PSORIASIS INCREASES RETINAL VEIN OCCLUSION RISK IN DIABETIC PATIENTS: A Nationwide Population-Based Study.

PURPOSE: The objective of this research was to explore how psoriasis is linked to the occurrence of retinal vein occlusion (RVO) in diabetic population. METHODS: This was a retrospective, nationwide, population-based cohort study that examined medical records from January 2009 to December 2012. The study focused on patients ≥20 years of age who had been diagnosed with Type 2 diabetes mellitus (DM). The authors compared the incidence rate of RVO between a group of patients with psoriasis and a group of patients without psoriasis until December 2018 in all subjects. RESULTS: Of the 2,745,689 Type 2 DM patients, 23,725 patients were classified in the psoriasis group and the rest of the 2,547,121 individuals in the control group. A total of 497 RVO cases occurred in the psoriasis group (3.14/1,000 person-years) and 42,388 RVO cases in the control group (2.44/1,000 person-years). According to multivariable Cox proportional hazard models, individuals with psoriasis had a significantly greater risk of developing RVO compared with control subjects (hazard ratio: 1.216, 95% confidence interval: 1.11-1.33) after adjustments for covariates. CONCLUSION: This study demonstrated that psoriasis was an independent risk factor for developing RVO in DM patients. Therefore, physicians need to be vigilant for the occurrence of RVO in DM patients who also have psoriasis.

A Phase 3, Randomized, Multi-center Clinical Trial to Evaluate the Efficacy and Safety of Neu-BoNT/A in Treatment of Primary Axillary Hyperhidrosis.

BACKGROUND: Botulinum toxin type A is widely used to treat primary axillary hyperhidrosis and has proven to be an effective and safe approach. Onabotulinumtoxin A was approved by the FDA as a treatment for primary axillary hyperhidrosis. This study aimed to evaluate the efficacy and safety of Neu-BoNT/A in subjects diagnosed with primary axillary hyperhidrosis. METHODS: The Hyperhidrosis Disease Severity Scale, gravimetric measurement of sweat, and Global Assessment Scale were analyzed at weeks 4, 8, 12, and 16 to determine the effect of treatment. Adverse events, physical examination, and vital signs were monitored. RESULTS: Subjects treated with Neu-BoNT/A showed statistically significant improvement by all 3 methods at weeks 4, 8, 12, and 16 (P value = 0.00). There were no severe adverse events or significant changes in vital signs, physical examination, or laboratory tests. CONCLUSION: Neu-BoNT/A can be effectively and safely used for primary axillary hyperhidrosis. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Investigation of Genetic Mutations in High-risk and Low-risk Basal Cell Carcinoma in a Non-Caucasian Population by Whole Exome Sequencing.

This study analysed genomic mutations in basal cell carcinoma using whole exome sequencing of DNA specimens obtained from 20 Korean patients. Histological evaluation determined that 15 (75%) were low-risk basal cell carcinomas, and 5 (25%) were high-risk basal cell carcinomas. Seventy-five percent of the basal cell carcinomas harboured somatic mutations in hedge-hog pathway genes (PTCH1, 40% and SMO, 50%) and 45% harboured mutations in TP53. LRP1B was the most frequently mutated gene in high-risk basal cell carcinomas, SMO was the most frequently mutated gene in low-risk basal cell carcinomas. Specifically, LRP1B, ROS1, PTCH1, KMT2C, NSD1 and ARID1A mutations were more frequent in high-risk basal cell carcinomas than in low-risk basal cell carcinomas. However, copy number gains of the ROS1 gene were observed only in low-risk basal cell carcinomas. Other basal cell carcinoma related genes found in this study include: KDR, KMT2D, FAT1, FAT4, GRIN2A, ERBB4, NOTCH2, PDE4DIP, TET1, ZFHX3 and PREX2. These results provide insight into basal cell carcinoma in non-Caucasians.

Association of Actinic Keratosis with Rheumatoid Arthritis and Psoriasis: A Nationwide Population-Based Study in Korea.

There have been no epidemiological studies identifying associations between systemic inflammatory diseases and actinic keratosis. This study used a large nationwide database to investigate the associations between actinic keratosis and systemic inflammatory diseases. Records of patients over 20 years of age newly diagnosed with actinic keratosis (n = 64,659) from 2012 to 2017 were analysed. A control population of individuals without actinic keratosis, matched for age, sex, and year of claim, who visited an outpatient clinic, was sampled at a ratio of 1:1 (n = 64,659). Both cohorts were analysed for the presence of systemic inflammatory diseases within at least 5 years prior to diagnosis of actinic keratosis. Patients with actinic keratosis exhibited higher odds ratios for rheumatoid arthritis (1.336; 95% confidence interval (95% CI) 1.161-1.537)) and psoriasis (1.513; 95% CI 1.435-1.595) compared with the control group on multivariate analysis. However, the proportions of Behçet's disease, Crohn's disease, ulcerative colitis, and multiple sclerosis in the actinic keratosis group were not statistically significant.

Cancer risk in patients with Behçet disease: A nationwide population-based dynamic cohort study from Korea.

BACKGROUND: Many studies have shown a link between inflammation and cancer development. However, there are few studies regarding the correlation between Behçet disease (BD) and cancer. OBJECTIVES: To determine the overall cancer risk and risk for specific cancers in patients with BD. METHODS: Patients with BD (n = 14,137; mean age, 44.2 ± 12.5 years; male patients, 32.4%) without known previous cancer were selected from the Korean National Health Insurance Database between 2007 and 2014. An age- and sex-matched control population of individuals without BD was randomly sampled at a ratio of 10:1. Both cohorts were followed for incident cancer until 2015. RESULTS: Overall, cancer was newly diagnosed in 451 patients with BD (3.19%) and 3975 controls (2.81%) during the follow-up period. Patients with BD showed a significantly higher risk for cancer compared with the controls (hazard ratio [HR], 1.134; 95% confidence interval [CI], 1.029-1.25), leukemia (HR, 5.801; 95% CI, 3.24-10.385), lymphoma (HR, 2.584; 95% CI, 1.559-4.283), oral cavity and pharyngeal cancer (HR, 2.113; 95% CI, 1.102-4.052), thyroid cancer (HR, 1.256; 95% CI, 1.05-1.501), and prostate cancer (HR, 1.784; 95% CI, 1.141-2.791). LIMITATIONS: The treatment or severity of diseases in each individual was not examined. CONCLUSIONS: Patients with BD had a higher risk for overall cancer compared with controls without BD. Physicians should carefully monitor patients with BD for the potential development of malignancies.

Subsequent vitiligo after hematopoietic stem cell transplantation: A nationwide population-based cohort study from Korea.

BACKGROUND: Subsequent vitiligo after hematopoietic stem cell transplantation (HSCT) has been described sporadically in case series. OBJECTIVE: To investigate the incidence and risk factors of subsequent vitiligo after HSCT. METHODS: A nationwide, population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2009 to 2013. All HSCT recipients who had undergone HSCT between 2010 and 2011 and not treatment for vitiligo in 2009 (to exclude preexisting active vitiligo) were included in the HSCT recipient group, and an age- and sex-matched control group without HSCT was also established. RESULTS: A total of 2747 HSCT recipients and 8241 controls were enrolled. Newly acquired vitiligo occurred in 1.06% of HSCT recipients between 2010 and 2013, and there was a significant increase (OR 3.130, 95% CI 1.859-5.271) in cases of vitiligo in HSCT recipients compared with controls (0.34%). Allogeneic HSCT (OR 5.593, 95% CI 1.628-19.213) and bone marrow-sourced stem cells (as compared with peripheral blood-sourced stem cells; OR 2.492, 95% CI 1.114-5.576) were independently associated with the development of vitiligo after HSCT. LIMITATIONS: Medical record review was not available. CONCLUSION: Vitiligo developed at a significantly increased rate after HSCT compared with controls. Allogeneic HSCT and bone marrow-sourced stem cells were independent risk factors.

Combination treatment of low-fluence Q-switched Nd:YAG laser and oral tranexamic acid for post-inflammatory hyperpigmentation due to allergic contact dermatitis to henna hair dye.

A 64-year-old female presented with facial hyperpigmentation. She had dyed her hair monthly with pure henna powder for the past seven months. After patch tests, the patient was diagnosed as post-inflammatory hyperpigmentastion due to allergic contact dermatitis to pure henna that has rarely been reported. The patient underwent Q-switched Nd:YAG laser treatment and was treated with oral tranexamic acid for 10 weeks. The hyperpigmentation on her forehead demonstrated substantial improvement.

Twenty-four-week multicenter, evaluator-blinded clinical study of the efficacy and safety of a dextran filler in the treatment of nasolabial folds.

BACKGROUND: Cross-linked dextran shows complete degradation in the vital tissue and has characteristics of neocollagenesis. However, its efficacy as a dermal filler in treating facial soft tissue defects has not been investigated. OBJECTIVE: To evaluate the efficacy and safety of subcutaneous injection of a dextran filler in treating nasolabial folds for 24 weeks. METHODS AND MATERIALS: Twenty patients were enrolled in this 24-week multicenter, evaluator-blinded clinical study. Each patient received a single session of a dextran filler treatment in both nasolabial folds, and no touch-up injections were given. Treatment efficacy was evaluated by blinded investigators at 4, 12, and 24 weeks after baseline. Safety data were collected from patient diaries and interviews at each follow-up visit. RESULTS: There were significant improvements (p<.0001) in the Wrinkle Severity Rating Scale scores compared with those at baseline with a mean decrease of 1.50±0.51 at 24 weeks. Only 1 mild treatment-related adverse event was noted throughout the 24-week follow-up period. CONCLUSION: Cross-linked dextran-derived injectable filler is considered to be a favorable measure in tissue augmentation of the nasolabial folds. Further investigation is needed to demonstrate the long-term efficacy and safety of dextran fillers.

Safety and efficacy of a novel injectable filler in the treatment of nasolabial folds: polymethylmethacrylate and cross-linked dextran in hydroxypropyl methylcellulose.

Nasolabial folds are a sign of aging and increasing number of people want filler injections in their nasolabial folds to look younger. Various dermal fillers are used for the correction of nasolabial folds. Recently, a novel injectible filler, polymethylmethacrylate (PMMA) and cross-linked dextran in hydroxypropyl methylcellulose, was introduced for facial contouring. This study was designed as a six-month, prospective, single-blinded, and open-label study in two centers located in Korea. Nineteen Korean patients received the novel filler injections on both nasolabial folds. At Weeks 4, 12, and 24, the efficacy and safety of the dermal filler were evaluated by blinded-investigators using clinical photographs. The mean Wrinkle Severity Rating Scale revealed significant decrease after dermal filler injections at each study visit. The decreased Wrinkle Severity Rating Scale was maintained for 6 months (p < 0.0001). The Global Aesthetic Improvement score showed an improvement greater than 2 in 95% of the per-proto col population 24 weeks after the injections. All patients (100%) experienced an improvement of their nasolabial folds at Week 24. There were no complications related to the novel filler injection. The novel dermal filler, PMMA, and cross-linked dextran in hydroxylpropyl methylcellulose, can be another safe and effective treatment option in the treatment of nasolabial folds.

Histology of a novel injectable filler (polymethylmethacrylate and cross-linked dextran in hydroxypropyl methylcellulose) in a rat model.

A novel injectable filler of polymethylmethacrylate (PMMA) and cross-linked dextran in hydroxypropyl methylcellulose was introduced in the commercial filler market. For soft tissue augmentation, safety and biocompatibility should be evaluated and the stability at the implantation site should be assessed using histologic evaluation. In order to evaluate the biocompatibility of the novel soft tissue filler, PMMA and cross-linked dextran in hydroxypropyl methylcellulose was subdermally injected into the skin of Sprague-Dawley Rats. Histologic evaluation was performed at 13 weeks and 12 months after the injection. Inflammatory cell infiltration, neovascularization, and fibrosis were scored according to defined grading systems. The mean score of the histologic evaluation was 5.7 and 3.9 at 13 weeks and 12 months, respectively. At 12 months after injection, the PMMA and cross-linked dextran in hydroxypropyl methylcellulose appeared to be kept in place through fine fibrous capsules. The mixture of PMMA and cross-linked dextran in hydroxypropyl methylcellulose can be safely applied for soft tissue augmentation with longevity of greater than 12 months.

Recent trends (1991-2010) of metastatic skin cancers in Korea.

The incidence of overall cancer has increased over time. The incidence of top-ranking cancers has changed in the 1990s and the 2000s. However, few studies have evaluated the trends in metastatic skin cancers during this period. We evaluated the recent trends in incidence, peak age and location of metastatic skin cancers from 1991 to 2010. This 20-yr survey was divided into two decades to determine the trends by comparing the statistics. Out of 694,466 outpatients (1991-2010), 174 (0.025%) were diagnosed with metastatic skin cancer. The incidence of metastatic skin cancer increased significantly from 20.64 per 100,000 outpatients in the 1990s to 28.70 per 100,000 outpatients in the 2000s (P = 0.030). The peak age of skin metastasis shifted from the 40s to the 50s in women, and from the 50s to the 60s in men. The percentage of metastatic skin cancers originating from intra-abdominal organs increased from 10% in the 1990s to 23.1% in the 2000s (P = 0.027). The percentage of metastatic skin cancers located on the abdomen increased from 7.1% in the 1990s to 15.4% in the 2000s (P = 0.011). The higher proportion of metastatic skin cancers located on the abdomen may be related to the increase in skin metastases from intra-abdominal organs.

Distant Metastatic Microcystic Adnexal Carcinoma.

Microcystic adnexal carcinoma (MAC) is a rare malignant neoplasm of ductal origin. MAC is a clinically aggressive, locally destructive tumor with a high rate of recurrence, but distant metastasis is rare. A 55-year-old male who had been taking immunosuppressants for 2 years after a liver transplantation due to hepatocellular carcinoma presented with a dermal nodule on the sole. He visited the clinic because the nodule, discovered 3 months ago, continued to increase in size. The histopathologic findings from the lesion were consistent with MAC. The patient underwent wide local excision and confirmed a histologically negative margin. After 11 months, the patient revisited with multiple skin nodules on the buttock, back, and right forearm that were distant from the primary tumor site. The lesions were histologically confirmed as MAC. We report a rare case of MAC with distant metastasis.

Identification of genetic mutations of cutaneous squamous cell carcinoma using whole exome sequencing in non-Caucasian population.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer worldwide. Recent studies have reported several genetic mutations in development of cSCC such as TP53, HRAS, and NOTCH1. Whole-exome sequencing (WES) of cSCC has not been reported in East Asian populations. OBJECTIVE: We aimed to investigate genetic mutations of cSCCs in Korean patients by WES. METHODS: cSCCs and paired peripheral blood samples were obtained from 19 Korean patients who underwent wide excision on the cheek from 2016 to 2020 and divided into moderate to poor-differentiated (MP-D) cSCCs (n = 9) and well-differentiated (W-D) cSCCs (n = 10) according to the histopathological evaluation. WES was performed for analysis of genomic mutations of cSCCs. RESULTS: The mean total mutation burden of MP-D cSCCs was higher than W-D cSCCs. Also, we observed proportionately more driver mutations in MP-D cSCC than W-D cSCC groups. CSMD3, COL22A1, FMN2, and ASXL3 mutations are highly frequent than the results of previous reports in cSCC of Caucasians. CONCLUSION: These results may aid in further our understanding of the complex process underlying tumorigenesis of cSCC in non-Caucasian populations.

Astaxanthin Protects Ultraviolet B-Induced Oxidative Stress and Apoptosis in Human Keratinocytes via Intrinsic Apoptotic Pathway.

Background: Ultraviolet radiation causes skin damage due to increased production of reactive oxygen species (ROS) and inflammatory intermediates and direct attack of DNA of skin cells. Astaxanthin is a reddish pigment that belongs to a group of chemicals called carotenoids and has protective effects as an antioxidant. Objective: To determine the beneficial effects of astaxanthin on damaged human skin after exposure to ultraviolet radiation. Methods: Normal human epidermal keratinocytes (NHEKs) were pre-treated with astaxanthin for 24 hours and exposed to ultraviolet B (UVB) irradiation. After 24 hours, the Cell Counting Kit-8 (CCK-8) assay measured cell viability, ROS assay and flow cytometry analysis assessed apoptosis, and western blotting was performed to determine expression of apoptosis-related proteins. Results: Astaxanthin significantly inhibited UVB-induced NHEKs cytotoxicity. Pretreatment of NHEKs with astaxanthin reduced UVB-induced ROS production. Astaxanthin caused significant inhibition of UVB-induced apoptosis, as evidenced by flow cytometry analysis and western blotting. Conclusion: These results suggest that astaxanthine has a beneficial effect of reducing damage caused by UVB by effectively inhibiting cell death and reducing ROS production in keratinocytes.

Incidence and death rate of sarcoidosis in Korea in association with metabolic diseases.

Sarcoidosis is a systemic granulomatous disease that affects a variety of organs. Although the etiology has not been fully understood, it is thought that diverse genetic and environmental factors interact with the immune system to develop granulomas. The incidence and death rate of sarcoidosis vary according to race. This study was conducted to identify the epidemiology of sarcoidosis in Korea and reveal its association with comorbid diseases such as diabetes mellitus, hypertension, and dyslipidemia in a population-based database. We retrospectively analyzed Korean National Health Insurance claims data between 2006 and 2017. The average annual incidence from 2006 to 2017 was 0.82/100 000 person-years and the all-cause death rate in sarcoidosis patients was 9.25/1000 cases. The incidence of sarcoidosis was higher in patients with diabetes mellitus, hypertension, and dyslipidemia than patients without those underlying diseases. Sarcoidosis patients with diabetes mellitus and hypertension showed an increased death rate after adjusting the confounding factors (hazard ratio [95% confidence interval], 1.66 [1.23-2.23] and 1.73 [1.29-2.31] respectively), however, patients with dyslipidemia showed a low death rate (HR = 0.64 [0.46-0.88]). In conclusion, we found that sarcoidosis is associated with diabetes mellitus, hypertension, and dyslipidemia and that diabetes mellitus and hypertension increase the risk of death in sarcoidosis patients. Extra caution is needed in sarcoidosis patients who already have these metabolic diseases.

Severe Scalp Psoriasis Microbiome Has Increased Biodiversity and Relative Abundance of Pseudomonas Compared to Mild Scalp Psoriasis.

Psoriasis is a chronic inflammatory skin disease associated with various factors. Recently, alterations in the gut and skin microbiomes have been shown to interact with host immunity, affect skin barrier function, as well as development and progression of psoriasis. We aimed to analyze the microbiota of the scalp of patients with psoriasis and determine the characteristics of the microbiome according to disease severity. We investigated the scalp microbiome of 39 patients with psoriasis scalp lesions and a total of 47 samples were analyzed. The patients were divided into mild, moderate, and severe groups according to the European recommendations for scalp psoriasis. For bacterial identification, we utilized the SILVA database targeting the V3 region of the 16 S rRNA gene. The mean Shannon index escalated along with disease severity, and the diversity of the scalp microbiome tended to increase with disease severity (R = 0.37, p < 0.01). The relative abundance of Pseudomonas was increased in severe scalp psoriasis (0.49 ± 0.22) compared to the mild group (0.07 ± 0.03, p = 0.029), and Diaphorobacter was enriched in the mild group (0.76 ± 0.16%) compared to the severe group (0.44 ± 0.22, p < 0.001). We identified that increased diversity of the scalp microbiome and the relative abundance of Pseudomonas are associated with the severity of scalp psoriasis.