Dermatology and Therapy最新文献

Introduction: Mild-to-moderate scalp seborrheic dermatitis (SD) is commonly managed by using anti-SD shampoos containing antifungal, anti-inflammatory, and keratolytic agents. A newly formulated anti-SD shampoo containing the patented combination of two antifungal actives has shown good clinical efficacy and tolerability in a previous two-phase randomized controlled trial.

Methods: A specific analysis of scalp SD-associated metabolome was conducted to identify molecular markers involved in SD symptoms, and examine the impact of the anti-SD shampoo on these compounds. The intervention scheme involved a 2-week phase of intensive product use (three times a week), followed by an 8-week parallel-group maintenance phase consisting of the test group using the study shampoo once a week, and the control group using a neutral shampoo.

Results: Following the intensive phase of the intervention, a significant decrease in the levels of SD markers (cathepsin S, interleukin-8, and histamine), inflammatory lipids (arachidonic acid, linoleic acid, and oxylipins), and metabolites involved in tryptophan metabolism (indolacetate and indolelactate) was observed. These changes were sustained during the maintenance phase in the test group only, supporting the clinical efficacy of the anti-SD shampoo. The integrated analysis of metabolome and fungal microbiome data suggested a positive correlation between the level of Malassezia fungi and that of two oxylipins (9,10,13-triHOME and 9-HODE), highlighting the pivotal role of these lipolytic fungi in SD conditions, and the involvement of newly identified proinflammatory lipid mediators. These oxylipins could be used as novel targets for developing alternative anti-SD strategies.

Conclusion: This approach allowed us to better characterize specific interactions within the scalp ecosystem providing deeper insights and unravelling new therapeutic pathways in SD like pro-inflammatory oxylipins.

Clinicaltrials:

Gov identifier: NCT06578962 (retrospectively registered on August 28, 2024).

Introduction: Topical corticosteroids are regarded as the first-line therapy for chronic hand eczema (CHE), despite a lack of substantial evidence from randomized controlled trials to confirm their efficacy. Topical benvitimod is a potential alternative for long-term maintenance.

Methods: A prospective, single-center, open-label randomized trial was conducted, using a parallel-group design and enrolling 64 patients who had moderate-to-severe CHE. Patients were randomly divided into two treatment groups: 32 patients used 1% benvitimod cream twice a day for 8 weeks, whereas the other 32 patients received halometasone cream on the same application schedule and duration. The percentage of patients who achieved "treatment success" at week 12 was the primary endpoint. Secondary endpoints included changes in physician-assessed Hand Eczema Severity Index (HECSI), patient-reported subjective scores, the relapse rate, and adverse events. Patient-reported subjective scores included Patient Global Assessment (PaGA), Dermatology Life Quality Index (DLQI), and Quality of Life in Hand Eczema Questionnaire (QOLHEQ).

Results: Fifty-nine patients completed the trial (30 in the benvitimod group and 29 in the halometasone group). The treatment success rate was 26.7% (8/30) in the benvitimod group and 24.1% (7/29) in the halometasone group (p = 0.824) at week 12. From baseline to week 12, the two groups demonstrated significant reductions in HECSI, PaGA, DLQI, and QOLHEQ scores (p < 0.05). However, no statistically significant differences were observed between the two groups. Among patients who achieved treatment success, 25.0% (2/8) patients in the benvitimod group and 57.1% (4/7) patients in the halometasone group relapsed at week 24 (p = 0.315). The main adverse events associated with benvitimod were skin pigmentation, pruritus, and skin dryness, none of which led to treatment discontinuation.

Conclusions: Benvitimod exhibits efficacy comparable to halometasone in managing moderate-to-severe CHE, along with a favorable safety and a low relapse rate.

Trial registration number: ChiCTR2100051948.

Introduction: Long-term disease and symptom control is a goal of atopic dermatitis (AD) therapy. This study assessed the long-term maintenance of disease and symptom control with as-needed application of ruxolitinib cream.

Methods: Patients aged ≥ 12 years with AD, an Investigator's Global Assessment (IGA) score of 2/3, and 3-20% affected body surface area were included in the phase 3 TRuE-AD1 and TRuE-AD2 studies. This analysis included patients randomized to twice-daily (BID) 1.5% ruxolitinib cream for 8 weeks and then as-needed (IGA ≥ 1) BID for up to 44 weeks (long-term safety [LTS] period).

Results: Among patients evaluated for disease control in the as-needed period (N = 428), IGA 0/1 (skin/almost clear skin) was achieved by 67.1% of patients at week 8. From week 8, 80-90% of patients with IGA 0/1 at a given visit maintained or improved their response at the next visit. Median time to worsening disease (IGA ≥ 2) was 36.1 weeks during the as-needed period, and IGA 0/1 was quickly recaptured. Patients spent a median 43.9% of the as-needed period off treatment due to lesion clearance. No itch/no sleep disturbance (Patient-Oriented Eczema Measure questions 1 and 2) was reported in 32.7%/71.8% of patients at week 8 and 36.2%/74.5% of patients at week 52. No new safety concerns emerged in the LTS period.

Conclusion: Continued disease and symptom control with substantial time off treatment makes 1.5% ruxolitinib cream an effective long-term option for patients with mild to moderate AD.

Trial registration: Clinicaltrials.gov, NCT03745638 and NCT03745651 (studies registered November 19, 2018).

Introduction: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition that significantly impairs quality of life (QoL) and imposes a substantial socioeconomic burden. Abrocitinib, a selective Janus kinase 1 inhibitor, has shown promise in clinical trials, yet real-word data in Chinese patients remain limited. This interim analysis of the AHEAD (Abrocitinib Chinese rEgistry on Atopic Dermatitis, ChiCTR2400086045) registry aims to characterize treatment patterns and early effectiveness in real-world settings.

Methods: AHEAD is an ongoing, prospective, multicenter, observational study enrolling adults with AD initiating abrocitinib across 42 sites in China. This interim analysis included data from 314 patients enrolled between 18 October 2023 and 30 April 2024, with assessments through week 12. Clinical effectiveness, QoL, adherence, and flare incidence were evaluated using validated physician- and patient-reported outcome measures.

Results: A total of 314 patients were enrolled. At baseline, most patients exhibited moderate to severe AD [mean Investigator's Global Assessment (IGA) score of 3.0; Eczema Area and Severity Index (EASI) score of 13.5] with impaired QoL [Dermatology Life Quality Index (DLQI) score of 12.0]. Treatment with abrocitinib led to rapid and sustained improvement across all measures through week 12: IGA (40% reduction), EASI (79%), Peak Pruritus Numerical Rating Scale (PP-NRS) (52%), Scoring AD (SCORAD) (62%), DLQI (48%), and Atopic Dermatitis Control Tool (ADCT) (55%). At week 12, 36.1% achieved IGA success (score of 0 or 1 with ≥ 2-grade improvement) and 61.6% reached EASI-75 (≥ 75% improvement in EASI). Improvements were observed as early as week 2. Adherence was high (96.8% with proportion of days covered ≥ 0.8), and flares were infrequent (7%).

Conclusion: Patients enrolled in AHEAD exhibited significant disease burden in AD signs and QoL. Abrocitinib provides early and sustained improvement in disease severity and QoL among Chinese adults with moderate to severe AD, with high adherence and low flare rates.

Trial registration: ChiCTR2400086045.

Introduction: Guselkumab, a selective p19 subunit-targeted IL-23 inhibitor, has shown high efficacy and a favorable safety profile in clinical trials of moderate-to-severe plaque psoriasis (PsO). However, real-world data on patient satisfaction with the guselkumab One-Press device, particularly in Portuguese clinical practice, are limited.

Methods: This real-world, prospective, multicenter, nationwide study evaluated patient satisfaction with self-administration of guselkumab using the One-Press device over 52 weeks in adults with moderate-to-severe plaque PsO. A total of 101 patients from 10 dermatology centers were enrolled between September 2022 and November 2023. Patient satisfaction was assessed using the Self-Injection Assessment Questionnaire (SIAQ) at baseline and week 20. Using the SIAQ, patients rated the One-Press device's acceptability across six domains predose and postdose (feeling about injections, self-confidence, and satisfaction with self-injection; postdose only: self-image, pain and skin reactions during or after the injection, and ease of self-injection device use). Quality of life (Dermatology Life Quality Index [DLQI]), clinical effectiveness (Investigator Global Assessment [IGA]), and safety were evaluated through week 52.

Results: Mean SIAQ PRE Module score increased significantly from 6.9 ± 1.8 at baseline to 8.3 ± 1.5 at week 20 (p < 0.001), indicating improved self-injection experience. Injection-related anxiety decreased from 63.4% to 48.9%. Mean DLQI score improved from 8.5 ± 6.9 at baseline to 1.5 ± 2.8 at week 20 and 1.1 ± 3.0 at week 52; 70.8% of patients achieved DLQI 0/1 by week 52. Despite nearly 90% having prior biologic or systemic therapy exposure, IGA 0/1 ("clear" or "almost clear") was achieved by 86.3% of patients at week 20 and 91.0% at week 52. A total of 198 adverse events (AEs) were reported in 62.4% of patients and were mainly mild, localized injection-site reactions. One serious AE was considered related to guselkumab.

Conclusions: In routine clinical practice in Portugal, guselkumab self-administered using the One-Press device demonstrated high patient satisfaction, substantial quality-of-life improvement, robust clinical effectiveness, and a favorable safety profile. These real-world findings support the usability and benefit-risk profile of self-administered guselkumab for patients with moderate-to-severe plaque PsO.

Introduction: Hand eczema and psoriasis present overlapping clinical features, complicating diagnosis and treatment selection. Traditional diagnostic methods rely on clinical assessment, patient history, allergy testing, and histopathology. However, recent advancements in molecular diagnostics offer promising alternatives. Accurate diagnosis is crucial for optimal therapy selection, particularly in occupational dermatology, where hand eczema is a common occupational disease.This study aims to assess the effectiveness of molecular diagnostics in distinguishing hand eczema from psoriasis, analyze disease severity and chronicity, and evaluate therapeutic changes and health-related quality of life (HrQoL) over a 2-year period.

Methods: A long-term cohort study was initiated in November 2020, enrolling 287 patients with suspected occupational skin disease. Molecular classification based on gene expression (CCL27 and NOS2) was performed on skin biopsies. Data collection included physician global assessment (PGA), Quality of Life in Hand Eczema Questionnaire (QOLHEQ), and Dermatology Life Quality Index (DLQI). Statistical analyses employed Cohen's kappa, χ² tests, Wilcoxon signed-rank tests, and 95% confidence intervals.

Results: Of 272 patients assessed via molecular diagnostics, 38.9% had clinically unclear diagnoses, with over 95% of these clarified through molecular classification. Dermatological and molecular diagnoses showed low agreement. Disease severity and chronicity significantly decreased over 2 years. Use of systemic therapies increased, while overall corticosteroid usage declined. HrQoL improved significantly, with DLQI scores decreasing by 50%.

Conclusions: Molecular diagnostics significantly enhance diagnostic accuracy for hand dermatoses, leading to targeted treatment adjustments. The observed therapy shift correlated with improved disease outcomes and HrQoL. As specialized systemic treatments emerge, precise diagnostic tools will be essential for optimizing patient care and reducing the burden of occupational skin diseases.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease often requiring continuous therapy. The objective with the ECZTEND trial was to assess the long-term safety and efficacy of tralokinumab treatment.

Methods: ECZTEND was a multicountry, open-label, 5-year extension trial conducted from September 2018 to July 2024 in patients (≥ 12 years) with moderate-to-severe AD who had received up to 1 year of tralokinumab treatment in a parent trial. Patients were eligible regardless of previous randomization (tralokinumab or placebo) or treatment response in the parent trial. The primary endpoint was the number of treatment-emergent adverse events (TEAEs) through week 268. Key secondary endpoints were Investigator's Global Assessment (IGA) and Eczema Area and Severity Index (EASI) through week 248.

Results: In total, 1672 patients were enrolled (4466.2 patient-years of exposure; median 2.6 years). Overall, 68.4% of patients (n = 1143) completed the trial period they consented to; 7.1% (n = 117) discontinued owing to lack of efficacy; and 4.2% (n = 72) owing to adverse events. The TEAE incidence rate was 114.3/100 patient-years with a pattern consistent with that observed in the parent trials albeit at lower rates. The majority (> 97%) of TEAEs were nonserious and of mild or moderate severity. Most (> 80%) were assessed as not related to tralokinumab by the investigator and resolved by the end of the trial. Common TEAEs (≥ 5%) included nasopharyngitis, atopic dermatitis, coronavirus infection, upper respiratory tract infection, conjunctivitis, and headache. The proportions of patients with IGA 0/1 and EASI-75/EASI-90 increased during the first 16 weeks and then remained stable through week 248 at ≥ 50% for IGA 0/1 and EASI-90, and ≥ 80% for EASI-75.

Conclusions: Long-term tralokinumab treatment for up to 6 years (parent trials plus ECZTEND) in patients ≥ 12 years with moderate-to-severe AD was well tolerated and maintained long-term efficacy. A graphical abstract is available for this article.

Trial registration: Clinicaltrials.gov listing: NCT03587805 (ECZTEND).

Introduction: Sensitive skin (SS) is a common clinical condition characterized by exaggerated sensory responses such as burning, stinging, itching, and irritation to otherwise nonpathological stimuli, most frequently affecting the face. The underlying mechanisms remain incompletely understood, particularly with regard to the role of the skin microbiome.

Methods: This study investigated the facial skin microbiota in Vietnamese adults with SS and examined its associations with clinical symptoms and skin physiological parameters. A total of 75 participants were enrolled, including 45 with SS and 30 with nonsensitive skin (NSS). Clinical assessment included evaluation of subjective symptoms, symptom regularity, time of symptom onset, trigger factors, and objective measurements of skin pH, sebum, hydration, transepidermal water loss (TEWL), erythema, and melanin index. Bacterial communities were profiled using 16S rRNA gene sequencing targeting the V3-V4 region.

Results: Participants with SS exhibited significantly higher erythema and TEWL across all sex and age subgroups, as well as elevated skin pH in female and middle-aged participants (p < 0.05). Alpha and beta diversity metrics did not differ significantly between SS and NSS groups. However, differential abundance analysis using Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC) identified 53 bacterial genera with significant compositional differences, indicating subtle community restructuring. A total of 32 genera, including Peredibacter, Enterobacter, and Marmoricola, were enriched in SS, whereas Streptococcus, Escherichia-Shigella, and Weissella were depleted. Correlation and stratified analyses further revealed genus-level associations with skin physiological parameters, clinical symptoms, anatomical locations, symptom regularity, and time since symptom onset.

Conclusions: SS is associated with subtle but distinct alterations in facial skin microbiome composition, in parallel with measurable changes in skin physiological parameters related to barrier function and reactivity. The results indicate associations between microbial composition, skin physiological parameters, and clinical characteristics in the SS phenotype, and offer a population-specific microbiome reference for Vietnamese facial skin.

Introduction: A matching-adjusted indirect comparison evaluated the short-term efficacy of lebrikizumab plus topical corticosteroids (TCS) versus dupilumab plus TCS in adults with moderate-to-severe atopic dermatitis (AD).

Methods: Individual patient data from the ADhere trial (lebrikizumab 250 mg every 2 weeks [Q2W] plus TCS) and aggregate data from the CHRONOS trial (dupilumab 300 mg Q2W plus TCS) were matched using the method of moments approach to adjust baseline differences. Matching was done at the study level (primary analysis) and at the study arm level (sensitivity analysis). Efficacy endpoints up to week 16 included the proportion of patients achieving an Investigator's Global Assessment of 0 or 1 (IGA 0/1); a ≥ 50%, ≥ 75%, and ≥ 90% improvement from baseline in the Eczema Area and Severity Index (EASI 50/75/90); a ≥ 4-point improvement from baseline in the Pruritus Numerical Rating Scale score (PNRS ≥ 4); and a ≥ 4-point improvement from baseline in the Dermatology Life Quality Index score (DLQI ≥ 4). Placebo-adjusted efficacy outcomes were compared using odds ratios (ORs), risk ratios (RRs), and risk differences (RDs) with 95% confidence intervals (CIs).

Results: At week 16, lebrikizumab plus TCS had comparable odds to dupilumab plus TCS of achieving EASI 75 (OR 1.14, 95% CI 0.42-3.09), IGA 0/1 (OR 1.39, 95% CI 0.42-4.59), PNRS ≥ 4 (OR 0.48, 95% CI 0.17-1.37), and DLQI ≥ 4 (OR 0.89, 95% CI 0.29-2.69). At earlier timepoints, lebrikizumab plus TCS had comparable odds to dupilumab plus TCS of achieving PNRS ≥ 4 at week 2 (OR 2.04, 95% CI 0.24-17.05) and week 4 (OR 3.59, 95% CI 0.90-14.36). RR and RD estimates were consistent with OR estimates of efficacy. Sensitivity analyses confirmed the findings of the primary analysis.

Conclusion: Lebrikizumab plus TCS was comparable to dupilumab plus TCS across all efficacy endpoints at week 16.

Chronic spontaneous urticaria (CSU) is a debilitating inflammatory skin disorder characterized by recurrent wheals and/or angioedema lasting beyond 6 weeks without identifiable triggers. Recent advances have shifted the understanding of CSU from a historically idiopathic condition to one increasingly recognized as an immune-mediated disease with distinct endotypes, including type I (autoallergic) and type IIb (autoimmune). This narrative review synthesizes contemporary insights into CSU pathophysiology, endotype classification, and systemic manifestations, while highlighting the substantial impact on quality of life, sleep, and psychological health. Advances in biomarker research, including total serum immunoglobulin E (IgE) levels, basophil activation tests (BAT), and eosinophil counts, support progress toward personalized treatment approaches. Therapeutically, management of CSU has evolved from empirical symptom control with H1 antihistamines toward mechanism-based precision medicine. Omalizumab remains the established second-line therapy, and dupilumab received US Food and Drug Administration (FDA) approval in 2025 for antihistamine-refractory disease. In parallel, several targeted therapies are under investigation, including Bruton's tyrosine kinase (BTK) inhibitors, anti-KIT antibodies, and Janus kinase (JAK) inhibitors. These therapeutic mechanisms may offer sustained benefit, though long-term outcomes require validation through controlled trials. Integration of psychological interventions, such as cognitive behavioral therapy combined with pharmacotherapy, underscores the need for holistic patient care. Despite these advances, challenges remain in biomarker validation, sequencing of new therapies, and bridging clinical trial evidence with real-world practice. Future directions include refining endotype-driven personalized care, conducting long-term real-world studies, and developing cost-effective, globally accessible treatment strategies to optimize patient outcomes.