Alopecia areata (AA) is an immune-mediated hair loss disorder that frequently co-occurs with chronic inflammatory skin disorders, such as atopic dermatitis, vitiligo, and psoriasis. Emerging evidence suggest that such comorbidity profiles represent clinical AA subtypes with distinct etiological underpinnings. However, mechanistic insights remain limited owing to a lack of molecular datasets from comorbid patient cohorts. In this study, we addressed this gap by leveraging publicly available case-control gene expression datasets from AA, atopic dermatitis, vitiligo, and psoriasis for an integrative analysis. Our results revealed a statistically significant overlap between gene expression signatures of AA and each chronic inflammatory skin disorder, suggesting that their co-occurrence is not coincidental. Downstream analyses of shared gene expression signatures suggested catecholamine signaling and hair/skin-pigmentation-related processes as possible drivers of AA and vitiligo codevelopment, whereas skin barrier defects and dysregulation of specific immune response pathways may underlie the comorbid development of AA with atopic dermatitis or psoriasis. This study provides a foundation for future mechanistic investigations into skin, hair follicle, and immune system interactions that drive distinct comorbid AA subtypes.

Upadacitinib is an oral selective Janus kinase 1 (JAK1) inhibitor that targets specific pathways in immune-inflammatory responses. It is increasingly being utilized in the treatment of certain autoimmune diseases. There have been reports of solid tumors and thromboembolic events associated with upadacitinib use. However, to date, no reports have linked upadacitinib therapy to leukemia. Here, we present the first documented case of acute promyelocytic leukemia (APL) complicated by lower extremity venous thrombosis following upadacitinib treatment for vitiligo. The patient maintained normal or mildly reduced platelet counts throughout the clinical course, with no significant coagulation abnormalities requiring component blood transfusions. The patient achieved complete remission following standard induction therapy with all-trans retinoic acid and arsenic trioxide, with an uneventful treatment course. Notably, this clinical presentation markedly differs from typical APL cases, demonstrating unique biological characteristics.

Vitiligo is a chronic autoimmune depigmenting disorder affecting 0.5%-2% of the global population, characterized by bidirectional interplay between psychological stress and disease progression, with accumulating evidence highlighting the central role and translational relevance of the neuro-endocrine-immune-cutaneous axis in its pathogenesis. Epidemiological data indicate over half of patients experience significant psychological stress prior to disease onset, while visible depigmentation markedly elevates the burden of depression and anxiety, establishing a self-amplifying pathogenic loop. Mechanistically, neural crest-derived melanocytes form functional "neuro-pigment units" with intraepidermal nerve endings, enabling bidirectional communication via neuropeptides including calcitonin gene-related peptide (CGRP) and substance P. Dynamic crosstalk among keratinocytes, sensory neurons, and melanocytes integrates neurotrophic and inflammatory signals to tightly regulate melanocyte survival and biological function. Sympathetic activation drives melanocyte injury via norepinephrine-mediated β2-adrenergic receptor signaling, while dopamine metabolites exacerbate apoptosis via the oxidative stress-Akt-Bad axis; context-dependent hypothalamic-pituitary-adrenal axis effects and light-melatonin-circadian clock disruption further promote immune dysregulation and melanocyte loss. Notably, neuromodulatory approaches like transcutaneous auricular vagus nerve stimulation show therapeutic promise by attenuating oxidative stress and limiting pathogenic CD8⁺ T-cell infiltration. These insights have fostered targeted strategies including CGRP receptor antagonists and dual antioxidant-neuroprotective natural compounds. Integrating neuroimmunological modulation with psychological and circadian interventions represents a promising precision medicine framework for vitiligo management.

Vitiligo is a multifaceted autoimmune skin disease characterized by the loss of epidermal melanocytes, yet its molecular basis remains poorly understood. To address the need for a specialized systems biology interface, we present VIRdb v3.0, an integrative database combining curated transcriptomics-based datasets with differentially expressed genes, a protein-protein interaction network highlighting regulatory hubs, and an enriched library of natural compounds and FDA-approved drugs targeting vitiligo-related proteins. The platform supports pathway enrichment, molecular docking, and cross-disease comparisons with autoimmune disorders to identify shared molecular signatures. Backend redevelopment using the Django framework enables scalability and real-time data integration. The updated platform now also supports z-score normalization of expression data, multi-gene pathway enrichment queries, and comparative gene-gene interaction networks for vitiligo and its comorbid autoimmune conditions. VIRdb v3.0 facilitates hypothesis generation, biomarker discovery, and therapeutic exploration, advancing vitiligo systems biology. The database is freely accessible at https://virdb.sbdaresearch.in/.

Natural killer (NK) cells show day-night variation in both number and effector function. We compile findings from human cohorts, animal models, and cell studies on how circadian timing shapes NK biology. Evidence spans daily changes in counts and readouts such as degranulation and IFN-γ; links to core clock modules (PER1/2, NFIL3/E4BP4, STRA13); and neuroendocrine inputs (sympathetic tone, glucocorticoids, melatonin). Acute sleep loss can transiently raise NK activity, whereas multi-day sleep deprivation or circadian misalignment lowers counts or function. Shift work studies and laboratory night-shift simulations show reductions in NK activity and phase-sensitive changes in transcriptional programs (e.g., AP-1/STAT), with effects amplified by irregular schedules and accumulated fatigue. Across cancer, depression, vitiligo, and infection, alterations are heterogeneous, often presenting as peak shifts or amplitude flattening rather than loss of rhythmicity. Photoperiod, season, age, and sex can modify these patterns. Current data support a circadian influence on NK biology, but the direction and magnitude of reported effects vary across species, sampling schedules, circadian phase definitions, tissue compartments, and NK-cell readouts. This heterogeneity underscores the need for longitudinal, high-frequency sampling with complementary continuous monitoring to define phase, amplitude, and stability across physiological and clinical contexts.

This document updates the scientific evidence and clinical practice regarding narrowband UVB phototherapy (NB-UVB) in dermatology. The review addresses indications, therapeutic regimens, safety aspects, combinations with systemic and biologic agents, and adaptation to special populations. NB-UVB remains a first-line therapy for psoriasis, vitiligo, atopic dermatitis, early mycosis fungoides, and photodermatoses due to its efficacy, safety, and cost-effectiveness. Emerging evidence supports its integration with next-generation systemic therapies. This update provides recommendations for its application in the era of targeted therapies, with an emphasis on efficiency and patient-centered care.

Cyclin-dependent kinase (CDK) 4/6 inhibitors are targeted therapies widely used in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Although these agents are generally well tolerated, several cutaneous adverse effects have been reported, including rare cases of vitiligo-like depigmentation. Such pigmentary changes may affect treatment adherence and quality of life. Interestingly, emerging evidence suggests a possible association between these immune-mediated skin manifestations and improved survival outcomes. Further studies are needed to better understand the underlying mechanisms, particularly the role of immune pathways, and to determine the potential prognostic significance of these reactions. We describe a 65-year-old woman with metastatic luminal A, HER2-negative breast cancer treated with ribociclib who developed multiple depigmented patches after 12 months of therapy. Lesions were stable and asymptomatic, allowing continuation of ribociclib. Ribociclib-induced vitiligo-like depigmentation is an under-recognized adverse effect. Early recognition and multidisciplinary management are key to optimizing oncologic care without compromising therapeutic benefit.

Vitiligo is an autoimmune skin disease characterized by the loss of epidermal melanocytes. Oxidative stress serves as a key initiating factor in its pathogenesis. Mitochondria, known as the powerhouse of the cell, perform multiple essential functions in eukaryotic cells and participate in melanocyte physiological processes. Lonp1 is a crucial mitochondrial matrix soluble protease involved in maintaining mtDNA stability, clearing aberrant proteins, and regulating mitochondrial homeostasis. Meanwhile, mitophagy serves as a crucial function within the mitochondrial quality control system, responsible for eliminating damaged mitochondria. Pyroptosis is a form of programmed cell death mediated by inflammasomes, accompanied by cell membrane pore formation and the release of inflammatory cytokines. This study confirmed that oxidative stress was associated with decreased Lonp1 in PIG1 cells, the human melanocyte line. This downregulation impairs mitochondrial homeostasis by suppressing the expression of PINK1, a key mitophagy-related protein, ultimately leading to activation of the NLRP3 inflammasome pathway, release of IL-1β, and induction of melanocyte pyroptosis.