Vulvar lichen sclerosus (VLS) is a chronic, distressing, inflammatory disease with an enormous impact on quality of life. Treatment goals are relieving symptoms, reversing signs and preventing anatomical changes. Despite the availability of numerous therapeutic options, treatment outcome may not be entirely satisfactory and a definitive cure does not exist. This may be due to the fact that the exact VLS etiopathogenesis remains unknown. The objectives of this paper were to review the most up-to-date knowledge on VLS etiopathogenesis and to consider the available therapies through the lens of a plausible pathogenetic model. An electronic search on both VLS etiopathogenesis and its treatment was performed using the National Library of Medicine PubMed database. Based on current knowledge, it is conceivable that various, heterogeneous environmental factors acting on a genetic background trigger an autoimmune, Th-1 response, which leads to a chronic inflammatory state. This, in turn, can determine both tissue and micro-vascular injury and activation of signaling pathways involved in fibroblast and collagen metabolism. This pathogenetic sequence may explain the effectiveness of anti-inflammatory treatments, mostly topical corticosteroids, in improving VLS clinical-pathological changes. Further deepening of the disease pathways will presumably allow key mediators to become new therapeutic targets and optimize the available treatments.

Urticaria is an inflammatory skin disorder that may occur in isolation or associated with angioedema and/or anaphylaxis. Clinically, it is characterized by the presence of smooth, erythematous or blanching, itchy swelling, called wheals or hives, which greatly vary in size and shape and last less than 24 h before fading to leave normal skin. Urticaria is the consequence of mast-cell degranulation that can be caused by immunological or non-immunological mechanisms. From a clinical point of view, many skin conditions can mimic urticaria and their recognition is mandatory for a correct management and therapeutic approach. We have reviewed all of the main relevant studies which addressed differential diagnosis of urticarial, published until December 2022. The National Library of Medicine PubMed database was used for the electronic research. The present review offers a clinical narrative overview, based on the available literature, of the principal skin disorders that can be misdiagnosed as urticaria (mainly autoinflammatory or autoimmune disorders, drug-induced reactions, and hyperproliferative diseases). The aim of this review is to provide clinicians a useful tool for correctly suspecting and identifying all of these conditions.

Introduction Atopic dermatitis (AD) is a chronic inflammatory skin condition that significantly affects the quality of life (QoL). Lebrikizumab, a biologic drug targeting interleukin-13, demonstrated efficacy and safety in clinical trials. However, real-world data remain limited, largely restricted to Asian populations. Methods This 16-week retrospective multicenter study included 78 adults from a predominantly white cohort with moderate-to-severe AD treated with lebrikizumab throughout 2024. Patients were both naïve and experienced with biologics or Janus kinase inhibitors (bio/JAKi-naïve or -experienced). The primary outcome for disease severity and therapeutic response was measured using the Eczema Area and Severity Index (EASI). Secondary outcomes included the Dermatology Life Quality Index (DLQI), itch- and sleep-numerical rating scales (NRS), body surface area (BSA), Investigator Global Assessment (IGA), SCORing Atopic Dermatitis (SCORAD), and Patient-Oriented Eczema Measure (POEM). Atopic Dermatitis Control Tool (ADCT) and minimal disease activity (MDA) were used to estimate disease control, and Hospital Anxiety and Depression Scales to monitor mental health status. Results At week 16, benefits in disease severity were observed for EASI (− 15.8 ± 9.4, p < 0.0001) and EASI head and neck (− 2.0 ± 1.7, p < 0.0001). QoL significantly improved in 70% of patients (DLQI reduction of − 12.6 ± 9.3, p < 0.0001), accompanied by decreased pruritus (Itch-NRS reduction of − 4.6 ± 3.2, p < 0.0001) and better sleep quality (sleep-NRS reduction of − 4.1 ± 3.4, p < 0.0001). A 76% reduction in BSA score was recorded, 85% of subjects improved their IGA index, with 62% achieving a score of 0–1, and SCORAD and POEM assessments significantly improved (p < 0.0001). Patients perceived a better control of the disease (ADCT, − 10.9 ± 7.1, p < 0.0001), and 14% of patients achieved MDA. Anxiety and depression levels decreased. Four mild adverse events were registered. Conclusions This is one of the first real-world multicenter studies in a predominantly adult white population showing that lebrikizumab is effective, safe and improves symptoms, QoL, and mental health in moderate-to-severe AD bio/JAKi-naïve and -experienced patients.

OX40 is a co-stimulatory immune checkpoint molecule that promotes the activation and the effector function of T lymphocytes through interaction with its ligand (OX40L) on antigen-presenting cells. OX40–OX40L axis plays a crucial role in Th1 and Th2 cell expansion, particularly during the late phases or long-lasting response. Atopic dermatitis is characterized by an immune dysregulation of Th2 activity and by an overproduction of proinflammatory cytokines such as interleukin (IL)-4 and IL-13. Other molecules involved in its pathogenesis include thymic stromal lymphopoietin, IL-33, and IL-25, which contribute to the promotion of OX40L expression on dendritic cells. Lesional skin in atopic dermatitis exhibits a higher level of OX40L+-presenting cells compared with other dermatologic diseases or normal skin. Recent clinical trials using antagonizing anti-OX40 or anti-OX40L antibodies have shown symptom improvement and cutaneous manifestation alleviation in patients with atopic dermatitis. These findings suggest the relevance of the OX40–OX40L axis in atopic dermatitis pathogenesis.

Background and Objectives: Complete clearance of vulvar lichen sclerosus (VLS) occurs in a minority of treated patients. Disease persistence may impact patient well-being. The main objective of this study was to assess if achieving a complete clearance with a corticosteroid treatment leads to a benefit in terms of patient suffering and quality-of-life (QoL) impairment. Methods: We performed an observational study on a cohort of VLS women, who applied mometasone furoate 0.1% ointment for 12 weeks. At treatment completion (T1), we compared the patients who achieved clearance in symptoms (Global Subjective Score [GSS] = 0) or in objective features (Global Objective Score [GOS] = 0) or in both with those who achieved a lower degree of improvement, on the basis of Pictorial Representation of Illness and Self-Measure (PRISM) and Dermatology Life Quality Index (DLQI) scores. Results: In the whole sample (n = 101), GSS, GOS, PRISM, and DLQI scores significantly improved after treatment from baseline; 34 patients (35.8%) achieved GSS = 0, 26 (25.7%) achieved GOS = 0, and 11 (11.5%) clearance of GSS and GOS. PRISM scores at T1 were significantly higher in patients who achieved clearance of symptoms when compared with those who did not, including patients achieving 50–99% GSS improvement from baseline. DLQI scores were lower in patients who achieved clearance of symptoms, signs, or both when compared with the others. Conclusions: VLS clearance corresponded to a significant improvement in the QoL of VLS patients, also in comparison with those who achieved a substantial but incomplete decrease of symptom and sign scores, and should become an ideal therapeutic goal.