Patients with atopic dermatitis prioritize treatment attributes of rapid effectiveness and safety. A survey of 1274 patients revealed a preference for oral dosing unless it posed higher risks, highlighting the role of safety in treatment decisions.

Nickel is the most frequent cause of allergic contact dermatitis (ACD). Recent studies have shown that epidermal skin-resident memory T (TRM) cells play a central role in ACD. However, how TRM cells accumulate and differentiate in the epidermis of allergic individuals repeatedly exposed to nickel is not known. To investigate how repeated exposure to nickel affects the clinical reaction and the accumulation and differentiation of epidermal TRM cells in individuals allergic to nickel. Twelve participants with nickel allergy were patch-tested three times with nickel with a 21-day interval by applying the patch to the same skin site each time. Two days after each patch test, the skin reactions were assessed and clinically scored. 21 days after each patch test, skin biopsies were taken and analysed by flow cytometry and single-cell RNA sequencing. The number of CD4+ and CD8+ T cells in the epidermis and the clinical score increased with each exposure to nickel. 90-95% of the T cells were CD69+ TRM cells. We found expanded Th2 and/or Th17-like CD4+ and cytotoxic CD8+ TRM cell clones in all participants; however, CD4+ TRM cells dominated in some participants, whereas CD8+ TRM cell dominated in others. We could not correlate specific T cell subtypes to the severity of the clinical response. As a common feature, all participants exhibited a polyclonal Treg cell population and exhausted-like populations of CD4+ and CD8+ TRM cells and Treg cells in the epidermis. In this study, we determined the complexity of epidermal T cells in allergic individuals repeatedly exposed to nickel, identifying several distinct clusters of effector and exhausted-like CD4+ and CD8+ TRM and Treg cells.

Many melanoma patients experience worry, anxiety, and distress. Screening for psychological distress can facilitate early identification and management. However, little is known about such distress in melanoma survivors (MS) and patients at high risk for melanoma (HRM). The primary outcome was to assess the melanoma-related worry in MS and HRM patients. Additionally, a secondary outcome was to determine the optimal Distress Thermometer (DT) cut-off for identifying those needing psycho-oncological support. We prospectively collected the distress-related patient-reported outcomes at the Department of Dermatology of the University Hospital in Basel, Switzerland, between 01/2021 and 01/2024. Validated questionnaires including the DT, Melanoma Worry Scale (MWS), Patient Health Questionnaire (PHQ-8), and Generalized Anxiety Disorder (GAD-7) were used to assess the primary outcome. For the secondary outcome, receiver operating characteristic (ROC) analysis were used to estimate the optimal DT cut-off. The study population comprised 430 individuals, including 175 (41%) MS and 255 (59%) HRM patients. Worry about getting a primary or subsequent melanoma was more prominent in MS with 26% compared to 16% of HRM patients. HRM patients had less melanoma worry compared to MS, with an odds ratio (OR) of 0.56 (95% CI: 0.34-0.93). Melanoma worry predictors included being divorced (OR:3.08, 95% CI:1.28-7.38) and younger (OR:0.97, 95% CI:0.95-0.99). HRM patients showed significant higher distress (median DT:4, interquartile (IQT):2,6) compared to MS (DT:2, IQT:1,5) (p-value<0.001). ROC analysis estimated DT of 3 as the optimal cut-off for MS (area under the curve [AUC]: 0.82, true positive rate [TPR]:0.95, false positive rate [FPR]:0.38), whereas DT of 6 was optimal in HRM (AUC: 0.77, TPR: 0.70, FPR: 0.22). While MS exhibit greater disease-specific worry, HRM show increased general distress, underscoring distinct psycho-oncological needs. Adopting tailored DT cut-offs (≥3 for MS, ≥6 for HRM) may improve the detection of clinically relevant distress in these subgroups. Importantly, however, interest in psychological support was observed across all DT scores, indicating the need for flexible, patient-centred approaches. These findings highlight the unmet need for psychosocial care in both MS and HRM populations and could aid dermatologists to screen patients in future practice regularly.

Bullous pemphigoid mainly affects the elderly, with various co-morbidities. The disease has a high mortality rate, due both to the disease itself and to the side-effects of systemic treatments. The aim of this study was to identify blood and skin predictive factors for therapeutic response at diagnosis, in order to offer our patients the most appropriate treatment for their condition as quickly as possible. A prominent Th2 response was identified in first-line resistant patients. It was found possible to predict resistance to first-line treatment in BP through skin IL-4, IL-13 and IL-5-expressing cells. By contrast, Clusters of differentiation 68 (CD68) and skin IFN-ɣ-expressing cells (Th1 profile) were associated with a sensitivity to first-line treatment.

Keratins are vital structural proteins forming intermediate filaments (IFs). They lead to various inherited skin fragilities when dysfunctional. The keratin tail domain is essential for the proper functioning of IF, with glycine loop variability prominent in certain keratin tails. However, the effects of glycine loop variations on the functioning of IFs, and the pathogenicity of excessive variations remain elusive. To clarify the pathogenic effects associated with excessive glycine loop variations. We employed whole-exome sequencing on a patient with epidermolysis bullosa (EB) lacking mutations in known EB-causing genes. Sanger sequencing was used to verify identified variations in the patient, the patient's family members, and a cohort of 319 healthy controls. The pathogenicity of identified variations was evaluated using in vitro and in vivo IF assembly experiments, mouse models, cellular experiments, and human skin three-dimensional (3D) models. We identified a compound heterozygous mutation in KRT10, comprising insertions of two and four tandem c.1654_1683 repeats at the c.1683_1684 position, which increased the number of glycine loops by two and four in the keratin 10 tail domain. Although insertions of one and two c.1654_1683 repeats were prevalent in healthy individuals (16.46% and 14.26% , respectively), four insertions were not detected. In vivo and in vitro experiments revealed that excessive glycine loops prevented the proper assembly of IFs. Experiments in mouse and human skin 3D models confirmed that an overabundance of glycine loops led to an EB-like phenotype. In KRT10, the insertions of limited c.1654_1683 repeats were prevalent and harmless in the general population. However, excessive insertions, exemplified by compound heterozygous mutations with insertions of two and four c.1654_1683 repeats, could be pathogenic. This study was novel in highlighting the pathogenicity of excessive glycine loop extension in the keratin tail domain, thereby establishing a paradigm for other human keratins with glycine-rich tail domains.

Pemphigus vulgaris (PV) is a severe autoimmune blistering disease characterized by immune inflammatory response imbalance. The role of the pro-inflammatory cytokine, Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), in the pathogenesis of PV remains unclear. To evaluate the inflammatory status in PV and investigate the proinflammatory cytokine TWEAK's role in both initiating and exacerbating inflammation, as well as its effects on desmoglein (Dsg) internalization at keratinocyte membranes induced by PV cell models and individual PV-IgG components. This study collected serum samples from 60 new-onset PV patients and 55 healthy controls to evaluate the correlation between serum anti-desmoglein (Dsg) antibody levels and disease severity, inflammatory cytokines (TWEAK, IL-1β, IL-2R, IL-6, IL-10, TNF-α), and chemokines (CCL2, CCL5, CXCL8). Subsequently, skin lesions from 9 patients were collected to analyze local TWEAK, PV-IgG expression and immune cell infiltration. Finally, an in vitro PV cell model was established to investigate the inflammatory potential and cell adhesion injury of PV-IgG, individual PV-IgG components, and TWEAK induction. Analysis of 60 new-onset PV patients revealed that serum anti-Dsg1 antibody levels were positively correlated with both the Pemphigus Disease Area Index (PDAI) score and the levels of inflammatory cytokines (TWEAK, IL-6, TNF-α) and chemokines (CCL5, CXCL8). Furthermore, infiltration of immune cells (neutrophils, macrophages, and T cells) was observed in the perilesional areas of skin lesions. In vitro experiments demonstrated that TWEAK exacerbates desmosomal internalization in keratinocytes triggered by PV-IgG components. Moreover, PV-IgG components induce over expression of TWEAK and CXCL8 in keratinocytes, whereas IL-6, TNF-α, and CCL5 were upregulated via TWEAK-dependent pathways, thereby amplifying inflammatory cascades. This study demonstrates elevated levels of inflammatory cytokines (TWEAK, IL-6, TNF-α) and chemokines (CCL5, CXCL8) in the circulation of PV patients, which correlate with disease severity. Additionally, localized immune dysregulation involving neutrophils, macrophages, and T cells was observed within PV skin lesions. In the end, we highlight TWEAK's involvement in enhancing chemokine expression and cell adhesion injury in pemphigus, which suggest a promising therapeutic avenue targeting TWEAK and inflammatory cytokines in pemphigus management.

Response to the recently published correspondence ‘Perianal melanosis’ by Zhao et al.