Prurigo nodularis (PN) is a chronic dermatological condition characterized by intensely pruritic nodules resulting from repeated scratching. Its pathogenesis involves neuroimmune dysregulation, inflammatory cytokines, and neural proliferation. Conventional treatments often provide limited relief, necessitating novel therapeutic approaches. This narrative review explores emerging biologics and small molecules for PN treatment, assessing their mechanisms, efficacy, and safety. A comprehensive literature search was conducted using PubMed, Google Scholar, and Web of Science for relevant studies up to February 2025. Additionally, ongoing clinical trials were identified through a verified international website. The search terms included “prurigo nodularis”, “biologic treatments”, “monoclonal antibodies”, “small molecules”, and “JAK inhibitors”. Among new treatment options, dupilumab, an IL-4 receptor antagonist, and nemolizumab, an IL-31 receptor inhibitor, demonstrated significant efficacy in reducing pruritus and lesion severity in PN patients. Other promising monoclonal antibodies include vixarelimab (OSMRβ inhibitor) and barzolvolimab (KIT inhibitor). Small molecules such as JAK inhibitors (upadacitinib, povorcitinib) also show potential by modulating inflammatory pathways. Clinical trials highlight their efficacy, safety, and long-term benefits. Emerging biologics and small molecules represent a transformative approach for PN management, offering targeted therapies that address underlying immunological and neurological mechanisms. Ongoing research and long-term studies are crucial to optimizing treatment strategies and improving patient outcomes.

Background/Objectives: Extramammary Paget’s disease (EMPD) is a rare cutaneous malignancy arising in areas rich in apocrine glands that poses diagnostic and therapeutic difficulties. Although surgery remains the standard of care, achieving clear margins is challenging and recurrence rates are high. This review explores the contribution of non-invasive imaging for diagnosis and monitoring, and evaluates conservative, non-surgical therapies as alternatives to radical surgery. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic review was conducted: eligible studies included interventional and observational research, as well as case series and reports, assessing non-invasive diagnostic methods or non-surgical treatments for EMPD. Data extraction and risk-of-bias evaluation were performed independently by multiple reviewers, and a narrative synthesis summarized therapeutic outcomes and diagnostic performance. Results: Of 808 identified records, 82 met the inclusion criteria: 66 focused on non-surgical therapies, 15 on diagnostic techniques, and one on both. Reflectance confocal microscopy (RCM) and photodynamic diagnosis (PDD) showed high concordance with histopathology, aiding both diagnosis and margin delineation. Among therapies, topical imiquimod and photodynamic therapy (PDT) demonstrated encouraging response rates, while radiotherapy, laser ablation, and systemic chemotherapy were less consistently reported. Evidence quality was limited by small cohorts, heterogeneous regimens, and variable follow-up. Conclusions: Non-invasive imaging enhances diagnostic accuracy and surgical planning, while non-surgical treatments—particularly imiquimod and PDT—offer viable alternatives in selected cases. Larger prospective studies are needed to establish standardized protocols and clarify long-term outcomes.

Background and Objectives: Oral Janus kinase (JAK) inhibitors have become an important therapeutic class in dermatology, with approved indications including atopic dermatitis and alopecia areata. Owing to their broad immunomodulatory effects and rapid onset of action, these agents are increasingly used off label for a variety of inflammatory skin disorders that are often refractory to standard therapies. The objective of this review was to provide a comprehensive overview of the published literature on the off-label dermatologic use of oral JAK inhibitors, summarizing clinical outcomes, safety profiles and treatment durations reported in real-world settings. Materials and Methods: A literature search was conducted in PubMed to identify case reports and case series describing off-label dermatologic use of baricitinib, abrocitinib, upadacitinib, and ritlecitinib. Extracted data included authorship and year, article type, treatment regimen, treatment duration and follow-up, prior systemic therapies, clinical outcomes, and reported adverse events. Results: A total of 136 articles were included, comprising 45 articles on abrocitinib (63 patients), 55 on upadacitinib (94 patients), 35 on baricitinib (45 patients), and 2 on ritlecitinib (2 patients). Across a wide spectrum of dermatological conditions, oral JAK inhibitors showed consistent clinical efficacy. Responses were frequently rapid and disease control was often maintained over several months of treatment. In many cases, dose reduction or treatment discontinuation did not lead to immediate relapse. Overall tolerability was favorable, with adverse events reported in a minority of patients and predominantly described as mild and transient. Conclusions: Although our data is limited to case-based literature, this review highlights the broad off-label therapeutic potential of oral JAK inhibitors in dermatology. Their rapid onset of action, sustained clinical responses, frequent maintenance of remission after dose tapering or discontinuation and generally acceptable safety profile support their consideration as treatment options in selected patients.

Introduction JAK inhibitors (JAKi) represent a novel therapeutic approach for treating the immune-mediated dermatologic diseases alopecia areata (AA) and atopic dermatitis (AD). JAKi have shown a favorable safety profile in controlled clinical trials; however, real-world safety data in routine dermatologic practice remain limited. The objective of this study is to evaluate the safety of JAKis (abrocitinib, baricitinib, upadacitinib, and ritlecitinib) in patients with AA or AD in a real-world setting. Methods We conducted a single-center retrospective observational study based on electronic medical record data from December 2020 to June 2025. Adult patients with a confirmed diagnosis of atopic dermatitis or alopecia areata who were treated as per routine clinical practice with a dermatologic JAKi were included. Adverse events (AE) were retrospectively collected. Results A total of 376 adult patients were included. AE events were observed across all agents and were predominantly mild to moderate. Mild total cholesterol increase, weight gain, and upper respiratory tract infection were the most common AE. Discontinuation was mainly driven by loss of efficacy, while AE-related discontinuations were less frequent and heterogeneous in nature. Importantly, only one case of venous thrombo-embolism was reported in a patient with other thrombotic risk factors, and no cases of major adverse cardiovascular events (MACEs) were recorded. Four cases of malignancies were reported. Notably, sex-specific differences emerged in metabolic adverse events, with weight gain occurring more frequently among female patients. Menstrual alteration, although rare, was a newly described safety event and was the leading cause of treatment discontinuation due to safety issues. Conclusion While no safety signals regarding MACEs or cancer emerged, other metabolic events, such as cholesterol increase, weight gain and menstrual alterations, were identified. These findings highlight that routine clinical practice represents a less controlled and more heterogeneous setting than randomized trials, underscoring the importance of continuous real-world safety monitoring to fully characterize treatment-associated risks.

Background: Psoriasis is a chronic inflammatory disease that frequently affects difficult-to-treat areas such as the scalp, nails, genitalia, and palms/soles, with significant physical and psychological burden. Bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, has shown rapid and durable efficacy in clinical trials, but real-world data in these subgroups remain limited. Methods: We performed a 52-week, single-center retrospective study including patients with psoriasis involving at least one difficult-to-treat area. Effectiveness was assessed using site-specific Physician’s Global Assessment (sc-PGA, f-PGA, sPGA-G, pp-PGA). The primary endpoint was the proportion of patients achieving a PGA 0/1 (clear or almost clear). Safety data were collected at each visit. Results: Eighty-five patients were included (61.8% male; mean age 48.1 years; mean Body Mass Index (BMI, 26.9 kg/m²). Difficult-to-treat areas involved were the scalp (70.6%), nails (41.2%), genitalia (27.1%), and palms/soles (24.7%). At week 52, sc-PGA 0/1 was achieved in 90.6% of patients, sPGA-G 0/1 in 81.3%, f-PGA 0/1 in 66.7%, and pp-PGA 0/1 in 87.5%. Mean PGA values progressively decreased across all sites. The most common adverse event was oral candidiasis (11.8%). Conclusions: Bimekizumab showed rapid, sustained, and clinically meaningful improvement across all difficult-to-treat areas with a favorable safety profile.

Background/Objectives: The efficacy of topical therapies in dermatology is often limited by the barrier function of the stratum corneum, which restricts drug penetration. Iontophoresis is a non-invasive transdermal delivery technique that uses a low-intensity electrical current to enhance the transport of charged and polar molecules across the skin. It has emerged as a strategy to improve local drug bioavailability while minimizing systemic exposure. We systematically reviewed the clinical evidence on the efficacy, safety, and pharmacologic performance of iontophoresis-assisted topical drug delivery in dermatologic diseases. Methods: This systematic review followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251234877). PubMed, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov were searched through 19 November 2025 without language restrictions. Records were screened against predefined eligibility criteria, and data were extracted on study design, participants, dermatologic indications, intervention/comparator, iontophoresis parameters, efficacy outcomes, and adverse events. The risk of bias was assessed using RoB 2 for randomized trials and the JBI checklist for non-randomized studies. Because of substantial clinical and methodological heterogeneity, the findings were synthesized narratively and no meta-analysis was performed. Results: Twenty-one studies published between 1990 and 2025 met the inclusion criteria, including 15 randomized and 6 non-randomized studies. Investigated conditions included psoriasis, eczema, melasma, post-inflammatory hyperpigmentation, herpes labialis, onychomycosis, chronic ulcers, systemic sclerosis-related digital ulcers, acne scarring, and actinic keratosis. Across studies, findings were mixed. The most consistent signals of benefit were observed in pigmentary disorders and infectious diseases, whereas results were more heterogeneous in inflammatory dermatoses and some studies did not show superiority over active comparators. Tolerability was generally favorable, with adverse events limited to mild, reversible local reactions such as erythema, tingling, burning, or transient irritation. No serious treatment-related adverse events were reported. Conclusions: Iontophoresis may represent a useful non-invasive delivery-enhancement strategy in selected dermatologic settings, particularly when topical efficacy is limited by anatomical or physicochemical barriers. However, heterogeneity in protocols, formulations, outcomes, and clinical indications limits direct comparison and does not support broad conclusions of efficacy across all dermatologic conditions. Larger, standardized trials are needed to clarify its therapeutic role, long-term efficacy, and indication-specific benefit.