The latest medical research on Dermatology

BRCA1-associated protein (BAP1) tumor predisposition syndrome (TPDS) is a cancer genodermatosis associated with high risk of uveal and cutaneous melanoma, basal cell carcinoma, and multiple internal malignant neoplasms, including mesothelioma and renal cell carcinoma. Early detection of the syndrome is important for cancer surveillance and genetic counseling of family members who are at risk.

To determine the prevalence of nail abnormalities in individuals with pathogenic germline variants in BAP1.

In this prospective cohort study, individuals who were known carriers of pathogenic BAP1 germline variants were consecutively enrolled between October 10, 2023, and March 15, 2024. Dermatologic evaluation for nail abnormalities was performed, including a history of nail abnormalities and associated symptoms, physical examination, medical photography, and nail biopsy for histopathology. This was a single-center study conducted at the National Institutes of Health Clinical Center.

Primary outcomes were the prevalence and spectrum of nail changes and histopathologic characterization.

Among 47 participants (30 female [63.8%]; mean [SD] age, 46.4 [15.1] years) ranging in age from 13 to 72 years from 35 families, nail abnormalities were detected in 41 patients (87.2%) and included leukonychia, splinter hemorrhage, onychoschizia, and distal nail hyperkeratosis. Clinical findings consistent with onychopapilloma were detected in 39 patients (83.0%), including 35 of 40 individuals aged 30 years or older (87.5%). Nail bed biopsy was performed in 5 patients and was consistent with onychopapilloma. Polydactylous involvement with onychopapillomas was detected in nearly all patients who had nail involvement (38 of 39 patients [97.4%]).

This study found that BAP1 TPDS was associated with a high rate of nail abnormalities consistent with onychopapillomas in adult carriers of the disease. Findings suggest that this novel cutaneous sign may facilitate detection of the syndrome in family members who are at risk and patients with cancers associated with BAP1 given that multiple onychopapillomas are uncommon in the general population and may be a distinct clue to the presence of a pathogenic germline variant in the BAP1 gene.

Psoriasis, a T cell-mediated chronic inflammatory skin condition, is characterized by the interaction of T cells with various cell types, forming an inflammatory microenvironment that sustains psoriatic inflammation. The homeostasis of these tissue-resident T cells are supported by fibroblasts, the primary structural cells in the dermis. In psoriasis, there is an increased expression of matrix metalloproteinase 2 (MMP2), mediating the structural alterations of skin tissues and the modulation of inflammation. Additionally, the CD100-PLXNB2 axis is known to enhance psoriasis inflammation via keratinocytes, and CD103 levels are associated with the severity of psoriasis upon relapse.

To elucidate the role of fibroblasts and the MMP2/CD100 axis in modulating psoriasis inflammation.

CD100 expression and function in psoriasis were assessed using immunofluorescence, ELISA, single-cell transcriptome sequencing, cellular interaction analyses, and qRT-PCR. CD8+ T cells from psoriasis patients were isolated using magnetic beads to investigate the regulatory effect of MMP2 on CD100 expression on their membranes. Single-cell transcriptome sequencing, spatial transcriptome sequencing, mimetic timing analysis, immunofluorescence, and flow cytometry were utilized to determine the origin of MMP2 and its impact on CD103+CD8+ T cells. The hypotheses were further validated in vivo using MMP2 and CD100 inhibitors.

Soluble CD100 (sCD100) was significantly upregulated in both psoriatic lesions and peripheral blood, amplifying psoriasis inflammation by promoting the production of inflammatory cytokines by keratinocytes, fibroblasts, and endothelial cells through the sCD100-PLXNB2 axis. Fibroblasts with high MMP2 expression (MMP2hi) exacerbate psoriasis symptoms by facilitating CD100 shedding from CD8+ T cell membranes. Additionally, it was demonstrated that fibroblasts enhance the upregulation of the CD8+ T cell residency factor CD103 in co-cultures with CD8+ T cells. Inhibitors targeting MMP2 and CD100 proved effective in reducing inflammation in a model of imiquimod-induced psoriasis.

Our findings underscore the pivotal role of MMP2hi fibroblasts in the amplification and recurrence of inflammatory responses in psoriasis. These fibroblasts augment psoriasis inflammation through the CD100-PLXNB2 axis by facilitating CD100 shedding on CD8+ T cell membranes and by upregulating CD103, thereby enhancing CD8+ T cell residency.

Basal cell carcinoma (BCC) is the most frequent malignancy reported in populations with fair skin. In most countries, BCCs are only partially or not at all recorded, and incidence data are lacking.

This study assessed the current incidence rates and trends in the only two French départements where BCCs have been recorded for several decades.

This regional population-based study thus used data from two French cancer registries (Doubs and Haut-Rhin) where first-time BCC diagnoses were recorded. The European age-standardised incidence rates (EASR) were calculated per 100 000 person-years (p-y). The trends and the annual percentages of change were assessed using join-point analysis.

In all, 48 989 patients were diagnosed with a first BCC in the study period. The median age at diagnosis was 69 years and the BCCs were mainly located on the head and neck (68.8%). In the Doubs area between 1980 and 2016, the EASR of BCC increased from 59.9 to 183.1 per 100 000 p-y. The annual increase for men was 5.73% before 1999 and 1.49% thereafter, and among women 4.56% before 2001 and 1.31% thereafter. In the Haut-Rhin area, the EASR increased from 139.2 in 1991 to 182.8 per 100 000 p-y in 2019. Among men, the EASR increased annually by 2.31% before 2000, and by 0.29% after 2000; among women, it increased by 0.95% over the entire period (1991-2019). In the most recent period and for these two départements, the age-specific incidence rates of BCC for men and women were close before the age of 60, except for the 40-49 age group, where the rates were significantly higher among women. For patients aged 60 years and over, men had much higher rates of BCC.

BCC incidence has increased since 1980 and is still rising, particularly among men and the elderly. A slowing was observed since 2000, which could be explained by a shift in the management of BCCs and by the possible efficacy of prevention actions. This study provides insight into the BCC burden in France and highlights the need to maintain effective prevention strategies, since incidence is still increasing.