Vecin Nicole, Balukoff Nathan C, Yaghi Marita, Gonzalez Tammy, Sawaya Andrew P, Strbo Natasa, Tomic-Canic Marjana, Lev-Tov Hadar, Pastar Irena
Miami HS Center, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
Wound Healing and Regenerative Medicine Research Program, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
JID Innov. 2025 Jan 21;5(3):100350. doi: 10.1016/j.xjidi.2025.100350. eCollection 2025 May.
Hidradenitis suppurativa tunnel structures lined with epithelium within the dermis are unique features of advanced disease stages that significantly impair patients' QOL. The presence of hidradenitis suppurativa tunnels is associated with a decreased likelihood of achieving a clinical response, even when receiving biological therapy. The cellular and molecular mechanisms underlying tunnel formation and pathology are only partially understood, which hampers the development of more effective targeted therapies. Tunnels create a unique microenvironment that drives a vicious cycle of hidradenitis suppurativa inflammation, with tunnel keratinocytes exhibiting an activated phenotype characterized by distinct gene expression signatures. In this review, we summarize the current literature and discuss aspects of the pathophysiology of tunnels, including the role of hair follicle epidermal stem cells in tunnel formation, potential role of fibroblast-mediated epithelial-mesenchymal transition, role of dermal papilla fibroblasts, and aberrant proinflammatory repair response contributing to the observed fibrosis and scarring. Finally, tunnel structures are characterized by unique microbial dysbiosis and an overabundance of Gram-negative anaerobes that are not targeted by current therapeutics. In addition to outlining the possible mechanisms of tunnel formation, we provide perspectives on the translation of current knowledge into more effective treatment approaches for patients with hidradenitis suppurativa tunnels.
化脓性汗腺炎真皮内由上皮细胞衬里的隧道结构是晚期疾病阶段的独特特征，会严重损害患者的生活质量。化脓性汗腺炎隧道的存在与实现临床缓解的可能性降低相关，即使在接受生物治疗时也是如此。隧道形成和病理的细胞及分子机制仅得到部分理解，这阻碍了更有效靶向治疗方法的开发。隧道创造了一个独特的微环境，驱动化脓性汗腺炎炎症的恶性循环，隧道角质形成细胞表现出以独特基因表达特征为特点的活化表型。在本综述中，我们总结了当前文献，并讨论了隧道病理生理学的各个方面，包括毛囊表皮干细胞在隧道形成中的作用、成纤维细胞介导的上皮-间质转化的潜在作用、真皮乳头成纤维细胞的作用，以及导致观察到的纤维化和瘢痕形成的异常促炎修复反应。最后，隧道结构的特征是独特的微生物群落失调和大量革兰氏阴性厌氧菌，而目前的治疗方法并未针对这些细菌。除了概述隧道形成的可能机制外，我们还提供了将当前知识转化为针对化脓性汗腺炎隧道患者更有效治疗方法的观点。
