Current Rheumatology Reports最新文献

Purpose of review: To summarize the current evidence on the adoption of the treat-to-target (T2T) strategy in pediatric rheumatic diseases (PRD).

Recent findings: The recent advances in the management of PRD have markedly increased the ability to achieve disease remission. Complete disease quiescence is regarded as the ideal therapeutic goal because its attainment leads to lesser long-term damage and physical disability, and to optimization of quality of life. Studies in adult rheumatic diseases have shown that patient outcomes are improved if complete suppression of the inflammatory process is aimed for by frequent adjustments of therapy according to quantitative indices. This approach, which underlies the T2T concept, has been applied in strategic trials in rheumatoid arthritis (RA). Furthermore, recommendations for the T2T have been issued for RA and other adult rheumatic diseases. There is currently a growing interest for the introduction of T2T in PRD, and recommendations for treating juvenile idiopathic arthritis (JIA) to target were promulgated. A similar initiative has been undertaken for childhood-onset systemic lupus erythematosus. Preliminary therapeutic studies have explored the T2T design in JIA. The T2T strategy is a modern therapeutic approach that holds the promise of improving the outcomes in patients with PRD.

Purpose of review: To review the impact of disease-modifying antirheumatic drugs (DMARDs) on COVID-19 severity and vaccine immunogenicity and to discuss COVID-19 outcomes in patients with rheumatoid arthritis (RA).

Recent findings: Rituximab is associated with severe COVID-19 and impaired vaccine immunogenicity via its B cell-depleting mechanism. JAK inhibitors and glucocorticoids have been modestly associated with severe COVID-19 and impaired vaccine immunogenicity. TNF inhibitors may have a protective effect against severe COVID-19 and do not appear to affect vaccine immunogenicity. Clinical trials have shown improved seroconversion and antibody titers when methotrexate is held around vaccine doses, but this may yield increased risk of RA flare. Patients with RA are also impacted by DMARD disruption, RA flares, and post-acute sequelae of COVID-19 after COVID-19 infection. Given the risks of COVID-19, rituximab should be used with caution in RA. Holding methotrexate doses around COVID-19 vaccination improves immunogenicity but may increase RA flare risk.

Purpose of review: Osteoarthritis (OA) is a complex heterogeneous disease with no effective treatments. Artificial intelligence (AI) and its subfield machine learning (ML) can be applied to data from different sources to (1) assist clinicians and patients in decision making, based on machine-learned evidence, and (2) improve our understanding of pathophysiology and mechanisms underlying OA, providing new insights into disease management and prevention. The purpose of this review is to improve the ability of clinicians and OA researchers to understand the strengths and limitations of AI/ML methods in applications to OA research.

Recent findings: AI/ML can assist clinicians by prediction of OA incidence and progression and by providing tailored personalized treatment. These methods allow using multidimensional multi-source data to understand the nature of OA, to identify different OA phenotypes, and for biomarker discovery. We described the recent implementations of AI/ML in OA research and highlighted potential future directions and associated challenges.

Purpose of review: To describe the current state of knowledge regarding COVID-19 in patients with systemic lupus erythematosus (SLE). We focus on (i) SARS-CoV-2 vaccination uptake, immunogenicity and safety, and (ii) outcomes of COVID-19 in patients with SLE and pertinent risk factors for adverse sequelae.

Recent findings: Notwithstanding the potential concern of patients about possible post-vaccination side-effects, the safety of anti-SARS-CoV-2 vaccines in patients with SLE has been undisputedly confirmed in numerous studies. Humoral immunogenicity is generally attained in SLE, although affected by the use of background immunosuppressive drugs, especially rituximab. The latter has also clearly been implicated with adverse COVID-19 outcomes in SLE, including need for hospitalization, mechanical ventilation and death. Although the wide adoption of vaccination has significantly improved COVID-19 outcomes, patients with SLE continue to pose challenges during the pandemic, mainly owing to administered immunosuppressive medications.

Purpose of review: Discuss the prognostic significance of kidney flares in patients with lupus nephritis, associated risk factors, and possible preventative strategies.

Recent findings: Recently performed clinical trials and observational cohort studies underscore the high frequency of relapses of kidney disease, following initial response, in patients with proliferative and/or membranous lupus nephritis. Analysis of hard disease outcomes such as progression to chronic kidney disease or end-stage kidney disease, coupled with histological findings from repeat kidney biopsy studies, have drawn attention to the importance of renal function preservation that should be pursued as early as lupus nephritis is diagnosed. In this respect, non-randomized and randomized evidence have suggested a number of factors associated with reduced risk of renal flares such as attaining a very low level of proteinuria (< 700-800 mg/24 h by 12 months), using mycophenolate over azathioprine, adding belimumab to standard therapy, maintaining immunosuppressive/biological treatment for at least 3 to 5 years, and using hydroxychloroquine. Other factors that warrant further clarification include serological activity and the use of repeat kidney biopsy to guide the intensity and duration of treatment in selected cases. The results from ongoing innovative studies integrating kidney histological and clinical outcomes, together with an expanding spectrum of therapies in lupus nephritis, are expected to facilitate individual medical care and long-term disease and patient prognosis.

Purpose of review: Axial spondyloarthritis (AxSpA) is among the rheumatology's most heritable complex diseases, yet precision medicine at clinics still needs to be explored. We reviewed the emerging concepts and recent developments in polygenic risk scores, Mendelian randomization, pharmacogenomics, single-cell sequencing, and spatial transcriptomics.

Recent findings: Polygenic risk score has resulted in encouraging results with potential diagnostic utility as it appears to outperform current diagnostic tools. Its performance and generalizability vary with ethnicity. Mendelian randomization has elucidated multiple causal associations, particularly between inflammatory bowel disease and AxSpA. Single-cell transcriptomics (particularly scRNA-seq and scATAC-seq) has identified numerous cell types, including synovial and blood immunological cells, to understand the contribution of both innate and adaptative immunity in AxSpA. Current molecular tools provide an exciting opportunity to advance precision medicine for AxSpA patients. However, extensive research and implementation strategies are still required before they can have an impact in the clinic.

Purpose of review: Individuals with post-acute sequelae of SARS-CoV-2 (PASC) complain of persistent musculoskeletal pain. Determining how COVID-19 infection produces persistent pain would be valuable for the development of therapeutics aimed at alleviating these symptoms.

Recent findings: To generate hypotheses regarding neuroimmune interactions in PASC, we used a ligand-receptor interactome to make predictions about how ligands from PBMCs in individuals with COVID-19 communicate with dorsal root ganglia (DRG) neurons to induce persistent pain. In a structured literature review of -omics COVID-19 studies, we identified ligands capable of binding to receptors on DRG neurons, which stimulate signaling pathways including immune cell activation and chemotaxis, the complement system, and type I interferon signaling. The most consistent finding across immune cell types was an upregulation of genes encoding the alarmins S100A8/9 and MHC-I. This ligand-receptor interactome, from our hypothesis-generating literature review, can be used to guide future research surrounding mechanisms of PASC-induced pain.

Purpose of review: Idiopathic inflammatory myopathies (IIM) are a complex family of autoimmune systemic disorders which often affect muscle and/or skin. IIM cause significant morbidity and mortality, but optimal treatment is uncertain. This review provides a practical guide for using intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) in the management of IIM, including dermatomyositis (DM), polymyositis (PM), immune-mediated necrotizing myositis (IMNM), and spontaneous inclusion body myositis (IBM), based on relevant recent literature and experience. We summarize pertinent considerations when using IVIG in special circumstances, including myositis-related dysphagia, interstitial lung disease (ILD), calcinosis cutis, and pregnant patients. This review also discusses IVIG safety, available formulations, and costs.

Recent findings: While IVIG has been used de facto for severe IIM for over 30 years, prior clinical trials of IVIG were notably limited. Recently, however, IVIG has proven safe and effective against IIM in several high-impact publications, including a large prospective, randomized placebo-controlled phase III study in DM. IVIG is useful against both muscular and extra-muscular manifestations in many types of IIM. It can be used as a first-line, steroid-sparring agent or as add-on to other treatments, tailored to specific clinical IIM scenarios. It is generally well-tolerated and has good safety profile, but accessibility and cost still limit its use.

Purpose of review: This article aims to review the challenges to diagnosis and management of calcium crystal deposition diseases and evaluate the literature published over the past 3 years.

Recent findings: The awaited development of classification criteria is an essential step in the progression of calcium crystal deposition disease clinical research. There have been recent improvements in the accuracy of imaging for the diagnosis of crystal deposition diseases with published definitions of characteristic features. Factors associated with acute flares of disease have been identified and an association with increased cardiovascular risk has been demonstrated. Targeted treatment options for calcium crystal diseases remain elusive. However, there have been advances in understanding the molecular mechanisms of disease revealing potential targets for future drug development. Calcium-crystal deposition diseases are increasing in incidence and prevalence as populations age and continue to associate with a high burden of disability. Despite this, calcium crystal deposition disease remains under-studied with a paucity of evidence-based treatment guidelines.

Purpose of review: This study aims to review recent studies on risk factors for syndesmophyte growth in ankylosing spondylitis (AS) and on treatment effects.

Recent findings: New genetic studies, including a genome-wide association study, provided only limited evidence of specific genetic associations with radiographic severity. Measures of inflammation, including vertebral osteitis and C-reactive protein level, were strongly associated with radiographic progression, while studies of adipokines had mixed results. Mesenchymal stem cells from HLA-B27 positive AS patients were found to promote vertebral ossification via a pathway of B27 misfolding, retinoic acid receptor-β activation, and increased bone alkaline phosphatase. Low vertebral trabecular bone density is associated with syndesmophyte growth, with reciprocal effects when bridged. Several observational studies suggested radiographic severity was reduced by treatment with tumor necrosis factor inhibitors, particularly when longer than 2 years. Syndesmophyte development in AS is the result of a complex, incompletely understood, interplay of inflammatory and mechanical factors.