Spondyloarthritis (SpA) encompasses a heterogeneous group of chronic inflammatory diseases that can affect both axial and peripheral joints, tendons and entheses. Among the extra-articular manifestations, inflammatory bowel disease (IBD) is associated with considerable morbidity and effects on quality of life. In everyday clinical practice, treatment of these conditions requires a close collaboration between gastroenterologists and rheumatologists to enable early detection of joint and intestinal manifestations during follow-up and to choose the most effective therapeutic regimen, implementing precision medicine for each patient's subtype of SpA and IBD. The biggest issue in this field is the dearth of drugs that are approved for both diseases, as only TNF inhibitors are currently approved for the treatment of full-spectrum SpA-IBD. Janus tyrosine kinase inhibitors are among the most promising drugs for the treatment of peripheral and axial SpA, as well as for intestinal manifestations. Other therapies such as inhibitors of IL-23 and IL-17, phosphodiesterase 4 inhibitor, α4β7 integrin blockers and faecal microbiota transplantation seem to only be able to control some disease domains, or require further studies. Given the growing interest in the development of novel drugs to treat both conditions, it is important to understand the current state of the art and the unmet needs in the management of SpA-IBD.

Late-onset SLE is usually milder and associated with lower frequency of LN and neuropsychiatric manifestations. The diagnosis of NPSLE is especially challenging in older patients because of increased incidence of neurological comorbidities. We performed a systematic review and meta-analysis to evaluate the differences in NPSLE manifestations in early-onset (<50-year-old) vs late-onset (≥50-year-old) SLE patients.

The complement system was described over 100 years ago, and it is well established that activation of this pathway accompanies the great majority of autoimmune and inflammatory diseases. In addition, over three decades of work in murine models of human disease have nearly universally demonstrated that complement activation is upstream of tissue injury and the engagement of pro-inflammatory mechanisms such as the elaboration of cytokines and chemokines, as well as myeloid cell recruitment and activation. With that background, and taking advantage of advances in the development of biologic and small-molecule therapeutics, the creation and clinical evaluation of complement therapeutics is now rapidly expanding. This article reviews the current state of the complement therapeutics field, with a focus on their use in diseases cared for or consulted upon by rheumatologists. Included is an overview of the activation mechanisms and components of the system, in addition to the mechanisms by which the complement system interacts with other immune system constituents. The various therapeutic approaches to modulating the system in rheumatic and autoimmune diseases are reviewed. To understand how best to clinically assess the complement system, methods of its evaluation are described. Finally, next-generation therapeutic and diagnostic advances that can be envisioned for the future are discussed.

To evaluate the evidence concerning systemic pharmacological treatments for SSc digital ulcers (DUs) to inform the development of evidence-based treatment guidelines.

Post-transcriptional regulation is a fundamental process in gene expression that has a role in diverse cellular processes, including immune responses. A core concept underlying post-transcriptional regulation is that protein abundance is not solely determined by transcript abundance. Indeed, transcription and translation are not directly coupled, and intervening steps occur between these processes, including the regulation of mRNA stability, localization and alternative splicing, which can impact protein abundance. These steps are controlled by various post-transcription factors such as RNA-binding proteins and non-coding RNAs, including microRNAs, and aberrant post-transcriptional regulation has been implicated in various pathological conditions. Indeed, studies on the pathogenesis of autoimmune and inflammatory diseases have identified various post-transcription factors as important regulators of immune cell-mediated and target effector cell-mediated pathological conditions. This Review summarizes current knowledge regarding the roles of post-transcriptional checkpoints in autoimmunity, as evidenced by studies in both haematopoietic and non-haematopoietic cells, and discusses the relevance of these findings for developing new anti-inflammatory therapies.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely related conditions characterized by systemic inflammation, a predominant IL-6 signature, an excellent response to glucocorticoids, a tendency to a chronic and relapsing course, and older age of the affected population. This Review highlights the emerging view that these diseases should be approached as linked conditions, unified under the term GCA-PMR spectrum disease (GPSD). In addition, GCA and PMR should be seen as non-monolithic conditions, with different risks of developing acute ischaemic complications and chronic vascular and tissue damage, different responses to available therapies and disparate relapse rates. A comprehensive stratification strategy for GPSD, guided by clinical findings, imaging and laboratory data, facilitates appropriate therapy and cost-effective use of health-economic resources. Patients presenting with predominant cranial symptoms and vascular involvement, who usually have a borderline elevation of inflammatory markers, are at an increased risk of sight loss in early disease but have fewer relapses in the long term, whereas the opposite is observed in patients with predominant large-vessel vasculitis. How the involvement of peripheral joint structures affects disease outcomes remains uncertain and understudied. In the future, all cases of new-onset GPSD should undergo early disease stratification, with their management adapted accordingly.

Natural language processing (NLP), a subclass of artificial intelligence, large language models (LLMs), and its latest applications, such as Generative Pre-trained Transformers (GPT), ChatGPT, or LLAMA, have recently become one of the most discussed topics. Up to now, artificial intelligence and NLP ultimately impacted several areas, such as finance, economics and diagnostic/scoring systems in healthcare. Another area that artificial intelligence has affected and will continue to affect increasingly is academic life. This narrative review will define NLP, LLMs and their applications, discuss the opportunities and challenges that components of academic society will experience in rheumatology, and discuss the impact of NLP and LLMs in rheumatology healthcare.

Osteoarthritis (OA) is a disabling condition that affects billions of people worldwide and places a considerable burden on patients and on society owing to its prevalence and economic cost. As cartilage injuries are generally associated with the progressive onset of OA, robustly effective approaches for cartilage regeneration are necessary. Despite extensive research, technical development and clinical experimentation, no current surgery-based, material-based, cell-based or drug-based treatment can reliably restore the structure and function of hyaline cartilage. This paucity of effective treatment is partly caused by a lack of fundamental understanding of why articular cartilage fails to spontaneously regenerate. Thus, research studies that investigate the mechanisms behind the cartilage regeneration processes and the failure of these processes are critical to instruct decisions about patient treatment or to support the development of next-generation therapies for cartilage repair and OA prevention. This Review provides a synoptic and structured analysis of the current hypotheses about failure in cartilage regeneration, and the accompanying therapeutic strategies to overcome these hurdles, including some current or potential approaches to OA therapy.

JIA is the most common type of arthritis in children and adolescents, causing joint damage, chronic pain and disability. Deconditioning is also prevalent in patients with JIA due to both inactivity and the disease progression, resulting in reduced cardiorespiratory fitness (CRF). We aimed to evaluate CRF of patients with JIA compared with healthy controls.

To evaluate the effectiveness and safety of current treatment strategies for the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome.

The association between chronic inflammation and increased risk of cardiovascular disease in rheumatoid arthritis (RA) is well established. In the general population, inflammation is an established independent risk factor for cardiovascular disease, and much interest is placed on controlling inflammation to reduce cardiovascular events. As inflammation encompasses numerous pathways, the development of targeted therapies in RA provides an opportunity to understand the downstream effect of inhibiting specific pathways on cardiovascular risk. Data from these studies can inform cardiovascular risk management in patients with RA, and in the general population. This Review focuses on pro-inflammatory pathways targeted by existing therapies in RA and with mechanistic data from the general population on cardiovascular risk. Specifically, the discussions include the IL-1, IL-6 and TNF pathways, as well as the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signalling pathway, and the role of these pathways in RA pathogenesis in the joint alongside the development of atherosclerotic cardiovascular disease. Overall, some robust data support inhibition of IL-1 and IL-6 in decreasing the risk of cardiovascular disease, with growing data supporting IL-6 inhibition in both patients with RA and the general population to reduce the risk of cardiovascular disease.

Bone marrow lesions (BMLs), which are early signs of osteoarthritis (OA) that are associated with the presence, onset and severity of pain, represent an emerging imaging biomarker and clinical target. Little is known, however, regarding their early spatial and temporal development, structural relationships or aetiopathogenesis, because of the sparsity of human early OA imaging and paucity of relevant tissue samples. The use of animal models is a logical approach to fill the gaps in our knowledge, and it can be informed by appraising models in which BMLs and closely related subchondral cysts have already been reported, including in spontaneous OA and pain models. The utility of these models in OA research, their relevance to clinical BMLs and practical considerations for their optimal deployment can also inform medical and veterinary clinicians and researchers alike.

VEXAS syndrome is an adult-onset autoinflammatory disease associated with hematologic symptoms. The disease affects primarily males, and leads to death of a significant proportion of the patients. VEXAS syndrome is caused by a somatic mutation of the UBA1 gene in hematopoietic progenitor cells. The clinical picture of the syndrome consists of a number of organ manifestations including those akin to rheumatic diseases, arthritis, myalgia, vasculitis and chondritis.

Fibromyalgia (FM) is considered a multifactorial disorder/syndrome with not fully understood etiology. Chronic generalized pain is the main symptom. A broad spectrum of factors is proposed to explain the etiology. Its multifactorial nature is inherently associated with challenges in diagnosis and therapy. Various evidence of etiology has been evaluated with the aim of establishing a novel therapeutic approach. The main issue in the diagnosis and management is to focus on the evaluation of strict diagnostic criteria to minimize under- and overdiagnosis. Fibromyalgia is a challenge for perioperative management because of the increased risk of possible complications and poorer outcomes, including postoperative pain chronification. The authors have proposed an up-to-date evaluation of perioperative management considering the current guidelines. Multimodal analgesia combined with tailored perioperative care is the most appropriate assessment. Interdisciplinary research with special interest in pain management, including perioperative medicine, seems to be the main theme for the future.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease. The sex hormones estrogen and testosterone may have an influence on the production of antibodies. In addition, the gut microbiota also shows an effect on the onset and progression of SLE. Hence, the molecular interplay between sex hormones in terms of gender difference, gut microbiota and SLE is being clarified day after day. The aim of this review is to investigate the dynamic relationship of the gut microbiota with sex hormones in systemic lupus erythematosus taking into account the bacterial strains shown to be affected, effects of antibiotics and other factors that affect the gut microbiome, which itself strongly affects the pathogenesis of SLE.

Preliminary data led licencing authorities to alert clinicians of an increased venous thrombotic risk associated to the use of Janus kinase (JAK) inhibitors (JAKi). We performed a systematic review to estimate the risk of venous and arterial thrombosis associated to JAKi for the treatment of immune-mediated inflammatory diseases (IMIDs).

The childhood-onset or juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogenous group of rare and serious autoimmune diseases of children and young people that predominantly affect the muscles and skin but can also involve other organs, including the lungs, gut, joints, heart and central nervous system. Different myositis-specific autoantibodies have been identified that are associated with different muscle biopsy features, as well as with different clinical characteristics, prognoses and treatment responses. Thus, myositis-specific autoantibodies can be used to subset JIIMs into sub-phenotypes; some of these sub-phenotypes parallel disease seen in adults, whereas others are distinct from adult-onset idiopathic inflammatory myopathies. Although treatments and management have much improved over the past decade, evidence is still lacking for many of the current treatments and few validated prognostic biomarkers are available with which to predict response to treatment, comorbidities (such as calcinosis) or outcome. Emerging data on the pathogenesis of the JIIMs are leading to proposals for new trials and tools for monitoring disease.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, characterized by asthma, eosinophilia and granulomatous or vasculitic involvement of several organs. The diagnosis and management of EGPA are often challenging and require an integrated, multidisciplinary approach. Current practice relies on recommendations and guidelines addressing the management of ANCA-associated vasculitis and not specifically developed for EGPA. Here, we present evidence-based, cross-discipline guidelines for the diagnosis and management of EGPA that reflect the substantial advances that have been made in the past few years in understanding the pathogenesis, clinical subphenotypes and differential diagnosis of the disease, as well as the availability of new treatment options. Developed by a panel of European experts on the basis of literature reviews and, where appropriate, expert opinion, the 16 statements and five overarching principles cover the diagnosis and staging, treatment, outcome and follow-up of EGPA. These recommendations are primarily intended to be used by healthcare professionals, pharmaceutical industries and drug regulatory authorities, to guide clinical practice and decision-making in EGPA. These guidelines are not intended to limit access to medications by healthcare agencies, nor to impose a fixed order on medication use.

Proteolysis of structural molecules of the extracellular matrix (ECM) is an irreversible post-translational modification in all arthropathies. Common joint disorders, including osteoarthritis and rheumatoid arthritis, have been associated with increased levels of matrix remodelling enzymes, including matrix metalloproteinases (MMPs). MMPs, in concert with other host proteinases and glycanases, destroy proteoglycans, collagens and other ECM molecules. MMPs may also control joint remodelling indirectly by signalling through cell-surface receptors or by proteolysis of cytokines and receptor molecules. After synthesis as pro-forms, MMPs can be activated by various types of post-translational modifications, including proteolysis. Once activated, MMPs are controlled by general and specific tissue inhibitors of metalloproteinases (TIMPs). In rheumatoid arthritis, proteolysis of the ECM results in so-called remnant epitopes that enhance and perpetuate autoimmune processes in susceptible hosts. In osteoarthritis, the considerable production of MMP-13 by chondrocytes, often concurrent with mechanical overload, is a key event. Hence, information about the regulation, timing, localization and activities of MMPs in specific disease phases and arthritic entities will help to develop better diagnostics. Insights into beneficial and detrimental effects of MMPs on joint tissue inflammation are also necessary to plan and execute (pre)clinical studies for better therapy and precision medicine with MMP inhibitors. With the advances in proteomics and single-cell transcriptomics, two critical points need attention: neglected neutrophil MMP biology, and the analysis of net proteolytic activities as the result of balances between MMPs and their inhibitors.

Dysphagia is a common debilitating clinical feature of IBM. However, the impact of dysphagia in IBM has been historically overlooked. This study aimed to identify, evaluate and summarize the evidence regarding the assessment and management of dysphagia in persons with IBM undergoing treatment.