Abstract
目的
评估银屑病关节炎(psoriatic arthritis，PsA)患者抑郁及焦虑的患病率，比较与类风湿关节炎(rheumatoid arthritis，RA)患者之间的差异，探索PsA患者发生抑郁及焦虑的相关因素。
方法
连续入选2018年5月至2019年9月就诊于北京大学第一医院风湿免疫科门诊的PsA和RA患者，采用抑郁自评量表和焦虑自评量表评估患者抑郁和焦虑情况，并进行对比。收集PsA患者的人口学及临床数据，包括性别、年龄、病程、疾病活动度及用药情况等，同时应用能量多普勒与灰阶超声评价关节及附着点病变。采用多因素Logistic回归分析相关因素。
结果
入选114例PsA患者，37例(32.5%)患有精神障碍，其中36例(31.6%)合并抑郁，15例(13.2%)合并焦虑。与201名RA患者相比较，PsA患者合并抑郁的比例更高(31.6% vs. 18.9%，P=0.011)，经过校正分析发现PsA比RA发生抑郁的风险更高(校正OR=2.7，95%CI：1.1~6.4);合并焦虑患者的比例也较RA有升高趋势(13.2% vs. 8.5%，P=0.185)，但差异无统计学意义。在PsA患者中，年龄(OR=0.95，P=0.008)、银屑病病程(OR=0.94，P=0.018)、疼痛视觉模拟评分(OR=1.47，P=0.011)、银屑病皮损面积及严重程度指数(psoriasis area and severity index，PASI)(OR=1.07，P=0.007)、超声附着点炎阳性(OR=4.13，P=0.009)是抑郁的相关因素; PASI(OR=1.07，P=0.001)是焦虑的相关因素。
结论
PsA患者患抑郁与焦虑的比例较高，其中抑郁患病风险更是高于RA患者。年龄小、银屑病病程短、银屑病皮疹重、疼痛评分高、存在超声附着点炎症的PsA患者更容易出现抑郁，银屑病皮疹重是PsA患者发生焦虑的相关因素。
Keywords: 银屑病关节炎, 抑郁, 焦虑, 患病率
Abstract
Objective
To determine the prevalence of depression and anxiety in patients with psoriatic arthritis (PsA), to investigate whether there is a difference in the prevalence of depression and anxiety between PsA and rheumatoid arthritis (RA) patients and to identify associated risk factors for depression and anxiety in PsA patients.
Methods
PsA and RA patients who visited Department of Rheumatology and Clinical Immunology in Peking University First Hospital from May 2018 to Sep 2019 were recruited. Self-rating anxiety scale and self-rating depression scale were surveyed and compared between PsA and RA patients. Demographics and clinical features including age, gender, disease duration, disease activity score, psoriasis area and severity index (PASI), and medical application were collected. Power Doppler and grey-scale ultrasound of joints, tenosynovitis and enthesis were performed. Multivariate Logistic regression was used to identify the factors associated with mood disorders and the odds ratio of depression and anxiety between the PsA and RA patients.
Results
Among the 114 enrolled PsA patients, 37 (32.5%) had mood disorders, in which 36 (31.6%) with depression and 15 (13.2%) with anxiety. Compared with 201 RA patients, PsA patients showed greater odds for depression [adjusted OR (95%CI): 2.7 (1.1-6.4)]. Depression was more often observed in the PsA than in the RA patients (31.6% vs. 18.9%, P=0.011). The similar trend for anxiety was also observed, although the difference was insignificant (13.2% vs. 8.5%, P=0.185). Age (OR=0.95, P=0.008), psoriasis duration (OR=0.94, P=0.018), pain visual analogue scale (OR=1.47, P=0.011), PASI score (OR=1.07, P=0.007) and presence of ultrasound enthesitis (OR=4.13, P=0.009) were identified as factors associated with depression in the PsA patients. PASI score (OR=1.07, P=0.001) was identified as associated factor for anxiety in the PsA patients.
Conclusion
The prevalence of depression and anxiety is elevated in PsA patients. Depression is significantly more prevalent in PsA patients than in RA patients. Younger age, shorter psoriasis duration, worse pain and presence of ultrasound enthesitis are associated with depression, while severe psoriasis rash is associated with both depression and anxiety in PsA patients.
Keywords: Psoriatic arthritis, Depression, Anxiety, Prevalence
银屑病关节炎(psoriatic arthritis，PsA)是一种慢性、进展性、自身免疫性关节炎性疾病，主要表现为外周关节炎、肌腱附着点炎、脊柱炎、银屑病皮疹等[1]。疾病会导致慢性关节肿痛、关节破坏、功能障碍甚至畸形，严重影响正常工作和生活质量[2]。PsA不仅影响身体健康，还会诱发精神障碍。长期遭受关节疼痛的折磨，面对关节残疾的恐惧，忍受暴露皮疹的自卑，这些都不可避免地给PsA患者带来巨大的精神压力，甚至引发抑郁与焦虑，进一步威胁健康并加重社会负担。既往国外研究中，PsA患者抑郁患病率高达9%~37%[3]，焦虑患病率为15%~30%[4]。
近年来，随着对关节炎达标治疗要求的提高，风湿免疫科医生往往把主要精力放在评价疾病活动度和药物调整上，而没有足够时间去询问患者精神症状，加之很多患者也不愿谈论自己抑郁和焦虑症状，因此，PsA患者伴发的精神障碍常常被忽视。有研究发现，高疾病活动度和关节疼痛程度与PsA发生抑郁和焦虑相关[5]，但关于相关因素的研究结果仍不一致。另外，与类风湿关节炎(rheumatoid arthritis，RA)相比，PsA不但会导致关节炎症，还会引发皮肤病变，关节功能和外观缺陷的双重影响可能会加重精神障碍[6]。在我国，PsA抑郁和焦虑患病情况及相关因素知之甚少，关于PsA与RA患者焦虑和抑郁患病率的比较也鲜有报道。本研究通过抑郁与焦虑问卷评分，评估PsA患者抑郁及焦虑的患病率，比较PsA和RA患者抑郁及焦虑的患病率差异，并对相关影响因素进行分析。
1. 资料与方法
1.1. 病例来源
连续入组2018年5月至2019年9月就诊于北京大学第一医院风湿免疫科的PsA及RA患者。PsA患者符合银屑病关节炎分类标准(Classification Criteria for Psoriatic Arthritis，CASPAR)[7]，RA患者符合1987年美国风湿病学会(American College of Rheumatology，ACR)[8]或2010年ACR/欧洲抗风湿病联盟(European League Against Rheumatism，EULAR)分类标准[9]。
1.2. 精神障碍评估
应用抑郁自评量表(self-rating depression scale，SDS)和焦虑自评量表(self-rating anxiety scale，SAS)评估抑郁和焦虑，量表用于评估近一周患者情况。SAS和SDS分别包括20道题目，每个题目赋值为1~4分，所有题目得分相加，再乘以1.25为最终的标准分。SDS标准分≥50定义为抑郁，50~59为轻度抑郁，60~69为中度抑郁，70以上为重度抑郁。SAS标准分≥50定义为焦虑，50~59为轻度焦虑，60~69为中度焦虑，70以上为重度焦虑[10]。
1.3. 临床评估及实验室检查
收集上述患者人口学信息，包括年龄、性别、银屑病病程、关节炎病程、身高、体质量、体重指数(body mass index，BMI)、腰围; 临床查体及评分，包括压痛关节数、肿胀关节数、疼痛视觉模拟评分(visual analogue scale，VAS)、患者总体评分(patient global assessment，PGA)、医生总体评分(evaluator global assessment，EGA)和健康评估问卷(health assessment questionnaire disability index，HAQ-DI)[11]; 银屑病皮损面积及严重程度指数(psoriasis area and severity index，PASI)评分[12]。实验室检查包括红细胞沉降率(erythrocyte sedimentation rate，ESR)和C反应蛋白(C-reactive protein，CRP)。应用基于28关节的疾病活动度评分(disease activity score based on 28-joint count，DAS28，又称DAS28-CRP)以及简化疾病活动度指标(simplified disease activity index，SDAI)评价PsA和RA疾病活动度[13-14]。应用PsA疾病活动指数(disease activity index for PsA，DAPSA)评估PsA疾病活动性[15]。
收集吸烟情况，分为不吸烟(从未吸烟)、曾经吸烟(入组前曾经吸烟、入组时已戒烟)、现在吸烟(平均1年吸烟10包以上，入组时仍在吸烟)[16]; 记录PsA合并代谢综合征[17]、合并甲病和眼炎情况，以及银屑病和/或PsA家族史情况。记录入组时用药情况，包括传统合成改善病情抗风湿药(conventional synthetic disease-modifying anti-rheumatic drugs，csDMARDs)、生物制剂、非甾体抗炎药等。
1.4. 肌肉骨骼超声检查
肌肉骨骼超声由一位有丰富超声检查经验，但是不知晓病情的风湿免疫科医生完成，对所有PsA患者以下30个关节进行扫查，包括双腕、双手第1~5掌指关节、双手第1~5近端指间关节、双手第1~5远端指间关节，每个关节部位进行纵向面和横断面扫描。此外，对以下8对附着点部位进行附着点炎检查，包括双侧肱骨内上髁(屈肌总腱附着点)、肱骨外上髁(伸肌总腱附着点)、鹰嘴粗隆(肱三头肌腱附着点)、髌骨上缘(股四头肌腱附着点)、髌骨下缘(髌腱上端附着点)、胫骨粗隆(髌腱下端附着点)、跟骨上缘(跟腱附着点)、跟骨下缘(跖筋膜附着点)。本研究采用GE E9超声设备，探头型号为ML6-15，频率为6~15 MHz。
滑膜增生、滑膜炎、腱鞘炎、骨侵蚀、附着点炎等肌肉骨骼超声病变定义均依照风湿病预后评估组织(Outcome Measures in Rheumatology，OMERACT)国际统一标准[18]。应用灰阶(grey scale，GS)来评价滑膜增生，采用Sukudlarek 2001年半定量分级标准将滑膜增生分为0~3级; 应用能量多普勒(power Doppler，PD)来评价滑膜炎，采用Sukudlarek 2001年半定量分级标准将滑膜炎分为0~3级[19]。应用半定量分级标准将腱鞘炎分为GS 0~3级和PD 0~3级[20]。GS滑膜增生总分为所有关节GS评分总和, PD滑膜炎总分为所有关节PD评分总和, PD腱鞘炎总分为所有腱鞘炎PD评分总和，GS腱鞘炎总分为所有关节腱鞘炎GS评分总和。超声附着点筛查阳性定义为双手腕30关节及8对附着点检查中至少一处急性附着点炎(两个垂直切面上见到肌腱/韧带附着点处的异常低回声和/或增厚，可伴有多普勒信号)。
1.5. 统计学方法
采用SPSS 24.0统计软件进行统计学分析。计量数据如符合正态分布采用x±s表示，两组间比较采用t检验; 如不符合正态分布则采用M(P25，P75)表示，两组间比较采用非参数检验(Mann-Whitney U检验)。计数资料采用χ2检验。应用多因素Logistic回归分析抑郁与焦虑的相关因素，用Logistic回归分析进行混杂因素矫正，以RA作为PsA对照，进行患病风险比较，计算PsA与RA患病率风险比。P < 0.05为差异有统计学意义。
2. 结果
2.1. PsA患者抑郁及焦虑的共存情况
共纳入114例PsA患者，女性55例(48.2%)，年龄(47.6±13.5)岁，银屑病病程14.0(7.0，24.3)年，DAS28-CRP为3.7±1.5，DAPSA评分为18.3±14.0，属于中等疾病活动度。入组时14例(12.3%)患者未应用过csDMARD药物，80例(70.2%)患者应用csDMARDs单药治疗，20例(17.5%)应用csDMARDs联合治疗。患有抑郁和/或焦虑情感障碍患者为37例(32.5%)，其中36例(31.6%)患有抑郁，轻度抑郁31例，中度抑郁5例; 15例(13.2%)存在焦虑，轻度焦虑14例，中度焦虑1例(表 1)。
表 1.
PsA、RA患者临床特点及抑郁和焦虑患病情况比较
Comparisons of clinical features and psychological disorders between PsA and RA patients
| Items | PsA (n=114) | RA (n=201) | P |
| Data are shown as n(%), x±s and M (P25, P75). PsA, psoriatic arthritis; RA, rheumatoid arthritis; TJC, tender joint count; SJC, swollen joint count; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; PGA, patient global assessment; EGA, evaluator global assessment; VAS, visual analogue scale; DAS28-CRP, disease activity score based on 28-joint count; SDAI, simplified disease activity index; HAQ, health assessment questionnaire; PASI, psoriasis area and severity index; csDMARDs, conventional synthetic disease-modifying anti-rheumatic drugs. | |||
| Female | 55 (48.2) | 166 (82.6) | < 0.001 |
| Age/years | 47.6±13.5 | 49.5±13.0 | 0.222 |
| Disease duration/years | 14.0 (7.0, 24.3) | 3.4 (1.0, 10.0) | < 0.001 |
| TJC 28 | 3.0 (1.0, 8.0) | 2.0 (0.0, 6.5) | 0.253 |
| SJC 28 | 2.0 (0.0, 6.0) | 1.0 (0.0, 3.5) | 0.054 |
| ESR/(mm/h) | 11.5 (5.0, 27.3) | 21.0 (10.0, 40.0) | < 0.001 |
| CRP/(mg/L) | 5.5 (2.0, 15, 6) | 6.1 (2.6, 14.8) | 0.176 |
| PGA (0-10) | 4.0 (2.0, 6.0) | 3.0 (2.0, 6.0) | 0.276 |
| EGA (0-10) | 3.0 (2.0, 5.0) | 2.0 (1.0, 5.0) | 0.124 |
| Pain VAS (0-10) | 3.8 (2.0, 5.0) | 3.0 (1.3, 5.0) | 0.615 |
| DAS28-CRP | 3.4±1.5 | 3.6±1.6 | 0.419 |
| SDAI | 14.1 (7.3, 24.4) | 10.6 (5.6, 24.0) | 0.067 |
| HAQ | 1.0 (0.0, 8.0) | 4.0 (0.5, 15.0) | 0.001 |
| PASI | 3.2 (0.8, 9.4) | 0.0 (0.0, 0.0) | < 0.001 |
| Mood disorder | |||
| Depression | 36 (31.6) | 38 (18.9) | < 0.001 |
| Anxiety | 15 (13.2) | 17 (8.5) | 0.185 |
| Cigarette smoking | < 0.001 | ||
| Non-smokers | 76 (66.7) | 170 (84.6) | |
| Ex-smokers | 14 (12.3) | 15 (7.5) | |
| Current smokers | 24 (21.1) | 16 (8.0) | |
| csDMARDs used | < 0.001 | ||
| csDMARDs-naive | 14 (12.3) | 66 (32.8) | |
| Single csDMARDs | 80 (70.2) | 49 (24.4) | |
| Combined csDMARDs | 20 (17.5) | 86 (42.8) | |
| Biological DMARDs used | 2 (1.8) | 4 (2.0) | 0.882 |
| Metabolic syndrome | 38 (33.3) | 19 (9.5) | < 0.001 |
2.2. PsA与RA发生抑郁和焦虑的患病率比较
与201例RA患者相比较，PsA患者抑郁患病率更高(31.6% vs. 18.9%，P=0.011)，焦虑患病率也较RA升高(13.2% vs. 8.5%，P=0.185)，但差异无统计学意义。与RA患者比较，PsA组女性比例低、病程长、ESR低、HAQ评分低、PSAI评分高、合并代谢综合征多, 吸烟及用药情况也存在差异(表 1)。应用Logistic回归对混杂因素进行校正分析发现，PsA比RA发生抑郁的风险更高(校正OR=2.7，95%CI：1.1~6.4，表 2)。
表 2.
预测抑郁患病风险模型(PsA与RA风险比，Logistic回归)
The factors for associated with depression (PsA vs. RA odds ratio, Logistic regression)
| Items | OR | 95%CI | P |
| Abbreviations as in Table 1. | |||
| PsA vs. RA | 2.70 | 1.14-6.44 | 0.025 |
| Age | 0.97 | 0.95-0.99 | 0.004 |
| Disease duration | 0.94 | 0.91-0.98 | 0.002 |
| SDAI | 1.00 | 0.98-1.03 | 0.977 |
| HAQ | 1.04 | 1.01-1.08 | 0.031 |
| PASI | 1.06 | 1.02-1.11 | 0.009 |
2.3. 抑郁与非抑郁PsA患者临床表现和超声特点比较
将114例PsA患者分为抑郁组(36例)和非抑郁组(78例)。与非抑郁组患者相比，抑郁组患者的年龄更小[(41.6±14.5)岁vs. (50.4±12.1)岁，P=0.001]，银屑病病程更短[10.0(5.3，15.8)年vs. 15.5(7.8，29.3)年，P=0.048]，疼痛VAS评分更高[4.0(3.0，6.0) vs. 3.0(2.0，5.0)，P =0.015], PSAI评分更高[4.4(1.2，29.4) vs. 2.6(0.7，7.7)，P=0.018], 超声发现附着点炎的比例更高(63.9% vs. 42.3%，P=0.032)。其他人口学特征、疾病活动度指标、伴发合并症及超声特点方面，两组间差异无统计学意义(表 3)。
表 3.
抑郁与非抑郁PsA患者临床表现和超声特点比较
Comparisons of clinical and ultrasonographic features between PsA patients with depression and without depression
| Items | PsA with depression (n=36) | PsA without depression (n=78) | P |
| Data are shown as n(%), x±s and M (P25, P75). PsO, psoriasis; DAPSA, disease activity index for psoriatic arthritis; NSAIDs, nonsteroidal anti-inflammatory drugs; PD, power Doppler; GS, grey scale; BMI, body mass index. Other abbreviations as in Table 1. | |||
| Female | 18 (50.0) | 37 (47.40) | 0.799 |
| Age/years | 41.6±14.5 | 50.4±12.1 | 0.001 |
| Disease duration of PsO/years | 10.0 (5.3, 15.8) | 15.5 (7.8, 29.3) | 0.048 |
| Disease duration of PsA/years | 3.5 (1.0, 9.5) | 3.3 (1.2, 8.5) | 0.932 |
| TJC 68 | 3.0 (1.3, 9.8) | 2.5 (1.0, 8.0) | 0.495 |
| SJC 66 | 3.0 (0.3, 6.0) | 2.0 (0.0, 5.3) | 0.641 |
| Pain VAS (0-10) | 4.0 (3.0, 6.0) | 3.0 (2.0, 5.0) | 0.015 |
| PGA (0-10) | 5.0 (3.0, 6.8) | 4.0 (2.0, 5.0) | 0.059 |
| EGA (0-10) | 3.0 (2.0, 5.0) | 3.0 (1.5, 4.3) | 0.207 |
| CRP/(mg/L) | 5.7 (2.4, 20.3) | 4.6 (1.9, 15.6) | 0.592 |
| ESR/(mm/h) | 12.5 (7.0, 27.0) | 11.0 (5.0, 28.3) | 0.676 |
| DAPSA | 17.4 (8.7, 27.7) | 14.2 (7.8, 24.4) | 0.239 |
| HAQ | 2.5 (0.0, 8.8) | 1.0 (0.0, 7.3) | 0.305 |
| PSAI | 4.4 (1.2, 29.4) | 2.6 (0.7, 7.7) | 0.018 |
| Ultrasonographic feathers | |||
| Synovitis GS total score | 1.5 (0.0, 3.8) | 1.5 (0.0, 4.0) | 0.957 |
| Synovitis PD total score | 0.0 (0.0, 1.0) | 0.0 (0.0, 2.0) | 0.414 |
| Tenosynovitis GS total score | 0.0 (0.0, 2.0) | 0.0 (0.0, 2.0) | 0.279 |
| Tenosynovitis PD total score | 0.0 (0.0, 1.0) | 0.0 (0.0, 1.0) | 0.528 |
| Presence of enthesitis | 23 (63.9) | 33 (42.3) | 0.032 |
| Bone erosion | 16 (44.4) | 32 (41.0) | 0.731 |
| csDMARDs used | 0.165 | ||
| csDMARDs-naive | 4 (11.1) | 10 (11.8) | |
| Single csDMARD | 22 (61.1) | 58 (74.4) | |
| Combined csDMARDs | 10 (27.8) | 10 (12.8) | |
| Biological DMARDs used | 1 (2.8) | 1 (1.3) | 0.534 |
| NSAIDs used | 12 (33.3) | 19 (24.4) | 0.317 |
| BMI/(kg/m2) | 23.2±2.8 | 24.0±3.0 | 0.178 |
| Waist circumference/cm | 82.3±10.5 | 84.6±8.5 | 0.250 |
| Onychosis | 16 (44.6) | 53 (62.4) | 0.069 |
| Ophthalmitis | 2 (5.6) | 1 (1.3) | 0.234 |
| Metabolic syndrome | 8 (22.2) | 30 (38.5) | 0.087 |
| Cigarette smoking | 0.902 | ||
| Non-smoker | 23 (63.9) | 53 (67.9) | |
| Ex-smoker | 5 (13.9) | 9 (11.5) | |
| Current smoker | 8 (22.2) | 16 (20.5) | |
| Family history of PsO/PsA | 17 (47.2) | 23 (29.5) | 0.065 |
2.4. 焦虑与非焦虑PsA患者临床表现和超声特点比较
将114例PsA患者分为焦虑组(15例)和非焦虑组(99例)。焦虑组患者的PSAI评分高于非焦虑组[7.6(0.6，39.0) vs. 3.0(0.8，8.4)，P=0.047]，其他人口学特征、疾病活动度指标、伴发合并症及超声特点方面，两组间差异无统计学意义(表 4)。
表 4.
焦虑与非焦虑PsA患者临床表现和超声特点比较
Comparisons of clinical and ultrasonographic features between PsA patients with anxiety and without anxiety
| Items | PsA with anxiety (n=15) | PsA without anxiety (n=99) | P |
| Data are shown as n(%), x±s and M (P25, P75). Abbreviations as in Table 1 and 3. | |||
| Female | 8 (53.3) | 47 (47.5) | 0.672 |
| Age/years | 42.8±16.8 | 48.3±12.8 | 0.140 |
| Disease duration of PsO/years | 11.0 (4.0, 20.0) | 14.0 (8.0, 26.0) | 0.401 |
| Disease duration of PsA/years | 7.0 (1.0, 12.0) | 3.0 (1.0, 8.0) | 0.233 |
| TJC 68 | 2.0 (0.0, 10.0) | 3.0 (1.0, 8.0) | 0.939 |
| SJC 66 | 2.0 (0.0, 6.0) | 2.0 (0.0, 5.0) | 0.963 |
| Pain VAS (0-10) | 3.0 (3.0, 6.0) | 4.0 (2.0, 5.0) | 0.343 |
| PGA (0-10) | 3.0 (2.0, 6.0) | 4.0 (2.0, 6.0) | 0.922 |
| EGA (0-10) | 2.0 (2.0, 5.0) | 3.0 (2.0, 5.0) | 0.806 |
| CRP/(mg/L) | 5.5 (1.3, 11.9) | 5.4 (2.0, 15.8) | 0.672 |
| ESR/(mm/h) | 11.0 (5.0, 21.0) | 12.0 (5.0, 29.0) | 0.540 |
| DAPSA | 14.5 (5.1, 31.5) | 15.7 (8.3, 24.4) | 0.983 |
| HAQ | 3.0 (0.0, 14.0) | 1.0 (0.0, 7.0) | 0.263 |
| PSAI | 7.6 (0.6, 39.0) | 3.0 (0.8, 8.4) | 0.047 |
| Ultrasonographic feathers | |||
| Synovitis GS total score | 0.0 (0.0, 2.0) | 2.0 (0.0, 4.0) | 0.147 |
| Synovitis PD total score | 0.0 (0.0, 0.0) | 0.0 (0.0, 2.0) | 0.270 |
| Tenosynovitis GS total score | 0.0 (0.0, 2.0) | 0.0 (0.0, 2.0) | 0.608 |
| Tenosynovitis PD total score | 0.0 (0.0, 0.0) | 0.0 (0.0, 1.0) | 0.200 |
| Presence of enthesitis | 7 (46.7) | 49 (49.5) | 0.838 |
| Bone erosion | 5 (33.3) | 43 (43.4) | 0.460 |
| csDMARDs used | 0.068 | ||
| csDMARDs-naive | 2 (13.3) | 12 (12.1) | |
| Single csDMARDs | 7 (46.7) | 73 (73.7) | |
| Combined csDMARDs | 6 (40.0) | 14 (14.1) | |
| Biological DMARDs used | 1 (6.7) | 1 (1.0) | 0.617 |
| NSAIDs used | 3 (20.0) | 28 (28.3) | 0.718 |
| BMI/(kg/m2) | 24.3±2.4 | 23.6±3.0 | 0.417 |
| Waist circumference/cm | 84.7±11.8 | 83.7±8.8 | 0.734 |
| Onychosis | 6 (40.0) | 58 (58.6) | 0.176 |
| Ophthalmitis | 0 | 3 (3.0) | 0.652 |
| Metabolic syndrome | 6 (40.0) | 32 (32.3) | 0.557 |
| Cigarette smoking | 0.266 | ||
| Non-smokers | 11 (73.3) | 65 (65.7) | |
| Ex-smokers | 3 (20.0) | 11 (11.1) | |
| Current smokers | 1 (6.7) | 23 (23.2) | |
| Family history of PsO/PsA | 7 (46.7) | 33 (33.3) | 0.313 |
2.5. PsA患者发生抑郁和焦虑的相关因素
将性别、年龄、银屑病病程、疼痛VAS评分、PASI评分、超声附着点炎阳性纳入PsA患者发生抑郁的多因素Logistic回归模型，结果发现，年龄(OR=0.95，P=0.008)、银屑病病程(OR=0.94，P=0.018)、疼痛VAS评分(OR=1.47，P=0.011)、PASI评分(OR=1.07，P=0.007)、超声附着点炎阳性(OR=4.13，P=0.009)是PsA抑郁的相关因素。将性别、年龄、PASI评分纳入PsA焦虑的多因素Logistic回归模型，结果显示，PASI评分(OR=1.07，P=0.001)是PsA患者发生焦虑的相关因素(表 5)。
表 5.
PsA患者发生抑郁/焦虑的相关因素(多因素Logistic回归)
The associated factors for depression/anxiety in PsA (multivariate Logistic regression)
| Items | OR | 95%CI | P |
| Abbreviations as in Table 1. | |||
| Associated factors for depression | |||
| Age | 0.95 | 0.91-0.99 | 0.008 |
| Disease duration | 0.94 | 0.90-0.99 | 0.018 |
| Pain VAS | 1.47 | 1.09-1.98 | 0.011 |
| PASI | 1.07 | 1.02-1.13 | 0.007 |
| Presence of ultrasound enthesitis | 4.13 | 1.42-12.05 | 0.009 |
| Associated factor for anxiety | |||
| PASI | 1.07 | 1.03-1.12 | 0.001 |
3. 讨论
PsA是累及关节、皮肤、眼等多系统的自身免疫性疾病，患者在承受躯体疾患痛苦的同时，往往合并抑郁或焦虑。精神障碍会严重影响个人的工作和生活，严重的抑郁患者还有自杀倾向，给家庭和社会带来巨大的健康问题和经济负担。另一方面，焦虑和抑郁与PsA的不良预后相关，会导致疾病不易缓解[21]、致残率升高和身体功能下降[22]。因此，有必要了解我国PsA合并抑郁和焦虑的患病情况及相关因素。
本研究中PsA患者抑郁患病率为31.6%，焦虑患病率13.2%，这一结果明显高于全人群抑郁和焦虑患病率的9%和7%[23]。Zhao等[24]对24篇相关研究进行系统综述及荟萃分析，结果显示PsA患者中20%(95%CI：8%~35%)为轻度以上抑郁，33%(95%CI：17%~53%)为轻度以上焦虑。Zusman等[25]筛选了一致性较好的18篇文献进行荟萃分析发现，PsA中抑郁的综合患病率为17%(95%CI：13%~21%)，焦虑的综合患病率为19%(95%CI：11%~29%)。与既往国外文献报道相似，本研究结果也显示，抑郁与焦虑在中国PsA患者中普遍存在。具体患病率的差异可能与入组人群的人种、疾病活动情况、病程、焦虑和抑郁量表选择不同相关。
在分析抑郁和焦虑的相关因素时，本研究结果提示年龄小、银屑病病程短的PsA更容易出现抑郁。既往研究中，Bacconnier等[26]对病程半年、1年及3年RA患者进行精神异常患病率比较，发现随着病程延长，患病率分别为47%、33%和26%，呈逐渐下降趋势。Overman等[27]对不同病程RA患者抑郁和焦虑的研究也得出类似结论。与RA相似，在疾病早期PsA新发的皮疹等症状作为重要的刺激因素，会让患者产生明显的躯体不适和巨大的心理压力，同时年龄较小的患者生活阅历少，抗压能力弱，心境不稳定，亦会产生悲观和压抑的情绪。PsA合并抑郁和焦虑中比较公认的相关因素包括银屑病皮疹与关节炎程度[28]。本研究结果验证了这一结论，即银屑病皮疹重的PsA更容易患抑郁和焦虑，VAS疼痛评分高的PsA更倾向于出现抑郁。单纯银屑病患者抑郁综合患病率为12%(95%CI：8%~18%)，是正常人群的1.57倍[29]，皮疹引起的瘙痒和外观缺陷会导致患者产生自卑和低落的情绪，甚至与社会隔离，导致焦虑和抑郁。而对于PsA的患者，银屑病皮疹和关节炎双重影响会加重精神障碍。多项研究证实PsA发生抑郁和焦虑与关节炎的疼痛程度相关，另外，PsA合并抑郁的比例高于单纯银屑病患者[30]，也从侧面反映了关节炎在PsA合并抑郁中发挥的重要作用。
超声是探查PsA滑膜炎、腱鞘炎、附着点炎等病变有效便捷的影像工具[31], 目前尚未见关于PsA超声病变与精神障碍关系的研究。本研究表明，有超声附着点炎的PsA更倾向于发生抑郁。风湿免疫科医生对PsA进行临床体检时，更加关注肿胀与压痛关节，对附着点的检查往往不全面。既往文献提示，超声比临床查体更加敏感，能够发现更多PsA中附着点炎的病变[32]。相比滑膜炎，附着点炎作为PsA特征性的病变，在疾病炎症中发挥的作用不容小觑。另有研究显示，炎性细胞因子可以通过大脑影响神经递质的分泌，诱发精神障碍[33]。因此，附着点炎产生的疼痛、功能障碍和神经递质的综合作用，可能是抑郁发生的来源。
此外，本研究还比较了PsA与RA患者抑郁和焦虑患病率，结果发现PsA比RA发生抑郁的风险更高(OR=2.7)。一项英国的病例对照研究显示，RA抑郁症患病风险比(hazard ratio, HR)为1.38，轻度银屑病的HR为1.30，重度银屑病的HR为1.71，RA与轻度银屑病的抑郁患病风险相当[34]。Sinnathurai等[35]研究发现PsA患者较RA患者合并抑郁的风险更高(OR=2.1)，与本研究结果接近。与RA相比，PsA除了会导致关节炎，还会引发严重皮肤病变，严重影响外形美观和社会交往，降低生活质量[6]，这可能是PsA比RA更容易发生抑郁的原因。
本研究存在一定局限性，比如研究为横断面时间点患病率的分析，但我们收集的人口学及临床资料较全面; 另外，本研究还发现了超声特点与抑郁和焦虑的关系，比较了PsA与RA患有焦虑和抑郁的风险。今后将开展前瞻性队列研究，进一步分析PsA患者抑郁和焦虑随病程、病情活动情况及药物治疗的变化。
PsA患者合并抑郁与焦虑比较常见，其中抑郁患病风险明显高于RA患者。年龄小、银屑病病程短、皮疹重、疼痛重、存在超声下附着点炎的PsA患者更容易出现抑郁，银屑病皮疹重更倾向于发生焦虑。因此，要重视PsA患者的身心共患病，加强抑郁和焦虑的早期识别，必要时采取积极有效的心理干预措施，以提高患者的生活质量和改善预后。
Funding Statement
国家自然科学基金(81901646、81771740、81971524)和北京大学第一医院青年临床研究专项基金(2019CR28)
Supported by National Natural Science Foundation of China (81901646, 81771740, 81971524) and Youth Clinical Research Project of Peking University First Hospital (2019CR28)
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