Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Clin Infect Dis. 2021 Nov 2;73(9):e2789-e2798. doi: 10.1093/cid/ciaa1901.
Cryptococcal meningoencephalitis (CM) is a major cause of mortality in immunosuppressed patients and previously healthy individuals. In the latter, a post-infectious inflammatory response syndrome (PIIRS) is associated with poor clinical response despite antifungal therapy and negative cerebrospinal fluid (CSF) cultures. Data on effective treatment are limited.
Between March 2015 and March 2020, 15 consecutive previously healthy patients with CM and PIIRS were treated with adjunctive pulse corticosteroid taper therapy (PCT) consisting of intravenous methylprednisolone 1 gm daily for 1 week followed by oral prednisone 1 mg/kg/day, tapered based on clinical and radiological response plus oral fluconazole. Montreal cognitive assessments (MOCA), Karnofsky performance scores, magnetic resonance imaging (MRI) brain scanning, ophthalmic and audiologic exams, and CSF parameters including cellular and soluble immune responses were compared at PIIRS diagnosis and after methylprednisolone completion.
The median time from antifungal treatment to steroid initiation was 6 weeks. The most common symptoms at PIIRS diagnosis were altered mental status and vision changes. All patients demonstrated significant improvements in MOCA and Karnofsky scores at 1 month (P < .0003), which was accompanied by improvements in CSF glucose, white blood cell (WBC) count, protein, cellular and soluble inflammatory markers 1 week after receiving corticosteroids (CS) (P < .003). All patients with papilledema and visual field deficits also exhibited improvement (P < .0005). Five out of 7 patients who underwent audiological testing demonstrated hearing improvement. Brain MRI showed significant improvement of radiological findings (P = .001). CSF cultures remained negative.
PCT in this small cohort of PIIRS was associated with improvements in CM-related complications with minimal toxicity in the acute setting.
隐球菌性脑膜脑炎（CM）是免疫抑制患者和既往健康人群死亡的主要原因。在后一种情况下，尽管进行了抗真菌治疗和脑脊液（CSF）培养均为阴性，但感染后炎症反应综合征（PIIRS）与不良的临床反应相关。目前关于有效治疗的数据有限。
2015 年 3 月至 2020 年 3 月，连续收治了 15 例既往健康的 CM 和 PIIRS 患者，在抗真菌治疗的基础上，给予辅助脉冲糖皮质激素递减治疗（PCT）。具体方案为：静脉滴注甲泼尼龙 1g/d，1 周后改为口服泼尼松 1mg/kg/d，根据临床和影像学反应逐渐减量，同时口服氟康唑。在 PIIRS 诊断时和甲泼尼龙治疗结束后，分别比较蒙特利尔认知评估量表（MOCA）、卡诺夫斯基表现评分、磁共振成像（MRI）脑扫描、眼科和听力检查以及 CSF 指标，包括细胞和可溶性免疫反应。
从抗真菌治疗到开始使用激素的中位时间为 6 周。PIIRS 诊断时最常见的症状是精神状态改变和视力变化。所有患者在 1 个月时 MOCA 和卡诺夫斯基评分均显著改善（P < 0.0003），并且在接受皮质类固醇治疗 1 周后 CSF 葡萄糖、白细胞（WBC）计数、蛋白、细胞和可溶性炎症标志物均得到改善（P < 0.003）。所有有视乳头水肿和视野缺损的患者也有改善（P < 0.0005）。接受听力测试的 7 例患者中有 5 例听力有所改善。MRI 显示脑影像学表现明显改善（P = 0.001）。CSF 培养仍为阴性。
在本小队列的 PIIRS 患者中，PCT 与 CM 相关并发症的改善相关，在急性治疗中具有最小的毒性。
