Targeted deep sequencing reveals genomic alterations of actinic keratosis/cutaneous squamous cell carcinoma in situ and cutaneous squamous cell carcinoma.

Actinic keratosis (AK) and cutaneous squamous cell carcinoma in situ (CIS) are two of the most common precursors of cutaneous squamous cell carcinoma (cSCC). However, the genomic landscape of AK/CIS and the drivers of cSCC progression remain to be elucidated. The aim of our study was to investigate the genomic alterations between AK/CIS and cSCC in terms of somatic mutations and copy number alterations (CNAs). We performed targeted deep sequencing of 160 cancer-related genes with a median coverage of 515× for AK (N = 9), CIS (N = 9), cSCC lesions (N = 13), and matched germline controls from 17 patients. cSCC harboured higher abundance of total mutations, driver mutations and CNAs than AK/CIS. Driver mutations were found in TP53 (81%), NOTCH1 (32%), RB1 (26%) and CDKN2A (19%). All AK/CIS and cSCC lesions (93.5%), except two, harboured TP53 or NOTCH1 mutations, some of which were known oncogenic mutations or reported mutations in normal skin. RB1 driver mutations were found in CIS/cSCC (36.4%) but not in AK. CDKN2A driver mutations were found more frequently in cSCC (30.8%) than in AK/CIS (11.1%). Among recurrent (≥3 samples) CNAs (gain in MYC and PIK3CA/SOX2/TP63; loss in CDKN2A and RB1), MYC (8q) gain and CDKN2A (9p) loss were more frequently detected in cSCC (30.8%) than in AK/CIS (11.1%). Ultraviolet was responsible for the majority of somatic mutations in both AK/CIS and cSCC. Our study revealed that AK/CIS lesions harbour prevalent TP53 or NOTCH1 mutations and that additional somatic mutations and CNAs may lead to cSCC progression in AK/CIS lesions.

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.

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.

Pigmented contact dermatitis and hair dyes: A retrospective case-control multicentre study in Korea.

BACKGROUND: Pigmented contact dermatitis (PCD), a rare variant of non-eczematous contact dermatitis, is clinically characterized by sudden-onset brown or grey pigmentation on the face and neck. It is hypothesized to be caused by repeated contact with low levels of allergens. OBJECTIVES: This study evaluated the risk of using hair dyes in patients with PCD in Korea. METHODS: A total of 1033 PCD patients and 1366 controls from 31 university hospitals were retrospectively recruited. We collected and analysed the data from the patient group, diagnosed through typical clinical findings of PCD and the control group, which comprised age/sex-matched patients who visited the participating hospitals with pre-existing skin diseases other than current allergic disease or PCD. RESULTS: Melasma and photosensitivity were significantly more common in the control group, and a history of contact dermatitis was more common in the PCD group. There were significantly more Fitzpatrick skin type V participants in the PCD group than in the control group. There was no significant difference in sunscreen use between the groups. Using dermatologic medical history, Fitzpatrick skin type and sunscreen use as covariates, we showed that hair dye use carried a higher PCD risk (odds ratio [OR] before adjustment: 2.06, confidence interval [CI]: 1.60-2.65; OR after adjustment: 2.74, CI: 1.88-4.00). Moreover, henna users had a higher risk of PCD (OR before adjustment: 5.51, CI: 4.07-7.47; OR after adjustment: 7.02, CI: 4.59-10.74), indicating a significant increase in the risk of PCD with henna dye use. Contact dermatitis history was more prevalent in henna users than in those using other hair dyes in the PCD group (17.23% vs. 11.55%). CONCLUSION: Hair dye use is a risk factor for PCD. The risk significantly increased when henna hair dye was used by those with a history of contact dermatitis.

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.

Impact of Chronic Kidney Disease Severity on the Risk of Prurigo Nodularis: A Population-Based Cohort Study.

While dialysis is linked with prurigo nodularis, little is known about the impact of non-dialysis chronic kidney disease on prurigo nodularis. The influence of chronic kidney disease on development of prurigo nodularis was measured using the Korean National Health Insurance and National Health Screening Program data, identifying 17,295,576 individuals without prior prurigo nodularis. Chronic kidney disease severity was determined by the estimated glomerular filtration rate (in ml/min/1.73 m2) calculated from serum creatinine, and proteinuria detected with urine dipstick. Prurigo nodularis incidence during follow-up was determined. Over a median follow-up period of 9.72 years, 58,599 individuals developed prurigo nodularis, with an incidence rate of 3.59 per 10,000 person-years. Among different variables, estimated glomerular filtration rate was the strongest risk factor for prurigo nodularis. Compared with estimated glomerular filtration rate ≥ 90, estimat-ed glomerular filtration rate 15-29 (hazard ratio 1.31, 95% confidence interval 1.05-1.62) and end-stage renal disease (hazard ratio 1.46, 95% confidence interval 1.25-1.69) were associated with higher risks. The presence of proteinuria independently increased the risk of prurigo nodularis, increased risks associated with estimated glomerular filtration rate 15-29 and end-stage renal disease, and caused risk associated with estimated glomerular filtration rate 30-59 to become significant. With differential impact of chronic kidney disease severity on the risk of prurigo nodularis, preservation of renal function would potentially translate into lower risk of prurigo nodularis.

Validation of Relationship between Patients' Descriptions of Pruritus and Patient-burden of Chronic Pruritus using Structural Equation Modelling.

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.

The Human Microbiota and Skin Cancer.

Skin cancer is the most common type of cancer in the US with an increasing prevalence worldwide. While ultraviolet (UV) radiation is a well-known risk factor, there is emerging evidence that the microbiota may also contribute. In recent years, the human microbiota has become a topic of great interest, and its association with inflammatory skin diseases (i.e., atopic dermatitis, acne, rosacea) has been explored. Little is known of the role of microbiota in skin cancer, but with the recognized link between microbial dysbiosis and inflammation, and knowledge that microbiota modulates the effect of UV-induced immunosuppression, theories connecting the two have surfaced. In this paper, we provide a comprehensive review of the key literature on human microbiota, especially the skin microbiota, and skin cancer (i.e., non-melanoma skin cancer, melanoma, cutaneous T cell lymphoma). Also, mechanistic perspectives as to how our microbiota influence skin cancer development and treatment are offered.

Itch intensity in prurigo nodularis is closely related to dermal interleukin-31, oncostatin M, IL-31 receptor alpha and oncostatin M receptor beta.

Prurigo nodularis (PN) is a chronic skin dermatosis with hyperkeratotic and intensely pruritic nodules. Managing PN-associated itch is difficult because its aetiology is still unknown. This study aimed to investigate the correlation between itch intensity in PN and the expression of a pruritogenic cytokine interleukin (IL)-31, its receptor complex components IL-31 receptor α (IL-31RA) and oncostatin M receptor ß (OSMRß), and oncostatin M (OSM), which is a ligand of OSMR ß, through immunofluorescence staining examination. Itch intensity in PN was closely correlated with the number of dermal IL-31(+) cells (Spearman's r = 0.551, p < 0.05), dermal IL-31RA(+) cells (r = 0.475, p < 0.05) and dermal OSM(+) cells (r = 0.505, p < 0.05). In addition, the number of dermal OSMRß (+) cells was increased in PN (t test, p < 0.05), despite not being correlated with itch intensity (Spearman's r = 0.375, p > 0.05). Major cellular sources of dermal IL-31 were T cells (27.0% of total IL-31-expressing cells) and macrophages (35.0%), while those of OSM were mainly T cells (49.8%) and mast cells (26.8%). IL-31RA-expressing dermal cells were mostly mast cells (49.3%) and macrophages (36.6%), and OSMRß was mainly expressed by macrophages (51.8%) in the dermis. These findings indicate that IL-31 (mainly from macrophages and T cells) and OSM (principally from T cells and mast cells) stimulate dermal cells expressing IL-31RA and OSMRß (e.g. macrophages), which may further promote itch and inflammation in PN. This complex dermal milieu of cell/cytokine/receptor network can be a therapeutic target for PN-associated itch.

A comparison of the safety, efficacy, and longevity of two different hyaluronic acid fillers in filler rhinoplasty: A multicenter study.

Filler rhinoplasty is a popular procedure in Asia, and it is of great importance to understand the clinical efficacy and durability of the different filler products that serve this purpose. Here, we aimed to evaluate and compare the safety, efficacy, and longevity of two different hyaluronic acid (HA) fillers in improving the nasal profile in Asians. A multicenter comparative trial was performed for 48 weeks after a single injection of a popular monophasic monodensified, and a newly developed biphasic HA filler. Assessments including patient satisfaction and three-dimensional (3D) imaging analysis were performed before, immediately after, 2 weeks, 12 weeks, 24 weeks, and 48 weeks after filler rhinoplasty. Twenty-eight Korean women underwent structured rhinoplasty were divided into monophasic monodensified (n = 14) and biphasic (n = 14) groups. There were significant changes in the facial profile following filler rhinoplasty throughout the study period. Overall, an increase of 1.75 mm in nose height, increase of 3.66° in the nasofrontal angle and 2.77° in the nasolabial angle, and radix elevation of 1.24 mm was noted at week 48 which was statistically different from the baseline values (P < .05). Between the different filler types, statistical difference was only noted in radix elevation (per milliliter of filler material) immediately after filler injection. No serious adverse event occurred during treatment or follow-up. Nonsurgical rhinoplasty with the specific HA filler products led to significant changes in the facial profile which persisted for 48 weeks. Overall, the clinical efficacy and safety were comparable between the two filler types except for radix elevation which was more prominent with C-C immediately after filler injection. J-V was superior to C-C in maintaining the radix elevation long term.

Metagenomic analysis of the dust particles collected from the suction tube and the suction funnel of a dermatological laser smoke evacuator system.

In the last few decades, there has essentially been an explosion in the use of lasers in medicine, especially in the area of cosmetic dermatology. Potentially harmful substances are liberated when tissues are vaporized with laser. This creates numerous risks, including the spread of infectious disease. Smoke evacuators are devices that capture and filter laser plume, thereby maintaining a safe environment for the surgical team and patient. Our aim was to characterize the microbial community structure within the suction tube and funnel of the smoke evacuator system, identify their origin, and evaluate pathogenicity. Dust particles were collected from the instruments with a cotton swab. DNA was extracted from the swabs and the transport media, and sequencing was performed using the Illumina HiSeq Xplatform. Metagenomic analysis was conducted using the Empowering the Development of Genomics Expertise (EDGE) Bioinformatics pipeline and custom Python scripts. The most abundant bacterial species were Micrococcus luteus and Brevibacterium casei in the suction tube, and Dermacoccus sp. Ellin 185 and Janibacter hoylei in the suction funnel. A total of 15 medium- to high-quality metagenome-assembled genomes (MAGs) were constructed where we found 104 antibiotic-resistant genes (ARGs) and 741 virulence factors. Findings indicate that the suction tube and funnel are likely a reservoir of virulence factor genes and ARGs, which can possibly be passed on to other bacteria via horizontal gene transfer. We would like to emphasize the health risk these microorganisms pose and the need to reevaluate the current hygiene standards with regard to the smoke evacuator system.

Validity and reliability of itch assessment scales for chronic pruritus in adults: A prospective multicenter study.

BACKGROUND: Several tools can provide a reliable and accurate evaluation of pruritus, including the visual analog scale (VAS), numeric rating scale (NRS), verbal rating scale (VRS), and multidimensional questionnaires such as the Itch Severity Scale (ISS). However, no single method is considered a gold standard. OBJECTIVE: We evaluated the validity and reliability of VAS, NRS, VRS, and ISS and their correlation with a pruritus-specific quality of life instrument, ItchyQoL. METHODS: A total of 419 patients (215 men and 204 women) with chronic pruritus (mean age, 46.58 years) recorded their pruritus intensity on VAS, NRS, VRS, and ISS. Retest reliability was analyzed in a second assessment 3 hours after the initial assessment. All participants answered ItchyQoL. RESULTS: A strong correlation between VAS, NRS, and VRS was found. ISS showed a low intercorrelation validity with these tools. However, ISS was more strongly correlated with ItchyQoL. The retest reliability scores were similar for VAS, NRS, and VRS but lower than the scores obtained for ISS. LIMITATIONS: Limitations include patient heterogeneity and recall bias. CONCLUSION: The assessment of pruritus is challenging because of the subjective symptoms and the multifactorial nature. Therefore, more studies are needed to determine the best strategy to assess itch intensity.

Rejuvenation of periocular region in Koreans: A multimodal approach combining botulinum toxin, fillers, and micro-focused ultrasound with visualization for optimal results.

Periorbital aging involves all layers of the skin, fat, and the bony orbit. Therefore, a multimodal approach is necessary. Twenty Korean subjects who required periorbital rejuvenation were enrolled in this study. First, micro-focused ultrasound with visualization (MFU-V) was performed across the supra-brow area, lateral canthus, and the infraorbital area. Next, the filler was injected into the sunken upper eyelid, lateral eyebrow, and the infraorbital area. Lastly, botulinum toxin was administered into the forehead, glabella, crow's feet, and the lateral orbital rim below the brow on the same day. Photographs were taken at baseline; immediately after treatment; and at 1, 4, and 12 weeks of follow-up. The average eyebrow height was increased by 3.5 mm, and the maximum height was elevated by 3.9 mm at week 12. Physician visual analogue scale (VAS) scores regarding the whole periorbital area and eyebrow ptosis were continuously improved throughout the observation period. Physician VAS scores for infraorbital hollow and superior sulcus deformity improved immediately after the procedure and were maintained at week 12. Adverse events were mild and transient. We believe that a multimodal approach combining MFU-V, fillers, and botulinum toxin results in significant periocular rejuvenation.

A survey on monopolar radiofrequency treatment: The latest update.

The aim of this questionnaire-based study was to measure the level of appreciation, practice patterns, and side effects of monopolar radiofrequency treatment among Korean dermatologists practicing the most updated monopolar radiofrequency device (Thermage FLX, Thermage Inc., Hayward, California). According to a total of 52 surveys analyzed, this latest device (Thermage FLX) was considered more effective (57.4%), faster with reduced treatment time (66.0%), and more painful (25.5%) compared with Thermage CPT. Asians in their 40s were considered to benefit most and skin thickness continued to be the most important determinant in terms of responsiveness to Thermage FLX. The interval between treatments was mainly 1 year (51.9%) with the 600 REP 4 cm2 new total tip being preferred by 86.5% of Thermage FLX users. The treatment energy and the complication rate of Thermage was lower than what we reported in 2017 and 2011 which is likely due to the optimized energy delivery of Thermage FLX and the subsequent gentle treatment. We hope our updated data enable dermatologists to better utilize monopolar radiofrequency in their practice.

Air Pollution and Atopic Dermatitis (AD): The Impact of Particulate Matter (PM10) on an AD Mouse-Model.

Air pollution reportedly contributes to the development and exacerbation of atopic dermatitis (AD). However, the exact mechanism underlying this remains unclear. To examine the relationship between air pollution and AD, a clinical, histological, and genetic analysis was performed on particulate matter (PM)-exposed mice. Five-week-old BALB/c mice were randomly divided into four groups (control group, ovalbumin (OVA) group, PM group, OVA + PM group; n = 6) and treated with OVA or PM10, alone or together. Cutaneous exposure to OVA and PM10 alone resulted in a significant increase in skin severity scores, trans-epidermal water loss (TEWL) and epidermal thickness compared to the control group at Week 6. The findings were further accentuated in the OVA + PM group showing statistical significance over the OVA group. A total of 635, 501, and 2149 genes were found to be differentially expressed following OVA, PM10, and OVA + PM10 exposure, respectively. Strongly upregulated genes included RNASE2A, S100A9, SPRR2D, THRSP, SPRR2A1 (OVA vs. control), SPRR2D, S100A9, STFA3, CHIL1, DBP, IL1B (PM vs. control) and S100A9, SPRR2D, SPRR2B, S100A8, SPRR2A3 (OVA + PM vs. control). In comparing the groups OVA + PM with OVA, 818 genes were differentially expressed with S100A9, SPRR2B, SAA3, S100A8, SPRR2D being the most highly upregulated in the OVA + PM group. Taken together, our study demonstrates that PM10 exposure induces/aggravates skin inflammation via the differential expression of genes controlling skin barrier integrity and immune response. We provide evidence on the importance of public awareness in PM-associated skin inflammation. Vigilant attention should be paid to all individuals, especially to those with AD.

Updates on the Risk of Neuropsychiatric and Gastrointestinal Comorbidities in Rosacea and Its Possible Relationship with the Gut-Brain-Skin Axis.

Rosacea is a common chronic cutaneous inflammatory disorder. Recently, patients with rosacea were identified as having a higher risk of developing various comorbidities such as cardiovascular disease, psychiatric disorders, neurologic disorders, and gastrointestinal disorders. However, the risks of some comorbidities in patients with rosacea are somewhat contradictory, depending upon the study design. Moreover, pathomechanisms associated with the comorbidities of patients with rosacea remain poorly elucidated. The purpose of this review was to provide the most up-to-date evidence on the risks of neuropsychiatric and gastrointestinal comorbidities in patients with rosacea. Moreover, the molecular pathomechanisms associated with neuropsychiatric and gastrointestinal comorbidities in patients with rosacea were evaluated based on recent studies. This review was also intended to focus more on the role of the gut-brain-skin axis in the association of neuropsychiatric and gastrointestinal comorbidities in rosacea.

Fractional Carbon Dioxide Laser as an "Add-on" Treatment for Vitiligo: A Meta-analysis with Systematic Review.

Treatment of vitiligo is challenging and requires a multidisciplinary approach. Fractional carbon dioxide (CO2) laser as an add-on to conventional treatment has been reported to be effective, but there is no consensus on its use. A systematic review was performed by searching major databases for relevant publications to February 2017. Six studies with 85 participants were included. For those with refractory vitiligo, the addition of fractional CO2 laser to routine treatment modalities was superior to conventional treatment alone in terms of > 50% re-pigmentation (risk ratio (RR) 4.90, 95% confidence interval (95% CI), 1.15-20.93; p = 0.03), physician improvement score (mean difference (MD) 0.81, 95% CI 0.33-1.29; p < 0.001), < 25% re-pigmentation (RR 0.64, 95% CI, 0.49-0.85; p=0.002) and patient satisfaction (MD 1.61, 95% CI 0.73-2.49; p< 0.001). Side-effects were minor. These results provide evidence supporting that fractional CO2 laser is a valuable treatment modality for patients with vitiligo, especially for those with refractory vitiligo.