Dermatology and Therapy最新文献

Introduction: Prurigo nodularis (PN/chronic prurigo) is characterised by intensely pruritic, symmetrically distributed nodules. In the PRIME (NCT04183335) and PRIME2 (NCT04202679) clinical trials, dupilumab demonstrated clinically meaningful and statistically significant improvements in itch versus placebo in patients with uncontrolled PN on topical therapies. This post hoc analysis evaluated the efficacy of dupilumab versus placebo in reducing the daily symptom burden (DSB) with respect to itch, skin pain, and sleep disturbance in patients with PN.

Methods: Pooled data from the PRIME and PRIME2 trials (N = 311) were utilised. DSB was assessed with three patient-reported outcomes (PROs): Worst Itch Numeric Rating Scale (WI-NRS), Skin Pain-NRS, and Sleep-NRS. Each PRO utilised a scale of 0-10 (0: no pruritus/no skin pain/worst possible sleep; 10: worst pruritus/worst skin pain/best possible sleep). The symptom intensity was categorised as no symptoms (0 for WI-NRS and Skin Pain-NRS; 10 for Sleep-NRS), mild (1-2 or 8-9), moderate (3-6 or 4-7), severe (7-8 or 2-3), and very severe (9-10 or 0-1). The proportion of patients experiencing only none-to-mild symptoms and the mean frequency of days with only such symptoms in the week before week 24 were compared between treatment arms.

Results: In the week before week 24, significantly higher proportions of patients treated with dupilumab had only none-to-mild symptom days than those receiving placebo with respect to WI-NRS (26.8% vs 7.6%), Skin Pain-NRS (38.6% vs 19.0%), and Sleep-NRS (28.8% vs 10.1%), with p < 0.0001. At week 24, patients treated with dupilumab had more days per week with none-to-mild itch (mean 2.4 vs 0.9), skin pain (3.4 vs 1.9), and sleep disturbance (2.7 vs 1.4) versus placebo.

Conclusion: Patients treated with dupilumab showed greater improvement in DSB with respect to itch, skin pain, and sleep disturbance than those receiving placebo.

Introduction: Post-inflammatory pigment alteration (PIPA) in skin previously affected by psoriasis is an important, often neglected problem. PIPA has a disproportionate negative impact in people with skin of color. The phase 3b VISIBLE study evaluated guselkumab efficacy and safety in participants with skin of color and moderate-to-severe plaque psoriasis (cohort A) or moderate-to-severe scalp psoriasis (cohort B). Here we report results from exploratory assessments of the quality-of-life impact of pigmentation changes as psoriasis lesions resolve and long-term skin clearance is achieved and of correlations between dyspigmentation and clinical and patient-reported outcomes.

Methods: Randomized (3:1) participants received guselkumab 100 mg or placebo with crossover to guselkumab at week 16. Patient-reported impact of dyspigmentation on quality of life was assessed via Skin Discoloration Impact Evaluation Questionnaire (SDIEQ). Correlations between SDIEQ, Psoriasis Area and Severity Index (PASI), and Dermatology Life Quality Index (DLQI) were assessed. Pigmentation journeys were tracked using standard and cross-polarized photographs evaluated for erythema, pigmentation, and skin tone evenness.

Results: Across treatment and Fitzpatrick skin type groups (N = 205), mean SDIEQ scores decreased from 8.4-9.5 (moderate impact) at baseline to 1.3-1.9 (mild impact) at week 48. Photographic improvements in pigmentation were also observed. The majority of guselkumab-treated participants achieved clear or almost clear skin at week 48. In cohort A, mean percent PASI improvement from baseline was 94.9%; in cohort B mean percent Psoriasis Scalp Severity Index improvement was 94.6%. At week 48, correlation between SDIEQ and DLQI (r = 0.7456; p < 0.001) was stronger than between PASI and DLQI (r = 0.3345; p < 0.001).

Conclusion: Following treatment with guselkumab, most participants achieved clear or almost clear skin and substantial improvements in skin discoloration. Exploratory analyses showed SDIEQ improvements impacted quality of life more than PASI improvements, suggesting greater attention to PIPA is warranted in comprehensive psoriasis management, especially for patients with skin of color.

Clinicaltrials:

Gov identifier: NCT05272150.

Introduction: Biologic therapies have transformed the management of moderate-to-severe psoriasis but are associated with long-term treatment burden and substantial healthcare costs. Dose spacing, defined as extending dosing intervals in patients with controlled disease, has emerged as a potential optimization strategy. However, data on real-world implementation and clinician perspectives remain limited.

Methods: We conducted a national, cross-sectional survey among Portuguese dermatologists experienced in prescribing biologic therapies for psoriasis. An anonymous, web-based questionnaire assessed clinicians' perspectives and real-world practices regarding biologic dose spacing, including eligibility criteria, preferred biologic classes, implementation strategies, outcomes after loss of disease control, and limiting clinical factors.

Results: Seventy-five dermatologists completed the survey (response rate 48.4%). All respondents considered dose spacing feasible. The most frequently cited eligibility criteria were absolute Psoriasis Area and Severity Index (PASI) ≤ 1, body surface area (BSA) ≤ 1%, and a 90% improvement in PASI (PASI 90). Interleukin-23 (IL-23) inhibitors were perceived as the most suitable class for dose spacing (93.3%). In routine practice, dose spacing was applied frequently by 30.7% of respondents and occasionally by 48.0%. Most clinicians (69.3%) required more than 12 months of sustained disease control before initiating dose spacing, predominantly using progressive extension of dosing intervals (96.0%). IL-23 inhibitors were the biologics most frequently dose-spaced in current practice. Following loss of disease control, 86.7% reported successful recapture of response after reintroduction of standard dosing. The main factors limiting dose spacing were a history of difficult-to-control psoriasis (77.3%) and concomitant psoriatic arthritis (72.0%).

Conclusion: Biologic dose spacing is already integrated into clinical practice in Portugal. Further prospective studies are needed to establish standardized criteria and guide safe implementation.

Artificial intelligence (AI) is increasingly being incorporated into dermatology, with hair disorders representing a particularly suitable field for its application. The assessment and management of alopecias rely heavily on visual evaluation, pattern recognition, longitudinal monitoring, and integration of heterogeneous clinical and biological data; processes that are often limited by interobserver variability and incomplete standardization. In recent years, AI-based approaches have been applied across multiple domains in the clinical assessment of hair disorders, including objective quantitative assessment, diagnostic support, personalized medicine, drug development, robotic-assisted procedures, and analysis of patient-reported outcomes and clinical communication. Among these applications, tools enabling automated and reproducible measurement of hair parameters are currently the most established in clinical practice, whereas diagnostic and predictive models remain largely investigational. This narrative review summarizes current and emerging applications of artificial intelligence in hair disorders, with a focus on their clinical relevance and practical implementation. In addition, methodological limitations, ethical considerations, and challenges related to external validation, interpretability, and data bias are discussed. Although AI-based tools are not yet able to replace clinical judgement, they hold significant potential to complement dermatologists' expertise and improve objectivity, efficiency, and personalization in the management of hair disorders.

Actinic keratosis (AK) represents an early stage of keratinocyte carcinogenesis and has long been attributed primarily to cumulative ultraviolet (UV) radiation-induced genetic damage. However, increasing evidence suggests that AK arises within a complex cutaneous microenvironment, in which chronic inflammation, oxidative stress, immune dysregulation, and alterations of the skin microbiota interact to promote and sustain field cancerization. UV exposure not only drives mutational events in epidermal keratinocytes, but also disrupts barrier integrity and local immune surveillance, reshaping microbial community structure on photodamaged skin. Recent studies reveal a characteristic profile in AK, characterized by reduced microbial diversity, depletion of protective commensals, and enrichment of opportunistic taxa, most notably Staphylococcus aureus. Experimental and clinical data suggest that S. aureus may act as a microbial cofactor in AK by amplifying proinflammatory and pro-oxidant signaling, inducing genotoxic stress, impairing DNA repair pathways, and modulating local immune responses in a manner consistent with early carcinogenic progression. Concurrent loss of commensal bacteria and fungi with immunomodulatory functions may further destabilize epidermal homeostasis, potentially reinforcing a self-perpetuating inflammatory loop. This perspective review synthesizes current molecular, immunologic, and microbial evidence to elucidate the role of host-microbe interactions in AK arising on chronically UV-exposed skin. Finally, we discuss how targeting inflammation-microbiota crosstalk may open new opportunities for risk stratification, prevention, and therapeutic intervention across the AK-cutaneous squamous cell carcinoma spectrum.

Introduction: Minimal disease activity (MDA) is an emerging therapeutic goal in atopic dermatitis (AD), providing a multidimensional assessment of disease control.

Methods: We conducted a retrospective multicenter study of adults with moderate-to-severe AD receiving biologics or JAK inhibitors. MDA was defined as Eczema Area and Severity Index (EASI) ≤ 3 and Pruritus Numerical Rating Scale (NRS) ≤ 1. Univariate analyses were performed to identify baseline predictors of sustained MDA at week 52 among patients who had previously achieved MDA at week 16.

Results: Among 197 patients with week 16 data, 107 (54.3%) achieved MDA. Of these, 59 had data at week 52, and 51 (86.4%) maintained MDA in a per-protocol analysis among patients with available follow-up. Sustained MDA was associated with the absence of hand involvement and fewer prior conventional treatments. No significant differences were found in gender, body mass index (BMI), baseline EASI score, or years of diagnostic delay. A younger age showed a trend toward a significant association with MDA loss. No statistically significant differences were found in the sustainability of MDA at week 52 between treatment groups (dupilumab, tralokinumab, and upadacitinib).

Conclusions: Sustained MDA among early responders is feasible in real-life AD practice. Baseline characteristics may help identify patients most likely to benefit from early targeted treatment.

Introduction: Wide local excision (WLE) is a standard component of cutaneous melanoma management, although prospective evidence supporting current margin recommendations remains limited. Surgical margins have progressively decreased. However, six randomized clinical trials comparing wider (3-5 cm) vs. narrower (1-2 cm) margins did not demonstrate significant reductions in local recurrence (LR) or survival benefits. Furthermore, wider margins are associated with increased morbidity and healthcare costs.

Methods: We systematically reviewed relevant published studies up to and including December 2025 to compare LR and survival outcomes between standard WLE and no or narrow-margin excisions. The analysis included adult and pediatric cases of superficial spreading, nodular, acral, and desmoplastic cutaneous melanoma; lentigo maligna was excluded.

Results: No prospective studies were found comparing WLE to the omission of WLE for cutaneous melanoma. Two retrospective studies reported no significant differences in LR or overall survival (OS) in patients who did not undergo WLE (n = 453). Regarding lateral margins, 30 retrospective studies were identified. Collectively, these studies suggest that narrower margins than those currently recommended are not associated with worse LR, disease-free survival, or OS for melanoma in situ and pT1-pT3 tumors (Breslow index ≤ 4 mm). However, findings for pT4 melanomas (Breslow index > 4 mm) remain inconsistent. Analysis of deep margins (n = 5 retrospective studies) largely supported more superficial excision strategies than current guidelines. Regarding acral melanoma, seven retrospective studies were located, all of which reported that narrower and shallower margins-including the preservation of plantar fat-did not adversely affect LR or survival. Conversely, in cases of desmoplastic melanoma, two retrospective studies were found with conflicting results regarding LR. In the pediatric population, evidence remains scarce; two retrospective studies evaluating narrow excision margins revealed no adverse impact on OS.

Conclusions: Current evidence suggests that narrower lateral margins and shallower deep excision strategies could be oncologically safe. However, the absence of an observed association with higher rates of LR or worse survival outcome should not be interpreted as proof of non-inferiority to standard WLE, given the predominance of observational data, heterogeneity across studies, and limited statistical power in smaller cohorts. High-quality prospective randomized trials are required. Ongoing randomized trials (MelMART-II, WoW, and ICEMAN) will play a key role in refining future surgical margin recommendations.

Introduction: Surgical excision is the standard treatment for basal cell carcinoma (BCC). For locally advanced BCC (laBCC) not suitable for surgery or radiotherapy, Hedgehog pathway inhibitors (HHIs) such as sonidegib are important options. Clinical observations have shown that sonidegib may lead to pigmentation and scarring, which can affect treatment evaluation. We evaluated the efficacy and safety of sonidegib in Chinese patients with laBCC and examined discrepancies between clinical/dermoscopic assessments and pathological findings, including posttreatment pathological changes.

Methods: This single-center retrospective study included 54 patients with laBCC treated with sonidegib 200 mg/day for ≥ 3 months (October 2022-July 2025). Response assessment integrated VISIA-based planimetric lesion-area regression, standardized dermoscopy, and dermoscopy-guided multi-site biopsy as the pathological gold standard. The primary endpoint was objective response rate (ORR); secondary endpoints included disease control rate (DCR) and safety.

Results: At 3 months, ORR was 87% (complete response [CR] 48%; partial response [PR] 39%), and DCR was 100%. Pathology showed complete clearance in 48.1% and residual tumor in 51.9%, with six cases showing apparent histologic subtype shifts. Dermoscopy in patients with complete remission still demonstrated a high false-positive rate (branching blood vessels 53.8%, blue-gray dots 61.5%), leading to decreased diagnostic specificity. Adverse events occurred in 81.5% of patients; 70.4% reported multiple events, most commonly muscle cramps (66.7%), dysgeusia (59.3%), and alopecia (55.6%). All events were grade 1-3, and no patient discontinued treatment as a result of toxicity.

Conclusion: In this real-world Chinese laBCC cohort, sonidegib produced a clinically meaningful response with a favorable safety profile. However, clinical and dermoscopic assessments showed substantial false positives due to posttreatment changes; pathological biopsy remains essential to confirm tumor clearance. Advanced noninvasive imaging (e.g., reflectance confocal microscopy) may further improve monitoring. Prospective studies with longer follow-up are warranted.

Introduction: Abrocitinib, a selective Janus kinase (JAK)-1 inhibitor, is approved for the treatment of moderate-to-severe atopic dermatitis (AD). Although several real-world studies evaluated the safety and efficacy of abrocitinib, most have been limited by small sample sizes, and there are limited data on South Korean patients with AD. In addition, real-world comparative data across oral JAK inhibitors for AD remain limited.

Methods: We conducted a retrospective, single-center cohort study at the National Medical Center in Seoul, Korea. Patients aged ≥ 12 years with moderate-to-severe AD (baseline EASI ≥ 7) who initiated abrocitinib between September 2022 and April 2024 were included in the primary cohort; additional cohorts treated with upadacitinib or baricitinib during predefined periods were analyzed for between-drug comparisons. Efficacy was assessed at baseline, week 2, and week 16 using the Eczema Area and Severity Index (EASI) and patient-reported outcomes (PROs). Safety was evaluated by adverse events (AEs), physical examinations, and laboratory tests.

Results: Of the 66 patients enrolled, 57 patients completed 16 weeks of abrocitinib treatment in the analysis. The mean EASI score significantly decreased after 16 weeks. At week 16, 94.4%, 72.2%, and 25.9% of patients with AD achieved EASI-50, -75, and -90, respectively. Additionally, of the 21 patients who had previously experienced biologics or other JAK inhibitors, 95.5%, 72.7%, and 22.7% achieved EASI-50, -75, and -90, respectively. Further analysis of the EASI breakdown showed improvements of more than 80% across all body regions, with the lower extremities showing the greatest reduction (87.5%) and lichenification exhibiting the highest symptom improvement (89.7%). In descriptive, unadjusted comparisons, abrocitinib showed numerically higher EASI-50 and EASI-75 response rates at week 16 than upadacitinib and baricitinib. Acne was the most frequent adverse event with abrocitinib (43.9%), followed by urticaria (24.6%) and herpes simplex infection (12.3%); no dose reductions or treatment discontinuations due to adverse events occurred.

Conclusion: Abrocitinib demonstrates real-world efficacy and safety in moderate-to-severe AD, including patients with inadequate responses to other dupilumab or JAK inhibitors, including those with prior exposure to biologics or other JAK inhibitors.

Introduction: Although recognition of prurigo nodularis (PN) and lichen simplex chronicus (LSC) of the scalp is usually straightforward, they may sometimes pose difficulties in terms of differential diagnosis with other similar dermatoses. The aim of this observational retrospective study was to assess dermoscopic features of PN and LSC of the scalp across fair- and dark-skinned individuals and compare them with those of clinical mimickers.

Methods: Fair-skinned (Fitzpatrick phototypes I-III) and dark-skinned (Fitzpatrick phototypes IV-VI) patients with a histological diagnosis of PN/LSC of the scalp, along with controls, were considered. All the images were randomly evaluated by two independent investigators to identify findings according to standardized criteria. Interobserver agreement was evaluated through Cohen's kappa coefficient, while Fisher's exact test with p value set at 0.01 was used for comparative analyses between cases and controls.

Results: The study included 79 cases, including 40 instances of PN/LSC of the scalp (27 with fair skin and 13 with dark skin) and 39 controls. The most common dermoscopic findings (> 1/3 of cases) of PN/LSC in both light and dark phototypes included sparse follicular plugs, broken hairs, purple structureless areas, broom-like hairs, and erosions. Additionally, purple dots, perivascular white halo and dotted vessels with unspecific distribution were also common in fair skin, while white lines (peripheral-radial) and structureless areas turned out to be as frequent in dark skin. Comparative analysis showed that dotted vessels, follicular plugs, broken hairs, broom-like hairs, purple structureless areas, and perivascular white halo were more common compared to control in light phototypes, whereas only erosions, peripheral white lines, and purple structureless areas reached statistical significance in dark-skinned patients (p < 0.01). Kappa values were 0.88 and 0.81 for fair and dark skin, respectively.

Conclusion:  Dermoscopy is a valuable adjunct in the non-invasive diagnosis of PN and LSC of the scalp, with good reproducibility across skin phototypes.