血管炎性周围神经病临床病理学研究

Clinicopathological study of vasculitic peripheral neuropathy

目的总结不同类型血管炎性周围神经病临床和病理学特点,提出病理诊断要点以指导临床诊断。方法回顾分析11例血管炎性周围神经病患者之临床表现、实验室检查和神经肌肉组织活检特点,观察神经、肌肉和皮肤组织病变。通过免疫组织化学染色检测神经微丝蛋白、髓鞘碱性蛋白、外周髓鞘蛋白22、S-100蛋白,以及人类白细胞抗原DR、CD68、CD3、CD20表达变化,分别观察神经轴索、髓鞘、施万细胞病变和炎性细胞浸润情况;免疫荧光染色检测免疫球蛋白IgA、IgM、IgG和补体C3在血管壁沉积情况;特殊染色检测肌肉病变程度。结果血管病变以神经束周和外膜小血管CD3+T细胞浸润为主,呈活动性血管炎(3例)或非活动性血管炎(8例)改变,8例中4例呈血管纤维闭塞性改变严重、炎性细胞浸润较轻,4例以血管周围炎为主、血管壁本身病变不明显。神经病变以轴索变性为主(6例)或轴索变性伴髓鞘松解和脱失(5例),大直径有髓纤维明显减少,甚至呈终末期改变。肌肉组织活检呈神经源性萎缩。病理诊断为系统性血管炎性周围神经病8例[原发性系统性血管炎5例(抗中性粒细胞胞质抗体相关性小血管炎2例、Churg-Strauss综合征1例、免疫相关性间质性肺疾病2例)和继发性系统性血管炎3例(干燥综合征)],以及非系统性血管炎性周围神经病3例。结论血管炎性周围神经病的神经改变以轴索病变为主,血管炎病理改变呈多样性,不能仅以活动性血管炎作为唯一的病理诊断标准。因此对于临床可疑血管炎性周围神经病患者应完善血液免疫学指标检查和神经组织活检,必要时联合肌肉组织活检以明确诊断。

Objective To summarize the clinical features and neuropathological characteristics in patients with vasculitic peripheral neuropathy （VPN）. Methods Clinical manifestations, laboratory examination and neuromuscular biopsy characteristics of 11 patients with VPN were retrospectively analyzed. The lesion of nerve, muscle and skin was observed under optical and electron microscope. Immunohistochemical analyses were carried out to detect neurofilament （NF）, myelin basic protein （MBP）, peripheral myelin protein 22 （PMP22） and S-100 protein （S-100） and further observing the neuropathy of neuraxon, myelin sheath and Schwann cells, and to detect human leukocyte antigen DR （HLA-DR）, CD68, CD3 and CD20 to observe inflammatory cell infiltration. Immunofluorescent staining was used to detect the deposition of IgA, lgM, IgG and addiment C3 on vascular wall. The staining of periodic acid-Schiff （PAS）, NADH-tetrazolium reductase （NADH-TR） and modified Gomori trichrome （MGT） were used to judge the myopathy. Results 1） Angiopathies were mainly manifested by small vessels of epineurium and perineurium, and infiltrated inflammatory cells were mainly CD3 ＋ T cells. Three patients had active vasculitis, and 8 patients had non-active vaseuhtis. Among these 8 patients, 4 patients mainly presented fibrous obliteration of blood vessel, with slight inflammatroy cell infiltration, and the other 4 patients mainly showed perivascular inflammation. 2） Neuropathy： 6 patients had axon degeneration, and 5 patients had axon degeneration associated with demyelination. All of them demonstrated a reduction in myelinated fibers, mainly large diameter myelinated fibers, even on end-stage. 3） Muscle biopsy showed neurogenic atrophy. 4） Clinicopathologic diagnosis： among these 11 patients, 8 patients were diagnosed as systemic vasculitic peripheral neuropathy （SVPN）, among whom 5 patients were diagnosed as primary systemic vasculitis [including 1 patient as Churg-Strauss syndrome （CSS）, 2 patients as anti-neutrophil cytoplasmic antibody （ANCA）-associated vasculitis and 2 patients as immuno-mediated interstitial lung disease （ILD）], and 3 patients were diagnosed as secondary systemic vaseulitis. The other 3 patients were diagnosed as nonsystemie vasculitic periphral neuropathy （NSVPN）. Conclusions The pathological features of VPN showed that the axonal degeneration was more serious than the myelin lesions because axons were more vulnerable to ischemia than Schwann cells, perineurial cells and fibroblasts. The pathology of VPN are diverse, which are associated with the disease progression and treatment, and therefore the hemoimmunologic parameters, nerve and muscle biopsy should be checked when the VPN is suspected.