Frew John W
The Skin Hospital, Darlinghurst, Sydney, Australia.
University of New South Wales, Sydney, Australia.
Br J Dermatol. 2025 Feb 3;192(Supplement_1):i3-i14. doi: 10.1093/bjd/ljae238.
Hidradenitis suppurativa (HS) is a complex inflammatory disease, with rapid advances being made in our understanding of the complex immunological pathogenesis of the condition. New insights into the genomic landscape of HS have identified a number of genes that contribute to the development of HS in a polygenic manner, contributing to inflammatory dysregulation and alterations in epidermal stem cell fate in the follicular unit. These genomic variations can explain unique aspects of the disease such as the development and presence of epithelialized tunnels and abnormalities in wound healing. From genetic and translational studies, it is likely that these genetic alterations predispose to an innate immune dysregulation that can be triggered through sex hormone-responsive transcription factors with hormonal changes such as puberty, pregnancy and the menstrual cycle. The role of sex hormones in HS also has direct effects upon the development and maturation of inflammatory cells such as monocytes, which has the potential to explain differential patient response to treatments such as interleukin-23 antagonism. The role of adipose tissue as an active immunological organ also plays a role in the immune dysregulation seen in the disease. Fibrotic tissue and immunologically active fibroblasts play a significant role in the perpetuation of inflammation and development of adaptive immune dysfunction in the disease. The cutaneous and gut microbiomes play significant roles in the activation of innate immunity, although conflicting data exist as to their central or peripheral role in disease pathogenesis. Overall, our understanding of disease pathogenesis in HS is moving toward a more nuanced, complex paradigm in which patient heterogeneity in presentation and immunological characteristics are moving closer to the identification of therapeutic biomarkers to guide therapeutic modalities in the management of this burdensome condition.
化脓性汗腺炎（HS）是一种复杂的炎症性疾病，我们对该疾病复杂的免疫发病机制的理解正在迅速发展。对HS基因组格局的新见解已经确定了许多以多基因方式促成HS发生的基因，这些基因导致炎症调节异常以及毛囊单位中表皮干细胞命运的改变。这些基因组变异可以解释该疾病的独特方面，例如上皮化隧道的形成和存在以及伤口愈合异常。从遗传学和转化研究来看，这些基因改变可能易导致先天性免疫失调，这种失调可通过性激素反应性转录因子随青春期、怀孕和月经周期等激素变化而触发。性激素在HS中的作用也对单核细胞等炎症细胞的发育和成熟有直接影响，这有可能解释患者对白细胞介素-23拮抗剂等治疗的不同反应。脂肪组织作为一个活跃的免疫器官，在该疾病中出现的免疫失调中也起作用。纤维化组织和具有免疫活性的成纤维细胞在该疾病炎症的持续存在和适应性免疫功能障碍的发展中起重要作用。皮肤和肠道微生物群在先天性免疫激活中起重要作用，尽管关于它们在疾病发病机制中的核心或外周作用存在相互矛盾的数据。总体而言，我们对HS疾病发病机制的理解正朝着一个更细致入微、复杂的范式发展，在这个范式中，患者在表现和免疫特征方面的异质性正越来越接近识别治疗生物标志物，以指导对这种负担沉重的疾病的治疗方式。
