Nature Reviews Rheumatology最新文献

Emerging evidence indicates that memory B cells are dysfunctional in systemic lupus erythematosus (SLE). They are hyporesponsive to signalling through the B cell receptor (BCR) but retain responsiveness to Toll-like receptor (TLR) and type I interferon signalling, as well as to T cell-mediated activation via CD40–CD154. Chronic exposure to immune complexes of ribonucleoprotein (RNP)-specific autoantibodies and TLR-engaging or BCR-engaging cargo is likely to contribute to this partially anergic phenotype. TLR7 or TLR8 signalling and the resulting production of type I interferon, as well as the sustained activation by bystander T cells, fuel a positive feedforward loop in memory B cells that can evade negative selection and permit preferential expansion of anti-RNP autoantibodies. Clinical trials of autologous stem cell transplantation or of B cell-targeted monoclonal antibodies and chimeric antigen receptor (CAR) T cells have correlated replenishment of the memory B cell population with relapse of SLE. Moreover, the BCR hyporesponsiveness of memory B cells might explain the failure of non-depleting B cell-targeting approaches in SLE, including BTK inhibitors and anti-CD22 monoclonal antibodies. Thus, targeting of dysfunctional memory B cells might prove effective in SLE, while also avoiding the adverse events of broad-spectrum targeting of B cell and plasma cell subsets that are not directly involved in disease pathogenesis.

Uveitis encompasses multiple different conditions that are all characterized by intra-ocular inflammation. Uveitis occurs in the context of many different rheumatological conditions and carries a substantial risk to vision. Uveitis can develop both at the early stages of rheumatic diseases, sometimes even preceding other clinical features, and at later stages of disease. Uveitis can also occur as either a direct or an indirect complication of therapies used to treat patients with rheumatic disease. Conversely, patients with uveitis of non-rheumatic aetiology sometimes require immunosuppression, a treatment option that is not readily accessible to ophthalmologists. Thus, collaborative working between rheumatologists and ophthalmologists is critical for optimal management of patients with uveitis. This Review is written with rheumatologists in mind, to assist in the care of patients with uveitis. We collate and summarize the latest evidence and best practice in the diagnosis, management and prognostication of uveitis, including future trends and research priorities.

Rheumatology faces a critical shortage of health-care professionals, exacerbated by an ageing patient population and escalating costs, resulting in widening gaps in care. Exponential advances in digital health technologies (DHTs) in the past 5 years offer new opportunities to address these challenges and could contribute to overall improved health care. However, keeping pace with innovations and integrating them into clinical practice can be challenging. This Review explores the transformative potential of DHTs for rheumatology in reshaping the entire patient pathway and redefining the roles of patients and providers, and discusses the potential barriers to DHT integration. Key technologies, such as large language models, clinical decision-support systems, digital therapeutics, electronic patient-reported outcomes, digital biomarkers, robots, self-sampling devices and artificial intelligence-based scribes, can be implemented along the patient pathway. A digital-first hybrid stepped-care patient pathway could combine in-person and remote care, enabling personalized and continuous monitoring through a digital safety net. The potential benefits and risks of transforming the traditional patient–provider relationship into a digital health triad with technology are discussed. Collaborative efforts are needed to navigate the evolving digital health landscape and harness the potential of DHTs to improve rheumatology care.

Over the past few decades, the connection between metabolism and various inflammatory and rheumatic diseases has been an area of active investigation. Nonetheless, the precise mechanisms underlying these relationships remain a topic of ongoing debate, owing in part to conflicting data. This discrepancy can be attributed to the predominant focus on peripheral mechanisms in research into the metabolic consequences of rheumatic diseases. However, a wealth of evidence supports the notion that the central nervous system, specifically the hypothalamus, has an important influence on metabolic homeostasis. Notably, links have been established between crucial hypothalamic mechanisms responsible for regulating energy balance (including food intake, thermogenesis, and glucose and lipid metabolism), such as AMP-activated protein kinase, and the pathophysiology of rheumatoid arthritis. This Review aims to comprehensively examine the current understanding of central metabolic control in rheumatic diseases and explore potential therapeutic options that target this pathophysiological mechanism.

Management of rheumatoid arthritis (RA) has evolved from simply the direct translation of drug efficacy results from clinical trials to patient care, to a more complex longitudinal process that considers not only drug efficacy but also the safety gestalt of a treatment and patient profiles and preferences, as well as health-economic factors. With numerous DMARDs available to treat RA, knowledge about trial efficacy becomes less important than data that inform an appropriate clinical strategy for their optimal selection and use. Overly ambitious approaches targeting the ‘maximum’ level of success could, for example, be prone to failure and create frustration, and lead to a large number of patients then being considered as ‘difficult to treat’. Safety profiles might be more informative than efficacy profiles for precision medicine approaches. Contemporary RA management strategies might therefore take a more holistic approach, beyond merely efficacy, to the setting of targets that lead to improved compliance rather than aspirational successes, with consideration of each patient’s multimorbidity profile and preferences, as well as the safety profile of each treatment. Ultimately, the goal remains unchanged: maximizing health-related quality of life; however, with a focus on optimal balance rather than superlatives.