The Journal of investigative dermatology最新文献

Ruxolitinib cream and narrow-band UVB phototherapy (NB-UVB) independently promote repigmentation in patients with vitiligo. This exploratory phase 2 study evaluated the efficacy and safety of adding NB-UVB to ruxolitinib cream therapy. Patients (≥12 years) with nonsegmental vitiligo and depigmented areas ≤10% total body surface area applied 1.5% ruxolitinib cream monotherapy twice daily to depigmented areas. At Week 12, patients with <25% improvement from baseline in total Vitiligo Area Scoring Index (

Skin is constantly exposed to environmental and iatrogenic stressors, and its response varies depending on the type of stress. Responses from these stressors include acute local and systemic multiorgan inflammation and delayed immunosuppression. Unfortunately, the mechanisms behind these effects regarding effectors remain unclear. In this review, we provide evidence for a pathway in which the damaged skin keratinocyte responds through formation of effector platelet-activating factor within microvesicle particles. This paper highlights the therapeutic potential of blocking this process through pharmacologic inhibition of the enzyme acid sphingomyelinase needed for microvesicle particle biogenesis.

The most common subtype of cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF), is characterized by proliferation of malignant T-cells in the skin. In the more clinically aggressive folliculotropic variant of MF (FMF), malignant T-cells localize to follicular epithelium while in classic MF (CMF), they infiltrate the dermis and epidermis. How the localization of neoplastic T cells to the follicular niche contributes to the clinical aggression in FMF is unclear. To uncover the tumor microenvironmental differences between perifollicular FMF and dermal CMF regions, we analyzed patient samples using spatial transcriptomics. Transcripts were collected from specific cell subsets within follicular (FMF) and dermal (CMF) regions of interest to compare gene expression, spatial deconvolution, and pathway activity. Our work revealed that the neoplastic CD4 T cells around the hair follicles in FMF had a highly inflammatory phenotype, better adaptation to cellular starvation, higher metabolic activity, and enhanced antigen presentation. In contrast, CTCL-associated macrophages in FMF exhibited an immunosuppressive phenotype with decreased interleukin-2 and interferon signaling. These findings suggest the follicular microenvironment may provide survival advantages to malignant T cells while promoting a dysregulated anti-tumor immune response. These observations provide insight into the mechanisms underlying the more aggressive clinical features of FMF versus CMF.

Nagashima-type palmoplantar keratosis (also referred to as SERPINB7-related palmoplantar epidermal differentiation disorder) is the most common form of palmoplantar keratoderma in East Asia. It is characterized by erythematous hyperkeratosis, palmoplantar hyperhidrosis, and a distinctive foot odor that significantly impairs QOL. In this study, we aimed to clarify the etiology of this odor by investigating the plantar microbiome and evaluating the therapeutic effects of topical benzoyl peroxide. Compared with healthy controls, individuals with Nagashima-type palmoplantar keratosis exhibited significantly higher objective odor scores; increased bacterial load, especially in the intertoe area; and reduced microbial diversity. Corynebacterium and Staphylococcus were the predominant dysbiotic flora species. The topical application of benzoyl peroxide significantly reduced foot odor and bacterial load; increased microbial diversity; and selectively decreased Corynebacterium abundance, particularly that of C tuberculostearicum. These changes correlate with the species-specific susceptibility of skin-resident bacteria to benzoyl peroxide. Our findings suggest that microbial dysbiosis, especially the overgrowth of Corynebacterium species, is central to the pathogenesis of foot odor in Nagashima-type palmoplantar keratosis. Topical benzoyl peroxide is a promising therapeutic intervention for mitigating dysbiosis and its associated foot odor. This study highlights the potential of microbiome-targeted therapies for symptom relief in inherited skin disorders such as Nagashima-type palmoplantar keratosis.

Chronic pruritus of unknown origin is a debilitating condition characterized by persistent itch without an identifiable cause, yet its underlying mechanisms remain elusive. Using single-cell RNA sequencing, we identified systemic immune dysregulation in patients with chronic pruritus of unknown origin, characterized by upregulated CCL3 expression in monocytes and NK cells. Plasma CCL3 levels effectively distinguished patients with chronic pruritus of unknown origin from healthy controls and strongly correlated with itch severity. Although CCL3 did not function as a direct pruritogen in mice, it enhanced sensory neuron sensitivity through CCR1, thereby amplifying scratching responses to diverse pruritogens. Furthermore, cutaneous CCL3 was markedly upregulated in a chronic dry-skin itch model. Inhibition of CCR1 or neutralization of CCL3 significantly suppressed scratching behavior in this model. Together, these findings identify CCL3 as a potential diagnostic biomarker for chronic pruritus of unknown origin and highlight the CCL3-CCR1 axis as a critical neuroimmune pathway underlying chronic itch. This CCL3-CCR1 signaling pathway may represent a promising therapeutic target for refractory pruritic disorders.