British Journal of Dermatology最新文献

Background: Vitiligo and autoimmune alopecia (AA) are caused by T cell-mediated autoimmunity in genetically predisposed individuals. Studies in vitiligo have reported reduced risks for malignant melanoma (MM), as well as for keratinocyte cancer (KC). Similarly, in AA, reduced risks for KC and MM have been reported. The driving mechanisms (genetic predisposition, immunological or other effects of the disease phenotypes, or environmental factors) remain unclear. Whether or not the immune-related genetic predisposition in vitiligo and AA offers 'inherent' protection against other types of cancer remains unresolved.

Objectives: To investigate the incidence and outcome of MM, squamous cell carcinoma (SCC) and noncutaneous cancers in vitiligo and AA, compared with the general population, and to investigate the corresponding risks in their respective siblings.

Methods: We performed a population-based matched cohort study using data from linkage of Swedish registers. We used Cox proportional hazards regression to calculate hazard ratios (HRs) contrasting patients with vitiligo or AA with the general population, as well as contrasting patients' siblings with siblings of individuals from the general population.

Results: Between 2006 and 2021, we included 15 030 patients with vitiligo and 18 541 with AA, along with, respectively, 17 853 and 21 821 of their siblings. Based on 17 MM events [crude incidence rate per 100 000 person-years (IR) = 16] and 23 SCC events (IR = 22) in vitiligo, along with 20 MM events (IR = 15) and 24 SCC events (IR = 18) in AA, the hazard ratio (HR) for MM was 0.53 [95% confidence interval (CI) 0.32-0.86] in vitiligo and 0.53 (95% CI 0.34-0.83) in AA. Regarding SCC, the HR was 0.81 (95% CI 0.53-1.24) in vitiligo and 0.65 (95% CI 0.43-0.98) in AA. Stage at diagnosis of MM did not differ substantially between patients and the general population. Among siblings, HRs for MM and SCC were not statistically significantly altered (0.82 ≤ HR ≤ 1.10; P > 0.05). In patients and their siblings, HRs for noncutaneous solid or haematological cancers were not reduced.

Conclusions: In vitiligo and in AA the decreased risk of cutaneous cancers extends beyond the cell type targeted by the autoimmune reaction. The general tendency towards somewhat reduced skin cancer risks among patients' siblings suggests a role for factors other than the disease phenotypes per se. Neither the vitiligo and AA phenotypes nor their immune-related genetic predispositions seem to offer any 'inherent' protection against noncutaneous malignancies.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i), a novel class of antidiabetic medication, have emerged as a key treatment option in diabetes management. Notably, SGLT2i promote glucose and sodium excretion through urine, a mechanism that may be implicated in the potential association between SGLT2i use and risk of atopic dermatitis (AD).

Objectives: To investigate the relationship between SGLT2i use and new-onset AD in people with diabetes.

Methods: This nationwide active-comparator cohort study used data from the Taiwan National Health Insurance database to investigate the association between SGLT2i use and AD risk. The study included adults with type 2 diabetes mellitus who initiated SGLT2i or DPP4i between May 2016 and December 2018, with no prescriptions for other SGLT2i or DPP4i in the 12 months prior to cohort entry. A total of 148 354 SGLT2i users were identified as the study group, while 322 703 DPP4i users were designated as the active comparator group. The primary outcome was the incidence of AD. To minimize potential confounding, inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics, medical history and ever having used medication between the two groups. Additionally, sensitivity analyses, subgroup analyses and sex-specific assessments were conducted to further validate the findings. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of developing AD.

Results: SGLT2i users had a lower incidence of AD (9.742 vs. 12.070 per 1000 PY) than DPP4i users. SGLT2i users had a significantly lower risk of AD compared with DPP4i users (HR 0.847) after IPTW adjustment. Different types of SGLT2i also showed a consistent protective effect for AD. Notably, the highest SGLT2i dosage was associated with the lowest risk of AD (IPTW-adjusted HR 0.647), consistent across sensitivity analyses. Additionally, men who use SGLT2i exhibited a much lower risk of AD (IPTW-adjusted HR 0.750) than women who use SGLT2i.

Conclusions: SGLT2i show a significant protective effect against AD in patients with diabetes compared with DPP4i. This robust finding, consistent across weighting and sensitivity analyses, supports SGLT2i use, with a strong protective effect also found in the dose-response analysis.

In 2019, a group of experts published the first European guidelines for the management of congenital ichthyoses after a multidisciplinary expert meeting held in 2016. An update of these guidelines and literature search was planned every 5 years, given the clinical, molecular and therapeutic advances, including the use of biologic therapies. We present here updated guidelines that have been developed by a reorganized multidisciplinary group of international experts. The evidence is based on a systematic review of recent literature, discussions and consensus reached at an expert conference held in June 2023. The guidelines provide summarized evidence and expert-based recommendations that aim to guide clinicians in the management of these rare and often complex diseases. These guidelines consist of two sections. This Part one covers topical and systemic therapies (including oral retinoids, biologics and Janus kinase inhibitors), future therapeutic approaches, psychosocial management, telemedicine, communicating the diagnosis and genetic counselling, prenatal diagnosis and preimplantation genetic testing.

Cutaneous T-cell lymphomas (CTCLs) are a group of rare and heterogenous diseases. There is currently no curative treatment for patients with advanced mycosis fungoides (MF) and Sézary syndrome (SS). The European Organisation for Research and Treatment of Cancer consensus recommendations for the treatment of MF/SS have been updated and focus on recently available treatments. Peginterferon, a new form of interferon, has a favourable risk-benefit profile for the treatment of patients with CTCL. Recently approved monoclonal antibodies (mABs) have completely modified the treatment algorithm of advanced CTCL treatment. Brentuximab vedotin is very efficient for tumours and transformed MF. Mogamulizumab can induce long-term remission in patients with SS. An international trial of lacutamab has recently been completed, for both SS and MF. Numerous novel targets have been identified, and several new mABs have been shown to be able to enhance specific immune responses and to induce targeted antibody-dependent cytotoxicity and cytophagocytosis. These new antibodies warrant further evaluation in controlled trials. Kinase inhibitors and chimeric antigen receptor T-cell therapy are promising new treatments. Finally, recent studies have demonstrated that allogeneic haematopoietic stem-cell transplantation can increase survival and quality of life in patients with advanced CTCL.

Background: The effectiveness of botulinum toxin A (BoNTA) in the treatment of Hailey-Hailey disease (HHD) has shown heterogeneity in recent studies. However, there is currently no research investigating the underlying mechanism behind the variability in patient response.

Objectives: To identify potential biomarkers and elucidate the underlying mechanisms of the heterogeneity in efficacy of BoNTA treatment for HHD.

Methods: Twelve patients with HHD were administered standardized injections of BoNTA, with the primary endpoint being ≥ 75% improvement in Improvement Global Assessment(IGA) from baseline to month 6. A comprehensive multiomics approach, including whole-exome sequencing (WES), bulk RNA sequencing (RNAseq), single-cell RNAseq and immunohistochemistry (IHC) was used to investigate potential mechanisms underlying the heterogeneity of therapeutic efficacy. Additionally, an in vitro experiment was conducted to validate cellular responses to BoNTA, providing further insights into the biologic mechanisms involved.

Results: Ten of 12 patients (83%) achieved the primary endpoint with BoNTA treatment, while 2 patients (17%) showed no response at month 6. WES did not find a significant association between the type of mutation in ATP2C1 in patients with HHD and their response to BoNTA treatment. Transcriptomic analysis and IHC of baseline skin lesions revealed an overactivated store-operated calcium entry (SOCE) pathway involving genes such as ITPKC and ORAI1 in keratinocytes, accompanied by activation of the NOD-like-receptor containing a pyrin domain 1 (NLRP1)/interleukin (IL)-18/IL-1β inflammatory cascade in BoNTA-resistant patients. We confirmed that loss of ATP2C1 triggered inflammatory responses in HaCaT cells in vitro. BoNTA demonstrated potential anti-inflammatory effects as a calcium antagonist, while upregulation of ORAI1/SOCE contributed to a diminished response to BoNTA.

Conclusions: BoNTA treatment in HHD exhibits interindividual variability. Although the type of ATP2C1 mutation has no direct association with patients' response, combined transcriptomic analysis and IHC indicate that upregulation of the ORAI1/SOCE pathway may contribute to treatment resistance and serve as biomarkers to predict patient responsiveness.