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.

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.

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.

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.

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.

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 .

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.

NaHCO3- and NaCl-Type Hot Springs Enhance the Secretion of Inflammatory Cytokine Induced by Polyinosinic-Polycytidylic Acid in HaCaT Cells.

BACKGROUND: Background: Hot springs have been traditionally used as an alternative treatment for a wide range of diseases, including rheumatoid arthritis, bronchial asthma, diabetes, hypertension, psoriasis and atopic dermatitis. However, the clinical effects and therapeutic mechanisms associated with hot springs remain poorly defined. OBJECTIVE: The purpose of this study was to demonstrate the different effects of hot springs on cellular viability and secretion of inflammatory cytokines on keratinocyte in two geographically representative types of hot springs: NaHCO3-type and NaCl-type, which are the most common types in South Korea. METHODS: We performed WST-1, BrdU measurements, human inflammatory cytokine arrays and enzyme-linked immunosorbent assay in HaCaT cells stimulated with toll-like receptor 3 by polyinosinicpolycytidylic acid. RESULTS: The interaction effects of cell viability and cell proliferation were not significantly different regardless of polyinosinic-polycytidylic acid stimulation and cultured hot springs type. Cytokine array and enzymelinked immunosorbent assay analysis showed increased expression of inflammatory cytokines such as interleukin6 and granulocyte-macrophage colony-stimulating factor by polyinosinic-polycytidylic acid stimulation, with expression levels differing according to hot springs hydrochemical composition. Cytokine reduction was not significant. CONCLUSION: The effects and mechanisms of hot springs treatment in keratinocytes were partially elucidated.

Positive association between actinic keratosis and internal malignancies: a nationwide population-based cohort study.

Little is known about the comorbidities in actinic keratosis patients. To evaluate the association of actinic keratosis with certain malignancies. All patients with actinic keratosis (n = 61,438) and age- and sex-matched control subjects (n = 307,190) at a 5:1 ratio were enrolled using data from the Korean National Health Insurance Service between the years 2007 and 2014. In subjects with actinic keratosis, overall cancer incidence was higher than that for controls after income level, habitat, diabetes, hypertension, and dyslipidemia were adjusted (Hazard Ratio [HR] = 1.43 [95% confidence interval 1.38-1.47]). The positive association of specific cancers were observed in the following order: skin cancer (HR = 3.43 [2.47-4.75]), oral cavity and pharyngeal cancer (HR = 1.99 [1.57-2.52]), lymphoma (HR = 1.59 [1.28-1.96]), leukemia (HR = 1.35 [1.03-1.77]), prostate cancer (HR = 1.35 [1.21-1.51]), renal cancer (HR = 1.29 [1.02-1.63]), liver cancer (HR = 1.21 [1.09-1.35]), thyroid cancer (HR = 1.20 [1.05-1.38]), and gastric cancer (HR = 1.13 [1.03-1.23]). Although further research on pathologic mechanism is needed, the implications of a positive correlation between actinic keratosis and internal organ malignancies has great significance.

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.

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 between vitiligo and smoking: A nationwide population-based study in Korea.

No study has examined the associations between vitiligo and smoking. The purpose of this study was to investigate the incidence of vitiligo according to smoking status. We used clinical data from individuals aged over 20 years who received a health examination in the National Insurance Program between 2009 and 2012 (n = 23,503,807). We excluded individuals with pre-existing vitiligo who had ever been diagnosed with vitiligo before the index year (n = 35,710) or who were diagnosed with vitiligo within a year of the index year (n = 46,476). Newly diagnosed vitiligo was identified using claims data from baseline to date of diagnosis or December 31, 2016 (n = 22,811). The development of vitiligo was compared according to self-reported smoking status by a health examination survey. The hazard ratio of vitiligo in current smokers was 0.69 (95% confidence interval; 0.65-0.72) with a reference of never-smokers after adjustment for age, sex, regular exercise, drinking status, body mass index, diabetes mellitus, hypertension, dyslipidemia, history of stroke, and history of ischemic heart diseases. The decreased risk of vitiligo in current smokers persisted after subgroup analysis of sex and age groups. The results suggested there are suppressive effects of smoking on the development of vitiligo. Further studies are needed to evaluate the mechanism of smoking on the development of vitiligo.