Giuseppe Paolo Antonio Gemma

Background: Guselkumab, a selective interleukin-23 inhibitor, is effective in moderate-to-severe plaque psoriasis, but real-world long-term data in elderly patients remain limited. Objective: To evaluate the long-term effectiveness of guselkumab in elderly patients with moderate-to-severe psoriasis in a real-world setting. Methods: This retrospective, multicenter study included 102 patients aged 65 years or older treated with guselkumab across seven Italian centers. PASI scores and PASI 75/90/100 responses were assessed as observed cases at weeks 4, 16, 28, and 52, and annually up to 4 years, with last-observation-carried-forward and non-responder imputation as sensitivity analyses. Subgroups by biologic experience and BMI were analyzed. Results: Mean PASI decreased from 12.4 to 0.3 at week 52, remaining low through year 4 (p < 0.001). At week 52 and year 4, PASI 90 was achieved by 89.7% and 86.5%, and PASI 100 by 79.3% and 73.0%, respectively. Responses were comparable between biologic-naïve and biologic-experienced patients. Obese patients had higher baseline PASI; after adjustment for baseline severity, responses did not differ from non-obese patients. Conclusions: Guselkumab was associated with high and durable PASI improvement in elderly patients, regardless of prior biologic exposure or body weight. The retrospective design and absence of systematic safety data warrant cautious interpretation.

Nicotinamide (NAM), the amide form of vitamin B3, has gained increasing attention in dermatology due to its potential role in both skin aging and non-melanoma skin cancer (NMSC) prevention. This review summarizes the biological rationale and current clinical evidence supporting the use of NAM and other NAD⁺ precursors in photoaging and cutaneous carcinogenesis. Chronic ultraviolet exposure induces DNA damage, oxidative stress, inflammation, immune dysregulation, and extracellular matrix remodeling, linking photoaged skin to increased susceptibility to actinic keratoses (AKs), squamous cell carcinoma (SCCs), and basal cell carcinoma (BCCs). Through the NAD⁺ salvage pathway, NAM contributes to the maintenance of intracellular NAD⁺ pools, thereby influencing energy metabolism, DNA repair, mitochondrial function, redox homeostasis, and the activity of NAD⁺-dependent enzymes. Preclinical studies indicate that NAM enhances DNA repair, reduces oxidative stress and inflammatory signaling, supports autophagy and mitophagy, and improves epidermal barrier function and extracellular matrix integrity. Clinically, the strongest evidence for anti-aging effects concerns topical NAM, which consistently improves wrinkles, texture irregularities, pigmentation, and barrier function. Oral NAM has demonstrated chemopreventive activity in high-risk patients with previous NMSC, particularly by reducing the incidence of new SCCs and AKs during active treatment. However, despite a strong mechanistic rationale, current evidence remains heterogeneous, and additional long-term, skin-focused clinical trials are needed to better define efficacy, safety, optimal dosing strategies, and patient selection.

The periocular region represents a highly sensitive anatomical area due to its functional relevance and aesthetic importance. It is frequently affected by a broad spectrum of cutaneous tumors, due to chronic exposure to ultraviolet radiation, hence an accurate diagnosis and lesion margin assessment is essential to guide appropriate treatment. Herein we summarize the current evidence on the use of reflectance confocal microscopy (RCM), optical coherence tomography (OCT), and line-field confocal optical coherence tomography (LC-OCT) for the assessment of periocular skin tumors. A comprehensive literature search was conducted in the main databases following PRISMA 2020 guidelines. Studies published between 2015 and 2025 evaluating the application of RCM, OCT, and LC-OCT in skin tumors of this area were included. RCM was the most extensively studied modality, demonstrating utility in the characterization of pigmented and non-pigmented periocular lesions and in the identification of basal cell carcinoma-specific features. OCT provided complementary information by enabling visualization of deeper tissue structures, particularly in non-melanoma skin cancers; LC-OCT showed high concordance with histopathology providing practical advantages in this area. As a conclusion, non-invasive imaging techniques represent valuable tools in the evaluation of periocular skin tumors, as they may enhance diagnostic confidence and support clinical decision-making.

Background and Objectives: Ritlecitinib is a selective Janus kinase 3 and TEC family kinase inhibitor approved for the treatment of severe alopecia areata (AA). Real‐world prospective data remain limited, particularly regarding response dynamics beyond mean severity scores. The objective of this study was to evaluate the real‐world effectiveness and safety of ritlecitinib in patients with severe AA and to characterize patterns of treatment response by integrating clinical severity metrics and trichoscopic findings. Methods: This prospective single‐center cohort study included adults with severe AA (baseline Severity of Alopecia Tool [SALT] ≥ 50) treated with ritlecitinib 50 mg once daily. Clinical assessments were performed at baseline and Weeks 4, 12, and 24. Outcomes included longitudinal changes in the SALT score, achievement of SALT ≤ 20, transitions across severity categories, and trichoscopic markers of disease activity and regrowth. Safety and laboratory parameters were monitored through Week 24. Results: Thirty patients completed follow‐up through Week 24. Mean SALT decreased from 79.7 ± 22.0 at baseline to 44.5 ± 37.2 at Week 24. Thirteen of 30 patients (43.3%; 95% CI: 27.4–60.8) achieved SALT ≤ 20 by Week 24. Distribution‐based analyses demonstrated a progressive shift toward lower SALT values and transitions from severe to milder disease categories in a subset of patients. Trichoscopic evaluation showed an early and progressive increase in regrowth hairs from Week 4 onward, while traditional activity markers remained frequently detectable. Patient‐reported outcomes also improved over follow‐up, with significant reductions in Skindex‐16 and HADS anxiety and depression scores. No serious adverse events or treatment discontinuations occurred; laboratory parameters remained largely stable. Conclusions: In this prospective real‐world cohort, ritlecitinib demonstrated clinically meaningful effectiveness and a favorable midterm safety profile in severe AA. Integrating continuous, categorical, and trichoscopic outcomes provides a nuanced characterization of treatment response beyond mean severity measures alone.

Background/Objectives: Sulfated hyaluronic acid (sHA) is a chemically modified derivative of native hyaluronic acid (HA), characterized by enhanced physicochemical stability and increased biological activity. Glycosaminoglycans (GAGs), including HA, are key regulators of skin structure, hydration, and immune homeostasis. This review aims to critically summarize current knowledge on the structural and functional properties of GAGs—particularly HA and its sulfated forms—and to explore their potential dermatological applications in skin aging and inflammatory diseases such as atopic dermatitis, psoriasis, and acne. Methods: A narrative literature review was conducted using PubMed and Scopus databases up to June 2025, including experimental, preclinical, and clinical studies investigating the biological effects, mechanisms of action, and dermatological uses of sHA compared with native HA and other HA derivatives. Results: Compared with HA, sHA demonstrates increased enzymatic resistance, higher charge density, and improved water-binding and antioxidant capacity. These properties contribute to the restoration of skin barrier function, modulation of oxidative stress and inflammation, and promotion of extracellular matrix remodeling. Preclinical evidence supports the efficacy of sHA in reducing dryness, irritation, and inflammatory responses in atopic dermatitis, psoriasis, and acne. Preliminary findings also suggest potential benefits in wound healing and skin barrier repair. Conclusions: sHA represents a promising multifunctional molecule in dermatology and cosmetology, capable of reducing inflammation and supporting tissue regeneration. However, current evidence remains limited to preliminary studies. Future controlled clinical trials are required to confirm efficacy, optimize formulations, and establish standardized treatment protocols.

Background: Acral melanocytic lesions often pose a diagnostic and therapeutic challenge for many clinicians. Reflectance confocal microscopy (RCM) is an imaging technique widely used for the assessment of skin cancers. The aim of this review is to explore the applicability of RCM for the diagnosis of nevi and melanoma on the acral sites. Methods: Study selection was conducted based on the application of RCM for acral melanocytic lesions. All types of articles (original articles, short reports, and single case reports) were included in the analysis following PRISMA updated guidelines. Results: The search retrieved 18 papers according to the selection criteria; after removing duplicate records and additional articles by one or more of the exclusion criteria, a total of seven studies were carefully evaluated. Conclusions: RCM seems a valuable and useful additional tool for the diagnosis of acral melanocytic lesions, and its use may decrease the need for invasive procedures to some extent. Visualization of deeper layers may be achieved through mechanical removal of the superficial stratum corneum.