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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.

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.

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.

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.

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.

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.

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.