction of apoptotic cells, and the expression of MMP-1 and IL-6 mRNA. N-oleoyl-phytosphingosine increased the expression of MMP-1 and IL-6 mRNA, while decreasing the expression of COX-2 mRNA. CONCLUSIONS: Topical cholesterol can protect the barrier-disrupted skin against UV-induced damage, while linoleic acid or N-oleoyl-phytosphingosine alone has the potential to aggravate the damage.

Gene mapping study for constitutive skin color in an isolated Mongolian population.

To elucidate the genes responsible for constitutive human skin color, we measured the extent of skin pigmentation in the buttock, representative of lifelong non-sun-exposed skin, and conducted a gene mapping study on skin color in an isolated Mongolian population composed of 344 individuals from 59 families who lived in Dashbalbar, Mongolia. The heritability of constitutive skin color was 0.82, indicating significant genetic association on this trait. Through the linkage analysis using 1,039 short tandem repeat (STR) microsatellite markers, we identified a novel genomic region regulating constitutive skin color on 11q24.2 with an logarithm of odds (LOD) score of 3.39. In addition, we also found other candidate regions on 17q23.2, 6q25.1, and 13q33.2 (LOD ≥ 2). Family-based association tests on these regions with suggestive linkage peaks revealed ten and two significant single nucleotide polymorphisms (SNPs) on the linkage regions of chromosome 11 and 17, respectively. We were able to discover four possible candidate genes that would be implicated to regulate human skin color: ETS1, UBASH3B, ASAM, and CLTC.

Linkage and association scan for tanning ability in an isolated Mongolian population.

Tanning ability is important, because it represents the ability of the skin to protect itself against ultraviolet (UV) radiation. Here, we sought to determine genetic regions associated with tanning ability. Skin pigmentation was measured at the outer forearm and buttock areas to represent facultative and constitutive skin color, respectively. In our study population consisting of isolated Mongolian subjects, with common histories of environmental UV exposure during their nomadic life, facultative skin color adjusted by constitutive skin color was used to indicate tanning ability. Through linkage analysis and family-based association tests of 345 Mongolian subjects, we identified 2 potential linkage regions regulating tanning ability on 5q35.3 and 12q13.2, having 6 and 7 significant single nucleotide polymorphisms (SNPs), respectively. Those significant SNPs were located in or adjacent to potential candidate genes related to tanning ability: GRM6, ATF1, WNT1, and SILV/Pmel17.

Intrinsic aging- and photoaging-dependent level changes of glycosaminoglycans and their correlation with water content in human skin.

BACKGROUND: Glycosaminoglycans (GAGs) have various structural and physiological regulatory functions in skin, including tissue water maintenance, due to their high water-holding capacity. OBJECTIVE: To investigate changes of GAGs during intrinsic aging and photoaging of human skin and their correlations with water content. METHODS: Samples of sun-protected buttock and sun-exposed forearm skin were obtained from young male (21-30 years, n=8) and female (20-33 years, n=8) subjects, as well as old male (70-78 years, n=8) and female (70-80 years, n=8) subjects, and their epidermal and dermal contents of hyaluronic acid (HA), total sulfated GAG (tsGAG), total uronic acid (tUA), and tissue water were measured. HA content was determined by enzyme-linked immunosorbent assay using HA-binding protein, tsGAG by the sulfated GAG assay kit using 1,9-dimethylmethylene blue, tUA by carbazole reaction, and tissue water by subtraction of tissue dry weight from wet weight. RESULTS: In the buttock, HA was higher in dermis than in epidermis, while tsGAG and tUA were higher in epidermis. In intrinsically aged buttock, epidermal HA and dermal tsGAG and tUA decreased. However, when analyzed for each gender, epidermal tsGAG, tUA, and tissue water decreased only in females. Forearm/buttock ratios of each molecule were compared for determination of photoaging-dependent changes. Forearm/buttock ratios of HA, tsGAG, tUA, and tissue water increased in aged dermis, but showed no change in aged epidermis. When analyzed for each gender, ratios of epidermal HA and tissue water increased only in aged females, while ratios of epidermal tsGAG, tUA, and tissue water decreased only in aged males. Correlations of water content with HA, tsGAG, and tUA were found in epidermis, but not with tsGAG in dermis. CONCLUSION: These intrinsic aging- and photoaging-dependent GAG changes and their correlations with water content provide new insights into the pathophysiology of dry skin in the elderly.

Temporary increase of PPAR-γ and transient expression of UCP-1 in stromal vascular fraction isolated human adipocyte derived stem cells during adipogenesis.

In this study, cells from the stromal vascular fraction of human subcutaneous tissues were induced to differentiate toward adipose cells in vitro for 2 weeks. During adipogenic differentiation, we followed the chronological changes in their morphology with Coherent anti-Stokes Raman scattering (CARS) microscopy and checked the PPAR-γ and UCP-1 expression with RT-PCR. On day 4 after inducing adipogenic differentiation, CARS imaging showed multiple small lipid droplets (LD) distributed peripherally along the cellular membrane. PPAR-γ began to express at this time and increased until day 14 at a steady rate. On day 7, the cells appeared as brown adipocytes with numerous small LD throughout the cytoplasm, and the mRNA level of UCP-1 rose abruptly by 6- to 7-fold. After an additional 7 days, CARS imaging showed the development of a large LD, which is characteristic of white adipocytes, and the mRNA level of UCP-1 slumped significantly. These results demonstrate the possibility that ADSC pass through a brown adipocyte-like stage while differentiating into white adipocytes.