Akiyama Masashi
Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
J Dermatol. 2025 Mar;52(3):400-407. doi: 10.1111/1346-8138.17585. Epub 2024 Dec 19.
Generalized pustular psoriasis (GPP) is a severe autoinflammatory keratinization disease (AiKD) characterized by acute flares of widespread sterile pustules and high fever. GPP is potentially life-threatening. Recently clarified genetic predisposing factors for GPP suggest that the excessive activation of innate immune pathways in the skin, including of interleukin (IL)-1 and IL-36 signaling, plays a significant role in the GPP pathogenesis. IL36RN, CARD14, AP1S3, MPO, SERPINA3, BTN3A3, and MEFV have been identified as GPP-related genes. The pathogenesis of GPP provoked by variants in these seven genes is tightly associated with the excessive activation of innate immune pathways and the resulting autoinflammation in the skin. Various biologics, including inhibitors for the tumor necrosis factor, IL-17, and IL-23 pathways, are used as treatments for GPP. The new understanding of the genetic background of GPP, mentioned above, indicates that the genetic predisposing factors are predominantly related to the excessive activation of innate immunity and autoinflammation. In this context, inhibitors of inflammatory signaling, including of the IL-1 and IL-36 pathways, have been used in clinical practice and investigated as potential future therapies.
泛发性脓疱型银屑病（GPP）是一种严重的自身炎症性角化病（AiKD），其特征为广泛的无菌性脓疱急性发作和高热。GPP有潜在的生命危险。最近明确的GPP遗传易感因素表明，皮肤中固有免疫途径的过度激活，包括白细胞介素（IL）-1和IL-36信号通路，在GPP发病机制中起重要作用。IL36RN、CARD14、AP1S3、MPO、SERPINA3、BTN3A3和MEFV已被确定为GPP相关基因。这七个基因的变异引发的GPP发病机制与固有免疫途径的过度激活以及由此导致的皮肤自身炎症密切相关。各种生物制剂，包括肿瘤坏死因子、IL-17和IL-23信号通路抑制剂，被用作GPP的治疗药物。上述对GPP遗传背景的新认识表明，遗传易感因素主要与固有免疫和自身炎症的过度激活有关。在这种情况下，炎症信号通路抑制剂，包括IL-1和IL-36信号通路抑制剂，已在临床实践中使用，并作为潜在的未来治疗方法进行研究。
