Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Clin Exp Dermatol. 2024 Sep 18;49(10):1217-1226. doi: 10.1093/ced/llae144.
Aseptic pustulosis involves inflammatory skin conditions with nonbacterial pustules on erythema, accompanied by neutrophil and eosinophil infiltration in the epidermis. Dysregulation of the interleukin (IL)-36 pathway leads to neutrophil aggregation and pustule formation. Variants in IL36RN, CARD14, AP1S3, MPO, SERPINA3 and BTN3A3 have been identified in generalized pustular psoriasis (GPP) in the past. Some patients with acrodermatitis continua of Hallopeau (ACH), palmoplantar pustulosis and acute generalized exanthematous pustulosis (AGEP) also exhibit mutations in IL36RN, CARD14 and AP1S3, albeit with regional and population-specific variations. This study aims to explore a shared genetic foundation among those with aseptic pustulosis. We performed Sanger sequencing on six genes in 126 patients with aseptic pustulosis. Genetic analysis identified IL36RN variants strongly associated with ACH, AGEP and subcorneal pustular dermatosis (SPD). Immunohistochemistry revealed elevated inflammatory cytokines in all subtypes. This study establishes a significant association between IL36RN variants and ACH, AGEP and SPD, emphasizing the IL-1/IL-36-chemokine-neutrophil axis as a common pathogenic mechanism. Targeting this axis holds promise for therapeutic interventions for aseptic pustulosis.
无菌性脓疱病涉及炎症性皮肤疾病，表现为红斑上的非细菌性脓疱，伴有表皮中性粒细胞和嗜酸性粒细胞浸润。白细胞介素 (IL)-36 通路的失调导致中性粒细胞聚集和脓疱形成。过去已在泛发性脓疱性银屑病 (GPP) 中鉴定出 IL36RN、CARD14、AP1S3、MPO、SERPINA3 和 BTN3A3 的变异。一些患有 Hallopeau 连续性肢端皮炎 (ACH)、掌跖脓疱病和急性泛发性发疹性脓疱病 (AGEP) 的患者也表现出 IL36RN、CARD14 和 AP1S3 的突变，尽管存在区域性和人群特异性的变异。本研究旨在探讨无菌性脓疱病之间的共同遗传基础。我们对 126 例无菌性脓疱病患者的六个基因进行了 Sanger 测序。遗传分析鉴定出与 ACH、AGEP 和亚表皮脓疱性皮病 (SPD) 强烈相关的 IL36RN 变异。免疫组织化学显示所有亚型的炎症细胞因子水平升高。本研究确立了 IL36RN 变异与 ACH、AGEP 和 SPD 之间的显著关联，强调了 IL-1/IL-36-趋化因子-中性粒细胞轴作为一种共同的致病机制。针对该轴可能为无菌性脓疱病的治疗干预提供新的途径。
