Reviews & Analysis

Underrepresentation of patients with non-white skin in rheumatology educational resources impairs practitioners’ competence in caring for patients with skin of colour and reduces patients’ confidence in the medical system. Medical publishers and educators should reconsider how to promote equal representation and care of patients with all skin types.

Monogenic autoinflammatory diseases are linked to various germline and somatic pathogenic variants but numerous factors must be considered to explain their large phenotypic variability. This Review discusses genotype–phenotype relationships and the potential molecular mechanisms that might explain this variability.

According to new data, overexpression of the nicotinamide adenine dinucleotide (NAD) hydrolase, CD38, in systemic sclerosis (SSc) leads to NAD depletion and fibrosis. These intriguing findings link inflammation, NAD metabolism and fibrosis and bare striking resemblance to age-related changes in SSc. Could DNA damage also connect these seemingly unrelated pathways?

The discovery that autoantibodies and other factors can predict the future onset of rheumatoid arthritis (RA) has encouraged the development of clinical trials looking at RA prevention. Although an exciting area of research, finding an approach that results in the successful completion of an RA prevention trial is challenging.

The transcription factor Sox9 is important for cartilage formation during development, but its role in postnatal growth plates and adult articular cartilage has been uncertain. New research is revealing essential roles for Sox9 in postnatal cartilage homeostasis and in preventing post-traumatic osteoarthritis, along with new mechanisms for chondrocyte-to-osteoblast transition.

Salivary gland dysfunction is an important characteristic of primary Sjögren syndrome (pSS). In this Review, the authors discuss various epithelial abnormalities in pSS and the mechanisms by which epithelial cell–immune cell interactions contribute to disease development and progression.

Type III interferons (IFNλs) affect innate and adaptive immune responses and are associated with the pathogenesis of autoimmune rheumatic diseases. In this Review, the authors provide an overview of IFNλs in rheumatic diseases and discuss therapeutic strategies to target them.

Immune-related disorders in patients with COVID-19 are increasingly being reported worldwide, with thousands of cases recorded of manifestations that can mimic a broad range of systemic and organ-specific inflammatory and autoimmune diseases.

The prevalence of rheumatic diseases is increasing in African countries, leading to an increased need for specialist rheumatologists and disease-modifying drugs. In this Review, the authors outline what is currently known about the state of rheumatic diseases in Africa.

Various drugs used in rheumatoid arthritis management have anti-inflammatory effects that can hinder atherosclerosis development and progression. However, these drugs can also concurrently have different pro-atherogenic effects, complicating the relationship between these drugs and cardiovascular involvement in rheumatoid arthritis.

Pathogenic, long-lived memory cells of the immune system present a barrier to resolution of chronic inflammatory rheumatic diseases. Approaches to selectively eliminate these cells while sparing protective immune memory cells could restore immunological tolerance and achieve treatment-free remission.

The accurate homogeneous differentiation of human induced pluripotent stem cells into chondrocytes is crucial for cartilage regenerative therapies. Discovery of the signalling pathways responsible for the differentiation of unwanted cell types during in vitro chondrogenesis could herald a breakthrough for in vitro cartilage generation.

Childhood-onset arthritis has historically been treated as a separate entity to adult-onset arthritis, with its own nomenclature and classification system. Biological evidence has revealed the limitations of the current approach, necessitating a fresh look at the classification of paediatric arthritis.

Myositis is a group of conditions that vary greatly in risk factors, clinical manifestations, laboratory markers, presumed pathogenetic mechanisms, treatment responses and prognoses. Approaches to divide myositis into mutually exclusive and stable phenotypes are being considered, but are we thinking comprehensively enough in our attempts at classification?

TNF inhibitors are used to treat various immune-related adverse events caused by immune checkpoint inhibitors (ICIs). However, whether TNF inhibition compromises the anticancer efficacy of ICI therapy is unknown. This Review discusses the relationship between TNF, TNF inhibition and cancer.

Intestinal dysbiosis is thought to be involved in the early stages of rheumatoid arthritis (RA). In this Review, the authors discuss the gut–joint axis in RA and the potentially pathogenic role of gut-derived immune cells in the joints.

The field of rheumatology is poised to categorize the phenotypes of systemic autoimmune diseases on the basis of measurable and quantifiable molecular signatures. Emerging efforts to identify similarities across diseases, predict clinical outcomes and predict response to therapy using quantitative, data-driven approaches could considerably change treatment paradigms.

A multitude of factors contribute to the development and progression of systemic lupus erythematosus (SLE) through their effects on immune cells and tissue resident cells. Ultraviolet light instigates skin inflammation in SLE, and now new findings suggest that neutrophils in the inflamed skin migrate to the kidneys, spreading the inflammatory response.

In this Consensus Statement, an expert panel from the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) recommends terminology for defining specific subgroups of individuals during the preclinical and early clinical phases of psoriatic arthritis to be used in research studies.

In this Review, the authors discuss macrophage activation syndrome (MAS) in relation to other cytokine storm scenarios, and provide a framework for understanding MAS within the spectrum of innate and adaptive immunity in the context of gain or loss of immune function.