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

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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)

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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
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