Dermatology and Therapy最新文献

Introduction: Chronic hand eczema (CHE) remains difficult to treat, particularly in patients unresponsive or intolerant to topical corticosteroids. Although topical delgocitinib, the first topical JAK inhibitor approved for CHE, provides a steroid-free alternative, comparative real-world data versus localized cream psoralen-ultraviolet A (PUVA) are missing. This retrospective real-world study compared the short-term effectiveness and patient-reported outcomes of topical delgocitinib and localized cream PUVA in patients with CHE under routine-care conditions.

Methods: This retrospective cohort study analyzed anonymized routine-care data of patients with moderate-to-severe CHE treated between 2024 and 2025 at a tertiary center. Patients received topical delgocitinib twice daily or localized cream PUVA with as-needed topical corticosteroids (TCS). Twenty-two patients per group completed 12 weeks of delgocitinib or 20-25 PUVA sessions plus TCS (per-protocol). Disease severity (Physician's Global Assessment, PGA), quality of life (Dermatology Life Quality Index, DLQI), and symptom numerical rating scales (pruritus, pain, sleep disturbance) were assessed at baseline and treatment end.

Results: Both therapies significantly improved all endpoints (p < 0.001). Median DLQI improvement was 10 with delgocitinib versus 7.5 with PUVA (p = 0.15). PGA 0/1 responses were 82% vs 73% (p = 0.72). DLQI improvement ≥ 4 points occurred in 91% vs 77% (p = 0.41). Relapses were more frequent after PUVA. Two delgocitinib non-responders improved with alitretinoin. Most delgocitinib responders continued proactive low-frequency use to maintain remission; one remained clear 3 months after stopping treatment.

Conclusion: Delgocitinib and PUVA provided comparable short-term clinical efficacy in CHE, with a numerically greater DLQI reduction for delgocitinib. Proactive delgocitinib maintenance may help sustain disease control. Subtype-adapted treatment strategies could further optimize outcomes.

Introduction: HS-20137 is a novel interleukin-23 inhibitor and is suggested to be effective for the treatment of psoriasis in a phase 1b study. Our study aimed to evaluate the efficacy and safety of HS-20137 in patients with moderate-to-severe plaque psoriasis in a larger and longer phase 2 study.

Methods: This was a randomized, double-blind, placebo-controlled phase 2 study up to 52 weeks. The study was conducted from September 2023 to February 2025 at 22 sites across mainland China and enrolled male and female adults with moderate-to-severe psoriasis. Dosing was scheduled at weeks 0 and 4, and subsequently every 8 weeks (Q8W) or Q12W. Eligible patients were randomized 1:1:1:1 to subcutaneously receive HS-20137 at doses of 100 mg Q8W, 200 mg Q8W, 200 mg Q12W, or placebo. Patients switched to receive HS-20137 200 mg Q8W at week 16 or week 28. The primary endpoint was the percentage of patients achieving at least 90% improvement in the Psoriasis Area and Severity Index (PASI 90) at week 16.

Results: In total, 159 participants were enrolled, with a mean (SD) PASI score of 25.8 (10.9). More patients treated with HS-20137 achieved PASI 90 compared to placebo (65.0%-76.9% in HS-20137 groups vs. 7.5% in placebo group, P < 0.001) at week 16, as well as PASI 100, investigator global assessment (IGA) score of 0/1, and IGA 0. The PASI score significantly decreased in all treatment groups (41.4%-46.2%) after the first injection by week 4 and was maintained through week 52. During the placebo-controlled period, treatment-emergent adverse event (TEAE) rates were similar among groups (77.5%-67.5%). Throughout the study, most TEAEs were mild; only one serious treatment-related AE occurred, and it resolved after treatment.

Conclusions: HS-20137 treatment was tolerable and effective in patients with psoriasis, supporting further investigation and development.

Trial registration: ChiCTR2300075645.

Introduction: Remibrutinib, an oral, highly selective Bruton's tyrosine kinase (BTK) inhibitor, was recently approved by the US Food and Drug Administration (FDA) for the treatment of chronic spontaneous urticaria (CSU). Dupilumab, an interleukin-4 receptor-α monoclonal antibody, was approved by the FDA for CSU in early 2025. Here, we report the design of RECLAIM (NCT06868212), a phase 3b study that aims to compare the efficacy of remibrutinib and dupilumab at early timepoints in patients with symptomatic CSU despite treatment.

Methods: This US-based, multicenter, randomized, double-blind, double-dummy study will include approximately 400 patients with moderate-to-severe CSU who remain symptomatic despite treatment with second-generation H₁-antihistamines (sgH₁-AHs). Patients will be randomized 1:1 to receive either oral remibrutinib (25 mg twice daily) or subcutaneous dupilumab (600 mg loading dose; 300 mg every 2 weeks), in addition to sgH₁-AHs. The study consists of a screening period of up to 4 weeks, a 12-week core treatment period, and a safety follow-up period of up to 12 weeks. Patients with chronic inducible urticaria or other skin diseases with symptoms of urticaria, angioedema, or chronic itching, and patients with prior use of remibrutinib, BTK inhibitors, or dupilumab, are excluded. The primary endpoint is absolute change from baseline in weekly Urticaria Activity Score (UAS7) at week 4. Secondary endpoints include: absolute change from baseline in UAS7 at week 1 and in weekly Itch Severity Score and Hives Severity Score at week 4; achievement of well-controlled disease (UAS7 ≤ 6) at weeks 2 and 4; complete disease control (UAS7 = 0) at week 4; and safety assessments.

Planned outcomes: RECLAIM will evaluate the early efficacy of remibrutinib versus dupilumab in patients with CSU. The study is currently recruiting patients.

Trial registration: ClinicalTrials.gov identifier, NCT06868212.

Introduction: Alopecia areata (AA) is an autoimmune disorder characterized by non-scarring hair loss due to immune dysregulation. Despite advances, its precise molecular mechanisms remain unclear. This study investigates plasma microRNA (miRNA) expression profiles in patients with AA to identify biological pathways influenced by miRNAs and potential therapeutic targets.

Methods: A total of 50 patients with AA were categorized as severe or mild on the basis of Severity of Alopecia Tool (SALT) scores. Plasma miRNA levels were compared with those of healthy controls and individuals with other immune-mediated skin diseases. In the discovery phase, 754 miRNAs were analyzed in 20 participants (5 severe AA, 5 mild AA, and 10 controls). Key miRNAs identified were then validated in a second cohort of 90 participants, including patients with AA, non-segmental vitiligo, atopic dermatitis (AD), psoriasis (PsO), and healthy controls, using real-time polymerase chain reaction (RT-PCR). Machine learning was used to classify patients on the basis of their miRNA profiles, and pathway enrichment analysis and drug targeting were conducted to explore therapeutic opportunities.

Results: In total, 19 miRNAs were significantly downregulated in AA, with 9 technically and clinically validated for both mild and severe forms. The top four miRNAs with the highest classification potential were miR-130b-3p, miR-296-5p, miR-424-5p, and miR-195-5p. Distinct upregulation patterns were identified in vitiligo, AD, and PsO. Machine learning models showed vital classification accuracy for AA (AUC = 0.94) and PsO (AUC = 0.88), with moderate performance for non-segmental vitiligo and AD. Pathway enrichment analysis highlighted immune-related pathways, including the interferon-gamma and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. Drug repositioning identified kinase inhibitors showing the most significant promise for reversing miRNA dysregulation.

Conclusions: This study identifies distinct plasma miRNA profiles in AA, with potential applications for both diagnosis and therapy. Machine learning validated its solid predictive accuracy, and pathway analysis highlighted key immune pathways in AA. These findings should be interpreted as exploratory and hypothesis-generating, pending further functional validation of candidate miRNAs.

Introduction: Although effective therapies are available for moderate-to-severe atopic dermatitis (AD), many eligible patients do not receive timely treatment escalation. This phenomenon, termed clinical inertia, is well described in chronic internal diseases but underexplored in dermatology. We aimed to quantify clinical inertia in AD and to identify patient-, physician-, and system-level barriers to treatment escalation.

Methods: We conducted a cross-sectional mixed-methods study at a tertiary dermatology center between November 2024 and March 2025. Forty adults with moderate-to-severe AD completed validated questionnaires on disease severity (POEM), quality of life (DLQI), treatment satisfaction (TPS), and medication beliefs (BMQ). Semi-structured interviews were conducted with 20 patients and analyzed using thematic content analysis.

Results: Despite moderate-to-severe disease, 30% of patients had not received systemic therapy. Key patient-reported barriers included low treatment expectations, fear of side effects, and acceptance of chronic symptoms. High treatment satisfaction scores were observed even in the presence of severe disease and poor quality of life. Interview data revealed five thematic barriers across patient-, physician-, and system-levels, including therapeutic nihilism, limited access to specialists, and fragmented communication pathways.

Conclusion: This study highlights a multifactorial pattern of clinical inertia in AD, with patient perception, therapeutic communication, and healthcare structures all playing a role. These findings underscore the need for structured shared decision-making (e.g., standardized risk-benefit counseling and written decision aids about systemic options), treat-to-target management (regular POEM/DLQI monitoring with predefined escalation triggers when targets are not met), and system-level improvements (clear referral pathways to AD specialists, adequate follow-up capacity, and streamlined approval processes for systemic therapies) to reduce delays in escalation and improve outcomes. As AD treatment options expand, addressing clinical inertia is critical to ensure timely and equitable care.

Lichen sclerosus is a chronic inflammatory disease of the skin and mucous membranes of unknown etiology. The disease most often affects the genital area, but the extragenital form of the disease is diagnosed in approximately 15-20% of patients. Extragenital lichen sclerosus manifests as porcelain-white papules that form plaques. The lesions can enlarge, affecting extensive areas of the skin. Characteristic lesions may be accompanied by hemorrhagic spots, blisters, and erosions. To date, extragenital lichen sclerosus-particularly the bullous variant-poses a therapeutic challenge for clinicians, characterized by high resistance to treatment. The aim of this review is to summarize the currently available knowledge about extragenital lichen sclerosus and its treatment methods.

Introduction: Discoid lupus erythematosus (DLE) is a chronic inflammatory scarring alopecia that may be accompanied by a broad range of systemic and extracutaneous comorbidities. However, the prevalence and magnitude of these associations have not been comprehensively quantified. Our objective was to systematically evaluate the prevalence and associated risk of comorbidities in patients with discoid lupus erythematosus.

Methods: We conducted a systematic review and random-effects meta-analysis in accordance with PRISMA 2020 guidelines, prospectively registered in PROSPERO (CRD420250656067). MEDLINE and Embase were searched from inception to June 2025. Observational studies reporting comorbidities in patients with DLE were included. Pooled prevalence estimates and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Between-study heterogeneity was assessed using the I² statistic. Sensitivity analyses excluding small studies (n < 50) were performed for prevalence outcomes, whereas the robustness of association analyses was assessed qualitatively owing to the limited number of contributing studies. Methodological quality was evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist.

Results: In total, 25 studies were included. Pooled prevalence estimates indicated a high frequency of systemic lupus erythematosus (SLE) (22.0%), hypertension (24.3%), depression (38.8%), and hypothyroidism (12.4%) among patients with DLE. Sensitivity analyses showed stable prevalence estimates for SLE and hypertension, with moderate variability for hypothyroidism and depression. Meta-analyses of case-control studies demonstrated significant associations between DLE and cardiovascular disease (OR 3.85, 95% CI 1.67-8.88), hypothyroidism (OR 2.55, 95% CI 1.79-3.61), hypertension (OR 2.22, 95% CI 1.91-2.58), depression (OR 2.21, 95% CI 1.71-2.85), and anxiety (OR 2.40, 95% CI 1.40-4.11). Associations with type 2 diabetes were more modest, while smoking was not significantly associated. Most association analyses were based on a limited number of studies.

Conclusions: Patients with discoid lupus erythematosus exhibit a substantial burden of systemic, cardiometabolic, endocrine, and psychiatric comorbidities. While prevalence estimates were generally consistent, associations should be interpreted cautiously owing to limited available evidence. These findings highlight the importance of comprehensive clinical assessment and multidisciplinary management of patients with DLE.

Trial registration: The study protocol was prospectively registered in PROSPERO (CRD420250656067).

Hidradenitis suppurativa (HS) is an insidious, chronic inflammatory skin disease, leading to a negative impact on a patient's quality of life and a poor prognosis. The pathogenesis of HS is complex and multifaceted including genetic, sex hormones, smoking, obesity, and immune dysregulation as the main contributing factors to the development of the disease. HS is challenging to treat and a multimodal approach, combining topical treatment, systemic therapy, and lifestyle modifications, is a strongly recommended strategy to manage the disease. Regular skin care, topical therapy, and intralesional intervention are the mainstay of the management in HS as monotherapy in mild disease, and in combination with systemic antibiotic or immunomodulatory agents in moderate-to-severe HS. The main aim of this review is to examine local therapeutic interventions that are currently available and under investigation for the treatment of HS.

Introduction: Recent trials with withdrawal arms in patients with psoriasis have highlighted the need for updated clinical guidance. The aim of this investigation was to compare the effects and safety of planned limited-time withdrawal versus continuous maintenance of interleukin (IL) inhibitors in patients with psoriasis.

Methods: On August 5, 2025, the following platforms were systematically searched: PubMed, Embase, Clarivate (Web of Science), Scopus, and Ovid. Titles and abstracts, followed by full-text articles, were independently screened by two reviewers, with any disagreements being resolved by a third reviewer. Certainty of evidence was evaluated via the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Network meta-analyses for the Psoriasis Area and Severity Index (PASI) 90 and PASI100 outcomes were performed. The risk ratio (RR) of relapse was ranked using the surface under the cumulative ranking curve (SUCRA) metric.

Results: A total of 7444 records were retrieved, 54 of which included data from 18 different trials. The data revealed a total of 2995 patients who were subjected to anti-IL withdrawal regimens that were eligible for comparison with anti-IL maintenance. For the PASI90 outcome, the network meta-regression, adjusted for a post-withdrawal follow-up duration of 40-48 weeks, indicated that bimekizumab demonstrated a RR for relapse (RR 5.36; 95% confidence interval (CI) 3.45-8.34; SUCRA 0.685) comparable to that of guselkumab (RR 7.45; 95% CI 4.97-11.19; SUCRA 0.412) and lower than that of ixekizumab (RR 17.45; 95% CI 10.22-29.80; SUCRA 0.006). No significant difference in adverse event rates was observed between the anti-IL withdrawal and maintenance groups.

Conclusions: Compared with continued treatment, planned withdrawal of anti-IL therapy is associated with a largely superior risk of relapse, without any reduction in the incidence of adverse events. Moreover, bimekizumab withdrawal demonstrated better outcomes than ixekizumab withdrawal did according to the PASI90 outcome.

Study registration: This study was prospectively registered on PROSPERO (identification number CRD420251118724).