Current Rheumatology Reviews - Volume 17, Issue 1, 2021

Viruses can induce autoimmune diseases, in addition to genetic predisposition and environmental factors. Particularly, coronaviruses are mentioned among the viruses implicated in autoimmunity. Today, the world's greatest threat derives from the pandemic of a new human coronavirus, called “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the responsible agent of coronavirus disease 2019 (COVID-19). First case of COVID-19 was identified in Wuhan, the capital of Hubei, China, in December 2019 and quickly spread around the world. This review focuses on autoimmune manifestations described during COVID-19, including pro-thrombotic state associated with antiphospholipid antibodies (aPL), acute interstitial pneumonia, macrophage activation syndrome, lymphocytopenia, systemic vasculitis, and autoimmune skin lesions. This offers the opportunity to highlight the pathogenetic mechanisms common to COVID-19 and several autoimmune diseases in order to identify new therapeutic targets. In a supposed preliminary pathogenetic model, SARS-CoV-2 plays a direct role in triggering widespread microthrombosis and microvascular inflammation, because it is able to induce transient aPL, endothelial damage and complement activation at the same time. Hence, endothelium might represent the common pathway in which autoimmunity and infection converge. In addition, autoimmune phenomena in COVID-19 can be explained by regulatory T cells impairment and cytokines cascade.

Interstitial lung disease (ILD) is the most common form of pulmonary impairment in patients with rheumatoid arthritis (RA). However, patients with RA or other arthritic diseases such as psoriatic arthritis (PsA) or peripheral spondyloarthritis (pSpA) are at a higher risk of developing several other pulmonary diseases, such as chronic obstructive lung disease (COPD), compared to patients without arthritis. This review aims at summarizing the current knowledge on the prevalence of pulmonary diseases in the above-mentioned forms of arthritis, the challenges faced by prevalence studies in detecting pulmonary diseases in patients with arthritis, as well as possible treatment options. Dyspnea, cough or other pulmonary symptoms in arthritis patients should prompt gradual diagnostic procedures considering pulmonary manifestations as a major cluster of differential diagnosis. However, treatment options often lack solid evidence-based guidelines and referrals to specialized centers are often necessary.

Hospitalizations are frequent in Systemic Lupus Erythematosus (SLE) and carry a significant economic burden. The focus of this review was to summarize the information available on the main causes of SLE hospitalizations over recent decades. A literature review was conducted, using PubMed and Scopus, for articles related to SLE hospital admissions from 1981 onward. Active disease/ flare and infection were the leading causes of admission across the study period. More recently, other comorbidities gained relevance, such as cardio and cerebrovascular disease, pregnancy-related morbidity, adverse drug reactions, thromboembolic events, malignancy and renal, pulmonary and gastrointestinal disease. African and Southeast Asian studies seemed to display particularly high percentages of patients admitted with active disease/flare, while European and North American studies appeared to report more admissions due to comorbidities and accumulated disease/treatment damage. Some data support a temporal change of certain admission causes, but the limited number, heterogeneity and variance among studies weakens a consistent analysis. In conclusion, despite the developments in SLE management, causes of hospitalization have not prominently changed across recent decades.

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease and an exclusion diagnosis that includes all forms of arthritis that persists for more than 6 weeks under the age of 16. Although there is not yet a cure for JIA, and recent advances in the therapeutic field have created a more hopeful present and future for the patients. In the past, therapies for JIA have depended on non-steroidal medication, conventional synthetic disease-modifying antirheumatic drugs and corticosteroids. However, over the last decades, the advent of biologic therapies in JIA contributed to the preservation of functional activity, control of pain, avoidance of joint damage, and extra-articular manifestations. Furthermore, over the last years, international institutions, such as the American College of Rheumatology, have released recommendations and guidelines for rheumatologists for optimal JIA management. All the above have revolutionized the treatment of JIA with promising outcomes. To this end, the relevant literature is reviewed and discussed appropriately.

Sarcopenia is a common condition in older adults, which causes the frequent occurrence of muscle fatigue. Muscle fatigue commonly develops among seniors. Muscle fatigue is a type of physical fatigue that occurs due to either motor or sensory dysfunctions. Current interventions developed to decrease the occurrence of muscle fatigue, which include either increasing rest periods or subdividing large tasks into small ones. The effectiveness of these interventions is highly contradicted. Recently, researchers discovered that mechanoreceptors are the main receptors of muscle fatigue, however, no clinical study investigated the effect of performing proprioceptive training to enhance the mechanoreceptors and decrease the occurrence of muscle fatigue. Performing proprioceptive training could improve muscle fatigue by improving its sensory part. The function of mechanoreceptors might consequently enhance fatigue and decrease the progression rate of sarcopenia. Thus, this review was conducted to suggest a novel approach of treatment to enhance fatigue and decrease Sarcopenia in seniors. This might be accomplished through increasing the firing rate of α- motor neurons, increasing the amount of Ca²⁺ ions in the neuromuscular junction, slowing the progression rate of Sarcopenia, and correcting movement deviations, which commonly occur with muscle fatigue in seniors. In conclusion, proprioceptive training could play an effective role in decreasing the progression rate of sarcopenia and enhancing the fatigability among seniors.

Background: Endostatin by its therapeutic value against rheumatoid arthritis has recently gained significant interest in biomedical science. A recent study revealed that various approaches have been made to prevent rheumatoid arthritis by either controlling or inhibiting the progression of angiogenesis. Objective: The main objective of the current manuscript is to enumerate the intrinsic role of endostatin in rheumatoid arthritis. Methods: A thorough and detailed review of literature from the papers published from the year 1997-2019 was studied for the preparation of the current article. Results: Endostatin is one such agent of the subfamily of ECM called as multiplexins obtained from proteolytic cleavage of XVIII and its carboxylic terminal fragments and is known for its antiangiogenic and antiproliferative property. The exact mechanism of endostatin is still unclear, but it acts by downregulating or inhibiting the responses of various factors, including Id1, Id3, matrix metalloproteinase, and Nuclear factor Kappa B that are liable for angiogenesis. The mutual effects on adipogenesis and angiogenesis, endostatin inhibits dietary-induced obesity and its related metabolic disorders, such as insulin resistance, glucose intolerance, and hepatic steatosis. Conclusion: The present review demonstrates the intrinsic usage of endostatin as a novel molecule in rheumatoid arthritis. It focuses on the status of the therapeutic potential of endostatin in inhibiting the activity of angiogenesis is also very well explored.

Background: Quantitative sensory testing (QST) methods have become widely used for the assessment of nervous system sensitization to nociceptive signalling in studies of people with knee osteoarthritis (OA). However, few standardised QST protocols have been developed. Variability in their execution may lead to differences in their interpretation. Objective: The proposed scoping review will seek to identify various QST methodologies being used in the assessment of sensitization and how sensitization is being defined in people with knee OA. Methods and Analysis: This scoping review will be guided by existing scoping review methodologies. Relevant studies will be extracted from the following electronic databases: Medical Literature Analysis and Retrieval System Online, ExcerptaMedica Database, Allied and Complementary Medicine Database and the Cumulative Index to Nursing Allied Health Literature. Independent screening of the abstracts and full articles and data extraction will be performed in pairs. Information extracted will focus on qualitative and quantitative data relevant to the content of the protocols from included studies. Data will be summarised in order to draw conclusions on the common elements used in QST protocols and definitions of sensitization for knee OA. Conclusion: This scoping review will provide insight into the most common methods of QST used in the assessment of nociceptive signaling in people with knee OA. This will potentially identify areas where a systematic review or other primary research may be required in order to develop fixed evidence-based protocols for QST in patients with knee OA.

Background: Rheumatoid arthritis (RA) is an autoimmune disease responsible for maximum human morbidity in modern life, whereas oxidative stress is the ultimate potential biomarker for determining disease activity in patients with RA. Objective: The present study scientifically validated the effectiveness of antioxidants commonly present in different food supplements to neutralize the free radicals mediated oxidative stress in isolated peripheral blood mononuclear lymphocytes (PBML) of patients with RA. Methods: The study population included patients with Rheumatoid arthritis, RA (n =15), who fulfilled the American College of Rheumatology criteria for RA. Peripheral blood was collected, and isolated mononuclear lymphocyte cells (PBML) were pretreated with phorbol myristate acetate (PMS) and furthermore, incubated with different concentrations of Naringenin, β carotene and Nacetyl cysteine (NAC) in an ex vivo condition. The resultant cell lysate was used for further studies for the determination of other oxidative biomarkers. The increase of superoxide and nitric oxide production was observed when PBML was treated PMS. Results: Importantly, the increased oxidative stress was effectively decreased by the selected plantderived compounds β-carotene and naringenin. Conclusion: The study scientifically evaluated the efficacy of the molecules validated by one-way ANOVA, followed by Dunnett’s post hoc test of significance. Collectively, our results indicate that both β carotene and naringenin may be a promising non-toxic food supplement in attenuating the oxidative stress associated pathology in RA, meriting further pharmacological studies on other inflammatory cells like neutrophils.

Background: The Total Knee Arthroplasty (TKA) is one of the most common surgical intervention in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Previous studies suggested a significant improvement in health status after TKA surgery. But we have little data about the Iranian population undergone TKA. In the current clinical study, we evaluated postoperatively health status using reliable tools of MOS SF-36 and WOMAC in OA and RA patients undergoing TKA. Methods: In this cohort study, patients with OA and/or RA who were candidates for TKA surgery were included. Using two reliable questionnaires, i.e., WOMAC and SF-36, the quality of life of patients was examined during a period of six months (three monthly intervals) after the surgery. All data were analyzed using IBM SPSS Statistics. Kolmogrov-Smirnov, Kendall’s tau, chi-square test and K-related Non-parametric tests were used. Results: Of the 2126 patients who underwent TKA, there were 2024 diagnosed osteoarthritis and 102 validated RA over one year. The mean ± SD of age and the average BMI were 68.0 ± 7.0 BMI 28.5 kg/m2, respectively. Regarding comorbidities and concurrent disorders, about 14% of cases were diabetic, 42% had cardiovascular diseases, 3% had respiratory diseases, and 12% involved with gastrointestinal diseases. The result of SF-36 dramatically increased during follow up. The central distributions of all domains in the SF-36 questionnaire indicated that most scores increased during the time after surgery. As a consequence, WOMAC and MOS FS-36 indicated statistically significant changes after TKA for those who are suffering from RA or OA. Conclusion: TKA is an effective surgical process, which improves the quality of life in OA and/or RA. In addition, WOMAC and SF-36 examining tools are likely reliable tools with similar results to assess patients’ quality of life after TKA surgery.

Background: Axial spondyloarthritis (axSpA) is a common group of chronic rheumatic inflammatory diseases, which usually affects the axial skeleton, and are more frequently observed in males than in females. Several differences have been brought up in the clinical presentation of axSpA, according to the patient’s gender. In fact; axSpA severity in women tends to be moderate, leading then, to an underdiagnosis in this category of patients. While male axSpA patients seem to set forth more spinal destructions on radiographs. Objective: As the main goal, our study aims to bring up the particularities of female axial spondyloarthritis, all the while comparing them with the male form. Materials and Methods: This is a cross-sectional study carried out in the period lying between January 2012 and December 2017, at a single rheumatology department in Morocco. All patients with an axial spondyloarthritis meeting the Assessment of SpondyloArthritis international Society (ASAS) classification criteria 2010, and who have been admitted in our department, during that period, were included. The data was recorded and analyzed using SPSS v20 univariate and bivariate analysis. A value of p <0.005 has been used to identify factors associated with axSpA in women. Results: A total of 277 patients were enrolled, of which 147 are female and 130 are male with a sex ratio of 1.1. Cervical stiffness was more common in men. On the other hand, women had more arthritis and enthesitis. However, no considerable divergences have been underscored between the two genders, neither in the prevalence of extra-articular manifestations, nor in disease activity BASDAI and BASFI. Men had more radiographic sacroiliitis compared to women (57.5% vs. 42.5%, p=0.01), more coxitis (66.7% vs. 33.3%, p = 0.0001). The Multivariate logistic regression analysis showed that female gender was associated with a greater age at the diagnosis onset (IC: 1.053-1.103, OR=1.07, p=0.001) and arthritis (IC: 2.37-4.26, OR=2.3, p=0.004). While the male sex was associated with a young age of onset (CI: 4.50-19.52, OR = 9.3), coxitis (CI: 2.53-4.23, OR = 3.3) and smoking (CI: 15.667-900.18, OR = 118.7). Conclusion: The comparison between male and female patients suffering from axial spondyloarthritis found many differences and similarities as well, in the disease expression. This study showed actually that women had the less severe form of spondyloarthritis.

Objective: To analyze the association between serum levels of osteoprotegerin (OPG) and Dickkopf-related protein 1 (DKK-1) and the annual percent change (Δ%) in bone mineral density (BMD) in patients with tightly controlled rheumatoid arthritis (RA). Methods: Observational mixed-study. RA patients followed-up with a tight-control strategy were included. Bone densitometries were performed at baseline (T0) and follow-up (T1) and serum levels of OPG and DKK-1 were measured by ELISA also in T0 and T1; additional clinical variables included disease activity measures, and treatment for RA and osteoporosis. Descriptive bivariate and multivariate analyses, stratified by gender, were performed. Results: We included 97 RA patients (70% female, with a mean age of 53 years, and 76% with low activity by DAS28); 95% were treated with DMARDs and 37% with anti-osteoporotic drugs. Mean time between T0 and T1 was 2.7 years. Most patients had their BMD improved. The mean Δ%BMD was +0.42% for lumbar spine, +0.15% for femoral neck and +0.91% for total femur. In men, baseline OPG was significantly associated with higher BMD loss (β coefficient -0.64) at the femoral neck. In women, DKK-1 was associated with higher BMD loss at the femoral neck (β coefficient -0.09), and total femur (β coefficient -0.11); however, DKK-1 was associated with lower BMD loss at the lumbar spine (β coefficient 0.06). Conclusion: In tightly controlled RA patients, we have found no evidence of bone loss. The role of DKK1 and OPG seems small and might be related to sex and location.

Introduction: There is a lack of robust data on hospitalised acute vertebral fragility fractures. This analysis aimed to report on the number of hospitalised vertebral fragility fractures treated in a large UK teaching hospital. This information would support better design of hospital services and resource allocation to manage this group of patients. Methods: Patients aged 50 years and over hospitalised with a vertebral fragility fracture from 1/2/2016 to 31/1/2017 were identified from radiology and hospital records. Patients sustaining vertebral fractures due to either major trauma or malignancy were excluded. Data was collected on patient demographics, fracture details, hospitalisation details and health outcomes. Results: 208 patients with acute vertebral fragility fractures were hospitalised over a 12 month period. The mean (SD) age was 80.5 (11) years, of which 68% were female. 94% presented to the Emergency Department (ED) as their first point of contact, of which 70% were subsequently hospitalised. Two-thirds presented with a single level vertebral fracture predominantly around the thoracolumbar region. The majority (87%) were non-operatively managed by general physicians, of which most were under Geriatric Medicine. The median length of stay was 12 (IQR 6-20) days and inpatient mortality was 3%. 52% of patients went on to have a bone health assessment. Conclusion: We have reported on the number of patients presenting to hospital with an acute vertebral fragility fracture over 12 months. This helps identify resources needed to design hospital services to manage them adequately.

Objective: Rheumatoid arthritis (RA) is the most prevalent autoimmune arthritis. Berberine is an alkaloid isolated from Berberis vulgaris, and its anti-inflammatory effect has been identified. Methods: Twenty newly diagnosed RA patients and 20 healthy controls participated. Peripheral mononuclear cells were prepared and stimulated with bacterial lipopolysachharide (LPS,1 μg/ml), exposed to different concentrations of berberine (10 and 50μM) and dexamethasone (10-7 M) as a reference. The toxicity of compounds was evaluated by WST-1 assay. The expression of TNF-α and IL-1β was determined by quantitative real-time PCR. Protein level of secreted TNF-α and IL-1β was measured by using ELISA. Results: Berberine did not have any toxic effect on cells, whereas Lipopolysaccharide (LPS) stimulation caused a noticeable rise in TNF-α and IL-1β production. Berberine markedly downregulated the expression of both TNF-α and IL-1β, and inhibited TNF-α and IL-1β secretion from LPS-stimulated PBMCs. Discussion: This study provided a molecular basis for anti-inflammatory effect of berberine on human mononuclear cells through the suppression of TNF-a and IL-1secretion. Our findings highlighted the significant inhibitory effect of berberine on proinflammatory responses of mononuclear cells from rheumatoid arthritis individuals, which may be responsible for antiinflammatory property of Barberry. We observed that berberine at high concentration exhibited anti-inflammatory effect in PBMCs of both healthy and patient groups by suppression of TNF-a and IL-1cytokines at both mRNA and protein levels. Conclusion: Berberine may inhibit the gene expression and production of pro-inflammatory cytokines by mononuclear cells in rheumatoid arthritis and healthy individuals without affecting cell viability. Future studies with a larger sample size are needed to prove the idea.

Background: Women with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are at high risk of cardiovascular diseases (CVD). The atherogenic index of plasma (AIP) is a new marker for the assessment of CVD. Objective: This study aimed to determine the predictive value of AIP with long-term CVD risk among women with RA and SLE. Methods: This is a cross-sectional study of 99 RA and 59 SLE women. Demographic, clinical, and biochemical data were obtained, and disease activities were calculated. For each patient, the longterm risk of CVD was calculated using the Framingham risk score (FRS); AIP was derived according to the logarithmic (triglycerides/high-density lipoproteins cholesterol). Results: The mean age of the RA and SLE patients was 47.97 ± 8.78 and 36.75 ± 9.09 years, respectively. The median (interquartile range) of AIP values in RA and SLE patients were 0.34 (-0.15, 1.02) and 0.33 (-0.53, 0.96), respectively, while FRS values of RA patients and SLE patients were 6.38 ± 5.58 and 4.86 ± 4.5, respectively (p >0.05). There was a moderate correlation between AIP and FRS in RA and SLE patients (r=0.42, p=0.002 and r=0.33, p=0.007, respectively). According to the multivariate regression analyses, we found that AIP value is an independent factor for FRS in RA (β: 4.13, 95% confidence interval; 1.71, 6.18; p=0.008) and in SLE patients (β: 6.19, 95% confidence interval; 2.58, 9.81; p<0.001). Conclusions: We reported that AIP can be used as an independent indicator for long-term CVD risk in RA and SLE patients.

Aim: The aim of this study was to investigate the effect of dietary education on cardiovascular risk factors in patients with rheumatoid arthritis. Methods: In this randomized clinical trial, 112 patients with rheumatoid arthritis were randomly assigned into two groups, intervention and control. Dietary education was provided for the intervention group in 4 sessions; anthropometric measurements, serum levels of RF, triglycerides, cholesterol, HDL, LDL, and fasting blood sugar were measured before and three months after the intervention. Data were analyzed using SPSS software and appropriate statistical tests. Results: The mean of total cholesterol (p <0.001), triglycerides (p = 0.004), LDL (p <0.001), systolic blood pressure (p = 0.001), diastolic blood pressure (p = 0.003), FBS and BMI (p <0.001) were decreased significantly in the intervention group after education compared the control group. Conclusion: Traditional care for rheumatoid arthritis patients is not enough. Patients need more education in order to improve their situation.