Ishida T, Kano Y, Mizukawa Y, Shiohara T
Department of Dermatology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Allergy. 2014 Jun;69(6):798-805. doi: 10.1111/all.12410. Epub 2014 Apr 17.
Drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms (DIHS/DRESS) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) represent contrasting poles of severe drug eruptions, and sequential reactivations of several herpesviruses have exclusively been demonstrated in the former. No previous studies, however, were extended beyond the acute stage. We sought to investigate whether herpesvirus reactivations could also be observed in SJS/TEN and beyond the acute stage of both diseases.
Patients with SJS (n = 16), SJS/TEN overlap (n = 2), TEN (n = 10), and DIHS/DRESS (n = 34) were enrolled. We performed a retrospective analysis of Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and cytomegalovirus (CMV) DNA loads sequentially determined by real-time polymerase chain reaction during a 2-year period after onset.
Persistently increased EBV loads were detected in SJS during the acute stage and long after resolution, but not in others. In contrast, high HHV-6 loads were exclusively detected in DIHS/DRESS during the acute stage. The dynamics of herpesvirus reactivation varied in DIHS/DRESS according to the use of systemic corticosteroids: While EBV loads were higher in patients not receiving systemic corticosteroids, CMV and HHV-6 loads were higher in those receiving them.
Distinct patterns of herpesvirus reactivation according to the pathological phenotype and to the use of systemic corticosteroids were observed during the acute stage and follow-up period, which may contribute, at least in part, to the difference in the clinical manifestations and long-term outcomes. Systemic corticosteroids during the acute stage may improve the outcomes in DIHS/DRESS.
药物性超敏反应综合征/伴有嗜酸性粒细胞增多和全身症状的药疹（DIHS/DRESS）以及史蒂文斯-约翰逊综合征（SJS）/中毒性表皮坏死松解症（TEN）代表了严重药疹的不同极端情况，并且仅在前一种情况中证实了几种疱疹病毒的相继激活。然而，以前的研究均未超过急性期。我们试图研究在SJS/TEN中以及在这两种疾病的急性期之后是否也能观察到疱疹病毒激活。
纳入SJS患者（n = 16）、SJS/TEN重叠患者（n = 2）、TEN患者（n = 10）以及DIHS/DRESS患者（n = 34）。我们对发病后2年内通过实时聚合酶链反应依次测定的爱泼斯坦-巴尔病毒（EBV）、人疱疹病毒6型（HHV-6）和巨细胞病毒（CMV）DNA载量进行了回顾性分析。
在SJS的急性期及缓解后很长时间均检测到EBV载量持续升高，但在其他疾病中未检测到。相反，仅在DIHS/DRESS的急性期检测到高HHV-6载量。DIHS/DRESS中疱疹病毒激活的动态变化因全身使用糖皮质激素而有所不同：未接受全身糖皮质激素治疗的患者EBV载量较高，而接受治疗的患者CMV和HHV-6载量较高。
在急性期和随访期间观察到根据病理表型和全身糖皮质激素使用情况而出现的不同疱疹病毒激活模式，这可能至少部分导致了临床表现和长期预后的差异。急性期使用全身糖皮质激素可能改善DIHS/DRESS的预后。
