Department of Neurology and Department of Pathology (Neuropathology) Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Neurotherapeutics. 2016 Jan;13(1):108-17. doi: 10.1007/s13311-015-0395-1.
The best-known peripheral neuropathies are those affecting the large, myelinated motor and sensory fibers. These have well-established immunological causes and therapies. Far less is known about the somatic and autonomic "small fibers"; the unmyelinated C-fibers, thinly myelinated A-deltas, and postganglionic sympathetics. The small fibers sense pain and itch, innervate internal organs and tissues, and modulate the inflammatory and immune responses. Symptoms of small-fiber neuropathy include chronic pain and itch, sensory impairment, edema, and skin color, temperature, and sweating changes. Small-fiber polyneuropathy (SFPN) also causes cardiovascular, gastrointestinal, and urological symptoms, the neurologic origin of which often remains unrecognized. Routine electrodiagnostic study does not detect SFPN, so skin biopsies immunolabeled to reveal axons are recommended for diagnostic confirmation. Preliminary evidence suggests that dysimmunity causes some cases of small-fiber neuropathy. Several autoimmune diseases, including Sjögren and celiac, are associated with painful small-fiber ganglionopathy and distal axonopathy, and some patients with "idiopathic" SFPN have evidence of organ-specific dysimmunity, including serological markers. Dysimmune SFPN first came into focus in children and teenagers as they lack other risk factors, for example diabetes or toxic exposures. In them, the rudimentary evidence suggests humoral rather than cellular mechanisms and complement consumption. Preliminary evidence supports efficacy of corticosteroids and immunoglobulins in carefully selected children and adult patients. This paper reviews the evidence of immune causality and the limited data regarding immunotherapy for small-fiber-predominant ganglionitis, regional neuropathy (complex regional pain syndrome), and distal SFPN. These demonstrate the need to develop case definitions and outcome metrics to improve diagnosis, enable prospective trials, and dissect the mechanisms of small-fiber neuropathy.
最著名的周围神经病变是那些影响大的、有髓鞘的运动和感觉纤维的病变。这些疾病有明确的免疫学原因和治疗方法。对于躯体和自主的“小纤维”（无髓鞘 C 纤维、薄髓鞘 A-德尔塔纤维和节后交感神经纤维）则知之甚少。小纤维感知疼痛和瘙痒，支配内脏器官和组织，并调节炎症和免疫反应。小纤维神经病的症状包括慢性疼痛和瘙痒、感觉障碍、水肿以及皮肤颜色、温度和出汗变化。小纤维多发性神经病（SFPN）还会引起心血管、胃肠道和泌尿系统症状，其神经起源通常未被识别。常规的电诊断研究无法检测到 SFPN，因此建议进行皮肤活检免疫标记以确认诊断。初步证据表明，免疫失调导致了一些小纤维神经病的发生。包括干燥综合征和乳糜泻在内的几种自身免疫性疾病与疼痛性小纤维节神经病和远端轴索性神经病有关，一些“特发性”SFPN 患者存在器官特异性免疫失调的证据，包括血清标志物。免疫失调性 SFPN 首先在儿童和青少年中引起关注，因为他们缺乏其他风险因素，例如糖尿病或有毒物质暴露。在这些患者中，初步证据表明是体液而不是细胞机制以及补体消耗导致了疾病。在经过精心选择的儿童和成年患者中，皮质类固醇和免疫球蛋白的初步疗效证据支持其治疗作用。本文综述了免疫因果关系的证据，以及针对小纤维为主的节段性神经炎、区域性神经病（复杂性区域疼痛综合征）和远端 SFPN 的有限免疫治疗数据。这些证据表明需要制定病例定义和结果指标，以改善诊断，为前瞻性试验提供可能，并剖析小纤维神经病的发病机制。
