Imaging holds a pivotal yet contentious role in the early diagnosis of axial spondyloarthritis. Although MRI has enhanced our ability to detect early inflammatory changes, particularly bone marrow oedema in the sacroiliac joints, the poor specificity of this finding introduces a substantial risk of overdiagnosis. The well intentioned push by rheumatologists towards earlier intervention could inadvertently lead to the misclassification of mechanical or degenerative conditions (eg, osteitis condensans ilii) as inflammatory disease, especially in the absence of structural lesions. Diagnostic uncertainty is further fuelled by anatomical variability, sex differences, and suboptimal imaging protocols. Current strategies-such as quantifying bone marrow oedema and analysing its distribution patterns, and integrating clinical and laboratory data-offer partial guidance for avoiding overdiagnosis but fall short of resolving the core diagnostic dilemma. Emerging imaging technologies, including high-resolution sequences, quantitative MRI, radiomics, and artificial intelligence, could improve diagnostic precision, but these tools remain exploratory. This Viewpoint underscores the need for a shift in imaging approaches, recognising that although timely diagnosis and treatment is essential to prevent long-term structural damage, robust and reliable imaging criteria are also needed. Without such advances, the imaging field risks repeating past missteps seen in other rheumatological conditions.

Once regarded as passive bystander cells of the tissue stroma, fibroblasts have emerged as active orchestrators of tissue homeostasis and disease. From regulating immunity and controlling tissue remodelling to governing cell growth and differentiation, fibroblasts assume myriad roles in guiding normal tissue development, maintenance and repair. By comparison, in chronic inflammatory diseases such as rheumatoid arthritis, fibroblasts recruit and sustain inflammatory leukocytes, become dominant producers of pro-inflammatory factors and catalyse tissue destruction. In other disease contexts, fibroblasts promote fibrosis and impair host control of cancer. Single-cell studies have uncovered striking transcriptional and functional heterogeneity exhibited by fibroblasts in both normal tissues and diseased tissues. In particular, advances in the understanding of fibroblast pathology in rheumatoid arthritis have shed light on pathogenic fibroblast states in other chronic diseases. The differentiation and activation of these fibroblast states is driven by diverse physical and chemical cues within the tissue microenvironment and by cell-intrinsic signalling and epigenetic mechanisms. These insights into fibroblast behaviour and regulation have illuminated therapeutic opportunities for the targeted deletion or modulation of pathogenic fibroblasts across many diseases.

Many monogenic autoinflammatory diseases, including DADA2 (deficiency of adenosine deaminase 2), HA20 (haploinsufficiency of A20), SAVI (STING-associated vasculopathy with onset in infancy), COPA syndrome, LAVLI (LYN kinase-associated vasculopathy and liver fibrosis) and VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, present predominantly with vasculitis and constitute a substantial subgroup of vasculitic conditions associated with a 'probable aetiology'. The spectrum of monogenic vasculitis encompasses all sizes and types of blood vessel, ranging from large vessels to medium-size and small vessels, and from the arterial side to the venous side of the vasculature. Monogenic vasculitis typically starts early in life during infancy or childhood; VEXAS syndrome, which presents in late adulthood, is an exception. The activation of myeloid cells via inflammasome and nuclear factor-κB pathways, type I interferon-enhanced autoimmune mechanisms and/or dysregulated adaptive immune responses have an important role in the development of immune-mediated endothelial dysfunction and vascular damage. Genetic testing is essential for the diagnosis of underlying monogenic autoinflammatory diseases; however, the penetrance of genetic variants can vary. Increased awareness and recognition of distinctive clinical findings could facilitate earlier diagnosis and allow for more-targeted treatments.

Osteoarthritis (OA) is a chronic disease primarily affecting older adults, mainly impacting the hip and knee joints. The increasing prevalence of OA contributes to rising healthcare demands and costs. Current OA treatment guidelines emphasize the importance of self-management education and guidance, particularly in promoting physical activity and weight management. In addition, improving sleep is crucial for managing OA. Developing effective self-management interventions necessitates a comprehensive understanding of the factors that facilitate these behaviors. Especially for changing health behaviors, it is important to focus on psychosocial factors. Therefore, this systematic review aimed to identify the psychosocial factors associated with physical activity, weight management, and sleep in adults with hip and/or knee OA.

Autoimmune rheumatic diseases are a heterogeneous group of conditions, including rheumatoid arthritis (RA) and systemic lupus erythematosus. With the increasing availability of large single-cell datasets, novel disease-associated cell types continue to be identified and characterized at multiple omics layers, for example, 'T peripheral helper' (TPH) (CXCR5- PD-1hi) cells in RA and systemic lupus erythematosus and MerTK+ myeloid cells in RA. Despite efforts to define disease-relevant cell atlases, the very definition of a 'cell type' or 'lineage' has proven controversial as higher resolution assays emerge. This Review explores the cell types and states involved in disease pathogenesis, with a focus on the shifting perspectives on immune and stromal cell taxonomy. These understandings of cell identity are closely related to the computational methods adopted for analysis, with implications for the interpretation of single-cell data. Understanding the underlying cellular architecture of disease is also crucial for therapeutic research as ambiguity hinders translation to the clinical setting. We discuss the implications of different frameworks for cell identity for disease treatment and the discovery of predictive biomarkers for stratified medicine - an unmet clinical need for autoimmune rheumatic diseases.

Systemic vasculitis, common forms of which include anti-neutrophil cytoplasmic antibody-associated small-vessel vasculitis, large-vessel vasculitis and Behçet syndrome, are frequently complicated by arterial or venous thrombotic events (AVTEs). Newly identified entities such as DADA2 (deficiency of adenosine deaminase 2) and VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, which are driven by genetic mutations, also exhibit vasculitic features and are associated with a high risk of AVTEs. AVTEs in systemic vasculitis, including monogenic forms of vasculitis, are due to the complex interaction of inflammation and coagulation. New insights into the pathogenetic mechanisms implicate endothelial dysfunction, immune complex deposition and the interplay of pro-inflammatory cytokines with prothrombotic factors, which collectively promote thrombus formation. AVTEs impose a substantial disease burden, complicate diagnosis and negatively affect prognosis by increasing the risk of morbidity and mortality. Early diagnosis and treatment are crucial to prevent lasting damage. Management strategies should target both thrombosis and underlying inflammation. Antithrombotic therapies, including low-dose aspirin, or oral anticoagulants should be used on the basis of individual thrombotic risk assessment. Immunosuppressive therapy is the cornerstone of treatment for arterial and venous thrombosis, particularly in Behçet syndrome, in which vascular inflammation has a crucial role in thrombotic complications.

Osteoarthritis (OA) is one of the most common degenerative diseases, and the number of patients has been constantly increasing. Non-steroidal anti-inflammatory drugs, glucocorticosteroids, opioids, etc., and surgical procedures, e.g. arthroplasty, are among the most common methods of treatment. There are reasons to believe that the gut microbiome (GMB) may influence inflammatory processes occurring in the pathomechanism of OA. The inflammatory processes occurring in the intestines may lead to disruption of tight junctions and increased concentrations of pro-inflammatory cytokines, resulting in increased permeability of intestines, causing low-grade inflammation, including in the joints. Methods of altering the GMB composition to reduce the inflammatory and joint degenerative processes are known only to some extent, and long-term research is required. Osteoarthritis, a particularly well-known and very widespread disease due to the aging population, is characterized by moderate and local inflammation. It occurs due to the effects of biomechanical cartilage wear with damage of joint structures, primarily through degenerative processes. OA represents a therapeutic challenge, and any element that can influence its inhibition is highly sought after. Therefore, these methods seem to offer a promising additional approach to treatment.

Systemic lupus erythematosus (SLE) is a complex, chronic autoimmune disease that causes multi-organ inflammation and damage. Left untreated or inadequately managed, SLE can lead to severe organ dysfunction, disability, and reduced quality of life. In Poland, the absence of standardized, evidence-based clinical guidelines tailored to local resources and practices has created inconsistencies in SLE management. The purpose of these guidelines is to provide clear, evidence-based recommendations for the treatment and management of adult patients with SLE in the Polish healthcare system. These recommendations aim to align clinical practices with international standards, optimize treatment strategies, standardize patient care, and improve health outcomes while guiding healthcare policy.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease influenced by genetic, environmental, and immunological factors. Variations in cytokine genes, including tumor necrosis factor α (TNF-α) and interleukin-10 (IL-10), have been implicated in SLE pathogenesis, but their associations remain uncertain owing to conflicting study results.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder usually characterized by multi-organ involvement. Its pathogenesis is complex and involves genetic and environmental factors, while immune responses usually mediate organ damage and promote fibrosis, which is a key feature of the disease. IgG4 responses, however, are not exclusive to IgG4-RD and can be encountered in other diseases with phenotypes that partially overlap that of IgG4-RD. Although IgG4-RD has clinical and histological hallmarks, the lack of validated diagnostic criteria often makes the diagnosis challenging, requiring a multi-dimensional approach that integrates clinical, radiological and serological data. The present Review covers recent advances in the understanding of disease drivers and its clinical phenotypes, mainly focusing on the differential diagnosis with potential IgG4-RD mimickers, namely histiocytoses, lymphoproliferative disorders, systemic vasculitides and other immune-mediated conditions. The Review also provides a schematic approach to IgG4-RD treatment, including a brief overview of glucocorticoid-sparing agents and emerging therapies, from B cell-depleting monoclonal antibodies to cytokine-targeting drugs, the majority of which are currently under investigation in randomized clinical trials.

Osteoarthritis (OA) is a leading cause of chronic pain worldwide, resulting in substantial disability and placing a substantial burden on patients and society. The hallmark symptom of OA is joint pain. Despite extensive research, new treatments for OA pain remain limited, partly owing to a lack of understanding of underlying pain mechanisms. For a long time, OA pain was seen as a reflection of nociceptive activity at the joint level, and the brain has been viewed as a passive recipient of such information. In this Review, we challenge these concepts and discuss how, over time, the activation of peripheral nociceptors leads to adaptations in the brain that dictate the properties and experience of OA pain. These adaptations are further influenced by the inherent properties of the brain. We review general concepts that distinguish pain from nociception, present evidence on the incongruity between joint injury and experience of OA pain, and review brain circuits that are crucial in the perception of OA pain. Finally, we propose a model that integrates nociception, spinal-cord mechanisms, and central nervous system dynamics, each contributing uniquely to pain perception. This framework has the potential to inform the development of personalized treatment strategies.

Chimeric antigen receptor (CAR)-based therapies developed for the treatment of haematological malignancies have recently been repurposed to treat refractory systemic autoimmune diseases. In this Review we critically discuss the current data available on the use of CAR-based therapy in systemic autoimmune diseases, the current challenges, and the potential next steps toward their implementation into clinical practice. Beyond the targeting of B cells via CD19, we discuss the advantages and potential pitfalls of targeting plasma cells (B-cell Maturation Antigen or CD138) and other non-immune targets, such as fibroblast activated protein, and of aiming to restore immune homeostasis using CAR T regulatory cells. Crucial points need to be addressed for CAR-based therapy to become a viable treatment option for patients with systemic autoimmune diseases.

Articular cartilage can withstand substantial compressive and shear forces within the joint and also reduces friction during motion. The exceptional mechanical properties of articular cartilage stem from its highly organized extracellular matrix (ECM). The ECM is composed mainly of collagen type II and is pivotal in conferring mechanical durability to the tissue within its proteoglycan-rich matrix. Articular cartilage is prone to injury and degeneration, and current treatments often fail to restore the mechanical function of this tissue. A key challenge is replicating the intricate collagen-proteoglycan network, which is essential for the long-lasting restoration and mechanical durability of the tissue. Understanding articular cartilage development, which arises between late embryonic and early juvenile development, is vital for the creation of durable therapeutic strategies. The development of the articular ECM involves the biosynthesis, fibrillogenesis and self-assembly of the collagen type II network, which, along with proteoglycans and minor ECM components, shapes the architecture of adult articular cartilage. A deeper understanding of these processes could inform biomaterial-based therapies aimed at improving therapeutic outcomes. Emerging biofabrication technologies offer new opportunities to integrate developmental principles into the creation of durable articular cartilage implants. Bridging fundamental biology with innovative engineering offers novel approaches to generating more-durable 3D implants for articular cartilage restoration.

Vascular ultrasound can be useful in the diagnostic investigation of patients with suspected giant cell arteritis. The clinical overlap between polymyalgia rheumatica and giant cell arteritis raises the prospect that vascular ultrasound can be used to identify features suggestive of giant cell arteritis in polymyalgia rheumatica, and has generated debate on whether all patients with polymyalgia rheumatica should undergo vascular ultrasound. However, before this approach becomes routine practice, more careful and detailed scrutiny is needed of its clinical necessity, patient benefit, and cost-effectiveness, where data are currently lacking. We argue that the case for universal vascular ultrasound screening in polymyalgia rheumatica is speculative and there is a greater necessity to direct resources to address misdiagnosis and overtreatment with glucocorticoids, which carry risks such as osteoporosis, diabetes, ocular morbidity, and infection.

Osteoarthritis (OA) is a chronic joint disease that has long been considered a simple wear-and-tear condition. Over the past decade, research has revealed that various inflammatory features of OA, such as low-grade peripheral inflammation and synovitis, contribute substantially to the pathophysiology of the disease. Technological advances in the past 5 years have revealed a large diversity of innate and adaptive immune cells in the joints, particularly in the synovium and infrapatellar fat pad. Notably, the presence of synovial lymphoid structures, circulating autoantibodies and alterations in memory T cell and B cell populations have been documented in OA. These data indicate a potential contribution of self-reactivity to the disease pathogenesis, blurring the often narrow and inaccurate line between chronic inflammatory and autoimmune diseases. The diverse immune changes associated with OA pathogenesis can vary across disease phenotypes, and a better characterization of their underlying molecular endotypes will be key to stratifying patients, designing novel therapeutic approaches and ultimately ameliorating treatment allocation. Furthermore, examining both articular and systemic alterations, including changes in the gut-joint axis and microbial dysbiosis, could open up novel avenues for OA management.

Psoriatic arthritis (PsA) is anatomically much more heterogeneous than rheumatoid arthritis, as, beyond synovitis, it often also involves enthesitis, peritendinitis, tenosynovitis, osteitis and periostitis. This heterogeneity currently precludes a gold standard for objectively defining resolution of inflammation following treatment, with enthesitis posing a particular challenge. Despite these difficulties, we apply lessons learned from rheumatoid arthritis to describe how patients with PsA and an inadequate response to therapy can be designated within two patient subgroups, characterized by persistent inflammatory PsA (PIPsA) and non-inflammatory PsA (NIPsA), respectively. The NIPsA phenotype is defined by the lack of ongoing joint inflammation, as confirmed through clinical assessment and imaging, along with normalized inflammatory marker levels. NIPsA might be associated with obesity, biomechanical-related pain, osteoarthritis, fibromyalgia, secondary post-inflammatory damage and central pain mechanisms. In this article, we frame PsA composite outcomes measures in relationship to the PIPsA and NIPsA phenotypes and propose that this approach might help to minimize unnecessary or ineffective cycling of PsA therapy in patients who acquire dominant non-inflammatory mechanisms and might also inform future trial design.

Imaging plays an important role in the clinical management of patients with large-vessel vasculitis (LVV), both to confirm the diagnosis at the time of initial presentation and to identify disease relapses in individuals with established disease. The big advantage of PET imaging over other non-invasive imaging modalities is the ability to employ targeted radionuclide probes to localize and track cellular pathways, providing in vivo assessments of disease activity. While 18F-fluorodeoxyglucose (FDG) has good diagnostic accuracy for LVV, this tracer is taken up by all glucose metabolizing cells in the vessel wall and so non-specific arterial uptake that is often unrelated to inflammatory disease activity can occur in patients despite a good clinical response to treatment. Advances in PET imaging technology and methods such as delayed imaging protocols and quantitative parametric imaging have the potential to improve the diagnostic accuracy of 18F-FDG in LVV. However, there is nevertheless a real clinical need for new PET tracers that target specific immune cells and inflammatory processes to inform about underlying disease pathology and guide individualized treatments for LVV. Many emerging PET tracers developed initially for oncology or atherosclerosis imaging could provide useful measures of disease activity in LVV, including tracers targeted to receptors on monocytes/macrophages, T and B lymphocytes and other inflammatory cells implicated in the pathogenesis of the disease. This focused review will discuss several of the most promising emerging PET radionuclide tracers for imaging vascular inflammation.

Eosinophil basic biology, including immunoregulatory functions, plays a complex role in a myriad of disorders where eosinophils play a role. Established in vivo and in vitro models and novel emerging techniques for studying eosinophils are integral to parsing the involvement of eosinophils in the pathogenesis of disorders including vasculitis. Knowledge of translational approaches from eosinophil-associated diseases and their application to eosinophilic vasculitis are highlighted. It is becoming increasingly evident that the roles of eosinophils in disease are complex. The use of targeted biological therapies and machine learning has the potential to reveal the contribution of eosinophils in disease pathology.

Both temporal artery biopsy (TAB) and imaging are widely used to support the diagnosis of giant cell arteritis (GCA). The objective of this study was to compare the use of TAB and imaging.

Hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA) both present with hypereosinophilia and organ damage induced by eosinophils. EGPA is also characterized by vasculitis and is associated with ANCA. Yet, discriminating HES from EGPA may be difficult in clinical practice as biomarkers to reliably differentiate between HES and EGPA are still lacking. In recent years, it has been demonstrated that targeting IL-5 is efficacious to treat HES and EGPA, and the use of anti-IL-5(R)-antibodies has become a mainstay of therapy in HES and these diseases. Nonetheless, it remains unclear whether anti-IL-5 strategies are sufficient to treat organ-threatening eosinophilic manifestations or vasculitic manifestations in EGPA.