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Background: As global life expectancy increases, an interest in maintaining health and beauty in old age has increased. As a barrier organ, the skin is an ideal model for studying both genetically-programmed (intrinsic) and environmentallyinduced (extrinsic) aging.Current Concepts: Among the extrinsic aging factors, solar ultraviolet radiation is the most important, accounting for 80% of facial skin aging. Other nongenetic factors include air pollution, cigarette smoke, nutrition, temperature, sleep, and stress. Through complex interplay, genome, exposome and microbiome all contribute to skin aging. Intrinsic aging causes thinning of the skin and fine wrinkles, while extrinsic aging leads to thick rubbery skin texture, deep wrinkles and dyspigmentation in exposed areas. Fibroblast senescence is a fundamental mechanism of skin aging, with these cells persisting and exhibiting a senescence-associated secretory phenotype which secrets proinflammatory cytokines. Chronic low-level inflammation associated with aging, termed inflamm-aging, is exacerbated by oxidative damage caused by extrinsic factors.Discussion and Conclusion: Understanding the pathogenesis of skin aging may help in developing anti-aging strategies in general. In addition to applying sunscreen every morning and retinoic acid every night, taking antioxidant-rich foods and maintaining a healthy lifestyle are all important for preventing skin aging.

Eccrine nevus is an extremely rare benign cutaneous hamartoma that usually occurs in childhood and adolescence. It has a wide range of clinical manifestations, and histological findings reveal a proliferation of structurally normal eccrine ducts. Herein, we present a case of eccrine nevus on the neck of an 8-year-old girl. Our literature review reveals that the head and neck region is a rare anatomical location for eccrine nevus as it has a predilection for extremities. Our review also suggests that overlying skin changes are common in eccrine nevus regardless of accompanying localized hyperhidrosis.

Knee disorders that compromise patients' lower leg movements and self-care may put these patients at greater risk of onychomycosis. However, little is known about the prevalence of onychomycosis in patients with knee diseases. This study evaluated the prevalence and characteristics of onychomycosis in patients with knee osteoarthritis. A total of 520 consecutive patients with symptomatic knee osteoarthritis who visited the Department of Orthopedics for a potential knee surgery were evaluated for onychomycosis by PCR-based reverse blot hybridization assay. Of the 520 patients, 308 (59.2%) were diagnosed with onychomycosis. Age (p = 0.004), male sex (p = 0.015), and being barefooted (p = 0.031) were statistically significant risk factors for onychomycosis. Knee disease severity, based on Kellgren-Lawrence grade, was associated with severity of onychomycosis. The impairment of physical function and self-care caused by knee disorders may increase the prevalence of onychomycosis in these patients.

Although pruritic external auditory canal (PEAC) is a relatively common symptom, particularly in the geriatric population, its pathophysiology and appropriate treatment remain to be elucidated. We compared the therapeutic efficacy of pimecrolimus, a topical calcineurin inhibitor (CI), and a moisturizing cream (MC) in patients with PEAC. Thirty-nine patients (73 ears) were prospectively enrolled and treated topically twice daily with the CI (n = 20, 39 ears) or the MC (n = 19, 34 ears) for two weeks. The change in itching sensation was evaluated subjectively using a self-questionnaire at immediately, one month, and two months after self-application, and objectively by changes in erythema grading. Although topical treatment with the CI resulted in a more rapid improvement than treatment with the MC in patients with PEAC, the final outcomes did not differ between the groups. Furthermore, similar improvements in erythema scores were noted. The results of this study suggest that the MC, which rejuvenates the normal physiological status of the ear canal skin, may greatly benefit those elderly patients more susceptible to PEAC, without any concerns about adverse events and underlying comorbidities. Expanding upon the understanding of the role of moisturizers in the treatment of pruritic ears merits attention, as this knowledge provides a good example of the clinical guidelines for the management of PEAC.

Background Little is known regarding oncoproteins other than platelet-derived growth factor subunit B in dermatofibrosarcoma protuberans (DFSP). Moreover, the risk factors for worse prognosis are controversial. Objective We sought to determine the clinicopathologic features and key factors for adverse outcome in DFSP, including the implication of expression of protein kinase B (Akt)/mammalian target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3), extracellular signal regulated kinase (ERK), cyclin D1, and programmed death ligand 1 (PD-L1). Methods Clinicopathologic and immunohistochemical analyses were performed for 44 DFSPs having wide local excision and 92 dermatofibromas as controls. Results Compared with the 35 nonrecurrent DFSPs, the 9 recurrent DFSPs exhibited larger tumor size, deeper invasion beyond the subcutis, and more diverse histologic subtype. The fibrosarcomatous subtype revealed frequent mitotic figures and a high cyclin D1–positive index. The 2 metastatic DFSPs (1 each of the fibrosarcomatous and myxoid subtypes) demonstrated 4 and 11 instances of local recurrence, respectively, as well as larger tumor size, deeper invasion beyond the subcutis, and high expression of cyclin D1. Expression of Akt/mTOR, STAT3, ERK, and PD-L1 ranged from none or low in the primary skin lesions to high in the corresponding metastatic sites. Akt/mTOR and ERK were expressed more frequently in DFSP than in dermatofibroma. Limitations Lack of information on patients before hospital evaluation. Conclusion Complex factors beyond fibrosarcomatous subtype may portend local recurrence or metastasis. Akt/mTOR, STAT3, ERK, and PD-L1 may be associated with development and/or progression of DFSP.

Abnormal histone modification by histone deacetylases (HDACs), including HDAC1 and sirtuin 1 (SIRT1), has been reported to play an important role in the pathogenesis of psoriasis by altering cell proliferation, differentiation, and inflammation. However, findings on the expression level of HDACs in psoriatic skin lack consistency. We assessed the expression of HDAC1, SIRT1, p63, and proliferating cell nuclear antigen (PCNA) in skin tissues from 23 patients with psoriasis (15 with plaque psoriasis and eight with guttate psoriasis) and five healthy individuals using immunohistochemistry, and analyzed their associations with clinical phenotypes of the disease. The expression of HDAC1 and keratinocyte proliferative markers, such as p63 and PCNA significantly increased, whereas that of SIRT1 decreased in the basal layer (P &lt, 0.05) of the patients with psoriasis compared to those in healthy controls. Among the patients with psoriasis, expression of HDAC1, p63, and PCNA was significantly higher in plaque psoriasis than in guttate psoriasis. There was no significant differences in the level of SIRT1 between the two clinical phenotypes. The findings of this study suggest that histone modifications are involved in the pathogenesis of psoriasis and may contribute to the formation of clinical phenotypes.

Background Particulate matter (PM) is an integral part of air pollution, which is a mixture of particles suspended in the air. Recently, it has been reported that PM is associated with increased risks of skin diseases, especially atopic dermatitis in children. However, it is unclear if PM directly goes into the skin and what mechanisms are involved in response to PM. Objective To see whether PM could penetrate into the barrier-disrupted skin, produce reactive oxygen species (ROS), and elicit an inflammatory response. Methods We collected PMs during a winter in Seoul and used cultured keratinocytes for in vitro study and tape-stripped BALB/c mice for in vivo study. Results Keratinocyte cytotoxicity increased in a dose-dependent manner by PM treatment. IL-8 and MMP-1 mRNA expression and protein levels were significantly increased compared to control by qPCR and ELISA, respectively. Cellular ROS production was increased by PM treatment, and antioxidant N-acetyl cysteine pretreatment prevented induction of inflammatory cytokines IL-8 and MMP-1. In PM-treated keratinocytes, electron-dense subcellular particles were observed by transmission electron microscopy. PM was observed inside hair follicles in both intact and barrier-disrupted skin in vivo. Additionally, intercellular penetration of PM was seen in the barrier-disrupted skin. Repeated PM application induced epidermal thickening and dermal inflammation with neutrophil infiltration. Finally, N-acetyl cysteine could ameliorate skin inflammation induced by PM application. Conclusion PM penetrates into the barrier-disrupted skin, causing inflammation, demonstrating detrimental effects in the skin.

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.

A few anecdotal case reports demonstrated that tofacitinib improved nail changes associated with AA.To investigate nail changes in patients with AA treated with tofacitinib and evaluate the relationship between nail and hair responses to tofacitinib.This is a retrospective study of 33 adult patients with moderate-to-severe AA treated with oral tofacitinib monotherapy for at least 4 months.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.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.

Eccrine poroma is a benign solitary tumor with acrosyringeal differentiation that usually occurs on the sole or either side of the foot. Rapid growth of eccrine poroma during pregnancy has rarely been reported. We demonstrate a unique case of a 37-year-old pregnant woman who suffered from enlarged eccrine poroma on her left palm, which was tiny for 10 years but suddenly grew to a size of bean-sized reddish brown colored, pedunculated mass during pregnancy. The patient denied a previous history of trauma or infection to the lesion. Histopathologic findings with a shave biopsy were consistent with eccrine poroma. After the tumor was completely removed by the shave biopsy, no recurrence was noted for 5 months.

Cutaneous lupus erythematosus (CLE) is an inflammatory, autoimmune disease encompassing a broad spectrum of subtypes including acute, subacute, chronic and intermittent CLE. Among these, chronic CLE can be further classified into several subclasses of lupus erythematosus (LE) such as discoid LE, verrucous LE, LE profundus, chilblain LE and Blaschko linear LE. To provide all dermatologists and rheumatologists with a practical guideline for the diagnosis, treatment and long-term management of CLE, this evidence- and consensus-based guideline was developed following the checklist established by the international Reporting Items for Practice Guidelines in Healthcare (RIGHT) Working Group and was registered at the International Practice Guideline Registry Platform. With the joint efforts of the Asian Dermatological Association (ADA), the Asian Academy of Dermatology and Venereology (AADV) and the Lupus Erythematosus Research Center of Chinese Society of Dermatology (CSD), a total of 25 dermatologists, 7 rheumatologists, one research scientist on lupus and 2 methodologists, from 16 countries/regions in Asia, America and Europe, participated in the development of this guideline. All recommendations were agreed on by at least 80% of the 32 voting physicians. As a consensus, diagnosis of CLE is mainly based on the evaluation of clinical and histopathological manifestations, with an exclusion of SLE by assessment of systemic involvement. For localized CLE lesions, topical corticosteroids and topical calcineurin inhibitors are first-line treatment. For widespread or severe CLE lesions and (or) cases resistant to topical treatment, systemic treatment including antimalarials and (or) short-term corticosteroids can be added. Notably, antimalarials are the first-line systemic treatment for all types of CLE, and can also be used in pregnant patients and pediatric patients. Second-line choices include thalidomide, retinoids, dapsone and MTX, whereas MMF is third-line treatment. Finally, pulsed-dye laser or surgery can be added as fourth-line treatment for localized, refractory lesions of CCLE in cosmetically unacceptable areas, whereas belimumab may be used as fourth-line treatment for widespread CLE lesions in patients with active SLE, or recurrence of ACLE during tapering of corticosteroids. As for management of the disease, patient education and a long-term follow-up are necessary. Disease activity, damage of skin and other organs, quality of life, comorbidities and possible adverse events are suggested to be assessed in every follow-up visit, when appropriate.

Nail unit melanoma is a type of acral lentiginous melanoma and requires histopathologic examination for a confirmed diagnosis. However, inadequate biopsy techniques make definitive diagnosis difficult. A 61-year-old man presented with progressive nail pigmentation for 15 years, which was clinically highly suspicious for malignancy. Acral lentiginous melanoma was not detected in punch and longitudinal biopsy specimens, but en bloc excision tissue revealed melanoma. Acral lentiginous melanoma is known to have a heterogeneous pathologic manifestation depending on the pigmented region and the time it takes to progress. In this regard, en bloc excision can be considered as a first-line biopsy technique to diagnose acral lentiginous melanoma, indolent subtype.

“Far East” populations refer to the people of China, Japan, Korea, Mongolia and Taiwan. The primary difference between photoaging in the Caucasian and Far East Asian skin is attributed to the higher protection conferred by more epidermal melanin in the latter population. Studies have shown that facial wrinkle onset in Asian women is delayed by approximately 10 years compared to Caucasians, appearing around 50 years of age. Melanin acts as a double-edged sword, however. Usually the first sign of photoaging in these populations is pigmented spots. Common pigmentary changes in photoaged Asian skin include solar lentigine, melasma, mottled pigmentation, postinflammatory hyperpigmentation, seborrheic keratosis and idiopathic guttate hypomelanosis. Asian skin is especially susceptible to UVA-induced pigmentation. Wrinkling is also a prominent feature of photodamage, and a significant correlation is found between wrinkles and dyspigmentation in both men and women. Cigarette smoking and sun exposure have multiplicative effects on wrinkling in Asians as well, and women tend to have more severe wrinkles than men, partially attributed to postmenopausal hypoestrogenism.

Keloid is an abnormal hyperproliferative scarring process with involvement of complex genetic and triggering environmental factors. Previously published dysregulated gene expression profile of keloids includes genes involved in tumor formation. Pleiotrophin (PTN) is a secreted, heparin-binding growth factor which is involved in various biological functions such as cell growth, differentiation, and tumor progression. Although PTN expression was reported to be increased in hypertrophic scars, there is no study on PTN expression in keloids, and previous microarray results are controversial. To clarify differential expression of PTN in keloids, we investigated the expression of PTN and its interacting molecules in keloid and control fibroblasts, and performed immunohistochemical staining of PTN using tissue arrays. The expressions of PTN, its upstream regulator platelet-derived growth factor subunit B (PDGF-B) and corresponding PDGF receptors were significantly downregulated in keloid fibroblasts compared to normal human fibroblasts, and the decreased PTN protein expression was confirmed by immunohistochemistry as well as Western blot. Moreover, functional downstream receptor protein tyrosine phosphatase β/ζ was significantly upregulated in keloid fibroblasts, supporting overall downregulation of PTN signaling pathway. The lowered PTN expression in keloids suggests a different pathomechanism from that of hypertrophic scars.