Idiopathic inflammatory myopathies are a group of rare autoimmune diseases characterized by chronic muscle inflammation and variable systemic involvement. Although conventional therapies, including corticosteroids and immunosuppressants, form the cornerstone of treatment, most patients do not achieve remission, underscoring the need for more effective options. Advances in understanding disease pathogenesis have led to the development of novel targeted therapies. Strategies aimed at disrupting key immune pathways, such as interferon signaling, T cell activation, and B cell maturation, have shown promising results. Additionally, innovative approaches such as engineered cellular therapies are currently explored. These treatments offer the potential to achieve deeper and more durable disease control, reduce corticosteroid dependence, and improve quality of life for the patients. In this chapter, we present the recent findings on novel therapies for the treatment of IIM (all subtypes except IBM) by discussing the rationale behind their use, their potential role in improving patient outcomes in the different IIM subtypes, as well as the limitations of their wide implementation. Future strategies and promising therapies under investigation are also highlighted.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that can affect many organ systems. This chapter provides a comprehensive overview of current knowledge regarding IgG4-RD, addressing key questions about disease mechanisms, diagnostic approaches, and therapeutic strategies. We examine the diverse clinical manifestations ranging from glandular enlargement to life-threatening vascular involvement, emphasizing the importance of recognizing both inflammatory and fibrotic disease phenotypes. Diagnostic approaches integrate clinical symptoms, imaging findings, histopathological features, and serological markers while excluding mimicking conditions. Treatment strategies have evolved significantly with the introduction of B cell depletion therapy, particularly inebilizumab. Current treatment paradigms must prioritize glucocorticoid-sparing approaches, though maintenance therapy considerations remain complex. Critical knowledge gaps persist regarding optimal biomarkers for disease activity, standardized remission criteria, and the precise etiopathogenesis of IgG4-RD. Despite therapeutic advances, challenges remain in balancing effective disease control with minimizing the harms of long-term immunosuppression, emphasizing the need for continued research into targeted therapies.

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting synovial joints and extra-articular organs. While conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) like methotrexate remain the cornerstone of therapy, nearly half of patients demonstrate inadequate response to monotherapy. This review provides a comprehensive overview of the evolving therapeutic landscape in RA, covering standard therapies, novel treatments, and precision medicine approaches. The treatment landscape has dramatically expanded with biologic DMARDs targeting TNF-α, IL-6, B and T cells, and more recently, targeted synthetic DMARDs such as the Janus kinase inhibitors (JAKi). Emerging therapies are discussed, including innovative cell-based approaches, that will likely continue to revolutionize the treatment o. Furthermore, treatment failure, in the context of difficult-to-treat disease and factors associated with this, are addressed. We explore biomarker-driven treatment selection utilizing autoantibodies, imaging, and synovial tissue analysis and address key challenges around drug safety concerns, managing comorbidities and difficult-to-treat RA. Finally, this article concludes with reflections on future directions and the role of machine learning, multi-omics technologies, while maintaining the focus on patient-centered approaches to care.

Osteoarthritis is major and growing public health problem. Major advances have occurred in terms of understanding the pathogenesis of the disease primarily due to advances in imaging. Both systemic and local factors are involved. Some of these are modifiable making them attractive targets for therapy and the development of precision medicine in osteoarthritis. A growing number of these trials selecting subgroups of osteoarthritis with specific imaging features have been completed with mixed results. In many cases, the interventional studies have not replicated the results of the basic science and human observational studies and the majority of trials have been negative with a few notable exceptions. There is an urgent need for greater choice of therapies in this condition.

Systemic lupus erythematosus (SLE) is an autoimmune disease that damages multiple organs. Glucocorticoids (GCs) have been a mainstay of the treatment of SLE, but it is strongly recommended to minimize GCs usage due to the toxicity of long-term use. Currently, development of molecular-targeted therapies based on pathological mechanisms is underway. Activation of B cells through T-B cell interaction play a central role in the pathogenesis, and treatments targeting B cells and co-stimulatory molecules are expected. In addition, many disease susceptibility genes are mediated in signaling by the innate immune mechanisms, such as dendritic cells involvement and cytokines production that stimulates acquired immunity, as well as kinases of intracellular signaling molecules that are described as targets. Furthermore, adoptive transfer of T cells engineered to target CD19 antigen by gene transfer of chimeric antigen receptor and by T cell engagers that recruit T cells and induce B cell cytotoxicity gather attention.

This update explores emerging therapeutic strategies aimed at novel targets implicated in the pathogenesis of axSpA. Recent clinical trials of bimekizumab, a monoclonal antibody targeting both IL-17A and IL-17F, and janus-kinase inhibitors have demonstrated significant and sustained improvements in clinical and imaging outcomes, with a favorable safety profile and reduced rates of uveitis. Investigational agents targeting GM-CSF and MK2 have not demonstrated efficacy, but the targeting of autoreactive T cell clonotypes shared among individuals with axSpA using depleting antibodies to the variable gene segment 9 of the T cell receptor beta chain appears promising. Preclinical investigation has focused on cytokines, such as macrophage inflammatory protein, and kinases, such as mammalian target of rapamycin and phosphoinositide 3-kinase, and transcriptional factors, such as retinoic acid receptor-related orphan receptor-yt that regulate expression of IL-17A and -F cytokines. Several advances in therapeutic technologies also hold promise for more effective therapeutics based on current targets.

Psoriatic disease is a heterogeneous and multifaceted disease affecting musculoskeletal, dermatologic, and systemic domains, with low sustained remission rates despite advances in therapy. Current treatments, primarily targeting TNF, IL-17, IL-23, PDE4 inhibitors and JAK-STAT pathways, remain insufficient for many patients, highlighting the need for novel therapeutic approaches. This review explores pipeline treatments in psoriatic disease, including new JAK-STAT inhibitors (TYK2, JAK1), next-generation IL-17 inhibitors, IL-23-targeted therapies, and novel immune-modulating agents. The emerging role of combination therapy is also discussed, with dual biologic and small-molecule approaches showing potential in refractory disease. Additionally, microbiome-targeted therapies and metabolic interventions, including probiotics and GLP-1 receptor agonists, are being investigated as adjunctive strategies to improve disease control. While these innovations offer exciting opportunities for personalized medicine, challenges remain regarding long-term safety, optimal treatment sequencing, and combination strategies. Further randomized controlled trials and real-world data are necessary to define the most effective and sustainable treatment approaches for psoriatic disease.

Rheumatological patients are at high risk of osteoporosis and fracture due to disease, treatments, comorbidity and physical and functional considerations. Treating osteoporosis optimally is paramount. Osteoporosis management is evolving rapidly beyond traditional therapies. This 2025 review examines available traditional therapies and novel pharmacological approaches developed. Key questions addressed include the mechanisms, efficacy, and safety of agents like the sclerostin inhibitor romosozumab, Parathyroid hormone targeted agents, cytokine inhibitors and the status of therapies targeting cathepsin K. We evaluate the growing importance of combined and sequential treatment strategies, particularly initiating potent anabolic or dual-action therapies followed by antiresorptives for high-risk patients. Furthermore, the review explores emerging therapeutic targets such as modulators of the Wnt pathway, inflammation, and bone cell metabolism, alongside advancements in drug delivery, gene therapy, and non-pharmacological interventions. Clinical implications for patient selection, monitoring, and navigating the expanding treatment landscape are discussed, highlighting future directions towards personalized osteoporosis care.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease that is rare and targets fibrosis and vasculopathy with autoantibodies present. There are guidelines in SSc that are evidence based and can facilitate appropriate treatment for many patients with SSc. However, there is no cure and in many patients the quality and quantity of life are significantly affected. Thus, novel therapies in SSc are warranted in order to try to prevent damage and increase quality of life and improve survival. This update will expand where the standard of care treatment in SSc may be enhanced by novel therapies and recent or ongoing trials. As few studies of Raynaud's phenomenon, digital ulcers, gastrointestinal, cardiac, renal and musculoskeletal systems in SSc are ongoing, they will not be included. This paper will concentrate on immune modification for skin involvement and interstitial lung disease and pulmonary hypertension. Potentially transformative treatments will be highlighted and where they may fit into a future improved standard of care for SSc patients.

Imaging of salivary glands (SG), particularly Salivary Glands Ultrasonography (SGUS) is increasingly used in patients with suspected Sjogren's disease (SD). SGUS is the first-line imaging modality. Numerous studies have highlighted this non-invasive, non-irradiating, and low-cost imaging modality. The OMERACT group has established a classification of SG structural damage based on B-mode findings, ranging from grade 0 (normal) to 3 (severe structural damage). SGUS abnormalities (≥ grade 2) have been reported in approximately 63 % of patients with SD. More recently, Hocevar et al. described a Doppler-based classification assessing SG parenchymal vascularization, graded from 0 (normal) to 3 (Doppler signals occupying the entire glandular surface) and could be used as a marker of disease activity and as a biomarker of response to therapy. Moreover, SGUS can be useful for looking for complications such as lymphoma. New ultrasound techniques are currently being developed, including elastography for assessing tissue stiffness, analysis of microvascularization using contrast-enhanced ultrasound with microbubbles, and analysis of minor salivary glands using the ultra-high frequency probe. The combination of several US modalities enhances both sensitivity and specificity of the technique, allowing for the development of a comprehensive multimodal imaging approach. Other imaging techniques can be performed for SD, such as MRI of the parotid glands, allowing analysis of the glandular parenchyma ("salt and pepper" appearance), and certain sequences (DWI-MR) should be performed when lymphoma or other tumors are suspected. 18-FDG PET-CT may be useful to detect systemic manifestations or complications in SD and new PET tracers are currently being developed.

Musculoskeletal ultrasound is a key tool in rheumatology for diagnosing and managing inflammatory arthritis. Traditional ultrasound systems, while effective, can be cumbersome and costly, limiting their use in many clinical settings. Handheld ultrasound (HHUS) devices, which are portable, affordable, and user-friendly, have emerged as a promising alternative. This review explores the role of HHUS in rheumatology, specifically evaluating its impact on diagnostic accuracy, ease of use, and utility in screening for inflammatory arthritis. The review also addresses key challenges, such as image quality, storage and data security, and the potential for integrating artificial intelligence to improve device performance. We compare HHUS devices to cart-based ultrasound machines, discuss their advantages and limitations, and examine the potential for widespread adoption. Our findings suggest that HHUS devices can effectively support musculoskeletal assessments and offer significant benefits in resource-limited settings. However, proper training, standardized protocols, and continued technological advancements are essential for optimizing their use in clinical practice.

Musculoskeletal ultrasound (MSUS) and magnetic resonance imaging (MRI) are advanced imaging techniques that are increasingly important in the diagnosis and management of rheumatoid arthritis (RA) and have significantly enhanced the rheumatologist's ability to assess RA disease activity and progression. This review serves as a five-year update to our previous publication on the contemporary role of imaging in RA, emphasizing the continued importance of MSUS and MRI in clinical practice and their expanding utility. The review examines the role of MSUS in diagnosing RA, differentiating RA from mimickers, scoring systems and quality control measures, novel longitudinal approaches to disease monitoring, and patient populations that may benefit most from MSUS. It also examines the role of MRI in diagnosing pre-clinical and early RA, disease activity monitoring, research and clinical trials, and development of alternative scoring approaches utilizing artificial intelligence. Finally, the role of MRI in RA diagnosis and management is summarized, and selected practice points offer key tips for integrating MSUS and MRI into clinical practice.

Cardiovascular diseases (CVD) and metabolic syndrome are common in patients with immune-mediated inflammatory diseases (IMID). These conditions exhibit significant interactions, between diseases and in relation to treatments, highlighting the need for rheumatologists to take an active role in their management. It is now known that inflammation mediated by adipokines is important in the pathogenesis of obesity and cardiovascular-kidney-metabolic (CKM) syndrome. Novel therapeutics developed for metabolic comorbidities have demonstrated pleiotropic benefit across a range of diseases. Some of them even possess anti-inflammatory and immuno-modulatory effects, serving as adjuncts to the management of IMID. On the other hand, anti-inflammatory drugs have been rigorously tested for their efficacy in CVD and colchicine has become the first anti-inflammatory drug approved for this purpose. This paper will focus on the novel therapeutics and new purposes of conventional drugs in the management of CVD and metabolic syndrome, with additional discussion of their relevance in IMID.

Sjögren's disease (SjD) is a chronic systemic autoimmune disorder that primarily involves lymphocytic infiltration of exocrine glands, with frequent extra-glandular manifestations. Historically, treatment options for SjD have been limited to alleviating symptoms, rather than treating the underlying cause or preventing disease progression. Furthermore, past clinical trials of therapies such as rituximab failed to demonstrate improvement in symptoms or disease activity. Recently, novel therapeutic strategies targeting underlying disease pathogenesis - including transcription factors, circulating RNA, and B and T cell activity - herald a paradigm shift. Given the complexities of diagnosis, clinical assessment and treatment in SjD, improved clinical trial design with enhanced patient stratification, greater inclusivity and better outcome measures are paramount in evaluating new therapeutics. This systematic review aims to provide a comprehensive overview of recent SjD therapeutic advances, assess trial inclusivity with respect to sex/gender and ethnicity, critically examine negative pivotal trials and highlight promising directions for future research.

Several viruses cause acute and chronic arthritis. Millions of people suffered from Chikungunya(CHIK) during the recent epidemics/outbreaks in Asia, Africa and the Americas. Almost 20-40 % failed to recover completely and suffered from chronic pain and arthritis sequel. A wide spectrum of clinical phenotypic arthritis was described. Non-specific arthralgias(NSA) and soft tissue pains were predominant although inflammatory arthritis (mostly undifferentiated)(IA-U) was substantial. Specifically, rheumatoid arthritis(RA) and spondyloarthritis(SpA) like disorders were described. The frequency of biomarkers such as rheumatoid factor(RF) was low. Arthritis was mostly non-erosive in population studies. Abnormal immune mechanisms and persistent specific CHIK virus (CHIKV) IgM and IgG antibodies were shown. The etiopathogenetic evidence was divided between intense joint tissue inflammation due to prolonged virus persistence and abnormal autoimmune mechanisms. There was no specific therapy. The symptomatic management was often combined with an empirical use of disease modifying anti rheumatoid drugs and steroids. Substantial research is required to address knowledge gaps and unravel evidence-based medicine.

Rheumatic manifestations of HIV infection encompass a wide spectrum of disorders, arising from direct viral effects, immune dysregulation, opportunistic infections, or antiretroviral therapy (ART)-induced complications. These manifestations can occur at any stage of HIV, and include arthralgia, HIV-associated arthritis, spondyloarthropathies (SpA), inflammatory myopathies, vasculitides, and opportunistic musculoskeletal infections. Arthralgia is common and self-limiting, whereas HIV-associated arthritis mimics rheumatoid arthritis. SpA, particularly reactive arthritis, psoriatic arthritis, and undifferentiated forms, often present atypically in HIV, with pathogenesis linked to immune dysfunction rather than HLA-B27. Inflammatory myopathies, including polymyositis and inclusion body myositis, exhibit distinct clinical features, often necessitating cautious immunomodulatory treatment. Opportunistic infections, such as septic arthritis and pyomyositis, are more frequent with advanced immunosuppression. The advent of HAART has modified the prevalence and presentation of these disorders, with immune reconstitution inflammatory syndrome (IRIS) emerging as a new challenge. Management strategies require balancing disease control with minimizing immunosuppressive risks.