British Journal of Dermatology最新文献

Background: Bullous pemphigoid (BP) is an autoimmune skin disease that mainly affects older people. Based on case series and small hospital-based studies, a number of drugs have been associated with BP. More reliable and precise estimates of associations between a broad selection of drugs/vaccines and BP will enable greater awareness of any potential increased risk of BP following the administration of certain medicines and help identify clinical, histological and genomic characteristics of drug-induced BP for different culprit drugs. Greater awareness could lead to earlier recognition or suspicion of BP and referral to a dermatologist for diagnosis. Earlier diagnosis may lead to less aggressive treatment and improved wellbeing.

Objectives: To determine the association between drugs/vaccines commonly prescribed to older people and the risk of developing BP.

Methods: We conducted a population-based nested case-control study between 1998 and 2021 using electronic primary care records from the Clinical Practice Research Datalink. We matched patients with BP with up to five controls. Exposures were drugs/vaccines commonly prescribed to older people. We used multivariable conditional logistic regression adjusting for multiple drug use. For antibiotics, in a sensitivity analysis, we considered that drugs may be prescribed for undiagnosed symptoms of BP that resemble skin infection (protopathic bias).

Results: Antibiotics were associated with the highest risk of BP [odds ratio (OR) 4.60, 95% confidence interval (CI) 4.40-4.80]. However, after adjusting for protopathic bias, the OR decreased to 2.08 (95% CI 1.99-2.17). Also, after adjusting for protopathic bias, of all the antibiotic classes and subclasses, penicillins [OR 3.44, 95% CI 3.29-3.60 (sensitivity analysis OR 1.74, 95% CI 1.66-1.84)] and penicillinase-resistant penicillins [OR 7.56, 95% CI 7.15-8.00 (sensitivity analysis OR 2.64, 95% CI 2.45-2.85)] had the strongest associations with BP risk. Other drugs strongly associated with increased risk were gliptins (OR 2.77, 95% CI 2.37-3.23) and second-generation antipsychotics (OR 2.58, 95% CI 2.20-3.03).

Conclusions: Healthcare professionals need to be aware of BP risk in older people, particularly when prescribing penicillinase-resistant penicillins, gliptins and second-generation antipsychotic drugs, to recognize and manage BP early. Owing to the low disease prevalence, we do not suggest avoiding certain drugs/vaccines to prevent BP. Further research should consider recency, dosage and duration of antibiotic treatments.

Background: Mycosis fungoides (MF) is a rare malignancy that is characterized by the presence of circulating tumour cells (CTCs) in a subgroup of patients. Reliably distinguishing MF from inflammatory skin conditions is challenging.

Objectives: To evaluate the potential benefits of next-generation sequencing (NGS)-based T-cell receptor rearrangement repertoire analysis in detecting clonal rearrangements in MF and inflammatory skin conditions.

Methods: Skin biopsies and blood samples from 33 patients with MF and 10 patients with inflammatory skin conditions were analysed using TRB and TRG NGS. Twenty-seven patients had early-stage IA (n = 19) and IB (n = 8) MF, and six had advanced-stage disease (IIB, n = 5; IIIA, n = 1).

Results: Analysis applying standard abundance thresholds identified at least one clonal rearrangement in the skin DNA of 97% (n = 32/33) of patients with MF and in 90% (n = 9/10) of those with inflammatory skin conditions. To enhance specificity, an abundance and distribution-based approach was applied, which considered only rearrangements that significantly stood out from the physiological background as clonal (MF, n = 29/33; inflammatory skin conditions, n = 1/10), allowing for highly sensitive (88%) and specific (90%) discrimination between MF and other inflammatory skin conditions. CTCs were detected in 46% (n = 11/24) of patients with early-stage MF and in 60% (n = 3/5) of those with late-stage MF.

Conclusions: NGS-based T-cell receptor repertoire analysis is a highly sensitive and specific method for the differential diagnosis of early-stage MF vs. inflammatory skin conditions, and for the sensitive molecular detection of CTCs.

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of diseases characterized by abnormal neoplastic T-cell growth in the skin. Mycosis fungoides (MF), the most common CTCL, manifests as erythematous skin patches and/or plaques, tumours or erythroderma. The disease may involve blood, lymph nodes and rarely viscera. Sézary syndrome (SS) is a unique leukaemia/lymphoma syndrome related to MF, which presents with blood and skin involvement at diagnosis. The pathogenesis of MF/SS is not fully elucidated. The presence of skin lesions at distant sites underpins a hypothesis that MF/SS lesions may develop through haematogenous seeding. Phenotypic similarities between malignant and normal T cells led to the notion that disease-initiating mutations occur in specific subtypes of mature T cells, which are responsible for most CTCLs. However, this mature T-cell precursor model is not always consistent with clinical observations and research on MF/SS pathogenesis. Here, we review evidence supporting an alternative model of pathogenesis for MF/SS involving haematogenous seeding as a key process responsible for the initiation and progression of the disease. According to this hypothesis, malignant transformation occurs at an early stage of T-cell development (probably in bone marrow or thymus), yielding circulating neoplastic T cells which colonize the skin where the microenvironment is most permissive for proliferation and evolution. These mutated precursor cells seed the skin where they find a suitable niche to develop into clinically perceptible disease. Subsequently, malignant T cells can re-enter the bloodstream, re-seed pre-existing lesions and seed new areas of the skin, causing synchronous and convergent changes in the transcriptomic profile of lesions and tumours, and clinical disease progression - 'consecutive haematogenous seeding' captures this temporal phenomenon. This model radically changes the current understanding of CTCL pathogenesis, transforming it from a primarily cutaneous disease with secondary involvement of blood, to a systemic disease, where the spread of malignant cells through the blood to the skin is not a phenomenon of advanced disease but is an essential component of pathogenesis. This understanding of MF/SS could have several clinical implications, including standardizing our approach to assessing blood tumour burden, potential advances in prognosis and monitoring, and investigating combination treatments to improve patient outcomes.

Background: Approved tralokinumab maintenance dosing regimens for treatment of moderate-to-severe atopic dermatitis (AD) include 300 mg every 2 weeks (Q2W) and every 4 weeks (Q4W). Clinicians may consider tralokinumab Q4W for patients whose skin has become clear or almost clear at week 16 with initial Q2W dosing.

Objectives: To identify predictive factors associated with maintained response after switching to tralokinumab Q4W, evaluate recapture of treatment response after relapse on Q4W, and assess treatment-emergent immunogenicity with tralokinumab Q4W.

Methods: These post hoc analyses utilized machine learning to identify predictive factors for maintained treatment response at week 52 using data from the week 16 responder population of the phase III ECZTRA 1 and 2 trials, i.e. patients who met Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) and/or ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16 with tralokinumab Q2W monotherapy. Top-ranked factors were then assessed individually and together to identify factors associated with a similar maintained efficacy at week 52 between patients rerandomized to tralokinumab Q2W or Q4W monotherapy at week 16. Additionally, the probability of recapturing IGA 0/1 and/or EASI 75 response after relapse was assessed in patients on tralokinumab Q4W transferred to the open-label arm.

Results: The two top-ranked predictive factors for maintained response at week 52 were IGA score at week 16 (76.1%) and worst daily pruritus numeric rating scale (NRS) < 3 at week 16 (56.5%). Patients whose AD reached stable clinical response scores of both IGA 0/1 and worst daily pruritus NRS < 3 from weeks 12-16 with tralokinumab Q2W similarly maintained IGA 0/1 response at week 52 regardless of dosing regimen beyond week 16 (72.0% of patients on Q2W and 72.2% of those on Q4W). Of patients who relapsed on Q4W, 94.6% recaptured treatment response after returning to Q2W dosing. The immunogenicity potential of tralokinumab was low, and patients with positive antidrug antibodies did not show loss of efficacy or higher incidences of adverse events.

Conclusions: These data suggest that Q4W is an effective dosing regimen for most patients who achieved stable disease control as shown by clear/almost clear skin and no itch to mild itch over 4 consecutive weeks on the initial regimen of tralokinumab Q2W.

Chronic wounds, defined by their prolonged healing process, significantly impair patients' quality of life and impose a hefty financial burden on healthcare systems worldwide. Sex- and gender-specific mechanisms regulate inflammation and infection, angiogenesis, matrix synthesis and cell recruitment. All of these processes contribute to cutaneous wound healing but remain largely understudied. This review aims to spotlight the innovative realm of bioengineering and nanomedicine, which is at the helm of revolutionizing complex chronic wound care. It underscores the significance of integrating patient sex into the development and (pre)clinical testing of these avant-garde treatment modalities, in order to enhance healing prospects for all patients regardless of sex. Moreover, we explore the representation of male and female patients in clinical trials of bioengineered and nanomedicine products. Finally, we examine the primary reasons for the historical neglect in translating sex-specific wound healing research into clinical practice and propose strategic solutions. By tackling these issues, the article advocates advanced treatment frameworks that could significantly improve healing outcomes for individuals of all sexes, thereby optimizing both efficacy and inclusivity in chronic wound management.