Review Articles

Matrix metalloproteinases contribute to irreversible joint remodelling in the pathogenesis of joint diseases, including rheumatoid arthritis and osteoarthritis. This article reviews several aspects of matrix metalloproteinase biology related to arthritis and discusses how they relate to opportunities for precision medicine and diagnosis.

Clinical heterogeneity in systemic lupus erythematosus (SLE) is a challenge to effective treatment. This Review describes advances in our understanding of genetic and epigenetic variations in SLE and the roles of immune profiling and biomarker identification in the progress towards precision medicine.

In this Review, Cutolo et al. provide an overview of the vitamin D endocrine system and explore the biological and clinical effects of vitamin D₃ on innate and adaptive immunity in the context of autoimmune rheumatic diseases and COVID-19.

This Review summarizes the genetic and epigenetic basis of primary Sjögren syndrome, including genetic interactions with factors such as sex and environment. Understanding these processes provides insight into the molecular basis of this disease and might reveal new treatment targets.

In systemic lupus erythematosus, renal involvement is known as lupus nephritis and it is associated with mortality and morbidity. This Review compares and contrasts the existing management guidelines for lupus nephritis and describes emerging therapeutic approaches and the feasibility of precision medicine.

Pope et al. review the current management (including both screening and treatment) of organ-based manifestations of systemic sclerosis as well as overall disease modification, with a focus on evidence from clinical trials and consensus recommendations.

Sarcopenia, which involves the generalized loss of skeletal muscle strength and mass, is commonly associated with rheumatoid arthritis. In this Review, the authors discuss the epidemiology, pathophysiology and identification of rheumatoid sarcopenia and present evidence for the therapeutic roles of physical activity, nutrition and pharmacotherapy.

In this Review, the authors describe the relationships between persistent DNA damage, inflammation and cellular senescence, which represent a common pathway that contributes to the pathology of many conditions, including rheumatic diseases.

Gastrointestinal dysmotility is a major complication of systemic sclerosis but remains poorly understood. In this Review, the authors discuss the current understanding of systemic sclerosis gastrointestinal disease, existing and emerging therapies, and promising directions for future research

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.

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.

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.

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.

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 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.