Association of human herpesvirus 6 reactivation with the flaring and severity of drug-induced hypersensitivity syndrome
Association of human herpesvirus 6 reactivation with the flaring and severity of drug-induced hypersensitivity syndrome
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DOI：
10.1111/j.1365-2133.2007.08167.x
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发表时间：
2007-11-01
影响因子：
10.3
通讯作者：
Shear, N. H.
中科院分区：
文献类型：
--
作者：
Tohyama, M.;Hashimoto, K.;Shear, N. H.
背景药物性超敏反应综合征（DIHS）是一种以发热、皮疹和内脏器官受累为主要临床表现的药物不良反应。在日本的绝大多数患者中，DIHS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呤醇。人类疱疹病毒6型（human herpesvirus 6，HHV 6）再激活与DIHS的关系已有多组报道，目的探讨DIHS的发作和严重程度与HHV 6再激活的关系。结果100例患者中有62例在发病后14 - 28天抗HHV-6 IgG抗体升高，其中1例在发病后14-28天抗HHV-6 IgG抗体升高，2例在发病后14-28天抗HHV-6 IgG抗体升高。这些患者患有严重的器官受累和延长的过程相比，38例患者显示没有重新激活的HHV-6。在62例患者中，有18例患者的血清样本中检测到大量的HHV-6 DNA。在这18例患者中，发热和肝炎等症状的加重与HHV-6再激活密切相关。值得强调的是，所有5例死亡患者和10例肾衰竭患者均属于HHV-6再激活组。结论对药物的免疫反应和HHV-6再激活共同导致DIHS的严重病程。HHV-6再活化的表现是DIHS诊断和预后的有用标志。
Background 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.Objectives To confirm the relationship between the flaring and severity of DIHS and HHV-6 reactivation.Methods 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.Results 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.Conclusions 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.