Skin neglected tropical diseases (NTDs) remain a major public health challenge in low- and middle-income countries, where frontline health workers (FHWs) often lack dermatological training. In response, the World Health...Skin neglected tropical diseases (NTDs) remain a major public health challenge in low- and middle-income countries, where frontline health workers (FHWs) often lack dermatological training. In response, the World Health Organization (WHO) created the Skin NTDs App-developed by UniversalDoctor-to support FHWs in resource-limited settings. Initially created as a digital adaptation of a WHO's training guide, the App evolved by incorporating another clinical decision support tool (CDST) from until No Leprosy Remains and an artificial intelligence (AI)-powered visual classifier (VC). Our purpose is to describe the WHO Skin NTDs App and evaluate its AI-powered VC. The VC was trained to identify 12 skin NTDs out of 13 through a convolutional neural network (DenseNet-121). Performance was assessed through sensitivity, specificity, accuracy, precision, F1-score, and per-class sensitivity from top-1 through top-5. The VC demonstrated high performance in internal evaluations, achieving 99.8% top-5 sensitivity across all diseases and top-1 accuracy above 75% for most diseases. Some underrepresented conditions (e.g., chromoblastomycosis, sporotrichosis) showed lower precision. In conclusion, the AI-powered WHO Skin NTDs App is a promising digital tool for capacity-building of FHW in underserved areas. Continued development, external validation, and integration into clinical workflows will be critical to assess its performance globally.
Daily molecular rhythms modulate skin physiology. However, the effects of chronic sun exposure on these rhythms remain unstudied. This study aimed to identify and compare rhythmic genes and pathways in photoprotected and...Daily molecular rhythms modulate skin physiology. However, the effects of chronic sun exposure on these rhythms remain unstudied. This study aimed to identify and compare rhythmic genes and pathways in photoprotected and chronically photoexposed human skin in vivo. Skin biopsies were taken from photoprotected (upper buttock) and photoexposed (dorsal forearm) skin of 20 subjects at noon, 6 PM, midnight, and 6 AM across a 24-hour cycle, and gene expression was quantified using RNA sequencing. Cosinor analysis identified cycling genes along with their amplitudes and peak expression phases. We found that fewer genes met the criteria for cycling in photoexposed skin than in photoprotected skin, and transcripts that cycled in both sites had lower amplitudes and advanced peak times in photoexposed skin than in photoprotected skin. We identified 480 genes with significantly different rhythmic properties between the skin sites. Genes involved in DNA repair, MYC targets, E2F, and G2M checkpoint pathways were enriched among those that showed higher amplitude oscillations in photoprotected skin. Genes involved in epithelial-mesenchymal transition and apical junction pathways showed higher amplitude oscillations in photoexposed skin. These results suggest that chronic UV exposure may disrupt and/or reprogram circadian output rhythms to further alter skin physiology.
Lim HW, Schalka S, Trautinger F
… +11 more, Baptista MS, Chien AL, Cole C, Gilaberte Y, González S, Hamzavi I, Krutmann J, Kohli I, Osterwalder U, Rodrigues M, Passeron T
Exposure to solar UVR is well-known to elicit photobiologic effects on the skin. However, exposure to visible light (VL) is now known to contribute to numerous cutaneous responses, such as post-inflammatory hyperpigmenta...Exposure to solar UVR is well-known to elicit photobiologic effects on the skin. However, exposure to visible light (VL) is now known to contribute to numerous cutaneous responses, such as post-inflammatory hyperpigmentation, and play a role in melasma and some photodermatoses. Unlike UVR, no standard methods have been agreed upon for assessing VL photoprotection. The aims of this modified Delphi consensus process were to convene an international panel of experts in VL photobiology to define the cutaneous effects of VL on the basis of current best evidence, determine the populations most in need of VL photoprotection, identify the best strategies for VL photoprotection, and recommend a standardized methodological approach for assessing the effects of VL on the skin. These 27 consensus statements are provided to guide and optimize future research, clinical practice, and product development for VL photoprotection.
Berryhill CA, East MP, Hanquier JN
… +2 more, Johnson GL, Angus SP
J Invest Dermatol
· 2026 May · PMID 42101388
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Kinases are central regulators of multiple signaling cascades, controlling processes such as cellular growth, proliferation, and differentiation. Given their vital role within the cell, dysregulated kinase activity contr...Kinases are central regulators of multiple signaling cascades, controlling processes such as cellular growth, proliferation, and differentiation. Given their vital role within the cell, dysregulated kinase activity contributes to several skin diseases, including melanoma and dermatitis. Poor disease response or resistance to targeted inhibitors can be driven by adaptive kinase responses. Genomic assays are highly informative but do not accurately capture kinase abundance and activity at the protein level. In this paper, we review 2 complementary mass spectrometry-based proteomics methods for functional kinome analysis that are readily applicable to dermatology research. Multiplexed inhibitor beads coupled with mass spectrometry (MIB-MS) uses broad-spectrum, immobilized kinase inhibitors to enrich for kinases in active conformation, providing an unbiased, pathway-level readout of kinase network dynamics, adaptive rewiring, and drug specificity. Internal standard triggered-parallel reaction monitoring (IS-PRM)-targeted proteomics, including the Thermo SureQuant acquisition method, leverages heavy peptide triggers to deliver sensitive, consistent quantification of predefined kinase peptides from limited input clinical specimens, including formalin fixed, paraffin embedded. We summarize optimized workflows, instrument set-up, sample requirements, technical considerations, and limitations. Together, MIB-MS and IS-PRM SureQuant offer orthogonal, scalable strategies to profile kinase networks in skin biology and to inform target discovery, biomarker development, and rational therapeutic strategies.
Teufelberger AR, Cerpes U, Dan AR
… +12 more, Bokanovic D, Fink-Puches R, Mahnke NA, Vera Ayala C, Chu Wang SY, Pyatilova P, Fedai K, Frischbutter S, Fessler J, Siebenhaar F, Kränke B, Wolf P
Hymenoptera venom immunotherapy (VIT) is usually effective in inducing long-term tolerance to the allergen. In patients with a clonal mast cell disease (CMD) and Hymenoptera venom-induced anaphylaxis, however, life-long...Hymenoptera venom immunotherapy (VIT) is usually effective in inducing long-term tolerance to the allergen. In patients with a clonal mast cell disease (CMD) and Hymenoptera venom-induced anaphylaxis, however, life-long VIT is recommended, as tolerance to the venom is often lost after VIT termination. We compared blood samples from patients with CMD and non-CMD with severe Hymenoptera venom-induced anaphylaxis before and more than 3 years after VIT to identify differences that might explain the lack of long-term tolerance in patients with CMD. Serum tryptase, IgE, IgG4, KIT D816V variation, as well as circulating T and B cell subsets, were analyzed. In addition, the cytokine response of wasp venom-stimulated PBMCs was measured. VIT-treated patients with CMD had higher numbers of CD8 effector memory T cells, while VIT-treated patients without CMD showed higher frequencies of CD8 central memory T cells compared to those in patients prior to VIT. The IL-6 response to wasp venom was lower in patients with CMD, regardless of anaphylaxis and therapy status. The generation of CD8 central memory T cells during VIT may be necessary for long-term tolerance to wasp venom after VIT.
The Mas-related G-protein-coupled receptor X2 is a promiscuous receptor expressed on mast cells that mediates IgE-independent mast cell activation and degranulation in response to a variety of diverse agonists and has be...The Mas-related G-protein-coupled receptor X2 is a promiscuous receptor expressed on mast cells that mediates IgE-independent mast cell activation and degranulation in response to a variety of diverse agonists and has been implicated in numerous inflammatory conditions, including atopic dermatitis (AD). We investigated whether the small-molecule Mas-related G-protein-coupled receptor X2 antagonist INCB000262 improves disease phenotype in the house dust mite + Staphylococcus aureus enterotoxin type B (HDM+SEB) mouse model of AD and further characterized mast cell-mediated aspects of disease. Mas-related G-protein-coupled receptor X2 knock-in mice were sensitized to HDM+SEB and orally dosed once daily with either vehicle or INCB000262 for 4 weeks, and efficacy and skin transcriptional changes were evaluated. INCB000262 attenuated HDM+SEB-induced AD in vivo, with improvements observed in skin thickness, transepidermal water loss, tissue weight, and overall clinical score. In addition, transcriptome changes induced by HDM+SEB exhibited a mast cell activation signature consistent with human AD lesional skin, which was attenuated by antagonist treatment. Overall, INCB000262, a Mas-related G-protein-coupled receptor X2 antagonist, attenuated HDM+SEB-induced AD disease phenotypes and mast cell-associated transcriptional changes, supporting further evaluation of INCB000262 as an oral treatment for AD and other mast cell-mediated diseases.
As skin color measurement shifts from subjective classification to quantitative assessment, the assumption that objective measures are unbiased requires scrutiny. We provide a physics-informed framework for interpreting...As skin color measurement shifts from subjective classification to quantitative assessment, the assumption that objective measures are unbiased requires scrutiny. We provide a physics-informed framework for interpreting visible-range skin measurements, clarifying terminology, describing light-chromophore interactions, and surveying tools and output metrics. The physics of light-tissue interaction constrains what any visible-range observation can reveal: melanin and hemoglobin absorb across overlapping wavelengths, and as melanin increases, hemoglobin's signature is masked. By analyzing over 15,000 spectra from the International Skin Spectra Archive, we demonstrate that this attenuation is systematic and most severe in the darkest skin, where data are scarcest. These limits arise from the physical properties of skin's biological constituents and consequently apply to any sensor operating in the visible range. This progressive masking reduces the sensitivity of visible-range erythema detection in more highly pigmented skin, representing an objective, physics-driven constraint rather than a subjective bias. We conclude with guidance on analytical methods, sampling strategies, and extended wavelengths to improve measurement validity across the full range of human skin pigmentation.
Acne vulgaris (AV) is clinically associated with inflammatory bowel disease, yet the biological mechanisms driving this association remain unclear. We investigated the shared genetic architecture of AV and inflammatory b...Acne vulgaris (AV) is clinically associated with inflammatory bowel disease, yet the biological mechanisms driving this association remain unclear. We investigated the shared genetic architecture of AV and inflammatory bowel disease (including ulcerative colitis and Crohn's disease) using data from GWASs. Although AV was genetically weakly correlated with inflammatory bowel disease, MiXeR analyses estimated that 28.2% of the causal variants for inflammatory bowel disease are also causal for AV, with distinct overlap for ulcerative colitis and Crohn's disease. Using the pleiotropic analysis under composite null hypothesis method, we identified 36 shared genomic risk loci, including 27 loci for AV that, to our knowledge, were previously unreported. Downstream functional mapping using MAGMA and S-MultiXcan revealed that these shared variants are predominantly enriched in immune-related tissues (eg, whole blood, spleen) rather than exclusively in the skin or gastrointestinal tracts. Furthermore, pathway analyses consistently highlighted the Jak-signal transducer and activator of transcription signaling cascade as a central shared mechanism. Our findings suggest that the clinical association between AV, ulcerative colitis, and Crohn's disease is driven by shared systemic immune dysregulation. This study provides a refined landscape of pleiotropic genes, prioritizing potentially causal drivers as targets for future mechanistic investigations.