Dermatology and Therapy最新文献

Introduction: Treating older patients with cutaneous neoplasms (CN) can be challenging as oncological resection and definitive external beam radiotherapy (EBRT) can both have limitations in terms of their therapeutic ratio at critical anatomical sites. Here, we present the cohort study results of high-dose-rate (HDR) mould-based brachytherapy (MbBT) for CN focusing on oncological outcomes and patient-reported outcome measures (PROMs), using custom or three-dimensional-printed moulds.

Methods: Between January 2019 and March 2024, 64 patients underwent MbBT. All patients were either deemed unsuitable for radical resection or definitive EBRT or refused them. Patients were prospectively enrolled in a database and underwent clinical evaluation at the end of treatment as well as after 30 and 90 days to assess acute and late toxicity. In addition, oncological follow-up and documentation of their quality of life and subjective cosmetic assessment was performed every 6 months thereafter.

Results: The median age was 80 years. Histology revealed 19 squamous cell carcinomas, 27 basal cell carcinomas, 2 lesions with both histologies, 9 melanocytic tumours and 7 lesions of other histologies. The median treatment dose was 39 Gy (range 30-45 Gy) at 3 Gy per fraction (range 3-4 Gy), administered once daily at 5 days per week. After a median follow-up of 679 days (interquartile range 361-1049 days), there were seven local recurrences (11%). Thirty-seven patients (58%) rated the cosmetic result as at least good, 23 (36%) rated the treatment as more tolerable than expected, while 16 (25%) rated it as at least bothersome. Apart from one grade 4 cataract, no other grade 4 late toxicity was documented.

Conclusions: High-dose-rate MbBT for CN is an effective and well-tolerated treatment option for older and frail patients who are not eligible for radical surgery or definitive EBRT.

Introduction: Chronic spontaneous urticaria (CSU) is characterized by itchy hives with or without angioedema recurring for > 6 weeks. Many patients experience a substantial disease burden despite H1-antihistamine treatment, including impaired health-related quality of life (HRQoL). In the current analysis, we evaluated the efficacy of dupilumab in improving HRQoL in omalizumab-naïve patients with CSU.

Methods: LIBERTY-CSU CUPID Study A was a double-blind, phase 3 trial that evaluated the efficacy and safety of dupilumab in patients aged ≥ 6 years with CSU who remained symptomatic despite H1-antihistamine treatment. Patients were randomized to receive dupilumab 300 mg every 2 weeks (q2w; n = 70) or placebo q2w (n = 68). The current analysis evaluated the change from baseline to week 12 and week 24 in the total scores of the Dermatology Life Quality Index (DLQI), Chronic Urticaria Quality of Life Questionnaire (CU-Q₂oL), and EuroQol (EQ)-Visual Analog Scale (VAS). Additional outcomes included changes from baseline to week 12 and week 24 in DLQI severity categories and the proportion of patients reporting "not at all/a little" effect on individual items of DLQI and CU-Q₂oL questionnaires.

Results: At week 24, dupilumab significantly improved total DLQI and CU-Q₂oL scores compared with placebo {difference: -3.2 (95% confidence interval [CI] -5.2 to -1.1; nominal p = 0.0026) and -8.6 (95% CI -14.6 to -2.6; nominal p = 0.0049), respectively}, as well as EQ-VAS score (difference: 6.0 [95% CI 0.9 to 11.2; nominal p = 0.0210]). Similar trends were observed for week 12. Significantly more dupilumab versus placebo recipients reported "no or little" effect for most of the DLQI and CU-Q₂oL items (nominal p < 0.05).

Conclusions: Dupilumab significantly improved HRQoL in omalizumab-naïve patients with CSU who remained symptomatic despite standard-of-care H1-antihistamine treatment. Quality-of-life improvement with dupilumab addresses an important goal of CSU treatment.

Clinical trial registration: ClinicalTrials.gov identifier: NCT04180488.

Introduction: Vulvar lichen sclerosus (VLS) is a chronic inflammatory dermatosis of unclear etiology, most often affecting postmenopausal women. It presents with itching, burning, pain, and progressive vulvar scarring and atrophy, leading to sexual dysfunction and increased risk of neoplastic transformation. High-potency corticosteroids are the standard first-line treatment, but many patients experience inadequate response or intolerance, resulting in recurrence. In such cases, 5-aminolevulinate (ALA) photodynamic therapy (PDT) may offer an alternative. The aim of this systematic review was to evaluate the effectiveness and safety of PDT in patients with VLS.

Methods: Searches of PubMed, Scopus, and Web of Science identified 238 papers, of which 13 met the inclusion criteria, comprising 441 women with VLS. Among these, one was a randomized controlled trial, one a non-randomized comparative study, seven were single-arm trials, and four were retrospective analyses.

Results: The collective evidence showed that PDT, particularly using 5-ALA as a photosensitizer, improved clinical symptoms such as pain and itching, skin histology, patients' quality of life as measured with the Dermatology Life Quality Index, and sexual functioning as measured with the Female Sexual Function Index. Adverse events were mainly procedure-related and resolved spontaneously within a few days.

Discussion: PDT appears to be a promising therapeutic option for VLS, particularly in patients with refractory disease unresponsive to conventional treatments. However, evidence for ALA-PDT remains limited, as current studies are small, use variable protocols, and involve heterogeneous populations. Further research is needed to address these gaps.

Conclusion: Available studies indicate that ALA-PDT is a safe, well-tolerated, and effective option for VLS, improving both symptoms and clinical signs, especially in refractory cases. Emerging evidence, including comparative and quality-of-life studies, supports its potential role in management, though large prospective trials are needed to refine protocols and establish guideline recommendations.

Chronic hand eczema (CHE) is defined as hand eczema that persists for more than 3 months or reoccurs at least two times a year. Although it is a distinct disease with a significant impact on quality of life, awareness of the disease and tailored treatment options remain limited. This limited awareness along with a lack of CHE-specific outcome measures can lead to inadequate disease management and recurrence. The Investigator Global Assessment of Chronic Hand Eczema (IGA-CHE) and the Hand Eczema Symptom Diary (HESD) are new, specific outcome measures validated in patients with CHE. They were developed based on recommendations from regulatory authorities to establish outcome measures that can accurately evaluate potential treatments for CHE. IGA-CHE is a clinician-reported outcome measure that assesses disease severity, while HESD (including the single-item HESD Itch and HESD Pain scores) is patient-reported and evaluates signs and symptoms of CHE. Overall, IGA-CHE and HESD are simple, reliable, responsive, and easy to use tools that can detect subtle changes in CHE signs and symptoms, providing a comprehensive assessment of disease severity. Their validation ensures these tools can accurately and consistently measure treatment outcomes, making them valuable in clinical trials and clinical practice. In this podcast, three dermatologists discuss two recently published studies evaluating IGA-CHE and HESD in patients with CHE, and focus on (1) the need for CHE-specific outcome measures in clinical trials and practices, (2) how the IGA-CHE and HESD outcome measures provide accurate assessments of disease severity and clinically meaningful responses to treatments, and (3) key differences from other common outcome measures used in CHE clinical trials. Podcast Audio (MP4 1,01,828 kb).

Introduction: Post-inflammatory hyperpigmentation (PIH) is common and distressing in skin of color. Ultraviolet (UV) radiation and visible light (VL) exacerbate PIH, yet most sunscreens do not target the oxidative and inflammatory pathways that drive it. This study evaluated a broad-spectrum sunscreen with sclareolide and niacinamide for mitigating PIH induced by combined UV/VL exposure and inflammatory stimuli.

Methods: In an investigator-masked, randomized, intra-individual study, 20 participants with Fitzpatrick skin types IV-V underwent controlled UV/VL exposure with or without tape stripping. The test product was applied daily for 20 days. The primary endpoint was change in ΔITA° at Day 22; clinical pigmentation/erythema and colorimetry (ΔL*, Δa*, Δb*, ΔE) were secondary endpoints.

Results: The sunscreen significantly prevented pigmentation at all protected sites. In stripped, exposed zones, protected skin improved by + 5.96 ΔITA° versus - 9.88 ΔITA° in unprotected skin (net protection ~ 16 ITA°, p < 0.001). In non-stripped, exposed areas, the difference was + 11.76 ΔITA° (p < 0.001). Secondary endpoints improved by 48-87%. No adverse events were reported.

Conclusions: A broad-spectrum sunscreen with sclareolide and niacinamide mitigates PIH induced by inflammation and VL in darker phototypes. These findings support preventive use in PIH-prone populations. Comparative studies with and without these ingredients are warranted.

Clinical trial registration: This study was registered with ISRCTN under the identifier ISRCTN11448711.

Introduction: Psoriasis (PsO) in the genital and scalp areas is associated with increased patient burden and impact on quality of life. Effective treatments for PsO in these high-impact areas are essential, though patients are frequently excluded from both biologic clinical trials and treatment because of their often low overall affected body surface area (BSA) despite the disproportionate impact of PsO on their quality of life. Recent guidance also considers these patients as candidates for advanced therapies. Here, we compare the efficacy and safety of risankizumab, an interleukin-23 inhibitor approved for the treatment of moderate-to-severe plaque psoriasis, versus placebo in the treatment of PsO in the genital or scalp region.

Methods: UnlIMMited (NCT05969223) is an ongoing phase 4, multicenter, randomized, double-blind, placebo-controlled study for adult patients with moderate-to-severe genital or scalp PsO in patients with < 10% BSA or ≥ 10% BSA involvement. Two parallel studies were conducted with study-G assessing genital PsO and study-S assessing scalp PsO. Patients were randomized 1:1 within each study to receive either 150 mg risankizumab or placebo at weeks 0 and 4. The primary endpoints for the studies were the achievement of static Physician's Global Assessment - Genital (sPGA-G) 0/1 for study-G and scalp Investigator Global Assessment (IGA) 0/1 for study-S, both assessed at week 16. Secondary endpoints are also reported at week 16 in each study assessing skin clearance, symptom resolution, and impact on quality of life. Safety was reported through the first 16 weeks.

Results: At week 16, in both studies, a significantly higher proportion of patients receiving risankizumab achieved the primary endpoints compared with placebo. In study-G, 69.1% of patients receiving risankizumab versus 13.0% of patients receiving placebo achieved sPGA-G 0/1 (P < 0.0001). In study-S, 60.8% of patients receiving risankizumab versus 13.0% of patients receiving placebo achieved scalp IGA 0/1 (P < 0.0001). No new safety signals were identified.

Conclusion: These results demonstrate that risankizumab is effective in the treatment of genital and scalp psoriasis at week 16, with no new safety signals identified.

Trial registration number: ClinicalTrials.gov identifier NCT05969223.

Introduction: Alopecia areata (AA) is a chronic autoimmune hair disorder with a substantial psychosocial impact, yet contemporary, population-scale estimates of incident psychiatric comorbidity are limited. To quantify the risk of incident psychiatric disorders in adults with newly diagnosed AA versus matched controls, we assessed sex differences, and explored pre- versus post-coronavirus disease 19 (COVID-19) patterns.

Methods: We conducted a multinational, retrospective cohort study using de-identified electronic health records (2015-2025) from TriNetX. Adults with AA (ICD-10 L63) and at least 6 months of prior records were matched 1:1 to general-examination controls without AA. Propensity score matching balanced age, sex, and major comorbidity domains. For the psychiatric outcomes, ICD-10 codes were used. Risk ratios (RRs), and time-to-event with hazard ratios (HRs) analyses were estimated overall, by sex, and by pre/post-pandemic epoch; multiple sensitivity analyses tested robustness.

Results: After matching, 57,389 patients with AA and 57,389 controls were analyzed. AA was associated with a markedly higher risk of any incident psychiatric disorder versus controls (RR = 4.49, 95% CI 4.30-4.70). The largest relative increases were seen in depression and anxiety, with smaller but notable rises in insomnia/parasomnia and substance use disorders. Suicidal behaviors and psychotic disorders also increased but remained rare. Women experienced a higher overall psychiatric burden-particularly depression, anxiety, and eating disorders-while men showed relatively higher rates of substance use. After COVID-19, the most significant increases were in anxiety, insomnia/parasomnia, eating disorders, self-harm, and suicide. These results were consistent across various sensitivity analyses.

Conclusions: Adults with AA have a significantly higher risk of experiencing various new psychiatric disorders, especially among women and following the COVID-19 pandemic. Regular mental health screening, prompt referrals, and combined dermatology-psychiatry care could enhance outcomes. Further prospective research, including assessments of disease severity and patient-reported data, is necessary.

Introduction: Tildrakizumab, an anti-interleukin (IL)-23p19 monoclonal antibody, is approved for the treatment of moderate-to-severe plaque psoriasis. Although pivotal clinical trials have shown its sustained efficacy and safety, real-world evidence (RWE) is crucial to assess its performance in routine clinical practice. The aim of this study is to evaluate the real-world effectiveness and safety of tildrakizumab in adult patients with moderate-to-severe plaque psoriasis in the Basque Country, northern Spain.

Methods: We conducted a multicenter, retrospective observational study, including 212 adult patients treated with tildrakizumab across five tertiary hospitals between November 2020 and April 2024. Clinical outcomes, including Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Physician Global Assessment (PGA) scores were collected at baseline and weeks 28, 52, 76, and 100-112. Safety data and reasons for treatment discontinuation were also recorded.

Results: Among the 212 patients (median age 52.7 years, 56.56% male), most had long-standing psoriasis (median duration: 20.9 years) and multiple comorbidities. Over 80% had previously received biologic therapy. At week 52, 68.8% of patients with follow-up achieved PASI ≤ 3, and 72.7% reached a PGA of 0/1. Median PASI decreased from 11.21 at baseline to 2.51 at week 52. No serious treatment-related adverse events were reported. Discontinuation occurred in 41 patients (19.3%), mainly owing to primary or secondary failure and patient decision.

Conclusions: Tildrakizumab demonstrated high effectiveness and a favorable safety profile in this large, real-world multicenter cohort. These findings support its role as a reliable therapeutic option for patients with moderate-to-severe plaque psoriasis in clinical practice.

Introduction: While bimekizumab has demonstrated rapid, superior clinical efficacy versus adalimumab and ustekinumab, with sustained responses through 4 years, its comparative and long-term impact on patient-reported outcomes (PROs) remains underexplored. Here, we report PROs with bimekizumab versus adalimumab/ustekinumab/placebo in phase 3 controlled trials, and over 4 years with bimekizumab.

Methods: Data were analyzed from BE SURE, BE VIVID, BE READY (52/56 weeks), and their open-label extension (OLE), BE BRIGHT (144 weeks; 4 years' total treatment). Patients were randomized to bimekizumab/adalimumab/ustekinumab/placebo during comparator-controlled periods; all received bimekizumab during BE BRIGHT. Proportions of patients reporting Psoriasis Symptoms and Impacts Measure (P‑SIM) = 0 and Dermatology Life Quality Index (DLQI) = 0 (both at item-level) were assessed during comparator‑controlled periods using non-responder imputation (NRI). Over 4 years, PROs were analyzed using modified NRI in patients who received continuous bimekizumab from baseline into the OLE.

Results: BE SURE included 478 patients (bimekizumab, 319; adalimumab, 159); BE VIVID included 567 (bimekizumab, 321; ustekinumab, 163; placebo, 83); BE READY included 435 (bimekizumab, 349; placebo, 86). In total, 771 patients received continuous bimekizumab into the OLE. A larger proportion of bimekizumab-treated patients achieved P-SIM = 0 across key items versus adalimumab (week 24; itching, 30.7% vs. 18.9%; skin pain, 43.9% vs. 30.2%; scaling, 39.2% vs. 19.5%), ustekinumab (week 16; itching, 31.2% vs. 17.8%; skin pain, 51.7% vs. 27.6%; scaling, 43.6% vs. 17.2%), and placebo. Similar trends were seen for other P-SIM items and in proportions of bimekizumab-treated patients reporting DLQI = 0 across items versus comparators. The patient-reported benefits of bimekizumab were demonstrated throughout the OLE, with 65.5-94.8% of patients reporting DLQI = 0 across items at 4 years.

Conclusions: Bimekizumab provided greater improvements in PROs versus comparators, with durable effects over 4 years. These findings reinforce bimekizumab's role in effective psoriasis management, linking clinical efficacy with sustained patient-reported benefits.

Trial registration: NCT03412747, NCT03370133, NCT03410992, NCT03598790. A Graphical Abstract is available for this article.