International Journal of Dermatology最新文献

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease with significant physical and psychosocial burden. Dupilumab, a monoclonal antibody targeting IL-4Rα, has proven to be effective for moderate-to-severe AD, but long-term real-world data remain limited.

Objective: The aim of this study is to evaluate the long-term effectiveness, safety, and achievement of minimal disease activity (MDA) in patients with moderate-to-severe AD treated with dupilumab over a 5-year period.

Methods: A retrospective single-center cohort study was conducted at the Dermatologic Clinic of the University of Turin, including 583 patients aged ≥ 6 years treated with dupilumab between November 2018 and January 2025. Effectiveness was measured by Eczema Area and Severity Index (EASI), Pruritus-Numerical Rating Scale (P-NRS), and Sleep Loss-Numerical Rating Scale (S-NRS) scores, Dermatology Life Quality Index (DLQI). MDA was defined as EASI-90 combined with P-NRS ≤ 1. Safety and drug survival were also assessed.

Results: Dupilumab treatment resulted in significant and sustained reductions in EASI and symptom scores over 5 years. The proportion of patients achieving MDA increased from 22.0% at 16 weeks to 56.0% at 208 weeks and remained stable at 55.3% through 5 years. Male sex and childhood onset may reduce treatment success, warranting further study. The safety profile was favorable, with low discontinuation rates, and conjunctivitis as the most common adverse event.

Conclusion: Our long-term real-world data support the sustained effectiveness and safety of dupilumab in moderate-to-severe AD, with over 55% of patients achieving and maintaining MDA at 5 years.

Chronic pruritus of unknown origin (CPUO) is a distressing condition characterized by persistent itch lasting over 6 weeks without an identifiable cause. The underlying mechanisms remain poorly understood, complicating diagnosis and treatment. This systematic review examines the diagnostic work-up and therapeutic approaches for CPUO, evaluating the quality of treatment studies using the Strength of Recommendation Taxonomy (SORT) algorithm. Our paper also uniquely integrates a review of potential pathogenic mechanisms. A comprehensive literature search was conducted in PubMed, EMBASE, Ovid MEDLINE, and Cochrane databases through September 2025 using terms including "CPUO," "chronic idiopathic pruritus," and "pruritus of unknown origin." Studies discussing pathogenesis, diagnostic strategies, or treatment were included. Treatment interventions were assessed based on the SORT algorithm. Of 228 identified records, 52 met inclusion criteria: 18 addressing pathogenesis, 5 discussing competing etiological hypotheses, 3 focusing on diagnostic work-up, 23 on treatment, and 3 on non-pharmacological therapies. CPUO pathogenesis appears multifactorial, involving Th2 dysregulation, neurogenic factors (JAK1, GRPR, TRPV4), metabolic alterations, and aging-related immune changes. Current diagnostic approaches emphasize exclusion of systemic, dermatologic, and neurologic causes. Treatment options include topical agents (calcineurin inhibitors, capsaicin), systemic immunomodulators (JAK inhibitors, dupilumab, nemolizumab), neuromodulators (gabapentin, pregabalin), and phototherapy. However, available treatment studies are of low quality, with few randomized controlled trials (RCTs). CPUO remains a challenging condition with unclear pathophysiology and limited high-quality therapeutic evidence. Further research, particularly RCTs, is needed to establish evidence-based management strategies.

Background: Psoriasis and depression frequently coexist, creating a complex, bidirectional relationship that complicates treatment. This study, integrating clinical assessments with transcriptomic and metabolomic analyses, hypothesizes that TYK2 (tyrosine kinase 2) inhibitors possess a dual therapeutic potential to simultaneously address both dermatological manifestations of psoriasis and the frequently accompanied depressive symptoms.

Methods: In a cohort of 298 psoriasis patients evaluated using the Hospital Anxiety and Depression Scale (HADS), participants were categorized into a TYK2 inhibitor group, a Janus kinase (JAK) inhibitor group, and a non-JAK pool (comprising interleukin [IL]-23 biologics, IL-17 biologics, and other treatments) to avoid overlapping JAK pathway inhibition. Statistical analysis was conducted using generalized linear models (GENMOD), with adjustments for the following covariates: age, sex, Psoriasis Area and Severity Index (PASI), body surface area (BSA), prior systemic or biologic therapy within 12 months, disease duration, and phototherapy history.

Results: For HADS-D scores, the TYK2 inhibitor group showed significantly lower values compared with the non-JAK pool (β = 1.23, 95% confidence interval [CI]: 0.37-2.10). However, no significant differences were observed when compared with the IL-23 biologics group (β = 0.67, 95% CI: -0.76-2.10) or the JAK inhibitor group (β = 0.84, 95% CI: -1.54-3.21). Transcriptomic analysis of peripheral blood revealed significant downregulation of genes related to the IL-6 receptor, long-term depression pathways, and Th17 cell differentiation, while pathways associated with neuronal activity were upregulated. Metabolomic profiling highlighted a decrease in kynurenic acid, which is known for its pro-inflammatory and depressive effects, and an increase in 1H-indole-3-propanoic acid, an anti-inflammatory metabolite with neuroprotective properties. It is important to note that these findings are based on exploratory omics analyses, for which false discovery rate (FDR) control was applied.

Conclusions: These findings provide a hypothesis that TYK2 inhibitors disrupt the persistent "peripheral inflammation-central depression" cycle by targeting the IL-23/Th17 axis and modulating the IL-6/tryptophan metabolic hub. This innovative, multi-targeted approach represents a possibility for treating psoriasis with comorbid depression, offering not only clinical improvements in both skin and mood symptoms but also enhanced patient adherence to treatment regimens.