Email Alert | RSS

Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (6): 1068-1073. doi: 10.19723/j.issn.1671-167X.2022.06.002

Previous Articles     Next Articles

A cross-sectional study on the clinical phenotypes of rheumatoid arthritis

Wen-xin CAI1,Shi-cheng LI2,3,Yi-ming LIU1,4,Ru-yu LIANG1,Jing LI1,Jian-ping GUO1,Fan-lei HU1,Xiao-lin SUN1,Chun LI1,Xu LIU1,Hua YE1,Li-zong DENG3,*(),Ru LI1,*(),Zhan-guo LI1,*()   

  1. 1. Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China
    2. Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou 215123, Jiangsu, China
    3. Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou Institute of Systems Medicine, Suzhou 215123, Jiangsu, China
    4. Department of Rheumatology and Immunology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
  • Received:2022-10-10 Online:2022-12-18 Published:2022-12-19
  • Contact: Li-zong DENG,Ru LI,Zhan-guo LI E-mail:denglz@ism.pumc.edu.cn;doctorliru123@163.com;zgli99@aliyun.com
  • Supported by:
    the National Natural Science Foundation of China(32141004)

RICH HTML

   

PDF (PC)

Abstract:

Objective: To explore the characteristics and clinical phenotypes of rheumatoid arthritis (RA) and provide the basis for further understanding, interventions and outcomes of this disease. Methods: RA patients attended at Peking University People's Hospital from 2018 to 2021 were enrolled in the study. Data collection included demographic data, the sites and numbers of joints involved, extra-articular manifestations (EAM), comorbidities and laboratory variables. Statistical and bioinformatical analysis was performed to establish clinical subtypes by clustering analysis based on the type of joint involved, EAM involvement and other autoimmune diseases overlapped. The characteristics of each subtype were analyzed. Results: A total of 411 patients with RA were enrolled. The mean age was (48.84±15.17) years, and 346 (84.2%) were females. The patients were classified into 4 subtypes: small joint subtype (74, 18.0%), total joint subtype (154, 37.5%), systemic subtype (100, 24.3%), and overlapping subtype (83, 20.2%). The small joint subtype had no medium or large joint involvement, and 35.1% had systemic involvement. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and platelet count (PLT) were lower than those in other subtypes, and the rates of positive rheumatoid factors (RF-IgA and RF-IgG) were significantly higher in the small joint subtype. The total joint subtype had both large and small joint involvement but no systemic involvement. The rate of morning stiffness and positive antinuclear antibodies (ANA) in this subtype were lower than those in other subtypes. In the systemic subtype, interstitial lung disease and secondary Sj?gren syndrome were the most common systemic involvements, with prominent levels of disease activity score 28-joint count (DAS28-ESR and DAS28-CRP). The overlapping subtype was commonly combined with Hashimoto's thyroiditis or primary Sj?gren syndrome. Female in the overlapping subtype was more common than in other subtypes. This subtype was characterized by hyperglobulinemia, hypocomplementemia and high rate of positive ANA, especially spotting type. Conclusion: Based on the clinical features, RA patients could be classified into 4 subtypes: small joint subtype, total joint subtype, systemic subtype, and overlapping subtype. Each subtype had its own clinical characteristics. They help for further understanding and a more individualized treatment strategy of RA.

Key words: Rheumatoid arthritis, Clinical phenotypes, Clustering analysis

CLC Number: 

  • R593.22

Figure 1

The distribution of RA subtypes (n=411)"

Table 1

Comparison of clinical characteristics of various subtypes of RA"

Items Small joint subtype (n=74) Total joint subtype (n=154) Systemic subtye (n=100) Overlapping subtype (n=83) F/χ2 P value
Female, n (%) 60 (81.1) 125 (81.2) 85 (85.0) 76 (91.6) 5.034 0.169
Onset Age/years，${\bar x}$±s 47.04±18.92 47.16±13.89 44.80±13.56 45.10±17.14 0.391 0.76
Diseae duration /months, ${\bar x}$±s 140.43±103.01 142.03±109.38 209.80±143.11 116.35±111.78 1.757 0.155
Family history, n (%) 8 (10.8) 19 (12.3) 11 (11.0) 7 (8.4) 0.845 0.839
History of smoking, n (%) 12 (16.2) 26 (16.9) 15 (15.0) 10 (12.0) 1.028 0.794
Morning stiffness time＞1 h，n (%) 44 (61.1) 70 (47.0) 56 (57.1) 45 (58.4) 5.415 0.144
TJC, M (P25, P75) 3.00 (0.50，16.00) 6.00 (2.00，14.00) 14.00 (4.00，23.00) 8.50 (2.00，18.75) 27.983 ＜0.001
SJC, M (P25, P75) 4.00 (1.50，12.00) 4.50 (1.75，13.25) 6.00 (2.00，16.00) 4.00 (2.00，12.00) 4.731 0.193
DAS28-ESR， M (P25, P75) 4.30 (3.82，5.82) 4.95 (4.02，5.92) 5.41 (4.51，6.95) 5.07 (3.86，5.99) 23.880 ＜0.001
DAS28-CRP， M (P25, P75) 3.63 (2.79，5.30) 4.30 (3.32，5.44) 4.80 (3.67，6.14) 4.12 (2.99，5.66) 26.062 ＜0.001
Small joint involvement, n (%) 74 (100.0) 125 (81.2) 92 (92.0) 67 (80.7) 20.929 ＜0.001
Medium/large joint involvement, n (%) 0 (0.0) 154 (100.0) 100 (100.0) 61 (73.5) 320.682 ＜0.001
Systemic involvement, n (%) 26 (35.1) 0 (0.0) 100 (100.0) 33 (39.8) 256.091 ＜0.001
Other AID overlapped, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 83 (100.0) 411.000 ＜0.001

Figure 2

The clinical features distribution of subtypes The small joint subtype had no medium or large joint involvement. The total joint subtype had both medium/large and small joint involvement but no systemic involvement. In the systemic subtype, interstitial lung disease and secondary Sj?gren syndrome were the most common systemic involvements. The overlapping subtype was commonly combined with Hashimoto's thyroiditis or primary Sj?gren syndrome. PIP, proximal interphalangeal; MCP, metacarpophalangeal; MTP, metatarsophalangeal joint; DIP, distal interphalangeal joint; ACJ, articulatio temporomandibularis joint; SCJ, sternoclavicular joint; ILD, interstitial lung disease; sSS, secondary Sj?gren syndrome; pSS, primary Sjogren syndrome; SLE, systemic lupus erythematosus; AIH, autoimmune hepatitis; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; SSc, systemic sclerosis; PsA, psoriatic arthritis; AS, ankylosing spondylitis; NS, nephrotic syndrome; IM, inflammatory myopathy; AIHA, autoimmune hemolytic anemia; ITP, idiopathic thrombocytopenic purpura; APS, antiphospholipid syndrome."

Table 2

Comparison of laboratory parameters of the four subtypes"

Items Small joint subtype (n=74) Total joint subtype (n=154) Systemic subtye (n=100) Overlapping subtype (n=83) χ2 P value
ESR/(mm/h) 37.00 (21.50，55.00) 42.00 (25.00，74.00) 60.00 (21.00，88.00) 41.00 (25.00，66.75) 21.580 ＜0.001
CRP/(mg/L) 10.56 (2.57，30.96) 19.60 (6.30，58.59) 21.70 (5.38，53.97) 12.94 (3.06，37.39) 25.918 ＜0.001
WBC/(×109/L) 5.70 (4.25，7.30) 6.15 (4.58，8.15) 5.90 (4.20，7.20) 5.65 (4.43，6.75) 4.362 0.225
NEU/(×109/L) 3.60 (2.45，4.60) 4.15 (2.68，5.40) 3.80 (2.50，5.20) 3.35 (2.70，4.78) 4.652 0.199
LYM/(×109/L) 1.30 (0.80，1.70) 1.40 (1.00，1.83) 1.30 (1.00，1.60) 1.30 (1.00，1.70) 2.604 0.457
HGB/(g/L) 119.00 (105.50，125.50) 113.50 (102.50，123.25) 112.00 (98.00，121.00) 111.50 (98.00，121.75) 3.695 0.296
PLT/(×109/L) 207.00 (179.00，276.00) 259.00 (211.00，315.50) 249.00 (185.00，295.00) 223.50 (197.75，266.00) 25.723 ＜0.001

Table 3

Comparison of immunologic parameters of the four subtypes"

Items Small joint subtype (n=74) Total joint subtype (n=154) Systemic subtype (n=100) Overlapping subtype (n=83) χ2 P value
γG/TP elevation/%, M (P25, P75) 17.40 (14.90，20.80) 20.50 (16.45，23.13) 19.90 (17.10，23.20) 22.25 (17.85，25.38) 12.892 0.005
IgA elevation 8 (11.1) 25 (16.9) 21 (22.1) 13 (15.7) 3.651 0.302
IgG elevation 6 (8.3) 35 (23.6) 20 (21.1) 21 (25.3) 8.597 0.035
IgM elevation 1 (1.4) 4 (2.7) 4 (4.2) 6 (7.2) 4.379 0.223
C3 reduction 17 (23.6) 16 (10.9) 15 (15.8) 21 (25.3) 10.060 0.018
RF-IgM 62 (83.8) 108 (70.6) 74 (75.5) 64 (77.1) 4.855 0.183
RF-IgA 15 (41.7) 17 (22.4) 9 (16.1) 9 (20.9) 8.486 0.037
RF-IgG 32 (45.1) 36 (24.8) 33 (33.3) 28 (34.6) 9.182 0.027
anti-CCP 66 (90.4) 125 (82.8) 87 (87.9) 72 (87.8) 3.008 0.39
APF 50 (70.4) 89 (61.4) 69 (69.7) 50 (61.7) 3.097 0.377
anti-MCV 28 (75.7) 47 (64.4) 33 (78.6) 27 (67.5) 3.263 0.353
GPI 25 (35.2) 56 (38.6) 46 (46.5) 29 (35.8) 3.067 0.381
ANA 24 (33.8) 31 (21.2) 34 (34.7) 37 (44.6) 14.306 0.003
Homogeneous type ANA 23 (32.4) 57 (39.0) 36 (36.7) 26 (31.3) 1.786 0.618
Spotting type ANA 20 (28.2) 31 (21.2) 26 (26.5) 34 (41.0) 10.364 0.016
1 Turesson C , O'Fallon WM , Crowson CS , et al. Extra-articular disease manifestations in rheumatoid arthritis: Incidence trends and risk factors over 46 years[J]. Ann Rheum Dis, 2003, 62 (8): 722- 727.
doi: 10.1136/ard.62.8.722
2 Li R , Sun J , Ren LM , et al. Epidemiology of eight common rheumatic diseases in China: A large-scale cross-sectional survey in Beijing[J]. Rheumatology (Oxford), 2012, 51 (4): 721- 729.
doi: 10.1093/rheumatology/ker370
3 Zhou Y , Wang X , An Y , et al. Disability and health-related quality of life in Chinese patients with rheumatoid arthritis: A cross-sectional study[J]. Int J Rheum Dis, 2018, 21 (9): 1709- 1715.
doi: 10.1111/1756-185X.13345
4 Aletaha D , Neogi T , Silman AJ , et al. 2010 rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative[J]. Arthritis Rheum, 2010, 62 (9): 2569- 2581.
doi: 10.1002/art.27584
5 Vij R , Strek ME . Diagnosis and treatment of connective tissue disease-associated interstitial lung disease[J]. Chest, 2013, 143 (3): 814- 824.
doi: 10.1378/chest.12-0741
6 Linn-Rasker SP , van der Helm-van Mil AHM , Breedveld FC , et al. Arthritis of the large joints, in particular, the knee, at first presentation is predictive for a high level of radiological destruction of the small joints in rheumatoid arthritis[J]. Ann Rheum Dis, 2007, 66 (5): 646- 650.
doi: 10.1136/ard.2006.066704
7 Drossaers-Bakker KW , Kroon HM , Zwinderman AH , et al. Radiographic damage of large joints in long-term rheumatoid arthritis and its relation to function[J]. Rheumatology (Oxford), 2000, 39 (9): 998- 1003.
doi: 10.1093/rheumatology/39.9.998
8 Lockshin MD , Levine AB , Erkan D . Patients with overlap autoimmune disease differ from those with 'pure' disease[J]. Lupus Sci Med, 2015, 2 (1): e000084.
doi: 10.1136/lupus-2015-000084
9 Wallace ZS , Zhang Y , Perugino CA , et al. Clinical phenotypes of IgG4-related disease: An analysis of two international cross-sectional cohorts[J]. Ann Rheum Dis, 2019, 78 (3): 406- 412.
doi: 10.1136/annrheumdis-2018-214603
10 Tarn JR , Howard-Tripp N , Lendrem DW , et al. Symptom-based stratification of patients with primary Sjögren's syndrome: Multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials[J]. Lancet Rheum, 2019, 1 (2): E85- E94.
doi: 10.1016/S2665-9913(19)30042-6
11 Platzer A , Alasti F , Smolen JS , et al. Trajectory clusters of radiographic progression in patients with rheumatoid arthritis: Associations with clinical variables[J]. Ann Rheum Dis, 2022, 81 (2): 175- 183.
doi: 10.1136/annrheumdis-2021-220331
12 Vergne-Salle P , Pouplin S , Trouvin AP , et al. The burden of pain in rheumatoid arthritis: Impact of disease activity and psychological factors[J]. Eur J Pain, 2020, 24 (10): 1979- 1989.
doi: 10.1002/ejp.1651
13 Lee YC , Frits ML , Iannaccone CK , et al. Subgrouping of patients with rheumatoid arthritis based on pain, fatigue, inflammation, and psychosocial factors[J]. Arthritis Rheum, 2014, 66 (8): 2006- 2014.
doi: 10.1002/art.38682
14 Terao C , Hashimoto M , Yamamoto K , et al. Three groups in the 28 joints for rheumatoid arthritis synovitis: Analysis using more than 17 000 assessments in the KURAMA database[J]. PLoS One, 2013, 8 (3): e59341.
doi: 10.1371/journal.pone.0059341
15 Curtis JR , Weinblatt M , Saag K , et al. Data-driven patient clustering and differential clinical outcomes in the brigham and women's rheumatoid arthritis sequential study registry[J]. Arthritis Care Res (Hoboken), 2021, 73 (4): 471- 480.
doi: 10.1002/acr.24471
[1] Hui WEI, Jingfeng ZHANG, Zhongqiang YAO, Jinxia ZHAO. Clinical characteristics and relevant factors of rheumatoid arthritis patients with anemia of chronic disease [J]. Journal of Peking University (Health Sciences), 2026, 58(2): 307-312.
[2] Tao WU, Jianzi LIN, Yafeng ZHU, Jianda MA, Peiwen JIA, Lijuan YANG, jie PAN, Yaowei ZOU, Ying YANG, Ye LU, Lie DAI. Serum inter-alpha-trypsin inhibitor heavy chain H3 is identified as a potential biomarker for myopenia in patients with rheumatoid arthritis using proteomic profiling [J]. Journal of Peking University (Health Sciences), 2025, 57(6): 1024-1031.
[3] Yan DING, Lifang WANG, Chaoran LI, Zhemin LU, Lianjie SHI. Rheumatoid arthritis combined with IgG4-related disease successfully treated with rituximab: A case report [J]. Journal of Peking University (Health Sciences), 2025, 57(6): 1203-1207.
[4] Ju YANG, Jing XU, Juhua DAI, Lianjie SHI. Expression of lumican protein in serum of patients with rheumatoid arthritis and its correlation with disease and immune activities [J]. Journal of Peking University (Health Sciences), 2025, 57(5): 911-918.
[5] Lianghua FENG, Lirong HONG, Yujia CHEN, Xueming CAI. Role and mechanism of ubiquitin-specific protease 35 in ferroptosis of rheumatoid arthritis-fibroblast like synoviocytes [J]. Journal of Peking University (Health Sciences), 2025, 57(5): 919-925.
[6] Peiwen JIA, Ying YANG, Yaowei ZOU, Zhiming OUYANG, Jianzi LIN, Jianda MA, Kuimin YANG, Lie DAI. Clinical characteristics of overlapping syndromes of low muscle mass in patients with rheumatoid arthritis and their impact on physical function [J]. Journal of Peking University (Health Sciences), 2024, 56(6): 1009-1016.
[7] Doudou MA, Zhemin LU, Qian GUO, Sha ZHU, Jin GU, Yan DING, Lianjie SHI. Successful treatment of rheumatoid arthritis complicated with myasthenia gravis with low-dose rituximab: A case report [J]. Journal of Peking University (Health Sciences), 2024, 56(6): 1110-1114.
[8] Rui YAN, Dan KE, Yan ZHANG, Li LI, Huanran SU, Wei CHEN, Mingxia SUN, Xiaomin LIU, Liang LUO. Diagnostic significance of serum chemokine CXCL-10 and Krebs von den lungen-6 level in patients with rheumatoid arthritis associated interstitial lung disease [J]. Journal of Peking University (Health Sciences), 2024, 56(6): 956-962.
[9] Liang ZHAO, Chenglong SHI, Ke MA, Jing ZHAO, Xiao WANG, Xiaoyan XING, Wanxing MO, Yirui LIAN, Chao GAO, Yuhui LI. Immunological characteristics of patients with anti-synthetase syndrome overlap with rheumatoid arthritis [J]. Journal of Peking University (Health Sciences), 2024, 56(6): 972-979.
[10] Yijun HAN, Xiaoli CHEN, Changhong LI, Jinxia ZHAO. Application status of methotrexate in patients with rheumatoid arthritis [J]. Journal of Peking University (Health Sciences), 2024, 56(6): 994-1000.
[11] Dongwu LIU, Jie CHEN, Mingli GAO, Jing YU. Rheumatoid arthritis with Castleman-like histopathology in lymph nodes: A case report [J]. Journal of Peking University (Health Sciences), 2024, 56(5): 928-931.
[12] Huina HUANG,Jing ZHAO,Xiangge ZHAO,Ziran BAI,Xia LI,Guan WANG. Regulatory effect of lactate on peripheral blood CD4+ T cell subsets in patients with rheumatoid arthritis [J]. Journal of Peking University (Health Sciences), 2024, 56(3): 519-525.
[13] Xiaofei TANG,Yonghong LI,Qiuling DING,Zhuo SUN,Yang ZHANG,Yumei WANG,Meiyi TIAN,Jian LIU. Incidence and risk factors of deep vein thrombosis in patients with rheumatoid arthritis [J]. Journal of Peking University (Health Sciences), 2024, 56(2): 279-283.
[14] Xue ZOU,Xiao-juan BAI,Li-qing ZHANG. Effectiveness of tofacitinib combined with iguratimod in the treatment of difficult-to-treat moderate-to-severe rheumatoid arthritis [J]. Journal of Peking University (Health Sciences), 2023, 55(6): 1013-1021.
[15] Qi WU,Yue-ming CAI,Juan HE,Wen-di HUANG,Qing-wen WANG. Correlation between dyslipidemia and rheumatoid arthritis associated interstitial lung disease [J]. Journal of Peking University (Health Sciences), 2023, 55(6): 982-992.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright © Journal of Peking University (Health Sciences), All Rights Reserved.
Powered by Beijing Magtech Co. Ltd