Reviews & Analysis

In this Review, the authors discuss the similarities and differences between intervertebral disc degeneration and osteoarthritis of the facet joint and argue that both diseases should be viewed as being part of the same molecular disease spectrum.

Bone regeneration is a dynamic and tightly regulated process, but various mechanisms can disrupt this process and cause healing impairment. This Review discusses the complex processes that occur during the early phases that might be targeted to prevent bone healing disorders.

Although elegant work has detailed the clinical presentation, immune response and disease outcome of multisystem inflammatory syndrome in children, many questions remain. Studies in 2022 have explored the nature of the vascular injury, the role of the SARS-CoV-2 spike protein and the association with the current variants of the virus.

Successful, long-term treatment of articular cartilage injuries is important for the prevention of osteoarthritis but remains a major challenge. Three studies in 2022 highlight new approaches to improving articular cartilage regeneration.

In this Review, the authors discuss how emerging insights into the tissue-specific pathogenetic mechanisms underlying clinical heterogeneity in psoriatic arthritis support the need for tissue-based precision therapy for the disease.

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’.