BackgroundLichen Sclerosus et Atrophicus (LSA) is a chronic inflammatory dermatosis of multifactorial aetiology, mainly affecting the genital area in both sexes and at any age. First-line therapy involves topical corticosteroids, whilst surgery, particularly circumcision in males, is reserved for non-responders or phimosis cases. Some patients show persistent disease post-surgery. The study aims to compare the effectiveness of circumcision versus topical corticosteroids in improving QoL in men with LSA, assess postoperative recurrence risk.MethodsA retrospective study of consecutive male patients with histological or clinical genital LSA were undergone. We collected clinical, anamnestic, and therapeutic data, including pre- and post-circumcision topical treatments. The DLQI questionnaire assessed quality of life according to treatment type.ResultsFifty-five males were analysed; 40% underwent circumcision. Of these, 83% used topical steroids before surgery and 68% resumed afterward (Steroid-Free Survival: 19 months). Resumption correlated with prior treatment (p = 0.043). QoL improved after circumcision and worsened with active therapy or phimosis (p = 0.002; p = 0.006).ConclusionCircumcision improves QoL, especially in phimosis, though relapses are frequent. Topical therapies are commonly employed but do not appear to significantly impact QoL. The results underline that LSA management should be personalised, combining medical and surgical approaches based on severity and patient response.

Patients with atopic dermatitis prioritize treatment attributes of rapid effectiveness and safety. A survey of 1274 patients revealed a preference for oral dosing unless it posed higher risks, highlighting the role of safety in treatment decisions.

Understanding how treatment responses evolve over time is essential for optimising therapeutic strategies in moderate-to-severe atopic dermatitis (AD). While clinical trials have demonstrated the efficacy of targeted therapies, real-world evidence describing longitudinal response trajectories remains limited. This study aimed to characterise temporal patterns of clinical response in patients with AD treated with dupilumab or upadacitinib in routine clinical practice. A multicentre real-world observational study was conducted using data from the Italian AD-Landscape platform, a structured clinical database collecting longitudinal information on patients receiving advanced systemic therapies for AD. Adult patients initiating dupilumab or upadacitinib between July 2019 and January 2026 were included if baseline and at least week-4 assessments were available. Disease severity and patient-reported outcomes were evaluated using the Eczema Area and Severity Index (EASI), Investigator’s Global Assessment (IGA), Pruritus Numerical Rating Scale (P-NRS) and Sleep Numerical Rating Scale (S-NRS) at baseline and at weeks 4, 16, 36 and 52. Categorical response thresholds (EASI75, EASI90 and EASI100) and safety outcomes were analysed descriptively. A total of 2625 patients were included (dupilumab n=2085; upadacitinib n=540). Both treatments produced rapid and sustained improvements in clinician-reported and patient-reported outcomes throughout the 52-week follow-up. Mean EASI scores decreased from 25.6 ± 6.5 to 2.2 ± 2.9 in the dupilumab group and from 19.1 ± 9.2 to 2.9 ± 5.7 in the upadacitinib group at week 52, respectively. Upadacitinib demonstrated faster early response kinetics, whereas dupilumab showed a progressive accumulation of clinical benefit over time, resulting in convergence of response rates during long-term follow-up. Safety findings were consistent with known mechanism-specific profiles. In this large real-world cohort, both dupilumab and upadacitinib provided substantial and sustained clinical improvements in moderate-to-severe AD. Distinct response kinetics were observed, with faster early responses with upadacitinib and progressively increasing responses with dupilumab, supporting a personalised approach to treatment selection in routine clinical practice.

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer with increasing incidence. The anti-PD-1 therapy cemiplimab has shown its antitumor activity in locally advanced (lacSCC) and metastatic cSCC (mcSCC). This retrospective study assessed the real-life effectiveness and safety of cemiplimab in 83 patients with lacSCC (n = 53) and mcSCC (n = 30). The objective response rate (ORR) was 49.4%, with a complete response (CR) in 15.7% and a partial response (PR) in 33.7%. The median progression-free survival (PFS) was 14 months (95% CI 9-55) and the median overall survival (OS) 19 months (95% CI 10-39). Half of patients (50.6%) experienced adverse events (AE) of any grade, with 8.4% discontinuing therapy due to the severe AEs. The subset of patients who experienced progression during therapy displayed younger age (p = 0.002), a higher disease stage at baseline (p = 0.003), and a nodal disease (p = 0.041). No differences in survival outcome emerged between patients with nodal vs. distant metastases, previous radiotherapy recipient vs. radiotherapy-naïve, and immunosuppressed vs. immunocompetent patients. Head&neck tumor site was associated with a longer OS after first progression (OS2, HR 0.29, 95% CI 0.09-0.89). This study supports the safe and effective use of cemiplimab in real life clinical practice yet highlights the need for further identification of new predictors of clinical response.

Dissecting cellulitis of the scalp (DC) and hidradenitis suppurativa (HS) share follicular occlusion, rupture, suppuration, tunnel formation, and scarring, yet are usually classified as separate diseases. Whether DC represents a site-modified scalp phenotype of the same core inflammatory process remains unresolved. To examine the DC-HS boundary and assess whether current evidence favors two distinct diseases or one follicular-occlusion spectrum, we performed a structured PubMed-based critical narrative review through June 25, 2026, evaluating direct comparative evidence and five prespecified domains: clinical morphology, topography, histopathology/pathobiology, follicular-occlusion clustering, and therapeutic response. Direct comparative evidence remains limited. A prospective trichoscopy study identified DC-compatible findings in 8 of 23 men with HS (35%). Across independent domains, however, the convergent pattern is more consistent with a shared core follicular-occlusion pathology whose phenotype may be modified by anatomical site than with two wholly unrelated processes. The current operational definition of scalp HS also creates a diagnostic paradox: an apparently similar scalp phenotype may be labeled scalp HS when intertriginous HS is present, but DC when it is isolated. This supports testing whether extra-scalp HS is a contextual classifier rather than a biological discriminator. We propose DC as a plausible scalp-predominant, site-modified phenotype within the HS/follicular-occlusion spectrum, while emphasizing that molecular equivalence is not yet proven. Resolving this distinction could affect trial eligibility, testing of HS-targeted therapies in DC, reciprocal screening, and outcome-measure development.

Psoriasis is a chronic inflammatory skin disease associated with significant physical and psychological burden. Tildrakizumab, an interleukin-23 p19 inhibitor, has demonstrated efficacy in treating moderate-to-severe plaque psoriasis both in clinical trials and real-world setting. However, limited data are available on the impact of the effective treatment of psoriasis on the psychological health of patients. The aim of this study was to assess changes in psychological well-being, as well as clinical and quality-of-life outcomes, in patients with moderate-to-severe plaque psoriasis treated with tildrakizumab in routine clinical practice in Italy. This was an interim analysis (IA) of a 52-week multicenter, prospective, observational study. Adults with moderate-to-severe plaque psoriasis initiating tildrakizumab were enrolled. Endpoints focused on well-being and psychological health and included changes, from baseline to week 28, in Depression, Anxiety, and Stress Scale-21 (DASS-21) scores, Dermatology Life Quality Index (DLQI), European Social Survey (ESS) items, and World Health Organization-Five Well-Being Index (WHO-5). Effectiveness was also monitored via Psoriasis Area and Severity Index (PASI), and safety via treatment-emergent adverse event reporting. A total of 115 patients were included (mean age 52.5 years, 60.8

BACKGROUND:Hidradenitis suppurativa (HS) is an autoinflammatory skin disorder, often associated with Down syndrome (DS), with a prevalence ranging from 2.1% to 3.02%. OBJECTIVES:Our aim was to describe the epidemiological and clinical features of patients with HS and concomitant DS in a relevant Italian cohort. METHODS:We conducted a real-life, multicentre, retrospective, and descriptive analysis of 70 HS-DS patients with 2-year follow-up. RESULTS:Seventy Caucasian adult patients (31 males and 39 females) affected by HS and DS were enrolled, with a mean age at baseline of 23.9 years. Mean body mass index (BMI) was 27.5 with obesity found in 20.9% of patients. Mean age at HS onset was 15.2, while at diagnosis was 18.6 with a diagnostic delay of 3.4 years. The groin was the most frequently involved site at HS onset and diagnosis, while the most common HS phenotype was the follicular one. At HS diagnosis, Hurley stage II was the most frequent with a median value of the International Hidradenitis Suppurativa Severity Score (IHS4) of 6 (moderate HS) while the most common therapy prescribed was systemic antibiotics, followed by topical treatments. Over follow-up, treatment patterns changed and IHS4, Dermatology Life Quality Index (DLQI) and pain numeric rating scale (NRS pain) scores decreased. CONCLUSIONS:Our patient cohort is characterized by female predominance, high BMI, early HS onset, predominance of follicular phenotype, and moderate disease severity. Given the recognized association between these two conditions, we recommend regular screening by pediatricians and dermatologists for early detection and management of HS in DS patients. Future comparative studies are needed to clarify which features may be specifically associated with HS and concomitant DS.

Metastatic Cutaneous Squamous Cell Carcinoma in VEXAS Syndrome. This case highlights the clinical dilemma of using PD-1 inhibitors in patients with VEXAS syndrome, emphasizing the delicate balance between therapeutic efficacy and immune-related toxicity. The use of the PD-1 inhibitor in patients with VEXAS syndrome presents a significant clinical challenge, requiring a careful risk-benefit assessment.

Moderate psoriasis, despite its clinical relevance, remains inconsistently defined in current guidelines, leading to heterogeneous treatment decisions and variable access to systemic therapy. A unified, clinically meaningful definition is currently lacking. To establish a consensus-based, operational definition of moderate psoriasis, we conducted a two-round modified Delphi process involving expert dermatologists. Fifteen Italian dermatologists with recognized expertise in psoriasis participated in a Delphi survey composed of 18 statements addressing clinical severity, quality of life, symptoms, involvement of special areas, and treatment response. Consensus was defined as a median score ≥ 7 with interquartile range (IQR) ≤ 2, or ≥ 75

BACKGROUND:Interleukin (IL)-23 inhibitors are highly effective therapies for psoriasis, but some patients may need to discontinue the treatment. Intraclass switching is a potential strategy, although data on its effectiveness remain limited. OBJECTIVES:To evaluate the patterns and effectiveness of intraclass switching among IL-23 inhibitors in a real-world setting. METHODS:This retrospective, multicentre study included adult patients with plaque psoriasis who switched between IL-23 inhibitors. Clinical and demographic data were analysed, and univariable and multivariable analyses identified predictors of treatment response. RESULTS:We analysed 116 patients (120 switches). Switching occurred from guselkumab (45.0%), tildrakizumab (44.2%) and risankizumab (10.8%), mainly due to secondary ineffectiveness (82.5%). Risankizumab was the most common post-switch agent (70.0%), followed by guselkumab (23.3%) and tildrakizumab (6.7%). Psoriasis Area and Severity Index 90% improvement (PASI 90) rates were 28.5% at week 16, 49.5% at week 36 and 60.7% at week 52. Fifteen patients (12.5%) withdrew from treatment, mainly due to lack of efficacy (10 patients, 67%) or adverse events (4 patients, 27%). Univariate analysis showed lower PASI 90 achievement in patients with psoriatic arthritis at weeks 16 after the switch (P = 0.02) and 36 (P = 0.02) and in those with body mass index (BMI) ≥ 25 kg m-2 at week 52 (P = 0.01). Patients switching from risankizumab had lower PASI 90 rates at weeks 16 (P = 0.04) and 36 (P = 0.03), while those switching to risankizumab had higher PASI 90 rates at week 16 (P = 0.02). Multivariate analysis confirmed BMI ≥ 25 kg m-2 was associated with reduced PASI 90 at weeks 36 (P = 0.04) and 52 (P = 0.04). CONCLUSIONS:Intraclass switching among IL-23 inhibitors is an effective strategy, with risankizumab emerging as the most favourable option.

Background:Psoriasis impacts psychological and quality-of-life (QoL). While biologic therapies demonstrated robust efficacy in reducing skin lesions, their broader psychosocial impact remains underexplored in real-world settings. This ambispective observational cohort study evaluated clinical, psychological, and health-related QoL (HRQoL) outcomes of biologic therapy in patients with moderate-to-severe plaque psoriasis treated in routine dermatological practice. Methods:A total of 133 patients undergoing biologic therapy at a referral center in Northern Italy were assessed. Baseline data (T0) were retrospectively extracted from medical records, while 6-month follow-up assessments (T1) were conducted prospectively. Clinical severity (PASI), depression (PHQ-9, BSI-18), anxiety and somatization (BSI-18), perceived stress (PSS), dermatology-specific QoL (DLQI), and general HRQoL (WHOQOL-BREF) were evaluated. Regression models identified baseline predictors of T1 psychological and QoL outcomes. Results:At follow-up, patients reported significant improvements in psychological wellbeing and QoL. PHQ-9 scores decreased markedly (p < 0.001), with the prevalence of moderate-to-severe depressive symptoms dropping from 28.6% to 5.3%. Substantial perceived stress (PSS ≥ 27) declined from 15.0% to 1.5%. DLQI scores showed a large effect size (p < 0.001), with 89.5% reporting minimal impact (DLQI 0-1) at follow-up. Regression analyses identified baseline psychological symptoms as the strongest predictors of follow-up psychological and QoL outcomes. Additional predictors included PASI, female sex, psychiatric comorbidity, and previous biologic therapy. At T1, 77.4% achieved complete skin clearance (PASI 100). Conclusion:Biologic therapies confer multidimensional benefits in moderate-to-severe psoriasis, extending beyond skin clearance to substantial reductions in psychological distress and improvements in QoL. These findings support a patient-centered model integrating dermatologic and mental health care.

BACKGROUND:Hyperinsulinemia and insulin resistance promote acne pathogenesis through reduced Forkhead box protein O1 (FOXO1) signaling and increased mechanistic target of rapamycin (MTOR) and insulin-like growth factor-1 (IGF1) activity. While oral myo-inositol (MI) and D-chiro-inositol (DCI) supplementation may improve insulin sensitivity, evidence regarding direct pathway modulation in acne-involved skin remains limited. In this exploratory, single-arm, uncontrolled study, we sought to investigate the effects of oral MI/DCI (3.6:1 ratio) on cutaneous expression of these biomarkers in adults with acne and metabolic comorbidities (polycystic ovary syndrome or metabolic syndrome). METHODS:Forty-five adults with active inflammatory acne on the back were enrolled across three subgroups of 15 - including women with polycystic ovary syndrome (PCOS), women with metabolic syndrome (MetS), and men with MetS. All participants received oral MI/DCI (1100 mg + 300 mg daily) for 12 weeks in a single-arm, open-label, pre-post biopsy study. Paired punch biopsies of acne-involved skin were obtained before and after supplementation, and FOXO1, MTOR, and IGF1 mRNA expression was quantified by qRT-PCR. Clinical response was assessed by Investigator Global Improvement rating. RESULTS:Following the 12-week supplementation, FOXO1 expression increased (Cohen's d = +1.13; p < 0.001), whereas MTOR (Cohen's d = -3.46; p < 0.001) and IGF1 (Cohen's d = -1.62; p < 0.001) decreased significantly compared with baseline. Changes were directionally consistent across all subgroups. Clinical improvements were observed in 82.2% of participants. Plasma testosterone in men remained stable (p = 0.638). CONCLUSIONS:In this exploratory, uncontrolled study, 12 weeks of oral MI/DCI supplementation (3.6:1 ratio) was associated with significant changes in insulin resistance pathway gene expression in acne-involved skin. These findings provide preliminary mechanistic support for further randomized, controlled trials evaluating MI/DCI as a potential adjunctive strategy in acne associated with metabolic comorbidities.