Reviews & Analysis

Methotrexate is commonly used in the treatment of inflammatory rheumatic diseases. In this Review, the authors discuss the potential hepatotoxicity of methotrexate, with particular consideration of the role of chronic liver disease, and suggest screening and monitoring strategies for patients receiving methotrexate.

In this Review, the authors discuss vascular involvement in Behçet syndrome and how the unusual pathogenesis involving an impaired immune-inflammatory response influences the treatment approach, which differs from that of other vasculitides.

Janus kinase inhibitors continue to show promise in a diverse range of indications, but administration of these drugs needs careful consideration of the benefits and risks. Among a plethora of publications in 2022, notable studies explored an important new indication and provided insights into safety concerns.

Electronic health records (EHRs) contain enormous amounts of real-world data that could inform researchers, doctors and patients about many aspects of rheumatology. However, EHRs are not yet fully utilized, mainly because automatic data extraction is difficult. Several studies in 2022 highlight the feasibility and clinical utility of computer-assisted EHR analysis.

In 2022, advances in the prediction of the response to treatment in rheumatoid arthritis resulted from gene-expression profiling in synovial biopsy samples, assessment of the expression of interferon-response genes in the blood, and the application of machine learning to patients’ clinical parameters and genetic variance.

Since the start of the SARS-CoV-2 vaccination campaign, our knowledge of the effects of vaccines in people with inflammatory rheumatic diseases has remained incomplete. In particular, the effects of immunomodulatory therapies on vaccine success are poorly understood. Three notable papers from the past year have helped to fill these knowledge gaps.

Cartilage calcification is a hallmark of osteoarthritis. In this Review, the authors discuss the molecular mechanisms of calcium crystal formation in chondrocytes, the effects of crystals on cells in the joint, and potential targets for the treatment of osteoarthritis and other calcification disorders.

In this Perspective, the authors propose a model in which an imbalance of threat and soothing systems leads to hyperactivation of the brain’s salience network, which, in conjunction with other mechanisms, contributes to fibromyalgia.

Research related to the role of the synovium and its cell constituents during the pathogenies of osteoarthritis (OA) has taken a back seat to that of the cartilage and chondrocytes. The influence of synoviocytes in OA is increasingly recognized, but are synoviocytes equal in their contributions to disease progression?

Glycosylation is a common modification that can affect protein stability and interactions. In this Review, the authors discuss the role of glycosylation in rheumatic diseases, as well as the therapeutic potential of glycosylation-based interventions.

The design of effective inhibitors of protein–protein interactions is challenging. In a new study, thermal fluctuation of protein structure was simulated to identify small-molecule candidates that inhibit protein–protein interactions. The application of this technique to other protein–protein interactions might facilitate the replacement of biologic agents with orally available small-molecule drugs.

Contemporary guidelines for the management of systemic lupus erythematosus (SLE) recommend prescribing hydroxychloroquine dosages of 5 mg/kg per day or lower to minimize toxicity. However, new evidence raises serious concerns about the risk of SLE flare associated with such doses. How do the benefits and risks of this controversial recommendation balance out?

Various types of immune cells are dysregulated in systemic sclerosis and contribute to the initiation and progression of fibrosis. In this Review, the authors summarize various immune cell defects implicated in this disease that are current or potential targets for therapy.

In this Review, the authors describe the involvement of characteristic hallmarks of ageing in rheumatic diseases, suggesting that these chronic conditions can be considered to be diseases of premature or accelerated ageing, in which anti-ageing drugs may have therapeutic benefits.

In this Perspective, with specific reference to rheumatoid arthritis, Lin, Cooles and Isaacs identify factors that have contributed to the relatively slow progress towards precision medicine for rheumatic diseases, and suggest strategies for closing this ‘precision gap’.

Structural modification of RNA by adenosine-to-inosine editing renders self-RNA invisible to RNA sensors of the innate immune system. Lack of RNA editing unleashes inflammatory responses that can lead to autoinflammation. A deeper understanding of the associated signalling pathways might reveal potential targets for drug discovery for autoinflammatory diseases.

In this Review, the authors discuss the use of immune-checkpoint inhibitors for treatment of cancer in patients with pre-existing autoimmune disease, including the possibility of the use of biologic DMARDs to enhance tumour responses while preventing severe immune-related adverse events.

This Review discusses how best to manage the reproductive health of patients with vasculitis, including the safety of contraception, the use of assisted reproductive technology, preservation of fertility during therapy, disease management in pregnancy and the use of medications compatible with pregnancy and lactation.

Although neutrophils are vital components of the innate immune system, they can also contribute to the inflammation and autoantibody formation that characterize a number of rheumatic diseases. The ability to specifically target neutrophils, and in particular activated neutrophils, could enable the direct delivery of drugs for therapeutic modulation of neutrophil activity.

The mitochondrion has multiple functions, including energy production, regulation of apoptosis and reactive oxygen species generation. Disruption of these mitochondrial processes can lead to pro-inflammatory immune responses. This Review discussions the role of mitochondria and mitochondrial dysfunction in rheumatic diseases.