Calabrese Laura, Romagnuolo Maurizio, D'Onghia Martina, Rubegni Pietro, Marzano Angelo V, Moltrasio Chiara
Department of Medical, Surgical and Neurological Sciences, Dermatology Section, University of Siena, Siena, Italy.
Institute of Dermatology, Catholic University of the Sacred Heart, Rome, Italy.
Exp Dermatol. 2024 Dec;33(12):e70022. doi: 10.1111/exd.70022.
Sweet syndrome (SS), originally described as acute febrile neutrophilic dermatosis, is a rare inflammatory skin condition, considered the prototype of neutrophilic dermatoses. It is characterised by the sudden onset of well-defined tender papules, plaques and nodules often accompanied by fever, neutrophilia and elevated markers of inflammation. Several variants have been described both clinically and histopathologically. Classifications include idiopathic, malignancy-associated, and drug-induced SS. The exact pathogenesis of SS is still unclear; however, recent findings have shed light on the role of dermal infiltrating neutrophils-in the context of innate immunity, and signalling pathways related to adaptive immunity. To critically analyse the current molecular landscape of SS and discuss the recent evidence supporting novel potential immune mediators and biological signalling pathways involved in SS pathogenesis. The methodology followed PRISMA guidelines and included two bibliographical databases, searching articles published until 17 December 2023. Titles, abstracts and full text were reviewed independently by two assessors, while other two investigators resolved any opinion differences. Of 3303 records identified through database search, 22 articles met the eligibility criteria for inclusion. We considered experimental studies that performed molecular analysis, in terms of cytokines quantification, gene expression and/or immunofluorescence/immunohistochemistry. As for the latter, only studies aimed at characterising the nature of the inflammatory infiltrate and potential mechanisms leading to distinct forms of cutaneous inflammatory cell influx were included. Overall, we described research on 202 SS patients (177 skin biopsies and 25 blood specimens) revealing the predominant role of neutrophil activation and abnormal proliferation as unifying mechanisms in different SS subtypes. Interestingly, we found that hyperactivation of the IL-1 pathway might occur only in a subset of SS patients and adaptive immunity could also play a role in the pathogenic scenario of SS, with a potential significant role of IL-17 axis. This systematic review provides a wealth of evidence on the molecular landscape of SS, although further research is needed to a deeper understanding of the patho-mechanisms of this rare disease and hopefully lead to targeted therapeutic approaches.
Sweet综合征（SS）最初被描述为急性发热性嗜中性皮病，是一种罕见的炎症性皮肤病，被认为是嗜中性皮肤病的原型。其特征为突然出现边界清晰的压痛性丘疹、斑块和结节，常伴有发热、嗜中性粒细胞增多和炎症标志物升高。临床上和组织病理学上都描述了几种变体。分类包括特发性、恶性肿瘤相关型和药物诱导型SS。SS的确切发病机制仍不清楚；然而，最近的研究结果揭示了真皮浸润性嗜中性粒细胞在固有免疫背景下的作用以及与适应性免疫相关的信号通路。为了批判性地分析SS当前的分子格局，并讨论支持参与SS发病机制的新型潜在免疫介质和生物信号通路的最新证据。该方法遵循PRISMA指南，包括两个文献数据库，搜索截至2023年12月17日发表的文章。标题、摘要和全文由两名评估人员独立审查，另外两名研究人员解决任何意见分歧。通过数据库搜索确定的3303条记录中，有22篇文章符合纳入标准。我们考虑了进行分子分析的实验研究，包括细胞因子定量、基因表达和/或免疫荧光/免疫组织化学。至于后者，仅纳入旨在表征炎症浸润性质和导致不同形式皮肤炎症细胞流入的潜在机制的研究。总体而言，我们描述了对202例SS患者（177份皮肤活检和25份血液标本）的研究，揭示了嗜中性粒细胞活化和异常增殖作为不同SS亚型统一机制的主要作用。有趣的是，我们发现IL-1通路的过度活化可能仅发生在一部分SS患者中，适应性免疫也可能在SS的致病过程中发挥作用，IL-17轴可能具有潜在的重要作用。本系统综述提供了大量关于SS分子格局的证据，尽管需要进一步研究以更深入地了解这种罕见疾病的发病机制，并有望导致针对性的治疗方法。
