Clinical and laboratory analysis of primary Sjögren′s syndrome complicated with neurological lesions

doi:10.16150/j.1671-2870.2019.01.010

Abstract

Abstract:

Objective: To investigate the clinical manifestations, electromyographic abnormalities and laboratory characteristics of primary Sjögren′s syndrome (pSS) complicated with peripheral neuropathy and to analyze the risk factor of pSS complicated with peripheral neuropathy. Methods: A retrospective analysis was performed on 132 pSS patients who met the 2002 American-European Consensus Group criteria for pSS at Tongji Hospital from January 2015 to September 2017. The patients were categorized into group with peripheral neuropathy (pSS-PNS) and group without peripheral neuropathy (pSS-nPNS). The clinical manifestations, corresponding examinations and laboratory characteristics of the two groups were compared. The data were analyzed by t test, χ² test and logistic regression analysis. Results: A total of 132 patients with pSS were enrolled in this study, including 12 males and 120 females. The ratio of male to female was 1∶10. Among them, 21 patients suffered from peripheral nervous system involvement and the prevalence rate was 15.9%(21/132). There were no significant differences in gender composition, age, onset age and course between the two groups. Compared with the group without peripheral neuropathy, joint swelling and pain (71.4% and 44.1%, P=0.02) were more common in the group with peripheral neuropathy, and CD8 [(21.25±13.11)% and（26.65±9.44）%, P=0.02] decreased significantly, ratio of CD4/CD8(2.80±1.45 vs 1.91±1.12, P=0.04) increased significantly. ESSDAI (European League Against Rheumatism Sjögren′s Syndrome Disease Activity Index) score [(4.71±0.46) and (2.80±0.17) ] was significantly higher in pSS-PNS group. ESSDAI (OR=1.836, 95%CI 1.169-2.883, P=0.008) was an independent risk factor for pSS with peripheral neuropathy. Conclusions: The clinical manifestations of pSS complicated with peripheral neuropathy are diverse, and the disease activity is high. High disease activity is an independent risk factor for Sjögren′s syndrome complicated with peripheral neuropathy.

Key words: Primary Sjögren′s syndrome, Peripheral nervous system lesions, Electromyography, CD4/CD8

CLC Number:

R593.2

WANG Yanqing, HUANG Wanxue, LIANG Yuanyuan, WU Zhenzhen, WANG Xuan, TANG Jianping. Clinical and laboratory analysis of primary Sjögren′s syndrome complicated with neurological lesions[J]. Journal of Diagnostics Concepts & Practice, 2019, 18(1): 51-55.

Figures/Tables 5

组别		抗SSA抗体（+）	抗SSB抗体（+）		抗SSA抗体及抗SSB抗体（+）		抗核抗体颗粒型（+）		抗核抗体均质型（+）	抗核抗体着丝点（+）		唾液腺 ECT		血红蛋白（g/L）		血小板（×10⁹）		白细胞（×10⁹）
pSS-PNS		16(76.1)	5(23.8)		5(23.8)		11(52.3)		1(4.7)	6(28.5)		19(90.4)		115.76±14.48		161.9±44.30		5.17±1.30
pSS-nPNS		84(75.6)	33(29.7)		32(29.7)		64(57.6)		3(2.7)	12(10.8)		89(80.1)		118.03±14.35		188.2±60.81		5.05±1.98
Z值		0.96	0.64		0.58		0.65		0.61	0.03		0.26		-0.54^*		-2.00^*		-1.40^*
P值		1.00	0.77		0.83		0.84		1.00	0.06		0.41		0.59		0.04		0.16
组别	红细胞（×10¹²）			淋巴细胞（×10⁹）		中性粒细胞（×10⁹）		C反应蛋白（mg/L）			红细胞沉降率（mm/h）		CD3(%)		CD4(%)		CD8(%)		CD4/CD8
pSS-PNS	3.93±0.46			1.84±0.71		2.76±0.88		161.95±44.30			5.17±1.30		71.6±13.84		47.7±14.36		21.25±13.11		2.80±1.45
pSS-nPNS	3.94±0.45			1.83±0.71		3.39±4.98		188.20±60.81			5.05±1.98		71.3±12.06		42.3±11.51		26.65±9.44		1.91±1.12
Z值	-0.27			-1.66		-0.15		-0.70			-0.29		-0.56		-1.04		-2.30		-2.02
P值	0.78			0.09		0.88		0.48			0.76		0.57		0.29		0.02		0.04
组别	CD19(%)			补体C₃(g/L)		补体C₄(g/L)		总补体(g/L)			IgA(g/L)		IgM(g/L)		IgG(g/L)		IgE(g/L)		IgG4(g/L)
pSS-PNS	12.0±10.17			0.91±0.22		0.24±0.15		35.20±16.35			2.75±1.13		1.10±0.90		14.92±4.79		122.5±220.2		0.46±0.61
pSS-nPNS	12.85±8.00			0.97±0.23		0.20±0.08		36.34±10.74			2.85±2.44		1.25±0.80		15.29±6.60		78.40±145.3		0.51±0.45
Z值	-0.57			-0.43		-1.19		-0.42			-0.64		-1.44		-0.15		0.53		-0.72
P值	0.56			0.66		0.23		0.67			0.52		0.15		0.88		0.59		0.46
别	肿瘤坏死因子α(μg/L)			IL-2R(ng/L)		IL-6(ng/L)		IL-8(ng/L)			RF(U/mL)		抗CCP (U/mL)		抗双链 DNA抗体
pSS-PNS	10.5±8.2			390±129.8		1.65±1.69		24.65±24.72			13.19±60.44		11.93±13.47		37.9±33.04
pSS-nPNS	9.1±6.3			382±172.2		2.21±2.17		27.50±34.86			8.33±20.87		48.6±228.17		75.6±78.39
Z值	-0.37			-0.22		-0.64		-0.72			-1.90		-0.02		0.41
P值	0.75			0.82		0.52		0.46			0.05		0.98		0.40

References 20

[1]	中华医学会风湿病学分会. 干燥综合征诊断及治疗指南[J]. 中华风湿病学杂志, 2010, 14(11):766-768.
[2]	Hsu CW, Su YJ, Chang WN, et al. The association between serological biomarkers and primary Sjögren′s syndrome associated with peripheral polyneuropathy[J]. Biomed Res Int, 2014, 2014:902492.
[3]	Ramos-Casals M, Solans R, Rosas J, et al. Primary Sjögren syndrome in Spain: clinical and immunologic expression in 1010 patients[J]. Medicine (Baltimore), 2008, 87(4):210-219.
[4]	Vitali C, Bombardieri S, Jonsson R, et al. Classification criteria for Sjögren′s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group[J]. Ann Rheum Dis, 2002, 61(6):554-558.
[5]	Seror R, Ravaud P, Bowman SJ, et al. EULAR Sjogren′s syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjögren′s syndrome[J]. Ann Rheum Dis, 2010, 69(6):1103-1109.
[6]	Carvajal Alegria G, Guellec D, Mariette X, et al. Epidemiology of neurological manifestations in Sjögren′s syndrome: data from the French ASSESS Cohort[J]. RMD Open, 2016, 2(1):e000179.
[7]	刘佩玲, 高照猛, 赵金霞, 等. 原发性干燥综合征合并神经系统受累的临床特点分析[J]. 中华风湿病学杂志, 2017, 21(6):375-380.
[8]	冯敏, 何菁, 丁艳, 等. 原发性干燥综合征患者合并周围神经病的临床和实验室特点[J]. 中华风湿病学杂志, 2013, 17(2):91-94.
[9]	陈梅卿, 李燕, 刘晓燕, 等. 原发性干燥综合征患者周围神经病变临床分析[J]. 中华风湿病学杂志, 2014, 18(7):455-459.
[10]	Mekinian A, Ravaud P, Hatron PY, et al. Efficacy of rituximab in primary Sjögren′s syndrome with peripheral nervous system involvement: results from the AIR registry[J]. Ann Rheum Dis, 2012, 71(1):84-87.
[11]	Aluri HS, Samizadeh M, Edman MC, et al. Delivery of bone marrow-derived mesenchymal stem cells improves tear production in a mouse model of Sjögren′s syndrome[J]. Stem Cells Int, 2017, 2017:3134543.
[12]	阮光峰, 黄家树, 黄琬雪, 等. 间充质干细胞对干燥综合征模型小鼠治疗效应的研究[J]. 同济大学学报(医学版), 2016, 37(1):7-11.
[13]	路臻豪, 汤建平. 间充质干细胞在干燥综合征发病机制中的作用与治疗前景[J]. 中华风湿病学杂志, 2013, 17(7):492-494.
[14]	Davis BN, Hilyard AC, Lagna G, et al. SMAD proteins control DROSHA-mediated microRNA maturation[J]. Nature, 2008, 454(7200):56-61.
[15]	Maurer B, Stanczyk J, Jüngel A, et al. MicroRNA-29, a key regulator of collagen expression in systemic sclerosis[J]. Arthritis Rheum, 2010, 62(6):1733-1743.
[16]	Cacchiarelli D, Martone J, Girardi E, et al. MicroRNAs involved in molecular circuitries relevant for the Duchenne muscular dystrophy pathogenesis are controlled by the dystrophin/nNOS pathway[J]. Cell Metab, 2010, 12(4):341-351.
[17]	Fleissner F, Jazbutyte V, Fiedler J, et al. Short communication: asymmetric dimethylarginine impairs angiogenic progenitor cell function in patients with coronary artery disease through a microRNA-21-dependent mechanism[J]. Circ Res, 2010, 107(1):138-143.
[18]	McCoy CE, Sheedy FJ, Qualls JE, et al. IL-10 inhibits miR-155 induction by toll-like receptors[J]. J Biol Chem, 2010, 285(27):20492-20498.
[19]	龚邦东, 路臻豪, 景波, 等. 间充质干细胞对干燥综合征患者活化CD4⁺T细胞miRNA表达谱的影响[J]. 中华风湿病学杂志, 2015(7):435-439.
[20]	房星星, 路臻豪, 汤建平, 等. MSCs通过促分泌TGF-β1、IL-6和IL-10抑制干燥综合征患者CD4⁺T细胞的活化增殖[J]. 同济大学学报(医学版), 2016, 37(4):31-35.

组别	年龄（岁）	发病年龄（年）	发病病程（个月）	住院时间（d）
pSS-PNS	57.56±14.45	49.7±13.86	97.20±101.04	8.67±2.85
pSS-nPNS	62.86±9.83	52.5±10.57	123.4±115.55	8.12±2.76
Z值	-1.80	-0.78	-1.20	-0.80
P值	0.07	0.43	0.22	0.44

肌电图表现	例数（n）
上肢神经损害	10
下肢神经损害	12
单神经病变	10
多神经病变	11
运动神经损害为主	13
感觉神经损害为主	8

组别	眼干	口干	皮疹	雷诺表现	口腔溃疡	龋齿	关节肿痛	肢体麻木	甲状腺累及	间质性肺炎
pSS-PNS	17（80.9）	19（90.4）	4（19）	4（19）	7（33.3）	14（66.6）	15（71.4）	13（61.9）	2（9.5）	8（38.0）
pSS-nPNS	76（68.4）	89（80.1）	26（23.4）	19（17.1）	21（18.9）	111（60.3）	49（44.1）	29（26.1）	16（14.1）	27（24.3）
χ²值	1.32	1.26	0.19	0.05	0.25	0.3	5.26	10.42	0.36	1.72
P值	0.31	0.36	0.78	0.76	0.61	0.63	0.02	0.001	0.73	0.19

变量	B	S.E.	Wals	OR值	P值	95% CI
ESSDAI	0.608	0.230	6.959	1.836	0.008	1.169~2.883
血小板计数	-0.005	0.007	0.442	0.995	0.506	0.982~1.009
CD8	-0.051	0.055	0.868	0.950	0.352	0.853~1.058
CD4/CD8	0.428	0.412	1.078	1.533	0.299	0.684~3.437
关节肿痛	-0.306	0.825	0.137	0.736	0.711	0.146~3.713