Systemic Manifestations and Complications of Rheumatoid Arthritis

A topical collection in Journal of Clinical Medicine (ISSN 2077-0383). This collection belongs to the section "Immunology".

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Editor


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Guest Editor
Director of Rheumatology & Clinical Trial Center, Ajou University School of Medicine,164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea
Interests: rheumatoid arthritis; systemic lupus erythematosus; autoimmunity; osteoporosis; biomarker; targeted treatment

Topical Collection Information

Dear Colleagues,

Rheumatoid arthritis (RA) is a systemic autoimmune disease predominantly involving small joints and causing joint deformity and functional loss. In addition, systemic manifestations, such as pulmonary, cardiovascular, and neurologic involvement, are commonly developed in RA patients with severe inflammation or long-standing disease duration. With adequate treatment to control inflammation, some of these complications of RA can be prevented. However, the treatment of RA also produces complications, such as cardiovascular, musculosketal, infectious, and neurologic problems. The knowledge of these complications as they develop in patients with RA is important in order to enable prevention and treatment. The Special Issue on “Systemic Manifestations and Complications of Rheumatoid Arthritis” is now open to your contributions. We look forward to your work on the diagnostic, preventive, and therapeutic aspect of various complications in patients with RA.

Prof. Dr. Chang-Hee Suh
Guest Editor

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Keywords

  • Rheumatoid arthritis
  • Complications of treatment
  • Osteoporosis and fracture
  • Glucocorticoid-induced osteoporosis
  • Cardiovascular disease
  • Lung involvement
  • Infection
  • Neurologic complication

Published Papers (22 papers)

2023

Jump to: 2022, 2021, 2020

14 pages, 608 KiB  
Article
Association of Tumor Necrosis Factor Inhibitors with the Risk of Nontuberculous Mycobacterial Infection in Patients with Rheumatoid Arthritis: A Nationwide Cohort Study
by Hyun Jin Park, Boyoon Choi, Yun-Kyoung Song, Yoon-Jeong Oh, Eun Bong Lee, In-Wha Kim and Jung Mi Oh
J. Clin. Med. 2023, 12(22), 6998; https://doi.org/10.3390/jcm12226998 - 9 Nov 2023
Viewed by 961
Abstract
Tumor necrosis factor inhibitors (TNFi) are proposed as a risk factor for nontuberculous mycobacteria (NTM) infection. Limited research investigates NTM infection risk in rheumatoid arthritis (RA) patients treated with TNFi compared to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), considering other concurrent or prior [...] Read more.
Tumor necrosis factor inhibitors (TNFi) are proposed as a risk factor for nontuberculous mycobacteria (NTM) infection. Limited research investigates NTM infection risk in rheumatoid arthritis (RA) patients treated with TNFi compared to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), considering other concurrent or prior non-TNFi antirheumatic drugs. We aimed to evaluate the NTM infection risk associated with TNFi using a real-world database. Patients with RA treated with TNFi or csDMARDs between 2005 and 2016 were identified utilizing the Korean National Health Insurance Service database. To minimize potential bias, we aligned the initiation year of csDMARDs for both TNFi and csDMARD users and tracked them from their respective treatment start dates. The association of TNFi with NTM infection risk was estimated in a one-to-one matched cohort using a multivariable conditional Cox regression analysis. In the matched cohort (n = 4556), the incidence rates of NTM infection were 2.47 and 3.66 per 1000 person-year in TNFi and csDMARD users. Compared to csDMARDs, TNFi did not increase the risk of NTM infection (adjusted hazard ratio (aHR) 0.517 (95% confidence interval, 0.205–1.301)). The TNFi use in RA patients was not associated with an increased risk of NTM infection compared to csDMARDs. Nevertheless, monitoring during TNFi treatment is crucial. Full article
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2022

Jump to: 2023, 2021, 2020

12 pages, 1500 KiB  
Article
Distal Interphalangeal Joint Involvement May Be Associated with Disease Activity and Affected Joint Distribution in Rheumatoid Arthritis
by Takahiro Mizuuchi, Tetsuji Sawada, Susumu Nishiyama, Koichiro Tahara, Haeru Hayashi, Hiroaki Mori, Eri Kato, Mayu Tago, Toshihiro Matsui and Shigeto Tohma
J. Clin. Med. 2022, 11(5), 1405; https://doi.org/10.3390/jcm11051405 - 4 Mar 2022
Cited by 1 | Viewed by 3702
Abstract
We investigated the relationship between distal interphalangeal (DIP) joint involvement and disease activity in 10,038 patients with adult-onset rheumatoid arthritis (RA). The affected joint distribution was investigated using the joint indices (JI) x, y, and z, corresponding to the upper [...] Read more.
We investigated the relationship between distal interphalangeal (DIP) joint involvement and disease activity in 10,038 patients with adult-onset rheumatoid arthritis (RA). The affected joint distribution was investigated using the joint indices (JI) x, y, and z, corresponding to the upper and lower joints, and the predominance of large-joint involvement, respectively. DIP joint involvement (defined by the presence of tenderness and/or swelling in DIP joints) was present in 206 (2.1%) of 10,038 patients with RA. Patients with RA exhibiting DIP joint involvement were significantly younger, and more frequently women. DIP joint involvement was positively associated with Disease Activity Score-28 using C-reactive protein, and clinical variables related to high RA disease activity, including JIs x and y, and was negatively associated with JI z. JI x was significantly higher than JI y in RA patients with DIP joint involvement. An odds ratio analysis revealed that small-to-medium sized and upper-extremity joints ranked first, second, and fourth among the eight variables significantly associated with DIP joint involvement. The correlation coefficients revealed that small-sized and upper-extremity joints ranked first and second among the five significant variables. DIP joint involvement, albeit rare, is significantly associated with high RA disease activity with predominance of small-sized and upper-extremity joints. Full article
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14 pages, 784 KiB  
Article
Efficacy and Safety of Rituximab in Autoimmune Disease—Associated Interstitial Lung Disease: A Prospective Cohort Study
by Natalia Mena-Vázquez, Rocío Redondo-Rodríguez, Marta Rojas-Gimenez, Carmen María Romero-Barco, Sara Manrique-Arija, Rafaela Ortega-Castro, Ana Hidalgo Conde, Rocío Arnedo Díez de los Ríos, Eva Cabrera César, Francisco Espildora, María Carmen Aguilar-Hurtado, Isabel Añón-Oñate, Lorena Pérez-Albaladejo, Manuel Abarca-Costalago, Inmaculada Ureña-Garnica, Maria Luisa Velloso-Feijoo, Maria Victoria Irigoyen-Oyarzábal and Antonio Fernández-Nebro
J. Clin. Med. 2022, 11(4), 927; https://doi.org/10.3390/jcm11040927 - 10 Feb 2022
Cited by 5 | Viewed by 2747
Abstract
Objectives: To analyze the efficacy and safety of rituximab (RTX) in connective tissue disease associated with interstitial lung disease (CTD-ILD). Methods: We performed a multicenter, prospective, observational study of patients with CTD-ILD receiving rituximab between 2015 and 2020. The patients were assessed using [...] Read more.
Objectives: To analyze the efficacy and safety of rituximab (RTX) in connective tissue disease associated with interstitial lung disease (CTD-ILD). Methods: We performed a multicenter, prospective, observational study of patients with CTD-ILD receiving rituximab between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline, at 12 months, and at the end of follow-up. The main outcome measure at the end of follow-up was forced vital capacity (FVC) > 10% or diffusing capacity of the lungs for carbon monoxide (DLCO) > 15% and radiological progression or death. We recorded clinical characteristics, time to initiation of RTX, concomitant treatment, infections, and hospitalization. A Cox regression analysis was performed to identify factors associated with worsening ILD. Results: We included 37 patients with CTD-ILD treated with RTX for a median (IQR) of 38.2 (17.7–69.0) months. At the end of the follow-up, disease had improved or stabilized in 23 patients (62.1%) and worsened in seven (18.9%); seven patients (18.9%) died. No significant decline was observed in median FVC (72.2 vs. 70.8; p = 0.530) or DLCO (55.9 vs. 52.2; p = 0.100). The multivariate analysis showed the independent predictors for worsening of CTD-ILD to be baseline DLCO (OR (95% CI), 0.904 (0.8–0.9); p = 0.015), time to initiation of RTX (1.01 (1.001–1.02); p = 0.029), and mycophenolate (0.202 (0.04–0.8); p = 0.034). Only 28 of the 37 patients (75.6%) were still undergoing treatment with RTX: two patients (5.4%) stopped treatment due to adverse events and seven patients (18.9%) died owing to progression of ILD and superinfection. Conclusion: Lung function improved or stabilized in more than half of patients with CTD-ILD treated with RTX. Early treatment and combination with mycophenolate could reduce the risk of progression of ILD. Full article
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2021

Jump to: 2023, 2022, 2020

13 pages, 890 KiB  
Article
Association between Rheumatoid Arthritis and Meniere’s Disease: A Longitudinal Follow-Up Study Using a National Health Screening Cohort
by So Young Kim, Dae Myoung Yoo, Ji Hee Kim, Mi Jung Kwon, Joo-Hee Kim and Hyo Geun Choi
J. Clin. Med. 2021, 10(23), 5694; https://doi.org/10.3390/jcm10235694 - 3 Dec 2021
Cited by 2 | Viewed by 1730
Abstract
This study aimed to evaluate the impact of pre-existing rheumatoid arthritis (RA) on the occurrence of Meniere’s disease (MD). The 2002–2015 Korean National Health Insurance Service—Health Screening Cohort data were retrospectively analyzed. A total of 3038 participants with RA were matched with 12,152 [...] Read more.
This study aimed to evaluate the impact of pre-existing rheumatoid arthritis (RA) on the occurrence of Meniere’s disease (MD). The 2002–2015 Korean National Health Insurance Service—Health Screening Cohort data were retrospectively analyzed. A total of 3038 participants with RA were matched with 12,152 control participants for demographic factors. The occurrence of MD was evaluated in both the RA and control groups. The hazard ratios (HRs) of RA for participants with MD were calculated using a stratified Cox proportional hazard model. Additionally, subgroup analyses were conducted. The rate of MD was not different between the RA and control groups (1.5% vs. 1.3%, standardized difference = 0.01). The HR was not higher in the RA group than in the MD group (adjusted HR = 1.03, 95% confidence interval = 0.73–1.44, p = 0.885). A higher HR of RA for participants with MD was found in the ≥60-year-old subgroup in the crude model but not in the adjusted model. An association between RA and MD was not found in any of the other subgroups. A previous history of RA was not related to an increased risk of MD. Full article
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12 pages, 475 KiB  
Article
Comparison of Indexes to Measure Comorbidity Burden and Predict All-Cause Mortality in Rheumatoid Arthritis
by Yun-Ju Huang, Jung-Sheng Chen, Shue-Fen Luo and Chang-Fu Kuo
J. Clin. Med. 2021, 10(22), 5460; https://doi.org/10.3390/jcm10225460 - 22 Nov 2021
Cited by 9 | Viewed by 2149
Abstract
Objectives: To examine the comorbidity burden in patients with rheumatoid arthritis (RA) patients using a nationwide population-based cohort by assessing the Charlson Comorbidity Index (CCI), Elixhauser Comorbidity Index (ECI), Multimorbidity Index (MMI), and Rheumatic Disease Comorbidity Index (RDCI) scores and to investigate their [...] Read more.
Objectives: To examine the comorbidity burden in patients with rheumatoid arthritis (RA) patients using a nationwide population-based cohort by assessing the Charlson Comorbidity Index (CCI), Elixhauser Comorbidity Index (ECI), Multimorbidity Index (MMI), and Rheumatic Disease Comorbidity Index (RDCI) scores and to investigate their predictive ability for all-cause mortality. Methods: We identified 24,767 RA patients diagnosed from 1998 to 2008 in Taiwan and followed up until 31 December 2013. The incidence of comorbidities was estimated in three periods (before, during, and after the diagnostic period). The incidence rate ratios were calculated by comparing during vs. before and after vs. before the diagnostic period. One- and 5-year mortality rates were calculated and discriminated by low and high-score groups and modified models for each index. Results: The mean score at diagnosis was 0.8 in CCI, 2.8 in ECI, 0.7 in MMI, and 1.3 in RDCI, and annual percentage changes are 11.0%, 11.3%, 9.7%, and 6.8%, respectively. The incidence of any increase in the comorbidity index was significantly higher in the periods of “during” and “after” the RA diagnosis (incidence rate ratios for different indexes: 1.33–2.77). The mortality rate significantly differed between the high and low-score groups measured by each index (adjusted hazard ratios: 2.5–4.3 for different indexes). CCI was slightly better in the prediction of 1- and 5-year mortality rates. Conclusions: Comorbidities are common before and after RA diagnosis, and the rate of accumulation accelerates after RA diagnosis. All four comorbidity indexes are useful to measure the temporal changes and to predict mortality. Full article
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11 pages, 1403 KiB  
Article
Elevated APE1/Ref-1 Levels of Synovial Fluids in Patients with Rheumatoid Arthritis: Reflection of Disease Activity
by In Seol Yoo, Yu-Ran Lee, Seong Wook Kang, Jinhyun Kim, Hee-Kyoung Joo, Su-Jin Yoo, Chan Keol Park, Ha-Reum Lee, Ji Ah Park and Byeong-Hwa Jeon
J. Clin. Med. 2021, 10(22), 5324; https://doi.org/10.3390/jcm10225324 - 16 Nov 2021
Cited by 2 | Viewed by 1717
Abstract
There is growing evidence that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) regulates inflammatory responses. Rheumatoid arthritis (RA) is an autoimmune disease, which is characterized with synovitis and joint destruction. Therefore, this study was planned to investigate the relationship between APE1/Ref-1 and RA. Serum and [...] Read more.
There is growing evidence that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) regulates inflammatory responses. Rheumatoid arthritis (RA) is an autoimmune disease, which is characterized with synovitis and joint destruction. Therefore, this study was planned to investigate the relationship between APE1/Ref-1 and RA. Serum and synovial fluid (SF) were collected from 46 patients with RA, 45 patients with osteoarthritis (OA), and 30 healthy control (HC) patients. The concentration of APE1/Ref-1 in serum or SF was measured using the sandwich enzyme-linked immunosorbent assay (ELISA). The disease activity in RA patients was measured using the 28-joint disease activity score (DAS28). The serum APE1/Ref-1 levels in RA patients were significantly increased compared to HC and OA patients (0.44 ± 0.39 ng/mL for RA group vs. 0.19 ± 0.14 ng/mL for HC group, p < 0.05 and vs. 0.19 ± 0.11 ng/mL for OA group, p < 0.05). Likewise, the APE1/Ref-1 levels of SF in RA patients were also significantly increased compared to OA patients (0.68 ± 0.30 ng/mL for RA group vs. 0.31 ± 0.12 ng/mL for OA group, p < 0.001). The APE1/Ref-1 concentration in SF of RA patients was positively correlated with DAS28. Thus, APE1/Ref-1 may reflect the joint inflammation and be associated with disease activity in RA. Full article
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12 pages, 602 KiB  
Article
The Relationship between Platelet Indices and Ultrasound, Clinical, Laboratory Parameters of Disease Activity in Patients with Rheumatoid Arthritis
by Bożena Targońska-Stępniak, Krzysztof Grzechnik and Robert Zwolak
J. Clin. Med. 2021, 10(22), 5259; https://doi.org/10.3390/jcm10225259 - 12 Nov 2021
Cited by 5 | Viewed by 1796
Abstract
(1) Background: A proper assessment of disease activity is crucial for the management of a patient with rheumatoid arthritis (RA). Platelets seem to be involved in joint inflammation pathophysiology. Platelet indices (PIs) are markers of platelet activation, and include platelet count (PC), mean [...] Read more.
(1) Background: A proper assessment of disease activity is crucial for the management of a patient with rheumatoid arthritis (RA). Platelets seem to be involved in joint inflammation pathophysiology. Platelet indices (PIs) are markers of platelet activation, and include platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT). The purpose of the study was to assess the relationship between PIs and disease activity markers, both systemic (clinical, laboratory) and local (ultrasound, US), in patients with RA; (2) Methods: The study group consisted of 131 consecutive RA patients. The following assessments were performed: joint counts, Disease Activity Score (DAS28), complete blood cell counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and US of 24 small joints; (3) Results: Mean values of PIs remained within the normal reference ranges. Values of PC, PCT, PDW were significantly associated with disease activity markers, both clinical (DAS28, joint counts) and laboratory (CRP, ESR). In patients with high disease activity, PC, PCT were significantly higher and PDW lower. PC was positively correlated with Power Doppler US (PDUS) score. In patients with features of RA severity (antibodies positivity, extra-articular manifestations) PC and PCT were positively associated with all US parameters (Grey Scale US, PDUS, Global scores); (4) Conclusions: In patients with RA, PC and PCT may serve as positive disease activity markers and PDW may serve as a negative marker. PIs may be used as reliable, inexpensive markers of RA systemic activity; they may also serve as markers of local inflammation in the joints affected by RA. Full article
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11 pages, 1285 KiB  
Article
Frequency and Factors of Indeterminate QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold PLUS Test Results in Rheumatic Diseases
by Sung Soo Ahn, Hyung Woo Kim and Younhee Park
J. Clin. Med. 2021, 10(19), 4357; https://doi.org/10.3390/jcm10194357 - 24 Sep 2021
Cited by 7 | Viewed by 2931
Abstract
We compared the results and differences of indeterminate rates between the QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold PLUS (QFT-PLUS) tests in patients with rheumatic diseases and analyzed the associated factors. Data of patients with rheumatic diseases who had undergone the QFT-GIT or [...] Read more.
We compared the results and differences of indeterminate rates between the QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold PLUS (QFT-PLUS) tests in patients with rheumatic diseases and analyzed the associated factors. Data of patients with rheumatic diseases who had undergone the QFT-GIT or QFT-PLUS test were used, and information regarding patient demographics, primary diagnosis, laboratory results, and medications was collected. Furthermore, indeterminate result rates of the patient cohort and healthy controls were also compared. A total of 177 (43.4%) and 231 (56.6%) patients had undergone QFT-GIT and QFT-PLUS tests, respectively. Among them, four (2.3%) and seven (3.0%) patients had indeterminate results, which did not differ between the QFT-GIT and QFT-PLUS groups. Indeterminate results were significantly higher among patients with rheumatic diseases than in healthy controls (2.7% vs. 0.2%, p < 0.001). Multivariate logistic regression revealed that the lymphocyte count (hazard ratio (HR) 0.998, 95% confidence interval (CI) 0.997, 1.000; p = 0.012) and albumin level (HR 0.366, 95% CI 0.150, 0.890; p = 0.027) were predictive of indeterminate results. A lymphocyte count of ≤810/mm3 and an albumin level of ≤3.7 mg/dL were capable of discriminating between indeterminate and determinate results. The QFT-GIT and QFT-PLUS tests have comparable diagnostic performances in patients with rheumatic diseases. Decreased lymphocyte and albumin levels contribute to indeterminate results. Full article
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17 pages, 4588 KiB  
Review
Decision-Making Strategy for the Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD)
by Hideaki Yamakawa, Takashi Ogura, Hideto Kameda, Tomoo Kishaba, Tae Iwasawa, Tamiko Takemura and Kazuyoshi Kuwano
J. Clin. Med. 2021, 10(17), 3806; https://doi.org/10.3390/jcm10173806 - 25 Aug 2021
Cited by 25 | Viewed by 7960
Abstract
Rheumatoid arthritis (RA) is a common type of autoimmune arthritis. Patient clinical outcomes might be influenced by numerous respiratory diseases, but interstitial lung disease (ILD) is the most important comorbidity. RA-associated ILD (RA-ILD) is divided into acute/subacute and chronic forms. In the acute/subacute [...] Read more.
Rheumatoid arthritis (RA) is a common type of autoimmune arthritis. Patient clinical outcomes might be influenced by numerous respiratory diseases, but interstitial lung disease (ILD) is the most important comorbidity. RA-associated ILD (RA-ILD) is divided into acute/subacute and chronic forms. In the acute/subacute course, if the disease is severe as indicated by a diffuse alveolar damage pattern, high-dose corticosteroids combined with antimicrobial agents should be promptly initiated while considering the differential diagnoses, primarily acute exacerbation (AE) of RA-ILD, drug-induced pneumonitis, and Pneumocystis pneumonia. As initial therapeutic management in the chronic course, the RA itself should be stabilized without delay; thereafter, the activity of ILD itself can be stabilized, considering the safety of each anti-rheumatic drug. The formation of the usual interstitial pneumonia (UIP) pattern is the most important determinant because lung function can worsen more quickly with this pattern. However, because clinicians can fail to identify specific radiological patterns, it is important to determine whether each patient with RA-ILD has UIP-like lesions such as subpleural reticulation, traction bronchiectasis, and honeycombing especially progressively enlarged cysts. In patients with progressive RA-ILD and high risk for infection or AE of ILD in whom fibrosis is dominant, clinicians should consider starting an anti-fibrotic agent. Full article
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10 pages, 304 KiB  
Article
Assessment of Subclinical Psychotic Symptoms in Patients with Rheumatoid Arthritis and Spondyloarthritis
by Juan L. Prados-Ojeda, Rogelio Luque-Luque, Rafael M. Gordillo-Urbano, Ipek Guler, Clementina López-Medina, Eduardo Collantes-Estévez and Alejandro Escudero-Contreras
J. Clin. Med. 2021, 10(16), 3461; https://doi.org/10.3390/jcm10163461 - 4 Aug 2021
Cited by 2 | Viewed by 1839
Abstract
Inflammatory and autoimmune processes have been associated with the onset of depressive and psychotic symptoms. Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are rheumatic diseases with an inflammatory etiology. A high prevalence of depressive and anxiety-related comorbidity has been reported for both diseases, with [...] Read more.
Inflammatory and autoimmune processes have been associated with the onset of depressive and psychotic symptoms. Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are rheumatic diseases with an inflammatory etiology. A high prevalence of depressive and anxiety-related comorbidity has been reported for both diseases, with no evidence of a greater prevalence of psychosis. The objective of the present study was to evaluate for the first time subclinical psychotic symptoms in patients with RA and SpA. This is a cross-sectional, single-center study including RA and SpA patients, as well as healthy controls. Abnormal psychotic experiences (positive, negative, and depressive symptoms) were evaluated using the Community Assessment of Psychic Experiences (CAPE-42). Functional capacity was evaluated using the Short-Form Health Survey SF-12. We compared the CAPE and SF-12 scores between the three groups. We recruited 385 individuals: 218 with RA, 100 with SpA, and 67 healthy controls. According to the CAPE scale, the frequency of subclinical psychotic symptoms was greater in patients than in healthy controls (RA, 1.90 vs. 1.63, p < 0.001; SpA, 1.88 vs. 1.63, p = 0.001). Distress was also greater in patients than in controls owing to the presence of symptoms. No differences were observed between the three groups for the mental dimension scores in the SF-12 Health Survey (43.75 in RA, 45.54 in SpA, and 43.19 in healthy controls). Our findings point to a greater prevalence of subclinical psychotic symptoms in patients with RA and patients with SpA than in the general population. The results suggest an association between inflammation and depression/subclinical psychotic symptoms. Full article
13 pages, 903 KiB  
Article
Anti-Inflammatory Effects of Low-Dose Glucocorticoids Compensate for Their Detrimental Effects on Bone Mineral Density in Patients with Rheumatoid Arthritis
by Ji-Won Kim, Ju-Yang Jung, Hyoun-Ah Kim and Chang-Hee Suh
J. Clin. Med. 2021, 10(13), 2944; https://doi.org/10.3390/jcm10132944 - 30 Jun 2021
Cited by 5 | Viewed by 1781
Abstract
Objectives: This study aimed to provide reliable information on the impact of low-dose glucocorticoids (GCs) on the bone mineral density (BMD) of patients with rheumatoid arthritis (RA). Methods: This retrospective study enrolled 933 patients with RA who continued the consumption of GCs (GC [...] Read more.
Objectives: This study aimed to provide reliable information on the impact of low-dose glucocorticoids (GCs) on the bone mineral density (BMD) of patients with rheumatoid arthritis (RA). Methods: This retrospective study enrolled 933 patients with RA who continued the consumption of GCs (GC group) and 100 patients who had discontinued consumption for >1 year (no-GC group). The BMD values were measured at baseline and follow-up, and the annual rate of change in BMD between the groups was compared using dual-energy X-ray absorptiometry. We used multiple linear regression analysis to identify the factors associated with changes in BMD. Results: The demographic characteristics and use of medical treatments affecting bone metabolism were similar between the two groups. Furthermore, there were no significant differences in the annual rate of changes in BMD and incidence of newly developed osteoporosis and incidental fractures between the two groups. Multiple linear regression analysis revealed that the disease activity score for 28 joints with erythrocyte sedimentation rate was the only factor affecting the annual rate of changes in BMD, and it was inversely proportional to changes in BMD. Conclusion: The benefits of GC therapy in attenuating inflammation compensate for the risk of osteoporosis if adequate measures to prevent bone loss are implemented in patients with RA. Full article
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9 pages, 859 KiB  
Article
Long-Term Outcomes of Surgical Aortic Valve Replacement in Patients with Rheumatoid Arthritis
by Markus Malmberg, Antti Palomäki, Jussi O. T. Sipilä, Päivi Rautava, Jarmo Gunn and Ville Kytö
J. Clin. Med. 2021, 10(11), 2492; https://doi.org/10.3390/jcm10112492 - 4 Jun 2021
Cited by 4 | Viewed by 1884
Abstract
Background: Patients with rheumatoid arthritis (RA) have increased risk of developing cardiovascular disease and events. Little is, however, known about the influence of RA to the outcomes after surgical aortic valve replacement (SAVR). Methods: In a retrospective, nationwide, multicenter cohort study, RA patients [...] Read more.
Background: Patients with rheumatoid arthritis (RA) have increased risk of developing cardiovascular disease and events. Little is, however, known about the influence of RA to the outcomes after surgical aortic valve replacement (SAVR). Methods: In a retrospective, nationwide, multicenter cohort study, RA patients (n = 109) were compared to patients without RA (n = 1090) treated with isolated SAVR for aortic valve stenosis. Propensity score-matching adjustment for baseline features was used to study the outcome differences in a median follow-up of 5.6 years. Results: Patients with RA had higher all-cause mortality (HR 1.76; CI 1.21–2.57; p = 0.003), higher incidence of major adverse cardiovascular events (HR 1.63; CI 1.06–2.49; p = 0.025), and they needed more often coronary artery revascularization for coronary artery disease (HR 3.96; CI 1.21–12.90; p = 0.027) in long-term follow-up after SAVR. As well, cardiovascular mortality rate was higher in patients with RA (35.7% vs. 23.4%, p = 0.023). There was no difference in 30-day mortality (2.8% vs. 1.8%, p = 0.518) or in the need for aortic valve reoperations (3.7% vs. 4.0%, p = 0.532). Conclusions: Patients with rheumatoid arthritis had impaired long-term results and increased cardiovascular mortality after SAVR for aortic valve stenosis. Special attention is needed to improve outcomes of aortic valve stenosis patients with RA after SAVR. Full article
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11 pages, 1202 KiB  
Article
Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activation and Bone Destruction in the Bone Marrow of Patients with Rheumatoid Arthritis
by Weronika Kurowska, Iwona Slowinska, Zbigniew Krogulec, Piotr Syrowka and Wlodzimierz Maslinski
J. Clin. Med. 2021, 10(8), 1778; https://doi.org/10.3390/jcm10081778 - 19 Apr 2021
Cited by 13 | Viewed by 2338
Abstract
Normalizing bone metabolism is a challenge in rheumatoid arthritis (RA). Studies in mice suggest that anti-citrullinated protein antibodies (ACPAs) can trigger osteoclast activation and bone resorption in the bone marrow. However, data on the presence and role of ACPAs in human bone marrow [...] Read more.
Normalizing bone metabolism is a challenge in rheumatoid arthritis (RA). Studies in mice suggest that anti-citrullinated protein antibodies (ACPAs) can trigger osteoclast activation and bone resorption in the bone marrow. However, data on the presence and role of ACPAs in human bone marrow are scarce. We investigated whether ACPAs can contribute to osteoclast activation and bone erosion in RA bone marrow. Anti-cyclic citrullinated peptide antibodies (anti-CCP Abs), osteoclast activation indicators–the tartrate-resistant acid phosphatase 5b (TRAP5b) and cathepsin K, and bone degradation marker–C-terminal telopeptide of type I collagen (CTX-I) were measured in the bone marrow and peripheral blood of RA patients using ELISAs. We found that ACPAs present in RA bone marrow was associated with increased amounts of TRAP5b, cathepsin K and CTX-I in this location. Levels of IL-8, the key mediator of anti-citrullinated protein antibody (ACPA)-induced bone resorption, were also elevated in bone marrow containing anti-CCP Abs and positively correlated with TRAP5b and cathepsin K concentrations. Higher levels of TRAP5b, cathepsin K, CTX-I and IL-8 in bone marrow compared to peripheral blood indicate local generation of these molecules. Our results complement data from animal studies and highlight the relevance of ACPAs and bone marrow in bone resorption in RA. Full article
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12 pages, 404 KiB  
Article
Systemic Inflammatory Parameters in Patients with Elderly-Onset Rheumatoid Arthritis (EORA) and Young-Onset Rheumatoid Arthritis (YORA)—An Observational Study
by Bożena Targońska-Stępniak, Krzysztof Grzechnik, Katarzyna Kolarz, Danuta Gągoł and Maria Majdan
J. Clin. Med. 2021, 10(6), 1204; https://doi.org/10.3390/jcm10061204 - 14 Mar 2021
Cited by 11 | Viewed by 2520
Abstract
Background: Rheumatoid arthritis (RA) occurs more often in elderly individuals. Elderly onset RA (EORA) (onset > 60 years) encompasses a specific subset of patients if compared with young onset RA (YORA) (onset at a younger age). There is a need to define reliable, [...] Read more.
Background: Rheumatoid arthritis (RA) occurs more often in elderly individuals. Elderly onset RA (EORA) (onset > 60 years) encompasses a specific subset of patients if compared with young onset RA (YORA) (onset at a younger age). There is a need to define reliable, simple markers to properly assess the inflammatory activity of RA. Hematological markers of systemic inflammation (Platelet-To-Lymphocyte (PLR) and Neutrophil-To-Lymphocyte (NLR) ratios) are novel measures of the inflammatory response. The goal of the study was to analyze the course of EORA vs. YORA patients and to assess associations between systemic and clinical disease activity markers, including PLR and NLR, in different subsets of patients. PLR and NLR have not previously been assessed in EORA and YORA. Methods: The study group consisted of 113 consecutive patients (63 EORA and 50 YORA). The following assessments were performed: joint counts, Disease Activity Score (DAS28), complete blood cell counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Results: EORA was characterized by significantly higher disease activity markers (conventional inflammatory and clinical), a lower rate of remission or low disease activity, and less frequent use of biological drugs and glucocorticoids. The NLR and PLR were positively correlated with disease activity markers. The PLR was significantly lower in EORA compared with in YORA. Conclusion: EORA and YORA patients differed significantly. In EORA, conventional disease activity markers were higher, the PLR was significantly lower. Full article
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11 pages, 993 KiB  
Article
Interstitial Lung Disease Worsens Short- and Long-Term Outcomes of Systemic Rheumatic Disease Patients Admitted to the ICU: A Multicenter Study
by Lorrain Banuls, Juliette Vanoverschelde, Fanny Garnier, Matthieu Amalric, Samir Jaber, Jonathan Charbit, Kevin Chalard, Marc Mourad, Nacim Benchabane, Racim Benomar, Noemie Besnard, Delphine Daubin, Vincent Brunot, Kada Klouche and Romaric Larcher
J. Clin. Med. 2021, 10(5), 1037; https://doi.org/10.3390/jcm10051037 - 3 Mar 2021
Cited by 1 | Viewed by 1702
Abstract
Critically ill patients with systemic rheumatic diseases (SRDs) have a fair prognosis, while those with interstitial lung disease (ILD) have a poorer outcome. However, the prognosis of SRD patients with ILD admitted to the intensive care unit (ICU) remains unclear. We conducted a [...] Read more.
Critically ill patients with systemic rheumatic diseases (SRDs) have a fair prognosis, while those with interstitial lung disease (ILD) have a poorer outcome. However, the prognosis of SRD patients with ILD admitted to the intensive care unit (ICU) remains unclear. We conducted a case–control study to investigate the outcomes of critically ill SRD-ILD patients. Consecutive SRD-ILD patients admitted to five ICUs from January 2007 to December 2017 were compared to SRD patients without ILD. Mortality rates were compared between groups, and prognostic factors were then identified. One hundred and forty critically ill SRD patients were included in the study. Among the 70 patients with SRD–ILD, the SRDs were connective tissue diseases (56%), vasculitis (29%), sarcoidosis (13%), and spondylarthritis (3%). Patients were mainly admitted for acute exacerbation of SRD-ILD (36%) or infection (34%). ICU, in-hospital, and one-year mortality rates in SRD-ILD patients were higher than in SRD patients without ILD (n = 70): 40% vs. 16% (p < 0.01), 49% vs. 19% (p < 0.01), and 66% vs. 40% (p < 0.01), respectively. Hypoxemia, high sequential organ failure assessment (SOFA) score, and admission for ILD acute exacerbation were associated with ICU mortality. In conclusion, ILD worsened the outcomes of SRD patients admitted to the ICU. Admissions related to SRD-ILD acute exacerbation and the severity of the acute respiratory failure were associated with ICU mortality. Full article
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9 pages, 233 KiB  
Article
Relationship between Tooth Loss and the Medications Used for the Treatment of Rheumatoid Arthritis in Japanese Patients with Rheumatoid Arthritis: A Cross-Sectional Study
by Hiroko Hashimoto, Shimpei Hashimoto and Yoshihiro Shimazaki
J. Clin. Med. 2021, 10(4), 876; https://doi.org/10.3390/jcm10040876 - 20 Feb 2021
Cited by 8 | Viewed by 2088
Abstract
Background: There is limited information regarding the association between tooth loss and the medications used for the treatment of rheumatoid arthritis (RA). Here, we examined the association between tooth loss, disease severity, and drug treatment regimens in RA patients. Method: This study recruited [...] Read more.
Background: There is limited information regarding the association between tooth loss and the medications used for the treatment of rheumatoid arthritis (RA). Here, we examined the association between tooth loss, disease severity, and drug treatment regimens in RA patients. Method: This study recruited 94 Japanese patients with RA. The severity of RA was assessed using the Steinbrocker classification of class and stage. Data on RA medications were obtained from medical records. We examined the associations between tooth loss, RA severity, and drug treatment regi mens using multinomial logistic regression analyses. Results: Patients with 1–19 teeth had significantly higher odds ratios (ORs) of taking methotrexate (MTX) (OR, 8.74; 95% confidence interval (CI), 1.11–68.8) and biologic disease-modifying antirheumatic drugs (bDMARDs) (OR, 21.0; 95% CI, 1.3–339.1) compared to those with 27–28 teeth when adjusted for RA severity (class). Furthermore, patients with 1–19 teeth had significantly higher ORs of taking MTX (OR, 9.71; 95% CI, 1.22–77.1) and bDMARDs (OR, 50.2; 95% CI, 2.55–990.6) compared to those with 27–28 teeth when adjusted for RA severity (stage). Conclusion: RA patients with fewer teeth were more likely to take stronger RA therapies, independent of RA severity and other factors. Full article
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Review
The Key Comorbidities in Patients with Rheumatoid Arthritis: A Narrative Review
by Peter C. Taylor, Fabiola Atzeni, Alejandro Balsa, Laure Gossec, Ulf Müller-Ladner and Janet Pope
J. Clin. Med. 2021, 10(3), 509; https://doi.org/10.3390/jcm10030509 - 1 Feb 2021
Cited by 44 | Viewed by 8922
Abstract
Comorbidities in patients with rheumatoid arthritis (RA) are often associated with poor health outcomes and increased mortality. Treatment decisions should take into account these comorbidities due to known or suspected associations with certain drug classes. In clinical practice, it is critical to balance [...] Read more.
Comorbidities in patients with rheumatoid arthritis (RA) are often associated with poor health outcomes and increased mortality. Treatment decisions should take into account these comorbidities due to known or suspected associations with certain drug classes. In clinical practice, it is critical to balance potential treatment benefit against the possible risks for comorbidities as well as the articular manifestations of RA. This review summarises the current literature relating to prevalence and risk factors for the important comorbidities of cardiovascular disease, infections, lymphomas and nonmelanoma skin cancers in patients with RA. The impact on patient outcomes and the interplay between these comorbidities and the therapeutic options currently available, including tumour necrosis factor inhibitors and newer biological therapies, are also explored. As newer RA therapies are developed, and patients gain wider and earlier access to advanced therapies, in part due to the emergence of biosimilars, it is important to consider the prevention or treatment of comorbidities as part of the overall management of RA. Full article
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11 pages, 442 KiB  
Article
A Pragmatic Application of Ultrasonography for the Assessment of Disease Activity in Patients with Early Inflammatory Arthritis
by Seoung Wan Nam and Taeyoung Kang
J. Clin. Med. 2021, 10(2), 283; https://doi.org/10.3390/jcm10020283 - 14 Jan 2021
Cited by 4 | Viewed by 1544
Abstract
The aim of the study was to examine the usefulness of targeted musculoskeletal ultrasonography (MSUS) in assessing the disease activity of patients with early inflammatory arthritis (EIA). Twenty-eight patients with EIA were enrolled. The MSUS examination of joints with arthritic signs (tenderness or [...] Read more.
The aim of the study was to examine the usefulness of targeted musculoskeletal ultrasonography (MSUS) in assessing the disease activity of patients with early inflammatory arthritis (EIA). Twenty-eight patients with EIA were enrolled. The MSUS examination of joints with arthritic signs (tenderness or swelling), measurement of 28-joint Disease Activity Score (DAS28), and its components were performed at four-week interval visits until power doppler (PD) US remission was achieved. Various MSUS parameters of grey scale (GS) and PD synovitis were measured. Pearson or Spearman correlation coefficients were determined for the purpose of the study. Data were gathered from a total of 85 visits. The Sum of GS grade correlated better with physical examination findings, while the Sum of PD grade correlated better with serum inflammatory markers and patient global health. However, Global OMERACT-EULAR Synovitis Score (GLOESS), which reflected both PD and GS grades, correlated evenly well with each clinical parameter. In addition, GLOESS correlated best with DAS28 in the overall study population (p < 0.01). Conclusively, our targeted MSUS parameters of arthritic joints, especially sums of semi-quantitative grades of synovitis, could be useful in monitoring patients with EIA. Full article
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2020

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8 pages, 701 KiB  
Article
Predictors of Flares in Patients with Rheumatoid Arthritis Who Exhibit Low Disease Activity: A Nationwide Cohort Study
by Yoon-Jeong Oh and Ki Won Moon
J. Clin. Med. 2020, 9(10), 3219; https://doi.org/10.3390/jcm9103219 - 7 Oct 2020
Cited by 2 | Viewed by 2099
Abstract
Using nationwide cohort data, this study evaluated predictors of flares in patients with rheumatoid arthritis (RA) who exhibit low disease activity (LDA) and the effects of flares on clinical outcomes. The Korean Observational Study Network for Arthritis (KORONA) registry is a nationwide Korean [...] Read more.
Using nationwide cohort data, this study evaluated predictors of flares in patients with rheumatoid arthritis (RA) who exhibit low disease activity (LDA) and the effects of flares on clinical outcomes. The Korean Observational Study Network for Arthritis (KORONA) registry is a nationwide Korean RA-specific cohort registry that collects data annually from 5.077 patients, with RA in 23 centers across South Korea. This study used data from 1.717 patients with RA who exhibited LDA [28–joint disease activity score (DAS28) < 3.2] at enrollment. Flares were defined as an increase in DAS28, compared with the previous value of > 1.2 or > 0.6, if the concurrent DAS28 was ≥ 3.2. Cox regression analysis was used to identify baseline predictors of flares. Of the 1.717 patients with RA, 566 (33.0%) experienced flares during the 2-year study period. An analysis of baseline characteristics of flare and non-flare groups revealed that more women and non-smokers were present in the flare group than in the non-flare group; the flare group also had higher scores on physician’s and patient’s pain and fatigue visual analogue scales (VAS) and the health assessment questionnaire (HAQ). In a multivariate analysis, physician’s VAS score, hemoglobin level, and HAQ score were significant predictors of flares. A high physician’s VAS score, low hemoglobin, and high HAQ score at baseline were significant predictors of flares in patients with RA who exhibited LDA. Full article
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11 pages, 719 KiB  
Article
Increased Risk of Temporomandibular Joint Disorder in Patients with Rheumatoid Arthritis: A Longitudinal Follow-Up Study
by Soo-Hwan Byun, Chanyang Min, Hyo-Geun Choi and Seok-Jin Hong
J. Clin. Med. 2020, 9(9), 3005; https://doi.org/10.3390/jcm9093005 - 17 Sep 2020
Cited by 10 | Viewed by 2678
Abstract
We evaluated the incidence of temporomandibular disorder (TMD) in patients with rheumatoid arthritis (RA) and examined the association between TMD and RA, through longitudinal follow-up. Population data from the Korean National Health Insurance Service-Health Screening Cohort from 2002 to 2015 was used. From [...] Read more.
We evaluated the incidence of temporomandibular disorder (TMD) in patients with rheumatoid arthritis (RA) and examined the association between TMD and RA, through longitudinal follow-up. Population data from the Korean National Health Insurance Service-Health Screening Cohort from 2002 to 2015 was used. From 514,866 subjects, 3122 with RA were matched with 12,488 controls in a 1:4 ratio. The crude and adjusted models (for obesity, smoking, alcohol consumption, blood pressure, blood glucose, total cholesterol, and Charlson Comorbidity Index scores) were calculated. Chi-square tests, Kaplan-Meier (KM) analysis, and two-tailed analyses were used for statistical analysis. Stratified Cox proportional hazard models were used to assess the hazard ratios (HR) and 95% confidence intervals (CI) for TMD in the RA group, compared to those in the control group. The adjusted HR for TMD in RA was 2.52 (95% CI = 1.70–3.74), compared to the control group. The results were consistent with the subgroup analyses, according to age and sex, except in men older than 60 years of age. KM analysis showed similar results. Hence, we found that patients with RA have a higher risk of TMD, and should be observed for symptoms of the initial stage of TMD to prevent the risk of aggravation. Full article
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11 pages, 810 KiB  
Article
The Relationship between Hematological Markers of Systemic Inflammation (Neutrophil-To-Lymphocyte, Platelet-To-Lymphocyte, Lymphocyte-To-Monocyte Ratios) and Ultrasound Disease Activity Parameters in Patients with Rheumatoid Arthritis
by Bożena Targońska-Stępniak, Robert Zwolak, Mariusz Piotrowski, Krzysztof Grzechnik and Maria Majdan
J. Clin. Med. 2020, 9(9), 2760; https://doi.org/10.3390/jcm9092760 - 26 Aug 2020
Cited by 31 | Viewed by 3185
Abstract
Background: An accurate measurement of disease activity is essential for the appropriate management of a patient with rheumatoid arthritis (RA). Hematological markers of systemic inflammation (Neutrophil-to-Lymphocyte (NLR), Platelet-to-Lymphocyte (PLR) and Lymphocyte-to-Monocyte (LMR) ratios) are reported to be novel, sensitive measures of inflammatory response, [...] Read more.
Background: An accurate measurement of disease activity is essential for the appropriate management of a patient with rheumatoid arthritis (RA). Hematological markers of systemic inflammation (Neutrophil-to-Lymphocyte (NLR), Platelet-to-Lymphocyte (PLR) and Lymphocyte-to-Monocyte (LMR) ratios) are reported to be novel, sensitive measures of inflammatory response, in addition to conventional markers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score (DAS28)). The goal of the study was to assess the relationship of NLR, PLR, and LMR with ultrasonography (US) parameters of disease activity in RA patients. Methods: The study group consisted of 126 consecutive RA patients (100 women, 26 men). The following assessments were performed: joint counts, DAS28, complete blood cell counts, ESR, CRP, and US of 24 small joints. Results: NLR and PLR were significantly positively correlated with all US parameters of disease activity (Grey Scale US, Power Doppler US, and Global scores). The mean values of NLR and PLR were significantly higher in patients with poor prognostic factors: moderate/high vs. low disease activity (NLR: p < 0.001; PLR: p = 0.007), anti-CCP positive vs. anti-CCP negative (NLR: p = 0.01; PLR: p = 0.006). In multiple regression tests, significant correlations were confirmed for: NLR and DAS28 (p = 0.04), and CRP (p = 0.001); PLR and Power Doppler US (p = 0.04), and ESR (p = 0.02). No correlation was found for LMR. Conclusion: NLR and PLR are associated with US disease activity parameters and may serve as reliable, inexpensive markers, with prognostic significance in RA. Full article
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5 pages, 178 KiB  
Editorial
Systemic Manifestations and Complications in Patients with Rheumatoid Arthritis
by Ji-Won Kim and Chang-Hee Suh
J. Clin. Med. 2020, 9(6), 2008; https://doi.org/10.3390/jcm9062008 - 26 Jun 2020
Cited by 21 | Viewed by 4291
Abstract
Rheumatoid arthritis (RA) is a systemic autoimmune disease with symmetrical peripheral polyarthritis, predominantly involving the small joints [...] Full article
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