Psoriatic arthritis (PsA) is a chronic immune mediated musculoskeletal condition that is associated with psoriasis. PsA is recognized not as an isolated articular disorder, but as a systemic inflammatory condition with interrelated involvement of the skin, joints, entheses, spine, and gut. The systemic nature of PsA extends beyond musculoskeletal and cutaneous involvement to include a broad spectrum of comorbid and related inflammatory conditions that contribute to disease burden, treatment complexity, and long-term outcomes. PsA is associated with significant comorbidities. This includes cardiovascular disease, obesity, diabetes, fatigue and sleep disorders, mental health disorders and end-organ complications involving the kidney, liver, and bone, as well as related immune-mediated conditions such as inflammatory bowel disease and uveitis. This chapter examines the comorbidity landscape in PsA and underscores its importance in guiding more integrated and effective care. There is particular emphasis on multi-disciplinary evaluation to guide management. We will also explore the updated guidelines for screening, diagnostics, and treatment recommendations in addition to updates in the digital age.
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood, and up to half of patients continue to experience active disease or complications into adulthood. Despite this, adult rheumatology care remains largely oriented toward adult-onset disease, creating a mismatch in expertise for patients with childhood-onset arthritis. As a result, adult providers must address clinical challenges unique to childhood-onset disease, including persistent inflammation, temporomandibular joint (TMJ) involvement, long-term medication exposure, chronic pain, psychosocial morbidity, and extra-articular manifestations such as uveitis. Transition gaps are common and contribute to medication discontinuation, loss to follow-up, and disease flare. This review summarizes the long-term outcomes of JIA relevant to adult rheumatologists and outlines best practices in screening and management across key domains, including uveitis, TMJ arthritis, mental health, and educational and vocational participation. The review also highlights evidence-based practical strategies for building transition-informed adult rheumatology practices.
Fatigue is a common, debilitating, and challenging symptom in rheumatic diseases. Despite its clinical significance, the concept of fatigue remains difficult to define, and no universally accepted definition has yet been established. It is generally characterised by an overwhelming, persistent, and debilitating sense of exhaustion that impairs functional capacity and limits the performance of everyday activities. Reported prevalence rates of fatigue among patients with musculoskeletal disorders vary considerably, ranging from 35% to 82%. In this review, we examine the impact of fatigue on patients' quality of life, discuss available instruments for its assessment, and consider factors contributing to fatigue, including disease activity and psychological determinants. Furthermore, we summarise experimental studies that have sought to elucidate the biological mechanisms underlying fatigue. The management of fatigue, encompassing both pharmacological and non-pharmacological approaches, is also addressed. Overall, the available evidence concerning fatigue in rheumatic diseases remains limited, and further research is warranted to clarify the contribution of biological mechanisms-such as inflammation, hormonal alterations, and dysfunction of the autonomic nervous system-to the pathogenesis of fatigue.
Pneumocystis jirovecii pneumonia (PJP) is a rare and potentially fatal opportunistic infection in patients with rheumatic diseases with mortality rates exceeding those seen in HIV-infected patients. Although PJP prophylaxis is highly effective, evidence-based guidelines specific to rheumatic disease are lacking resulting in substantial variability in clinical practice. This review examines the existing PJP literature with a focus on efficacy of prophylaxis, adverse effects, and risk factors across rheumatic diseases to inform a pragmatic, risk-stratified approach to prophylaxis. Certain conditions including ANCA-associated vasculitis during induction therapy, anti-MD5+ dermatomyositis and VEXAS syndrome warrant routine prophylaxis in the setting of high-dose glucocorticoid use whereas others conditions, such as Giant Cell Arteritis, do not justify routine prophylaxis. This review provides a practical framework to assist the practicing clinician in making individualized decisions regarding PJP prophylaxis in rheumatic disease.
Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune diseases with variable extramuscular involvement of the skin, lungs, and other organ systems. Dermatomyositis (DM) is the prototype IIM with skin involvement, but the presence of DM-specific rashes in other IIMs raises questions about whether these conditions are distinct entities, overlapping diseases, or subsets within a DM spectrum. Importantly, distinct cutaneous phenotypes of IIMs may correlate with certain autoantibodies and risk of malignancy or interstitial lung disease. In this review, we outline characteristic DM rashes and describe their prevalence in other IIMs, most notably in antisynthetase syndrome and overlap myositis. We emphasize salient skin findings that may inform diagnosis and prognosis, including some atypical, subtle, or unusual presentations. Finally, we review established and emerging therapies for management of amyopathic or refractory cutaneous DM.
Hair loss is a common clinical concern with significant diagnostic and psychosocial implications, particularly in patients with rheumatologic disease. This review examines the association between rheumatologic conditions and alopecia, exploring underlying mechanisms, clinical presentations, and diagnostic considerations. Rheumatologic diseases may precipitate hair loss through a variety of immune, fibrotic, and vascular mechanisms. In addition, pharmacologic therapies commonly used to treat rheumatologic diseases, as well as coexisting autoimmune scalp disorders, can also contribute to alopecia. Recognition of shared mechanisms linking autoimmune disease and hair loss is essential for identification of systemic disease, adverse therapeutic effects, or distinct dermatologic conditions. For optimal diagnosis and management, a structured approach to hair loss should be taken by obtaining a targeted history, physical examination, and laboratory testing or biopsy. Increased awareness of the relationship between alopecia and rheumatologic disease enhances interdisciplinary collaboration, ultimately facilitating earlier diagnosis, more efficient treatment and, most importantly, better patient outcomes.
The global epidemiology, regional variation, sex- and ethnicity-based disparities, disease burden, and organ-specific involvement in systemic sclerosis were reviewed. A qualitative systematic search of PubMed/MEDLINE, EMBASE, SciELO, and the Cochrane Library was conducted following PRISMA 2020 guidelines. Forty-seven studies reporting incidence, prevalence, organ involvement, mortality, or quality of life were included. Global prevalence ranged from 0.9 to 37.9 per 100,000 and incidence from 0.05 to 4.1 per 100,000 person-years, with marked geographic heterogeneity across the globe. Women were predominantly affected (4-6:1), whereas men showed more severe disease and higher mortality. African-descent, Indigenous American, and some South Asian populations had higher frequencies of diffuse cutaneous systemic sclerosis, interstitial lung disease, and reduced survival. Pulmonary involvement accounted for most disease burden, with interstitial lung disease in 35-55% and pulmonary arterial hypertension in 6-12%. These findings highlight substantial epidemiologic heterogeneity and the need for early detection and standardized care in expert centers.
Psoriasis (PsO) and psoriatic arthritis (PsA) are immune-mediated diseases characterized by chronic systemic inflammation, including inflammation of the skin and joints. Recent advances in animal models, single-cell transcriptomics, spatial transcriptomics, and proteomics have greatly enhanced our understanding of disease pathogenesis. Mouse models exhibit key features of skin and joint inflammation, facilitating analysis of molecular pathways, and identification of therapeutic targets. Single-cell and spatial transcriptomic analyses have revealed cell-type-specific contributions to inflammation, highlighting interactions between keratinocytes, T cells, fibroblasts, and dendritic cells that drive psoriatic pathology. In psoriatic synovium, type 17 tissue-resident memory T cells, monocytes, and fibroblasts contribute to local inflammation and joint damage, whereas the roles of B cells and plasma cells are less clear. Proteomic and metabolomic profiling in patients with PsA has identified circulating protein signatures and metabolites associated with disease progression, sex-specific differences, and response to therapy. The integration of these multiomic approaches provides a detailed map of immune-stromal-epithelial crosstalk across skin, synovium, and entheses, uncovering mechanisms that were previously inaccessible. These insights have implications for predicting disease progression, identifying novel therapeutic targets, and optimizing treatment strategies. Collectively, advances in animal models and multiomic profiling are reshaping our understanding of PsO and PsA, providing a framework for future research, disease monitoring, and therapeutic development.
Idiopathic inflammatory myopathies (IIM), including immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), anti-synthetase syndrome (ASyS), overlap myositis and polymyositis, are heterogeneous autoimmune diseases characterized by immune-mediated skeletal muscle injury and frequent extra-muscular organ involvement. Despite recent therapeutic advances, many IIM patients have persistent disease activity, medication toxicity, or steroid dependence with current treatments. Increasing evidence implicates autoreactive B cells and autoantibody-producing plasma cells as central drivers of disease activity in several IIM subtypes, providing a strong rationale for B-cell- targeted therapies. While monoclonal antibody-based B-cell depletion strategies such as rituximab have demonstrated variable efficacy, their inability to effect persistent, intense depletion of tissue autoreactive B-cell populations often limit their success. Chimeric antigen receptor T-cell (CAR-T) and related cellular immunotherapies were originally developed against hematologic malignancies, but have recently emerged potentially transformative therapeutic options for autoimmune diseases. CAR-T cells targeting CD19 and other B-cell antigens have demonstrated the capacity to induce deep and durable B-cell depletion, and may even lead to "immune reset" with long-lived autoimmunity remission in diseases such as systemic lupus erythematosus and systemic sclerosis. Early clinical experiences now suggest that CAR-T therapy may offer similar promise in refractory IIM, particularly in phenotypes that include pathogenic autoantibodies, such as ASyS, DM, IMNM. This review provides a synopsis of current knowledge on the immunopathogenesis of IIM relevant to CAR-T and other cellular immunotherapy, outlines CAR-T technology and the mechanistic rationale for its use in IIM, and critically appraises emerging clinical CAR-T treatment data in IIM. We also discuss safety considerations, practical challenges, and future directions, with a focus on how CAR-based immunotherapies may reshape treatment paradigms for refractory inflammatory myopathies.
Rheumatology as a specialty is moving past cytokine inhibitors which have dominated the therapeutic landscape since the turn of the century, with novel cell-targeting therapies emerging to treat immune-mediated multisystem inflammatory diseases such as systemic lupus, systemic sclerosis, small vessel vasculitides, and inflammatory myositis. Like many inflammatory arthritides, axial spondyloarthritis (axSpA) therapeutics has been limited to either inhibitors of TNF and IL-17, or blocking intracellular signaling of cytokines through Janus Kinase inhibitors. This systematic review chronicles the clinical progress made in the field of selective T cell depleting agents, the potential for novel cellular targeting therapies using Chimeric Antigen Receptor - T (CAR-T) therapy, as well the challenges posed by this approach for treatment of axSpA. A review of the MEDLINE, OVID and clinicaltrials.gov databases was performed which revealed no ongoing or completed open label or completed registered clinical trials. However recent data have highlighted potential for selective CD8+ T cell targets with proof of concept using a monoclonal antibody against TRBV9+ CD8+ T cells from a published case study and one randomized placebo-controlled trial, as well as other emerging therapeutics that are shifting focus from cytokine-based therapeutics to T cell targeting agents. In this review, we identified emerging therapeutic platforms of cellular immunotherapy, potential therapeutic targets, and discuss potential adverse effects related to cell-targeting therapies. While at present there is a dearth of clinical data on cellular targeting treatment options in axSpA, ongoing investigations into the pathogenesis of axSpA and identification of new molecular targets may help facilitate opportunities to develop CAR-T and other cell-based therapies for treatment of axSpA.
Immune checkpoint inhibitors (ICI) have transformed the field of oncology and can induce a durable cancer treatment response in select cancer patients. ICI binding to these checkpoints allows the immune system to be activated in order to target tumor death, but this activation also brings multiple off-target side effects called immune related adverse events (irAE's) including rheumatic irAE's. Review aims will explore novel insights into rheumatic irAE's etiology and etiopathology including ICI-inflammatory arthritis, ICI-Polymyalgia Rheumatica, ICI-activated osteoarthritis, sicca-like syndrome, and ICI induced myositis. This chapter will review rheumatic irAE's and define their proposed mechanisms, which include generalized immune activation owing to checkpoint neutralization, direct off-target effects of checkpoint inhibitors and epitope spreading. Research using cellular profiling methods such as single cell transcriptomics and T cell profiling have helped explore the novel mechanism of these heterogenous rheumatic irAE's. Future goals of research include gaining a better understanding of pathogenesis of rheumatic irAE's to help target precision rheumatic irAE treatment.
Cardiac sarcoidosis (CS) results from the formation of non-necrotizing granulomas infiltrating the myocardium, resulting in a wide variety of clinical presentations including fatal arrhythmias and cardiomyopathy. Correctly identifying CS from its many mimics, including several rheumatologic conditions, is crucial for treating patients and preventing significant morbidity and mortality. In this review, we discuss diagnostic strategies for CS, methods to differentiate it from clinically similar cardiac pathologies with a focus on other rheumatologic conditions involving the heart, and approaches to CS management and treatment.
Interstitial lung disease (ILD) is a major source of morbidity and the leading cause of mortality in people with systemic sclerosis (SSc). There have been advancements in the treatment of ILD. In this article, we review the American College of Rheumatology (ACR) and the American College of Chest Physicians (CHEST) guidelines for the screening, monitoring and treatment of SSc-ILD. We highlight additional pharmacologic and non-pharmacologic interventions that should be considered in those with SSc-ILD. Finally, we summarize the ACR guidelines for vaccinations in those with SSc-ILD, and recommendations for holding immunosuppressive therapies to maximize immunogenicity of the vaccines.
Systemic sclerosis (SSc) is a complex systemic autoimmune rheumatic disease with marked clinical heterogeneity. Cutaneous manifestations affecting the hands and wrists include vascular insufficiency, early edema (puffy fingers), followed by progressive skin fibrosis and atrophy (sclerodactyly). This progressive skin tightening results in joint stiffness, deformity, functional impairment and reduced quality of life. Beyond skin changes, hand involvement may also include inflammatory arthritis, joint contractures, tendon friction rubs, Raynaud phenomenon, digital ulcers, acro-osteolysis, and calcinosis, all of which can further impair hand function, significantly affecting individuals’ ability to perform routine occupational and daily tasks requiring grasping, gripping, and fine motor dexterity. In this article, we synthesize the evidence evaluating manual therapy, prescribed hand exercises, self-administered hand exercise protocols, telerehabilitation, paraffin wax, therapeutic ultrasound, manual lymphatic drainage, and dynamic splinting to improve hand function in people with SSc.
Axial spondyloarthritis (axSpA) is an immune-mediated inflammatory condition that is associated with significant disease burden. While the use of biologic and targeted synthetic disease modifying antirheumatic drugs have led to significant improvements in disease outcomes, a substantial proportion of patients continue to face challenges with pain despite effective control of their inflammatory state. Chronic pain is one of the leading causes of disability and remains an unmet research and clinical need in axSpA. Phenotyping pain is essential to understand the etiology of symptoms and to aid in selecting the appropriate management plan in axSpA. In this review, we aim to highlight the mechanisms of pain, its phenotypes, and novel assessment tools. We also review our approach to managing chronic pain in axSpA and discuss future directions in this field.
Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease that develops in a substantial proportion of patients with psoriasis (PsO). Understanding its epidemiology is essential for improving early recognition, risk stratification, and preventive strategies. This review summarizes current evidence on the global prevalence and incidence of PsA in both the general population and among individuals with PsO. Population-based studies estimate PsA prevalence at approximately 0.1-0.2%, with considerable geographic variability. Among patients with PsO, approximately 20% develop PsA, although this proportion varies according to age, disease severity, classification criteria, and region. Incidence rates in the general population range from 3 to 41 per 100,000 person-years, with evidence of increasing prevalence over time in several countries, likely reflecting improved recognition and diagnostic practices. Risk factors for PsA development include severe PsO, nail involvement, obesity, and the presence of musculoskeletal symptoms, particularly inflammatory arthralgia. Emerging data suggest that advanced systemic therapies for PsO may influence future PsA incidence, although prospective evidence is still needed. Significant heterogeneity in epidemiological estimates is driven by methodological differences, diagnostic criteria, healthcare systems, and underdiagnosis. A better understanding of epidemiological trends and transition phases from PsO to PsA may support earlier identification and optimized multidisciplinary management strategies.
Systemic sclerosis (SSc) is characterized by profound clinical heterogeneity due to dysregulated communication between vascular, immune, and stromal compartments. This review synthesizes genetic and epigenetic determinants of SSc with observations from transcriptomic, proteomic, and metabolomic studies. We highlight emerging cellular- and molecular-level insights into vasculopathy, immune dysregulation, and fibroblast activation in SSc. Finally, we discuss how these mechanistic discoveries inform the development of targeted, precision-medicine based therapeutic approaches in SSc.
Despite major therapeutic advances, a substantial proportion of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), experience persistent symptoms, functional limitations, and reduced quality of life. Historically, heterogeneous terminology has limited comparability across studies for this population. To address this gap, three international initiatives, GRAPPA, EULAR, and ASAS, have proposed consensus definitions for two nested states: a broad category of “difficult-to-manage” (D2M) or “complex-to-manage” (C2M) disease and a more stringent “treatment-refractory” (TR) subset requiring objective inflammation and multi-mechanism therapeutic failure. This review synthesises these frameworks, highlighting shared principles and key differences. While all definitions adopt a dual-tiered structure, PsA-specific definitions reflect its multidomain nature, incorporating peripheral joints, entheses, skin, nails, axial involvement, and comorbidities; conversely, axSpA definitions are axial-centric, while other domains may play a role in determining D2M/TD disease as well. These distinctions have implications for trial design, biomarker discovery, and management strategies. Harmonisation, prospective validation, and biomarker-driven stratification remain essential to optimise outcomes and advance precision medicine.
Psoriatic arthritis (PsA) is a heterogeneous, immune-mediated inflammatory disease characterised by multidomain clinical involvement, including peripheral arthritis, enthesitis, axial disease, dactylitis, and skin and nail manifestations, alongside a substantial burden of comorbidity. Over the recent decades, therapeutic options for PsA have expanded, with the introduction of multiple biologic and targeted compounds targeting tumour necrosis factor, the IL-23/IL-17 axis, and Janus kinase signalling. These advances have improved outcomes for many patients; however, incomplete responses, domain-specific refractory disease, treatment intolerance, and loss of efficacy remain common. In addition, current treatment strategies are largely reactive, reflecting limited ability to predict treatment response or align immune mechanism with clinical phenotype. This review summarises the current PsA treatment landscape and its limitations, and examines emerging therapeutic directions that aim to address disease heterogeneity and unmet need. These include combinatorial and sequential treatment strategies, next-generation biologics and oral agents, immunometabolic modulation, selective targeting of pathogenic immune cell populations and upstream inflammatory, immune tolerance-based approaches. It is with hope that these developments highlight a shift from incremental therapeutic expansion towards a integrated, targeted and ultimately, more informed treatment approach.
