Wung Peter K, Holbrook Janet T, Hoffman Gary S, Tibbs Andrea K, Specks Ulrich, Min Y-I, Merkel Peter A, Spiera Robert, Davis John C, St Clair E William, McCune Joseph, Ytterberg Steven R, Allen Nancy B, Stone John H
Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, Md, USA.
Am J Med. 2005 Dec;118(12):1416. doi: 10.1016/j.amjmed.2005.06.012.
To evaluate the risk factors for herpes zoster as well as the incidence and timing of this complication in patients who were treated with immunosuppression because of active Wegener's granulomatosis.
We studied the 180 Wegener's granulomatosis patients in the Wegener's Granulomatosis Etanercept Trial (WGET). Herpes zoster events during WGET were documented prospectively. Follow-up questionnaires were employed to describe the location, treatment, and complication(s) of herpes zoster and its therapy. Univariate and multivariate analyses were performed to evaluate risk factors, including history of herpes zoster, for the occurrence of herpes zoster during the trial. All analyses were based on the time to first occurrence of herpes zoster.
Eighteen patients (10% of the WGET cohort) suffered a total of 19 herpes zoster episodes over a mean follow-up period of 27 months. The annual incidence of herpes zoster in the WGET cohort was 45 cases/1000 patient-years (95% confidence interval [CI]: 27, 70). The median time from enrollment to the occurrence of herpes zoster in the subgroup of patients with that complication was 16.5 months (+/- 9.4). Fifteen of the 19 herpes zoster events (79%) occurred between months 6 and 36, many months after the period of most intensive immunosuppression. In univariate analyses, history of serum creatinine > or =1.5 mg/dL before enrollment was associated with a relative risk (RR) of 3.0 (95% CI: 1.1, 7.8) for herpes zoster during WGET (P=.03). In multivariate analyses, serum creatinine > or =1.5 mg/dL was associated with an RR of 6.3 (95% CI: 2.0, 19.8; P=.002), and female sex with an RR of 4.6 (95% CI: 1.6, 13.2; P=.004).
Renal dysfunction and female sex were consistently strong risk factors for herpes zoster events in this population. Contrary to expectation, most herpes zoster events did not occur during periods of most intensive immunosuppression. These data may inform studies of interventions designed to prevent herpes zoster in patients on treatment for immune-mediated diseases.
评估因活动性韦格纳肉芽肿接受免疫抑制治疗的患者发生带状疱疹的危险因素、该并发症的发生率及发生时间。
我们对韦格纳肉芽肿依那西普试验（WGET）中的180例韦格纳肉芽肿患者进行了研究。前瞻性记录WGET期间的带状疱疹事件。采用随访问卷描述带状疱疹的发生部位、治疗及并发症情况。进行单因素和多因素分析以评估包括带状疱疹病史在内的试验期间发生带状疱疹的危险因素。所有分析均基于首次发生带状疱疹的时间。
18例患者（占WGET队列的10%）在平均27个月的随访期内共发生19次带状疱疹发作。WGET队列中带状疱疹的年发病率为45例/1000患者年（95%置信区间[CI]：27，70）。发生该并发症的患者亚组中，从入组到发生带状疱疹的中位时间为16.5个月（±9.4）。19次带状疱疹事件中的15次（79%）发生在第6至36个月之间，在免疫抑制最强烈的时期之后数月。在单因素分析中，入组前血清肌酐≥1.5mg/dL的病史与WGET期间带状疱疹的相对风险（RR）为3.0（95%CI：1.1，7.8）相关（P = 0.03）。在多因素分析中，血清肌酐≥1.5mg/dL与RR为6.3（95%CI：2.0，19.8；P = 0.002）相关，女性与RR为4.6（95%CI：1.6，13.2；P = 0.004）相关。
肾功能不全和女性一直是该人群发生带状疱疹事件的强烈危险因素。与预期相反，大多数带状疱疹事件并非发生在免疫抑制最强烈的时期。这些数据可为旨在预防免疫介导疾病治疗患者发生带状疱疹的干预研究提供参考。
