Four major medical societies involved with hydroxychloroquine (HCQ) therapy concur on the need for common principles and cooperation to minimize the risk of ocular toxicity. At a daily dosage of ≤5 ...mg/kg/day actual body weight, the risk of retinal toxicity from HCQ is <2% for usage up to 10 years. Widespread adoption of more sensitive testing techniques, such as optical coherence tomography and automated visual fields, by eye care providers will allow the detection of early toxicity and thus preserve the patient’s visual function. Baseline testing is advised to rule out confounding disease when a patient is started on HCQ. Annual screening with sensitive tests should begin no more than 5 years after treatment initiation. Providers should be sensitive to the medical value of HCQ, and not stop the drug for uncertain indications. It is important to note that effective communication among prescribing physicians, patients, and eye care providers will optimize the utility and safety of HCQ.
Abstract Objective Arthroplasty remains prevalent for patients with rheumatoid arthritis (RA), but outcomes are not equivalent to patients with osteoarthritis, and complications including infection ...are increased. The objective of this article is to review the current evidence supporting perioperative medication management. Challenges are discussed such as continuing potent disease-modifying therapy (DMARDs) and biologics, which may increase infection risk, versus withholding these medications, which may result in disease flares. Methods Published literature regarding arthroplasty in RA has been reviewed and discussed. Results Some DMARDs such as methotrexate and hydroxychloroquine appear safe in the perioperative period. Anti-TNFα biologics should be withheld due to increase in infection risk, while the impact of rituximab and abatacept on infection risk has not been as clearly defined. Conclusion This article provides an overview of arthroplasty in RA, summarizes the evidence supporting perioperative medication management including corticosteroids, and identifies areas where further study is needed.
Droplet-based single-cell RNA-seq has emerged as a powerful technique for massively parallel cellular profiling. While this approach offers the exciting promise to deconvolute cellular heterogeneity ...in diseased tissues, the lack of cost-effective and user-friendly instrumentation has hindered widespread adoption of droplet microfluidic techniques. To address this, we developed a 3D-printed, low-cost droplet microfluidic control instrument and deploy it in a clinical environment to perform single-cell transcriptome profiling of disaggregated synovial tissue from five rheumatoid arthritis patients. We sequence 20,387 single cells revealing 13 transcriptomically distinct clusters. These encompass an unsupervised draft atlas of the autoimmune infiltrate that contribute to disease biology. Additionally, we identify previously uncharacterized fibroblast subpopulations and discern their spatial location within the synovium. We envision that this instrument will have broad utility in both research and clinical settings, enabling low-cost and routine application of microfluidic techniques.
Macrophages tailor their function according to the signals found in tissue microenvironments, assuming a wide spectrum of phenotypes. A detailed understanding of macrophage phenotypes in human ...tissues is limited. Using single-cell RNA sequencing, we defined distinct macrophage subsets in the joints of patients with the autoimmune disease rheumatoid arthritis (RA), which affects ~1% of the population. The subset we refer to as HBEGF
inflammatory macrophages is enriched in RA tissues and is shaped by resident fibroblasts and the cytokine tumor necrosis factor (TNF). These macrophages promoted fibroblast invasiveness in an epidermal growth factor receptor-dependent manner, indicating that intercellular cross-talk in this inflamed setting reshapes both cell types and contributes to fibroblast-mediated joint destruction. In an ex vivo synovial tissue assay, most medications used to treat RA patients targeted HBEGF
inflammatory macrophages; however, in some cases, medication redirected them into a state that is not expected to resolve inflammation. These data highlight how advances in our understanding of chronically inflamed human tissues and the effects of medications therein can be achieved by studies on local macrophage phenotypes and intercellular interactions.
Objective
In this study, we sought to refine histologic scoring of rheumatoid arthritis (RA) synovial tissue by training with gene expression data and machine learning.
Methods
Twenty histologic ...features were assessed in 129 synovial tissue samples (n = 123 RA patients and n = 6 osteoarthritis OA patients). Consensus clustering was performed on gene expression data from a subset of 45 synovial samples. Support vector machine learning was used to predict gene expression subtypes, using histologic data as the input. Corresponding clinical data were compared across subtypes.
Results
Consensus clustering of gene expression data revealed 3 distinct synovial subtypes, including a high inflammatory subtype characterized by extensive infiltration of leukocytes, a low inflammatory subtype characterized by enrichment in pathways including transforming growth factor β, glycoproteins, and neuronal genes, and a mixed subtype. Machine learning applied to histologic features, with gene expression subtypes serving as labels, generated an algorithm for the scoring of histologic features. Patients with the high inflammatory synovial subtype exhibited higher levels of markers of systemic inflammation and autoantibodies. C‐reactive protein (CRP) levels were significantly correlated with the severity of pain in the high inflammatory subgroup but not in the others.
Conclusion
Gene expression analysis of RA and OA synovial tissue revealed 3 distinct synovial subtypes. These labels were used to generate a histologic scoring algorithm in which the histologic scores were found to be associated with parameters of systemic inflammation, including the erythrocyte sedimentation rate, CRP level, and autoantibody levels. Comparison of gene expression patterns to clinical features revealed a potentially clinically important distinction: mechanisms of pain may differ in patients with different synovial subtypes.
Objective
Although rates of arthroplasty have increased dramatically, rates among patients with rheumatoid arthritis (RA) are reported to be decreasing. It is not known if this is also the case among ...patients with other inflammatory arthritides. This study was undertaken to evaluate rates of arthroplasty due to RA, juvenile idiopathic arthritis (JIA), spondyloarthritis (SpA), and a composite group of patients with inflammatory arthritides (IA), compared to arthroplasty rates among patients without inflammatory or autoimmune conditions.
Methods
Administrative discharge databases (State Inpatient Databases of the Healthcare Cost and Utilization Project, New York Department of Health Statewide Planning and Research Cooperative System, California Statewide Health Planning and Development) were used to compare rates of knee, hip, and shoulder arthroplasty occurring from 1991 to 2005.
Results
Of 2,839,325 arthroplasties in 1991–2005, 2.7% were performed in patients with IA. The rate of arthroplasty for noninflammatory conditions doubled (124.5 per 100,000 persons in 1991 versus 247.5 per 100,000 persons in 2005), while the rate for IA remained stable at 5.1 per 100,000. Rates of arthroplasty for RA decreased slightly (4.6 per 100,000 versus 4.5 per 100,000) and those for JIA decreased by nearly 50% (0.22 per 100,000 versus 0.13 per 100,000), but the rate of arthroplasty for SpA increased by nearly 50% (0.22 per 100,000 versus 0.31 per 100,000). Age at the time of arthroplasty increased for patients with RA (mean ± SD 63.4 ± 12.7 years versus 64.9 ± 12.8 years), JIA (30.9 ± 12.2 years versus 36.7 ± 14.9 years), and SpA (54.3 ± 16.1 years versus 60.4 ± 13.9 years). However, the mean age at the time of arthroplasty among non‐IA cases decreased (71.5 ± 11.8 years versus 69.0 ± 12.0 years).
Conclusion
This population‐based study is the first to show that arthroplasty rates have decreased significantly among patients with JIA and minimally among patients with RA, and have increased among patients with SpA. The increased age at the time of arthroplasty among patients with JIA and SpA suggests that these patients are increasingly able to defer surgical interventions. Further research is needed to assess the ongoing effect of biologic agents on the need for arthroplasties in patients with IA.
Tumour necrosis factor α inhibitors (TNFis) are widely used in RA patients who undergo surgery, and optimal perioperative management must balance the risk of infection with the risk of post-operative ...flare. The purpose of this study is to examine the impact of TNFi exposure on surgical site infections (SSIs) in RA patients undergoing elective orthopaedic surgery by systematic review and meta-analysis.
A systematic review of the literature and meta-analysis were performed using PUBMED, EMBASE and the Cochrane Central Register of Controlled Trials, through May 2014. Two independent reviewers screened titles and abstracts, and analysed selected papers in detail. Included studies assessed RA patients with or without TNFi exposure prior to orthopaedic surgery, and described post-operative infections. Study quality was assessed using the Oxford Centre for Evidence-based Medicine Levels of Evidence. Meta-analyses of the individual study odds ratios (ORs) were conducted, and each pooled OR was calculated using a random effects model.
Eight observational studies and three case control studies met inclusion criteria; risk of bias was low in eight studies and moderate in three. Publication bias was not apparent. These studies represent 3681 patients with recent exposure to TNFis (TNFi+) and 4310 with no recent exposure to TNFis (TNFi-) at the time of surgery. The TNFi+ group had higher risk of developing SSI compared with patients in the TNFi- group (random effects model: OR 2.47 (95% CI 1.66, 3.68); P < 0.0001).
Data from the available literature suggest that there is an increased risk of SSIs in RA patients who use or have recently used TNFis at the time of elective orthopaedic surgery. Prospective studies to confirm these findings and establish the optimal withhold and restart time of TNFis, in the context of other risk factors for infection in RA patients such as higher disease activity, corticosteroid use, smoking and diabetes, are needed.
Inflammation of non-barrier immunologically quiescent tissues is associated with a massive influx of blood-borne innate and adaptive immune cells. Cues from the latter are likely to alter and expand ...activated states of the resident cells. However, local communications between immigrant and resident cell types in human inflammatory disease remain poorly understood. Here, we explored drivers of fibroblast-like synoviocyte (FLS) heterogeneity in inflamed joints of patients with rheumatoid arthritis using paired single-cell RNA and ATAC sequencing, multiplexed imaging and spatial transcriptomics along with in vitro modeling of cell-extrinsic factor signaling. These analyses suggest that local exposures to myeloid and T cell-derived cytokines, TNF, IFN-γ, IL-1β or lack thereof, drive four distinct FLS states some of which closely resemble fibroblast states in other disease-affected tissues including skin and colon. Our results highlight a role for concurrent, spatially distributed cytokine signaling within the inflamed synovium.
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