British Journal of Dermatology最新文献

Background: The lack of attention to Chronic Hand Eczema (CHE) and the lack of a specific International Classification of Diseases code for CHE may have limited the assessment of CHE prevalence. To date, prevalence estimates have primarily been derived from (partly small) single-country studies.

Objectives: To estimate the annual prevalence of self-reported physician-diagnosed CHE across socio-demographic characteristics among adults in Canada, France, Germany, Italy, Spain, and the United Kingdom (UK).

Methods: In this observational Chronic Hand Eczema epidemiology, Care, and Knowledge of real-life burden (CHECK) study, a questionnaire was administered to adults between 18 and 69 years old in the general population, recruited through online panels. Quotas and minor weighting adjustments were performed to ensure that the participants were representative of the general population regarding sex, age, region, employment status, urban/rural setting, and, in the UK only, ethnicity. Additional weights were applied to account for population size differences when aggregating country results. Information on self-reported physician-diagnosed CHE was collected. CHE was defined, in accordance with the European Society of Contact Dermatitis, as having hand eczema continuously for three months or more or at least two flares in the past 12 months. CHE annual prevalence with 95% confidence intervals (CIs) was determined for each country, and by subgroups of sex, age, employment, and urban/rural.

Results: Among 60,131 participants, 2,847 self-reported physician-diagnosed CHE, yielding an annual prevalence of 4.7% (CI: 4.6-4.9). Subgroup analyses revealed the CHE prevalence was significantly higher in females than males (5.6% [5.4-5.9] vs. 3.8% [3.6-4.1]; P<0.001), in employed versus unemployed participants (5.3% [5.1-5.6] vs. 3.3% [3.1-3.6]; P<0.001), and in urban versus rural residents (5.0% [4.8-5.2] vs. 3.7% [3.4-4.1]; P<0.001). The prevalence was highest among those aged 30-39 years (6.5% [6.0-7.0]) and lowest in those aged 60-69 years (2.6% [2.3-3.0]).

Conclusions: This large multi-national study is the first to assess CHE prevalence in Europe and Canada using a consistent definition across a broad geographical population. This study reveals that CHE is a common skin disease with annual prevalence of 4.7%, with higher prevalence among females, individuals aged 30-39, those employed, and those living in urban areas.

Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic disorder due to pathogenic variants in the COL7A1 gene. In this study we determined the association between different categories of COL7A1 variants and clinical disease severity in 236 RDEB patients in North America. Published reports or in-silico predictions were used to assess the impact of pathogenic variants in COL7A1 on type VII collagen (C7) protein function. Three impact categories were postulated: genotypes that would likely cause a low impact on C7 function (splice B/missense, missense/missense), medium impact [premature termination codon (PTC)/splice B, splice A/splice B, PTC/missense, splice A/missense, splice B/splice B] and high impact (PTC/PTC, PTC/splice A, splice A/splice A). Splice A variants are predicted to cause downstream PTCs while splice B variants cause in-frame exon skipping and are therefore less deleterious. Severity of functional impact was significantly associated with history of gastrostomy tube placement, esophageal dilation, hand surgery, anemia, renal disease, chronic wounds, diffuse skin involvement and history of squamous cell carcinoma. Odds of death were 3.25 (1.24-8.50, p=0.02) higher in the high vs medium impact group. High impact group patients had worse clinical outcomes. Functional genotype categories are a feasible approach to risk stratify patients based on predicted C7 function.

Background: The prevalence and burden of atopic dermatitis (AD) are disproportionately high in individuals with skin of colour (SOC). Previous research shows that risk for xerosis and/or dyspigmentation is heightened in this population and may be more bothersome. However, there are no patient-reported instruments developed specifically for these disease sequelae in patients with SOC.

Objectives: To develop and perform content validation of patient-reported outcome (PRO) questionnaires to assess AD-related xerosis and dyspigmentation in patients with SOC.

Methods: A targeted literature review was conducted to understand and identify AD-related disease sequelae and quality-of-life impacts relevant to patients with SOC and any instruments used to assess AD in the target population. Two draft PRO questionnaires assessing xerosis (X-AD) and dyspigmentation (D-AD) were developed and refined following advice meetings with clinical experts (N = 3). Questionnaire content validity was explored during hybrid concept elicitation (CE) and cognitive-debriefing (CD) interviews with adult and adolescent patients with SOC who have moderate-to-severe AD (N = 15).

Results: Ten concept-focused articles, three websites, 17 labels, one United States Food and Drug Administration compendium and one clinical trial confirmed xerosis and dyspigmentation were important AD-related disease sequelae. Patients with SOC (46.7% female; age range 12.2-76.1 years) reported that each questionnaire was relevant to their AD experience in an appropriate recall timeframe, were readily understood and meaningful responses were easy to select. The final X-AD consisted of one 11-point numeric rating scale (NRS) assessing xerosis severity and two items assessing the level of bother associated with xerosis appearance and feeling over the past week (0-4 verbal rating scale). The final D-AD consisted of two 11-point NRS items assessing dyspigmentation severity and two items assessing the level of bother associated with how dyspigmentation looked over the past week.

Conclusions: The X-AD/D-AD questionnaires were well understood and effective in capturing the experiences of xerosis and dyspigmentation in the target population in an appropriate and comprehensive way. The study supports the initial development of the questionnaires in accordance with regulatory guidelines and best practices, however psychometric validation is required to evaluate the properties of each questionnaire and develop score interpretation guidelines.

Background: The current management of psoriasis does not differentiate between young and old patients in selecting the safest and/or most effective biologic.

Objectives: To explore the effect of age at treatment initiation in response to biologics in patients with moderate-to-severe psoriasis in the UK and Eire.

Methods: Data from patients registering to the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007-2024 on first course of Tumour Necrosis Factor (TNF), interleukin (IL) 12/13, IL-17 and IL-23 inhibitors (i) with at least 6 months' follow-up were included. Patients aged ≥16 years at registration were grouped into 16-24, 25-34, 35-44, 45-54, 55-64, 65-74, and ≥75 year cohorts with 45-54 years as the Reference Cohort. Biologic survival was defined as the time between treatment initiation to its discontinuation associated with ineffectiveness or occurrence of adverse events (AEs). Adjusted hazard ratio (aHR) with 95% confidence interval (CI) was estimated using a flexible parametric model to compare discontinuing therapy between age groups. Each model included exposure (biologic class), effect modifier (age groups), interaction terms, baseline demographic, clinical, and disease severity covariates.

Results: There were 14,294 patients included; 847 (6%) 16-24; 2,502 (18%) 25-34; 3,575 (25%) 35-44; 3,863 (27%) 45-54; 2,338 (16%) 55-64; 954 (7%) 65-74; and 215 (2%) ≥75 years. The interaction effects model showed individuals aged 16-24 years were more likely to discontinue TNFi due to ineffectiveness compared with the Reference Cohort (45-54 years) [aHR (95% CI) 1.30 (1.10, 1.55)]. For survival associated with AEs, individuals aged 55-64 years were at higher risk of discontinuing TNFi and IL12/23i [1.33 (1.13, 1.56) and 1.34 (1.03, 1.75), respectively], those aged 65-74 years were more likely to discontinue TNFi, IL-12/23i and IL-17i [1.89 (1.54, 2.31), 2.00 (1.47, 2.73) and 1.69 (1.08, 2.64), respectively] whereas individuals aged ≥75 years were at higher risk of discontinuing the four biologic classes.

Conclusions: Psoriasis patients aged 16-24 years are more likely to stop TNFi due to ineffectiveness whereas those aged ≥55 years are more likely to stop biologics due to AEs. These large real-world findings provide important information for clinicians treating people with moderate-to-severe psoriasis across all age groups.

Background: Hidradenitis Suppurativa (HS) is a chronic inflammatory skin condition with a greater prevalence and disease burden in patients who identify as African American and those with a family history of HS, suggesting a strong genetic component to its pathogenesis.

Objective: To evaluate the relationship between plasma inflammatory protein expression, HS disease severity, and genetic ancestry in a diverse cohort of patients with Hidradenitis Suppurativa.

Methods: We performed a case-control study of patients with HS compared to age-, sex-, and ethnicity-matched healthy controls. We profiled circulating inflammatory proteins using Olink High-throughput proteomics and determined genetic ancestry from whole-genome sequencing data.

Results: Using linear regression, we identified novel proteins associated with HS after adjusting for age, sex, and ethnicity. Our analysis also revealed differences in the inflammatory proteome linked to disease severity. Specifically, we found that plasma IL6 levels can distinguish between different Hurley stages, indicating that IL6 may serve as a marker of disease severity. Additionally, we observed variations in inflammatory protein levels based on genetic ancestry: patients with predominantly African ancestry exhibited higher levels of inflammatory proteins associated with neutrophilic inflammation, while those with predominantly European ancestry showed increased levels of Th1-related inflammatory proteins.

Limitations: Single-center study. Limited sample size. Unable to account for treatment status or comorbidities that may influence the level of inflammatory cytokines.

Conclusion: Genetic ancestry and disease severity influence the plasma inflammatory profile in patients with HS.