Quantitative measurement of hair diameter diversity as a diagnostic indicator of androgenetic alopecia in Korean males: A cross-sectional study.

Background: The conventional 20% threshold for hair diameter diversity (HDD), widely accepted for diagnosing androgenetic alopecia (AGA) in the vertex area, has not quantitatively analyzed. Objective: To validate the HDD 20% threshold for AGA and develop a refined, Korean-specific criterion. Methods: This study involved 240 male patients with AGA, categorized by the V stages of the basic and specific classification. Phototrichogram images of the vertex region were analyzed using Image J software for hair thickness measurement. Results: Receiver operating characteristic curve analysis determined the 45 µm hair diameter threshold as the most diagnostic for AGA, with an area under the curve value of 0.884 and a Youden index of 0.659. Optimal AGA diagnosis was achieved when over 21% of hair had a diameter of ≤45 µm. Limitations: Restriction to Korean male limits its applicability to a broader population, and using a specific hair diameter threshold does not account for individual variations in hair characteristics. Conclusion: The study validates the conventional HDD 20% threshold and proposes a more appropriate 45 µm threshold for Korean males, beyond the 40 µm. It concludes that while the HDD 20% remains a key method for early detection of vertex AGA, the definition of thin hair should be ethnicity-specific.

Quantitative Analysis of Hair Luster in a Novel Ultraviolet-Irradiated Mouse Model.

Hair luster is a key attribute of healthy hair and a crucial aspect of cosmetic appeal, reflecting the overall health and vitality of hair. Despite its significance, the advancement of therapeutic strategies for hair luster enhancement have been limited due to the absence of an effective experimental model. This study aimed to establish a novel animal model to assess hair gloss, employing ultraviolet (UV) irradiation on C57BL/6 mice. Specifically, UVB irradiation was meticulously applied to the shaved skin of these mice, simulating conditions that typically lead to hair luster loss in humans. The regrowth and characteristics of the hair were evaluated using a dual approach: an Investigator's Global Assessment (IGA) scale for subjective assessment and an image-based pixel-count method for objective quantification. These methods provided a comprehensive understanding of the changes in hair quality post-irradiation. To explore the potential reversibility of hair luster changes, oral minoxidil was administered, a treatment known for its effects on hair growth and texture. Further, to gain insights into the underlying biological mechanisms, bulk RNA transcriptomic analysis of skin tissue was conducted. This analysis revealed significant alterations in the expression of keratin-associated protein (KRTAP) genes, suggesting modifications in hair keratin crosslinking due to UV exposure. These changes are crucial in understanding the molecular dynamics affecting hair luster. The development of this new mouse model is a significant advancement in hair care research. It not only facilitates the evaluation of hair luster in a controlled setting but also opens avenues for the research and development of innovative therapeutic strategies. This model holds promise for the formulation of more effective hair care products and treatments, potentially revolutionizing the approach towards managing and enhancing hair luster.

A Case of Vancomycin-Induced Drug Reaction with Eosinophilia, Systemic Symptoms and Multiorgan Involvement Proven Using Lymphocyte Transformation Test.

Drug-induced hypersensitivity syndrome (DiHS), also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a rare but potentially life-threatening condition induced by drug hypersensitivity that leads to significant morbidity and mortality and often occurs in patients undergoing combination antibiotic therapy. Due to a recent increase in the incidence of methicillin-resistant Staphylococcus aureus infections, the occurrence of vancomycin-induced DiHS/DRESS has increased rapidly. However, because of insufficient pharmacogenetic data on vancomycin-induced drug eruptions in Asians coupled with the risk of re-eliciting the symptoms by provocation tests, confirmation of the culprit drug in vancomycin-induced DiHS/DRESS is often challenging. Here, we report a case of vancomycin-induced DiHS/DRESS, where the causal relationship was confirmed using a lymphocyte transformation test (LTT). A 51-year-old woman was treated with combination antibiotics, including vancomycin, for infective pericarditis. The patient subsequently developed fever, facial edema, generalized rash followed by multiple internal organ involvement, including the kidney, lung, liver, and heart. Thus, based on the International Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria, the case was diagnosed as 'definite' DiHS/DRESS, although the culprit drug was obscured by combination antibiotic therapy. The LTT confirmed that vancomycin, but not other glycopeptide antibiotics, specifically induced T-cell proliferation in this case. Collectively, our case suggests that clinicians can utilize LTT to identify the causative medication of DiHS/DRESS when the clinical information is limited to defining the culprit drug.

Pellino-1 promotes intrinsic activation of skin-resident IL-17A-producing T cells in psoriasis.

BACKGROUND: Psoriasis is a chronically relapsing inflammatory skin disease primarily perpetuated by skin-resident IL-17-producing T (T17) cells. Pellino-1 (Peli1) belongs to a member of E3 ubiquitin ligase mediating immune receptor signaling cascades, including nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) pathway. OBJECTIVE: We explored the potential role of Peli1 in psoriatic inflammation in the context of skin-resident T17 cells. METHODS: We performed single-cell RNA sequencing of relapsing and resolved psoriatic lesions with analysis for validation data set of psoriasis. Mice with systemic and conditional depletion of Peli1 were generated to evaluate the role of Peli1 in imiquimod-induced psoriasiform dermatitis. Pharmacologic inhibition of Peli1 in human CD4+ T cells and ex vivo human skin cultures was also examined to evaluate its potential therapeutic implications. RESULTS: Single-cell RNA sequencing analysis revealed distinct T-cell subsets in relapsing psoriasis exhibiting highly enriched gene signatures for (1) tissue-resident T cells, (2) T17 cells, and (3) NF-κB signaling pathway including PELI1. Peli1-deficient mice were profoundly protected from psoriasiform dermatitis, with reduced IL-17A production and NF-κB activation in γδ T17 cells. Mice with conditional depletion of Peli1 treated with FTY720 revealed that Peli1 was intrinsically required for the skin-resident T17 cell immune responses. Notably, pharmacologic inhibition of Peli1 significantly ameliorated murine psoriasiform dermatitis and IL-17A production from the stimulated human CD4+ T cells and ex vivo skin explants modeling psoriasis. CONCLUSION: Targeting Peli1 would be a promising therapeutic strategy for psoriasis by limiting skin-resident T17 cell immune responses.

Safety, Efficacy, and Drug Survival of Colchicine in Recurrent Aphthous Stomatitis in a Real-World Setting.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common disorder characterized by episodic ulcerations in the oral mucosa. Although colchicine has been a common systemic treatment for RAS, there is still considerable uncertainty regarding its efficacy and drug survival in this setting. OBJECTIVE: We aimed to study drug survival, efficacy, and safety of colchicine for the treatment of RAS, especially in the real clinical setting. METHODS: Between 2012 and 2016, 150 patients given colchicine for RAS were selected for a single-centre retrospective study of real-world efficacy and drug survival. RESULTS: Among the 114 patients who qualified, 81.6% showed moderate or substantial responses (>25% improvement). Gastrointestinal complications (16.7%), neutropenia (3.5%), and liver enzyme elevation (4.4%) were reported within 2 weeks after initiating treatment. Delayed adverse manifestations were rare. One year after onset, colchicine use was sustained in roughly one-half (49.5%) of patients, whereas many (30.3%) had discontinued the drug, primarily due to lack of efficacy or adverse events. In Cox proportional hazard analysis, minor ulcers were identified as potential determinants of longer drug survival owing to less probability of non-efficacy. However, major ulcers had emerged as predictors of early discontinuation due to lack of efficacy. CONCLUSION: In patients with RAS, colchicine may be an effective and safe treatment amenable to long-term maintenance. Monitoring of adverse events within 2 weeks after initiating treatment is advisable to ensure safe administration.

Skin manifestation as an explaining factor of heterogeneity in Behçet's disease: A focused analysis in full-blown conditions.

Behçet's disease (BD), a chronic multi-systemic disorder, presents diverse clinical manifestations depending on patient ethnicity and geographic region. Use of varying diagnostic criteria augments clinical heterogeneity. We aimed to characterize heterogenous manifestations in patients with full-blown BD fulfilling the major diagnostic criteria in use. We retrospectively analyzed 338 patients diagnosed with complete BD based on Japanese diagnostic criteria, which fulfill both International Study Group (ISG) criteria and the International Criteria for BD (ICBD). Unbiased clustering analysis was performed to elucidate the heterogeneous spectrum, followed by subgroup analysis of identified clusters. Results of unbiased clustering analysis identify dominant skin lesion type as an important factor that determines clustering among the heterogenous BD patients. Regression analysis reveals that presence of predominantly papulopustular lesions has protective effect for vascular involvement compared to other skin phenotypes. In conclusion, unbiased clustering analysis highlights that dermatologic manifestation can be a factor to understand the heterogeneity of BD and determining the dominant type of skin lesions may help clinicians predict major vascular involvement.

Non-thermal atmospheric pressure plasma activates Wnt/ß-catenin signaling in dermal papilla cells.

There is an unmet need for novel, non-pharmacological therapeutics to treat alopecia. Recent studies have shown the potential biological benefits of non-thermal atmospheric pressure plasma (NTAPP), including wound healing, angiogenesis, and the proliferation of stem cells. We hypothesized that NTAPP might have a stimulatory effect on hair growth or regeneration. We designed an NTAPP-generating apparatus which is applicable to in vitro and in vivo experiments. The human dermal papilla (DP) cells, isolated fresh hair follicles, and mouse back skin were exposed with the NTAPP. Biological outcomes were measured using RNA-sequencing, RT-PCR, Western blots, and immunostaining. The NTAPP treatment increased the expression levels of Wnt/ß-catenin pathway-related genes (AMER3, CCND1, LEF1, and LRG1) and proteins (ß-catenin, p-GSK3ß, and cyclin D1) in human DP cells. In contrast, inhibitors of Wnt/ß-catenin signaling, endo-IWR1 and IWP2, attenuated the levels of cyclin D1, p-GSK3ß, and ß-catenin proteins induced by NTAPP. Furthermore, we observed that NTAPP induced the activation of ß-catenin in DP cells of hair follicles and the mRNA levels of target genes of the ß-catenin signaling pathway (CCND1, LEF1, and TCF4). NTAPP-treated mice exhibited markedly increased anagen induction, hair growth, and the protein levels of ß-catenin, p-GSK3ß, p-AKT, and cyclin D1. NTAPP stimulates hair growth via activation of the Wnt/ß-catenin signaling pathway in DP cells. These findings collectively suggest that NTAPP may be a potentially safe and non-pharmacological therapeutic intervention for alopecia.

Clinical characteristics and histopathologic changes of morphea: A single-center, retrospective study of 137 patients.

BACKGROUND: The clinicopathologic correlations and prognostic risk factors for refractory disease in morphea (localized scleroderma) are poorly described. OBJECTIVE: To investigate the association between clinical characteristics and histopathologic features of morphea and identify risk factors for refractory disease. METHODS: We retrospectively reviewed the clinical and histopathologic features, treatment regimens, and clinical responses for 137 patients with biopsy-proven morphea from January 2008 to May 2019. Multivariate analysis was conducted to identify factors associated with poor treatment response. RESULTS: We detected associations between the pattern and degree of sclerosis and the anatomic site of the lesion, as well as between severe inflammation and concomitant autoimmune disease. Additionally, both bottom-heavy sclerosis and increased inflammation were associated with functional limitations/clinical symptoms. Based on our multivariate analysis, we found that increased risk of poor treatment response was correlated with tissue eosinophils and basal pigmentation. LIMITATIONS: This was a single-center retrospective study. CONCLUSION: Skin biopsy samples could show specific features of morphea, including eosinophil infiltration and basal pigmentation, which may indicate the need for aggressive treatment and frequent monitoring.

Randomized controlled study for the anti-aging effect of human adipocyte-derived mesenchymal stem cell media combined with niacinamide after laser therapy.

BACKGROUND: Recent advancements in laser-assisted drug delivery have emphasized the importance of post-laser use of active ingredients. AIMS: We evaluated the effect of topical post-laser treatment with adipocyte-derived stem cell-containing medium (ADSC-CM) in combination with niacinamide through a double-blind, randomized, vehicle-controlled study. PATIENTS/METHODS: Twenty-five patients with aging skin underwent ablative fractional laser (AFL) treatment on both sides of the face for skin rejuvenation. Moisturizers with or without ADSC-CM plus 2% niacinamide was applied to the designated sides of faces for 3 weeks. The wrinkle and the melanin indices were assessed using a specialized digital photography analyzer. Additional in vitro assays were performed. RESULTS: The wrinkle index, melanin index, patient satisfaction score, and the investigator's global esthetic improvement scale (GAIS) after use of ADSC-CM plus niacinamide were significantly higher than after use of the vehicle cream. The in vitro UVB irradiation assays with human keratinocytes showed decreased levels of pro-inflammatory cytokines upon incubation with ADSC-CM plus niacinamide, and the cell scratch assay displayed decreased MMP-1 and MMP-2 expression as well as increased Type 1 collagen expression. CONCLUSIONS: We demonstrated that post-laser topical application of ADSC-CM in combination with niacinamide has anti-aging effect on skin.

Application of single-cell RNA sequencing on human skin: Technical evolution and challenges.

The bulk tissue RNA sequencing technique measures the average gene expression of potentially heterogeneous cellular subsets of human skin. However, single-cell RNA sequencing (scRNA-seq) enables both profiling of gene expression measurements at a single-cell resolution and identification of cellular heterogeneity. This recent technical advance has broadened the understanding of many aspects of skin biology, such as development, oncogenesis, and immunopathogenesis. However, due to the low number of mRNAs detectable in an individual cell and the alteration of transcriptomes during sample preparation, scRNA-seq data are often extremely noisy. Moreover, unstandardized methodologies for sample preparation, capturing, and bioinformatic analysis (e.g., batch correction or integration) hamper reliable inter-study comparisons. Nevertheless, sophisticated bioinformatic analysis and integrative omics-based approaches are making up for these limitations. Here, we discuss both the advantages and technical challenges of scRNA-seq, a promising tool opening new horizons in dermatological research.

Patients with non-ambulatory cerebral palsy have higher sclerostin levels and lower bone mineral density than patients with ambulatory cerebral palsy.

Bone loss is a serious clinical issue in patients with cerebral palsy (CP). Sclerostin has garnered interest as a key mechanosensor in osteocytes, leading to considerations of the therapeutic utilization of anti-sclerostin medications. This study was undertaken to determine associations among mechanical unloading, sclerostin levels, and bone imbalance in patients with CP. A total of 28 patients with CP participated in this cross-sectional study. The following measurements were taken: anthropometrics, clinical diagnosis of CP subtype and ambulatory status, bone mineral density (BMD) z-scores at the lumbar spine and hip, and blood biochemical markers, including sclerostin, parathyroid hormone (PTH), osteocalcin, C-terminal telopeptide, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, creatinine, calcium, and phosphorus. In analysis according to CP subtype, patients with spastic CP showed significantly lower BMD z-scores at the lumbar spine and femur neck regions than patients with dyskinetic CP. In analysis according to ambulatory status, patients with non-ambulatory CP showed significantly lower BMD z-scores at all lumbar spine and femoral sites, lower PTH and creatinine levels, and higher plasma sclerostin levels than patients with ambulatory CP. In regression analysis, ambulatory status was a significant determinant of plasma sclerostin levels. This study is the first to report on sclerostin levels and BMD in patients with CP, based on the hypothesis that patients who lack sufficient weight-bearing activities would show increased sclerostin levels and decreased BMD scores, compared with patients who sustain relatively sufficient physical activity. Therefore, this report may provide clinical insights for clinicians considering ambulatory status, sclerostin levels, and bone loss in patients with CP.