Alessia Paganelli

Lichen sclerosus (LS) is a chronic immune-mediated and fibrosing mucocutaneous disorder with a multifactorial pathogenesis. Although autoimmune mechanisms and genetic susceptibility are well recognized, the contribution of exogenous triggers and contact allergens remains debated. This narrative review critically evaluates whether irritants, allergens, mechanical trauma, microbial dysbiosis, and infectious agents should be interpreted as primary etiological factors or as secondary disease modifiers in LS. A literature search was conducted in PubMed, Scopus, and Web of Science from database inception to June 2026, focusing on studies addressing epithelial barrier dysfunction, Koebnerization, contact dermatitis, patch testing, microbiome alterations, infectious triggers, immune pathways, and clinical management. Current evidence suggests that barrier dysfunction and cutaneous fragility may create a permissive microenvironment in which mechanical stress, irritants, contact allergens, repeated topical exposure, and microbial alterations can amplify inflammation and symptoms. Patch-testing studies support the clinical relevance of allergic contact dermatitis in selected patients with persistent or treatment-refractory symptoms, but do not establish contact allergy as a primary cause of LS. Similarly, microbiome and infectious data remain associative rather than causal. Overall, exogenous factors in LS are neither a complete myth nor a primary explanation for the disease; their relevance lies mainly in disease modulation and personalized management in selected patients.

Introduction: Lichen sclerosus (LS) is a chronic inflammatory dermatosis predominantly affecting the anogenital region of both women and men. Sexual dysfunction remains among the most debilitating and overlooked consequences of the disease, as available patient-reported outcome measures are either restricted to one sex or capture sexual health only partially. The aim of the present work is to validate the Qualisex questionnaire (in its the Italian version) in patients with LS and to evaluate its psychometric properties, factor structure, convergent, discriminant validity, and sex symmetry. Methods: A cross-sectional study was conducted on 211 patients (167 women, 44 men; mean age 52.9 years) with a confirmed diagnosis of LS. Participants completed the Italian Qualisex, Skindex-29, DASS-21, and sexual-health-specific scales, the Female Sexual Function Index (FSFI) for women, and the International Index of Erectile Function (IIEF) for men. Construct validity was assessed via Principal Component Analysis (PCA), and reliability via Cronbach’s α. Convergent and discriminant validities were evaluated against standard psychometric batteries. Results: Item 2 was removed due to low communality (0.167). PCA on the remaining 9 items revealed a two-factor structure accounting for 72.5% of total variance: Component 1 (“Sexual Functioning and Satisfaction”, 59.89%) and Component 2 (“Partner Devaluation”, 12.66%). Internal consistency was high (α= 0.911 overall; α= 0.841 in women; α= 0.899 in men). Qualisex scores correlated strongly with Skindex-29 Social Functioning (r = 0.582) and Emotions (r = 0.531) subscales, as well as FSFI (r = −0.391) and IIEF (ρ = −0.566). Discriminant validity was supported by low-to-moderate correlations with DASS-21 domains (r < 0.38). While FSFI and IIEF showed significant negative correlations with age (p = 0.002), Qualisex remained age-independent across sexes (p > 0.05). Conclusion: The 9-item Italian Qualisex is a reliable, sex-symmetrical, and age-independent patient-reported outcome measure for assessing sexual health impairment in LS, successfully isolating disease-specific distress from physiological aging and general distress.

Lichen sclerosus (LS) is a chronic dermatosis characterized by persistent inflammation, progressive fibrosis, and an elevated risk of vulvar squamous cell carcinoma. While ultra-potent topical corticosteroids remain the gold standard of care, the necessity for long-term maintenance therapy raises concerns regarding cumulative toxicity, underscoring the critical need for adjunctive therapies that target underlying pathogenic mechanisms. Vitamin E, traditionally recognized for its antioxidant and membrane-protective properties, has emerged as a promising candidate due to its broad immunomodulatory effects, including its regulatory impact on innate and adaptive immunity and its anti-inflammasome activity. However, the available clinical evidence remains limited to topical formulations, and corresponding efficacy data are scarce. In this Perspective article, we critically analyze the current clinical evidence on oral vitamin E in LS, delineate its immunological mechanisms, and incorporate insights from real-world clinical practice at a tertiary referral center, which should be interpreted as hypothesis-generating given the observational, uncontrolled design. Furthermore, we explore the potential of oral vitamin E formulations, address the pharmacokinetic challenges associated with conventional delivery, and propose future research avenues—such as optimized delivery systems and active metabolite formulations—to fully elucidate the therapeutic role of oral vitamin E in LS management.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis of the anogenital region with limited therapeutic options. Emerging evidence implicates dysregulation of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway in LS pathogenesis, supporting investigation of targeted therapies. We report a series of 6 patients treated with topical ruxolitinib for vulvar LS, applied twice daily. Clinical outcomes were assessed using the Clinical Scoring System (CSS) and Patient Global Assessment (PtGA) over a mean follow‐up of 7.5 months. All patients reported early symptomatic improvement in pruritus and burning. In parallel, PtGA scores showed significant improvement ( p < 0.05). No local or systemic adverse events were observed. These findings suggest that topical JAK–STAT inhibition may represent a steroid‐sparing option for achieving symptomatic improvement in LS, particularly in patients with concomitant autoimmune conditions. Larger controlled studies are warranted to confirm these preliminary observations.

Background: Accurate non‐invasive assessment of cutaneous lesions requires integration of diagnostic information with real‐world management outcomes. Reflectance confocal microscopy (RCM) is increasingly used as a second‐level tool after dermoscopy, but evidence linking diagnostic agreement, histological verification, and management across melanocytic and non‐melanocytic lesions remains limited. Methods: This retrospective observational study included 886 patients with 1057 cutaneous lesions evaluated by combined dermoscopy and RCM at a tertiary referral center between October 2023 and September 2024. Lesions were classified as benign melanocytic, malignant melanocytic, benign non‐melanocytic, or malignant non‐melanocytic. RCM–dermoscopy agreement was assessed using observed agreement and Cohen's kappa; chi‐square testing evaluated diagnostic association. Histology‐based performance analyses were restricted to histologically confirmed lesions. Results: Among 931 lesions with both classifications available, observed agreement was 37.8%, with fair agreement by Cohen's kappa ( κ = 0.211; 95% confidence interval [CI], 0.172–0.251). Diagnostic distributions were significantly associated ( χ ² = 571.3, df = 9, p < 0.001), with substantial discordance, particularly within melanocytic categories. Histopathological confirmation was available for 225 lesions (21.3%), indicating verification bias. In the dedicated melanocytic excision subset, 162 excised lesions yielded 41 melanomas, resulting in a numbers needed to excise (NNE) value of 3.95. Malignant non‐melanocytic detection yield was 39.0% among histologically confirmed excised non‐melanocytic lesions. Conclusions: In this real‐world tertiary referral cohort, RCM integrated with dermoscopy supported lesion stratification and management across diagnostic categories. The significant association but fair agreement between modalities highlights their complementary role. Diagnostic performance estimates should be interpreted within the histology‐confirmed subset and in light of verification bias. image