Rheumatic Diseases: New Progress in Clinical Research and Pathogenesis

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Hematology and Immunology".

Deadline for manuscript submissions: closed (10 April 2023) | Viewed by 24612

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Special Issue Editors


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Guest Editor
Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan
Interests: rheumatoid arthritis; T cells; non-coding RNAs; systemic lupus erythematosus

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Guest Editor
1. Graduate Institute of Long-Term Care, Tzu Chi University of Science and Technology, Hualien City, Hualien 970302, Taiwan
2. Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada
Interests: bibilometrics; epidemiology; health survey; complementary medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Rheumatic diseases are a diverse group of autoimmune disorders that primarily affect the joints, bones, muscles, and connective tissues. Rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, and ankylosing spondylitis, are chronic diseases that cause a dysregulation of the immune system. Different types of rheumatic diseases are associated with a wide array of clinical manifestations and complex pathogeneses.

The purpose of this Special Issue is to encourage researchers to share their latest research and to summarize the recent advances in clinical and pathologic aspects of the rheumatic disease. We invite authors to submit original articles and review articles focusing on pertinent topics and new advances in rheumatic diseases.

Prof. Dr. Ming-Chi Lu
Dr. Malcolm Koo
Guest Editors

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Keywords

  • rheumatoid arthritis
  • systemic lupus erythematosus
  • Sjögren's syndrome
  • ankylosing spondylitis
  • rheumatic diseases

Published Papers (11 papers)

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Editorial

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3 pages, 247 KiB  
Editorial
Rheumatic Diseases: New Progress in Clinical Research and Pathogenesis
by Malcolm Koo and Ming-Chi Lu
Medicina 2023, 59(9), 1581; https://doi.org/10.3390/medicina59091581 - 31 Aug 2023
Viewed by 860
Abstract
Rheumatic diseases encompass a group of disorders that primarily target the musculoskeletal system, including joints, bones, muscles, and connective tissue [...] Full article

Research

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9 pages, 314 KiB  
Article
Predictive Factors of the Use of Rituximab and Belimumab in Spanish Lupus Patients
by O. Capdevila, F. Mitjavila, G. Espinosa, L. Caminal-Montero, A. Marín-Ballvè, R. González León, A. Castro, J. Canora, B. Pinilla, E. Fonseca and G. Ruiz-Irastorza
Medicina 2023, 59(8), 1362; https://doi.org/10.3390/medicina59081362 - 25 Jul 2023
Cited by 2 | Viewed by 2078
Abstract
Objectives: To analyze the characteristics and the predictive factors of the use of rituximab and belimumab in daily practice in patients from the inception cohort Registro Español de Lupus (RELES). Material and methods: The study included 518 patients. We considered patients [...] Read more.
Objectives: To analyze the characteristics and the predictive factors of the use of rituximab and belimumab in daily practice in patients from the inception cohort Registro Español de Lupus (RELES). Material and methods: The study included 518 patients. We considered patients treated with biologics who received at least one dose of rituximab or belimumab, and possible indications of those manifestations registered at the same time or in the previous 2 months of the start of the therapy. Results: In our cohort, 37 (7%) patients received at least one biological treatment. Rituximab was prescribed in 26 patients and belimumab in 11. Rituximab was mainly prescribed for hemolytic anemia or thrombocytopenia (11 patients, 42%), lupus nephritis and neuropsychiatric lupus (5 patients each, 19%). Belimumab was mostly used for arthritis (8 patients, 73%). In the univariate analysis, the predictive factors at diagnosis for the use of biologic therapy were younger age (p = 0.022), a higher SLEDAI (p = 0.001) and the presence of psychosis (p = 0.011), organic mental syndrome (SOCA) (p = 0.006), hemolytic anemia (p = 0.001), or thrombocytopenia (p = 0.01). In the multivariant model, only younger age, psychosis, and hemolytic anemia were independent predictors of the use of biologics. Conclusions: Rituximab is usually given to patients with hematological, neuropsychiatric and renal involvement and belimumab for arthritis. Psychosis, hemolytic anemia and age at the diagnosis of lupus were independent predictive factors of the use of biological agents. Their global effects are beneficial, with a significant reduction in SLE activity and a low rate of side effects. Full article
11 pages, 647 KiB  
Article
Relationship between Chinese Herbal Medicine Use and Risk of Sjögren’s Syndrome in Patients with Rheumatoid Arthritis: A Retrospective, Population-Based, Nested Case-Control Study
by Hou-Hsun Liao, Hanoch Livneh, Miao-Chiu Lin, Ming-Chi Lu, Ning-Sheng Lai, Hung-Rong Yen and Tzung-Yi Tsai
Medicina 2023, 59(4), 683; https://doi.org/10.3390/medicina59040683 - 30 Mar 2023
Cited by 1 | Viewed by 2162
Abstract
Background and Objectives: Sjögren’s Syndrome (SS) is a common extra-articular feature among subjects with rheumatoid arthritis (RA). While Chinese herbal medicine (CHM) has been used to treat symptoms of RA for many years, few studies have examined its efficacy in guarding against [...] Read more.
Background and Objectives: Sjögren’s Syndrome (SS) is a common extra-articular feature among subjects with rheumatoid arthritis (RA). While Chinese herbal medicine (CHM) has been used to treat symptoms of RA for many years, few studies have examined its efficacy in guarding against the SS onset. This study aimed to compare risk of SS for RA patients with and without use of CHM. Materials and Methods: Data obtained for this nested case-control study were retrieved from Taiwanese nationwide insurance database from 2000–2013. Cases with SS claims were defined and matched to two randomly selected controls without SS from the recruited RA cohorts. Risk of SS in relation to CHM use was estimated by fitting multiple conditional logistic regression. Results: Patients aged between 20 and 80 years were included and 916 patients with incident SS were matched to 1832 non-SS controls by age, sex and index year. Among them, 28.1% and 48.4% cases ever received CHM therapy, respectively. After adjusting for baseline characteristics, CHM use was found to be related to a lower risk of SS among them (adjusted odds ratio = 0.40, 95% confidence interval: 0.34–0.47). A dose-dependent, reverse association, was further detected between the cumulative duration of CHM use and SS risk. Those receiving CHM therapy for more than 730 days showed a significantly reduced risk of SS by 83%. Conclusions: Findings of this study indicated that the add-on CHM formula, as part of RA care, may be a beneficial treatment for prevention against the incident SS. Full article
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9 pages, 639 KiB  
Article
Antibodies against Serum Anti-Melanoma Differentiation-Associated Gene 5 in Rheumatoid Arthritis Patients with Chronic Lung Diseases
by Shomi Oka, Takashi Higuchi, Hiroshi Furukawa, Kota Shimada, Akira Okamoto, Atsushi Hashimoto, Akiko Komiya, Koichiro Saisho, Norie Yoshikawa, Masao Katayama, Toshihiro Matsui, Naoshi Fukui, Kiyoshi Migita and Shigeto Tohma
Medicina 2023, 59(2), 363; https://doi.org/10.3390/medicina59020363 - 14 Feb 2023
Cited by 1 | Viewed by 1704
Abstract
Chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway diseases (ADs), are common complications of rheumatoid arthritis (RA). Rheumatoid factor (RF) and anti-citrullinated peptide antibodies are reported to be associated with CLD in RA patients. The presence of anti-melanoma differentiation-associated gene [...] Read more.
Chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway diseases (ADs), are common complications of rheumatoid arthritis (RA). Rheumatoid factor (RF) and anti-citrullinated peptide antibodies are reported to be associated with CLD in RA patients. The presence of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies (Abs) is associated with clinically amyopathic dermatomyositis developing into rapidly progressive ILD. However, few studies on anti-MDA5 Abs in RA have been published. Here, we analyzed the association of anti-MDA5 Abs with CLD complications in RA. Anti-MDA5 Abs were quantified in sera from RA patients with or without CLD. Anti-MDA5 Ab levels were higher in RA patients with ADs than without (mean ± SDM, 4.4 ± 2.4 vs. 4.0 ± 4.2, p = 0.0001). AUC values of anti-MDA5 Ab and RF ROC curves were similar in RA patients with or without CLD (0.578, 95%CI 0.530–0.627 and 0.579, 95%CI 0.530–0.627, respectively, p = 0.9411). Multiple logistic regression analysis of anti-MDA5 Abs and clinical characteristics yielded an MDA5-index with a higher AUC value than anti-MDA5 Ab alone (0.694, 95%CI 0.648–0.740, p = 5.08 × 10−5). Anti-MDA5 Abs were associated with ADs in RA patients and could represent a biomarker for CLD, similar to RF. The involvement of anti-MDA5 Abs in the pathogenesis of ADs in RA is proposed. Full article
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10 pages, 305 KiB  
Article
How Did the Two Years of the COVID-19 Pandemic Affect the Outcomes of the Patients with Inflammatory Rheumatic Diseases in Lithuania?
by Jolanta Dadonienė, Gabija Jasionytė, Julija Mironova, Karolina Staškuvienė and Dalia Miltinienė
Medicina 2023, 59(2), 311; https://doi.org/10.3390/medicina59020311 - 08 Feb 2023
Cited by 1 | Viewed by 1479
Abstract
Background and objectives: the COVID-19 pandemic globally caused more than 18 million deaths over the period of 2020–2021. Although inflammatory rheumatic diseases (RD) are generally associated with premature mortality, it is not yet clear whether RD patients are at a greater risk [...] Read more.
Background and objectives: the COVID-19 pandemic globally caused more than 18 million deaths over the period of 2020–2021. Although inflammatory rheumatic diseases (RD) are generally associated with premature mortality, it is not yet clear whether RD patients are at a greater risk for COVID-19-related mortality. The aim of our study was to evaluate mortality and causes of death in a retrospective inflammatory RD patient cohort during the COVID-19 pandemic years. Methods: We identified patients with a first-time diagnosis of inflammatory RD and followed them up during the pandemic years of 2020–2021. Death rates, and sex- and age-standardized mortality ratios (SMRs) were calculated for the prepandemic and pandemic periods. Results: We obtained data from 11,636 patients that had been newly diagnosed with inflammatory RD and followed up until the end of 2021 or their death. The mean duration of the follow-up was 5.5 years. In total, 1531 deaths occurred between 2013 and 2021. The prevailing causes of death in the prepandemic period were cardiovascular diseases, neoplasms, and diseases of the respiratory system. In the pandemic years, cardiovascular diseases and neoplasms remained the two most common causes of death, with COVID-19 in third place. The SMR of the total RD cohort was 0.83. This trend was observed in rheumatoid arthritis and spondyloarthropathy patients. The SMR in the group of connective-tissue diseases and vasculitis was higher at 0.93, but did not differ from that of the general population. The excess of deaths in the RD cohort during the pandemic period was negative (−27.2%), meaning that RD patients endured the pandemic period better than the general population did. Conclusions: The COVID-19 pandemic did not influence the mortality of RD patients. Strict lockdown measures, social distancing, and early vaccination were the main factors that resulted in reduced mortality in this cohort during the pandemic years. Full article
14 pages, 354 KiB  
Article
Efficacy of Siwan Traditional Therapy on Erythrocyte Sedimentation Rate, Lipid Profile, and Atherogenic Index as Cardiac Risk Factors Related to Rheumatoid Arthritis
by Noha F. Mahmoud, Nashwa M. Allam, Islam I. Omara and Howida A. Fouda
Medicina 2023, 59(1), 54; https://doi.org/10.3390/medicina59010054 - 27 Dec 2022
Cited by 3 | Viewed by 1998
Abstract
Background and Objectives: The most frequent cause of mortality in rheumatoid arthritis (RA) patients is cardiovascular disease (CVD). Inflammation, dyslipidemia, and decreased physical activity are some of the main risk factors for CVD. Siwan sand therapy is a type of traditional therapy [...] Read more.
Background and Objectives: The most frequent cause of mortality in rheumatoid arthritis (RA) patients is cardiovascular disease (CVD). Inflammation, dyslipidemia, and decreased physical activity are some of the main risk factors for CVD. Siwan sand therapy is a type of traditional therapy used in Egypt to treat RA. The approach of this therapy depends on the experience of the healers. The aim of the current study was to compare the effects of three sessions of Siwan traditional therapy to five sessions on common CVD risk factors and physical function in rheumatoid arthritis patients. Materials and Methods: Thirty patients (9 male and 21 female) were assigned into two groups of equal size: group (A) received three sessions of Siwan traditional therapy in the form of a sand bath. Group (B) received the same form of therapy for five days. Erythrocyte sedimentation rate (ESR), lipid profile, atherogenic index of plasma (AIP), and a health assessment questionnaire (HAQ) were measured before and after treatment. Results: There was a significant increase above normal within group (A) for ESR (p = 0.001), triglycerides (TG; p = 0.015), total cholesterol (Tot-Chol; p = 0.0001), and low-density lipoprotein (LDL; p = 0.0001). However, there were no considerable differences in high-density lipoprotein (HDL; p = 0.106), very low-density lipoprotein (VLDL; p = 0.213), AIP (p = 0.648), and HAQ (p = 0.875). For the second group, there were significant changes within group B only in Tot-Chol (p = 0.0001), HDL (p = 0.0001), VLDL (p = 0.0001), AIP (p = 0.008), and HAQ (p = 0.014). There was a significant difference between both groups regarding HDL (p = 0.027), LDL (p = 0.005), AIP (p = 0.029), ESR (p = 0.016), and HAQ (p = 0.036). Conclusions: For RA patients, five days of Siwan traditional therapy caused significant changes regarding inflammation, Tot-Chol, LDL, HDL, AIP, and functional activity when compared to three days of Siwan hot sand therapy. Full article
10 pages, 1319 KiB  
Article
Association of Clinical Manifestations of Systemic Lupus Erythematosus and Complementary Therapy Use in Taiwanese Female Patients: A Cross-Sectional Study
by Ming-Chi Lu, Chia-Wen Hsu, Hui-Chin Lo, Hsiu-Hua Chang and Malcolm Koo
Medicina 2022, 58(7), 944; https://doi.org/10.3390/medicina58070944 - 17 Jul 2022
Cited by 5 | Viewed by 2030
Abstract
Background and Objectives: Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that affects predominantly women in the childbearing years. Patients may seek complementary therapies to manage their health and to reduce symptoms. However, to our knowledge, no studies have explored [...] Read more.
Background and Objectives: Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that affects predominantly women in the childbearing years. Patients may seek complementary therapies to manage their health and to reduce symptoms. However, to our knowledge, no studies have explored the association between clinical manifestations of SLE and complementary therapies. Therefore, this study aimed to investigate the association of complementary therapies with common clinical manifestations in Taiwanese female patients with SLE. Materials and Methods: A cross-sectional study was conducted at a regional teaching hospital in southern Taiwan. Outpatients from the rheumatology clinic who met the inclusion criteria were consecutively recruited. Demographic data, clinical manifestations of SLE, and types of complementary therapy use were determined using paper-based questionnaire. Multiple logistic regression analyses were conducted to investigate the use of complementary therapies associated with clinical manifestations of SLE. Results: Of the 317 female patients with SLE, 60.9% were 40 years or older. The five SLE clinical manifestations with the highest prevalence were Raynaud’s phenomenon (61.2%), photosensitivity (50.2%), Sjögren’s syndrome (28.4%), arthralgia and arthritis (22.1%), and renal involvement (14.5%). Multiple logistic regression analyses revealed that Raynaud’s phenomenon was significantly associated with fitness walking or strolling (adjusted odds ratio [aOR] 1.77; p = 0.027) and fish oil supplements (aOR 3.55, p < 0.001). Photosensitivity was significantly and inversely associated with the use of probiotics (aOR 0.49; p = 0.019). Renal involvement was significantly associated with the use of probiotics (aOR 2.43; p = 0.026) and visit to the Chinese medicine department in a hospital (aOR 3.14, p = 0.026). Conclusions: We found that different clinical manifestations of SLE were associated with the use of different complementary therapies. Health care providers should have up-to-date knowledge of common complementary therapies and be ready to provide evidence-based advice to patients with SLE. Full article
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9 pages, 901 KiB  
Article
Risk of Spine Surgery in Patients with Rheumatoid Arthritis: A Secondary Cohort Analysis of a Nationwide, Population-Based Health Claim Database
by Chien-Han Chen, Chia-Wen Hsu and Ming-Chi Lu
Medicina 2022, 58(6), 777; https://doi.org/10.3390/medicina58060777 - 08 Jun 2022
Cited by 2 | Viewed by 2348
Abstract
Background and Objectives: To study the risk of spine surgery, including cervical and lumbar spine surgeries in patients with rheumatoid arthritis (RA) compared with those without a diagnosis of RA. Materials and Methods: This is a secondary data analysis using population-based [...] Read more.
Background and Objectives: To study the risk of spine surgery, including cervical and lumbar spine surgeries in patients with rheumatoid arthritis (RA) compared with those without a diagnosis of RA. Materials and Methods: This is a secondary data analysis using population-based health claim data. We identified newly diagnosed adult patients with RA between January 2000 and December 2012, according to the International Classification of Diseases, Ninth revision, clinical modification code 714.0 from Taiwan’s National Health Insurance Research Database. Using data frequency-matched by 10-year age intervals, sex and index year with the RA cohort at a ratio of 5:1, we assembled a comparison cohort. All patients were followed until the study outcomes occurred (overall spine surgery, cervical spine surgery, or lumbar spine surgery) or the end of follow-up. Adjusted incidence rate ratios (aIRR) were calculated using Poisson regression analysis with age group, socioeconomic status, geographical region, and osteoporosis included as potential confounders. Results: We identified 1287 patients with RA and 6435 patients without RA. The incidence of overall spine surgery (aIRR = 2.13, 95% confidence interval (CI) = 1.49–3.04) and lumbar spine surgery (aIRR = 2.14, 95% CI = 1.46–3.15) were all significantly higher in the RA cohort. Moreover, females over 45 years of age were particularly at risk for lumbar spine surgery. In RA patients, older age and the combination with the diagnosis of osteoporosis had an elevated risk for overall and lumbar spine surgery. Conclusion: Patients with RA had an increased risk of receiving spine surgery. Physicians should be vigilant for possible spinal problems in women and older patients with RA. Full article
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Review

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25 pages, 1144 KiB  
Review
Role of Inflammatory Cytokines in Rheumatoid Arthritis and Development of Atherosclerosis: A Review
by Dražen Bedeković, Ivica Bošnjak, Sandra Šarić, Damir Kirner and Srđan Novak
Medicina 2023, 59(9), 1550; https://doi.org/10.3390/medicina59091550 - 26 Aug 2023
Cited by 4 | Viewed by 1615
Abstract
Uncontrolled chronic inflammation results in cardiovascular disease and early death. In this review, we studied the impact of rheumatoid arthritis on the cardiovascular system, including the early and accelerated development of atherosclerosis and its clinical manifestations, focusing on the inflammatory mechanisms leading to [...] Read more.
Uncontrolled chronic inflammation results in cardiovascular disease and early death. In this review, we studied the impact of rheumatoid arthritis on the cardiovascular system, including the early and accelerated development of atherosclerosis and its clinical manifestations, focusing on the inflammatory mechanisms leading to arterial wall damage, rapid atherosclerotic plaque formation, and thrombosis. Furthermore, the effect of medications used to treat rheumatoid arthritis on the cardiovascular system was studied. The effect of chronic inflammation and medication on traditional cardiovascular risk factors is not the main subject of this review. We observed that uncontrolled chronic inflammation and some medications directly impact all the stages of atherosclerosis. In conclusion, reducing inflammation and maintaining long-term remission in rheumatoid arthritis may prevent early atherosclerosis. We believe that this review will encourage a better interdisciplinary approach to the management of these patients and further research in this field. Full article
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47 pages, 1726 KiB  
Review
Synthetic Pharmacotherapy for Systemic Lupus Erythematosus: Potential Mechanisms of Action, Efficacy, and Safety
by Angélica María Téllez Arévalo, Abraham Quaye, Luis Carlos Rojas-Rodríguez, Brian D. Poole, Daniela Baracaldo-Santamaría and Claudia M. Tellez Freitas
Medicina 2023, 59(1), 56; https://doi.org/10.3390/medicina59010056 - 27 Dec 2022
Cited by 4 | Viewed by 3865
Abstract
The pharmacological treatment of systemic lupus erythematosus (SLE) aims to decrease disease activity, progression, systemic compromise, and mortality. Among the pharmacological alternatives, there are chemically synthesized drugs whose efficacy has been evaluated, but which have the potential to generate adverse events that may [...] Read more.
The pharmacological treatment of systemic lupus erythematosus (SLE) aims to decrease disease activity, progression, systemic compromise, and mortality. Among the pharmacological alternatives, there are chemically synthesized drugs whose efficacy has been evaluated, but which have the potential to generate adverse events that may compromise adherence and response to treatment. Therapy selection and monitoring will depend on patient characteristics and the safety profile of each drug. The aim of this review is to provide a comprehensive understanding of the most important synthetic drugs used in the treatment of SLE, including the current treatment options (mycophenolate mofetil, azathioprine, and cyclophosphamide), review their mechanism of action, efficacy, safety, and, most importantly, provide monitoring parameters that should be considered while the patient is receiving the pharmacotherapy. Full article
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8 pages, 292 KiB  
Review
Increased Risk of Common Orthopedic Surgeries for Patients with Rheumatic Diseases in Taiwan
by Min-Chih Hsieh, Malcolm Koo, Chia-Wen Hsu and Ming-Chi Lu
Medicina 2022, 58(11), 1629; https://doi.org/10.3390/medicina58111629 - 11 Nov 2022
Cited by 3 | Viewed by 2409
Abstract
Background and Objectives: Rheumatic diseases, including rheumatoid arthritis, ankylosing spondylitis, psoriasis, and systemic lupus erythematosus (SLE), are characterized by chronic arthritis or spondyloarthritis, which can lead to joint and spine destruction. Our previous studies showed that the risk of common orthopedic surgeries, including [...] Read more.
Background and Objectives: Rheumatic diseases, including rheumatoid arthritis, ankylosing spondylitis, psoriasis, and systemic lupus erythematosus (SLE), are characterized by chronic arthritis or spondyloarthritis, which can lead to joint and spine destruction. Our previous studies showed that the risk of common orthopedic surgeries, including total knee replacement (TKR), total hip replacement (THR), or spine surgery, was increased in patients with rheumatoid arthritis, ankylosing spondylitis, psoriasis, and SLE. The aim of this review was to summarize the risk of TKR, THR, cervical spine, and lumbar spine surgery on the basis of studies conducted using data from Taiwan’s National Health Insurance Research Database (NHIRD). Materials and Methods: The risk of TKR, THR, cervical spine surgery, and lumbar spine surgery in patients with rheumatoid arthritis, ankylosing spondylitis, psoriasis, and SLE was summarized from the results of our previous studies and unpublished findings based on NHIRD data. Results: Patients with rheumatoid arthritis and psoriasis and men with ankylosing spondylitis showed an increased risk of TKR. Patients with rheumatoid arthritis, ankylosing spondylitis, and women with SLE showed an increased risk of receiving THR. Only patients with ankylosing spondylitis had an increased risk of cervical spine surgery, and patients with rheumatoid arthritis or ankylosing spondylitis showed an increased risk of lumbar spine surgery. Although the risk of THR, TKR, or spine surgery in these patients has declined in the era of biologics use, direct evidence for the effects of biologics agents is not yet available. Conclusions: There was an increased risk of common orthopedic surgery in patients with rheumatoid arthritis, ankylosing spondylitis, psoriasis, and SLE. Clinicians should be vigilant to reduce the increased risk of TKR and THR in young and middle-aged patients with rheumatoid arthritis, THR in young patients with ankylosing spondylitis, and young female patients with SLE, as well as cervical spine surgery in young patients with ankylosing spondylitis. Full article
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