Tocilizumab for focal segmental glomerulosclerosis secondary to multicentric Castleman’s disease
Tocilizumab for focal segmental glomerulosclerosis secondary to multicentric Castleman’s disease
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托珠单抗治疗继发于多中心卡斯尔曼病的局灶性节段性肾小球硬化症
DOI：
10.1007/s00277-019-03616-y
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发表时间：
2019
影响因子：
3.5
通讯作者：
Kurokawa Mineo
中科院分区：
文献类型：
--
作者：
Ebisawa Kazutoshi;Masamoto Yosuke;Tokushige Junji;Nishi Hiroshi;Honda Kenjiro;Hinata Munetoshi;Toyama Kazuhiro;Nangaku Masaomi;Kurokawa Mineo
多中心Castleman病（MCD）是一种淋巴增生性疾病，伴有全身症状和多器官功能障碍，由白细胞介素(IL)-6过量引起。局灶节段性肾小球硬化（FSGS）是一种罕见的MCD并发症，其治疗方法尚未达成共识。尽管托珠单抗阻断IL-6对MCD[1]非常有效，但其对MCD继发的FSGS的作用尚不清楚。在此，我们报告了第一例tocilizumab成功治疗MCD继发的FSGS。一名41岁的日本男性通过腹股沟淋巴结活检诊断为MCD，由于症状轻微而未接受治疗。他的艾滋病毒呈阴性。由于HHV-8相关MCD在日本极其罕见，因此未对HHV-8状态进行评估。年复一年，贫血进展缓慢，23年后，患者63岁，血红蛋白水平降至5.3 g/dl。此时，尿蛋白与肌酐比值（UPCR）增加到5.4 g/gCr。口服强的松龙1 mg/kg，此后蛋白尿控制在0.5-1 g/gCr。血红蛋白水平维持在9-10 g/dl。但eGFR降至40 ml/min/1.73 m2以下。为了更好地控制蛋白尿，tocilizumab的剂量为8mg /kg，每2周给药。残余症状消失，UPCR降至0.15 g/gCr。CRP水平从10-12 mg/dl降至1 - 3mg /dl，肾功能停止恶化。3年后，蛋白尿复发，UPCR达到3.6 g/gCr，而其他标志物如CRP和血红蛋白水平保持不变。进行肾活检以进一步评估。肾脏组织学检查显示22例肾小球中1例节段性硬化，22例肾小球中2例基底膜粘连（图1）。免疫荧光染色显示IgM轻度沉积。电镜检查可见弥漫性足突冲蚀，但未见电子致密沉积。未见淀粉样纤维。根据这些发现，他被诊断为FSGS。就在肾活检之前，我们将tocilizumab的频率从每月2次增加到每月3次，这逐渐降低了他的UPCR水平。他的CRP水平也从1 - 2mg /dl降至1mg /dl以下。因此，在托珠单抗强化治疗4个月后，UPCR水平继续下降至0.8 g/gCr，此后一直保持稳定。
Dear Editor, Multicentric Castleman’s disease (MCD) is a lymphoproliferative disorder accompanying systemic symptoms and multi-organ dysfunction by excessive interleukin (IL)-6 [1]. Focal segmental glomerulosclerosis (FSGS) is an uncommon complication of MCD and no consensus has been achieved on its treatment [2]. Although pharmacological IL-6 blockade by tocilizumab is highly effective for MCD [1], its effect against FSGS secondary to MCD is unknown. Herein, we report a first case of FSGS secondary to MCD successfully treated by tocilizumab. A 41-year-old Japanese man diagnosed with MCD by inguinal lymph node biopsy had been observed without therapy because of mild symptoms. He was negative for HIV. HHV-8 status was not evaluated because of the extreme rarity of HHV-8-associated MCD in Japan [3]. Anemia had progressed slowly from year to year, and 23 years later, when he was 63 years old, his hemoglobin level decreased to 5.3 g/dl. At this time, urinary protein to creatinine ratio (UPCR) had increased to 5.4 g/gCr. Oral prednisolone at 1 mg/kg was administered and proteinuria was controlled at 0.5–1 g/gCr thereafter. Hemoglobin levels were maintained at 9–10 g/dl. However, his eGFR decreased to below 40 ml/min/1.73 m2. To achieve better control of proteinuria, tocilizumab at a dose of 8 mg/kg was administered every 2 weeks. His residual symptoms had disappeared and UPCR diminished to 0.15 g/gCr. CRP levels decreased from 10–12 to 1–3 mg/dl and deterioration of renal function was stopped. Three years later, proteinuria recurred and UPCR reached 3.6 g/gCr, while other markers such as CRP and hemoglobin levels remained unchanged. Renal biopsy was performed for further evaluation. The histological examination of the kidney demonstrated segmental sclerosis in 1 of 22 glomeruli and basement membrane adhesion in 2 of 22 glomeruli (Fig. 1). Immunofluorescence staining demonstrated mild deposition of IgM. The electron microscopic examination showed diffuse foot process effacement but no electron dense deposits. No amyloid fibril was observed. Based on these findings, he was diagnosed with FSGS.Just before renal biopsy, we increased the frequency of tocilizumab from twice to three times a month, which gradually lowered his UPCR levels. His CRP levels were also lowered from 1–2 mg/dl to below 1 mg/dl. Accordingly, UPCR levels continued to decrease to reach 0.8 g/gCr 4 months after intensification of tocilizumab therapy and have been stable thereafter.
影响因子：
8
作者：
Estrada, Chelsea C.;Paladugu, Praharshasai;Mallipattu, Sandeep K.
通讯作者：
Mallipattu, Sandeep K.
影响因子：
20.3
作者：
Fajgenbaum, David C.;Uldrick, Thomas S.;Lim, Megan S.
通讯作者：
Lim, Megan S.
影响因子：
2.3
作者：
Yuan, Xiang-Gui;Hu, Wen;Zhao, Xiao-Ying
通讯作者：
Zhao, Xiao-Ying