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Cutaneous metastasis from gastric adenocarcinoma is uncommon, and the eyelid is a rare metastatic site. Three patterns of clinical presentation of eyelid metastasis have been described: nodular, infiltrative, and ulcerated. The infiltrative pattern, also known as an inflammatory diffuse pattern or mask-like metastasis, can be easily misdiagnosed as cellulitis or contact dermatitis. Here, we report a case of gastric adenocarcinoma in a 75-year-old man who presented with a localized erythematous plaque on his eyelid that developed four months earlier. The patient had been treated with an antimicrobial agent owing to suspicion of preseptal cellulitis. Gastric adenocarcinoma metastasis was diagnosed on the basis of histopathological examination and immunophenotyping (i.e., cytoplasmic epithelial membrane antigen, cytokeratin- 7, cytokeratin-20, and carcinoembryonic antigen). For patients with malignant neoplasms, persistent skin lesions similar to cellulitis or contact dermatitis should be suspected of metastasis derived from an internal malignancy, even for very rare sites of metastasis.

The clinical features of localized nasal rosacea have not been described in detail. This study was designed to analyze the subtypes and severity of localized nasal rosacea. Our present study included 30 patients with localized nasal rosacea. The erythematotelangiectatic subtype (13/30, 43.3%) was the most common type, followed by the phymatous subtype (9/30, 30%). The duration of rosacea was shorter and the severity of localized nasal rosacea was lower in the erythematotelangiectatic subtype cases compared with the patients with mixed or phymatous subtypes. Almost all of the papulopustular eruptions or phymatous lesions were associated with erythematotelangiectatic lesions. These findings suggest that the erythematotelangiectatic subtype may be considered the initial phase of localized nasal rosacea.

Azole antimycotic agents are known to have anti-inflammatory and anti-cancer effects, which are mediated through their effects on the p38-cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) pathway, as well as anti-oxidant effects. Furthermore, pyridinyl imidazole compounds, such as SB203580 have recently been shown to inhibit melanogenesis. Accordingly, we hypothesized that azole antifungal agents might affect skin pigmentation. We herein investigated the effect of clotrimazole, the most commonly used azole antifungal agent, on melanogenesis. Intriguingly, clotrimazole reduced the melanin content in human melanocytes and mouse melanocytes, as well as in B16F10 mouse melanoma cells. Clotrimazole reduced levels of tyrosinase protein without altering mRNA expression. Simultaneous treatment with a proteasomal inhibitor restored both the suppression of melanin synthesis, and the downregulation of tyrosinase level, by clotrimazole. Clotrimazole also induced the phosphorylation of extracellular signal-regulated kinase (ERK) and PI3K/Akt, while each inhibitor of these two signals abolished the decrease of melanin synthesis by clotrimazole. Thus, our data suggest that clotrimazole inhibits melanin synthesis by promoting the proteasomal degradation of tyrosinase, which is mediated through activation of the ERK and Akt signaling pathways. These results may indicate a new role for clotrimazole as a molecular-mechanism-based, safe depigmenting agent for topical management of hyper-pigmentary sequelae related to fungal infection, or for other skin inflammatory disorders.

The progression of androgenetic alopecia is closely related to androgen-inducible transforming growth factor (TGF)-β1 secretion by hair follicle dermal papilla cells (DPCs) in bald scalp. Physiological levels of androgen exposure were reported to increase reactive oxygen species (ROS) generation. In this study, rat vibrissae dermal papilla cells (DP-6) transfected with androgen receptor showed increased ROS production following androgen treatment. We confirmed that TGF-β1 secretion is increased by androgen treatment in DP-6, whereas androgeninducible TGF-β1 was significantly suppressed by the ROSscavenger, N-acetyl cysteine. Therefore, we suggest that induction of TGF-β1 by androgen is mediated by ROS in hair follicle DPCs. [BMB Reports 2013; 46(9): 460-464]

Non-ablative fractional laser photothermolysis (NAFP) has been used effectively in the treatment of photodamaged skin and scars, with short post-operative recovery times; but, studies evaluating its adverse events and complication rates in Asian population have been limited.To determine the frequency and range of adverse events associated with NAFP treatment in Korean patients.We retrospectively evaluated the outcomes of 754 1550-nm erbium-doped and 102 1927-nm thulium fiber fractional laser treatments in patients with skin phototypes III-IV treated at a single center. Adverse events were identified and tabulated, as were patient demographics and laser parameters.From 856 treatments, there were 43 adverse events (5.0%), the most frequent being prolonged erythema (1.8%), post-inflammatory hyperpigmentation (1.1%) and aggravation of melasma (0.9%). Less frequently observed adverse events included herpes simplex outbreak (0.6%) and acneiform eruption (0.2%). There were no reports of long-term adverse events.Non-ablative fractional laser skin treatment has a relatively low complication rate. The adverse events found were temporary and did not result in long-term or severe sequelae such as hypertrophic scarring, atrophic scarring or permanent pigmentary alteration.

Hyaluronic acid (HA) fillers are frequently used for the correction of facial soft-tissue defects.To compare the efficacy and safety of a novel monophasic HA filler (mono-HA), and a well-studied biphasic HA filler (bi-HA), in the treatment of moderate to severe nasolabial folds.In this randomized, evaluator-blinded, split-face comparative study, subjects were randomized for injections with mono-HA or bi-HA on the left or right side of the face. Efficacy was determined by calculating the change in the Wrinkle Severity Rating Score (WSRS) relative to baseline. Local safety was assessed on the basis of subject diary entries which recorded erythema, swelling, induration, pruritus, irritation, mass, hematoma, pain, and dryness.At week 24, the mean improvement in the WSRS from baseline was 2.18 ± 0.42 for the mono-HA side and 2.16 ± 0.41 for the bi-HA side. Both fillers were well-tolerated and adverse reactions were mild and transient in most cases.Mono-HA has a non-inferior efficacy to bi-HA in the treatment of moderate to severe nasolabial folds.

A recent study suggested that a cell-free extract of human adipose stem cells (hASCs-E) has beneficial effects on neurological diseases by modulating the host environment. Here, we investigated the effects of hASCs-E in several experimental models of stroke in vitro (oxygen and glucose deprivation, OGD) and in vivo (transient or permanent focal cerebral ischemia and intracerebral hemorrhage, ICH). Ischemia was induced in vitro in Neuro2A cells, and the hASCs-E was applied 24 h before the OGD or concurrently. Focal cerebral ischemia was induced by unilateral intraluminal thread occlusion of the middle cerebral artery (MCA) in rats for 90 min or permanently, or by unilateral MCA microsurgical direct electrocoagulation in mice. The ICH model was induced with an intracerebral injection of collagenase in rats. The hASCs-E was intraperitoneally administered 1 h after the stroke insults. Treatment of the hASCs-E led to a substantially high viability in the lactate dehydrogenase and WST-1 assays in the in vitro ischemic model. The cerebral ischemic and ICH model treated with hASCs-E showed decreased ischemic volume and reduced brain water content and hemorrhage volume. The ICH model treated with hASCs-E exhibited better performance on the modified limb placing test. The expression of many genes related to inflammation, immune response, and cell-death was changed substantially in the ischemic rats or neuronal cells treated with the hASCs-E. These results reveal a neuroprotective role of hASCs-E in animal models of stroke, and suggest the feasible application of stem cell-based, noninvasive therapy for treating stroke.

Background: The injection of botulinum toxin is now commonly used for many therapeutic and cosmetic purposes but because of its increased use more adverse events are being reported. Objective: To retrospectively evaluate and analyze the safety of botulinum toxin injections in terms of purpose and the type of toxin administered. Materials and methods: Data were collected on 1819 patients who underwent a total of 5310 treatments between 2005 and 2011 at a single tertiary medical center. Information on the dosage, treatment purpose, type of botulinum toxin, and any adverse events associated with these treatments were collected and analyzed. The generalized estimating equation (GEE) with the logistic link function was used to estimate the overall frequencies of adverse events. A multivariable GEE with the logistic link function was used to identifythe factors associated with adverseevents.Results :A mong the 5310 botulinum toxin treatments in our study cohort, 2258 of which (42.5%) were used to treat hemifacial spasm, 184 adverse events (3.73%) were recorded, 114 (2.26%) muscle-related, and 71 (1.47%) muscle-unrelated. The highest number of adverse events (8.29%) was associated with the treatment of blepharospasm and the lowest (1.07%) with masseter hyperplasia. By multivariate analysis, the odds ratio for females was 1.577 (95% confidence interval [CI] = 1.052–2.364; p = 0.027) and for the dose was 1.006 (95% CI = 1.002–1.010; p = 0.005). When compared with upper face wrinkles, the odds ratio was 2.510 (95% CI = 1.400– 4.499; p = 0.002) for blepharospasm, 0.375 (95% CI = 0.202–0.695; p = 0.002) for cervical dystonia, and 0.114 (95% CI: 0.015–0.862; p = 0.035) for masseter hyperplasia. Conclusion: When injecting botulinum toxin for cosmetic purposes, practitioners should be cautious, especially when targeting the areas around the eyes, as these treatments are prone to cause adverse events.

Background: Masseter hypertrophy can be ameliorated by botulinum toxin. Objective: To compare the efficacy and safety of RimabotulinumtoxinB (BTX-B) and OnabotulinumtoxinA (BTX-A) in the treatment of masseter hypertrophy. Methods: Sixteen women with bilateral masseter hypertrophy received single injections of BTX-A or BTX-B at a dose ratio of 1:50 or 1:70 in a 24-week double-blind randomized split-face study. Results: Both BTX-A and BTX-B produced significant improvements in masseter hypertrophy. The maximum volume reduction, as determined by computed tomography scanning, at week 12 was comparable between BTX-A and BTX-B at a dose ratio of 1:70 (15.6 and 14.2%, respectively). At week 24, only masseters treated with BTX-A maintained a significant volume reduction. Investigator ratings and patient satisfaction scores paralleled objective computed tomography measurements. Conclusion: Both BTX-A and BTX-B are effective in the treatment of masseter hypertrophy. BTX-B, at a dose ratio of 1:70, has a comparable efficacy but a shorter duration of action than BTX-A.

Background Recent studies have evaluated the expression of programmed death-1 (PD-1) and its prognostic value in malignant T-cell lymphomas. Objectives This study investigated whether the positivity of PD-1 was associated with the clinical characteristics of cutaneous extranodal NK/T-cell lymphoma (ENKTL) and evaluated its effects on survival outcomes. Methods Forty-one patients with cutaneous ENKTL were included. Clinical features and survival outcomes were analysed according to the positivity of PD-1. Results There was no significant difference between primary cutaneous ENKTL and secondary cutaneous ENKTL in the expression of PD-1. The degree of disease dissemination was not affected by the positivity of PD-1. Higher positivity for PD-1 was associated with lesions presenting erythematous to purpuric patches that are mainly composed of small tumour cells. Cutaneous ENKTL presenting nodular lesions had a significantly lower number of PD-1-positive infiltrating cells than those with other clinical morphologies. There was no significant effect of PD-1 expression on outcomes such as overall and progression-free survival. Limitations This study used a retrospective design and had a small sample size. Conclusion Higher PD-1 positivity is associated with small-cell-predominant cutaneous ENKTL. However, PD-1 expression has no prognostic value in cutaneous ENKTL.

Telangiectasia macularis eruptiva perstans (TMEP) is a rare subtype of cutaneous mastocytosis, characterized by telangiectatic tan to brown macules on the trunk and extremities. Although TMEP has been descried as an uncommon disease in the literature, we often encounter patients with TMEP lesions in the outpatient clinic. We aimed to assess the clinical and histopathological characteristics of acquired bilateral TMEP, and the pathophysiological mechanism of acquired bilateral TMEP among these patients. We retrospectively reviewed 30 patients (28 men and 2 women) with acquired bilateral TMEP; multiple telangiectatic dark red to brown macules that were symmetrically distributed. The clinical characteristics and general histopathological findings of lesional skin were investigated. The number of mast cells was evaluated using immunohistochemical analysis with an antibody directed against c-kit (CD117). Acquired bilateral TMEP was predominantly localized on the sun-exposed area: the upper arm in 30 patients (100%), forearm in 19 patients (63.3%) and anterior chest in 15 patients (50%). A total of 16 patients (53.3%) showed at least one aggravating factor, including UV irradiation, alcohol use and heat exposure. Compared with the mast cell numbers in 19 age- and biopsy site-matched healthy controls (91 ± 29.0/mm2 ), the number of mast cells in the papillary dermal skin of acquired bilateral TMEP patients was significantly increased (159 ± 37.2/mm2 , P < 0.01). In addition, a significant difference in vessel numbers in the papillary dermis was observed between acquired bilateral TMEP patients and healthy controls (10.5 ± 1.9 vs 5.4 ± 1.0/mm2 , P < 0.01). Acquired bilateral TMEP is a relatively common disorder in middle-aged Asian men. An increased number of mast cells and dilated vessels might be a photoaging-related reactive process of chronic sun-exposure, which consequently leads to the formation of characteristic telangiectatic hyperpigmentary macules through certain melanogenic mediators.

Although ablative fractional laser for the facial photodamaged skin was effective and safe, there have been only limited reports regarding the efficacy and safety of fractional Er:YAG laser treatments for photodamaged facial skin in Asians.Our objective was to assess the efficacy and safety of the Er:YAG laser (2940 nm) using the ''ablative'' fractional resurfacing mode to treat photodamaged facial skin.A total of 29 Korean patients were treated for photodamaged facial skin using a fractional Er:YAG laser. The number of treatments was mean 2.3 sessions at two-week intervals. Independent investigators assessed the efficacy using standardized photographs. The patients' satisfaction rate was also evaluated.For dyspigmentation, 62.5% of the treated patients showed improvement greater than 26%. Regarding wrinkles, 50% of the treated patients showed improvement greater than 26%. All patients showed various degrees of improvement in skin laxity. Assessing the overall features, 62.5% of the study subjects showed improvement greater than 26%, and most of them (91.7%) reported that their subjective satisfaction rate was above 'slight satisfaction'. Downtime accounted for approximately one week in most patients.A fractional Er:YAG laser can deliver an effective and minimally invasive treatment for photodamaged facial skin in Asians.

Background Optimum dose ratios of rimabotulinumtoxinB (BTX-B) and onabotulinumtoxinA (BTX-A) have not been determined for forehead wrinkles. Objective To compare the efficacy and safety of BTX-B and BTX-A for the treatment of forehead lines. Methods Twenty-two women (mean age, 40 years) with symmetrical moderate to severe forehead lines were randomized to receive single intramuscular injections of BTX-A and BTX-B on either side of the forehead, at a potency ratio of 1 : 70 or 1 : 100. Subjects were followed-up for 16 weeks. Four physicians evaluated patients’ photographs according to the 4-point Facial Wrinkling Grade (FWG). Clinical Improvement Scale (CIS) was calculated by subtracting FWG score at each visit from that at baseline. Patient satisfaction scores and adverse events were also recorded. Results Both BTX-A and BTX-B were effective for the treatment of forehead lines. At both potency ratios, BTX-A had a longer duration of action than BTX-B, while BTX-B led to faster improvement than BTX-A. There was no significant difference in CIS between 700 U and 1000 U BTX-B treatments. Adverse effects were mild and transient. Conclusion Both BTX-A and BTX-B were effective and well tolerated for the treatment of forehead wrinkles at potency ratios of 1 : 70 and 1 : 100.

Prurigo pigmentosa is a recurrent dermatosis with severe pruritus and several peculiar clinical features. Its exact etiology and pathogenesis are unclear. The aim of this study was to investigate the clinical features and chronological changes in the histopathology of prurigo pigmentosa in Korean patients and to assess the etiology of this condition. We reviewed the medical records, clinical photographs and biopsy specimens from 50 patients diagnosed with prurigo pigmentosa. Mean age at diagnosis was 23.7 years (range, 15-61 years). Prurigo pigmentosa started as urticarial papules or plaques, changing first to papulovesicles and then to reticulated brownish macules. The most frequent sites were the back and chest, especially depressed areas such as the central back and inter-mammary area. Dietary change was suspected as a cause of prurigo pigmentosa in 17 patients. Histopathologically, early-stage lesions had dermatitis herpetiformis-like features; fully-developed lesions displayed impetigo-like or acute, generalized, exanthematous, pustulosis-like features; and late lesions presented with post-inflammatory hyperpigmentation-like features. Oral minocycline, with or without dapsone, was effective in inhibiting the appearance of new lesions, but did not prevent recurrence. Prurigo pigmentosa is not rare in Korea, is apparently associated with dietary modification and preferentially involves the depressed regions of the trunk.

Fractional photothermolysis (FP) therapy and chemical peels have been reported to be effective in patients with recalcitrant melasma. However, there is little information to compare the efficacy of single treatment session in Asian women. The aim of this study was to examine the efficacy, long-lasting outcomes and safety of a single session of 1550-nm erbium-doped FP in Asian patients, compared with trichloroacetic acid (TCA) peel with a medium depth. Eighteen Korean women (Fitzpatrick skin type III or IV) with moderate-to-severe bilateral melasma were randomly treated with a single session of 1550-nm FP on one cheek, and with a 15% TCA peel on the other cheek. Outcome measures included an objective melasma area severity index and subjective patient-rated overall improvement at 4 and 12 weeks after treatment. Melasma lesions were significantly improved 4 weeks after either treatment, but melasma recurred at 12 weeks. Post-inflammatory hyperpigmentation developed in 28% of patients at 4 weeks but resolved in all but one patient by 12 weeks. There was no difference between FP treatment and TCA peeling with respect to any outcome measure. FP laser and TCA peel treatments were equally effective and safe when used to treat moderate-to-severe melasma, but neither treatment was long-lasting. We suggest that multiple or periodic maintenance treatments and/or supplemental procedures may be required for the successful treatment of melasma in Asian women.

Annular elastolytic giant cell granuloma (AEGCG) which is considered as a variant of granuloma annulare usually presents as annular papule or plaque with central atrophy and elevated erythematous margins. Thus facial involvement may cause cosmetic problem. We present a case of a 58-year-old woman diagnosed with AEGCG who underwent pulsed dye laser therapy and intralesional injection of polydeoxyribonucleotide. AEGCG successfully treated with three times of regular treatment sessions. Pulsed dye laser therapy and intralesional injection of polydeoxyribonucleotide can be an effective treatment option for facial AEGCG which shows persistent and unresponsive course in spite of various treatments.

BACKGROUND Fractional photothermolysis (FP) constitutes an effective modality of skin resurfacing by delivering thermal energy into multiple arrays of microscopic treatment zones. Radiofrequency (RF) can induce volumetric heating of dermis depending on electrical properties of target tissue. OBJECTIVES To evaluate the efficacy and safety of a novel bipolar RF-based fractional device for the treatment of photoaged Asian faces. METHODS Twenty-six Korean women (mean age 56, skin phototype III-IV) received three consecutive fractional RF treatments at 4- to 6-week intervals. Outcome assessments included standardized photography physician evaluation of fine lines, pores, smoothness and tightness, brightness, and overall appearance; degree of elastosis; subjective improvement scale; and patient satisfaction. RESULTS Fractional RF treatments produced moderate (26–50%) and incremental improvements in each category of physician evaluation. In particular, degree of smoothness and tightness, brightness, and overall appearance improved significantly 6 weeks after the third session from before the third session. The degree of elastosis was 5.46 at baseline, which decreased significantly to 4.05 at 6-week follow-up. Patient self-assessment paralleled the physician assessment. Adverse events were limited to mild erythema, swelling, and scabs, which usually shed 3.9 days after treatment. CONCLUSION Fractional bipolar RF treatment is an effective treatment for facial photodamage in Asians, with a favorable safety profile. The authors have indicated no significant interest with commercial supporters.

Summary Purpose: Stem cell–based therapies are being considered for various neurologic diseases, such as epilepsy. Recent studies have suggested that some effects of transplanted stem cells are due to bystander effects that modulate the host environment, rather than direct effects of cell replacement. The extract from human adipose stem cells (ASCs) that secrete multiple growth factors including cytokines and chemokines may be a potential source of bystander effects for the treatment of epilepsy, in which inflammation is thought to play an important role. Here, we investigated the effects of a cytosolic extract of human ASCs (ASCs-E) in a mouse model of epilepsy. Methods: Human ASCs-E, boiled ASCs-E, or fibroblast-extract (fibroblast-E) was intraperitoneally administrated to C57BL/6 mice 15 min before pilocarpine-induced status epilepticus (SE) or during chronic epileptic stage. Blood–brain barrier (BBB) leakage was evaluated by measuring Evans blue dye extravasation. Spontaneous recurrent seizure (SRS) was investigated by long-term video–electroencephalography (EEG) monitoring. The mice performed elevated plus maze, open-field, light/dark transition, and novel object recognition tasks. Key Findings: Acute application of human ASCs-E before SE led to earlier attenuation of seizure spike activities after treatment with diazepam, reduction of BBB leakage, and inhibition of the development of epilepsy. Human ASCs-E treatment (for 7 days) during the chronic epileptic stage suppressed SRS and reduced abnormal epileptic behavioral phenotypes. However, neither boiled ASCs-E nor fibroblast-E had any effects in the experimental epilepsy model. Significance: Our results demonstrate that human ASCs-E prevents or inhibits epileptogenesis and SRS in mice. They also suggest a stem cell–based, noninvasive therapy for the treatment of epilepsy.

Activating transcription factor 3, a member of the activating transcription factor/cyclic adenosine monophosphate response element-binding family of transcription factors, is an adaptive response gene that plays an oncogenic role in the development of various cancers. To our knowledge, few information are available on the possible role of activating transcription factor 3 in skin cancer. In this study, we investigated the expression of activating transcription factor 3 in basal cell carcinomas (n = 5), actinic keratoses (n = 7), squamous cell carcinomas (n = 19), and Bowen disease (n = 14) by immunohistochemistry. In results, activating transcription factor 3 was significantly expressed in squamous cell carcinomas (15/19), suggesting that it is involved in the pathogenesis of squamous cell carcinomas but not in basal cell carcinomas (0/5). In addition, higher expression of activating transcription factor 3 was observed in squamous cell carcinomas that were metastatic (P < .01) or arose in organ transplant recipients (P < .05). Therefore, activating transcription factor 3 appears to play an oncogenic role in the development of squamous cell carcinomas and may be related to the biologic behavior of them.

Background Most glomus tumours are located in the digits, especially in subungual areas. Less is known, however, about the clinical characteristics of extradigital glomus tumours. Objectives The aim of this study was to characterize extradigital glomus tumours and compare their clinical, pathological and immunohistochemical characteristics with those of digital glomus tumours. Methods We retrospectively reviewed the charts of 110 patients with digital and 42 patients with extradigital glomus tumours, treated at a single centre from 1991 to 2010. We also investigated the immunohistochemical expression of substance P and TRPV1 in the biopsy specimens from patients with digital (n = 5) and extradigital (n = 5) glomus tumours. Results Compared with patients with digital glomus tumours, patients with extradigital tumours were significantly older (P = 0.009) and showed a significantly greater male predominance (P

Tissue pericytes respond to injury, and support vascular and tissue regeneration. The presence of pericytes in the circulation may provide an attractive framework for tissue regeneration. Here, we detected multipotent pericyte-like cells in the circulating blood and determined its profiles during cerebral ischemia. Pericyte-like cells were isolated from the peripheral blood of acute stroke patients or asymptomatic individuals with vascular risk factors by fluorescence or magnetic activated cell sorting with anti-PDGF receptor-beta (PDGFRβ) antibody. The morphologic and molecular features of circulating PDGFRβ(+) cells were compared with tissue pericytes, and the associations with respect to quantity in the blood, culture outcome, and patient characteristics were analyzed. We found an increase in circulating PDGFRβ(+) cells in acute stroke patients compared to controls and a correlation with neurologic impairment. The isolated PDGFRβ(+) cells expressed mesenchymal stem cell markers, proliferated, and were multipotent under permissive culture conditions. The multipotent nature of these cells was comparable to fat-derived PDGFRβ(+) cells. These cells could be obtained by pharmacologic stimulation using bone marrow mobilizer. Circulating PDGFRβ(+) cells will be useful for future research involving endogenous recovery or autologous cell-based therapy.

J.-E. Kim, H. Sung, M.-N. Kim, C.-H. Won, S.-E. Chang, M.-W. Lee, J.-H. Choi, K.-C. Moon. Synchronous infection with Mycobacterium chelonae and Paecilomyces in a heart transplant patient. Transpl Infect Dis 2011: 13: 80–83. All rights reserved Abstract: A 41-year-old male who was 3 years status post heart transplant presented with a 3-month history of painful erythematous nodules and ulcers on his lower legs and right hand. First, Mycobacterium chelonae infection was revealed through several biopsies with molecular sequence analysis, and combination treatment, including clarithromycin, was started. During the treatment, lesions of the legs showed an improvement, but a fluctuant erythematous nodule on the thumb did not respond. Repetitive biopsy from the thumb ultimately identified Paecilomyces species and the patient was treated with itraconazole and terbinafine sequentially. Our case is the first report, to our knowledge, of synchronous infection with non-tuberculous mycobacteria (NTM) and Paecilomyces in a solid organ transplant recipient. Our findings highlight the importance of recognizing cutaneous NTM infections or deep mycoses, as well as the importance of choosing an appropriate treatment.

Photodynamic therapy using topical 5-aminolevulinic acid (ALA) has been successful in treating acne vulgaris, but sun avoidance for at least 48 hours after treatment is necessary due to the risk of post-treatment photosensitivity. Recently, a lower concentration of liposome-encapsulated 5-ALA was introduced to minimize this risk.To evaluate the efficacy and safety of liposome-encapsulated 0.5% 5-ALA in the photodynamic therapy of inflammatory acne and its effects on sebum secretion in Asian skin.Thirteen Korean subjects with inflammatory acne were administered 0.5% ALA spray before photoradiation treatment. Photoradiation was performed at 3.5-6.0 J/cm(2) three times during each of two visits, performed 2 weeks apart. Improvement of acne was evaluated subjectively and objectively based on the Korean Acne Grading System. Sebum secretion was measured quantitatively at each visit.The mean reduction in acne grade at the end of the treatment was 43.2%. Of the patients, 69.2% reported improvements in subjective skin oiliness, but fewer showed objective reductions in sebum secretion as determined by the Sebumeter® SM10. No serious adverse events were observed.Photodynamic therapy using liposome-encapsulated 0.5% 5-ALA improved inflammatory acne with minimal side effects in Asians.

Ectopic adrenocorticotropic hormone (ACTH) syndrome is a rare cause of generalised hyperpigmentation. The clinical features are due to the excessive ectopic secretion of adenocorticotropin by diverse neuroendocrine or non-endocrine tumours. Here, we describe a rare case of ectopic ACTH syndrome developing from recurring thymic neuroendocrine carcinoma, which first presented as generalised hyperpigmentation.

Adipose tissue is one of the richest sources of mesenchymal stem cells. Even more interesting is the fact that adipose-derived stem cells (ASCs) show an outstanding ability to regenerate damaged skin. Thus, ASCs are a popular and feasible treatment in clinical dermatology.This review discusses the potential applications of ASCs and conditioned medium of ASC (ASC-CM) to skin, and briefly touches on the mechanisms by which ASCs promote skin regeneration.Clinically, processed lipo-aspirated (PLA) cells are commonly used for treatment of aged skin; however, the use of PLA cells for cosmetic purposes is not convenient, because PLA cells are prepared from patients. Alternatively, cosmetics that contain ASC-CM can be pre-made from healthy volunteers such that they are immediately available for clinical treatment of aged skin. Cell-based therapies are adequate for improvement of wrinkles or for soft tissue augmentation, whereas ASC-CM has merit for amelioration of skin tone. When culturing ASCs for the production of cosmetic raw materials, hypoxic culture conditions and transduction of specific genes into ASCs may increase the regenerative protein content of the conditioned medium.Application of ASCs and ASC-CM to dermatology shows promising results for skin regeneration.

Background Eruptive pseudo-angiomatosis (EPA) is a rare, relatively newly described cutaneous disorder characterized by the sudden onset of several bright red, angioma-like papules surrounded by blanched halo. Its aetiology is unknown; however, viral infection or mosquito bites have been speculated as possible causes. Objective This study aims to determine the clinical and histopathological features of EPA, and whether it is associated with Epstein–Barr virus (EBV) infection. Methods We conducted a retrospective chart review of 25 EPA cases from 2006 to 2008. In order to determine latent EBV infection, EBV-encoded small RNA (EBER) in situ hybridization was performed in 18 subjects. To determine EPA's distinguishing histological characteristics, we compared the cases with 22 control cases of perivascular lymphocytic infiltration for haematoxylin and eosin, CD3, CD4, CD8, CD31 and c-kit staining patterns. Results The patient sample's female-to-male ratio was 2.1 : 1, and the patients’ age ranged from 5 to 79 years (average 46 years). The lesions appeared during the months of July to September in all but 3 patients. Skin biopsies demonstrated capillary ectasia with perivascular mononuclear cellular infiltrates in the upper dermis. Most patients were otherwise healthy, and routine laboratory results were all normal except in one patient who had diabetes. The skin lesions faded without any treatment in 1–2 weeks. Results of EBER in situ hybridization were all negative. The only histological distinguishing feature of EPA was the presence of intravascular neutrophils, which was found to be present in 19 of the 20 EPA cases (95%), in contrast to only 3 of the 22 control subjects (14%) (P

Background: Topical tacrolimus is an effective anti-inflammatory therapy for acute and chronic states of atopic dermatitis (AD) in both adults and children. Topical tacrolimus has particular use at sensitive areas such as the face, anogenitals, and skin folds of neck and extremities. However, many AD patients also experience aggravated symptoms on trunk. Objective: The aim of this study was to investigate the efficacy and safety of topical tacrolimus for AD patients with truncal lesions. Methods: AD patients with truncal lesions who were aged ≥2 years were recruited from 20 centres in Korea. They received treatment with topical tacrolimus ointment twice daily during 4 weeks. The primary end point was change of the local eczema area and severity index (EASI) of the trunk from baseline to day 28. The secondary end points were changes in the patient global assessment (PGA) score and itch visual analogue scale (VAS) score of the trunk between baseline and day 28. Results: Two hundred and ninety- one patients were recruited, and 176 patients completed the full 4-week treatment course. By the end of the treatment, the mean local EASI of the trunk (2.2±4.71) was significantly decreased from that at baseline (4.71±4.03, p＜0.001). PGA (1.71±1.15) and itch VAS score of the trunk (2.61±2.19) on day 28 were also profoundly decreased compared with the baseline (2.96±1.07 and 5.15±2.47, respectively). No serious adverse events were observed during the study period. Conclusion: Topical tacrolimus is an effective and safe therapy for truncal lesions in AD patients. (Ann Dermatol 30(2) 173∼178, 2018)

We report a case of a 69-year-old man with metastatic cutaneous duodenal gastrointestinal stromal tumor, which led to find multiple metastases on orbital muscle and scalp. The patient presented with a rapidly growing chest nodule with mild tenderness. He underwent surgical resection for duodenal gastrointestinal stromal tumor and had been treated with imatinib for three years. Histopathological examination of the chest nodule was consistent with gastrointestinal stromal tumor. A brain magnetic resonance imaging of follow work-up revealed multiple metastases at the left superior rectus muscle and occipital scalp. Under the diagnosis with imatinib-resistant duodenal gastrointestinal stromal tumors, a second-line therapy with sunitinib was tried. After six weeks, his skin lesion was completely improved and other metastatic cancers showed a response of stable disease. This is the first reported case of a cutaneous metastasis from duodenal GIST. This report emphasizes the importance of a full-skin examination in patients with a medical history of gastrointestinal stromal tumor which leads to find multiple metastases.

Background: Although the photoprotective effects of β-carotene are thought to originate from its antioxidant properties, some studies documented pro-oxidant effects of β-carotene. Objective: Our purpose was to determine the effects of 2 different doses of dietary β-carotene on wrinkles and elasticity, procollagen gene expression and ultraviolet (UV)-induced DNA damage in human skin. Methods: Thirty healthy female subjects over the age of 50 years were randomized and received 2 different doses (30 and 90 mg/day) of β-carotene for 90 days. The baseline status was used as control. At baseline and completion of the study, facial wrinkles and elasticity were measured objectively. Buttock skin was taken to determine the type I procollagen, matrix metalloproteinase-1 and fibrillin-1 mRNA levels, and UV-induced thymine dimer and 8-hydroxy-2′-deoxyguanosine formation. Results: β-Carotene improved facial wrinkles and elasticity significantly only in the low-dose group. The minimal erythema dose decreased significantly only in the high-dose group. Type I procollagen mRNA levels were significantly increased to 4.4 ± 1.6 times the baseline level only in the low-dose group, and procollagen immunostaining increased accordingly. UV-induced thymine dimer staining was reduced in the low-dose group but tended to increase in the high-dose group. 8-hydroxy-2′-deoxyguanosine staining was significantly reduced in the low-dose group. Conclusions: 30 mg/day of β-carotene supplementation is demonstrated to prevent and repair photoaging.

Objective Adipose-derived stem cells (ASCs) are readily accessible and secrete multiple growth factors. Here, we show that ASC transplantation rescues the striatal pathology of Huntington disease (HD) models. Methods ASCs were isolated from human subcutaneous adipose tissue. In a quinolinic acid (QA)-induced rat model of striatal degeneration, human ASCs (1 million cells) were transplanted into the ipsilateral striatal border immediately after the QA injection. In 60-day-old R6/2 mice transgenic for HD, ASCs (0.5 million cells) were transplanted into each bilateral striata. In in vitro experiments, we treated mutant huntingtin gene-transfected cerebral neurons with ASC-conditioned media. Results In the QA model, human ASCs reduced apomorphine-induced rotation behavior, lesion volume, and striatal apoptosis. In R6/2 transgenic mice, transplantation of ASCs improved Rota-Rod performance and limb clasping, increased survival, attenuated the loss of striatal neurons, and reduced the huntingtin aggregates. ASC-transplanted R6/2 mice expressed elevated levels of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and reactive oxygen defense enzymes and showed activation of the Akt/cAMP-response element-binding proteins. ASC-conditioned media decreased the level of N-terminal fragments of mutant huntingtin and associated apoptosis, and increased PGC-1α expression. Interpretation Collectively, ASC transplantation slowed striatal degeneration and behavioral deterioration of HD models, possibly via secreted factors. Ann Neurol 2009;66:671–681

Previous studies have shown that topical steroid and shampoo containing zinc pyrithione provide clinical benefits for treatment of scalp seborrheic dermatitis. But the clinical efficacy of topical tacrolimus, a newly developed calcineurin inhibitor on seborrheic dermatitis, is not well investigated yet. We wanted to compare the clinical efficacy of topical tacrolimus with that of conventional treatment (zinc pyrithione shampoo and topical betamethasone) for treatment of seborrheic dermatitis of the scalp. Patients with seborrheic dermatitis of the scalp were randomly allocated to receive topical betamethasone, topical tacrolimus or zinc pyrithione shampoo. Some patients were instructed to continue the treatments for 8 weeks and the others to discontinue the treatments at week 4. We evaluated the efficacy using a clinical severity score, dandruff score and sebum secretion at baseline, week 4 and week 8. All treatment groups showed significant improvements in clinical assessment after 4 weeks. While the patients treated by zinc pyrithione improved continuously even after cessation of the treatment, the patients treated by betamethasone lotion or tacrolimus ointment were aggravated clinically. Topical tacrolimus was as effective as topical betamethasone, and showed more prolonged remission than topical betamethasone. To treat seborrheic dermatitis of the scalp, we think that the combination therapy of topical steroid or topical tacrolimus, and zinc pyrithione is recommended.

Culture conditions affect the development of mammalian embryos in vitro. Kinetin belongs to the family of N6-substituted adenine derivates and promotes cell division, synthesis of DNA repair enzymes, superoxide dismutase activity, and ribosomal RNA transcription. We investigated the effects of kinetin on in vitro development of parthenogenetic and nuclear transfer (NT) porcine embryos. These embryos were cultured with or without kinetin in either BSA- or polyvinyl alcohol-containing medium for 7 days. mRNA expression of three developmentally important genes, HSP70, Glut-1, and poly[A] polymerase in NT embryos was analyzed. Regardless of kinetin supplementation, the proportion of blastocysts and blastocyst cells were not significantly different in parthenogenetic embryos. However, kinetin supplementation increased expansion and hatching rates in all groups. In somatic cell NT embryos, kinetin increased the proportion of embryos developed to blastocysts from 7.5% to 15.4% in medium supplemented with PVA. However, gene expression levels of HSP70, poly[A] polymerase and Glut-1 mRNA were not significantly different in NT blastocysts. The present study indicates that kinetin not only improves blastocyst expansion and cell number of parthenogenetic porcine embryos but also enhances NT porcine embryo development in a completely defined culture condition in vitro. Mol. Reprod. Dev. 75: 1701–1709, 2008. © 2008 Wiley-Liss, Inc.

Chronic ultraviolet (UV) exposure is the major cause of photoaging that causes skin wrinkling, roughness, dryness, laxity, and pigmentation. Recently, increasing efforts are being made to understand the relationship between foods and skin health. Ginsenosides are present in ginseng (Ginseng Radix Rubra) extract, and are known to have biomedical properties, such as, anti-oxidant and anti-inflammatory effects. In this study, we investigated whether KTNG0345 prepared from red ginseng extracts delivered orally reduces skin wrinkling and ultraviolet B (UVB)-induced wrinkle formation in hairless mouse skin. KTNG0345 was administrated orally to the mice (5 times a week) during the period of UVB-irradiation (3 times a week) for 8 weeks at three different doses of 300 ㎎/㎏, 500 ㎎/㎏ and 1000 ㎎/㎏ (w/v). UV doses were increased weekly by 1 MED (1MED = 75 mJ/㎠) up to 4 MED and then maintained at this level. After the 8-week administration period, it was found that orally administered KTNG0345 significantly inhibited UVB-induced wrinkle formation in a dose-dependent manner. Increases in skin thickness caused by UVB were prevented by KTNG0345. Moreover, it also significantly inhibited matrix metalloproteinases (MMP) -13 and MMP-9 expressional inductions by UVB. In addition, KTNG0345 was observed to prevent UVB-induced water loss of epidermis in hairless mouse skin. Our results demonstrate that orally administered KTNG0345 has anti-wrinkling effects in hairless mouse skin, and suggest that dietary red ginseng and herbal mixture may be considered a functional beauty food for preventing UVB-induced skin wrinkles.

A relationship has been suggested between mast cells (MCs) and male pattern hair loss (MPHL), because of histological evidence of perifollicular fibrosis and increased mast cell numbers. Two paired punch biopsies were taken from balding vertexes and non-balding occipital promontory areas of ten patients with MPHL (Ludwig-Hamilton IIIv to IV) and from five normal subjects aged from 20 to 35 years. Masson trichrome and Victoria blue staining were performed to observe collagen frameworks and elastic fiber structures. Numbers of immunoreactive MCs stained with anti-tryptase or anti-chymase antibody were counted. It was found that collagen bundles were significantly increased in balding vertexes than in non-balding occiput scalp skin. A near 4-fold increase in elastic fibers was observed in both vertex and occiput scalp skins with MPHL versus controls. Total numbers of MCs (tryptase-positive) in site-matched scalp samples were about 2-fold higher in MPHL subjects than in normal controls. Percentage elastic fiber (%) was found to be relatively well-correlated with tryptase and chymase-positive MCs. These findings suggest that accumulated MCs might be responsible for increased elastic fiber synthesis in MPHL, and indicate that future investigations are warranted.

The tripeptide-copper complex, described as a growth factor for various kinds of differentiated cells, stimulates the proliferation of dermal fibroblasts and elevates the production of vascular endothelial growth factor, but decreased the secretion of transforming growth factor-beta1 by dermal fibroblasts. Dermal papilla cells (DPCs) are specialized fibroblasts, which are important in the morphogenesis and growth of hair follicles. In the present study, the effects of L-alanyl-L-histidyl-L-lysine-Cu2+ (AHK-Cu) on human hair growth ex vivo and cultured dermal papilla cells were evaluated. AHK-Cu (10(-12) - 10(-9) M) stimulated the elongation of human hair follicles ex vivo and the proliferation of DPCs in vitro. Annexin V-fluorescein isothiocyanate/propidium iodide labeling and flow cytometric analysis showed that 10(-9) M AHK-Cu reduced the number of apoptotic DPCs, but this decrease was not statistically significant. The ratio of Bcl-2/Bax was elevated, and the levels of the cleaved forms of caspase-3 and PARP were reduced by treatment with 10(-9) M AHK-Cu. The present study proposed that AHK-Cu promotes the growth of human hair follicles, and this stimulatory effect may occur due to stimulation of the proliferation and the preclusion of the apoptosis of DPCs.

Background: 5% topical minoxidil solution has been widely used to stimulate new hair growth and help stop hair loss in men with androgenetic alopecia (AGA). However, it is not convenient for patients to continue applying the solution twice daily on a regular basis. Tretinoin is known to increase the percutaneous absorption of minoxidil and, therefore, to enhance the response of AGA to minoxidil. For this reason, it was assumed that tretinoin would be helpful in alleviating the inconvenience associated with the recommended twice-daily application of minoxidil. Objective: To compare the efficacy and safety of therapy using a combined solution of 5% minoxidil and 0.01% tretinoin once daily with those of the conventional 5% topical minoxidil therapy applied twice daily in the treatment of AGA. Methods: A total of 31 male patients (aged 28–45 years, mean 39.7 ± 4.5) with AGA (Hamilton-Norwood classification type III–V) were randomly assigned into two groups, one in which 5% minoxidil was applied to the scalp twice daily and the other in which the combined agent was applied once daily at night together with a vehicle placebo in the morning. The efficacy parameters were: (i) changes in total hair count, non-vellus hair count, anagen hair ratio, linear hair growth rate, and mean hair diameter assessed by macrophotographic image analysis; and (ii) the patient’s and investigator’s subjective assessments. Results: After therapy, increases in the macrophotographic variables of total hair count and non-vellus hair count were shown in both treatment groups. There were no statistically significant differences between the two treatment groups with respect to changes in macrophotographic variables or scores on subjective global assessments by patients and the investigator. The incidence of adverse effects such as pruritus or local irritation was similar in the 5% minoxidil group (4 of 14 subjects) and the combined agent group (5 of 15 subjects). Conclusion: The efficacy and safety of combined 5% minoxidil and 0.01% tretinoin once-daily therapy appear to be equivalent to those of conventional 5% minoxidil twice-daily therapy for the treatment of AGA.

BACKGROUND The histopathological features of rosacea have not been described in detail. OBJECTIVE To evaluate the histopathological features of rosacea according to clinical characteristics such as subtype and severity. METHODS We retrospectively analyzed histopathological findings in 226 patients with rosacea, which included 52 patients with the erythematotelangiectatic rosacea (ETR) and 174 patients with the papulopustular rosacea (PPR) subtype. The frequency of each histopathological finding was compared between subtypes. Histopathological features were also compared according to the severity, through subgroup analysis within each subtype group. RESULTS Perivascular and perifollicular lymphohistiocytic infiltration were common dermal findings in both subtype groups, but the intensity of dermal inflammatory infiltration was higher in PPR than in ETR. Follicular spongiosis and exocytosis of inflammatory cells into hair follicles were noted in both subtypes; but these findings were significantly more common in the PPR subtype. Vascular changes (telangiectasia and proliferation) and solar elastosis were common histopathological findings in both subtypes, with no difference in frequency between subtype groups. Demodex mites were identified in about 40% of patients, and the frequency of demodex mites did not differ between subtype groups. The intensity of perifollicular inflammation and the presence of follicular inflammatory reactions were dependent on the severity of rosacea in both subtype groups. CONCLUSIONS The intensity of inflammatory reactions, especially perifollicular infiltration, was higher in PPR patients than in ETR patients. Rosacea has a spectrum of histopathological features that are related to clinical progression between rosacea subtypes.