Neurologic Manifestations of Rheumatologic Disorders.

OBJECTIVE: This article provides an overview of the neurologic manifestations of sarcoidosis and select rheumatologic disorders. An approach to the assessment and differential diagnosis of characteristic clinical presentations, including meningitis and vasculitis, is also reviewed. A review of treatment options is included as well as discussion of distinct areas of overlap, including rheumatologic disease in the setting of neuromyelitis spectrum disorder and demyelinating disease in the setting of tumor necrosis factor-α inhibitors. LATEST DEVELOPMENTS: An increased understanding of the immune mechanisms involved in sarcoidosis and rheumatologic diseases has resulted in a greater diversity of therapeutic options for their treatment. Evidence directing the treatment of the central nervous system (CNS) manifestations of these same diseases is lacking, with a paucity of controlled trials. ESSENTIAL POINTS: It is important to have a basic knowledge of the common CNS manifestations of rheumatologic diseases and sarcoidosis so that they can be recognized when encountered. In the context of many systemic inflammatory diseases, including systemic lupus erythematosus, IgG4-related disease, and sarcoidosis, CNS disease may be a presenting feature or occur without systemic manifestations of the disease, making familiarity with these diseases even more important.

Macrophage Activation Syndrome in the Setting of Rheumatic Diseases.

Patients with established rheumatic disorders may develop complications of macrophage activation syndrome due to severe flares of the underlying disease (adult-onset Still's disease, SLE); however, in most other rheumatic disorders, MAS develops in association with identified viral or other infectious triggers. It is therefore important to pursue appropriate studies to identify potential infectious triggers in rheumatic disease patients who develop MAS. Management is best directed toward treatment of the triggering infections and combinations of high-dose corticosteroids, calcineurin inhibitors, and biologic therapies targeting IL-1 and/or IL-6 to suppress the associated cytokine storm.

The risk and risk factors of chikungunya virus infection and rheumatological sequelae in a cohort of U.S. Military Health System beneficiaries: Implications for the vaccine era.

BACKGROUND: Understanding the risk of chikungunya virus (CHIKV) infection and rheumatic sequelae across populations, including travelers and the military, is critical. We leveraged healthcare delivery data of over 9 million U.S. Military Health System (MHS) beneficiaries to identify cases, and sampled controls, to estimate the risk of post-CHIKV rheumatic sequelae. METHODOLOGY/PRINCIPAL FINDINGS: MHS beneficiary CHIKV infections diagnosed 2014-2018 were identified from the Disease Reporting System internet, TRICARE Encounter Data Non-Institutional, and Comprehensive Ambulatory/Professional Encounter Record systems. Non-CHIKV controls were matched (1:4) by age, gender, beneficiary status, and encounter date. The frequency of comorbidities and incident rheumatic diagnoses through December 2018 were derived from International Classification of Diseases codes and compared between cases and controls. Poisson regression models estimated the association of CHIKV infection with rheumatic sequelae. We further performed a nested case-control study to estimate risk factors for post-CHIKV sequelae in those with prior CHIKV. 195 CHIKV cases were diagnosed between July 2014 and December 2018. The median age was 42 years, and 43.6% were active duty. 63/195 (32.3%) of CHIKV cases had an incident rheumatic diagnosis, including arthralgia, polyarthritis, polymyalgia rheumatica, and/or rheumatoid arthritis, compared to 156/780 (20.0%) of controls (p < 0.001). CHIKV infection remained associated with rheumatic sequelae (aRR = 1.579, p = 0.008) after adjusting for prior rheumatic disease and demography. Those with rheumatic CHIKV sequelae had a median 7 healthcare encounters (IQR 3-15). Among CHIKV infections, we found no association between post-CHIKV rheumatic sequelae and demography, service characteristics, or comorbidities. CONCLUSIONS/SIGNIFICANCE: CHIKV infection is uncommon but associated with rheumatic sequelae among MHS beneficiaries, with substantial healthcare requirements in a proportion of cases with such sequelae. No demographic, clinical, or occupational variables were associated with post-CHIKV rheumatic sequelae, suggesting that prediction of these complications is challenging in MHS beneficiaries. These findings are important context for future CHIKV vaccine decision making in this and other populations.

GLIM criteria-based identification of severe malnutrition and its relationship with the risk of mortality among older Chinese adults with arthritis or rheumatism.

BACKGROUND: Malnutrition is a well-known risk factor for mortality among older adults. Arthritis and rheumatism are characterized by chronic inflammation and are also related to malnutrition as diagnosed using the Global Leadership Initiative on Malnutrition (GLIM) criteria. This study was thus developed to examine the associations linking malnutrition and all-cause death among older adults in China, employing the GLIM criteria to assess malnutrition. METHODS: Two waves of the China Health and Retirement Longitudinal Study from 2013 and 2018 were used to conduct this study. Moderate malnutrition was defined as low BMI (< 18.5 and < 20 for individuals < 70 and 70 + years of age, respectively), an unintended 10-20% decrease in weight, or low muscle mass based on the sex-specific lowest 20% of the height-adjusted muscle mass as < 5.039 kg/m2 in women and < 6.866 kg/m2 in men. Severe malnutrition was defined as a > 20% unintended decrease in weight only or the combination of both low muscle mass and an unintended reduction of over 10% in weight. Associations between malnutrition and the risk of all-cause death were assessed through Cox regression analyses. RESULTS: Overall, this study enrolled 1766 subjects 60 + years of age, of whom 57.36% (1033/1766) were female. Malnutrition was estimated to affect 418 (23.67%) of these individuals at baseline, with 21.06% and 2.60% affected by moderate and severe malnutrition, respectively. Over the 5-year follow-up, 189 of these individuals died. Covariate-adjusted Cox regression analyses confirmed a significant association between severe malnutrition and the risk of death in this cohort (HR = 2.196, 95%CI 1.125-4.286, P = 0.021). CONCLUSIONS: Severe malnutrition, identified through screening based on the GLIM criteria, was associated with an increased risk of all-cause death among older Chinese adults with arthritis or rheumatism.

Identifying the genetic association between common rheumatic diseases and vitiligo.

BACKGROUND: Although observational studies have suggested a correlation between vitiligo and rheumatic diseases, conclusive evidence supporting a causal relationship is still lacking. Therefore, this study aims to explore the potential causal relationship between vitiligo and rheumatic diseases. METHODS: Using genome-wide association studies, we performed a two-sample Mendelian randomization (MR) analysis. In our analysis, the random-effects inverse variance weighted (IVW) method was predominantly employed, followed by several sensitivity analyses, which include heterogeneity, horizontal pleiotropy, outliers, and "leave-one-out" analyses. RESULTS: The genetically predicted vitiligo was associated with an increased risk of rheumatoid arthritis (RA) (OR, 1.47; 95% confidence interval [CI], 1.29-1.68; p < 0.001), and systemic lupus erythematosus (SLE) (OR, 1.22; 95% CI, 1.06-1.39; p = 0.005). The causal associations were supported by sensitivity analyses. In Sjögren's syndrome and ankylosing spondylitis, no causal relationship with vitiligo was found in the study. CONCLUSION: Our MR results support the causal effect that vitiligo leads to a higher risk of RA and SLE. Individuals with vitiligo should be vigilant for the potential development of RA and SLE. Managing and addressing this potential requires regular monitoring.

Potential association of rheumatic diseases with bone mineral density and fractures: a bi-directional mendelian randomization study.

BACKGROUND: Previous studies have implicated rheumatoid arthritis as an independent risk factor for bone density loss. However, whether there is a causal relationship between rheumatic diseases and bone mineral density (BMD) and fractures is still controversial. We employed a bidirectional Mendelian analysis to explore the causal relationship between rheumatic diseases and BMD or fractures. METHODS: The rheumatic diseases instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Analyses were performed for the three rheumatic diseases: ankylosing spondylitis (AS) (n = 22,647 cases, 99,962 single nucleotide polymorphisms [SNPs]), rheumatoid arthritis (RA) (n = 58,284 cases, 13,108,512 SNPs), and systemic lupus erythematosus (SLE) (n = 14,267 cases, 7,071,163 SNPs). Two-sample Mendelian randomization (MR) analyses were carried out by using R language TwoSampleMR version 0.5.7. The inverse-variance weighted (IVW), MR-Egger, and weighted median methods were used to analyze the causal relationship between rheumatic diseases and BMD or fracture. RESULTS: The MR results revealed that there was absence of evidence for causal effect of AS on BMD or fracture. However, there is a positive causal relationship of RA with fracture of femur (95% CI = 1.0001 to 1.077, p = 0.046), and RA and fracture of forearm (95% CI = 1.015 to 1.064, p = 0.001). SLE had positive causal links for fracture of forearm (95% CI = 1.004 to 1.051, p = 0.020). Additionally, increasing in heel bone mineral density (Heel-BMD) and total bone mineral density (Total-BMD) can lead to a reduced risk of AS without heterogeneity or pleiotropic effects. The results were stable and reliable. There was absence of evidence for causal effect of fracture on RA (95% CI = 0.929 to 1.106, p = 0.759), and fracture on SLE (95% CI = 0.793 to 1.589, p = 0.516). CONCLUSIONS: RA and SLE are risk factors for fractures. On the other hand, BMD increasing can reduce risk of AS. Our results indicate that rheumatic diseases may lead to an increased risk of fractures, while increased BMD may lead to a reduced risk of rheumatic diseases. These findings provide insight into the risk of BMD and AS, identifying a potential predictor of AS risk as a reduction in BMD.

Is there a role for novel supplements in the management of fatigue in rheumatic diseases?

Fatigue is a common symptom of rheumatic diseases and frequently persists even when patients are in a near-remission state. In seeking options to manage troublesome symptoms such as fatigue, complementary and alternative medicines (CAM) are often used by patients despite a lack of evidence base behind such treatment strategies. CAM use is further promoted by social media and 'influencer' marketing without rigorous process to ensure scientific accuracy. One mechanism of recent interest in the CAM market is enhancing cellular pathways of nicotinamide adenine dinucleotide (NAD+), purported to restore mitochondrial function. However, clinical trials of NAD+ pathway supplements lack rigorous trial design, many declare conflicts of interest, and safety data is limited. Ultimately, CAM use by our patients is unavoidable. To adequately inform patients about CAM, we need to keep updated on both the latest scientific literature and social media trends. In so doing, we can then propose to patients how standard-of-care therapies, evidence-based lifestyle modifications and CAM might safely and effectively integrate to form a treatment plan.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Antimalarial Drugs at the Intersection of SARS-CoV-2 and Rheumatic Diseases: What Are the Potential Opportunities?

Background and Objectives: The coronavirus disease of 2019 (COVID-19) pandemic has posed a serious threat to humanity and is considered a global health emergency. Antimalarial drugs (ADs) have been used in the treatment of immuno-inflammatory arthritis (IIA) and coronavirus infection (COVID-19). The aim of this review is to analyze the current knowledge about the immunomodulatory and antiviral mechanisms of action, characteristics of use, and side effects of antimalarial drugs. Material and Methods: A literature search was carried out using PubMed, MEDLINE, SCOPUS, and Google Scholar databases. The inclusion criteria were the results of randomized and cohort studies, meta-analyses, systematic reviews, and original full-text manuscripts in the English language containing statistically confirmed conclusions. The exclusion criteria were summary reports, newspaper articles, and personal messages. Qualitative methods were used for theoretical knowledge on antimalarial drug usage in AIRDs and SARS-CoV-2 such as a summarization of the literature and a comparison of the treatment methods. Results: The ADs were considered a "candidate" for the therapy of a new coronavirus infection due to mechanisms of antiviral activity, such as interactions with endocytic pathways, the prevention of glycosylation of the ACE2 receptors, blocking sialic acid receptors, and reducing the manifestations of cytokine storms. The majority of clinical trials suggest no role of antimalarial drugs in COVID-19 treatment or prevention. These circumstances do not allow for their use in the treatment and prevention of COVID-19. Conclusions: The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for COVID-19. Furthermore, the need for high doses in the treatment of viral infections increases the likelihood of gastrointestinal side effects, the prolongation of QT, and retinopathy. Large randomized clinical trials (RCTs) have refuted the fact that there is a positive effect on the course and results of COVID-19.

The Diagnostic Role of Skin Manifestations in Rheumatic Diseases in Children: A Critical Review of Paediatric Vasculitis.

Skin lesions are frequently observed in children with rheumatic diseases, particularly in conditions such as IgA vasculitis (IgAV) and Kawasaki disease (KD). In paediatric vasculitis, the presence of skin lesions serves as an early indicator, emphasising the importance of timely diagnosis to prevent complications, such as cardiac or renal involvement. Conversely, autoinflammatory disorders like juvenile systemic lupus erythematosus (SLE) and juvenile dermatomyositis (DM) may manifest with cutaneous manifestations either at the onset of disease or during its progression. Identifying these skin lesions prior to the appearance of systemic symptoms offers an opportunity for early diagnosis and treatment, which has a positive influence on the outcomes. Additionally, it is noteworthy that specific rheumatological conditions, such as acute rheumatic fever (ARF) or oligoarticular or polyarticular forms of juvenile idiopathic arthritis (JIA), may exhibit occasional, but significant skin involvement, which is strongly correlated with an unfavourable prognosis. The assessment of skin is important in the holist approach to assessing patients for potentially systemic/multisystem disorder and helps distinguish discrete conditions.

A systematic review and meta-analysis of the association between the D-dimer and rheumatic diseases.

INTRODUCTION: There is good evidence that specific autoimmune rheumatic diseases (RDs), for example, rheumatoid arthritis and systemic lupus erythematosus (SLE), are associated with a state of hypercoagulability and an increased risk of venous thromboembolism (VTE). However, limited information regarding this association is available for other autoimmune or autoinflammatory RDs. We sought to address this issue by conducting a systematic review and meta-analysis of the association between the d-dimer, an established marker of hypercoagulability and VTE, and RDs and the possible clinical and demographic factors mediating this association. METHODS: We searched the electronic databases PubMed, Web of Science, and Scopus from inception to January 31, 2024. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively. RESULTS: In 31 studies selected for analysis (2724 RD patients and 3437 healthy controls), RD patients had overall significantly higher d-dimer concentrations when compared to controls (standard mean difference = 0.93, 95% CI 0.76-1.10, p < .001; I2 = 86.1%, p < .001; moderate certainty of evidence). The results were stable in a sensitivity analysis. Significant associations were observed between the effect size of the between-group differences in d-dimer concentration and age, specific RD and RD category, RD duration, fibrinogen, plasminogen activator inhibitor, C-reactive protein, and erythrocyte sedimentation rate. CONCLUSIONS: Overall, patients with RDs have significantly higher d-dimer concentrations when compared with healthy controls, indicating a state of hypercoagulability. The alterations in d-dimer concentrations are mediated by age, specific RD and RD category, RD duration, and markers of anticoagulation and inflammation. Further research is warranted to investigate d-dimer concentrations across the spectrum of RDs and their utility in predicting and managing VTE in these patients (PROSPERO registration number: CRD42024517712).

Is yearly interferon gamma release assay latent tuberculosis infection screening warranted among patients with rheumatological diseases on disease-modifying drugs in non-endemic settings?

OBJECTIVE: Patients living with rheumatologic diseases on disease-modifying antirheumatic drugs (DMARD) are at an increased risk of developing tuberculosis (TB). Current guidelines recommend screening for latent tuberculosis infection (LTBI) before initiating DMARD. However, data is lacking on the value of yearly screening for LTBI. METHODS: A retrospective chart review was conducted on adult patients (≥ 18 years) with rheumatologic disease on DMARD followed longitudinally in the outpatient rheumatology clinics between 2017-2021. Collected data included patient demographics, rheumatologic diagnosis, medications, TB-related risk factors, interferon gamma release assay (IGRA) results, LTBI diagnosis and treatment. Descriptive statistics were performed. RESULTS: Among 339 patients, 81 (23.9%) were male, 259 (76.4%) were white, and 93 (27.5%) were Latinx. Inflammatory arthritis (84.1%) was the most common rheumatic diagnosis. Common DMARD were JAK inhibitors (19.2%), TNF-alpha inhibitors (18.9%), and IL-17 A inhibitors (18.0%). Only 2 patients at baseline had positive IGRA, and both had a history of treated LTBI. Positive IGRA tests were recorded in 1 (0.7%), 3 (1.8%), 3 (1.3%), and 3 (1.1%) in the years 2018, 2019, 2020, and 2021, respectively. Four patients converted from negative to positive during serial yearly IGRA testing. After reviewing the IGRA test and TB risk factors, only one patient was considered newly diagnosed with LTBI, requiring 4 months of rifampin. CONCLUSION: In a non-endemic area, serial IGRA testing of low-risk patients on DMARD yielded very low rate of newly diagnosed LTBI. A targeted LTBI screening based on TB-related risk factors should be performed prior to IGRA testing rather than universal yearly screening in a non-endemic setting.

Novel electrical therapy to improve sleep disturbance in patients with autoimmune rheumatic diseases.

OBJECTIVES: Sleep disturbance is common in autoimmune rheumatism diseases (ARD) and it plays an important role in activating disease and affects the quality of life. This study aims to evaluate the efficacy and acceptability of the novel electrical therapy on sleep disturbance in ARD patients and its effect on immunologic factors. METHODS: A total of 51 ARD patients (26 treatment group and 25 control group) with sleep disturbance were enrolled in this study. Sleep parameters and immunological indicators (serum level of 12 cytokines and immune function) were collected. The novel electrical therapy was prescribed for 15-30 min 3-6 times a day. The Pittsburg Sleep Index (PSQI) was assessed before and after 3 months' treatment by Mi Energy equipment. Immune function and serum levels of cytokines of all participants at baseline and after treatment were tested with flow cytometry and flow immunofluorescence, respectively. Correlation analysis was used to analyze the relationship between sleep disturbance and immunologic factors. Multiple linear regression analysis was employed to investigate the risk of sleep disturbance in ARD. RESULTS: The global score of PSQI (Baseline: 12.81 ± 4.07, After novel electrical therapy: 4.88 ± 2.76) was effectively improved after 3 months of adjuvant therapy by electrical therapy. We also found that serum levels of IL-8 and IL-1ß statistically significantly decreased after novel electrical therapy. This adjuvant therapy can also significantly decrease the percentage of CD4 + CD8 + T cell, effector memory CD8 + T cell, Memory CD8 + T cell, Th17 cell, and plasma cell and significantly can increase the percentage of naïve CD8 + T cell, Th2 cell, and Tfh2 cell. Nevertheless, all serum level of 12 cytokines and the percentage of immune cells did not correlate with the PSQI global score except the Tc17 cell. Furthermore, age is an independent risk factor influencing PSQI scores (OR = 1.15, p < 0.05) in patients with autoimmune diseases through multiple linear regression analysis. CONCLUSIONS: Novel electrical therapy can effectively improve sleep disturbance in patients with ARD. It can also change the serum level of some cytokines (IL-8 and IL-1ß) and percentage of immune cells (CD4 + CD8 + T cell, effector memory CD8 + T cell, Memory CD8 + T cell, Th17 cell, naïve CD8 + T cell, Th2 cell, Tfh2 cell, and plasma cell).

Osteoporosis and fracture risk are multifactorial in patients with inflammatory rheumatic diseases.

Patients with inflammatory rheumatic and musculoskeletal diseases (iRMDs) such as rheumatoid arthritis, connective tissue diseases, vasculitides and spondyloarthropathies are at a higher risk of osteoporosis and fractures than are individuals without iRMDs. Research and management recommendations for osteoporosis in iRMDs often focus on glucocorticoids as the most relevant risk factor, but they largely ignore disease-related and general risk factors. However, the aetiopathogenesis of osteoporosis in iRMDs has many facets, including the negative effects on bone health of local and systemic inflammation owing to disease activity, other iRMD-specific risk factors such as disability or malnutrition (for example, malabsorption in systemic sclerosis), and general risk factors such as older age and hormonal loss resulting from menopause. Moreover, factors that can reduce fracture risk, such as physical activity, healthy nutrition, vitamin D supplementation and adequate treatment of inflammation, are variably present in patients with iRMDs. Evidence relating to general and iRMD-specific protective and risk factors for osteoporosis indicate that the established and very often used term 'glucocorticoid-induced osteoporosis' oversimplifies the complex inter-relationships encountered in patients with iRMDs. Osteoporosis in these patients should instead be described as 'multifactorial'. Consequently, a multimodal approach to the management of osteoporosis is required. This approach should include optimal control of disease activity, minimization of glucocorticoids, anti-osteoporotic drug treatment, advice on physical activity and nutrition, and prevention of falls, as well as the management of other risk and protective factors, thereby improving the bone health of these patients.