Single-Cell and Spatial Transcriptome Analysis of Dermal Fibroblast Development in Perinatal Mouse Skin: Dynamic Lineage Differentiation and Key Driver Genes.

Several single-cell RNA studies of developing mouse skin have elucidated the molecular and cellular processes involved in skin development. However, they have primarily focused on either the fetal or early postnatal period, leaving a gap in our understanding of skin development. In this study, we conducted a comprehensive time-series analysis by combining single-cell RNA-sequencing datasets collected at different stages of development (embryonic days 13.5, 14.5, and 16.5 and postnatal days 0, 2, and 4) and validated our findings through multipanel in situ spatial transcriptomics. Our analysis indicated that embryonic fibroblasts exhibit heterogeneity from a very early stage and that the rapid determination of each lineage occurs within days after birth. The expression of putative key driver genes, including Hey1, Ebf1, Runx3, and Sox11 for the dermal papilla trajectory; Lrrc15 for the dermal sheath trajectory; Zfp536 and Nrn1 for the papillary fibroblast trajectory; and Lrrn4cl and Mfap5 for the fascia fibroblast trajectory, was detected in the corresponding, spatially identified cell types. Finally, cell-to-cell interaction analysis indicated that the dermal papilla lineage is the primary source of the noncanonical Wnt pathway during skin development. Together, our study provides a transcriptomic reference for future research in the field of skin development and regeneration.

Risk of Skin Cancer and Actinic Keratosis in Patients with Rosacea: A Nationwide Population-based Cohort Study.

The association between rosacea and skin cancer remains inconclusive, with conflicting reports. The aim of this nationwide population-based cohort study was to determine the risk of skin cancer in patients with rosacea. A rosacea cohort (n = 11,420) was formulated and evaluated from 2010 to 2019. The incidence rate ratios of actinic keratosis, cutaneous melanoma, keratinocyte carcinoma and gastric, colorectal, and liver cancer were analysed in comparison with a matched control group, and multivariable stratified Cox proportional hazards model analysis was performed. The risk of actinic keratosis and keratinocyte carcinoma was increased in the rosacea group compared with the control group, with adjusted hazard ratios of 6.05 (95% confidence interval 3.63-10.09) and 2.66 (1.53-4.61), respectively. The risk of cutaneous melanoma and gastric, colorectal and liver cancer was not increased, with adjusted hazard ratios of 1.69 (0.25-11.37), 0.81 (0.59-1.10), 0.91 (0.69-1.18) and 1.32 (0.89-1.95), respectively. These results reveal an increased risk of actinic keratosis and keratinocyte carcinoma in patients with rosacea.

Good Clinical Responders to Topical Timolol in Patients with Infantile Hemangiomas: A 7-Year Retrospective Study of 328 Korean Patients.

BACKGROUND: Topical timolol is widely used for treatment of superficial infantile hemangioma (IH). However, little is known about factors that affect the response to topical timolol treatment. OBJECTIVE: This study aimed to investigate the efficacy, safety, and predictive value for good response to topical timolol for IH. METHODS: A retrospective review of medical records and clinical photos of 328 patients with IH treated with topical timolol 0.5% solution was conducted. Serial clinical photographs were compared with those at the initial visit using a 100-mm visual analogue scale (VAS). Treatment response was defined as an improvement of at least 75% from baseline in IH lesions within 12 months of treatment. RESULTS: Overall, IH patients treated with topical timolol showed significant improvement from baseline, showing that the final VAS score within 12 months of treatment was 69.7±20.4. The multivariable logistic regression analysis showed age at initiation of treatment (p=0.007), length of gestation and fetal growth (p=0.03), depth (p=0.01), and flexural area (p=0.007) were significantly associated with treatment response. Only four patients (1.1%) reported local irritation. CONCLUSION: This study demonstrated that topical timolol treatment was an effective and well-tolerated treatment for IHs. Physicians are encouraged to consider several patient- or lesional factors that might affect treatment response to achieve better clinical outcomes.

One-Year Effectiveness and Safety of Dupilumab Treatment for Moderate-to-Severe Atopic Dermatitis in Korean Patients: A Real-World Retrospective Analysis.

Dupilumab was the first biological drug to be approved for adult patients with moderate-to-severe atopic dermatitis (AD), and its use is growing exponentially worldwide. Though its therapeutic efficacy and favorable safety profile have been demonstrated, data on real-world long-term experience with the drug are only beginning to accumulate. Herein, we present a retrospective analysis of Korean patients with moderate-to-severe AD who were treated with dupilumab. We observed excellent overall treatment efficacy with the mean Eczema Area and Severity Index (EASI) score decreased from 28.2 to 3.2 at week 52. Notably, the therapeutic effect was maintained despite the considerable number of patients requiring an increase in treatment intervals due to the financial burden in a real clinical setting. In contrast to the previous reports, paradoxical head and neck erythema/dermatitis was rare in our study group, and pre-existing dermatitis in the very region, as well as in the hands, responded well to dupilumab treatment. Additionally, we were able to discontinue dupilumab treatment for two patients who achieved complete clearance of AD symptoms (EASI and Investigator's Global Assessment [IGA] scores of 0) for more than three months. There have been no flare-up events of AD in these patients; with topical corticosteroids alone, one of them has been completely disease-free for 43 weeks and the other has been maintaining an IGA score of 1 for 66 weeks. Furthermore, conjunctivitis was again confirmed to be the most frequent side effect associated with dupilumab, and it generally responded well to conventional conjunctivitis treatment.

Eccrine Nevus on the Neck: A Case Report and Review of the Literature.

Eccrine nevus is an extremely rare benign cutaneous hamartoma that usually occurs in childhood and adolescence. It has a wide range of clinical manifestations, and histological findings reveal a proliferation of structurally normal eccrine ducts. Herein, we present a case of eccrine nevus on the neck of an 8-year-old girl. Our literature review reveals that the head and neck region is a rare anatomical location for eccrine nevus as it has a predilection for extremities. Our review also suggests that overlying skin changes are common in eccrine nevus regardless of accompanying localized hyperhidrosis.

Prevalence and Characteristics of Onychomycosis in Patients with Knee Osteoarthritis: A Single-centre Prospective Cross-sectional Study.

Knee disorders that compromise patients' lower leg movements and self-care may put these patients at greater risk of onychomycosis. However, little is known about the prevalence of onychomycosis in patients with knee diseases. This study evaluated the prevalence and characteristics of onychomycosis in patients with knee osteoarthritis. A total of 520 consecutive patients with symptomatic knee osteoarthritis who visited the Department of Orthopedics for a potential knee surgery were evaluated for onychomycosis by PCR-based reverse blot hybridization assay. Of the 520 patients, 308 (59.2%) were diagnosed with onychomycosis. Age (p = 0.004), male sex (p = 0.015), and being barefooted (p = 0.031) were statistically significant risk factors for onychomycosis. Knee disease severity, based on Kellgren-Lawrence grade, was associated with severity of onychomycosis. The impairment of physical function and self-care caused by knee disorders may increase the prevalence of onychomycosis in these patients.

Clinical analysis of Pseudomonas aeruginosa-positive and -negative green nail syndrome cases: A single center retrospective analysis.

Green nail syndrome (GNS) is a paronychial infection mainly due to Pseudomonas aeruginosa, characterized by green discoloration of the nail plate. Although the diagnosis of GNS may be straightforward with its distinctive color change, the clinical management of the disease can be sometimes confusing, especially when the bacterial culture result is inconsistent. There is, however, a paucity of comprehensive reviews regarding the treatment of GNS in the actual clinical setting. In this retrospective review of 34 patients, we found that GNS mostly occurs on a single digit (79.4%) on the big toe or thumb (85.3%) with frequent concurrent fungal infection (67.6%). The prevalence of inconsistent bacterial culture result with no evidence of P. aeruginosa was unexpectedly high (n = 22, 64.7%), in which case coagulase-negative staphylococci were most frequently detected. The P. aeruginosa-negative group did not demonstrate any statistically significant differences compared with the P. aeruginosa-positive group, and it still responded well to the typical topical and/or oral fluoroquinolone treatment. GNS without the evidence of P. aeruginosa may be a more common occurrence than reported in the literature, and it can be managed successfully with the same strategy employed to treat P. aeruginosa-positive cases. It may result from the low detection rate of P. aeruginosa due to the limited sensitivity of the test, or inadequate amount and/or contamination of the sample, warranting close scrutiny by clinicians.

Various skin manifestations related to inflammatory bowel disease: A nationwide cross-sectional study on the Korean population.

Inflammatory bowel disease (IBD) presents with various extraintestinal manifestations. As part of them, various skin diseases are suggested to be related to IBD. We aimed to identify the epidemiology and risk of developing skin manifestations in patients with IBD. We used Korean insurance claims data and selected patients with IBD and age/sex-matched non-IBD subjects between 2013 and 2017 using the diagnosis code and prescription records of IBD-specific medications. The prevalence and risk of concurrent skin diseases were estimated. We identified 64 837 patients with IBD. Reactive skin eruptions including pyoderma gangrenosum and erythema nodosum were associated with IBD with highest odds ratios among three categories of reactive, inflammatory, and autoimmune skin diseases. Inflammatory skin diseases including rosacea, psoriasis, atopic dermatitis, hidradenitis suppurativa, and acne conglobata were significantly associated with IBD, but the association was less marked compared to reactive skin eruptions. The patients with IBD also had a higher risk of autoimmune skin diseases including vitiligo and alopecia areata than non-IBD subjects. We determined that IBD was related to various skin diseases including reactive, inflammatory, and autoimmune skin diseases. Considering these relationships can allow better management of patients with IBD and comorbid skin diseases.

Treatment of pediatric periorificial dermatitis with topical calcineurin inhibitor and topical/oral metronidazole.

Pediatric periorificial dermatitis is a papulopustular eruption found around the facial orifices in children. Although the treatment of the disease has been largely anecdotal and experience-based, studies have shown that topical calcineurin inhibitors, as well as other topical and oral antibiotics, such as metronidazole, can be effective treatment options. However, most of the studies with a sizable number of patients have been based on the Caucasian population. Herein, we evaluated the clinical efficacy of topical calcineurin inhibitors and topical/oral metronidazole in 24 Korean patients with pediatric periorificial dermatitis. The majority of the patients showed a complete response to treatment.

Bidirectional relationship between atopic dermatitis and inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND: Recently, atopic dermatitis has been suggested as a systemic inflammatory disorder that can accompany other inflammatory diseases, including inflammatory bowel disease. However, comprehensive reviews that specifically focus on the association between inflammatory bowel disease and atopic dermatitis are lacking. OBJECTIVE: To determine the association between inflammatory bowel disease and atopic dermatitis. METHODS: We searched for relevant studies from MEDLINE, EMBASE, and the Cochrane Library from inception to November 22, 2019. Considering a potential bidirectional relationship, studies reporting inflammatory bowel disease in patients with atopic dermatitis and atopic dermatitis in patients with inflammatory bowel disease were evaluated separately. RESULTS: We included 10 studies with 95,291,110 patients (4 studies on the prevalence of atopic dermatitis in inflammatory bowel disease, 2 on the prevalence and incidence of inflammatory bowel disease in atopic dermatitis, and 4 on either the prevalence or incidence of inflammatory bowel disease in atopic dermatitis). Meta-analyses revealed a statistically significant association between inflammatory bowel disease and atopic dermatitis in both directions (4 studies on atopic dermatitis prevalence in inflammatory bowel disease, odds ratio 1.39, 95% confidence interval 1.28-1.50; 5 on inflammatory bowel disease prevalence in atopic dermatitis, odds ratio 1.35, 95% confidence interval 1.05-1.73; and 3 studies on inflammatory bowel disease incidence in atopic dermatitis, relative risk 1.46, 95% confidence interval 0.98-2.17). LIMITATIONS: A small number of observational studies were reviewed. CONCLUSION: Published literature suggests a bidirectional relationship between inflammatory bowel disease and atopic dermatitis.