ASEPTIC-MENINGITIS ASSOCIATED WITH HIGH-DOSE INTRAVENOUS IMMUNOGLOBULIN THERAPY - FREQUENCY AND RISK-FACTORS
ASEPTIC-MENINGITIS ASSOCIATED WITH HIGH-DOSE INTRAVENOUS IMMUNOGLOBULIN THERAPY - FREQUENCY AND RISK-FACTORS
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DOI：
10.7326/0003-4819-121-4-199408150-00004
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发表时间：
1994-08-15
影响因子：
39.2
通讯作者：
DALAKAS, MC
中科院分区：
文献类型：
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作者：
SEKUL, EA;CUPLER, EJ;DALAKAS, MC
目的：静脉注射免疫球蛋白广泛用于治疗各种自身免疫性疾病。在观察了接受治疗的患者的无菌性脑膜炎的情况后，我们研究了接受大剂量静脉注射免疫球蛋白治疗的患者的无菌性脑膜炎的频率和相关危险因素。设计：前瞻性队列研究的回顾性分析。设置：三级研究转诊中心。患者：54例患有各种免疫相关神经肌肉疾病的连续患者参与正在进行的高剂量（2 g/kg）治疗试验静脉注射免疫球蛋白。测量：无菌性脑膜炎的证据，相关的危险因素，血清IgG渗透到脑脊液中，脑脊液IgG的清除率的患者记录分析。结果：54例患者中，6例（11%; 95%CI，4%至23%）无菌性脑膜炎完成输液后24小时内。症状持续3至5天，包括严重头痛、脑膜炎、恐惧症和发烧。脑脊液显示4例患者出现白细胞增多（1例患者白细胞计数高达1169 × 10（6）/L），3例患者出现嗜酸性粒细胞增多，所有患者均出现IgG升高（1例患者高达正常上限的7倍）。24小时后重复脑脊液和血清研究显示，脑脊液IgG清除率为46%，而1例患者的血清IgG清除率为11%。脑脊液培养呈阴性。8例有偏头痛病史的患者中有4例（50%; CI，16%至84%）发生了无菌性脑膜炎，但46例无偏头痛病史的患者中只有2例（4%; CI，0.5%至15%）发生了无菌性脑膜炎（P = 0.003）。无菌性脑膜炎复发偏头痛的患者，尽管使用不同的商业静脉注射免疫球蛋白制剂和较慢的速度infrings.Conclusion：无菌性脑膜炎的患者接受高剂量静脉注射免疫球蛋白治疗的发展。有偏头痛病史的患者在接受静脉注射免疫球蛋白治疗时更容易发展为无菌性脑膜炎，而与商业制剂的类型或输注速率无关。可能的刺激因素包括IgG本身，每种制剂中的各种稳定产品，治疗引发的细胞因子释放，或偏头痛患者的脑血管敏感性。
Objective: Intravenous immunoglobulin is widely used to treat various autoimmune disorders. After observing instances of aseptic meningitis in treated patients, we studied the frequency and associated risk factors for aseptic meningitis in patients treated with high-dose intravenous immunoglobulin.Design: Retrospective analysis of a prospective cohort study.Setting: Tertiary research referral center.Patients: 54 consecutive patients with various immune-related neuromuscular diseases participating in ongoing therapeutic trials of high-dose (2 g/kg) intravenous immunoglobulin.Measurements: Analysis of patient records for evidence of aseptic meningitis, associated risk factors, penetration of serum IgG into the cerebrospinal fluid, and clearance of cerebrospinal fluid IgG.Results: Of 54 patients, 6 (11%; 95% CI, 4% to 23%) developed aseptic meningitis within 24 hours after completion of the infusions. Symptoms, lasting 3 to 5 days, included severe headache, meningismus, photophobia, and fever. Cerebrospinal fluid showed pleocytosis in 4 patients (leukocyte count as high as 1169 x 10(6)/L in one patient), eosinophilia in 3 patients, and IgG elevation in all patients (as great as 7 times the upper limit of normal in one patient). Repeat cerebrospinal fluid and serum studies after 24 hours showed a 46% cerebrospinal fluid IgG clearance compared with an 11% clearance of serum IgG in one patient. Cerebrospinal fluid cultures were negative. Aseptic meningitis developed in 4 of 8 patients (50%; CI, 16% to 84%) with a history of migraine but in only 2 of 46 (4%; CI, 0.5% to 15%) patients without such a history (P = 0.003). Aseptic meningitis recurred in patients who had migraine despite the use of different commercial intravenous immunoglobulin preparations and slower rates of infusion.Conclusion: Aseptic meningitis develops in patients receiving high-dose intravenous immunoglobulin therapy. patients with a history of migraine are more likely to develop aseptic meningitis while receiving intravenous immunoglobulin therapy, regardless of the type of commercial preparation or the infusion rate. Possible inciting factors include the IgG itself, various stabilizing products within each of the preparations, cytokine release triggered by the therapy, or cerebrovascular sensitivity in migraineurs.