Frew John W
Skin Hospital, Darlinghurst, Sydney, Australia; University of New South Wales, Sydney, Australia; Laboratory of Translational Cutaneous Medicine, Ingham Institute, Sydney, Australia; Department of Dermatology, Liverpool Hospital, Sydney, Australia.
J Am Acad Dermatol. 2024 Dec;91(6S):S12-S16. doi: 10.1016/j.jaad.2024.08.052.
The pathogenesis of hidradenitis suppurativa is complex and multifaceted. Our understanding of disease mechanisms is in constant flux with new genetic, inflammatory, and microbiological insights upending previous paradigms and enlightening us as to the complex connections between different drivers of disease. This updated review integrates novel genetic insights from genome wide association studies, along with novel basic science data from single cell transcriptomic studies and recent interventional translational work to inform our evolving understanding of the disease. The overarching premise is that hidradenitis suppurativa is a chronic autoinflammatory disorder characterized by inflammatory dysregulation in a background of stem cell fate aberrations highly responsive to hormonal and metabolic changes. Genetic drivers are linked to both hair follicle stem cell fate and cellular response to androgen signaling. The complex mixed inflammatory circuits involve both innate and adaptive immunity, with activation of inflammatory fibroblast subsets and tertiary lymphoid organs in chronic disease. Interplay between inflammation, the cutaneous and gut microbiomes are observed both pre- and posttherapy, however causality remain unclear. Metabolic syndrome, sex hormones and insulin resistance are all interlinked, with adipose tissue being a hormonally active organ able to modulate endogenous sources of sex hormones. Future enquiry regarding factors contributing to disease progression and the identification of novel therapeutic targets will aid in more effective therapeutic strategies for management of this burdensome disease.
化脓性汗腺炎的发病机制复杂且多方面。随着新的遗传学、炎症学和微生物学见解颠覆了以往的模式，并让我们了解到疾病不同驱动因素之间的复杂联系，我们对疾病机制的理解也在不断变化。这篇更新的综述整合了全基因组关联研究中的新遗传学见解，以及单细胞转录组研究中的新基础科学数据和近期的介入性转化研究工作，以增进我们对该疾病不断发展的理解。总体前提是，化脓性汗腺炎是一种慢性自身炎症性疾病，其特征是在对激素和代谢变化高度敏感的干细胞命运异常背景下出现炎症失调。遗传驱动因素与毛囊干细胞命运和细胞对雄激素信号的反应都有关联。复杂的混合炎症回路涉及先天免疫和适应性免疫，在慢性疾病中炎症成纤维细胞亚群和三级淋巴器官会被激活。在治疗前后均观察到炎症、皮肤和肠道微生物群之间的相互作用，然而因果关系仍不明确。代谢综合征、性激素和胰岛素抵抗都相互关联，脂肪组织是一个能够调节内源性性激素来源的具有激素活性的器官。未来对导致疾病进展的因素进行探究以及确定新的治疗靶点，将有助于制定更有效的治疗策略来管理这种负担沉重的疾病。
