Chan Amanda C Y, Shahana R, Siah Kewin T H, Foo Nicholas, Chan Yee-Cheun, Ng Kay W P, Quek Amy M L, Rathakrishnan Rahul, Ng Shi-Yang, Schwarz Herbert, Mak Anselm, Sharma Vijay Kumar
Division of Neurology, Department of Medicine, National University Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
J Neuroimmunol. 2025 Apr 15;401:578559. doi: 10.1016/j.jneuroim.2025.578559. Epub 2025 Feb 17.
BACKGROUND & AIMS: We evaluated the efficacy of rituximab in patients with anti-TS-HDS, anti-FGFR3 and anti-plexin D1 small fiber neuropathy (SFN) who failed to respond to conventional treatments and immunotherapy.
We reviewed 111 patients diagnosed with SFN - 83 definite SFN, 9 had positive antibody titers towards TS-HDS, FGFR3 or plexin-D1 and received symptomatic treatment, in addition to trials of intravenous immunoglobulin (IVIg) and/or corticosteroids. Five patients who failed to respond were offered rituximab (two intravenous 1 g infusions, two weeks apart). Clinical parameters and questionnaires were compared.
Two patients were positive for anti-TS-HDS, one for anti-plexin D1 and two for anti-FGFR3 antibodies. Therapeutic efficacy was assessed by circulating CD19 B cell levels with flow cytometry. Clinical questionnaires, including Visual Analogue Scale (VAS), Rasch Transformed 13-item SFN Symptom Inventory Quotient (RT-SFN-SIQ), Small Fiber Neuropathy-specific Rasch-built overall disability scale (SFN-RODS) and the Composite Autonomic Symptom Scale (COMPASS-31) were obtained prior to rituximab infusion, and at 4 weeks and 4 months post-infusion. Significantly improved VAS was seen at 4 months after rituximab, while a trend towards improvement was seen in RT-SFN-SIQ, and SFN-RODS. COMPASS-31 score remained static.
This study illustrates the efficacy and potential role of anti-CD20 monoclonal antibody in antibody-associated immune SFN, especially in those who fail to respond to IVIg or corticosteroid. Further randomized controlled trials and larger prospective studies are needed to determine the effectiveness and safety of Rituximab in seropositive patients with SFN.
我们评估了利妥昔单抗对常规治疗及免疫疗法无效的抗TS-HDS、抗FGFR3和抗丛状蛋白D1小纤维神经病变（SFN）患者的疗效。
我们回顾了111例被诊断为SFN的患者——83例确诊为SFN，9例抗TS-HDS、FGFR3或丛状蛋白D1抗体滴度呈阳性，并接受了对症治疗，此外还进行了静脉注射免疫球蛋白（IVIg）和/或皮质类固醇试验。5例治疗无效的患者接受了利妥昔单抗治疗（两次静脉输注1 g，间隔两周）。比较了临床参数和问卷调查结果。
2例患者抗TS-HDS呈阳性，1例抗丛状蛋白D1呈阳性，2例抗FGFR3抗体呈阳性。通过流式细胞术检测循环CD19 B细胞水平评估治疗效果。在输注利妥昔单抗前、输注后4周和4个月时，获取了临床问卷，包括视觉模拟量表（VAS）、拉施转换的13项SFN症状量表商数（RT-SFN-SIQ）、小纤维神经病变特异性拉施构建的整体残疾量表（SFN-RODS）和复合自主神经症状量表（COMPASS-31）。利妥昔单抗治疗4个月后VAS显著改善，而RT-SFN-SIQ和SFN-RODS有改善趋势。COMPASS-31评分保持不变。
本研究说明了抗CD20单克隆抗体在抗体相关免疫性SFN中的疗效及潜在作用，尤其是在对IVIg或皮质类固醇治疗无效的患者中。需要进一步的随机对照试验和更大规模的前瞻性研究来确定利妥昔单抗在血清阳性SFN患者中的有效性和安全性。
