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【摘要】 目的 研究类风湿关节炎患者的泪液动力学与一些免疫因子的相关性。方法 对10例住院诊断为类风湿关节炎的患者进行研究。对患者进行基础泪液分泌试验(Schirmer Ⅰ test)及泪膜破裂时间(BUT)检查。收集患者红细胞沉降率(ESR),免疫球蛋白M(IgM),风湿因子(RF),抗环瓜氨酸肽抗体(anti-CCP antibody)检查结果。前两项作为类风湿关节炎的活动指标,后两项作为诊断指标。通过Pearson相关分析检验对泪液动力学指标与免疫因子之间的相关性。结果 患者的平均SchirmerⅠ试验是右眼(8.8±7.6)mm,左眼(5.8±3.4)mm,平均BUT为右眼(4.3±3.2)s,左眼(4.6± 3.5)s。双眼的SchirmerⅠ试验及BUT差异无统计学意义。患者的右眼基础泪液分泌或BUT与ESR、IgM、RF及anti-CCP抗体均没有统计学相关关系。结论对于类风湿关节炎患者,无论其活动性如何,均应该关注患者的干眼情况。
【关键词】泪液动力学;类风湿关节炎
Correlation between tear dynamics and immunological factors in patients with rheumatoid arthritis
GUO Hui,LAN Yu-qing,HU Yu-xin,et al.Department of Ophthalmology,Sun Yat-sen Memorial Hospital of Sun Yat-sen University,Guangzhou 510120,China
【Abstract】 Objective To evaluate the correlation between tear dynamics and some immunological factors in rheumatoid arthritis(RA)patients.Methods In 10 RA patients,the tear dynamics were assessed by the Schirmer Ⅰ test and tear break-up time(BUT).Edimentation rate(ESR),immunoglobulin M(IgM),rheumatoid factors(RF)and Anti-citrullinated protein antibody(Anti-ccp antibody)were collected.The first two were correlated with the RA activity and the last two were correlated with the diagnoses of RA.Pearson correlation test was used to analyze the correlation between the two indexes of the right eye and the four immunological factors respectively.Results The mean SchirmerⅠtest was (8.8±7.6)mm in the right eyes and(5.8±3.4)mmin the left eyes.The mean BUT was (4.3±3.2)seconds in the right eyes and(4.6± 3.5)seconds in the left eyes.No difference was observed in SchirmerⅠtest as well as BUTbetween the right eyes and the left eyes.No correlations were found between SchirmerⅠtest of the right eyes and ESR,IgM,RF nor Anti-ccp antibody.Also,no correlations were found between BUT of the right eyes and ESR,IgM,RF nor Anti-ccp antibody.Conclusion Abnormality of tear dynamics is common in RA patients and should be taken into consideration regardless of the RA activity and the immunological factors about the diagnoses of RA.More studies should be conducted to prove the results in this paper.
【Key words】
Tear dynamic; Rheumatoid arthritis
干眼即一组由不同原因引起泪膜和或眼表异常的状况[1]。国外的文献报道干眼在普通人群中的发病率为5%~17%[2-4],而在类风湿关节炎中的发病率为19%~31%[5,6],虽然干眼在青少年类风湿关节炎中的发生率仅10.9%,但是与对照组相比有显著统计学差异[7]。更有报道认为类风湿的严重性对于干眼的发生存在相关性[8]。因此,为了探究干眼的程度与类风湿关节炎的关系,对我院住院诊断为类风湿关节炎的患者进行眼部检查,以分析泪液动力学与一些风湿相关因子的相关性。
1 资料和方法
1.1 临床资料
收集2010年1~3月在中山大学附属第二医院风湿科住院诊断为类风湿关节炎的连续病例。入选患者均没有长期使用眼药水的病史。将合并糖尿病、系统性红斑狼疮、原发性干燥综合征、曾进行眼部手术的患者剔除。共10例,男2例,女8例,男女比例1:4,年龄24~69岁,平均50岁。
1.2 检查项目
1.2.1 眼部检查 眼部检查均由同一医师进行。裂隙灯下行0.25%角膜荧光(fluorescent,Fl)染色,泪膜破裂时间(break up time,BUT)检查;基础泪液分泌试验(Schirmer Ⅰ test,SⅠt):结膜囊表面麻醉后,将滤纸置于下睑内1/3,记录5 min时长。
1.2.2 实验室检查 收集患者红细胞沉降率(ESR),IgM,类风湿因子(RF),抗环瓜氨酸肽抗体(anti-CCP antibody)数据。
1.3 统计方法 本研究中对患者各检查指标进行正态分布检验,如果符合正态分布则对双眼检查指标进行配对t检验,否则用配对秩合检验;选取右眼检查指标与实验室检查指标进行相关分析,如果参数符合正态分布用pearson相关系数,否则用spearman相关系数。统计均用SPSS 13.0软件包进行分析。设定P<0.05作为差异有统计学意义。
2 结果
对各组检测指标进行正态分布检验,均符合正态分布。10例患者的SchirmerⅠ检验平均为右眼(8.8±7.6)mm,左眼(5.8±3.4)mm,BUT均为右眼(4.3±3.2)s,左眼(4.6±3.5)s。双眼的SchirmerⅠ检验及BUT均没有统计学差异(前者P=0.163,后者P=0.604)。右眼的SchirmerⅠ检验及BUT与ESR、IgM、RF和Anti-ccp抗体的相关分析见表1。
表1
泪液动力检验与免疫因子的相关分析P值
ESRIgMRFAnti-ccp antibody
SⅠt0.180.120.320.37
BUT0.450.860.190.25
3 讨论
类风湿关节炎是一种系统性免疫混乱疾病,导致炎症性、对称性多关节炎,并容易引起关节结构破坏、变形、功能丧失[9]。干眼或泪液功能异常综合征是泪液或眼表的多因素疾病,导致眼部不适、视力下降或泪膜不稳定[10]。泪液功能单位包括泪腺、眼表、眼睑、睑板腺及相关的感觉、运动神经[11]。泪液功能单位任何组成部分的功能障碍均可以导致干眼的发生。与干眼发生的危险因素包括年龄、激素、药物、免疫、营养、基因、感染、炎症、外伤或精神因素[8]。虽然众多的文献均表明干眼与类风湿关节炎密切相关[9,12],但是干眼的严重程度与类风湿关节炎的活动性的内在联系却至今不明确。因此,本文针对该问题对类风湿关节炎的患者的泪液动力学及一些与类风湿关节炎相关的免疫因子进行相关分析。
RF是一种自身免疫抗体,在类风湿关节炎的诊断中广泛应用,大约80%的类风湿关节炎患者显示阳性结果。Anti-ccp抗体与RF对于类风湿关节炎的诊断的敏感度相似,但是前者较后者的特异性更强。RF及Anti-ccp抗体对于早期的类风湿关节炎的诊断有一定的价值。如果RF及Anti-ccp抗体均阳性,对于类风湿关节炎诊断的特异性增加至95%[13]。ESR及IgM均反映炎症的活动情况。对于泪液缺乏性干眼的检查,最常用和最简单的是Schirmer Ⅰ检验[14],有文章报道基础泪液分泌实验对于诊断Sjogren综合征有77%的敏感度及72%的特异度[15]。因此,本文将泪眼动力学指标与上述四个炎症因子进行相关分析,期待找出干眼与类风湿关节炎的一些内在联系。
通过统计学分析,类风湿关节炎患者的泪液动力学指标(Schirmer Ⅰ检验与BUT)与RF、Anti-ccp抗体、ESR及IgM均没有统计学相关关系。MIHO等[16]的研究中指出,在没有合并Sjogren综合征的类风湿关节炎患者中,Schirmer Ⅰ检验及BUT与ESR或Lansbury指数没有相关关系。Polanska的研究也指出干眼与RF及类风湿关节炎的严重程度没有相关关系[17],这些研究的结论与本文结论相似。
虽然目前干眼的发病机制没有完全清楚,但是炎症是最常见的因素[18]。在过去的研究中,有认为虽然唾液的分泌与血清免疫因子抗核抗体和抗SSA/SSB存在相关关系,但是基础泪液分泌与这些免疫因子之间没有相关关系[19]。然而,也有研究发现血清抗RO/SSA与基础泪液分泌成负相关,与干眼症状评分成正相关[20]。此外,一些细胞因子如白细胞介素-2、白细胞介素-4、白细胞介素-5、白细胞介素-6、白细胞介素-10、γ-干扰素、α-肿瘤坏死因子、白细胞介素-1β和白细胞介素-8均在干眼患者的泪液中明显升高[21]。干眼与一系列炎症因子的内在联系还有待进一步深入研究。
本文的研究有一定的局限性。虽然本文的研究结果与既往国外的研究结果有相符的地方,但是本文的研究例数不多,而且没有将是否合并Sjogren综合征的类风湿关节炎患者进行分组统计。此外,由于干眼症可以由于药物的使用导致,如果仅对首诊类风湿关节炎的患者进行研究可以更好的排除这些干扰因素。因此,日后的研究可以巡这些方面进一步改进。
根据本文的结果对于临床有一些提示。干眼的发生虽然在类风湿关节炎的患者中多见,但是实验室未确诊的类风湿关节炎的患者并不能排除干眼的发生,而且,干眼的加重不一定与类风湿关节炎的活动成正相关;此外,即使患者没有干眼症状,泪液动力学可能已经发生异常[14],因此,对于类风湿关节炎确诊或疑似患者均应该关注有无泪液动力学异常,及早对症治疗,以避免干燥性角结膜炎甚至角膜溃疡的发生。
参考文献
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[8] Wolfe F,Michaud K.Prevalence,risk,and risk factors for oral and ocular dryness with particular emphasis on rheumatoid arthritis.The Journal of rheumatology,2008,35(6):1023-1030.
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[14] Hay EM,Thomas E,Pal B,Hajeer A,Chambers H,Silman AJ.Weak association between subjective symptoms or and objective testing for dry eyes and dry mouth:results from a population based study.Annals of the rheumatic diseases,1998,57(1):20-24.
[15] Vitali C,Moutsopoulos HM,Bombardieri S.The European Community Study Group on diagnostic criteria for Sjogren’s syndrome.Sensitivity and specificity of tests for ocular and oral involvement in Sjogren’s syndrome.Annals of the rheumatic diseases,1994,53(10):637-647.
[16] Fujita M,Igarashi T,Kurai T,Sakane M,Yoshino S,Takahashi H.Correlation between dry eye and rheumatoid arthritis activity.American journal of ophthalmology,2005,140(5):808-813.
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[18] Behrens A,Doyle JJ,Stern L,et al.Dysfunctional tear syndrome:a Delphi approach to treatment recommendations.Cornea,2006,25(8):900-907.
[19] Haga HJ.Clinical and immunological factors associated with low lacrimal and salivary flow rate in patients with primary Sjogren’s syndrome.The Journal of rheumatology,2002,29(2):305-308.
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【关键词】泪液动力学;类风湿关节炎
Correlation between tear dynamics and immunological factors in patients with rheumatoid arthritis
GUO Hui,LAN Yu-qing,HU Yu-xin,et al.Department of Ophthalmology,Sun Yat-sen Memorial Hospital of Sun Yat-sen University,Guangzhou 510120,China
【Abstract】 Objective To evaluate the correlation between tear dynamics and some immunological factors in rheumatoid arthritis(RA)patients.Methods In 10 RA patients,the tear dynamics were assessed by the Schirmer Ⅰ test and tear break-up time(BUT).Edimentation rate(ESR),immunoglobulin M(IgM),rheumatoid factors(RF)and Anti-citrullinated protein antibody(Anti-ccp antibody)were collected.The first two were correlated with the RA activity and the last two were correlated with the diagnoses of RA.Pearson correlation test was used to analyze the correlation between the two indexes of the right eye and the four immunological factors respectively.Results The mean SchirmerⅠtest was (8.8±7.6)mm in the right eyes and(5.8±3.4)mmin the left eyes.The mean BUT was (4.3±3.2)seconds in the right eyes and(4.6± 3.5)seconds in the left eyes.No difference was observed in SchirmerⅠtest as well as BUTbetween the right eyes and the left eyes.No correlations were found between SchirmerⅠtest of the right eyes and ESR,IgM,RF nor Anti-ccp antibody.Also,no correlations were found between BUT of the right eyes and ESR,IgM,RF nor Anti-ccp antibody.Conclusion Abnormality of tear dynamics is common in RA patients and should be taken into consideration regardless of the RA activity and the immunological factors about the diagnoses of RA.More studies should be conducted to prove the results in this paper.
【Key words】
Tear dynamic; Rheumatoid arthritis
干眼即一组由不同原因引起泪膜和或眼表异常的状况[1]。国外的文献报道干眼在普通人群中的发病率为5%~17%[2-4],而在类风湿关节炎中的发病率为19%~31%[5,6],虽然干眼在青少年类风湿关节炎中的发生率仅10.9%,但是与对照组相比有显著统计学差异[7]。更有报道认为类风湿的严重性对于干眼的发生存在相关性[8]。因此,为了探究干眼的程度与类风湿关节炎的关系,对我院住院诊断为类风湿关节炎的患者进行眼部检查,以分析泪液动力学与一些风湿相关因子的相关性。
1 资料和方法
1.1 临床资料
收集2010年1~3月在中山大学附属第二医院风湿科住院诊断为类风湿关节炎的连续病例。入选患者均没有长期使用眼药水的病史。将合并糖尿病、系统性红斑狼疮、原发性干燥综合征、曾进行眼部手术的患者剔除。共10例,男2例,女8例,男女比例1:4,年龄24~69岁,平均50岁。
1.2 检查项目
1.2.1 眼部检查 眼部检查均由同一医师进行。裂隙灯下行0.25%角膜荧光(fluorescent,Fl)染色,泪膜破裂时间(break up time,BUT)检查;基础泪液分泌试验(Schirmer Ⅰ test,SⅠt):结膜囊表面麻醉后,将滤纸置于下睑内1/3,记录5 min时长。
1.2.2 实验室检查 收集患者红细胞沉降率(ESR),IgM,类风湿因子(RF),抗环瓜氨酸肽抗体(anti-CCP antibody)数据。
1.3 统计方法 本研究中对患者各检查指标进行正态分布检验,如果符合正态分布则对双眼检查指标进行配对t检验,否则用配对秩合检验;选取右眼检查指标与实验室检查指标进行相关分析,如果参数符合正态分布用pearson相关系数,否则用spearman相关系数。统计均用SPSS 13.0软件包进行分析。设定P<0.05作为差异有统计学意义。
2 结果
对各组检测指标进行正态分布检验,均符合正态分布。10例患者的SchirmerⅠ检验平均为右眼(8.8±7.6)mm,左眼(5.8±3.4)mm,BUT均为右眼(4.3±3.2)s,左眼(4.6±3.5)s。双眼的SchirmerⅠ检验及BUT均没有统计学差异(前者P=0.163,后者P=0.604)。右眼的SchirmerⅠ检验及BUT与ESR、IgM、RF和Anti-ccp抗体的相关分析见表1。
表1
泪液动力检验与免疫因子的相关分析P值
ESRIgMRFAnti-ccp antibody
SⅠt0.180.120.320.37
BUT0.450.860.190.25
3 讨论
类风湿关节炎是一种系统性免疫混乱疾病,导致炎症性、对称性多关节炎,并容易引起关节结构破坏、变形、功能丧失[9]。干眼或泪液功能异常综合征是泪液或眼表的多因素疾病,导致眼部不适、视力下降或泪膜不稳定[10]。泪液功能单位包括泪腺、眼表、眼睑、睑板腺及相关的感觉、运动神经[11]。泪液功能单位任何组成部分的功能障碍均可以导致干眼的发生。与干眼发生的危险因素包括年龄、激素、药物、免疫、营养、基因、感染、炎症、外伤或精神因素[8]。虽然众多的文献均表明干眼与类风湿关节炎密切相关[9,12],但是干眼的严重程度与类风湿关节炎的活动性的内在联系却至今不明确。因此,本文针对该问题对类风湿关节炎的患者的泪液动力学及一些与类风湿关节炎相关的免疫因子进行相关分析。
RF是一种自身免疫抗体,在类风湿关节炎的诊断中广泛应用,大约80%的类风湿关节炎患者显示阳性结果。Anti-ccp抗体与RF对于类风湿关节炎的诊断的敏感度相似,但是前者较后者的特异性更强。RF及Anti-ccp抗体对于早期的类风湿关节炎的诊断有一定的价值。如果RF及Anti-ccp抗体均阳性,对于类风湿关节炎诊断的特异性增加至95%[13]。ESR及IgM均反映炎症的活动情况。对于泪液缺乏性干眼的检查,最常用和最简单的是Schirmer Ⅰ检验[14],有文章报道基础泪液分泌实验对于诊断Sjogren综合征有77%的敏感度及72%的特异度[15]。因此,本文将泪眼动力学指标与上述四个炎症因子进行相关分析,期待找出干眼与类风湿关节炎的一些内在联系。
通过统计学分析,类风湿关节炎患者的泪液动力学指标(Schirmer Ⅰ检验与BUT)与RF、Anti-ccp抗体、ESR及IgM均没有统计学相关关系。MIHO等[16]的研究中指出,在没有合并Sjogren综合征的类风湿关节炎患者中,Schirmer Ⅰ检验及BUT与ESR或Lansbury指数没有相关关系。Polanska的研究也指出干眼与RF及类风湿关节炎的严重程度没有相关关系[17],这些研究的结论与本文结论相似。
虽然目前干眼的发病机制没有完全清楚,但是炎症是最常见的因素[18]。在过去的研究中,有认为虽然唾液的分泌与血清免疫因子抗核抗体和抗SSA/SSB存在相关关系,但是基础泪液分泌与这些免疫因子之间没有相关关系[19]。然而,也有研究发现血清抗RO/SSA与基础泪液分泌成负相关,与干眼症状评分成正相关[20]。此外,一些细胞因子如白细胞介素-2、白细胞介素-4、白细胞介素-5、白细胞介素-6、白细胞介素-10、γ-干扰素、α-肿瘤坏死因子、白细胞介素-1β和白细胞介素-8均在干眼患者的泪液中明显升高[21]。干眼与一系列炎症因子的内在联系还有待进一步深入研究。
本文的研究有一定的局限性。虽然本文的研究结果与既往国外的研究结果有相符的地方,但是本文的研究例数不多,而且没有将是否合并Sjogren综合征的类风湿关节炎患者进行分组统计。此外,由于干眼症可以由于药物的使用导致,如果仅对首诊类风湿关节炎的患者进行研究可以更好的排除这些干扰因素。因此,日后的研究可以巡这些方面进一步改进。
根据本文的结果对于临床有一些提示。干眼的发生虽然在类风湿关节炎的患者中多见,但是实验室未确诊的类风湿关节炎的患者并不能排除干眼的发生,而且,干眼的加重不一定与类风湿关节炎的活动成正相关;此外,即使患者没有干眼症状,泪液动力学可能已经发生异常[14],因此,对于类风湿关节炎确诊或疑似患者均应该关注有无泪液动力学异常,及早对症治疗,以避免干燥性角结膜炎甚至角膜溃疡的发生。
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