特应性皮炎（AD）前沿文献精读特辑（Clin Exp Dermatol / J Dermatol Sci / J Eur Acad Dermatol Venereol）

BACKGROUND: Tissue resident memory (TRM) cells are of interest in chronic inflammatory skin diseases as they are believed to facilitate flares in the same anatomical area. IL-15 is an essential growth factor for the survival of TRM in the skin compartment. A main source of IL-15 are tissue-resident cells. OBJECTIVE: The purpose of this study was to explore the role of IL-15 in the chronification process of atopic dermatitis (AD). METHODS: Primary human keratinocytes and fibroblasts were cultured and exposed to a range of stimuli in order to assess their IL-15 expression and production, which were measured by qPCR and ELISA, respectively. RNAseq and PCR were performed from lesional and non-lesional atopic dermatitis (AD) biopsies. RESULTS: We tested a range of type I and type II response-associated cytokines and PAMPs on primary human fibroblasts and keratinocytes. The main inducer for IL-15 in keratinocytes proved to be IFNγ, while fibroblasts showed responsiveness to long-term exposure to IL-4. Transcriptomic analyses of AD skin biopsies confirmed that IL-15 was associated with a higher IFN signature and longer disease duration, and a significant correlation was observed between IL-15 and the TRM molecules CCR8 and CD69. CONCLUSION: The epidermal compartment responds to IFNs with IL-15 expression. Analysis of patient-derived skin biopsies highlights higher expression of IL-15 in the context of a Th1 shift known to occur in chronic AD. These data suggest that flares require prompt intervention to avoid consolidation of an IFNγ-driven tissue memory.

Eczema action plans have emerged as a management tool for eczema. Recent studies investigated the efficacy of eczema action plans in improving quality of life and disease severity. This study aims to examine the effectiveness of eczema action plans in improving eczema. A search was conducted using the MEDLINE, Embase and Scopus databases for clinical trials evaluating eczema action plans in eczema management. Five studies (four randomized, one nonrandomized) showed no objective improvement in atopic dermatitis severity or quality of life with eczema action plans. Eczema action plans improved patient knowledge, confidence and satisfaction, but these did not translate to clinical outcomes, possibly due to complex regimens hindering adherence.

Atopic dermatitis (AD) is a chronic inflammatory skin condition with a substantial impact on quality of life. It is challenging to control with traditional therapies. The introduction of biologic agents and systemic Janus kinase inhibitors (JAKis) has improved therapeutic outcomes; however, many patients exhibit incomplete responses to these agents. Add-on strategies include traditional systemic drugs or phototherapy added to biologic agents or JAKis to enhance treatment outcomes. However, their use in these subsets of patients is underexplored. To assess these approaches, the authors conducted a literature review focused on add-on treatments in cases of moderate-to-severe AD with incomplete responses to biologics or JAKis. Relevant studies were identified and examined, with particular attention to changes in clinical outcomes and adverse event profiles. Data limitations included variability in study designs and outcome measures. The results consistently show that add-on therapies achieve larger reductions in validated clinical scores (e.g. Eczema Area and Severity Index; EASI) and higher responder rates (e.g. ≥ 75% improvement in EASI) than monotherapy. The use of traditional systemic agents as add-on treatment, even for a short period, can enhance partial responses to biologic agents or JAKis, leading to more effective disease control. Also, emerging data suggest that combining biologics with JAKis or vice versa may benefit patients who do not achieve adequate relief from either as monotherapy. While these findings are encouraging, several issues remain, among these the lack of large studies, the optimal timing, the cost-effectiveness, the long-term safety and the real-world feasibility. Further well-designed clinical trials are needed to establish standardized add-on regimens, guiding clinicians towards personalized AD treatment.