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Background In 2015, the Korean Atopic Dermatitis Association (KADA) working group published consensus guidelines for treating atopic dermatitis (AD). Objective We aimed to provide updated consensus recommendations for systemic treatment of AD in South Korea based on recent evidence and experience. Methods We compiled a database of references from relevant systematic reviews and guidelines on the systemic management of AD. Evidence for each statement was graded and classified based on thestrength of the recommendation. Forty-two council members from the KADA participated in three rounds of voting to establish a consensus on expert recommendations. Results We do not recommend long-term treatment with systemic steroids forpatients with moderate-to-severe AD due to the risk of adverse effects. We recommend treatment with cyclosporine or dupilumab and selective treatment with methotrexate or azathioprine for patients with moderate-to-severe AD. We suggest treatment with antihistamines as an option for alleviating clinical symptoms of AD. We recommend selective treatment with narrowband ultraviolet B for patients with chronic moderate-to-severe AD. We do not recommend treatment with oral antibiotics for patients with moderate-to-severe AD but who have no signs of infection. We did not reach a consensus on recommendations for treatment with allergen-specific immunotherapy, probiotics, evening primrose oil, orvitamin D for patients with moderate-to-severe AD. We also recommend educational interventions and counselling for patients with AD and caregivers to improve the treatment success rate. Conclusion We look forward to implementing a new and updated consensus of systemic therapy in controlling patients with moderate-to-severe AD.

Patients with chronic itch describe their pruritus in a wide variety of ways. However, these subjective descriptions are often not taken into consideration by physicians. This study aimed to validate patients’ descriptions of pruritus, and to investigate the relationship between various descriptions of pruritus and the patient burden of chronic pruritus by examining the mediating effects of sleep disturbance and sexual dysfunction on patient’s quality of life, as predicted by various descriptions of pruritus. Exploratory and confirmatory factor analyses were performed to identify the factor structure measured by 11 descriptions of pruritus. The study then analysed differences in the degree of sleep disturbance, sexual dysfunction, and quality of life deterioration factors using a structural equation modelling method. Using data from 419 patients with chronic pruritus, 11 descriptions of pruritus were classified into 2 groups: (i) sensory pruritus (i.e. stinging, stabbing, burning, painful, formication, throbbing, and cold) that are linked with descriptions of pruritus patterns; and (ii) affective pruritus (i.e. annoying, unbearable, worrisome, and warm) from patient reports of psychological or emotional distress. The study found that affective pruritus decreases patient’s quality of life either directly or indirectly through sleep disturbance. In conclusion, clues about a patients’ sleep disturbance or poor quality of life can be obtained through their descriptions of pruritus.

Although deep learning algorithms have demonstrated expert-level performance, previous efforts were mostly binary classifications of limited disorders. We trained an algorithm with 220,680 images of 174 disorders and validated it using Edinburgh (1,300 images; 10 disorders) and SNU datasets (2,201 images; 134 disorders). The algorithm could accurately predict malignancy, suggest primary treatment options, render multi-class classification among 134 disorders, and improve the performance of medical professionals. The area under the curves for malignancy detection were 0.928 ± 0.002 (Edinburgh) and 0.937 ± 0.004 (SNU). The area under the curves of primary treatment suggestion (SNU) were 0.828 ± 0.012, 0.885 ± 0.006, 0.885 ± 0.006, and 0.918 ± 0.006 for steroids, antibiotics, antivirals, and antifungals, respectively. For multi-class classification, the mean top-1 and top-5 accuracies were 56.7 ± 1.6% and 92.0 ± 1.1% (Edinburgh) and 44.8 ± 1.2% and 78.1 ± 0.3% (SNU), respectively. With the assistance of our algorithm, the sensitivity and specificity of 47 clinicians (21 dermatologists and 26 dermatology residents) for malignancy prediction (SNU; 240 images) were improved by 12.1% (P0.0001) and 1.1% (P0.0001), respectively. The malignancy prediction sensitivity of 23 non-medical professionals was significantly increased by 83.8% (P0.0001). The top-1 and top-3 accuracies of four doctors in the multi-class classification of 134 diseases (SNU; 2,201 images) were increased by 7.0% (P = 0.045) and 10.1% (P = 0.0020), respectively. The results suggest that our algorithm may serve as augmented intelligence that can empower medical professionals in diagnostic dermatology.

Background: The effects of diabetes mellitus (DM) on mortality and morbidities in burn patients have not been sufficiently elucidated. Objective: The present study aimed to investigate the effects of DM on the mortality, length of hospital stay, and number of operations in burn patients. Methods: A retrospective cohort study was performed using medical records of 3,220 burn patients. Multiple logistic regression, linear regression, and Poisson regression models were used to determine whether DM increases mortality in patients with burn injury, whether DM prolongs length of hospital stay in burn survivors, and whether DM increases the number of operations in burn survivors, respectively. Results: After adjusting for potential confounding factors, DM significantly increased odds of death in burn patients (adjusted odds ratio 3.225 [95% confidence interval 1.405∼7.400], p=0.006). DM also increased the mean length of hospital stay in burn survivors (adjusted mean ratio 1.312 [95% confidence interval 1.198∼1.437], p＜0.001). Furthermore, DM significantly increased the mean number of operations in burn survivors (adjusted mean ratio 1.576 [95% confidence interval 1.391∼ 1.785], p＜0.001). Conclusion: DM increases mortality, elongates hospital stay and makes more operations required in patients with burn injury. (Ann Dermatol 31(1) 51∼58, 2019)

Studies have shown that stem cells and their derivatives, including conditioned media (CM), have inhibitory effects on skin pigmentation. However, evidence supporting the skin brightening effect of exosomes derived from stem cells is lacking. We studied the antipigmentation effect in vitro and skin brightening efficacy in vivo of exosomes derived from human adipose tissue-derived mesenchymal stem/stromal cells (ASC-exosomes). Exosomes were isolated from the CM of ASCs using the tangential flow filtration method. ASC-exosomes reduced intracellular melanin levels in B16F10 melanoma cells regardless of the presence of the &alpha, melanocyte-stimulating hormone (&alpha, MSH). The skin brightening efficacy of a cosmetic formulation containing ASC-exosomes was assessed in human volunteers with hyperpigmentation in a prospective, split-face, double-blind, randomized placebo-controlled study. The ASC-exosome-containing formulation statistically decreased the melanin contents compared to the placebo control. However, the melanin-reduction activity was limited and diminished along with time. A further improvement in efficient transdermal delivery of ASC-exosomes will be helpful for more profound efficacy. In summary, these results suggest that ASC-exosomes can be used as a cosmeceutical for skin brightening.

Background The diagnostic performance of convolutional neural networks (CNNs) for diagnosing several types of skin neoplasms has been demonstrated as comparable with that of dermatologists using clinical photography. However, the generalizability should be demonstrated using a large-scale external dataset that includes most types of skin neoplasms. In this study, the performance of a neural network algorithm was compared with that of dermatologists in both real-world practice and experimental settings. Methods and findings To demonstrate generalizability, the skin cancer detection algorithm (https://rcnn.modelderm.com) developed in our previous study was used without modification. We conducted a retrospective study with all single lesion biopsied cases (43 disorders; 40,331 clinical images from 10,426 cases: 1,222 malignant cases and 9,204 benign cases); mean age (standard deviation [SD], 52.1 [18.3]; 4,701 men [45.1%]) were obtained from the Department of Dermatology, Severance Hospital in Seoul, Korea between January 1, 2008 and March 31, 2019. Using the external validation dataset, the predictions of the algorithm were compared with the clinical diagnoses of 65 attending physicians who had recorded the clinical diagnoses with thorough examinations in real-world practice. In addition, the results obtained by the algorithm for the data of randomly selected batches of 30 patients were compared with those obtained by 44 dermatologists in experimental settings; the dermatologists were only provided with multiple images of each lesion, without clinical information. With regard to the determination of malignancy, the area under the curve (AUC) achieved by the algorithm was 0.863 (95% confidence interval [CI] 0.852–0.875), when unprocessed clinical photographs were used. The sensitivity and specificity of the algorithm at the predefined high-specificity threshold were 62.7% (95% CI 59.9–65.1) and 90.0% (95% CI 89.4–90.6), respectively. Furthermore, the sensitivity and specificity of the first clinical impression of 65 attending physicians were 70.2% and 95.6%, respectively, which were superior to those of the algorithm (McNemar test; p < 0.0001). The positive and negative predictive values of the algorithm were 45.4% (CI 43.7–47.3) and 94.8% (CI 94.4–95.2), respectively, whereas those of the first clinical impression were 68.1% and 96.0%, respectively. In the reader test conducted using images corresponding to batches of 30 patients, the sensitivity and specificity of the algorithm at the predefined threshold were 66.9% (95% CI 57.7–76.0) and 87.4% (95% CI 82.5–92.2), respectively. Furthermore, the sensitivity and specificity derived from the first impression of 44 of the participants were 65.8% (95% CI 55.7–75.9) and 85.7% (95% CI 82.4–88.9), respectively, which are values comparable with those of the algorithm (Wilcoxon signed-rank test; p = 0.607 and 0.097). Limitations of this study include the exclusive use of high-quality clinical photographs taken in hospitals and the lack of ethnic diversity in the study population. Conclusions Our algorithm could diagnose skin tumors with nearly the same accuracy as a dermatologist when the diagnosis was performed solely with photographs. However, as a result of limited data relevancy, the performance was inferior to that of actual medical examination. To achieve more accurate predictive diagnoses, clinical information should be integrated with imaging information., Seung Seog Han and colleagues compare the performance of a neural network algorithm with that of dermatologists in diagnosis of skin neoplasms., Author summary Why was this study done? The diagnostic performance of artificial intelligence based on deep learning algorithms has been demonstrated to be superior to or at least comparable with that of dermatologists. However, the difference in diagnostic efficiency between algorithms and dermatologists was determined using experimental reader tests with limited clinical information related to the photographed skin abnormalities. Most studies performed internal validation, which indicates that both the training and validation images were selected from the same source. In addition, only a small number of disorders have been validated in the previous studies. Thus, practical limitations and biases have complicated translation to actual practices. What did the researchers do and find? The performance of the neural network algorithm was compared with that of standard dermatologic practice for diagnosing almost all types of skin neoplasms on a large scale. The algorithm could successfully screen malignancy, without lesion preselection by a dermatologist. Under experimental settings, in which only images were provided for diagnosis, the performance of the algorithm was comparable with that of the 44 dermatologists who performed the reader test. However, the performance of the algorithm was inferior to that of the attending physicians who actually consulted with patients. This highlights the value of clinical data, in addition to visual findings, for accurate diagnosis of cutaneous neoplasms. What do these findings mean? Given photographs of abnormal skin findings, the algorithm can work ceaselessly to determine the need for dermatologic consultation at a performance level comparable with that of dermatologists. To further improve the algorithm’s performance, metadata, such as past medical history, should be integrated with the clinical images.

A variety of applications of human adipose tissue stem cell-derived exosomes have been suggested as novel cell-free therapeutic strategies in the regenerative and aesthetic medical fields. This study evaluated the clinical efficacy and safety of adipose tissue stem cell-derived exosomes as an adjuvant therapy after application of fractional CO2 laser for acne scars. A 12-week prospective, double-blind, randomized, split-face trial was performed. A total of 25 patients received 3 consecutive treatment sessions of fractional CO2 laser to the whole face, with a follow-up evaluation. Post-laser treatment regimens were applied; for each patient, one side of the face was treated with adipose tissue stem cell-derived exosomes gel and the other side was treated with control gel. Adipose tissue stem cell-derived exosomes-treated sides had achieved a significantly greater improvement than the control sides at the final follow-up visit (percentage reduction in echelle d'evaluation clinique des cicatrices d'acne scores: 32.5 vs 19.9%, p < 0.01). Treatment-related erythema was milder, and post-treatment downtime was shorter on the applications of human adipose tissue stem cell-derived exosomes-treated side. In conclusion, the combined use of this novel material with resurfacing devices would provide synergistic effects on both the efficacy and safety of atrophic acne scar treatments.

Exosomes are nano-sized vesicles that serve as mediators for cell-to-cell communication. With their unique nucleic acids, proteins, and lipids cargo compositions that reflect the characteristics of producer cells, exosomes can be utilized as cell-free therapeutics. Among exosomes derived from various cellular origins, mesenchymal stem cell-derived exosomes (MSC-exosomes) have gained great attention due to their immunomodulatory and regenerative functions. Indeed, many studies have shown anti-inflammatory, anti-aging and wound healing effects of MSC-exosomes in various in vitro and in vivo models. In addition, recent advances in the field of exosome biology have enabled development of specific guidelines and quality control methods, which will ultimately lead to clinical application of exosomes. This review highlights recent studies that investigate therapeutic potential of MSC-exosomes and relevant mode of actions for skin diseases, as well as quality control measures required for development of exosome-derived therapeutics.

Atopic dermatitis (AD) is a multifactorial, heterogeneous disease associated with epidermal barrier disruption and intense systemic inflammation. Previously, we showed that exosomes derived from human adipose tissue-derived mesenchymal stem cells (ASC-exosomes) attenuate AD-like symptoms by reducing multiple inflammatory cytokine levels. Here, we investigated ASC-exosomes&rsquo, effects on skin barrier restoration by analyzing protein and lipid contents. We found that subcutaneous injection of ASC-exosomes in an oxazolone-induced dermatitis model remarkably reduced trans-epidermal water loss, while enhancing stratum corneum (SC) hydration and markedly decreasing the levels of inflammatory cytokines such as IL-4, IL-5, IL-13, TNF-&alpha, IFN-&gamma, IL-17, and TSLP, all in a dose-dependent manner. Interestingly, ASC-exosomes induced the production of ceramides and dihydroceramides. Electron microscopic analysis revealed enhanced epidermal lamellar bodies and formation of lamellar layer at the interface of the SC and stratum granulosum with ASC-exosomes treatment. Deep RNA sequencing analysis of skin lesions demonstrated that ASC-exosomes restores the expression of genes involved in skin barrier, lipid metabolism, cell cycle, and inflammatory response in the diseased area. Collectively, our results suggest that ASC-exosomes effectively restore epidermal barrier functions in AD by facilitating the de novo synthesis of ceramides, resulting in a promising cell-free therapeutic option for treating AD.

In psoriasis treatment, not all body regions improve simultaneously after clinical interventions.This study was aimed at evaluating clinical responses across body regions, which may differentially influence patient treatment plans.This prospective, observational, and multi-center study was conducted in Koreans who adhered to ustekinumab treatment based on criteria per local label and reimbursement guidelines. A total of 581 were included in this analysis.The mean (±standard deviation) psoriasis area severity index (PASI) score at baseline, age, disease duration, and body surface area (%) were 18.9±9.69, 44.2±13.29 years, 11.3±9.65 years, and 27.8±17.83, respectively. Across the head and neck, upper extremities, trunk, and lower extremities, the correlation between the PASI sub-scores for the upper and lower extremities was the highest (r=0.680). The mean PASI sub-score for the lower extremities was the highest at baseline. PASI90 and PASI100 scores were the highest for the head and neck region, indicating the highest response rates, while those for the lower extremities were consistently low at all visits.We found differences in regional ustekinumab responses, with the lower extremities being the most difficult to treat. These findings should be considered in psoriasis treatment.

BACKGROUNDThe aim of this study was to validate the performance of algorithm (http://rcnn.modelderm.com) for the diagnosis of benign and malignant skin tumors.METHODSWith external validation dataset (43 disorders; 40,331 clinical images from 10,426 patients; January 1, 2008 – March 31, 2019), we compared the prediction of algorithm with the clinical diagnosis of 65 attending physicians at the time of biopsy request.RESULTSFor binary-task classification of determining malignancy, the AUC of the algorithm was 0.863(95% CI 0.852-0.875) with unprocessed clinical photographs. The sensitivity/specificity of the algorithm at the predefined high-sensitivity and high-specificity threshold were 79.1%(76.9-81.4)/76.9%(76.1-77.8) and 62.7%(59.9- 65.5)/90.0%(89.4-90.6), respectively. The sensitivity/specificity calculated by the clinical diagnosis of attending physicians were 88.1%/83.8%(Top-3) and 70.2%/95.6%(Top-1), which were superior to those of algorithm.For multi-task classification, the mean Top-1,2,3 accuracies of the algorithm were 42.6±20.7%, 56.1±22.8%, 61.9±22.9%, and those of clinical diagnosis were 65.4±17.7%, 73.9±16.6%, 74.7±16.6%, respectively.In the reader test with images from 30-patients batches, the sensitivity / specificity of the algorithm at the predefined threshold were 66.9%±30.2% / 87.4%±16.5%. The sensitivity / specificity derived from the first diagnosis of 44 the participants were 65.8%±33.3% / 85.7%±11.0%, which were comparable with those of the algorithm (Wilcoxon signed-rank test; P=0.61 / 0.097).CONCLUSIONSOur algorithm could diagnose skin tumors at dermatologist-level when diagnosis was made solely with photographs, demonstrating its potential as a mass screening tool in telemedicine setting. However, due to limited data relevancy, the performance was inferior to that of actual medical examination. Clinical information should be integrated with imaging information to achieve more accurate predictions.

We tested the use of a deep learning algorithm to classify the clinical images of 12 skin diseases-basal cell carcinoma, squamous cell carcinoma, intraepithelial carcinoma, actinic keratosis, seborrheic keratosis, malignant melanoma, melanocytic nevus, lentigo, pyogenic granuloma, hemangioma, dermatofibroma, and wart. The convolutional neural network (Microsoft ResNet-152 model; Microsoft Research Asia, Beijing, China) was fine-tuned with images from the training portion of the Asan dataset, MED-NODE dataset, and atlas site images (19,398 images in total). The trained model was validated with the testing portion of the Asan, Hallym and Edinburgh datasets. With the Asan dataset, the area under the curve for the diagnosis of basal cell carcinoma, squamous cell carcinoma, intraepithelial carcinoma, and melanoma was 0.96 ± 0.01, 0.83 ± 0.01, 0.82 ± 0.02, and 0.96 ± 0.00, respectively. With the Edinburgh dataset, the area under the curve for the corresponding diseases was 0.90 ± 0.01, 0.91 ± 0.01, 0.83 ± 0.01, and 0.88 ± 0.01, respectively. With the Hallym dataset, the sensitivity for basal cell carcinoma diagnosis was 87.1% ± 6.0%. The tested algorithm performance with 480 Asan and Edinburgh images was comparable to that of 16 dermatologists. To improve the performance of convolutional neural network, additional images with a broader range of ages and ethnicities should be collected.

Malignancy is a concern in cardiac transplant recipients, but the temporal trends of de novo malignancy development are unknown.The goal of this study was to describe the temporal trends of the incidence, types, and predictors of de novo malignancy in cardiac transplant recipients.The authors analyzed the temporal trends of post-transplant incidence, types, and predictors of malignancy using 17,587 primary adult heart-only transplant recipients from the International Society for Heart and Lung Transplantation registry. The main study outcomes included the incidence of, types of, and time to de novo malignancy.The risk of any de novo solid malignancy between years 1 and 5 after transplantation was 10.7%. The cumulative incidence by malignancy type was: skin cancer (7.0%), non-skin solid cancer (4.0%), and lymphoproliferative disorders (0.9%). There was no temporal difference in the time to development according to malignancy type. However, the cumulative incidence of de novo solid malignancy increased from 2000 to 2005 vs. 2006 to 2011 (10.0% vs. 12.4%; p 0.0001). Survival in patients after de novo malignancy was markedly lower than in patients without malignancy (p 0.0001). Older recipients and patients who underwent transplantation in the recent era had a higher risk of de novo malignancy.More than 10% of adult heart transplant recipients developed de novo malignancy between years 1 and 5 after transplantation, and this outcome was associated with increased mortality. The incidence of post-transplant de novo solid malignancy increased temporally, with the largest increase in skin cancer. Individualized immunosuppression strategies and enhanced cancer screening should be studied to determine whether they can reduce the adverse outcomes of post-transplantation malignancy.

Background The natural course of atopic dermatitis (AD) in infancy, childhood, and adolescence is not yet completely known. Objective To investigate the prevalence and risk factors of atopic dermatits among 19-year-old Korean male subjects. Methods All 19-year-old Korean males must undergo medical examination for conscription. We precisely evaluated the prevalence of AD in three Korean provinces using the information from this physical checkup. AD was diagnosed by experienced dermatologists according to the Hanifin and Rajka criteria. The disease severity was assessed by the scoring of atopic dermatitis (SCORAD) index. In order to investigate the risk factors for AD, a questionnaire was administered to all subjects regarding parental atopic history, geographical characteristics of past habitation, past economic status, number of siblings, parental occupation, etc. Results The point prevalence in the Korean provinces ranged from 1.15% to 1.44%. In multivariable analysis, a parental history of AD was a significant risk factor in all 3 disease-onset groups (infancy, childhood, and adolescent onset). In the infancy-onset group, low economic status was also a significant risk factor for AD. The SCORAD index was significantly higher in AD subjects with early onset and those living in small-sized habitations. Moreover, erythema, edema, lichenification, dryness of skin, and sleep loss appeared to be more severe in early-onset cases. Conclusion The younger the age of disease onset, the more severe the clinical outcomes in 19-year-old male subjects. In addition, active AD treatment at younger ages might affect the prevalence and the severity of AD in adulthood.

An optimized therapeutic regimen involving a non-ablative fractionated laser or radiofrequency therapy for acne scars has not yet been established. To evaluate whether the combination of a non-ablative fractional laser (NAF) and fractional micro-needling radiofrequency (FMR) has clinical advantages for the treatment of atrophic acne scars compared with NAF alone, a 16-week prospective, randomized split-face study was performed. Each facial side of a patient was treated with 3 sessions of either NAF with FMR or NAF alone, with a 4-week interval between each session. Although both sides demonstrated significant decreases in the échelle d’évaluation clinique des cicatrices d’acné (ECCA) score, the facial side treated using the combination regimen demonstrated greater improvement in ECCA score regarding degree and onset time than the NAF-treated side. Histopathological and immunohistochemical results confirmed the clinical findings. This study demonstrated that a combination regimen involving NAF and FMR could be a viable option with satisfactory efficacy.

Objectives To investigate longitudinal changes in behavior and quality-of-life (QoL) in children with sleep disordered breathing (SDB) after adenotonsillectomy (AT). Methods This study prospectively enrolled 148 children who underwent AT for SDB. Caregivers filled out Korean attention deficit hyperactivity disorder (ADHD) rating scale (K-ARS) and Korean version of the obstructive sleep apnea-18 (KOSA-18) at preoperative 1 day, postoperative 1 month, and postoperative 6 months. Longitudinal changes in K-ARS and KOSA-18 were evaluated and compared among subgroups. Results Both K-ARS and KOSA-18 scores improved immediately at postoperative 1 month and were maintained at postoperative 6 months. The mean preoperative K-ARS scores of the non-ADHD, ADHD-trait, and overt-ADHD groups showed uniformly immediate and sustained improvements. Also, the mean preoperative KOSA-18 scores of the small, moderate, and large impact groups were significantly improved both at postoperative 1 month and 6 months. The changes in behavior and QoL showed no significant differences with regard to the aforementioned factors. Conclusion After AT, we may expect immediate and sustained improvements in behavior and QoL in children with SDB regardless of preoperative symptom severity. Moreover, by performing AT, improvements in behavior and QoL are expected regardless of sex, age, allergic trait, or concurrent coblation-assisted turbinoplasty. These findings may help our colleague physicians counselling pediatric SDB patients and their caregivers.

Background: Despite the autologous serum skin test (ASST) and autologous plasma skin test (APST) is widely used test accessing whether a patient with chronic spontaneous urticaria (CSU) has autoreactivity or not, the clinician often encounter difficulty making correlation between the test result and clinical implications. Objective: This study was aimed to find any clinical and laboratory findings related to the ASST and APST response. Agreement and correlation between the two tests was also analyzed. Methods: A retrospective study was conducted on 300 CSU patients who underwent ASST, APST. The subjects were divided into four groups according to the skin test result. Also, the degree of serum and plasma response was recorded. Results: Both ASST and APST positive group had shorter duration of the disease, higher incidence of at least one episode of angioedema than negative group. There were no significant differences in the positivity for autoantibodies including antinuclear, ds-DNA, and thyroid-related between the two groups. The predicted positive rate of ASST and APST according to age showed bimodal peak and decreasing pattern according to disease duration. Predicted positivity of both tests declined with increase in total immunoglobuline E (IgE) level. In the correlation study, the two tests showed high correlation coefficients. Conclusion: ASST and APST positivity may be related to disease duration and severity of CSU. The two tests showed a generally consistent result. Autoreactivity may be gradually lost as disease continues. We suggest the autoreactivity in CSU could arise independently from IgE mediated immune process. (Ann Dermatol 32(4) 280∼288, 2020)

The role of eating frequency (EF) in obesity development has been debated, and few studies have investigated Asian populations. Diet quality might affect the association between EF and obesity. Therefore, we investigated the association between EF and obesity indicators in a representative sample of Korean adults with consideration to diet quality. This cross-sectional study used data of 6951 participants aged 19–93 years (male 49·8 %, female 50·2 %) from the Fourth Korean National Health and Nutrition Examination Survey. EF was assessed using a questionnaire, and diet quality was defined as mean adequacy ratio (MAR). To explore the association between EF and obesity indicators, we used multiple linear regression analyses with and without interaction terms between diet quality and EF. EF was inversely associated with each obesity indicator, including body fat percentage (BF%), BMI and waist circumference (WC), showing a significant linear trend (PPvalue of the interaction term EF×diet quality=0·008 in the regression model for BF%

Although there have been reports of the successful diagnosis of skin disorders using deep learning, unrealistically large clinical image datasets are required for artificial intelligence (AI) training. We created datasets of standardized nail images using a region-based convolutional neural network (R-CNN) trained to distinguish the nail from the background. We used R-CNN to generate training datasets of 49,567 images, which we then used to fine-tune the ResNet-152 and VGG-19 models. The validation datasets comprised 100 and 194 images from Inje University (B1 and B2 datasets, respectively), 125 images from Hallym University (C dataset), and 939 images from Seoul National University (D dataset). The AI (ensemble model; ResNet-152 + VGG-19 + feedforward neural networks) results showed test sensitivity/specificity/ area under the curve values of (96.0 / 94.7 / 0.98), (82.7 / 96.7 / 0.95), (92.3 / 79.3 / 0.93), (87.7 / 69.3 / 0.82) for the B1, B2, C, and D datasets. With a combination of the B1 and C datasets, the AI Youden index was significantly (p = 0.01) higher than that of 42 dermatologists doing the same assessment manually. For B1+C and B2+ D dataset combinations, almost none of the dermatologists performed as well as the AI. By training with a dataset comprising 49,567 images, we achieved a diagnostic accuracy for onychomycosis using deep learning that was superior to that of most of the dermatologists who participated in this study.

Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans.

Assessment of exposure to cosmetic products via the skin is important for evaluating the risks associated with the use of these products. However, few exposure studies have been conducted with babies, particularly in Asia. The aim of our study was to assess the exposure to selected cosmetic products in babies under the age of 36 months, over both winter and summer months. We evaluated exposure for seven cosmetic baby care products identified in a previous web-based survey as being commonly used by Korean parents. Parents were instructed to use their baby's products as per their usual habit, recording usage for each product on a daily basis over a 14-day period. Products were weighed at the start and completion of the study, with the change in weight used to determine the total amount of product used. Descriptive statistics for daily exposure were calculated. In this study, daily exposure for different products was influenced by sex, age groups and seasons. Of specific note, 3.51% of the lotion in a wet wipe was transferred to the skin. In conclusion, we provide baseline exposure data for baby products, with exposure being based on parents' usual use of the products.

Background: For hair care products that are used almost everyday, it is important to estimate the cumulative dosage of long-term exposure and to assess the effects on the human body. Little data are available to evaluate actual daily usage in Asian populations. Objective: Reliable exposure data for hair care products is essential to conduct safety assessments. Methods: We evaluated the actual usage pattern and amounts by checking the daily log over a 2-week period, to obtain all the data regarding the participants’ hair care preferences. And, statistical analyses were conducted to analyze the daily use amount (g/d) and daily usage per hair length (g/cm/d), and other variables by sex, age group, and hair oiliness. Results: Throughout this study, we found that female users consumed significantly larger daily amounts of shampoo and rinse. Male groups used more hair gel and spray than female groups. Interestingly, all the hair care products studied scored higher levels of usage among men when calibrated per unit length. Koreans tend to use lesser amount of rinse although their hairs are usually thicker than the Western hairs. Conclusion: This study provides exposure information for commonly used hair care products, which will be useful for risk assessment purposes. (Ann Dermatol 31(3) 307∼314, 2019)

Despite daily exposure to chemicals in cosmetic products, there are few studies on the exposure levels to cosmetics particularly in Asians. We sought to investigate the usage pattern of cosmetics, including eye makeup products, fragrances, color makeups, and hair and nail care products, in Koreans. An online survey of 1,800 participants (908 males and 892 females, aged 15-59 years) from 5 Metropolitan cities (Seoul, Incheon, Daejeon, Daegu, and Busan) in Korea was conducted. For overall types of cosmetics, the proportion of users was 7.1% (range: 0.0-46.3%) in males and 30.7% (range: 1.0-82.8%) in females. The most prevalently used product was perfume (46.3%) in males and lipstick (82.8%) in females. In addition, the mean number of application for overall types of cosmetics was 22.7 (range: 4.6-49.4) times per month in male users and 24.8 (range: 4.2-62.0) in female users. The usage pattern was significantly altered according to demographic and socioeconomic factors, including age group, occupation, and income. This work estimated the prevalences and frequencies of use of a wide collection of cosmetics from a large number of Koreans and found that the usage pattern was significantly associated with demographic and socioeconomic factors.

Background: Increasing evidence suggests a pivotal role for neuronal inflammation in response to replicating varicella zoster virus in the development of postherpetic neuralgia (PHN). Objective: In this study, we investigated the value of serum levels of various inflammatory markers in acute herpes zoster (HZ) as predictors for the development of PHN. Methods: A total of 116 patients with acute HZ were enrolled in this study. We measured scores on the pain visual analogue scale (VAS) at baseline and at 1, 3, and 6 months after diagnosis of HZ. We defined PHN as pain greater than 1 on the VAS lasting for more than 6 months. Serum samples for laboratory assay, including complete blood count were obtained at the initial visit. Correlations between the levels of each inflammatory marker and the development of PHN were evaluated. Results: Levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lymphocyte count, and albumin showed significant correlations with development of PHN in univariate analysis. Levels of ESR, CRP, and lymphocyte count also showed significant correlations in multivariate analysis. ESR level showed stronger correlations with development of PHN than levels of CRP and lymphocyte count. Conclusion: In this study, we confirmed that elevated ESR was an independent and significant predictor of PHN in patients with acute HZ. To validate these results, further well-designed, randomized clinical trials are needed. (Ann Dermatol 30(2) 158∼163, 2018)

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)

Chronic spontaneous urticaria (CSU) is a complex idiopathic disease of the skin with various cellular infiltrations. Although mast cells are key effector cells in the pathogenesis of CSU, CD4+ T helper 2 cells also have particular roles in the development and maintenance of CSU. Periostin is known as a downstream molecule of interleukin (IL)-4 and IL-13, key cytokines of type 2 immune responses. In this study, we examined periostin and IL-13 levels in the sera of patients with CSU (n=84) and healthy normal controls (NCs, n=43). Periostin levels were significantly lower in the CSU group than in NCs (71.4±21.8 vs 85.1±22.4 ng/mL, P=0.04). Periostin levels were also lower in the severe CSU group than those in mild CSU (59.7±18.0 vs 73.4±22.0 ng/mL, P=0.04). However, IL-13 levels were significantly higher in patients with CSU than in NCs (508.5±51.2 vs 200.7±13.3 pg/mL, P=0.001). In conclusion, periostin and IL-13 may be independently related to the pathogenesis of CSU.

Dear Editor: Here, we describe a case of acquired dermal melanocytosis involving the dorsum in an Asian woman. A 45-year-old Korean woman presented with a 3-year history of a relatively well-demarcated, pale, blue-grayish, asymptomatic round patch on her interscapular back area (Fig. 1). Hypertrichosis was not observed within the lesion. Physical examination revealed no other similar lesions elsewhere. The patient denied any history of preceding inflammatory changes, trauma, bruises, tattoos, or metal contact on her back. She also denied taking heavy metals or any medicines that may result in hyperpigmentation and had no family history of similar skin lesions. Histopathologic examination revealed multiple spindle-shaped brown pigment-containing cells scattered among collagen fibers in the dermis (Fig. 2A, B). Immunohistochemical staining demonstrated these cells were positive for S100 protein (Fig. 2C) and negative for HMB-45 (data not shown). In addition, the brown pigment stained positive with Fontana-Masson stain, which is indicative of melanin (Fig. 2D), but not with Perls Prussian blue stain for hemosiderin (data not shown). Furthermore, immunohistochemistry revealed CD68-positive cells scattered in the dermis (Fig. 2E). Therefore, the patient was diagnosed with acquired dermal melanocytosis of the back, but no treatment was administered in accordance with the patient's wishes. Fig. 1 A relatively well-demarcated pale blue-grayish round patch on the interscapular area. Fig. 2 Histopathologic examinations and immunohistochemistry. (A, B) Multiple spindle-shaped brown pigment-containing cells scattered among collagen fibers in the dermis (HE A: ×100, B: ×200). (C) Immunohistochemical staining showed ... Dermal melanocytosis is defined by the presence of melanin-containing dendritic melanocytes in the dermis and can be differentiated on the basis of lesion onset and location1. Congenital forms of dermal melanocytosis include Mongolian spot, nevus of Ota, and nevus of Ito. Acquired forms of dermal melanocytosis include nevus of Hori and nevus of Sun, which involve the bilateral and unilateral malar areas, respectively. Acquired dermal melanocytosis located in areas besides the face is very rare; previously reported non-facial sites include the extremities and back1,2. Some of these reported cases were associated with malignancies including melanoma, physical trauma, oral estrogen, and eczema2. Although the pathogenesis of acquired dermal melanocytosis is unclear, one possibility is that dermal melanocytes may pre-exist in an immature state; they subsequently become activated by various stimuli including ultraviolet exposure, sex hormones, and inflammation3,4. This is supported by the observation that dermal melanocytes are also found in the normal-appearing skin neighboring the lesions of acquired dermal melanocytosis5. Nevertheless, the origin of the pre-existing dermal immature melanocytes is not fully understood. They may descend from the basal layer of the epidermis, migrate from hair bulbs, or improperly migrate during the embryonic period4. Acquired dermal melanocytosis does not usually fade; the pigment persists in contrast with Mongolian spots. This persistence may be associated with the extracellular sheath encircling dermal melanocytes, which has been observed in ultrastructural studies4. The extracellular sheaths of Mongolian spots usually fade over time, whereas those of nevus of Ota gradually thicken over time. Extracellular sheaths are also observed in acquired dermal melanocytosis and presumably play a role in protecting dermal melanocytes4. In conclusion, we report a case of acquired dermal melanocytosis with an unusual location that has not been described previously.

Postherpetic neuralgia (PHN) is one of the most severe sequelae of herpes zoster events. Several risk factors have been reported for PHN, including old age, severe skin rash, and intense pain. This study therefore aims to evaluate the usefulness of the Self-completed Leeds Assessment of Neuropathic Symptoms and Signs pain scale (S-LANSS) in conjunction with previously reported risk factors for predicting PHN. A group of herpes zoster patients (N = 305) were included in the cohort study. Subjects were asked for their demographic information, clinical symptoms and signs, intensity of pain by visual analog scale (VAS), and S-LANSS. They were followed up in clinical visits or via telephone for 12 months. Nineteen patients (6.2%) suffered from PHN in this study. Using logistic regression, 3 risk factors for PHN were identified: age ≥70 years, high VAS scores, and high S-LANSS scores. Prediction of PHN using VAS (≥8) and S-LANSS (≥15) criteria achieved a sensitivity of 78.9% and specificity of 78.0%. Prediction of PHN in elderly patients (≥70 years), using the criteria of VAS (≥6) and S-LANSS (≥15) as well, achieved 100% sensitivity and 57.1% specificity. S-LANSS could be a useful prediction tool for PHN, particularly if combined with previously well-known risk factors and VAS. Perspective Among acute herpes zoster patients, subjects with characteristics of neuropathic pain showed high frequency of PHN. The tools for screening neuropathic pain like S-LANSS could be helpful for predicting PHN and enabling early intervention of pain management.

Background Fractional laser resurfacing treatment has been extensively investigated and is widely used. However, the mechanism underlying its effects is poorly understood because of the ethical and cosmetic problems of obtaining skin biopsies required to study the changes after laser treatment. Objective To evaluate the usefulness of human skin explants for the investigation of fractional photothermolysis. Methods Full-thickness discarded skin was treated in 4 ways: no treatment (control), fractional carbon dioxide laser, fractional Er:YAG laser, and fractional 1,550-nm erbium-doped fiber laser. Both treated and non-treated skin samples were cultured ex vivo at the air-medium interface for 7 days. Frozen tissue was sectioned and stained with hematoxylin & eosin for histologic examination and nitro blue tetrazolium chloride for viability testing. Results Skin explants cultured for up to 3 days exhibited histologic changes similar to those observed in in vivo studies, including microscopic treatment zones surrounded by a thermal coagulation zone, re-epithelialization, and formation of microscopic epidermal necrotic debris. However, the explant structure lost its original form within 7 days of culture. The viability of skin explants was maintained for 3 days of culture but was also lost within 7 days. Conclusion The skin explant model may be a useful tool for investigating the immediate or early changes following fractional photothermolysis, but further improvements are required to evaluate the long-term and dermal changes.

Background: Physicians can play a crucial role in the knowledge that patients have about a disease and its prognosis. Recently, patients with atopic dermatitis (AD) are increasingly turning from western medicine to oriental herbal medicine. However, their awareness of AD and attitude toward Western medicine and oriental herbal medicine clinics are scarcely reported. Objective: The aim of this study was to determine the understanding of AD among patients and their parents and to identify their awareness of and attitude toward Western medicine and oriental herbal medicine as treatments for AD. Methods: An online questionnaire was administered to 500 consenting respondents with AD (age, 16∼49 years) and parents of children with AD (age, 0∼15 years). Results: The mean percentage of correct answers to questions about AD was 52.54%. A parental history of AD was independently associated with higher respondent`s knowledge about the disease and its treatment. The satisfaction with treatment outcomes was highest among patients treated at private clinic of dermatology specialists (49.4%), while lowest among those treated at oriental herbal medicine clinics (38.4%). Many participants were aware that oriental herbal medicine requires a longer treatment period for a cure and does not burden the skin, while steroid phobia was seen in most of participants. Conclusion: Physicians need to educate AD patients and their parents about the disease and its treatment. Misconceptions for Western medicine and oriental herbal medicine among AD patients and parents should be corrected to improve their prognosis. (Ann Dermatol 28(6) 725∼732, 2016)

Background Avoidance behavior against positive allergens detected by using multiple allergen simultaneous test (MAST)-immunoblot assay in patients with urticaria has been rarely reported. Objective We aimed to assess the avoidance behavior of patients with urticaria against positive allergens detected with a MAST. Methods One hundred and one urticaria patients who showed positivity to at least one allergen on a MAST completed a questionnaire regarding their test results. The avoidance behavior of the patients was evaluated, and relevant determining factors of avoidance success/failure were statistically assessed. Results We detected 144 different data (n=51, food allergens; n=17, pollen allergens; and n=76, aeroallergens) from 101 patients with urticaria. The avoidance failure rates were 33.3% for food allergens, 70.6% for pollen allergens, and 30.3% for aeroallergens. The pollen group showed a significantly higher avoidance failure rate than the food and aeroallergen groups (p

Epidermal stem cells (SC) are believed to be resistant to environmental damage for the purpose of self renewal. Most promising SC markers include integrin a6 and p63. The aim of our study was to determine whether the integrin a6+p63+ cell fraction representative of the epidermal progenitor or SC is increased after ultraviolet B (UVB) irradiation and to clarify the hypothesis that epidermal SC are resistant to high-dose UVB damage. We irradiated early passage normal human keratinocytes (NHK) with 0, 25, 50, and 100 mJ/cm2 UVB. The percentage of cell death was calculated. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting analyses were performed to identify integrin a6 and p63, and flow cytometry analysis with integrin a6 and p63 antibodies was done. After 50 and 100 mJ/cm2 UVB, integrin a6+p63+cells were found to be much increased by fluorescence-activated cell sorting. Expression of integrin a6 and p63 was increased in NHK after UVB irradiation, which was shown with real-time RT-PCR and western blotting analyses. We concluded that an increase of integrin a6+p63+ cells after high-dose UVB may suggest that the putative progenitor or SC are resistant to UVB irradiation.

Papulonodular mucinosis (PNM) is a rare variant of lupus erythematosus (LE) eruptions, and PNM is characterized histologically by diffuse dermal mucin without any typical epidermal inflammatory changes. We herein describe a case of papular mucinosis that was characterized by several erythematous papules on the lower back of a 32-year-old man with systemic LE. It is interesting that he didn't display any other skin manifestations of LE such as malar rash, discoid rash and photosensitivity during the previous 2 years. He achieved remission of his PNM without recurrence after 5 months treatment with topical steroids, in addition to receiving systemic antimalarials and steroids.

Merkel cell carcinoma is a rare aggressive primary cutaneous neuroendocrine skin cancer arising from the basal epidermis. Although the majority of patients with non-melanoma skin cancer are cured by local treatment, patients with Merkel cell carcinoma have a poor outcome characterized by locoregional and distant relapse. No standard treatment protocol for Merkel cell carcinoma exists. But, there is mounting evidence that combined treatment, incorporating adjuvant radiotherapy, improves the outcome (locoregional control and disease-free survival) compared with surgery alone in most patients. Herein we report a case of Merkel cell carcinoma treated with wide local excision and post-operative radiotherapy.