Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are common inflammatory skin diseases influenced by environmental factors, but disease-specific environmental pathways remain poorly defined. This study developed a machine learning model to predict monthly disease prevalence and characterize distinct environmental conditions associated with each disease. We analyzed nationwide health insurance claims data for AD, ACD, and corns (control) from six major South Korean cities from 2012 to 2017, constituting 432 city-month records per disease. The M5P model tree algorithm predicted relative monthly prevalence based on meteorological data (temperature, humidity, precipitation, diurnal temperature range) and air pollutants (SO₂, NO₂, CO, PM10), with performance evaluated using Pearson Correlation Coefficient (CC) and Mean Absolute Error (MAE). Analysis of 3,990,692 AD and 16,890,182 ACD cases showed that the combined weather-pollution model achieved high accuracy for AD (CC = 0.839, MAE = 0.038) and ACD (CC = 0.932, MAE = 0.049). Mean temperature was the primary splitting variable for both diseases, but with different thresholds and secondary modulators. For AD, the initial split occurred at 17.4°C; above this, high PM10 (>44μg/m³) was associated with higher prevalence. For ACD, a notable split was identified at 11.65°C; below this, low humidity (<62%) appeared to be a key contributing factor. PM10 was a consistent predictor for both diseases. While temperature is a universal primary driver for both AD and ACD, the diseases follow distinct environmental pathways. AD is modulated by air pollution in warmer conditions, whereas ACD is sensitive to humidity in cooler conditions. This data-driven approach provides insights into disease-specific environmental triggers for public health interventions.

BackgroundCurrent guidelines to treat atopic dermatitis (AD) overlook disease heterogeneity, limiting personalized care. This study assessed NuGel, a topical GPCR19 agonist, for efficacy, safety, and predictive baseline biomarkers in AD patients.MethodsIn a multicenter, double-blind, randomized, placebo-controlled Phase 2a trial (August 2020–September 2021, five hospitals, 80 participants), patients received placebo, 0.3% NuGel, or 0.5% NuGel twice daily for four weeks.ResultsNuGel (0.3% [Nu0.3] and 0.5% [Nu0.5]) was well-tolerated, with no adverse drug reactions or serious adverse events. Nu0.3 showed a significant decrease in EASI score from baseline (-12.2%, [-30.3%, 5.9%], p = 0.04). Treatment with Nu0.5 resulted in a numerically decreased EASI score (-11.9%, [-34.9%, 11.1%], p > 0.05), which is comparable with placebo group (-2.9%, [-21.5%, 15.6%], p > 0.05). No significant difference was observed between groups (p>0.05). Plasma proteomic analysis identified biomarkers associated with blood coagulation, complement activation, and cell adhesion as predictors of response to Nu0.5. Patients with baseline profiles characterized by K2C5high, ENTP6low, or CRKlow demonstrated significant clinical improvement when treated with Nu0.5 compared to the placebo group. Among these, the CRKlow subgroup, comprising 54.3% of the biomarker analysis set, showed a ΔEASI of -61.3% [-99.9, -22.8; p = 0.003] and a ΔIGA of -35.2% [-58.2, -12.1; p = 0.004] compared to the placebo group. The biomarker signature demonstrated high predictive accuracy (AUC = 0.92, p = 0.002). Logistic regression analysis revealed that the threshold of predicted probability derived from the baseline plasma level of K2C5 and ENTP6 successfully stratified 100% of participants who responded to Nu0.5 (ΔEASI from baseline ≤ -50%), whereas none (0%) in the placebo group responded (p = 0.035).ConclusionBaseline biomarkers, such as K2C5, ENTP6, and CRK, may serve as predictors of clinical improvement in AD patients treated with Nu0.5, highlighting the potential for personalized treatment strategies. Further research is required to validate these findings in larger patient cohorts.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT04530643.

Department of Dermatology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea; College of Pharmacy, Chungnam National University, Daejeon, Korea; Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea; Division of Clinical Epidemiology, Medical Research Collaborating Center, Biomedical Research Institution, Seoul National University Hospital, Seoul, Korea; Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea; Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Korea; Department of Dermatology, Dongguk University Ilsan Hospital, Goyang, Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by an accumulation of activated histiocytes within the affected tissues. It is a heterogeneous disease that includes the classical (nodal) and extra-nodal variants. The cutaneous form of the disease without the characteristic lymphadenopathy is rare and is often misdiagnosed as other dermatologic diseases. Misdiagnosis as lymphoproliferative and infectious diseases such as lymphoma and tuberculosis have been reported in the literature. Herein, we report a case of facial cutaneous RDD with successful surgical treatment. In addition, we provide dermoscopic findings and literature review as dermoscopy can be a useful adjuvant tool in the diagnosis of cutaneous RDD.

Dermal fibroblasts lose stem cell potency after birth, which prevents regenerative healing. However, the underlying intracellular mechanisms are largely unknown. We uncover the postnatal maturation of papillary fibroblasts (PFs) driven by the extensive Twist2-mediated remodeling of chromatin accessibility. A loss of the regenerative ability of postnatal PFs occurs with decreased H3K27ac levels. Single-cell transcriptomics, assay for transposase-accessible chromatin sequencing (ATAC-seq), and chromatin immunoprecipitation sequencing (ChIP-seq) reveal the postnatal maturation trajectory associated with the loss of the regenerative trajectory in PFs, which is characterized by a marked decrease in chromatin accessibility and H3K27ac modifications. Histone deacetylase inhibition delays spontaneous chromatin remodeling, thus maintaining the regenerative ability of postnatal PFs. Genomic analysis identifies Twist2 as a major regulator within chromatin regions with decreased accessibility during the postnatal period. When Twist2 is genetically deleted in dermal fibroblasts, the intracellular cascade of postnatal maturation is significantly delayed. Our findings reveal the comprehensive intracellular mechanisms underlying intrinsic postnatal changes in dermal fibroblasts.

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.

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.

The environment surrounding a newborn undergoes remarkable changes throughout the birth. Specifically, the initial warm, humid, and relatively sterile conditions become cool, dry, and full of exposome (pathogens and mechanical stress). Neonatal skin protects newborns from the surrounding environment. However, it scores as functionally incompetent according to non-invasive, on-surface measurements [ 1 Fluhr J.W. Bellemère G. Ferrari C. De Belilovsky C. Boyer G. Lachmann N. et al. age-dependent transformation of skin biomechanical properties and micromorphology during infancy and childhood. J. Invest. Dermatol. 2019; 139: 464-466 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar , 2 Fluhr J.W. Darlenski R. Taieb A. Hachem J.P. Baudouin C. Msika P. et al. Functional skin adaptation in infancy - almost complete but not fully competent. Exp. Dermatol. 2010; 19: 483-492 Crossref PubMed Scopus (102) Google Scholar ]. With the limited availability of human newborn skin tissue, transcriptomic studies on postnatal maturation remain rare. To fill this knowledge gap, our study assessed a mouse skin single-cell RNA sequencing (scRNA-seq) dataset to investigate transcriptomic changes occurring during the neonatal maturation period. We focused on interfollicular keratinocytes (IFKs), the primary cells in the epidermis. The results point to primary candidate genes related to postnatal maturation, including biomechanical change [ [1] Fluhr J.W. Bellemère G. Ferrari C. De Belilovsky C. Boyer G. Lachmann N. et al. age-dependent transformation of skin biomechanical properties and micromorphology during infancy and childhood. J. Invest. Dermatol. 2019; 139: 464-466 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar ].

Alopecia induced by aging or side effects of medications affects millions of people worldwide and impairs the quality of life; however, there is a limit to the current medications. Here, we identify a small transdermally deliverable 5-mer peptide (GLYYF; P5) that activates adiponectin receptor 1 (AdipoR1) and promotes hair growth. P5 sufficiently reproduces the biological effect of adiponectin protein via AMPK signaling pathway, increasing the expression of hair growth factors in the dermal papilla cells of human hair follicle. P5 accelerates hair growth ex vivo and induces anagen hair cycle in mice in vivo. Furthermore, we elucidate a key spot for the binding between AdipoR1 and adiponectin protein using docking simulation and mutagenesis studies. This study suggests that P5 could be used as a topical peptide drug for alleviating pathological conditions, which can be improved by adiponectin protein, such as alopecia.

BACKGROUND:Asivatrep is a potent and selective antagonist of transient receptor potential vanilloid subfamily V member 1 (TRPV1), which plays an important role in itch and inflammation in atopic dermatitis (AD). OBJECTIVE:This current study aimed to evaluate the efficacy and safety of asivatrep cream in patients with AD. METHODS:For this phase 3 double-blind, vehicle-controlled study, patients aged ≥12 years with mild to moderate AD were enrolled and randomly assigned 2:1 to the 1.0% asivatrep or vehicle group for 8 weeks of twice-daily application (n = 240). The primary end point was the proportion of patients with an Investigator's Global Assessment score (IGA) of 0 or 1 at week 8. Standard safety assessments were conducted. RESULTS:At week 8, significantly more patients in the asivatrep group (36.0%) than in the vehicle group (12.8%) had IGA scores of 0 or 1 (P < .001); significantly more had ≥2 points of improvement on the IGA from baseline score (20.3% vs 7.7%; P = .01). The mean percentage reduction in the Eczema Area and Severity Index (EASI) score was 44.3% for the asivatrep group and 21.4% for the vehicle group at week 8 (P < .001). Significantly more asivatrep-treated patients experienced an improvement of at least 50%, 75%, and 90% on the EASI than the vehicle group. The mean ± SD change in the pruritus visual analog scale score at week 8 was -2.3 ± 2.4 for the asivatrep group and -1.5 ± 2.4 for the vehicle group (P = .02). No significant safety issues were reported. CONCLUSION:Asivatrep improved clinical signs and symptoms of AD and was well tolerated.

Chronic inflammatory skin diseases (CISDs) negatively impact a large number of patients. Injection of triamcinolone acetonide (TA), an anti-inflammatory steroid drug, directly into the dermis of diseased skin using needle-syringe systems is a long-established procedure for treating recalcitrant lichenified lesions of CISDs, referred to as TA intralesional injection (TAILI). However, TAILI causes severe pain, causing patients to be stressed and reluctant to undergo treatment. Furthermore, the practitioner dependency on the amount and depth of the injected TA makes it difficult to predict the prognosis. Here, candle flame ("candlelit")-shaped TA-loaded dissolving microneedles (Candlelit-DMN) are designed and fabricated out of biocompatible and biodegradable molecules. Candlelit-DMN distributes TA evenly across human skin tissue. Conjoined with the applicator, Candlelit-DMN is efficiently inserted into human skin in a standardized manner, enabling TA to be delivered within the target layer. In an in vivo skin inflammation mouse model, Candlelit-DMN inserted with the applicator effectively alleviates inflammation by suppressing inflammatory cell infiltration and cytokine gene expression, to the same extent as TAILI. This Candlelit-DMN with the applicator arouses the interest of dermatologists, who prefer it to the current TAILI procedure.

Incontinentia pigmenti (IP) is a rare X-linked skin disease caused by mutations in the IKBKG gene, which is required for activation of the nuclear factor-kappa B signalling pathway. Multiple systems can be affected with highly variable phenotypic expressivity. We aimed to clarify the clinical characteristics observed in molecularly confirmed Korean IP patients. The medical records of 25 females confirmed as IP by molecular genetic analysis were retrospectively reviewed. The phenotypic score of extracutaneous manifestations was calculated to assess the disease severity. The IKBKG gene partial deletion or intragenic mutations were investigated using long-range PCR, multiplex ligation-dependent probe amplification and direct sequencing methods. Among the 25 individuals, 18 (72%) were sporadic cases. All patients showed typical skin manifestations at birth or during the neonatal period. Extracutaneous findings were noted in 17 (68%) patients; ocular manifestations (28%), neurological abnormalities (28%), hair abnormalities (20%), dental anomalies (12%), nail dystrophy (8%). The common exon 4-10 IKBKG deletion was observed in 20 (80%) patients. In addition, five intragenic sequence variants were identified, including three novel variants. The phenotype scores were highly variable, ranging from abnormal skin pigmentation only to one or more extracutaneous features, although no significant difference was observed for each clinical characteristic between the group with sequence variants and that with common large deletion. Our cohort with IP showed heterogeneity of extracutaneous manifestations and high incidence of sporadic cases. Long-term monitoring with multidisciplinary management is essential for evaluating the clinical status, providing adequate genetic counselling and understanding the genotype-phenotype correlation in IP.

Alopecia arises due to inadequate hair follicle (HF) stem cell activation or proliferation, resulting in prolongation of the telogen phase of the hair cycle. Increasing therapeutic and cosmetic demand for alleviating alopecia has driven research toward the discovery or synthesis of novel compounds that can promote hair growth by inducing HF stem cell activation or proliferation and initiating the anagen phase. Although several methods for evaluating the hair growth-promoting effects of candidate compounds are being used, most of these methods are difficult to use for large scale simultaneous screening of various compounds. Herein, we introduce a simple and reliable in vitro assay for the simultaneous screening of the hair growth-promoting effects of candidate compounds on a large scale. In this study, we first established a 3D co-culture system of human dermal papilla (hDP) cells and human outer root sheath (hORS) cells in an ultra-low attachment 96-well plate, where the two cell types constituted a polar elongated structure, named “two-cell assemblage (TCA).” We observed that the long axis length of the TCA gradually increased for 5 days, maintaining biological functional integrity as reflected by the increased expression levels of hair growth-associated genes after treatment with hair growth-promoting molecules. Interestingly, the elongation of the TCA was more prominent following treatment with the hair growth-promoting molecules (which occurred in a dose-dependent manner), compared to the control group (p < 0.05). Accordingly, we set the long axis length of the TCA as an endpoint of this assay, using a micro confocal high-content imaging system to measure the length, which can provide reproducible and reliable results in an adequate timescale. The advantages of this assay are: (i) it is physiologically and practically advantageous as it uses 3D cultured two-type human cells which are easily available; (ii) it is simple as it uses length as the only endpoint; and (iii) it is a high throughput system, which screens various compounds simultaneously. In conclusion, the “TCA” assay could serve as an easy and reliable method to validate the hair growth-promoting effect of a large volume of library molecules.

The main factors involved in the pathogenesis of atopic dermatitis (AD) are skin barrier abnormality, allergy/immunology, and pruritus. Considering how oxidative stress influences these factors, antioxidant agents may be effective candidates in the treatment of AD. To evaluate the effect of Caffeoyl–Pro–His amide (CA-PH), an antioxidant agent, on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like phenotypes in BALB/c mice. Topical sensitization and challenge by DNCB were performed on the dorsal skin of BALB/c mice to induce AD-like cutaneous lesions, phenotypes, and immunologic response. CA-PH was applied topically for 2 weeks to assess its effects on DNCB-induced AD-like phenotypes. As a result, CA-PH relieved DNCB-induced AD-like phenotypes quantified by dermatitis severity score, scratching duration, and trans-epidermal water loss. Histopathological analysis showed that CA-PH decreased epidermal thickening, the number of mast cells, and eosinophil infiltration in dermis. Immunohistochemical staining revealed that CA-PH recovered skin barrier-related proteins: filaggrin, involucrin, and loricrin. As for the immunologic aspects, CA-PH treatment lowered mRNA or protein levels of interleukin (IL)-4, IL-6, IL-17a, IL-1b, IL-31, and IL-33 levels and thymic stromal lymphopoietin (TSLP) levels in cutaneous tissue, reducing the DNCB-induced serum IgE level elevation. In conclusion, topical CA-PH may be a therapeutic option for the treatment of AD.