Reviews & Analysis

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.

Among the limited quality and quantity of evidence on vaccination use in individuals with rheumatic and musculoskeletal diseases, a new guideline, developed with a rigorous methodology, provides useful support to clinicians and patients in making health-related decisions. Most recommendations are conditional, serving as a call to action for further research.

Osteoarthritis has many appearances and can stabilize or progress aggressively. However, there is not yet an aetiological classification of osteoarthritis subtypes. Can in silico approaches, despite difficulties in validation, help with the identification of experimentally challenging subtypes? And if they can, will these approaches translate to clinical benefits?

The involvement of citrulline-specific CD4⁺ T cells in anti-citrulline protein antibody-positive rheumatoid arthritis (RA) is well described, whereas less attention has been given to CD8⁺ T cells. New data suggest that CD8⁺ T cells also contribute to citrulline-specific immune responses in RA.

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.

An ambitious project to update the classification of vasculitis syndromes has culminated in the development of new classification criteria for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, Takayasu arteritis and giant cell arteritis. Endorsed by the ACR and EULAR, the new criteria reflect progress in the understanding and assessment of these conditions.

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.

Next-generation sequencing has led to the discovery of multiple rare autoinflammatory diseases, together with their corresponding disease-causing mutations, creating opportunities to develop personalized medicine and providing useful insight into more common forms of autoimmunity and autoinflammation.

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

The mechanisms underlying the genetic association between HLA-B27 and ankylosing spondylitis, including the contribution of endoplasmic reticulum aminopeptidase 1 (ERAP1), continue to elude the field. New findings support the involvement of the unfolded protein response and highlight the therapeutic potential and limitations of targeting ERAP1 in this disease.

The phenotypic and functional heterogeneity of synovial tissue fibroblasts are well described, whereas the cellular and molecular mechanisms that establish this diverse fibroblast repertoire in the adult joint have remained unclear. When is the fate of synovial fibroblast repertoire determined, and what are the consequences for arthritis development as adults?

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.