Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Pediatric Nephrology, Severance Children's Hospital, Seoul, Republic of Korea.
Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea.
Med Hypotheses. 2017 Oct;108:42-45. doi: 10.1016/j.mehy.2017.07.018. Epub 2017 Jul 17.
Henoch-Schönlein Purpura (HSP, IgA vasculitis) is an immunoglobulin A (IgA) mediated disorder characterized by systemic vasculitis with variable presentation, frequently affecting the skin, mucous membrane, joints, kidneys, and rarely lungs and the central nervous system. Interestingly, enhanced production of interleukin-8 (IL-8) levels are found during active disease and increased levels have been reported in supernatants from human umbilical venous endothelial cells after stimulation with sera from patients affected by HSP. While corticosteroid therapy is currently the recommended treatment for HSP, dapsone, an anti-leprosy agent, has also recently been suggested to have therapeutic efficacy due to its ability to suppress IL-8. Moreover, in addition to IL-8 suppression, dapsone has been reported to exert various anti-inflammatory effects by inhibiting the generation of toxic free radicals, myeloperoxidase mediated halogenation that converts HO to HOCl, leukocyte chemotaxis, production of tumor necrosis factor, and other anti-inflammatory molecules. This review aims to provide a solid hypothesis for the pathogenesis of vasculitis in HSP. Moreover, we highlight potential mechanistic actions of dapsone in hopes that dapsone may be considered as an alternative viable treatment for patients affected by HSP.
过敏性紫癜(HSP,IgA 血管炎)是一种免疫球蛋白 A(IgA)介导的疾病,其特征为全身性血管炎,表现多样,常累及皮肤、黏膜、关节、肾脏,罕见累及肺和中枢神经系统。有趣的是,在疾病活动期发现白细胞介素-8(IL-8)水平升高,且有报道称,在人脐静脉内皮细胞的上清液中加入 HSP 患者血清刺激后,IL-8 水平升高。虽然目前皮质类固醇治疗是 HSP 的推荐治疗方法,但由于其抑制 IL-8 的能力,抗麻风病药物氨苯砜最近也被认为具有治疗效果。此外,除了抑制 IL-8 外,氨苯砜还通过抑制有毒自由基的产生、髓过氧化物酶介导的将 HO 转化为 HOCl 的卤化、白细胞趋化作用、肿瘤坏死因子的产生和其他抗炎分子来发挥各种抗炎作用。本综述旨在为 HSP 血管炎的发病机制提供一个坚实的假说。此外,我们强调了氨苯砜的潜在作用机制,希望氨苯砜可以被考虑作为 HSP 患者的一种可行的替代治疗方法。