Investigating Distinct Skin Microbial Communities and Skin Metabolome Profiles in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by genetic predisposition, environmental factors, immune dysregulation, and skin barrier dysfunction. The skin microbiome and metabolome play crucial roles in modulating the skin's immune environment and integrity. However, their specific contributions to AD remain unclear. We aimed to investigate the distinct skin microbial communities and skin metabolic compounds in AD patients compared to healthy controls (HCs). Seven patients with AD patients and seven HCs were enrolled, from whom skin samples were obtained for examination. The study involved 16S rRNA metagenomic sequencing and bioinformatics analysis as well as the use of gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) to detect metabolites associated with AD in the skin. We observed significant differences in microbial diversity between lesional and non-lesional skin of AD patients and HCs. Staphylococcus overgrowth was prominent in AD lesions, while Cutibacterium levels were decreased. Metabolomic analysis revealed elevated levels of several metabolites, including hypoxanthine and glycerol-3-phosphate in AD lesions, indicating perturbations in purine metabolism and energy production pathways. Moreover, we found a positive correlation between hypoxanthine and glycerol-3-phosphate and clinical severity of AD and Staphylococcus overgrowth. These findings suggest potential biomarkers for monitoring AD severity. Further research is needed to elucidate the causal relationships between microbial dysbiosis, metabolic alterations, and AD progression, paving the way for targeted therapeutic interventions.

Risk of Developing Hypertension in Atopic Dermatitis Patients Receiving Long-term and Low-dose Cyclosporine: A Nationwide Population-based Cohort Study.

BACKGROUND: Cyclosporine (CS) is a first-line immunosuppressive agent used to manage moderate to severe atopic dermatitis (AD). To date, the risk of developing hypertension associated with the long-term use of low-dose CS in AD patients is understudied. OBJECTIVE: To determine the cumulative dose-dependent effect of CS on the risk of developing hypertension in patients with AD. METHODS: A nationwide population-based retrospective cohort with 1,844,009 AD patients was built from the Korean National Health Insurance System database from 2005 to 2009. A Cox proportional-hazard regression analysis was performed according to patients' CS treatment history adjusted for potential confounders. RESULTS: Current use of CS was associated with an increased risk of developing hypertension (adjusted hazard ratio, 4.442; 95% confidence interval, 3.761-5.247). Among the current CS users, a higher cumulative dose of CS (≥39,725 mg) or longer cumulative use of CS (≥182 days), was significantly associated with an increased risk of developing hypertension. CONCLUSION: The incidence of CS-associated hypertension is very low when using low-dose treatment regimens for AD. However, the current use or a high cumulative dose of CS for treating patients with AD increases the risk of developing hypertension. Precaution is needed when prescribing CS for long-term treatment of AD.

Interaction between the microbiota and the skin barrier in aging skin: a comprehensive review.

The interplay between the microbes and the skin barrier holds pivotal significance in skin health and aging. The skin and gut, both of which are critical immune and neuroendocrine system, harbor microbes that are kept in balance. Microbial shifts are seen with aging and may accelerate age-related skin changes. This comprehensive review investigates the intricate connection between microbe dynamics, skin barrier, and the aging process. The gut microbe plays essential roles in the human body, safeguarding the host, modulating metabolism, and shaping immunity. Aging can perturb the gut microbiome which in turn accentuates inflammaging by further promoting senescent cell accumulation and compromising the host's immune response. Skin microbiota diligently upholds the epidermal barrier, adeptly fending off pathogens. The aging skin encompasses alterations in the stratum corneum structure and lipid content, which negatively impact the skin's barrier function with decreased moisture retention and increased vulnerability to infection. Efficacious restoration of the skin barrier and dysbiosis with strategic integration of acidic cleansers, emollients with optimal lipid composition, antioxidants, and judicious photoprotection may be a proactive approach to aging. Furthermore, modulation of the gut-skin axis through probiotics, prebiotics, and postbiotics emerges as a promising avenue to enhance skin health as studies have substantiated their efficacy in enhancing hydration, reducing wrinkles, and fortifying barrier integrity. In summary, the intricate interplay between microbes and skin barrier function is intrinsically woven into the tapestry of aging. Sound understanding of these interactions, coupled with strategic interventions aimed at recalibrating the microbiota and barrier equilibrium, holds the potential to ameliorate skin aging. Further in-depth studies are necessary to better understand skin-aging and develop targeted strategies for successful aging.

Deciphering Childhood Rosacea: A Comprehensive Review.

Childhood rosacea is a lesser known, yet significant, skin condition presenting diagnostic and treatment challenges. Although often underdiagnosed due to unclear diagnostic criteria, it manifests similarly to adult rosacea, with features such as papulopustular, telangiectasia, granulomatous, idiopathic facial aseptic granuloma, and ocular rosacea. The complex pathophysiology involves genetic, immunological, and environmental factors. Distinguishing childhood rosacea from conditions like acne, steroid rosacea, sarcoidosis, and lupus vulgaris is crucial but complicated by the lack of established criteria. Treatment strategies, mainly extrapolated from adult management protocols, include topical therapies, systemic medications, and laser treatments, adapted for pediatric patients. Special attention is given to ocular rosacea, often preceding skin manifestations, necessitating multidisciplinary care. The review underscores the urgent need for clear diagnostic guidelines, increased awareness, and tailored pediatric treatment protocols to improve patient outcomes and mitigate the condition's evolution into adulthood.

Clinical Efficacy of 5-Fluorouracil and Bleomycin in Dermatology.

Bleomycin and 5-fluorouracil (5-FU) are widely used in various dermatological disorders. Both drugs are well-recognized as antineoplastic drugs and exert their effect by blocking the cell cycle. Topical and intralesional formulations are available and have been studied in both non-neoplastic and cancerous lesions. However, data comparing the effect of bleomycin and 5-FU in the dermatological disorders are limited. This review outlines the action mechanisms of both drugs and compares their clinical efficacies in a wide range of dermatologic diseases including hypertrophic scar, wart, skin cancer, vascular malformation, hemangioma, and vitiligo, and discusses the overall safety of the drugs. Intralesional bleomycin treatment is effective in hypertrophic scars and warts, but intralesional 5-FU may also be considered since it is cheaper and less painful. Moreover, intralesional 5-FU and bleomycin injection is a viable option for premalignant lesions (i.e., actinic keratosis) and inoperable skin cancers. Both bleomycin and 5-FU have been applied as treatment adjuncts for vitiligo, with 5-FU showing a slightly better outcome. Both agents have a good safety profile, and no serious side effects have been reported following their use in the field of dermatology.

Increased risk of sleep disturbances in patients with rosacea: A nationwide population-based cohort study.

Rosacea is a chronic inflammatory skin disorder linked to various mental disorders, but little is known about the impact of rosacea on sleep disorders. The aim of this study is to confirm the association of rosacea with sleep disorders using a large administrative data set. This nationwide population-based retrospective cohort study enrolled 1129 individuals with rosacea and 11 017 age- and sex-matched controls without rosacea from the Korean National Health Insurance System database from 2002 to 2015. The prevalence of sleep disorder (7.8%) was significantly higher in patients with rosacea than in controls (5.81%; p < 0.001). Rosacea was associated with an increased risk of sleep disorder (adjusted odds ratio [aOR], 1.287 [95% confidence interval (CI), 1.022-1.623]). Among a variety of sleep disorders, patients with rosacea were likely to have an increased risk of insomnia (aOR, 1.318 [95% CI, 1.002-1.743]). In subgroup analysis, female patients with rosacea (aOR, 1.297 [95% CI, 1.010-1.722]) and those with rosacea and dyslipidemia (aOR, 1.417 [95% CI, 1.062-1.891]) were at a higher risk of having a sleep disorder. Rosacea is associated with an increased risk of having sleep disorders. The management of modifiable risk factors is important for managing sleep disorders in patients with rosacea.

Metformin: A Potential Treatment for Acne, Hidradenitis Suppurativa and Rosacea.

Metformin is a widely used drug for treatment of diabetes mellitus, due to its safety and efficacy. In addition to its role as an antidiabetic drug, numerous beneficial effects of metformin have enabled its use in various diseases. Considering the anti-androgenic, anti-angiogenic, anti-fibrotic and antioxidant properties of metformin, it may have the potential to improve chronic inflammatory skin diseases. However, further evidence is needed to confirm the efficacy of metformin in dermatological conditions, This review focuses on exploring the therapeutic targets of metformin in acne vulgaris, hidradenitis suppurativa and rosacea, by studying their pathogeneses.

Atopic Dermatitis and the Risk of Myocardial Infarction and All-Cause Mortality: A Nationwide Population-Based Cohort Study.

PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with various comorbidities. However, inconsistent results on the risk of myocardial infarction (MI) and mortality have been reported in patients with AD. This study was aimed to evaluate the risk of MI and all-cause mortality in patients with AD. METHODS: This nationwide population-based retrospective cohort study enrolled 56,205 adults ≥ 20 years of age with AD and 3,825,609 controls without AD from the Korean National Health Service (NHIS) database from 2009 to 2016. RESULTS: The risk of MI (adjusted hazard ratio [aHR], 1.111, 95% confidence interval [CI], 1.050-1.176) was increased in patients with AD. By AD severity, patients with moderate-to-severe AD had a higher risk of MI (aHR, 1.163, 95% CI, 1.080-1.251) than individuals without AD. The risk of all-cause mortality was only increased for patients with moderate-to-severe AD (aHR, 1.096, 95% CI, 1.040-1.155) compared to individuals without AD. In subgroup analysis, an increased risk of MI was observed in female, non-obese, non-smoking, non-diabetic, and non-dyslipidemic patients with moderate-to-severe AD compared to individuals without AD. An increased risk of all-cause mortality was observed in patients with moderate-to-severe AD compared to non-AD controls among individuals ≥60 years of age and non-smokers. CONCLUSIONS: The risk of MI and all-cause death was increased in patients with moderate-to-severe AD. Even without well-known risk factors for MI and mortality, patients with AD require the proper management and screening for comorbidities to prevent MI and decrease all-cause mortality.

Psychological Burden and Willingness to Pay Among Korean Rosacea Patients and Their Association With Rosacea Phenotype and Severity: A Multi-Center Cross-Sectional Study.

BACKGROUND: Rosacea is a chronic inflammatory disorder that can adversely affect the patient's quality of life (QOL). However, few studies have examined the association between the psychological burden and willingness to pay (WTP) with rosacea features and severity. OBJECTIVES: The study aimed to determine the overall psychological burden and WTP among Korean rosacea patients and identify factors that may contribute, such as patient demographics, clinical features, and rosacea severity. METHODS: This prospective cross-sectional study recruited Koreans with rosacea. All were asked to complete a questionnaire on their demographics, rosacea-related symptoms, self-rated severity, dermatology life quality index (DLQI), and WTP. The clinical features were assessed by a board-certified dermatologist. The investigator's global assessment and global flushing severity score (GFSS) were used to determine the clinical severity of rosacea. Multiple regression analysis was conducted to identify factors contributing to the psychological burden and WTP. RESULTS: Out of 201 rosacea patients, 147 (73.1%) were female, and 54 (26.9%) males, with a median age of 50.1 years. Their median DLQI score was 8 (interquartile range [IQR]): 4.0-13.0). The median WTP per month for the control of rosacea was $100, with relative WTP (WTP/household income per month x 100) being 3.3%. According to the multiple regression model, phymatous change (ß = .153, p = .030), DLQI score (ß = .152, P = .045), and GFSS (ß = .154, P = .041) contributed most to the WTP. CONCLUSION: Rosacea patients experience substantial psychological and economic burdens. More vigorous treatment should be performed for those with phyma and severe flushing whose QOL is most severely affected.

Burden of Disease and Unmet Needs in the Diagnosis and Management of Atopic Dermatitis in Korea.

Atopic dermatitis (AD) is a chronic inflammatory skin condition associated with a significant disease burden in Korea. AD is highly prevalent among Korean children, adolescents, and adults, and can cause physical discomfort, psychological distress, and social isolation for those affected. Despite advances in our understanding of AD, there are still many unmet needs in diagnosing and managing the disease in Korea. One of the challenges in diagnosing AD is the lack of a definitive biomarker for AD in Korea, and there is a need for more effective, safe, and cost-effective treatments for AD. Therefore, finding out the current epidemiology, burden of AD, and how AD is currently being diagnosed in Korea and reviewing management options available in Korea will help resolve the unmet needs of AD patients in Korea. Addressing these and other unmet needs in AD management and diagnosis in Korea may improve outcomes for those affected by this challenging condition.

Increased Risk of Glaucoma in Patients with Rosacea: A Nationwide Population-Based Cohort Study.

Rosacea is a chronic inflammatory skin disorder associated with various ocular manifestations. However, little is known about the association between rosacea and glaucoma. This study aimed to determine the risk of glaucoma in patients with rosacea. This nationwide population-based retrospective cohort study enrolled 1056 individuals with rosacea and 10,440 age- and sex-matched controls without rosacea from the Korean National Health Insurance System (NHIS) database from 2002 to 2015. The incidence rate of glaucoma was 1215.4 per 100,000 person-years (PYs) in patients with rosacea and 741.3 per 100,000 PYs in patients without rosacea. A significantly higher cumulative incidence probability of glaucoma was observed in patients with rosacea than in non-rosacea controls (p = 0.0004). Rosacea was associated with an increased risk of developing glaucoma (adjusted hazard ratio [aHR], 1.659; 95% confidence interval [CI], 1.245-2.211) compared to those without rosacea. In subgroup analysis, increased risk of glaucoma was observed in patients with rosacea younger than 50 years (aHR, 1.943; 95% CI, 1.305-2.893), females (aHR, 1.871; 95% CI, 1.324-2.644), and patients with hypertension (aHR, 1.561; 95% CI, 1.037-2.351) compared to those without rosacea. Rosacea is associated with an increased risk of developing glaucoma. Proper screening for glaucoma should be conducted in rosacea patients younger than 50 years, females, and patients with hypertension to better control the disease and prevent vision loss from glaucoma.

Increased Risk of Dementia in Patients with Atopic Dermatitis: A Nationwide Population-Based Cohort Study.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with bimodal incidence peaks in early childhood and middle-aged and older adults. Few studies have focused on the risk of dementia in AD. The aims of this study were to analyse the incidence, and risk factors for dementia in patients with AD. This nationwide population-based retrospective cohort study enrolled 38,391 adults ≥ 40 years of age with AD and 2,643,602 controls without AD from the Korean National Health Insurance System (NHIS) database from 2009 to 2016. The cumulative incidence probability of all-cause dementia, Alzheimer's disease, or vascular dementia at 8 years was 50, 39, and 7 per 1,000 person-years in patients with AD, respectively. The adjusted risks of all-cause dementia (hazard ratio (HR), 1.072; 95% confidence interval (95% CI) 1.026-1.120), and Alzheimer's disease (HR 1.051; 95% CI 1.000-1.104) were increased in patients with AD. The effect of AD on the development of all-cause dementia and Alzheimer's dementia varied according to age and diabetes mellitus (all p for interaction, < 0.05). The risks of all-cause dementia and Alzheimer's disease were increased in patients with AD. Management of modifiable risk factors is important for preventing dementia in patients with AD.

Itch and Janus Kinase Inhibitors.

Itch is a common skin symptom, with complex aetiology and pathogenesis. It is mediated by 2 pathways, the histaminergic and non-histaminergic pathways. Chronic itch is understood to be processed by the latter and is difficult to treat with traditional pruritus therapies. The Janus kinase and signal transducer and activator of transcription pathway is a signalling mechanism that regulates gene expression through various cytokines. Janus kinase inhibitors, which have been tested and used for several autoimmune diseases, have also been shown to be effective for itch through clinical trials and case reports. Janus kinase inhibitors could be a good choice for pruritus in atopic dermatitis, psoriasis, and other diseases, such as prurigo nodularis and lichen planus, with rapid itch relief compared with conventional treatments. The most common adverse effects reported include nasopharyngitis, acne, and elevated blood creatine phosphokinase levels. Janus kinase inhibitors are currently prescribed with warnings about a potential increase in malignancies and cardiovascular diseases and usage in people of older ages. This review aims to provide knowledge about itch and the Janus kinase and signal transducer and activator of transcription pathway and to analyse the current evidence for itch relief by Janus kinase inhibitors.

Allergic Sensitization Pattern in the Korean Dermatologic Patients.

BACKGROUND: Avoiding causative allergens is important for controlling the clinical course of allergic diseases. Allergen sensitization is influenced by many factors including the environment and lifestyle. The socioeconomic development, climate, and lifestyle changes have increased the prevalence of allergic diseases worldwide. However, there is little information about changes in the trend of the common allergens over time. OBJECTIVE: This study was aimed at identifying the trends of the common allergens in Korea over a 10-year period based on the results of the multiple allergosorbent test chemiluminescent assay (MAST-CLA). METHODS: We retrospectively reviewed the medical records of 5,760 patients aged ≥18 years who visited the Dermatology Department at a tertiary hospital over a period of 10 years. The serum total immunoglobulin (Ig) E and specific IgE levels to 41 allergens were determined using MAST-CLA, along with the clinical diagnosis, duration of illness, white blood cell count and eosinophil percentage. RESULTS: Dermatophagoides farinae, Dermatophagoides pteronyssinus, and house dust were the most prevalent allergens during the 10 years period, but the percentage of higher class responses has decreased in recent years. The number of patients sensitized to house dust (p<0.001), dogs (p=0.005), and cats (p<0.001) increased while that of patients sensitized to cockroaches (p<0.001) and storage mites (p<0.001) decreased over time. There were no significant changes in the total number of sensitizing allergens over time. CONCLUSION: The common allergens have changed over time. Based on the findings of this study, physicians and patients should consider changing their strategies for disease prevention and management.

Truncal Acne: An Overview.

Acne is a relatively common disease of the pilosebaceous units. Many aspects of facial acne have been studied. However, there is limited evidence regarding truncal acne. Truncal acne is also observed in a significant number of patients, but it is often ignored by patients and clinicians. Although the pathogenesis of facial and trunk acne is considered to be similar, the characteristics of the skin on the trunk and face are thought to be different. As truncal acne can cause scars on large areas of the body and adversely affect the quality of life of patients, more attention should be given to patients with truncal acne. Although only a few studies have been published to date, the epidemiology, etiology, severity assessment tool, assessments of the quality of life, and new treatments targeting truncal acne are currently being studied. Therefore, in this review, the latest knowledge on truncal acne will be discussed.