Department of Dermatology, National Hospital Organization Shikoku Cancer Center, Matsuyama, 791-0280, Japan.
Department of Dermatology, Ehime University Graduate School of Medicine, Toon, 791-0295, Japan.
J Dermatol. 2020 May;47(5):476-482. doi: 10.1111/1346-8138.15294. Epub 2020 Mar 11.
Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction characteristically associated with sequential reactivation of herpesviruses, such as human herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). Since systemic corticosteroids are thought to result in viral reactivation due to their immunosuppressive effects, we clarified the influence of systemic corticosteroid therapy on viral reactivation in DIHS/DRESS. Viral DNA in peripheral whole blood and serum sIL-2R level were measured during the disease course in twenty DIHS/DRESS patients. Six of seven patients treated without corticosteroids experienced HHV-6 viremia associated with elevated serum sIL-2R levels. In contrast, high-dose corticosteroids started within 1 week after onset tended to inhibit the occurrence of HHV-6 reactivation with remarkable suppression of serum sIL-2R level. Low-dose corticosteroids or late-start high-dose corticosteroids did not suppress occurrence of HHV-6 viremia and the increase of sIL-2R levels. HHV-6 load in the blood was clearly correlated with the serum sIL-2R level. On the other hand, increased CMV load were found in patients treated with corticosteroids regardless of the start time. The frequency of detection of EBV DNA in peripheral blood was similarly observed in all groups. In conclusion, high-dose corticosteroids started within 1 week tended to suppress HHV-6 reactivation through suppression of T cell activation. However, CMV proliferation was promoted by corticosteroids regardless of the start time. These observations suggested that careful consideration should be given to the dose and timing of administration of systemic corticosteroids in the treatment of DIHS/DRESS.
药物诱导的超敏反应综合征(DIHS)/药物反应伴嗜酸性粒细胞增多和全身症状(DRESS)是一种严重的药物不良反应,其特征与疱疹病毒(如人类疱疹病毒 6(HHV-6)、EB 病毒(EBV)和巨细胞病毒(CMV))的顺序再激活有关。由于全身皮质类固醇由于其免疫抑制作用而被认为导致病毒再激活,因此我们阐明了全身皮质类固醇治疗对 DIHS/DRESS 中病毒再激活的影响。在二十例 DIHS/DRESS 患者的疾病过程中测量了外周全血中的病毒 DNA 和血清 sIL-2R 水平。在未接受皮质类固醇治疗的六名患者中,有七名患者出现与血清 sIL-2R 水平升高相关的 HHV-6 血症。相比之下,在发病后 1 周内开始使用大剂量皮质类固醇往往会抑制 HHV-6 再激活的发生,并显著抑制血清 sIL-2R 水平。小剂量皮质类固醇或晚发大剂量皮质类固醇不能抑制 HHV-6 血症和 sIL-2R 水平的升高。血液中的 HHV-6 载量与血清 sIL-2R 水平明显相关。另一方面,在接受皮质类固醇治疗的患者中发现 CMV 载量增加,无论开始时间如何。在所有组中均观察到外周血中 EBV DNA 的检测频率相似。总之,在发病后 1 周内开始的大剂量皮质类固醇通过抑制 T 细胞激活而抑制 HHV-6 再激活。然而,无论开始时间如何,皮质类固醇均可促进 CMV 增殖。这些观察结果表明,在治疗 DIHS/DRESS 时,应仔细考虑全身皮质类固醇的剂量和给药时间。