Novel therapeutic targets in rheumatoid arthritis

Rheumatoid arthritis (RA) is the most common chronic systemic autoimmune disease worldwide. Although incurable, there are available therapies to effectively control the disease activity and minimize the joint damage. Numerous cytokines, enzymes and other forms of proteins have been implicated in the disease process of RA. In general, pharmacological therapies in RA target cytokine pathways. Despite a wide variety of disease modifying antirheumatic drugs (DMARD), a significant proportion of patients remain refractory to the available therapies. Hence, the search for newer drugs with different modes of actions is an ongoing process. The present review aimed to explore novel therapeutic targets in RA based on data from the literature. Inhibitors of spleen tyrosine kinase, choline kinase, galectin 3 and hypoxia-inducible factor may have a promising role in thetreatment of RA. Besides, cell based therapies which may enhance the levels of systemic tristetraprolin could be beneficial in RA

Serum matrix metalloproteinase-3 predicts radiographic joint damage and functional disability in rheumatoid arthritis

The search for novel biomarkers has taken centre stage in the past decades of research in Rheumatoid Arthritis (RA). The purpose of the present study was to determine the correlation of serum matrix metalloproteinase-3 (MMP-3) with disease activity, joint damage and functional disability in patients with RA. We consecutively recruited RA patients who were under follow-up at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Information on the RA disease characteristics were obtained from the medical records and all RA patients were assessed for DAS28 (disease activity score based on 28 joints) and Stanford Health Assessment Questionnaire (HAQ) 8-item Disability Index (HAQ-DI). The hand radiographs of the RA patients were assessed for joint damage using the Modified Sharp Score (MSS). Serum MMP-3 levels from RA patients and healthy controls were measured using the ELISA method. We recruited a total of 77 RA patients and 18 healthy controls. The serum MMP-3 levels were significantly higher among the RA patients (p<0.05). There were significant correlations between the serum MMP-3 levels and MSS (r =0.327) and HAQ-DI (r=0.256), both p<0.05. The mean serum MMP levels in RA patients with radiographic joint erosions was significantly higher than in patients without erosions (p<0.05). Likewise, the subjects with significant functional impairment i.e HAQ-DI ≥1; had significantly higher mean MMP-3 levels compared to RA patients without significant disability (p<0.05). Using multivariate analysis, HAQ-DI remained the independent predictor of serum MMP-3 in RA patients. Serum MMP-3 is a potential biomarker and predictor of radiographic joint damage and functional disability in RA

Rheumatoid Arthritis: Refractory to Infliximab, a Tumor Necrosis Factor Inhibitor

Rheumatoid arthritis is one of the commonest autoimmune diseases. It is a chronic, progressive, systemic inflammatory disorder affecting the synovial joints and typically producing symmetrical arthritis. If left untreated, it leads to joint destruction and thus deformity and disability

Subclinical atherosclerosis among rheumatoid arthritis patients without overt cardiovascular risk factors

Objective. To determine the associated factors of subclinical atherosclerosis measured with carotid intima media thickness (CIMT) among rheumatoid arthritis (RA) patients without any overt traditional cardiovascular (CV) risk factors. Methods. Forty RA patients with matched age and gender healthy controls were recruited. Carotid ultrasound was performed to all subjects. CIMT was considered to be abnormally thickened if it was more than the 75th percentile matched for age and sex reference values. Univariate and multivariate analyses were performed to determine the association between the sociodemographics and disease characteristics of RA with thickened CIMT. Results. Abnormally thickened CIMT were observed in 11 RA patients (27.5%) and in 4 control subjects (10%), p = 0.04. It was highly prevalent among RA patients with active disease (54.5% vs 17.2%), p = 0.02. Patients with thickened CIMT also tend to have erosive disease, p = 0.06. Seropositive rheumatoid factor (RF) patients also had significantly higher CIMT values as compared with sero-negative patients, p = 0.03. Multivariable logistic regression analysis revealed that active disease was independently associated with thickened CIMT. Conclusions. RA patients are at risk for subclinical atherosclerosis despite absence of traditional CV risk co morbidities and active disease was the independent factor associated with it

Chronic necrotizing pulmonary aspergillosis presenting as bilateral pleural effusion: a case report

<p>Abstract</p> <p>Introduction</p> <p>Chronic necrotizing pulmonary aspergillosis is an uncommon subacute form of <it>Aspergillus </it>infection. It typically occurs in immunocompromised individuals and in those with underlying lung disease. This interesting case highlights the occurrence of this entity of aspergillosis in an immunocompetent middle-aged woman with atypical radiological findings. To the best of our knowledge this is the first case report of chronic necrotizing pulmonary aspergillosis presenting with pleural effusion.</p> <p>Case presentation</p> <p>Our patient was a 64-year-old Malay woman with a background history of epilepsy but no other comorbidities. She was a lifelong non-smoker. She presented to our facility with a six-month history of productive cough and three episodes of hemoptysis. An initial chest radiograph showed bilateral pleural effusion with bibasal consolidation. Bronchoscopy revealed a white-coated endobronchial tree and bronchoalveolar lavage culture grew <it>Aspergillus niger</it>. A diagnosis of chronic necrotizing pulmonary aspergillosis was made based on the clinical presentation and microbiological results. She responded well to treatment with oral itraconazole.</p> <p>Conclusions</p> <p>The radiological findings in chronic necrotizing pulmonary aspergillosis can be very diverse. This case illustrates that this condition can be a rare cause of bilateral pleural effusion.</p

Has the median nerve involvement in rheumatoid arthritis been overemphasized?

Abstract Rheumatoid arthritis (RA) is a well and widely recognized cause of carpal tunnel syndrome (CTS). In the rheumatoid wrist, synovial expansion, joint erosions and ligamentous laxity result in compression of the median nerve due to increased intracarpal pressure. We evaluated the published studies to determine the prevalence of CTS and the characteristics of the median nerve in RA and its association with clinical parameters such as disease activity, disease duration and seropositivity. A total of 13 studies met the eligibility criteria. Pooled data from 8 studies with random selection of RA patients revealed that 86 out of 1561 (5.5%) subjects had CTS. Subclinical CTS, on the other hand, had a pooled prevalence of 14.0% (30/215). The cross sectional area of the median nerve of the RA patients without CTS were similar to the healthy controls. The vast majority of the studies (8/13) disclosed no significant relationship between the median nerve findings and the clinical or laboratory parameters in RA. The link between RA and the median nerve abnormalities has been overemphasized throughout the literature. The prevalence of CTS in RA is similar to the general population without any correlation between the median nerve characteristics and the clinical parameters of RA

Has the median nerve involvement in rheumatoid arthritis been overemphasized?

ResumoA artrite reumatoide (AR) é uma causa bem e amplamente reconhecida de síndrome do túnel do carpo (STC). No punho acometido pela artrite reumatoide, a expansão sinovial, as erosões articulares e a frouxidão ligamentar resultam em compressão do nervo mediano decorrente do aumento da pressão intracarpal. Avaliaram‐se os estudos publicados para determinar a prevalência de STC e as características do nervo mediano na AR e sua associação com parâmetros clínicos, como a atividade e duração da doença e a soropositividade. Preencheram os critérios de elegibilidade 13 estudos. Os dados agrupados dos oito estudos com seleção aleatória de pacientes com AR revelaram que 86 de 1.561 (5,5%) indivíduos tinham STC. Por outro lado, a STC subclínica teve uma prevalência combinada de 14% (30/215). A área de seção transversa do nervo mediano dos pacientes com AR sem STC foi semelhante à de controles saudáveis. A grande maioria dos estudos (8/13) não apresentou relação significativa entre os achados no nervo mediano e os parâmetros clínicos ou laboratoriais na AR. A ligação entre a AR e as anormalidades do nervo mediano foi excessivamente valorizada em toda a literatura. A prevalência de STC na AR é semelhante à da população em geral, sem qualquer correlação entre as características do nervo mediano e os parâmetros clínicos da AR.AbstractRheumatoid arthritis (RA) is a well and widely recognised cause of carpal tunnel syndrome (CTS). In the rheumatoid wrist, synovial expansion, joint erosions and ligamentous laxity result in compression of the median nerve due to increased intracarpal pressure. We evaluated the published studies to determine the prevalence of CTS and the characteristics of the median nerve in RA and its association with clinical parameters such as disease activity, disease duration and seropositivity. A total of 13 studies met the eligibility criteria. Pooled data from 8 studies with random selection of RA patients revealed that 86 out of 1561 (5.5%) subjects had CTS. Subclinical CTS, on the other hand, had a pooled prevalence of 14.0% (30/215). The cross sectional area of the median nerve of the RA patients without CTS were similar to the healthy controls. The vast majority of the studies (8/13) disclosed no significant relationship between the median nerve findings and the clinical or laboratory parameters in RA. The link between RA and the median nerve abnormalities has been overemphasised throughout the literature. The prevalence of CTS in RA is similar to the general population without any correlation between the median nerve characteristics and the clinical parameters of RA

The clinical significance of vitamin D in systemic lupus erythematosus: a systematic review.

BACKGROUND: Vitamin D deficiency is more prevalent among SLE patients than the general population. Over the past decade, many studies across the globe have been carried out to investigate the role of vitamin D in SLE from various clinical angles. Therefore, the aim of this systematic review is to summarise and evaluate the evidence from the published literature; focusing on the clinical significance of vitamin D in SLE. METHODS: THE FOLLOWING DATABASES WERE SEARCHED: MEDLINE, Scopus, Web of Knowledge and CINAHL, using the terms "lupus", "systemic lupus erythematosus", "SLE and "vitamin D". We included only adult human studies published in the English language between 2000 and 2012.The reference lists of included studies were thoroughly reviewed in search for other relevant studies. RESULTS: A total of 22 studies met the selection criteria. The majority of the studies were observational (95.5%) and cross sectional (90.9%). Out of the 15 studies which looked into the association between vitamin D and SLE disease activity, 10 studies (including the 3 largest studies in this series) revealed a statistically significant inverse relationship. For disease damage, on the other hand, 5 out of 6 studies failed to demonstrate any association with vitamin D levels. Cardiovascular risk factors such as insulin resistance, hypertension and hypercholesterolaemia were related to vitamin D deficiency, according to 3 of the studies. CONCLUSION: There is convincing evidence to support the association between vitamin D levels and SLE disease activity. There is paucity of data in other clinical aspects to make firm conclusions

Potential Therapeutic Application and Mechanism of Action of Stem Cell-Derived Extracellular Vesicles (EVs) in Systemic Lupus Erythematosus (SLE)

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that affects nearly 3.41 million people globally, with 90% of the cases affecting women of childbearing age. SLE is a complex disease due to the interplay of various immunological pathways and mechanisms. This scoping review aims to highlight the latest research findings on the therapeutic mechanisms of action of EVs in SLE. Relevant research articles were identified using the PRISMA framework from databases such as PubMed/MEDLINE (National Library of Medicine), Scopus (Elsevier), and Web of Science: Core Collection (Clarivate Analytics) from July 2023 to October 2023. Eleven studies met the inclusion criteria and thus were included in this scoping review. The findings showed that EVs have therapeutic effects on ameliorating the disease progression of SLE. EVs can reduce the pro-inflammatory cytokines and increase the anti-inflammatory cytokines. Moreover, EVs can increase the levels of regulatory T cells, thus reducing inflammation. EVs also have the potential to regulate B cells to alleviate SLE and reduce its adverse effects. The scoping review has successfully analysed the therapeutic potential in ameliorating the disease progression of SLE. The review also includes prospects to improve the effects of EVs further to increase the therapeutic effects on SLE