Reviews & Analysis

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.

Glucocorticoids are common medications that are used in research trials and clinical practice. Measuring the toxicity of glucocorticoids in children is complicated by various factors such as age and growth. A standardized tool could help to record these toxicities across different specialities in a systematic manner.

New research reinforces the fact that most recommendations in rheumatology are not informed by comparative efficacy randomized controlled trials. Performing these studies is time and resource intensive. Policies and funding to perform these studies in a timely and resource constraint manner are essential.

Often viewed as merely an inconsequential episode of acute joint pain, gout flare has also been associated with an increased risk of acute myocardial infarction and stroke. New findings suggest the risk is highest within the first 60 days of gout flare, and could be influenced by flare treatment.

New research shows that TNF can directly induce osteoclastogenesis from transforming growth factor-β (TGFβ)-primed macrophages and that knockout of TGFβ signalling limits TNF-induced arthritic bone erosion in mice, suggesting that TGFβ inhibition could enhance the effect of anti-TNF therapy in rheumatoid arthritis.

In this Review, the authors discuss the roles of sex and gender in relation to axial spondyloarthritis. Although evidence now suggests that the disease has equal prevalence in men and women, important differences occur in phenotypes, response to therapy and outcomes.

In this Review, the authors summarize the genetic factors associated with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). They describe the findings from genetic association studies, their pathogenic significance and their implications for the classification, management and prognosis of AAV.

Transitional care in rheumatology has been debated for over three decades and yet unmet needs of young people are still being reported. Why the slow progress? Perhaps we need to stop talking about transitional care in rheumatology and talk more about developmentally appropriate health care for young people with rheumatic conditions.

In this Review, Psarras, Wittmann and Vital discuss evidence of the production of type I interferons by cells and tissues other than haematopoietic cells. These interferons can have local effects, and their roles in the pathogenesis of systemic lupus erythematosus suggest the value of interferon-blocking therapies for treatment of this condition.

In this Review, the authors summarize and discuss regional differences in the prevalence and incidence of rheumatoid arthritis (RA), and describe temporal trends associated with the disease as well as evidence related to risk factors.

Multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease are both hyperinflammatory disorders associated with infectious diseases, but are they distinct syndromes or do they exist along a continuum? A comparison of the host immune response in these illnesses provides surprising new insights.

Lack of understanding of the immunology of sarcoidosis has limited therapeutic progress. However, evidence from a small open-label trial suggests that treatment with the Janus kinase inhibitor tofacitinib can improve sarcoidosis symptoms, predominantly by inhibiting type 1 immunity.

Gout can be effectively treated with long-term urate-lowering therapy. Current guidelines advocate the use of a treat-to-target serum urate strategy, with a target serum urate concentration of <5 mg/dl (<0.30 mmol/l) or <6 mg/dl (<0.36 mmol/l), but specific targets are under debate. In this Review, the authors consider the rationale and evidence for the recommendations.

In this Review, the authors discuss age-related arthropathy and the similarities and differences between childhood loss of immune tolerance and adult development of immune-mediated arthritis, and develop three hypotheses describing age-related mechanisms that contribute to the onset of arthritis.

This Review summarizes our understanding of sex- and gender-related differences in psoriatic arthritis, with a focus on disease progression and outcomes, underlying mechanisms and response to therapies.

The paradoxical increase in gout flare risk upon initiation of urate-lowering therapy presents challenges for the measurement and analysis of gout flares in clinical trials of urate-lowering therapy. In this Perspective, the authors highlight these issues and discuss potential solutions.

In patients with autoimmune rheumatic disease, methotrexate therapy has been associated with poor immune response to vaccines, including those intended to provide protection against COVID-19. Emerging evidence supports the practice of temporarily discontinuing this treatment in order to improve immunogenicity.

Assessing systemic sclerosis (SSc) disease activity is challenging, and improved outcome measures are needed. This Review describes clinical and biochemical outcome measures of distinct features of SSc, with an emphasis on the dermatological manifestations and interstitial lung disease, including insights into biomarkers gained from single-cell RNA sequencing.