News & Views in 2023

Newly published European guidelines for the management of systemic lupus erythematosus (SLE) and lupus nephritis, specifically recommending early and aggressive use of new medications, signal that the old paradigm of SLE management is shifting. Although it presents challenges, this shift is welcome — and is likely to have far-reaching implications.

Emerging data suggest that the frequency of long-term opioid use is high among individuals with rheumatic and musculoskeletal diseases, which is of concern given the risks of opioid misuse. But is long-term opioid use really that high or is the situation more complicated?

Rheumatoid arthritis synovium contains phenotypically and functionally heterogeneous fibroblast-like synoviocytes. Cutting-edge analyses have now defined at least four distinct states of these cells related to their location in the synovium, epigenetic imprinting and the influence of microenvironment mediators.

The rise in the use of digital health-care technologies such as electronic patient-reported outcome measures enables a transformation of the traditional care model. In light of the increasing demand for rheumatologists, telehealth could enable more efficient usage of scarce face-to-face appointments.

Drug-free remission is a treatment goal in rheumatoid arthritis that can be achieved by tapering and discontinuation of biologic DMARDs. However, newly published real-world evidence suggests that DMARD discontinuation occurs less frequently than results of clinical trials suggest, so it is important to question what the ultimate goal of treatment should be.

The pathogenesis of juvenile dermatomyositis (JDM) is complex and various evidence implicate a role for type I interferons. Could the use of a bioengineered paediatric skeletal muscle model provide insight into this disease and have potential for high throughput testing of therapeutic agents?

The rarity of various forms of vasculitis, as well as other rheumatic diseases, presents difficulties in studying the genetics of these diseases as well as for evaluating treatments. Might new approaches, such as joint genetic analyses and drug repurposing, provide opportunities to learn more about these diseases and identify new therapies and serve as a basis for basket clinical trials?

No drugs are yet approved for the treatment of primary Sjögren syndrome, despite a large number of clinical trials. Non-conventional approaches can help to identify novel therapeutic targets. Using a drug-repositioning transcriptomic approach, interferon has emerged once again as a major target for intervention in this disease process.

Understanding why individuals with Down syndrome are highly predisposed to autoimmunity has broad mechanistic and therapeutic implications. New work identifies novel potential mechanistic pathways driving increased autoimmunity-relevant CD11c⁺ B cells and provides the broadest view to date of the repertoire of autoantibodies generated in individuals with Down syndrome.

Given that intra-articular injections for the knee of treatments such as hyaluronic acid, stem cells and platelet-rich plasma are advised against or only weakly recommended by current clinical-practice guidelines, why do people continue to seek information about these treatments?

Emerging research suggests that chimeric antigen receptor T cell therapy could be an effective treatment for a range of difficult-to-treat autoimmune diseases, and sophisticated approaches are in tests, yet initial reports also highlight several questions that remain to be answered.

Among the wide range of drugs now available for the treatment of psoriatic arthritis, the best option for an individual patient remains unclear. Emerging real-world evidence from several Nordic registries suggests that differences exist in the response rates to different classes of biologic and targeted synthetic DMARDs in psoriatic arthritis.

The full picture of post-COVID-19 autoimmune diseases and their prevalence is lacking despite numerous case reports and small series. Two studies that use large cohorts now highlight that SARS-CoV-2 infection is linked to a substantially increased risk of developing a diverse spectrum of new-onset autoimmune diseases.

The onset of the destructive autoimmune joint disease rheumatoid arthritis (RA) is preceded by the development of autoantibodies to multiple citrullinated proteins. Research has now shown that citrullination modifies antigen processing, resulting in the production of cryptic epitopes, suggesting a new model for RA autoantibody development.

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.

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.

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?