Cutaneous lupus erythematosus (CLE) is an autoimmune skin condition associated with a considerable treatment burden and diminished quality of life. The absence of a consensus outcome measure to evaluate therapeutic response has posed a challenge to CLE drug development. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) was developed in response to this need, incorporating morphological components including erythema, scale, dyspigmentation and scarring, to reflect disease activity and damage. Numerous studies have demonstrated the utility of CLASI in capturing relevant aspects of disease from clinician- and patient-based perspectives; however, no regulatory precedent for use of clinical trial data employing CLASI to evaluate treatment response in CLE exists. Thus, the Lupus Accelerating Breakthroughs Consortium commissioned a working group of members from industry, academia, the US Food and Drug Administration (FDA) and CLE patient advocates to address the potential knowledge gaps with CLASI through evidence-based research. Upon reviewing and submitting these data to the FDA, the working group reached alignment that CLASI is a suitable outcome measure for CLE clinical trials, enabling a clearer regulatory path for clinical drug development. The group recognizes the need for additional information to assess what degree of change in CLASI captures clinically meaningful improvement.

Systemic sclerosis (SSc) is a prototypical systemic immune-mediated fibrosing disease that affects the skin, the lungs, the heart, the kidneys and the intestinal tract. Similar to many other fibrotic diseases, SSc is associated with high morbidity and mortality and therapeutic options are limited. Fibrosis arises from a complex interplay of vascular damage, inflammation and prolonged, misdirected repair responses. The progressive accumulation of extracellular matrix perturbs the physiological tissue architecture and commonly leads to failure of the affected organs. Understanding the mechanisms of fibrotic tissue remodelling can lead to the identification of preclinical targets. Novel fibrosis-promoting cell subpopulations, the interplay of fibroblasts with B cells and macrophages, the nerve-fibroblast axis, matrikines and matricryptins, senescence, profibrotic transcription factors, developmental pathways and epigenetic tissue memory are all important drivers of fibrotic tissue remodelling that might offer potential for novel therapies to improve outcomes for patients with SSc and possibly other fibrotic conditions.

Psoriatic arthritis develops in up to one-third of individuals with psoriasis, typically following a prolonged subclinical phase. Diagnostic delays are common, often exceeding 2 years, and can result in irreversible joint damage. The growing recognition of this latent period has fuelled interest in earlier identification and interception. However, efforts are hampered by inconsistent definitions of early or subclinical psoriatic arthritis, insufficient prognostic tools, and an absence of consensus on the outcome for interception studies. This Review synthesises a rapidly evolving field, offering a framework organised around four crucial questions: first, what defines progression from psoriasis to psoriatic arthritis? Second, who is most at risk of transition? Third, how can progression be reliably measured using imaging, molecular biomarkers, or digital health technologies? Fourth, when should preventive intervention be considered? We critically examine new conceptual models, the limitations of existing classification criteria, advances in imaging and biomarker research, and the promise of digital phenotyping. Addressing the current challenges in definitions, risk stratification, measurement, and trial design is essential for the development of biologically grounded, ethically robust interception strategies.

Raynaud's phenomenon (RP) is a vasospastic disorder classified into primary (PRP) and secondary (SRP) forms. Infrared thermography (IRT), a non-invasive imaging technique assessing skin surface temperature, has emerged as a valuable tool in evaluating microvascular dysfunction in RP. This review analyzed literature from 2010 to 2025 across PubMed, Scopus, Web of Science, and Embase using key words including "Raynaud's phenomenon," "infrared thermography," and "cold provocation test." Studies focusing on diagnostic accuracy, differentiation of PRP from SRP, and monitoring treatment response were included. Infrared thermography demonstrates strong sensitivity and specificity, especially through parameters such as distal-dorsal temperature difference and rewarming kinetics. It offers a comfortable, reproducible alternative to traditional methods such as the finger systolic pressure test. However, lack of standardized imaging protocols and equipment variability limit its widespread use. Advancements in device calibration, artificial intelligence integration, and protocol harmonization could enhance IRT's clinical utility in diagnosing and monitoring RP.

Total knee arthroplasty (TKA) is effective for treating end-stage osteoarthritis but often results in significant blood loss, necessitating optimized management strategies. A literature review of meta-analyses, systematic reviews, and clinical trials was conducted using PubMed and Google Scholar. The acronym TKA-BLED encapsulates effective blood loss management strategies. Tranexamic acid: reduces blood loss by 591 ml and decreases transfusion rates. Keep femoral canal closed: saves 381 ml by minimizing hidden loss. Apply cryotherapy: conserves 264 ml while reducing pain and swelling. Be aware of tourniquet use: limits intraoperative loss but increases total postoperative blood loss and complications. Limit drain use: retains 318 ml through the tamponade effect. Elevate the knee: decreases blood loss by up to 257 ml. Decrease operative time: saves 14 ml per minute. The TKA-BLED protocol effectively reduces blood loss and transfusion needs, improving patient outcomes. More research is needed to validate its long-term efficacy.

Axial spondyloarthropathy (axSpA) belongs to a group of chronic, progressive inflammatory diseases with a variety of clinical manifestations, including musculoskeletal and extra-articular symptoms. The most common extra-articular manifestation in patients with axSpA is uveitis, which usually involves the anterior segment, can be recurring, and is a vision-threatening complication. Ocular complications can result from the disease itself, as well as from the therapy used to treat it. Treatment for axSpA is based on both pharmacological and non-pharmacological management. Biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) are an effective and constantly evolving form of axSpA therapy; however, their application and side effects remain under study. The aim of this article is to summarize current knowledge about the efficacy of biologic and targeted synthetic DMARDs in non-infectious uveitis in axSpA and delineate their effect on the organ of vision.

In rare and complex connective tissue diseases, patient partnership is essential to address diagnostic delays, fragmented care, unmet needs, and the research agenda. European Reference Network (ERN) ReCONNET, the network dedicated to rare and complex connective tissue diseases, has implemented a structured and transferable model of patient partnership. Patients contribute to every phase of research and care development: from identifying unmet needs to co-authoring scientific publications. Patient input also shapes educational initiatives and strategic planning. By institutionalising partnership through governance structures and shared decision-making processes, ERN ReCONNET shows that involving patients as equal stakeholders enhances the relevance, quality, and effect of activities. This Personal View was co-written with the direct partnership of authors with lived experience of rare and complex connective tissue diseases and reports a model that can be adapted to other rare diseases and rheumatological settings, promoting a culture of patient-centred innovation in health-care systems.

Engaging people with lived experience in research improves research quality, relevance, and translation. Yet, people with lived experience are infrequently engaged in rheumatology research even though they can make important contributions to research planning, implementation, interpretation, and dissemination. Engagement levels might include consulting (by providing perspectives on a single topic or problem), advising (via two-way interactions with researchers to make recommendations on one or more aspects of a study), or partnering (by engaging with researchers to make decisions together). Evidence on strategies for engaging people with lived experience, including the research stages during which engagement might be most meaningful, levels of engagement, and how to align specific purposes and activities, is limited. We review principles (defined roles and responsibilities, alignment of engagement purpose and activities, collaborative relationships between researchers and people with lived experience, and recognition of the contributions of people with lived experience) and considerations for specific approaches to engagement to guide researchers on how to meaningfully and effectively engage people with lived experience in rheumatology research.

There are several pressing reasons to re-examine shingles and strategies for its prevention through vaccination. Firstly, the UK has recently recommended the introduction of a national childhood varicella vaccination programme, and this may impact the epidemiology of shingles. Secondly, treatments for immune-mediated inflammatory diseases are increasingly targeting immunological pathways essential for antiviral defence. Thirdly, we now have access to a highly efficacious shingles vaccine. This review article will explore each of these developments in a way that is globally relevant, incorporating international recommendations.

Despite growing evidence supporting the benefits of physical activity in patients with rheumatic and musculoskeletal diseases (RMDs), both clinicians and patients often remain cautious-particularly regarding higher intensities. Although exercise is universally recommended in international guidelines for these populations, it is frequently accompanied by warnings to engage only in moderate-intensity training. The primary objective of this systematic review was to examine the effectiveness and safety of high-intensity, land-based exercise in patients with inflammatory rheumatic conditions, compared with usual care, no intervention, or low-intensity exercise. We aimed to determine whether high-intensity exercise leads to an increase in disease activity, pain intensity, or impairment of function.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterized by complex pain mechanisms that extend beyond inflammation. Although inflammatory nociceptive pain - primarily mediated by pro-inflammatory cytokines - represents the classic pathway and therapeutic target, many patients continue to experience pain despite suppression of inflammation. This residual pain often reflects non-inflammatory processes, including nociplastic and neuropathic pain. Central sensitization, a key mechanism of nociplastic pain, contributes to pain amplification and poor response to treatment. Fibromyalgia, considered the typical phenotype of nociplastic pain, can co-occur with axSpA and is associated with increased symptom burden and reduced efficacy of anti-inflammatory therapies. Neuropathic pain, albeit less common, can result from structural complications and requires targeted therapeutic approaches. In addition, biological sex differences further influence pain perception and treatment outcomes: female patients report more widespread pain, show higher rates of central sensitization and have a worse response to biologic therapies than male patients. Current treatment paradigms are effective for inflammation-driven symptoms but often fail to address the broader spectrum of pain phenotypes in axSpA. Future work should include the development of biomarkers to differentiate pain mechanisms, the refinement of assessment tools and the evaluation of multimodal therapies that target both inflammation and pain processes. This evolving understanding necessitates a shift from an inflammation-centric to a mechanism-informed approach to pain management in axSpA.

This scoping review aimed to evaluate the extent and impact of duplication bias within contemporary idiopathic inflammatory myopathy (IIM) research.

Timely referral in Rheumatoid Arthritis (RA) is critical for early diagnosis and initiation of treatment, which are crucial to improve patient outcomes and limit radiographic progression. Optimized referral criteria, whether applied by clinicians or healthcare artificial intelligence systems, can facilitate faster and more accurate decisions regarding patient assessment by a Rheumatologist. Despite this need, a validated and widely adopted referral tool for RA is still lacking.

Glucocorticoid pulse therapy is commonly prescribed by rheumatologists worldwide for a wide variety of serious and potentially life-threatening diseases. Pulse therapy also has the potential to lower the cumulative glucocorticoid burden, which has already been proven in systemic lupus erythematosus and giant cell arteritis. The standard practice in rheumatology is to administer this therapy intravenously, but current literature suggests that oral methylprednisolone is a non-inferior option for clinical outcomes and safety. Integrating oral methylprednisolone pulse therapy into rheumatological practice might have considerable benefits, not only for patients but also for society as a whole. In this Viewpoint, we provide a review of oral methylprednisolone pulse therapy covering pharmacology, safety, patient preference, sustainability, and its possible use in rheumatology practice. We aim to increase awareness among rheumatologists of the potential use of oral glucocorticoid pulse therapy as this modest change in clinical practice has major benefits.

TNF is a central regulator of immune responses, inflammation and programmed cell death, and has an essential role in maintaining tissue and immune homeostasis. Abnormal TNF signalling is implicated in a broad spectrum of physiological and pathological processes, as exemplified by monogenic disorders arising from dysregulation of core components of the TNF pathway. These rare conditions encompass various autoinflammatory syndromes, immunodeficiencies, autoimmune diseases and neurodegenerative conditions, and offer unique insights into the molecular mechanisms driving pathology via TNF-mediated inflammation and cell death. Collectively, these diseases underscore the importance of tightly regulated TNF signalling for immune balance and illustrate how distinct molecular defects can produce overlapping clinical phenotypes. Variability in pathway integration and tissue-specific gene expression further shapes disease presentation, whereas disruption of post-translational modifications and cell-death regulators have emerged as central pathogenic mechanisms. Together, these insights highlight the need for precise genetic and mechanistic understanding to inform diagnosis and therapeutic strategies.

Endosomal traffic governs various core processes that maintain immune homeostasis and self-tolerance, including receptor signalling, antigen processing, cytokine secretion and cellular metabolism. Traffic-regulated receptors - both intracellular and on the cell surface - modulate immune sensing of infection, nutrient availability and endogenous stress signals arising from cellular or tissue injury. In rheumatic diseases, such as systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, systemic sclerosis, Sjögren syndrome and osteoarthritis, mounting evidence implicates disruptions in endosomal pathways as important drivers of disease onset and progression. Dysregulated endosomal trafficking contributes to type I interferon activation via signalling through Toll-like receptors, aberrant autoantigen presentation, and altered expression of metabolite transporters in immune cells and target organs. Endosome trafficking mediates autophagosome formation, the production of exosomes and the turnover of organelles, such as mitochondria that generate oxidative stress, thereby controlling chronic inflammation and connective tissue remodelling. Therefore, understanding the molecular architecture of endosomal recycling pathways and their integration with immune cell function can provide important insight into rheumatic diseases. Restoring trafficking fidelity - through modulation of RAB GTPases, endosomal Toll-like receptor signalling, metabolic reprogramming, autophagic flux and extracellular vesicle biology - represents a promising therapeutic strategy.

Autoimmune rheumatic diseases (AIRDs), such as rheumatoid arthritis and systemic lupus erythematosus, substantially affect quality of life, with viral infections increasingly recognized as potential but underappreciated triggers of worsening preexisting AIRD symptoms. Despite growing evidence that post-viral infections are associated with heightened autoimmune activity and disease flares, the precise mechanisms underlying the complex virus-autoimmune response remain poorly understood. As AIRD is most prevalent in women, hormonal factors might have a role in AIRD pathogenesis. Hormones can influence immune regulation, potentially affecting the risk and severity of viral-induced AIRD flares. Given the global rise of viral disease outbreaks with increasing evidence of viral persistence in AIRD pathology, this Review addresses a critical knowledge gap in understanding the immune crosstalk during viral-induced AIRD flares. We place an emphasis on emerging viruses and their potential role in AIRD flares, exploring mechanisms of immune dysregulation, chronic inflammation, molecular mimicry, viral persistence and emerging therapeutic strategies to mitigate virus-induced AIRD exacerbations. This Review is aimed at shedding light on the mechanisms by which emerging viruses promote AIRD flares, serving as a practical guide to improve clinical management and therapeutic innovations.

To compare the clinical efficacy and safety of biological disease-modifying antirheumatic drugs (DMARDs) and Janus kinase(JAK) inhibitors in patients with early rheumatoid arthritis (RA).

Juvenile idiopathic arthritis (JIA) is the most prevalent chronic rheumatic disease in children, primarily affecting the joints but also influencing various organ systems, including the endocrine system. The interplay between JIA and endocrine dysfunctions remains an area of growing interest, as autoimmune and inflammatory mechanisms may contribute to the development of comorbid conditions. This review explores genetic markers associated with both JIA and endocrine disorders, the role of immune system dysregulation, and the impact of disease-modifying therapies on hormonal function. Additionally, the effects of chronic inflammation on endocrine homeostasis and metabolic regulation are discussed. Particular attention is given to conditions such as type 1 diabetes, Hashimoto's thyroiditis, and Cushing's syndrome, which may either precede JIA, arise as complications, or be exacerbated by its treatment. Effective JIA management requires an understanding of these mechanisms and a multidisciplinary approach.

Biological treatments are indicated in familial Mediterranean fever (FMF) patients with colchicine resistance or intolerance. Interleukin-1 (IL-1) inhibitors may not yield sufficient efficacy and safety. Interleukin-6 inhibitors (tocilizumab - TCZ) have been suggested to be potentially beneficial. This systematic literature review aimed to evaluate the existing data on the efficacy and safety of IL-6 inhibitors in the treatment of FMF.