British Journal of Dermatology最新文献

Background: The biological therapy nemolizumab has been shown to improve the signs and symptoms of prurigo nodularis (PN) to a significantly greater extent than placebo over 16 weeks of treatment. We now report efficacy and safety data over 68 weeks.

Objectives: To evaluate the long-term impact of nemolizumab on pruritus, disease severity, quality of life, and topical corticosteroid usage in patients with PN in Japan, and to confirm the safety profile.

Methods: Asian patients aged ≥13 years were randomly assigned (1:1:1) to receive nemolizumab 30 mg, 60 mg, or placebo, with concomitant medium-potency topical corticosteroids, every 4 weeks for 16 weeks. For the subsequent 52 weeks, nemolizumab treatment was continued, while placebo-treated patients were reallocated to either the 30-mg or 60-mg nemolizumab groups. Efficacy outcome measures included the Peak Pruritus Numerical Rating Scale (PP-NRS), 5-level itch scale, Investigator's Global Assessment (IGA), the number of PN nodules, Insomnia Severity Index, Dermatology Life Quality Index, and use of topical corticosteroids. Safety measures included the frequency of treatment-emergent adverse events (TEAEs).

Results: In the modified intention-to-treat population (n=226), nemolizumab provided sustained and continuing improvements in efficacy between weeks 16 and 68. In patients who received nemolizumab 30 mg, the PP-NRS had decreased by 60.5% at week 16 and 78.6% at week 68; respective decreases in the 60-mg group were 55.1% and 76.5%. Across all treatment groups, a large proportion of patients had improvements indicating a reduction from moderate-to-severe to mild pruritus, IGA improvements indicating a reduction in PN severity, a decrease in the number of nodules, and rapid and durable improvements in sleep and daily life activities. Nemolizumab-treated patients were also able to reduce the daily quantity of medium-potency and higher topical corticosteroids used by at least half. There was no indication of relapse in pruritus, PN severity, or quality of life scores following treatment cessation. Most TEAEs were mild and were similar to those reported in prior studies.

Conclusions: Nemolizumab elicited continuous and durable improvements across multiple measures of pruritus, PN severity, and quality of life over 68 weeks of treatment, with no new safety concerns. (Funded by Maruho; jRCT number, 2011200017).

Background: Hidradenitis suppurativa (HS) is a long-term skin condition where evidence for management after first line treatment fails is limited, and practice varies across the UK. Both medical and surgical treatment options are potential avenues for treatment. Furthermore, patient perspectives on HS treatments have received little attention in research to date.

Aim: To explore patients' views and experiences of treatment for HS to inform clinical care.

Methods: A nested qualitative study within a prospective cohort study. Interviews with 35 participants were completed by telephone. Purposive sampling was undertaken. Framework analysis was used to develop themes.

Results: Views on treatments: Past experiences and knowledge informed patient beliefs and whether an individual felt a treatment option was appropriate or a good 'fit' for them at a specific moment in time. Healthcare professional recommendations can be influential on both patient's views and which treatment option they ultimately receive. Experiences of treatments: There were positive experiences across all treatment types used within the study. Negative experiences included side effects of medications, lack of efficacy, delays to procedures, and burden of wound care. However, even when personal experiences were not wholly positive for an individual, participants often believed the same treatment may potentially help others with HS, due to the importance placed on personalisation of treatment.

Conclusions: This paper has implications for how healthcare professionals discuss treatment options with people with HS. A 'one size fits all' approach is inappropriate, and shared decision making that elicits patient beliefs and preferences is crucial.

Background: Despite novel therapeutic options, the long-term management of cutaneous T cell lymphoma (CTCL) remains challenging. Extracorporeal photopheresis (ECP) is an immunomodulating photochemotherapy associated with higher overall survival when used for the treatment of leukemic forms of CTCL. Its exact mode of action is not fully elucidated. Immunogenic cell death (ICD) is pivotal in cancer immunotherapy, marked by the release of damage-associated molecular patterns that enhance dendritic cell (DC) maturation and cytotoxic T lymphocyte responses.

Objectives: This study explores ICD in patients with leukemic forms of CTCL during ECP and its effect on DC activation.

Methods: We conducted in vitro studies with peripheral blood mononuclear cells (PBMCs) from healthy donors and ex vivo experiments with white blood cells (WBCs) from patients with leukemic forms of CTCL undergoing ECP. We assessed cell viability, apoptosis, and ICD markers (ATP, HMGB1, calreticulin) using flow cytometry, ELISA, and qPCR. Engulfment assays evaluated DC activation by ECP-treated CD4+ T cells.

Results: ECP-treated healthy PBMCs and WBCs from patients with leukemic forms of CTCL showed significant induction of ICD hallmarks, including ATP release, HMGB1 secretion, and calreticulin surface exposure. In the patients with leukemic forms of CTCL, calreticulin expression was mainly present in CD4+CD26- T cells, indicating greater ICD susceptibility of malignant T cells. ECP-treated CD4+ T cells were phagocytosed by DCs, a process which we found to be dependent on ICD signals.

Conclusions: ECP induces ICD in malignant T cells and, to a lesser extent, in healthy T cells, facilitating DC activation. These findings suggest that ECP enhances targeted immune responses against malignant T cells in leukemic forms of CTCL, offering new insights into its therapeutic mechanisms and potential applications in cancer immunotherapy.

Background: Patients with psoriasis have a higher baseline risk of herpes zoster (HZ) than the general population. This has raised concerns that TNF-α inhibitor use may be associated with an increased risk of HZ. However, the risk profiles for newer biologics, including IL-17 inhibitor (IL-17i), IL-12/23 inhibitor (IL-12/23i) and IL-23 inhibitor (IL-23i), remain uncertain.

Objective: To compare HZ and postherpetic neuralgia (PHN) risks among different biologics, including ustekinumab, secukinumab, ixekizumab, guselkumab, etanercept and adalimumab, with traditional systemic treatments (TST).

Methods: We conducted a retrospective cohort study by analyzing data from Taiwan's National Health Insurance Research Database (NHIRD 2011-2021). We included patients with psoriasis or psoriatic arthritis aged 20 years and above who had been treated with biologics or TST for at least six months. We classified patients by individual biologics or TST and followed them up for 2.5 years from drug initiation until the occurrence of outcome events or death. The primary outcome was the diagnosis of HZ. We used inverse probability of treatment weighting (IPTW) to adjust for covariates, including patient age, sex, comorbidities and co-medications. We used Cox proportional hazards models to evaluate the risk of HZ among different biologics.

Results: In total, we identified 815, 1870, 1095, 2327, 261, 303 and 98 patients with psoriasis receiving etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, brodalumab and guselkumab, respectively. Compared to patients receiving TST, for those receiving ustekinumab and guselkumab the risk of HZ trended lower (weighted HR: 0.82, 95% CI: 0.61-1.11; 0.48, 0.22-1.02), while for those receiving adalimumab it was statistically significantly higher (weighted HR: 1.63, 95% CI: 1.22-2.18). Additionally, ustekinumab was associated with a reduced risk of PHN (HR: 0.22, 95% CI: 0.08-0.64). There were no significant differences in the risk of HZ between TST and either etanercept, secukinumab, ixekizumab or brodalumab.

Conclusions: The findings suggested ustekinumab and guselkumab may be associated with a reduced risk of HZ and PHN, compared to TST. This study could have significance for real-world practice.

More than 50 palmoplantar epidermal differentiation disorders (pEDDs) have been reported in the literature. Various descriptors have been used to name these conditions including clinical features often designated as acronyms or evocative terms, names of clinicians and of geographical locations. Not only has this nomenclature been criticized for its lack of methodological consistency, it has progressively lost its clinical relevance. Indeed, the advent of a wide range of pathogenesis-targeting therapeutic solutions for these disorders has raised the need for a novel classification of pEDDs, based on their causative genetic defects, to provide clinicians with genuine therapeutic guidance. Here, we present a novel classification scheme for pEDDs and its application in the form of a practical algorithm for the rapid diagnosis of pEDDs.

Background: Growing evidence has shown that cholesterol metabolism abnormalities involve carcinogenesis. Proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors have been reported to inhibit tumour progression and prevent ultraviolet-related skin damage.

Objectives: To investigate the association of PCSK9 inhibitors with the risk of nonmelanoma skin cancer (NMSC).

Methods: This retrospective cohort study analysed data from the US Collaborative Network in the TriNetX database. Adults aged ≥ 40 years with atherosclerotic cardiovascular disease (ASCVD) under statin therapy between 2016 and 2022 were identified. A target trial design was used to compare the risk of NMSC, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), in patients also treated with PCSK9 inhibitors or continuing statin treatment (the control group). Each head-to-head comparison involved propensity score matching. Hazard ratios (HRs) were estimated using Cox proportional hazard models. Stratified analyses based on age, sex, Fitzpatrick skin type and immune status were also performed.

Results: A total of 73 636 patients with ASCVD were analysed. Compared with the control group, patients with ASCVD initiating PCSK9 inhibitors had lower risks of developing NMSC [HR 0.78, 95% confidence interval (CI) 0.71-0.87], BCC (HR 0.78, 95% CI 0.69-0.89) and cSCC (HR 0.79, 95% CI 0.67-0.93). Subanalyses revealed a reduced risk of NMSC with each PCSK9 inhibitor, namely evolocumab and alirocumab. Stratified analyses showed similar results in patients aged 65-79 years, those older than 80 years and in men.

Conclusions: Our study indicated that patients with ASCVD taking PCSK9 inhibitors have a lower risk of incident NMSC than those not taking PCSK9 inhibitors.