目的:为了证明静脉内免疫球蛋白(IVIG)的复合和非长度依赖性(NLD)穿孔活检标本在纯小纤维神经病(SFN)中的治疗效果,成纤维细胞生长因子-3(FGFR-3),或神经丛蛋白D1抗体。SFN的患病率越来越高,超过30%的病例可能是免疫介导的。TS-HDS,FGFR-3和神经丛蛋白D1自身抗体已被证明存在于44%-55%的隐源性SFN病例中,暗示了一种免疫机制。报告显示IVIG对这种情况有效,但在最近的一项试验中,基于长度依赖性(LD)IVIG治疗后数据存在一些争议.
方法:在回顾性研究中,从2021年1月到2022年5月测试的3种抗体的所有纯SFN病例都被列出,分离并分析接受IVIG治疗的患者皮肤活检时表皮神经纤维密度(ENFD)的变化,以及针对SFN的问卷和疼痛评分。
结果:91名纯SFN患者进行了抗体检测。其中60例(66%)为血清阳性,31(34%)为血清阴性。17名血清阳性患者(13名女性患者,4名男性患者,6个FGFR-3,2个TS-HDS,4神经丛蛋白D1,2与所有3种抗体,1带有FGFR-3和神经丛蛋白D1,1带有FGFR-3和TS-HDS,1例TS-HDS和神经丛蛋白D1)接受IVIG治疗。其中,2名患者因副作用停止治疗,其余15人完成了至少6个月的IVIG。其中,12进行了IVIG后皮肤活检,其中,11(92%)的平均复合ENFD改善了55.1%(P=0.01)。NLD-ENFD试样提高了42.3%(P=0.02),LD-ENFD标本提高了99.7%(P=0.01)。神经丛蛋白D1-SFN患者的复合ENFD改善了139%(P=0.04)。此外,14名患者接受了IVIG前/IVIG后问卷,平均疼痛减少2.7(P=0.002)。
结论:IVIG在免疫SFN中显示出新型抗体的疾病修饰作用,尤其是神经丛蛋白D1-SFN,以及显著改善疼痛。应检查NLD-ENFD以及LD-ENFD以查看此效果。进一步的随机对照试验着眼于NLD-ENFD以及LD-ENFD的改善,连同疼痛和特定于SFN的问卷,需要证实这些发现。
OBJECTIVE: To demonstrate treatment efficacy on composite and non-length-dependent (NLD) punch biopsy specimens from intravenous immunoglobulin (IVIG) in pure small-fiber neuropathy (SFN) with trisulfated heparin disaccharide (TS-HDS), fibroblast growth factor-3 (FGFR-3), or Plexin D1 antibodies. SFN has an increasing prevalence, and over 30% of cases may be immune-mediated. TS-HDS, FGFR-3, and Plexin D1 autoantibodies have been shown to be present in 44%-55% of cryptogenic SFN cases, suggesting an immune mechanism. Reports have shown IVIG to be effective for this condition, but some controversy exists based on length-dependent (LD) post-IVIG treatment data in a recent trial.
METHODS: In a retrospective review, all pure SFN cases tested for the 3 antibodies from January 2021 to May 2022 were tabulated, and patients who underwent IVIG treatment were separated and analyzed for changes in epidermal nerve fiber density (ENFD) on skin biopsy, as well as SFN-specific questionnaire and pain scores.
RESULTS: Ninety-one patients with pure SFN had antibody testing. Sixty of these (66%) were seropositive, and 31 (34%) were seronegative. Seventeen seropositive patients (13 female patients, 4 male patients, 6 FGFR-3, 2 TS-HDS, 4 Plexin D1, 2 with all 3 antibodies, 1 with FGFR-3 and Plexin D1, 1 with FGFR-3 and TS-HDS, and 1 with TS-HDS and Plexin D1) underwent IVIG treatment. Of these, 2 patients stopped treatment due to side effects, and the remaining 15 completed at least 6 months of IVIG. Of these, 12 had a post-IVIG skin biopsy, and of these, 11 (92%) had a 55.1% improved mean composite ENFD (P = 0.01). NLD-ENFD specimens improved by 42.3% (P = 0.02), and LD-ENFD specimens improved by 99.7% (P = 0.01). Composite ENFD in Plexin D1-SFN patients improved by 139% (P = 0.04). In addition, 14 patients had questionnaires pre-IVIG/post-IVIG, and average pain decreased by 2.7 (P = 0.002).
CONCLUSIONS: IVIG shows disease-modifying effect in immune SFN with novel antibodies, especially Plexin D1-SFN, as well as significantly improved pain. NLD-ENFD should be examined as well as LD-ENFD to see this effect. Further randomized controlled trials looking at NLD-ENFD as well as LD-ENFD improvement, along with pain and SFN-specific questionnaires, are needed to confirm these findings.