特应性皮炎（AD）前沿文献精读特辑（Am J Clin Dermatol / Dermatol Ther (Heidelb) / J Invest Dermatol）

BACKGROUND: Moderate-to-severe atopic dermatitis (AD) often requires prolonged systemic therapy. As disease control is achieved, optimizing dose tapering and identifying factors associated with sustained response are increasingly relevant. OBJECTIVE: The aim was to identify factors associated with maintained disease control following dose tapering of biologics and small-molecule inhibitors used for AD. METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Embase, and the Cochrane Library were searched from 2010 to present, along with manual reference screening. Studies evaluating dose tapering or withdrawal of dupilumab, tralokinumab, lebrikizumab, abrocitinib, baricitinib, or upadacitinib were included. Extracted data included study design, patient characteristics, tapering or withdrawal strategies, and follow-up duration. Outcomes of interest were sustained response, relapse rates, and predictors of long-term disease control. RESULTS: Nineteen studies (4375 patients) were included. Sustained response rates post-tapering varied across abrocitinib (0-60%), baricitinib (45-61%), dupilumab (30-100%), lebrikizumab (67-82%), tralokinumab (25-50%), and upadacitinib (47-61%). Lower baseline disease activity and early clinical improvement were frequently identified as potential predictors of durability. For dupilumab, older age, lower body mass index (BMI), and prurigo nodularis phenotype were associated with sustained response in selected cohorts. For tralokinumab, longitudinal stability across multiple visits outperformed single-time-point assessments. Abrocitinib outcomes favored milder disease without allergic comorbidities, whereas upadacitinib showed higher relapse rates after withdrawal. CONCLUSIONS: In selected patients with moderate-to-severe AD achieving stable disease control, dose tapering appeared to preserve efficacy more frequently than abrupt withdrawal, although response rates and durability varied across therapeutic classes, study designs, and outcome definitions. Predictors of sustained response were drug specific, and longer prospective studies are needed to inform individualized tapering strategies.

INTRODUCTION: Atopic dermatitis and psoriasis (PsO) are common chronic inflammatory skin diseases traditionally considered distinct, driven by Th2 and Th1/Th17 pathways, respectively. However, evidence reveals that some patients may present with both eczematous and psoriatic lesions, either simultaneously or sequentially. This study's objective was to establish an Italian consensus on the clinical definition and management of eczema-psoriasis overlap. METHODS: A steering committee of eight dermatologists identified three key areas: problem definition, clinical presentation and therapeutic management. Forty-three statements were drafted and distributed to 131 dermatologists for evaluation via an eDelphi process, using a 1-9 numeric rating scale. Consensus was defined as a mean score ≥ 7. RESULTS: Of the 131 invited participants, 104 responded (79.4%). Consensus was reached for 42/43 statements. The only statement that failed to achieve consensus concerned the influence of respiratory atopic comorbidities on biologic choice in PsO; as a result of its dichotomous nature, it was not revised or re-voted on. CONCLUSIONS: Eczema and PsO exist on a continuum of immune dysregulation, which may manifest sequentially or concomitantly, with phenotypic switches that can be spontaneous or drug induced. Assessment of risk factors for drug-induced forms should guide therapeutic choices. Mild cases can often be managed with topical therapies, while moderate-to-severe forms may require broader T cell-targeting treatments.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by heterogeneous pathophysiology and considerable interindividual variability in clinical manifestations. Due to this diversity, multiple diagnostic criteria have been established for AD. Variability in these criteria can substantially affect diagnostic accuracy and, consequently, the outcomes of genome-wide association studies (GWAS), whose reliance on this diagnosis variability has not been thoroughly examined. In this study, we conducted GWAS of AD using two diagnostic definitions within the same cohort: self-reported physicians' diagnoses and dermatologists-confirmed diagnoses. GWAS based on self-reported physicians' diagnoses identified previously reported AD-associated loci, whereas single-variant findings from the smaller dermatologist-confirmed GWAS were interpreted primarily as exploratory. Pathway-specific polygenic risk score analysis suggested enrichment of inflammation-related pathways in the self-reported diagnosis GWAS, whereas central nervous system-related pathways, including hippocampal neuronal apoptosis and microglial inflammation, in the dermatologist-confirmed diagnosis GWAS. Furthermore, Mendelian randomization analysis revealed that AD contributes to right hippocampal shrinkage. These findings imply that diagnostic definitions can influence AD GWAS results and generate a hypothesis that genetic liability to AD is linked to hippocampal pathology.