Tohyama M, Hashimoto K, Yasukawa M, Kimura H, Horikawa T, Nakajima K, Urano Y, Matsumoto K, Iijima M, Shear N H
Department of Dermatology, Ehime University School of Medicine, Toon-city, Ehime 791-0295, Japan.
Br J Dermatol. 2007 Nov;157(5):934-40. doi: 10.1111/j.1365-2133.2007.08167.x. Epub 2007 Sep 13.
Drug-induced hypersensitivity syndrome (DIHS) is an adverse reaction with clinical signs of fever, rash and internal organ involvement. In the vast majority of patients in Japan, the causative drugs for DIHS are limited to the following eight: carbamazepine, phenytoin, phenobarbital, zonisamide, mexiletine, dapsone, salazosulfapyridine and allopurinol. The association of human herpesvirus (HHV)-6 reactivation with DIHS has been reported by various groups.
To confirm the relationship between the flaring and severity of DIHS and HHV-6 reactivation.
We evaluated 100 patients with drug rash and systemic symptom(s) caused by the drugs associated with DIHS. HHV-6 reactivation was examined by serological antibody assay and quantitative real-time polymerase chain reaction assay of serial serum samples.
Anti-HHV-6 IgG titres increased in 62 of 100 patients, 14-28 days after the onset of symptoms. These patients suffered from severe organ involvement and a prolonged course compared with 38 patients showing no reactivation of HHV-6. Significant amounts of HHV-6 DNA were detected in serum samples from 18 of the 62 patients. Flaring of symptoms such as fever and hepatitis was closely related to HHV-6 reactivation in these 18 patients. It should be emphasized that all five patients with fatal outcome and 10 patients with renal failure were in the HHV-6 reactivation group.
A combination of immunological reaction to a drug and HHV-6 reactivation results in the severe course of DIHS. The demonstration of HHV-6 reactivation is a useful marker of diagnosis as well as prognosis in DIHS.
药物性超敏反应综合征（DIHS）是一种伴有发热、皮疹及内脏器官受累临床症状的不良反应。在日本，绝大多数DIHS患者的致病药物仅限于以下八种：卡马西平、苯妥英、苯巴比妥、唑尼沙胺、美西律、氨苯砜、柳氮磺胺吡啶和别嘌醇。多个研究团队报道了人类疱疹病毒（HHV）-6再激活与DIHS之间的关联。
证实DIHS的发作及严重程度与HHV-6再激活之间的关系。
我们评估了100例由与DIHS相关药物引起的药疹及全身症状患者。通过血清学抗体检测及系列血清样本的定量实时聚合酶链反应检测HHV-6再激活情况。
100例患者中有62例在症状出现后14 - 28天抗HHV-6 IgG滴度升高。与38例未出现HHV-6再激活的患者相比，这些患者存在严重的器官受累且病程延长。62例患者中有18例血清样本中检测到大量HHV-6 DNA。在这18例患者中，发热和肝炎等症状的发作与HHV-6再激活密切相关。应当强调的是，所有5例死亡患者及10例肾衰竭患者均在HHV-6再激活组。
对药物的免疫反应与HHV-6再激活共同作用导致DIHS病情严重。HHV-6再激活的证实是DIHS诊断及预后的有用标志物。
