同时评估大动脉炎患者的不宁腿综合征、神经性疼痛、疾病活动和生活质量：一项横断面研究-动脉网

Simultaneous evaluation of restless leg syndrome, neuropathic pain, disease activity, and quality of life in patients with Takayasu arteritis: a cross-sectional study

Nature 等信源发布 2025-01-25 11:49

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Abstract

摘要

We aimed to investigate the frequency of restless legs syndrome (RLS) and neuropathic pain (NeP) in patients with Takayasu arteritis (TAK), and their relationship with disease activity, and quality of life (QoL). In this prospective case-control study, we evaluated 30 patients with TAK and 28 healthy subjects.

。在这项前瞻性病例对照研究中，我们评估了30名TAK患者和28名健康受试者。

Demographic, clinical, and current treatment-related data were also recorded. RLS diagnosis was confirmed in both groups according to the International Restless Legs Study Group criteria. The Douleur neuropathic-4 questionnaire (DN4) confirmed the frequency of neuropathic pain, and the quality of life was confirmed by the Short Form 36 (SF-36) health survey questionnaire.

还记录了人口统计学，临床和当前治疗相关数据。根据国际不宁腿研究组的标准，两组均确诊为RLS。Douleur neuropathic-4问卷（DN4）证实了神经性疼痛的频率，生活质量通过简表36（SF-36）健康调查问卷得到证实。

Univariate logistic regression analyses were performed to estimate the odds ratio (OR) for factors associated with NeP in patients with TAK. There was no statistically significant difference in the diagnosis of RLS between the TAK group and the control group (.

进行单因素logistic回归分析以估计TAK患者与NeP相关因素的优势比（OR）。TAK组和对照组之间RLS的诊断无统计学差异（。

= 0.195). The prevalence of NeP was significantly higher in TAK patients than in healthy controls (

0.195）。TAK患者的NeP患病率明显高于健康对照组(

= 0.011). The SF-36 subscale scores for physical functioning (

0.011）。SF-36身体机能分量表得分(

= 0.01) and general health (

= 0.01）和一般健康(

= 0.002) were significantly lower in the TAK group than in the control group. Vasculitis Damage Index (VDI) scores were considerably higher in patients with NeP (

0.002）显着低于对照组。NeP患者的血管炎损伤指数（VDI）评分明显较高(

= 0.004). In univariate analyses, VDI decreased unbound iron-binding capacity, and SF36 mental component summary were predictors associated with NeP. This study revealed that the frequency of NeP was higher in patients with TAK than in the healthy population, and the patients with TAK were negatively affected in terms of NeP and QoL rather than RLS..

= 0.004）。在单因素分析中，VDI降低了未结合的铁结合能力，SF36心理成分总结是与NeP相关的预测因子。这项研究表明，TAK患者的NeP频率高于健康人群，TAK患者在NeP和QoL方面受到负面影响，而不是RLS。。

Introduction

简介

Takayasu arteritis (TAK) is a rare granulomatous panarteritis affecting the aorta and its main branches, characterized by lymphocytic infiltration and granuloma formation, especially in the media and adventitia layers of the vessel wall. In the following period, degeneration, adventitial fibrosis, and neovascularization occur in the internal elastic lamina of the media layer.

大动脉炎（TAK）是一种罕见的肉芽肿性大动脉炎，影响主动脉及其主要分支，其特征是淋巴细胞浸润和肉芽肿形成，尤其是在血管壁的中膜和外膜层。。

. Patients may present with constitutional symptoms such as weakness, fatigue, muscle, and joint pain caused by systemic inflammation, and claudication in the extremities because of decreased blood flow due to vascular involvement

。患者可能会出现体质症状，例如全身炎症引起的虚弱，疲劳，肌肉和关节疼痛，以及由于血管受累导致血流量减少而导致四肢跛行

Restless legs syndrome (RLS) is a neurological disorder defined by a leg discomfort that occurs at night and at rest and the need to move the limbs to reduce this feeling

不宁腿综合征（RLS）是一种神经系统疾病，由夜间和休息时发生的腿部不适以及需要移动四肢以减轻这种感觉所定义

. Many studies have shown that RLS, seen with a frequency of 5–10% in the general population

许多研究表明，RLS在普通人群中的发生率为5-10%

, increases in frequency in rheumatic diseases

，风湿性疾病的频率增加

. Because of RLS symptoms can resemble and be confused with symptoms of rheumatological diseases, rheumatologists need to be able to identify, differentiate, diagnose, and treat RLS

由于RLS症状可能类似于风湿病的症状，并与风湿病的症状混淆，因此风湿病学家需要能够识别，鉴别，诊断和治疗RLS

Peripheral neuropathy is a clinical condition that occurs due to the involvement of vasa nervorum, especially in medium and small vessel vasculitis

周围神经病是一种由于神经血管受累而发生的临床疾病，尤其是在中、小血管炎中

. The prevalence of neuropathic pain (NeP) has been shown to increase in vasculitis including cryoglobulinemic vasculitis, polyarteritis nodosa (PAN), eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and granulomatosis polyangiitis (GPA)

神经病理性疼痛（NeP）的患病率在血管炎中有所增加，包括冷球蛋白性血管炎，结节性多动脉炎（PAN），嗜酸性肉芽肿伴多血管炎（EGPA），显微镜下多血管炎（MPA）和肉芽肿性多血管炎（GPA）

. Although TAK, is a large vessel vasculitis, it can rarely present with clinical findings such as sudden vision loss and sensorineural hearing loss that suggest small vessel involvement

尽管TAK是一种大血管血管炎，但它很少出现临床表现，例如突然视力丧失和感觉神经性听力丧失，提示小血管受累

. Additionally, some studies have shown that quality of life (QoL) decreases in TAK. Especially in active disease, physical component summary (PCS) and mental component summary (MCS) scores of short form-36 (SF-36) were lower than in healthy controls and patients in remission

此外，一些研究表明，TAK的生活质量（QoL）下降。特别是在活动性疾病中，简表36（SF-36）的身体成分总结（PCS）和心理成分总结（MCS）得分低于健康对照组和缓解期患者

In addition to the classic symptoms of claudication, arthralgia and myalgia, patients with TAK may present with atypical symptoms such as discomfort, numbness, tingling, burning, freezing and a desire to move the legs. These atypical symptoms suggest the differential diagnosis of RLS and NeP. Although TAK is a large vessel vasculitis, considering the cases presenting with small vessel involvement, peripheral neuropathy may develop due to the involvement of the vasa nervorum.

除了跛行，关节痛和肌痛的典型症状外，TAK患者还可能出现非典型症状，例如不适，麻木，刺痛，灼热，冻结和想要移动腿部。这些非典型症状提示RLS和NeP的鉴别诊断。尽管TAK是一种大血管血管炎，但考虑到小血管受累的病例，由于神经血管受累，可能会发生周围神经病变。

Previous studies have evaluated NeP and RLS in various systemic vasculitis.

先前的研究已经评估了各种系统性血管炎中的NeP和RLS。

. To our knowledge, our study is the first to investigate NeP and RLS frequency and association with disease activity and QoL in TAK patients.

据我们所知，我们的研究首次调查了TAK患者的NeP和RLS频率以及与疾病活动和生活质量的关系。

Patients and methods

患者和方法

This cross-sectional case-control study was conducted between June-December 2022 at the Erciyes University Rheumatology outpatient clinic. The study complies with the Declaration of Helsinki and was approved by the local ethics committee (25.05.2022, Approval no.2022/424). All participants provided written informed consent prior to any study examination.

这项横断面病例对照研究于2022年6月至12月在埃尔西耶斯大学风湿病门诊进行。该研究符合赫尔辛基宣言，并得到当地伦理委员会的批准（2022年5月25日，批准号2022/424）。所有参与者在任何研究检查之前都提供了书面知情同意书。

The study comprised patients diagnosed with TAK who fulfilled the 1990 ACR criteria. All patients were included in the trial, with the exception of five patients with diabetes mellitus who participated in normal outpatient clinic visits during the study period..

该研究包括符合1990年ACR标准的诊断为TAK的患者。除五名在研究期间参加正常门诊就诊的糖尿病患者外，所有患者均被纳入试验。。

Participants underwent clinical interviews, physical examinations, blood tests (mean HGB, MCV, ferritin and iron levels), imaging for necessary patients, and surveys on the same day they came for their routine outpatient examination within the six-month period. Informed consent form was provided from all patients.

。所有患者均提供了知情同意书。

Demographic (age, sex, height, and weight), clinical (age at diagnosis, symptom onset, disease duration, diagnostic delay, comorbid diseases), and current treatment-related data were recorded. The exclusion criteria was followings: age under 18 years, presence of neuropsychiatric, musculoskeletal diseases, diabetes mellitus (DM), advanced pulmonary and cardiac insufficiency, a history of malignancy, and trauma in the last three months..

记录人口统计学（年龄，性别，身高和体重），临床（诊断年龄，症状发作，疾病持续时间，诊断延迟，合并症）和当前治疗相关数据。。。

Measures

Diagnosis of restless leg syndrome

不宁腿综合征的诊断

1.1

International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria

国际不宁腿综合征研究小组（IRLSSG）共识标准

The IRLSSG Assessment Scale was used

采用IRLSSG评估量表

and patients who met all five diagnostic criteria were diagnosed with RLS.

符合所有五个诊断标准的患者被诊断出患有RLS。

1.2.

The International RLS Study Group Rating Scale (IRLSSG-RS).

国际RLS研究小组评定量表（IRLSSG-RS）。

IRLSSG-RS was used to define the disease severity

IRLSSG-RS用于定义疾病的严重程度

. The maximum score on this scale is 40, graded as mild between 1 and 10, moderate between 11 and 20, severe between 21 and 30, and very severe between 31 and 40.

。该量表的最高得分为40，分为1至10之间的轻度，11至20之间的中度，21至30之间的重度以及31至40之间的非常严重。

Douleur neuropathique-4 questionnaire (DN4)

神经性疼痛-4问卷（DN4）

The Turkish version of the DN4 was used to assess the neuropathic pain

土耳其版的DN4用于评估神经性疼痛

. This questionnaire consists of 18 questions about neuropathic pain, including 10 ‘yes/no’ items; the score is calculated by summing the ‘yes’ answers and ranges from ‘0’ (no neuropathic pain) to ‘10’ (most severe neuropathic pain). Patients with a score of 4 and greater were considered to have neuropathic pain..

该问卷由18个关于神经性疼痛的问题组成，包括10个“是/否”项目；分数是通过将“是”答案相加得出的，范围从“0”（无神经性疼痛）到“10”（最严重的神经性疼痛）。得分为4分及以上的患者被认为患有神经性疼痛。。

Short Form 36 (SF-36) health survey questionnaire

简表36（SF-36）健康调查问卷

Health status was evaluated by using the 36-item SF-36 validated in Turkish by Koçyiğit et al.

通过使用Koçyiğit等人在土耳其验证的36项SF-36评估健康状况。

. Item scores can be summarized into PCS and MCS scores. Raw SF-36 scores, MCS, and PCS scores were calculated according to standardized protocols.

。根据标准化方案计算原始SF-36评分，MCS和PCS评分。

Vasculitis Damage Index (VDI)

血管炎损伤指数（VDI）

The VDI is a generic evaluation index developed to evaluate damage in systemic vasculitis

VDI是一种通用的评估指标，用于评估系统性血管炎的损伤

. This index assessed damage in vasculitis with 64 items under 10 organ-based systems and 11 headings classified as “other” at the end. Damage was defined explicitly as pathology lasting longer than three months from the onset of vasculitis symptoms. This single-page damage assessment form considers having at least one positive item as damage..

该指数评估了血管炎的损害，其中10个基于器官的系统下有64个项目，最后有11个标题被归类为“其他”。损伤明确定义为从血管炎症状发作开始持续超过三个月的病理。此单页损坏评估表将至少有一个阳性项目视为损坏。。

Indian Takayasu Clinical Activity Score 2010 (ITAS2010)

ITAS2010, ITAS with acute phase response (ITAS-A) score, was used to determine disease activity status

ITAS2010，ITAS急性期反应（ITAS-A）评分，用于确定疾病活动状态

. ITAS is an activity measure with only six organ systems and scores predominantly vascular elements (0–2). New onset symptoms and signs in the last three months are marked during the assessment. Active disease is defined as > 1 point for ITAS2010 and > 4 points for ITAS-A. When calculating ITAS-A, ITAS2010 is first calculated, and then acute phase response values are scored 1–3 points within specific ranges and added to the ITAS2010 score..

ITAS是一种活动度量，只有六个器官系统，得分主要是血管元素（0-2）。。活动性疾病定义为ITAS2010>1分，ITAS-A>4分。在计算ITAS-A时，首先计算ITAS2010，然后在特定范围内对急性期反应值评分1-3分，并将其添加到ITAS2010评分中。。

Hata angiographic classification

Hata血管造影分类

Vascular involvement of the patients was indicated according to the HATA (olso named as NUMANO criteria) angiographic classification

根据HATA（olso命名为NUMANO标准）血管造影分类显示患者血管受累

Statistical analysis

统计分析

The Shapiro-Wilk test was used to assess normality of data distribution. Descriptive statistics for numerical data are expressed as the mean ± standard deviation or the median (interquartile range [IQR]), whereas those for categorical data are expressed as the number and the percentage. The independent samples t-test was used for the comparison of normally distributed variables between the two independent groups, and the Mann-Whitney U test was used for the comparison of non-normally distributed variables.

Shapiro-Wilk检验用于评估数据分布的正态性。。独立样本t检验用于比较两个独立组之间的正态分布变量，Mann-Whitney U检验用于比较非正态分布变量。

The Pearson’s chi-squared test was used for the comparison of categorical variables. The relationships between the vascular damage index and the quality of life were evaluated using Spearman’s correlation analysis. To estimate the odds ratio (OR) for factors associated with NeP in patients with TAK, logistic regression analyses were performed.

皮尔逊卡方检验用于分类变量的比较。使用Spearman相关分析评估血管损伤指数与生活质量之间的关系。为了估计TAK患者与NeP相关因素的优势比（OR），进行了逻辑回归分析。

Collinearity was examined with the variance inflation factor (VIF). All statistics were performed using SPSS Windows version 23.0 (IBM Corp., Armonk, NY, USA). A p value of < 0.05 was considered to be statistically significant..

用方差膨胀因子（VIF）检查共线性。所有统计数据均使用SPSS Windows 23.0版（IBM Corp.，Armonk，NY，USA）进行。p值<0.05被认为具有统计学意义。。

Results

结果

The study enrolled 30 patients with TAK and 28 healthy subjects, excluding 10 patients. The mean age was 43.3 ± 11.7 years in the patient group and 44.7 ± 11.0 years in the control group, and no significant difference was found between both groups (

该研究招募了30名TAK患者和28名健康受试者，不包括10名患者。患者组的平均年龄为43.3±11.7岁，对照组为44.7±11.0岁，两组之间无显着差异(

= 0.637). Eight patients (26.7%) were diagnosed under the age of 30, seven patients (23.3%) were diagnosed between the ages of 30 and 40, and fifteen patients (50%) were diagnosed above the age of 40. When the age at symptom onset was controlled, 11 (36.7%) patients were below 30 years of age, 10 (33.3%) patients were between 30 and 40 years of age, and 9 (30%) patients were above 40 years of age.

= 0.637）。8名患者（26.7%）被诊断为30岁以下，7名患者（23.3%）被诊断为30至40岁之间，15名患者（50%）被诊断为40岁以上。当症状发作年龄得到控制时，11名（36.7%）患者年龄在30岁以下，10名（33.3%）患者年龄在30至40岁之间，9名（30%）患者年龄在40岁以上。

The female sex ratio was similar (.

女性性别比例相似（。

= 1.000), and there were 27 (90%) women in the patient group and 25 (89.3%) in the control group. The median BMI was 27.4 (7.7) kg/m2 in the TAK group and 25.1 (7.0) kg/m2 in the control group, and no significant difference (

，患者组有27名（90%）女性，对照组有25名（89.3%）。TAK组的中位BMI为27.4（7.7）kg/m2，对照组为25.1（7.0）kg/m2，无显着差异(

= 0.913) was detected between the groups. Other demographic and clinical treatment-related parameters are presented in Table

组间检测到0.913）。表中列出了其他人口统计学和临床治疗相关参数

Table 1 Demographic and clinical characteristics of the patients.

表1患者的人口统计学和临床特征。

Full size table

全尺寸表

The most frequent comorbidity in TAK patients was hypertension, with 36.7%. According to Hata angiographic classification, type V (46.7%) was the most common. According to IRLSSG criteria, no statistically significant difference was found in the diagnosis of RLS between the TAK group and the healty control group (.

TAK患者最常见的合并症是高血压，占36.7%。根据Hata血管造影分类，V型（46.7%）是最常见的。根据IRLSSG标准，TAK组和健康对照组之间的RLS诊断无统计学差异（。

= 0.195). In TAK patients, the prevalence of NeP was significantly higher than in healthy controls (

=0.195）。在TAK患者中，NeP的患病率明显高于健康对照组(

= 0.011, Table

===0.011，表

). Physical functioning (

)。身体机能(

= 0.01) and general health (

= 0.01）和一般健康(

= 0.002) subscale scores of the of the SF-36 were significantly lower in the patient group than in the control group.

0.002）患者组SF-36的分量表得分显着低于对照组。

No significant differences were found in TAK patients with and without NeP regarding the use of glucocorticoids, biological disease-modifying agents (bDMARDs), conventional synthetic (non-biological) disease-modifying agents (csDMARDs), and immunosuppressives (for all;

在使用糖皮质激素，生物疾病调节剂（bDMARDs），常规合成（非生物）疾病调节剂（csDMARDs）和免疫抑制剂（all）；

> 0.05). According to ITAS-A scores, there were five active patients and 25 inactive patients. No significant difference was found between these two groups regarding SF36 subcomponents and SF36 PCS/MCS sum scores (

>0.05）。根据ITAS-A评分，有5名活动患者和25名非活动患者。在SF36子成分和SF36 PCS/MCS总分方面，这两组之间没有发现显着差异(

> 0.05; Data not shown).

>0.05；数据未显示）。

Data regarding the comparison of demographic, clinical, and laboratory findings in patients with and without RLS are presented in Table

表中列出了有无RLS患者的人口统计学，临床和实验室检查结果的比较数据

Table 2 Comparison of demographic, clinical, and laboratory findings in patients with and without restless leg syndrome.

表2患有和不患有不宁腿综合征的患者的人口统计学，临床和实验室检查结果的比较。

Full size table

全尺寸表

No significant differences were observed between patients with and without NeP in gender, age, BMI, symptom onset, delay in diagnosis, mean HGB, MCV, ferritin and iron levels (for all;

有和没有NeP的患者在性别，年龄，BMI，症状发作，诊断延迟，平均HGB，MCV，铁蛋白和铁水平方面没有显着差异（所有；

> 0.05). VDI scores were significantly higher with NeP patients(

>0.05）。NeP患者的VDI评分明显更高(

= 0.004). ITAS-A scores were similar (

=0.004）。ITAS-A得分相似(

> 0.05). IUBC values were substantially lower with NeP than without NeP (

>0.05）。NeP组的IUBC值明显低于无NeP组(

= 0.002). Furthermore, when QoL was analyzed in both groups, emotional well-being (

= 0.002）。此外，当对两组的生活质量进行分析时，情绪幸福感(

= 0.001), energy fatigue (

=0.001），能量疲劳(

= 0.002), general health (

=0.002），一般健康状况(

< 0.001), and SF36-MCS

<0.001），和SF36-MCS

= 0.006) scores were significantly lower in TAK patients with NeP (Table 3).

NeP患者的TAK评分显着降低（表3）。

Table 3 Comparison of demographic, clinical, and laboratory findings in patients with and without neuropathic pain.

表3有无神经性疼痛患者的人口统计学，临床和实验室检查结果的比较。

Full size table

全尺寸表

Logistic regression analysis was performed to investigate predictors associated with NeP in TAK patients. In univariate analyses, VDI [odds ratio (OR): 2.219, 95% confidence interval (CI): 1.126–4.375,

进行逻辑回归分析以调查TAK患者中与NeP相关的预测因素。在单变量分析中，VDI[优势比（OR）：2.219，95%置信区间（CI）：1.126-4.375，

= 0.021], UIBC [odds ratio (OR): 0.978, 95% confidence interval (CI): 0. 960-0.995

=0.021]，UIBC[优势比（OR）：0.978，95%置信区间（CI）：0。960-0.995

= 0.014], SF36MCS [odds ratio (OR): 0.938, 95% confidence interval (CI): 0.893–0.986

=0.014]，SF36MCS[优势比（OR）：0.938，95%置信区间（CI）：0.893-0.986

= 0.011] were the predictors associated with NeP. No superiority among the three predictors was detected across multiple models (for all;

[0.011]是与NeP相关的预测因子。在多个模型中未检测到三个预测因子之间的优势（全部）；

> 0.05) (Table

>>0.05）（表

Table 4 Identification of the associated factors with neuropathic pain.

表4确定与神经性疼痛相关的因素。

Full size table

全尺寸表

The Spearman correlation analysis showed a moderately significant negative correlation between VDI and SF-36 subcomponents ‘energy fatigue’ (rho=-0.484,

Spearman相关分析显示VDI和SF-36子成分“能量疲劳”之间存在中度显着的负相关（rho=-0.484，

= 0.007) and ‘general health’ (rho=-0.411,

= 0.007）和“一般健康”（rho=-0.411，

= 0.024). No significant correlation was found between other SF-36 subcomponents and VHI (

==0.024）。其他SF-36子成分与VHI之间未发现显着相关性(

> 0.05).

Discussion

讨论

In this study, 23.3% of patients with TAK had NeP, according to the DN4 questionnaire. NeP was significantly higher in TAK patients than control group, and compared with healthy controls some SF-36 subcomponents (general health and physical functioning) were significantly lower. Also, the NeP group had significantly higher VDI scores.

根据DN4问卷，在这项研究中，23.3%的TAK患者患有NeP。TAK患者的NeP显着高于对照组，与健康对照组相比，一些SF-36亚组分（一般健康和身体机能）显着降低。此外，NeP组的VDI得分明显较高。

Another significant result of the study was that TAK patients with NeP had differences in UIBC, VDI, and some SF-36 components (energy fatigue, emotional well-being, general health, and SF36-MCS) compared to those without NeP. In addition, low UIBC and VDI were the two most significant predictors associated with NeP in TAK patients.

该研究的另一个重要结果是，与没有NeP的患者相比，患有NeP的TAK患者在UIBC，VDI和一些SF-36成分（能量疲劳，情绪健康，一般健康和SF36-MCS）方面存在差异。此外，低UIBC和VDI是TAK患者中与NeP相关的两个最重要的预测因子。

On the other hand, the frequency of RLS in TAK patients was similar to the healty subjects..

另一方面，TAK患者的RLS频率与健康受试者相似。。

Peripheral neuropathic pain is particularly likely seen in systemic vasculitis affecting small and medium-sized vessels. The development of neuropathy due to the involvement of capillaries, venules, arterioles, and small vessels in the peripheral nervous system is often observed

周围神经性疼痛特别可能见于影响中小血管的系统性血管炎。经常观察到由于周围神经系统中毛细血管，小静脉，小动脉和小血管的参与而导致神经病变的发展

. In a cross-sectional study of 572 GPA, 218 MPA, and 165 EGPA patients, vasculitic neuropathy was 19% in GPA, 23% in MPA, and 65% in EGPA

在一项针对572名GPA，218 MPA和165名EGPA患者的横断面研究中，血管炎性神经病在GPA中为19%，在MPA中为23%，在EGPA中为65%

. In a study evaluating 348 PAN patients, 74.1% of patients had peripheral neuropathy

在一项评估348名PAN患者的研究中，74.1%的患者患有周围神经病变

. Peripheral neuropathy is not expected in TAK, which is a large vessel vasculitis. There is no previous study in the literature evaluating the frequency of NeP in TAK. In this study, the frequency of NeP in patients with TAK was 23.3%, significantly higher than in healthy subjects.

TAK是一种大血管炎，预计不会出现周围神经病变。文献中没有评估TAK中NeP频率的研究。在这项研究中，TAK患者的NeP频率为23.3%，明显高于健康受试者。

In a prospective study comprising 52 patients with both painful neuropathy and/or pain free neuropathy, and 44 healthy controls, protein levels of interleukin (IL)-2, tumor necrosis factor-alpha (TNF-α), IL-4, IL-10 and blood mRNA were analyzed. Protein, TNF mRNA and IL-2 mRNA levels were two times higher in patients with painful neuropathy than in controls, and TNF mRNA, IL-2 and protein levels were approximately two times higher in patients with painful neuropathy than in pain free neuropathy.

在一项前瞻性研究中，包括52名患有疼痛性神经病和/或无痛性神经病的患者和44名健康对照者，分析了白细胞介素（IL）-2，肿瘤坏死因子-α（TNF-α），IL-4，IL-10和血液mRNA的蛋白水平。疼痛性神经病患者的蛋白质，TNF mRNA和IL-2 mRNA水平是对照组的两倍，疼痛性神经病患者的TNF mRNA，IL-2和蛋白质水平大约是无痛性神经病患者的两倍。

In another prospective study of 133 patients with neuropathy, sural nerve biopsies and/or skin punch biopsies were performed on all patients and skin punch biopsies were performed on healthy controls. The gene expression of anti-inflammatory and pro-inflammatory cytokines in the sural nerve did not differ between neuropathies of diverse etiologies; however, in painful neuropathies, the expression of IL-10 and IL-6 was found to be higher than in pain-free neuropathies.

在另一项针对133例神经病变患者的前瞻性研究中，对所有患者进行了腓肠神经活检和/或皮肤穿刺活检，并对健康对照组进行了皮肤穿刺活检。腓肠神经中抗炎和促炎细胞因子的基因表达在不同病因的神经病之间没有差异；然而，在疼痛性神经病中，发现IL-10和IL-6的表达高于无痛性神经病。

In a study which Park et al. divided 49 patients with TAK into stable disease and active disease groups and compared them with 12 healthy subjects. Interferon (IFN)-gamma, TNF-alpha IL-6, IL-12 and IL-18 levels were measured in blood samples. Serum IL-6, IL-18 and TNF-alpha levels of TAK patients were significantly higher than controls, and similiarly serum IL-6 and IL-18 levels were higher in the active disease group than in the remission group.

在Park等人的一项研究中，将49名TAK患者分为稳定疾病组和活动疾病组，并与12名健康受试者进行比较。在血液样本中测量干扰素（IFN）-γ，TNF-αIL-6，IL-12和IL-18水平。TAK患者的血清IL-6，IL-18和TNF-α水平显着高于对照组，活动性疾病组的血清IL-6和IL-18水平高于缓解组。

. Increased levels of cytokines such as TNF-alpha and IL-6, which are common in both NeP and TAK pathogenesis, may be one of the reasons for the increased frequency of NeP in patients with TAK.

在NeP和TAK发病机制中常见的细胞因子如TNF-α和IL-6水平升高，可能是TAK患者NeP频率增加的原因之一。

Peripheral nervous system involvement typically results from axonal, focal or multifocal ischemic neuropathy due to arteriolar occlusion of the vasa nervorum, generally the epineural arteries

周围神经系统受累通常是由于神经血管（通常是神经外膜动脉）的小动脉闭塞引起的轴突，局灶性或多灶性缺血性神经病

. Although rare, large vessel involvement has been reported in small and medium vessel vasculitis

.虽然罕见，但据报道中小型血管炎有大血管受累

. Although TAK is a large vessel vasculitis, some cases in the literature present with small vessel involvement

虽然TAK是一种大血管血管炎，但文献中的一些病例表现为小血管受累

. In this context, the increased frequency of NeP in patients with TAK may be related to undetected small vessel involvement. Alternatively, it may be related to decreased blood flow distal of large vessels with near-total/total occlusion. NeP etiology includes hereditary, infectious, ischemic (atherosclerosis), DM, immune-mediated, infiltrative (malignancy, lymphoma), drugs and toxins, coagulopathies, etc.

在这种情况下，TAK患者NeP频率的增加可能与未发现的小血管受累有关。或者，它可能与大血管远端血流减少有关，几乎完全/完全闭塞。NeP病因包括遗传性，感染性，缺血性（动脉粥样硬化），DM，免疫介导的，浸润性（恶性肿瘤，淋巴瘤），药物和毒素，凝血病等。

. This study excluded patients with known NeP, DM, and malignancy. When the association between drug use and NeP was considered, no significant difference was found between the groups with and without NeP in terms of steroid, csDMARD, and bDMARD use. ITAS-A scores were similar in both groups with and without NeP.

。当考虑药物使用与NeP之间的关联时，在类固醇，csDMARD和bDMARD使用方面，有和没有NeP的组之间没有发现显着差异。有和没有NeP的两组ITAS-A评分相似。

This may be interpreted that in people with active disease, the pain caused by claudication is not perceived as neuropathic pain..

这可能被解释为，在活动性疾病患者中，跛行引起的疼痛不被视为神经性疼痛。。

One of the other significant results of our study was that VDI, UIBC, and SF36-MCS were predictors associated with NeP in patients with TAK. Damage due to elevated inflammatory cytokines such as TNF and IL-6 may explain the relationship between VDI and NeP. The association between SF-36 and NeP may be related to the higher tendency for depression and anxiety in patients with TAK, as shown by Yilmaz et al.[16], Moreover, this may be related to the worse scores of some SF36 components (energy fatigue, emotional well-being, general health), including SF-36 MCS..

我们研究的另一个重要结果是VDI，UIBC和SF36-MCS是TAK患者与NeP相关的预测因子。由TNF和IL-6等炎性细胞因子升高引起的损伤可能解释了VDI和NeP之间的关系。如Yilmaz等人（16）所示，SF-36和NeP之间的关联可能与TAK患者抑郁和焦虑的较高趋势有关，此外，这可能与某些SF36成分（能量疲劳，情绪健康，一般健康）的得分较差有关，包括SF-36 MCS。。

Our study found no statistically significant difference in RLS diagnosis between TAK patients and the control group according to IRLSSG criteria (16.7% vs. 3.6%). Falup Pecurarıu et al.

我们的研究发现，根据IRLSSG标准，TAK患者与对照组之间的RLS诊断无统计学差异（16.7%比3.6%）。Falup-Pecurarıu等人。

reported a higher prevalence of RLS in systemic lupus erythematosus (SLE) patients (34.62%) compared to healthy controls (7.69%). Ediz et al.

据报道，与健康对照组（7.69%）相比，系统性红斑狼疮（SLE）患者的RLS患病率更高（34.62%）。Ediz等人。

showed that the prevalence of RLS was significantly higher in patients with Behçet’s disease (29.4%) compared to healthy controls (4.8%). Also, the frequency of RLS is considerably higher in rheumatologic diseases in previous studies

结果显示，与健康对照组（4.8%）相比，贝塞特病患者（29.4%）的RLS患病率显着更高。此外，在以前的研究中，风湿性疾病中RLS的频率要高得多

. In our study, although the frequency of RLS was numerically higher in the patient group compared with the control group, this difference was not statistically significant. This may be due to the small sample size. In a study investigating the frequency of RLS in patients with GPA, there was no significant correlation between RLS and VDI, and no significant risk factor for the occurrence of RLS other than cardiovascular damage could be identified.

在我们的研究中，尽管与对照组相比，患者组的RLS频率在数值上更高，但这种差异在统计学上并不显着。这可能是由于样本量小。在一项调查GPA患者RLS发生频率的研究中，RLS与VDI之间没有显着相关性，除心血管损伤外，没有发现RLS发生的重要危险因素。

. Falup Pecurarıu et al. [4] in patients with SLE showed that the prevalence of RLS was higher in SLE patients (34.62%) compared to controls (7.69%). Still, they could not detect a relationship between RLS and iron deficiency anemia, although it was higher in patients with RLS. In our study, anemia parameters were similar in patients with and without RLS..

Falup-Pecurarıu等[4]在SLE患者中显示，与对照组（7.69%）相比，SLE患者的RLS患病率更高（34.62%）。尽管如此，他们仍无法检测到RLS与缺铁性贫血之间的关系，尽管RLS患者的缺铁性贫血程度更高。在我们的研究中，患有和不患有RLS的患者的贫血参数相似。。

The PCS and MCS summary scores were worse than the mean scores for the healthy population of the same age, as well as nationally reported scores for diabetes, hypertension and coronary heart disease in a study by Abularrag et al.

在Abularrag等人的一项研究中，PCS和MCS总分比同年龄健康人群的平均得分以及全国报告的糖尿病，高血压和冠心病得分差。

assessing the QoL of 158 TAK patients. In the same study, multivariate predictors of better physical QoL were shown to be younger age, disease remission, and not using immunomodulatory drugs. In another study with 165 patients, all TAK patients had statistically significantly lower SF36 subcomponents compared to healthy controls, and most of the SF-36 subgroup parameters except mental health were statistically lower in active TAK patients.

评估158名TAK患者的生活质量。在同一项研究中，更好的身体生活质量的多变量预测指标显示年龄较小，疾病缓解，不使用免疫调节药物。在另一项针对165名患者的研究中，与健康对照组相比，所有TAK患者的SF36亚组分在统计学上均显着降低，并且除心理健康外，大多数SF-36亚组参数在活动性TAK患者中均在统计学上较低。

. In our study, the significant difference in only two parameters and the similarity of the other parameters with healthy controls may be related to the inactive of 83% of the patients. Energy fatigue, emotional well-being, general health, and SF36-MCS scores were significantly lower in the NeP group.

在我们的研究中，只有两个参数的显着差异以及其他参数与健康对照的相似性可能与83%的患者不活跃有关。NeP组的能量疲劳，情绪健康，一般健康和SF36-MCS评分显着降低。

Considering that SF36-MCS is among the predictors associated with NeP, NeP should be kept in mind in TAK patients with atypical symptoms incompatible with claudication; patients should be questioned in this respect, and appropriate treatment should be initiated..

考虑到SF36-MCS是与NeP相关的预测因子之一，对于非典型症状与跛行不相容的TAK患者，应牢记NeP；在这方面应询问患者，并应开始适当的治疗。。

The strength of this study is that RLS, NeP, disease acitivity, and QoL were evaluated simultaneously in patients with TAK for the first time in the literature. However, the study had some limitations. First, the sample size is limited due to the single-center data and the relatively low prevalence.

这项研究的优势在于，在文献中首次同时评估了TAK患者的RLS，NeP，疾病活动性和生活质量。然而，这项研究有一些局限性。首先，由于单中心数据和相对较低的患病率，样本量有限。

Second, other chronic painful syndromes, such as fibromyalgia, which can affect QoL, were not assessed. Finally, due to the number of patients in the study, the evaluation of RLS, NeP, and QoL parameters in different subgroups according to the Hata angiographic classification was not performed. Also, a disadvantage of the study is the inability to conduct nerve conduction investigations in patients with NEP..

其次，没有评估其他可能影响生活质量的慢性疼痛综合征，如纤维肌痛。最后，由于研究中的患者数量，未根据Hata血管造影分类对不同亚组的RLS，NeP和QoL参数进行评估。此外，该研究的一个缺点是无法对NEP患者进行神经传导检查。。

Conclusion

结论

This study revealed that the frequency of NeP was higher in patients with TAK than in the healthy population, and the patients with TAK were negatively affected in terms of NeP and QoL rather than RLS. The presence of NeP in these patients is strongly associated with VDI and some components of QoL. In addition, disease severity scores are inversely related to some QoL scores (energy fatigue and general health) in patients with TAK.

这项研究表明，TAK患者的NeP频率高于健康人群，TAK患者在NeP和QoL方面受到负面影响，而不是RLS。这些患者中NeP的存在与VDI和QoL的某些组成部分密切相关。此外，TAK患者的疾病严重程度评分与某些生活质量评分（能量疲劳和一般健康）呈负相关。

Further studies are needed to better understand the relationship between RLS, NeP, disease activity, and QoL in patients with TAK..

需要进一步的研究来更好地了解TAK患者的RLS，NeP，疾病活动和生活质量之间的关系。。

Data availability

数据可用性

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

本研究中使用和/或分析的数据集可根据合理要求从通讯作者处获得。

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Acknowledgements

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We/I would like to thank the Proofreading & Editing Office of the Dean for Research at Erciyes University for copyediting and proofreading service for this manuscript.

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Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Erciyes University, Kayseri, 38030, Turkey

Emel Oğuz Kökoğlu, Melih Kızıltepe, Tuğba Kahraman Denizhan & Abdurrahman Soner Şenel

埃梅尔·科奥卢之子、梅利赫·凯尔特佩、杜加·卡拉曼·德尼詹和阿卜杜拉赫曼·索纳·谢内尔

Division of Rheumatology, Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Erciyes University, Kayseri, Turkey

土耳其凯塞里埃尔西耶斯大学医学院物理医学与康复系风湿病科

Hüseyin Kaplan

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Division of Rheumatology, Department of Physical Medicine and Rehabilitation, Bursa High Specialization Health Application and Research Center - University of Health Sciences, Bursa, Turkey

土耳其布尔萨健康科学大学布尔萨高专业健康应用与研究中心物理医学与康复系风湿病科

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EOK: contributed to the project coordination; conception and design of the study; data collection; statistical analysis; article writing and critical review of the content; obtaining, analyzing, and interpreting data; critical review of the literature; final approval of the final version of the manuscript.

EOK：为项目协调做出了贡献；研究的概念和设计；数据收集；统计分析；文章写作和内容的批判性评论；获取、分析和解释数据；对文献进行批判性审查；稿件最终版本的最终批准。

MK: contributed to the project coordination; conception and design of the study; data collection; obtaining, analyzing, and interpreting data; critical review of the literature; final approval of the final version of the manuscript. HK: statistical analysis; article writing and critical review of the content; obtaining, analyzing, and interpreting data; critical review of the literature; final approval of the final version of the manuscript.

MK：为项目协调做出了贡献；研究的概念和设计；数据收集；获取、分析和解释数据；对文献进行批判性审查；最终批准手稿的最终版本。香港：统计分析；文章写作和内容的批判性评论；获取、分析和解释数据；对文献进行批判性审查；稿件最终版本的最终批准。

SŞ: article writing and critical review of the content; obtaining, analyzing, and interpreting data; critical review of the literature; final approval of the final version of the manuscript. TKD: article writing and critical review of the content; obtaining, analyzing, and interpreting data; critical review of the literature; final approval of the final version of the manuscript.

SŞ：文章写作和内容的批判性评论；获取、分析和解释数据；对文献进行批判性审查；最终批准手稿的最终版本。TKD：文章写作和内容的批判性评论；获取、分析和解释数据；对文献进行批判性审查；稿件最终版本的最终批准。

ASŞ: article writing and critical review of the content; obtaining, analyzing, and interpreting data; critical review of the literature; final approval of the final version of the manuscript..

ASŞ：文章写作和内容的批判性审查；获取、分析和解释数据；对文献进行批判性审查；稿件最终版本的最终批准。。

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Kökoğlu, E.O., Kızıltepe, M., Kaplan, H.

Kokoğlu，E.O.，Kızıltepe，M.，Kaplan，H.

et al.

等人。

Simultaneous evaluation of restless leg syndrome, neuropathic pain, disease activity, and quality of life in patients with Takayasu arteritis: a cross-sectional study.

同时评估大动脉炎患者的不宁腿综合征，神经性疼痛，疾病活动和生活质量：一项横断面研究。

Sci Rep

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, 3158 (2025). https://doi.org/10.1038/s41598-024-83110-2

, 3158 (2025).https://doi.org/10.1038/s41598-024-83110-2

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2024年7月25日

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