摘要目的 通过皮肤环钻活检检测疑似或确诊糖尿病周围神经病变(DPN)患者的小纤维神经损伤情况并分析不同类型DPN患者的临床及皮肤病理特征.方法 收集2015年12月至2018年2月诊治的疑似或确诊DPN的患者37例,所有患者行皮肤环钻活检并通过免疫荧光染色进行表皮内神经纤维密度(IENFD)计数,同时行周围神经损伤症状及体征检查、神经传导速度检测.采集15例无糖尿病及周围神经病变者作为正常对照组.使用正常对照组IENFD的第五百分位数作为DPN的诊断切点.采用χ2检验分析皮肤环钻活检对DPN诊断率的影响,独立样本t检验及秩和检验比较仅小纤维神经受累的DPN患者与大小纤维神经均受累的DPN患者临床及皮肤病理特征差异性.结果正常对照组小腿平均IENFD为(13.4±0.8)根/mm,诊断切点为13.0根/mm;大腿平均IENFD为(21.1±5.9)根/mm,诊断切点为11.4根/mm.根据该切点,纳入的37例糖尿病患者中35例可确诊DPN,包括8例仅小纤维神经受累者及27例大小纤维神经均受累者,DPN诊断率由73％(27/37)提高至95％(35/37)(P<0.05).仅小纤维神经受累者较大小纤维神经均受累者糖化血红蛋白水平低,糖尿病视网膜病变、肾病、心血管自主神经病变发生率低.仅小纤维神经受累者较大小纤维神经均受累者大腿IENFD高[(8.8±2.6)比(4.5±1.8)根/mm,t=5.424,P<0.01],两组患者小腿IENFD均较正常对照组显著下降,但组间未见统计学差异[(1.5±1.2)比(2.5±1.3)根/mm,t=-1.965,P>0.05].结论 皮肤环钻活检可显著提高DPN确诊率及临床诊断率,是临床诊断糖尿病小纤维神经病变的重要工具.

abstractsObjective To detect small fiber neuropathy in patients with possible or established diabetic peripheral neuropathy (DPN) by skin punch biopsy and explore clinical characteristics and pathological features in different DPN patients. Methods A total of 37 patients were collected with possible or established DPN from December 2015 to February 2018. All patients underwent skin punch biopsy, intra epidermal nerve fiber density (IENFD) calculation, nerve conduction studies and clinical examination of neurological signs and symptoms. Fifteen healthy subjects were set as control. Chi-square test was used to analyze the impact of biopsy on DPN diagnosis rate. Student t test and Wilcoxon rank sum test were utilized to compare the difference of clinical characteristic and pathological feature between two subtypes of DPN patients. Results The average IENFD in control was (13.4 ± 0.8) fiber/mm in calf and (21.1 ± 5.9) fiber/mm in thigh while the diagnostic cutoff point of DPN was 13.0 fiber/mm in calf and 11.4 fiber/mm in thigh, respectively. Among total 37 patients, 35 were diagnosed as small fiber neuropathy by using skin punch biopsy and the proportion of DPN raised from 73％(27/37) to 95％(35/37) (P<0.05), which included 8 patients with primarily small fiber neuropathy and 27 patients with mixed small and large fiber neuropathy. Patients with primarily small fiber neuropathy had lower level of glycated hemoglobin A1c, lower&nbsp;proportion of diabetic retinopathy, nephropathy and cardiovascular autonomic neuropathy and higher IENFD in thigh [(8.8 ± 2.6) vs (4.5 ± 1.8) fiber/mm, t=5.424, P<0.01] than patients with mixed small and large fiber neuropathy. IENFD in calf was not significantly different between groups [(1.5±1.2) vs (2.5±1.3) fiber/mm, t=-1.965, P>0.05]. Conclusion Skin punch biopsy can significantly improve DPN diagnosis rate and is an important tool for identifying diabetic small fiber neuropathy.