Arlington Heights, IL; Stritch School of Medicine, Loyola University Chicago, Maywood, IL; Department of Neurology, University of Southern California, Los Angeles, CA; and Department of Neurology, Barrow Neurological Institute, Phoenix, AZ.
J Clin Neuromuscul Dis. 2022 Sep 1;24(1):26-37. doi: 10.1097/CND.0000000000000423.
Up to 50% of small fiber neuropathy (SFN) cases are idiopathic, but novel antibodies to Trisulfated Heparin Disaccharide (TS-HDS) and fibroblast growth factor receptor 3 (FGFR-3) have been implicated in half of these cases; the role of anti-Plexin D1 is less clear. We aimed to clarify presentation and management of these patients.
An 18-month retrospective analysis revealed 54 cases of cryptogenic SFN who had testing for the 3 autoantibodies. Demographics, clinical features, epidermal nerve fiber density, and Quantitative Sudomotor Axon Reflex Test results were analyzed. Intravenous immunoglobulin (IVIG) treatment response was assessed.
In total, 44.4% of patients had antibodies (62.5% TS-HDS, 29.2% FGFR-3, and 20.8% Plexin D1). Male patients were more likely to be FGFR-3 positive (P = 0.014). Facial involvement was more common in seropositive patients (P = 0.034), and patients with a higher Utah Early Neuropathy Scale score had a higher TS-HDS titer (P = 0.0469), but other clinical features were not significantly different. Seropositive patients trended toward a higher SFN screening list score (P = 0.16), abnormal Quantitative Sudomotor Axon Reflex Test (P = 0.052), and prior erroneous diagnosis (P = 0.19). In patients who completed IVIG, examinations and questionnaires improved and mean epidermal nerve fiber density increased by 297%.
TS-HDS, FGFR-3, and Plexin D1 antibodies are present in a high proportion of cryptogenic SFN cases with more facial involvement, and greater disease severity is associated with higher antibody titers. They are often misdiagnosed but may respond subjectively and objectively to IVIG.
多达 50%的小纤维神经病 (SFN) 病例为特发性，但新型抗三硫酸肝素二糖 (TS-HDS) 和成纤维细胞生长因子受体 3 (FGFR-3) 抗体已被认为与其中一半病例有关；抗 Plexin D1 的作用尚不清楚。我们旨在阐明这些患者的表现和治疗方法。
一项为期 18 个月的回顾性分析显示，54 例隐源性 SFN 患者进行了 3 种自身抗体检测。分析了人口统计学、临床特征、表皮神经纤维密度和定量汗反射试验结果。评估了静脉注射免疫球蛋白 (IVIG) 治疗反应。
共有 44.4%的患者存在抗体（62.5%为 TS-HDS，29.2%为 FGFR-3，20.8%为 Plexin D1）。男性患者 FGFR-3 阳性的可能性更高（P = 0.014）。血清阳性患者面部受累更常见（P = 0.034），且 Utah 早期神经病量表评分较高的患者 TS-HDS 滴度更高（P = 0.0469），但其他临床特征无显著差异。血清阳性患者 SFN 筛查清单评分较高（P = 0.16）、定量汗反射试验异常（P = 0.052）和先前误诊的趋势更明显（P = 0.19）。在完成 IVIG 治疗的患者中，检查和问卷结果改善，平均表皮神经纤维密度增加 297%。
TS-HDS、FGFR-3 和 Plexin D1 抗体存在于很大比例的隐源性 SFN 病例中，这些患者面部受累更多，疾病严重程度与抗体滴度更高相关。它们经常被误诊，但可能对 IVIG 主观和客观地产生反应。
