特应性皮炎（AD）前沿文献精读特辑（J Eur Acad Dermatol Venereol / JID Innov / Dermatol Ther (Heidelb)）

Psoriasis and atopic dermatitis (AD) are traditionally viewed as distinct inflammatory skin diseases driven by type 17 and type 2 immune pathways, respectively. Increasing use of targeted therapies has revealed a treatment-associated phenotype switch between these conditions, the so-called 'flip-flop' phenomenon, characterized by sustained emergence of eczematous features in patients treated for psoriasis or psoriasiform disease in those treated for AD. Robust real-world data on this entity remain limited. OBJECTIVES: To characterize treatment-associated phenotype switching between psoriasis and AD in a large real-world cohort, focusing on clinical features, implicated therapies, management strategies and outcomes. METHODS: We conducted a retrospective, multicentre, multinational observational study across 17 dermatology centres in six countries. Patients with psoriasis or AD who developed a clinician-defined, persistent phenotype switch temporally associated with systemic or biologic therapy and requiring treatment modification were included. Demographic, clinical, therapeutic and outcome data were collected and analysed descriptively. RESULTS: A total of 148 patients were included: 101 (68.2%) developed eczematous features while treated for psoriasis (PsO → eczematous), and 47 (31.8%) developed psoriasiform disease while treated for AD (AD → psoriasiform). PsO → eczematous patients were older and had more cardiometabolic comorbidities, whereas atopic comorbidities were more frequent in the AD → psoriasiform group. PsO → eczematous switches occurred mainly under interleukin (IL)-17 and IL-23 inhibitors, while AD → psoriasiform switches occurred exclusively during biologic therapies targeting type 2 inflammation, predominantly dupilumab. Treatment was modified in all patients. Janus kinase (JAK) inhibitors were the most frequently used strategy in both switch directions, particularly in PsO → eczematous cases. Marked clinical improvement was observed across phenotypes following therapeutic adjustment. CONCLUSIONS: Treatment-associated phenotype switching between psoriasis and AD is a reproducible, bidirectional and clinically relevant real-world phenomenon reflecting immune plasticity rather than paradoxical disease induction. Recognition of this entity is essential to guide appropriate therapeutic adaptation, with JAK inhibitors emerging as a commonly effective management option.

BACKGROUND AND AIM: PF-07242813 (anti-CD1a) was designed to inhibit T-cell proinflammatory signaling. This analysis evaluated the safety and pharmacokinetics of single ascending doses and multiple ascending doses (MADs) of PF-07242813 in healthy participants and the pharmacodynamics of a single dose in patients with atopic dermatitis (AD). METHODS: In part 1, healthy participants (aged 18-55 years) received PF-07242813 intravenously (single ascending doses), subcutaneously (MADs) or intravenously (MADs), or placebo. In part 2, patients with moderate-to-severe AD (aged 18-65 years) were randomized (2:1) to receive 1000 mg PF-07242813 intravenously or placebo. Endpoints included safety and pharmacokinetic outcomes in healthy participants and efficacy endpoints in patients with AD. RESULTS: Of the 122 participants (single ascending doses: n = 57; MADs: n = 40; AD: n = 25), 41 reported treatment-emergent adverse events (mostly mild); headache (4.9%) and alanine transaminase increase (4.9%) were the most common. Peak serum PF-07242813 concentrations occurred at 0.6-2 hours (intravenously, single ascending doses) and 73-169 hours (subcutaneously, MADs). Overall, PF-07242813 did not demonstrate clinical benefit in patients with AD. CONCLUSIONS: CD1a blockade is not sufficient to produce a clinical effect in patients with AD. PF-07242813 was well tolerated and may be useful for CD1a pathway analyses. This study is registered at ClinicalTrials.gov (identifier NCT04668066).

INTRODUCTION: Patients with atopic dermatitis (AD) often experience severe skin disease, intense itching, sleep disturbance, and impaired quality of life (QoL). This study aimed to generate a clinically credible, data-driven conceptual disease model (CDM) of AD using baseline data from the phase 3 ARCADIA 1 trial of nemolizumab in patients with moderate-to-severe AD (NCT03985943). METHODS: Latent constructs were defined for skin severity, itch severity, sleep disturbance, and QoL/health status using validated clinical outcome assessments (COAs). Baseline COA data were obtained for the adult intent-to-treat population in ARCADIA 1. Structural equation modelling was conducted to assess direct and indirect relationships among AD domains. Factor loadings were calculated to evaluate COA-to-latent construct relationships, and regression coefficients were calculated to ensure that constructs had clinically interpretable directionality. To achieve consensus on the final model structure, model development and refinement were complemented by a modified Delphi process. Dermatologists with extensive experience managing moderate-to-severe AD and conducting AD clinical trials iteratively reviewed COA selection and latent construct definitions and proposed directional pathways. RESULTS: COA data from 807 adults with moderate-to-severe AD were used to generate the CDM. In the model, itch severity has a substantial impact on QoL, exerting both a direct effect (β = 0.427) and an indirect effect via sleep disturbance (itch severity → sleep disturbance: β = 0.702; sleep disturbance → QoL: β = 0.431). A significant bidirectional relationship between skin severity and itch severity is also observed (β = 0.367). COAs show strong loadings on their respective latent constructs. CONCLUSIONS: The CDM identifies itch severity as a central driver of the patient burden in moderate-to-severe AD and supports prioritization of itch and sleep disturbance in clinical assessment, therapeutic planning, and outcome evaluation in AD. Our model, whose validity is strengthened by expert consensus, can potentially guide clinical decision-making and evaluation of treatment responses across key domains of AD burden.

INTRODUCTION: Atopic dermatitis (AD) is thought to arise from the interplay of skin barrier dysfunction, type 2 immune dysregulation, and cutaneous dysbiosis, the last of these characterized by reduced bacterial diversity and predominance of Staphylococcus aureus. The urban exposome, including air pollution and reduced environmental microbial diversity, may modulate this dysbiosis. We hypothesized that patients with AD residing in a metropolitan area with a higher pollutant burden would show greater skin dysbiosis, reflected by a higher relative abundance of S. aureus, than patients residing in a municipality with a lower pollutant load and greater environmental biodiversity. METHODS: This cross-sectional, comparative study enrolled ten children (6-12 years) and ten adults (20-31 years) with active AD, without specific treatment in the preceding 30 days, residing in the metropolitan region of São Paulo or in Botucatu, an interior municipality of São Paulo State, Brazil. Skin swabs were collected from eczematous lesions and characterized by 16S ribosomal RNA (rRNA) gene (V3-V4) sequencing. Alpha and beta diversity and the relative abundance of S. aureus, S. epidermidis, and S. hominis were compared between municipalities and age groups using generalized linear models, Bray-Curtis dissimilarity, principal coordinates analysis (PCoA), and permutational multivariate analysis of variance (PERMANOVA). RESULTS: The sample (n = 20) had a predominance of male sex (60%) and moderate AD severity (75%). A total of 658 taxa were identified. Alpha diversity did not differ by municipality or age group, and PERMANOVA revealed no global difference in bacterial community composition (p > 0.1). However, participants residing in the metropolitan municipality showed a significantly higher relative abundance of S. aureus and higher proportions of S. aureus relative to total bacteria and to other staphylococci than those residing in the interior municipality. CONCLUSION: Despite similar overall microbial diversity, patients with AD living in a metropolitan municipality showed selective enrichment of S. aureus compared with those in a less polluted interior municipality. These exploratory findings generate the hypothesis that the urban exposome contributes to cutaneous dysbiosis in AD and warrant confirmation in larger studies with objective exposure measurement.

INTRODUCTION: Residual disease is relatively common in dupilumab-treated patients with atopic dermatitis (AD). Adjunctive topical treatment, including topical corticosteroids or non-steroidal treatments, are often needed. In this study, we evaluated the clinical characteristics and outcomes of patients with AD on dupilumab with residual disease who were subsequently treated with roflumilast cream. METHODS: This was a retrospective chart review conducted at a single academic center. Electronic medical records were searched to identify patients with AD who were prescribed dupilumab and were subsequently prescribed roflumilast cream for persistent or residual disease between July 2022 and January 2026. RESULTS: Of the 676 cases of AD identified and included in this review, there were 30 cases of dupilumab-treated patients with residual AD disease. One additional patient with de novo facial erythema on dupilumab was described qualitatively. Following roflumilast cream treatment, physician-documented clinical improvement was reported in 83% (25/30) of these patients. Of 18 patients with patient-reported outcomes, ten reported improvement with roflumilast cream (including resolution of disease, near resolution, or significant improvement with decreased flares); five reported reduced pruritus (1 with fully resolved itch); three reported no improvement; and one discontinued roflumilast cream due to burning. No additional adverse events were documented in the medical records. CONCLUSIONS: In this retrospective case series, adjunctive roflumilast cream was associated with physician-documented clinical improvement in most dupilumab-treated patients with residual AD.