Fibromyalgia syndrome (FMS) is a condition characterized by widespread musculoskeletal pain, often involving a neuropathic component. While pathophysiology remains vague, increasing evidence suggests that small fiber pathology (SFP) may be present in a significant subset of patients, indicating a peripheral nervous system contribution. This systematic review aims to evaluate the utility of skin biopsy as a diagnostic tool for patients with FMS, with special focus on SFP. A comprehensive database search was conducted to identify studies assessing intraepidermal nerve fiber density (IENFD) via skin biopsy in individuals diagnosed with FMS. The included studies demonstrated a reduction in IENFD in a substantial proportion of FMS patients, with reported prevalence ranging widely from 30% to over 85%. Small fiber pathology occurs in a significant proportion of individuals with FMS. Skin biopsy emerges as a valuable diagnostic tool. Further research is needed to better understand the underlying mechanism of SFP in FMS.

Capillaroscopy is a non-invasive examination used for imaging of capillary vessels of the papillary layer of the finger nailfold. It allows the detection of microcirculation disorders in systemic connective tissue diseases. According to the "Fast Track" algorithm recommended by the European Alliance of Associations for Rheumatology, capillaroscopic findings should be categorized as a scleroderma or non-scleroderma pattern. Scleroderma microangiopathy may also occur in polymyositis and "scleroderma spectrum" diseases such as dermatomyositis, mixed connective tissue disease, or undifferentiated connective tissue disease. These capillaroscopic features are called scleroderma-like microangiopathy. Numerous studies have shown a correlation between capillaroscopic patterns and the severity of organ involvement. Available data indicate the occurrence of capillaroscopic changes in patients with other systemic connective tissue diseases, such as systemic lupus erythematosus, Sjögren's disease, rheumatoid arthritis, and antiphospholipid syndrome. The importance of capillaroscopy in diseases beyond the scleroderma spectrum requires further investigation.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis defined by asthma, hypereosinophilia, and multiorgan involvement. Differentiating EGPA from other eosinophilic disorders is crucial because management differs substantially. The aim of the study is to summarize the pathogenesis, epidemiology, genetics, clinical manifestation, and treatment of EGPA and to provide a comparative differential diagnosis of eosinophilic disorders.

Large language models have generated intense interest in clinical artificial intelligence (AI), yet their evolution from passive chatbots into agentic systems capable of autonomous planning, tool use, and multistep execution represents a distinct technological paradigm. Unlike conversational AI, which makes suggestions and awaits review, agentic systems act independently and can chain clinical decisions across electronic health records, laboratory data, and patient communications. Rheumatology, with its decades-long disease trajectories, multimodal data streams, and iterative treatment adjustments, is a field well suited to such automation, but also particularly vulnerable to its failures. Errors in autonomous chains compound silently, verification demands exceed those of any previous clinical decision support tool, and the foundational tasks most suited to automation are precisely those through which trainees develop clinical expertise. This Viewpoint critically appraises the agentic AI landscape, analyses its applications and risks within rheumatology, and proposes a tiered governance framework to ensure meaningful human oversight.

Neurodevelopmental disorders affect a substantial proportion of children and represent a major public health challenge worldwide. Emerging evidence highlights complex interactions among genetic, environmental and immune factors - particularly during the critical window of neurodevelopmental vulnerability. These insights raise the possibility that children with juvenile systemic autoimmune and autoinflammatory diseases are at an increased risk of developing neurodevelopmental disorders. Early onset and delayed treatment of these autoimmune and autoinflammatory diseases seem to increase this vulnerability. Growing awareness of these associations is transforming paediatric rheumatology, highlighting the need for early screening, multidisciplinary management, and personalized interventions that target both inflammatory disease and neurodevelopment. International research collaborations, biomarker discovery and long-term follow-up are crucial for closing knowledge gaps and subsequently advancing care and outcomes. Recognizing and tackling neurodevelopmental disorders as frequent comorbidities of juvenile systemic autoimmune and autoinflammatory diseases is vital for improving educational attainment, psychosocial wellbeing and lifelong quality of life in children with chronic inflammatory conditions.

The treat-to-target (T2T) strategy, which involves predefined therapy objectives and a focused monitoring system, has substantially improved the management of rheumatoid arthritis (RA). These benefits probably result from a reduction in undertreatment, prevention of overtreatment and thus an improvement in long-term outcomes for both articular manifestations and comorbidities. However, T2T has also revealed a subgroup of patients who, despite following guideline-based treatment, do not reach the predefined outcomes. This finding has led to the emerging concept of 'difficult-to-treat' (D2T) RA. D2T-RA might reflect true pharmacological refractoriness, but D2T-RA is also increasingly recognized as having broader underlying causes, including psychosocial distress, comorbidities, chronic pain syndromes and patient or system-related barriers. If these underlying factors remain unidentified, unnecessary treatment escalation can occur, which could worsen long-term outcomes. Although T2T focuses on predefined targets and regular monitoring, which works well for the majority of patients, the structured multidomain approach characteristic of the D2T framework might provide a guide for managing patients who do not reach these targets despite guideline-based care. For this population, the D2T approach could offer better stratification and serve as a practical, precision-medicine-oriented extension of T2T by providing a more mechanism-informed, personalized management strategy. Integrating this D2T perspective into T2T practices keeps the strengths of T2T while also offering individualized care for patients with more complex disease trajectories, representing an unmet need.

Despite major scientific advances, delivering high-quality care for children with inflammatory rheumatic and musculoskeletal diseases remains challenging. The field of paediatric rheumatology lies at the intersection of different disciplines, and requires excellent highly specialised medical expertise based on rapidly deepening knowledge in rheumatology and immunology. At the same time, this field relies on compassionate paediatricians understanding the needs of developing children as a vulnerable population. Training pathways and professional recognition vary widely between countries, and formal subspecialty accreditation is available inconsistently. Based on a Europe-wide expert survey, this Viewpoint examines why paediatric rheumatology is still not universally recognised as a distinct subspecialty and how insufficient access to formal accreditation leads to fragmented representation and low visibility of this discipline. We argue that stronger international advocacy involving patients and families is urgently required to support the sustainable development of the field and to ensure equitable, evidence-based, developmentally and psychologically appropriate care for all affected children.

Anti-synthetase syndrome (ASyS) is a rare autoimmune disorder defined by anti-synthetase antibodies. While malignancy is established in DM, its association with ASyS remains unclear. We aimed to estimate malignancy prevalence in ASyS and assess whether autoantibody subtype, age, sex or clinical features influence malignancy risk.

Inborn errors of metabolism comprise a clinically diverse group of conditions that arise from the decreased activity of an enzyme or metabolite transporter and subsequent blockade in a metabolic pathway. These disorders are typically considered in the differential diagnosis of critically ill neonates or young children presenting with hypoglycaemia, metabolic acidosis or hyperammonaemia. However, beyond these classic presentations, a broader group of inborn errors of metabolism can manifest more subtly, with progressive articular and multi-systemic involvement that mimics or overlaps with typical features of rheumatological disease. Consequently, these conditions might be misdiagnosed for years as rheumatological diseases, including juvenile idiopathic arthritis, systemic sclerosis, idiopathic inflammatory myopathies and systemic lupus erythematosus. Moreover, these disorders provide unique opportunities to understand the complex interplay between metabolism and immune function. With the growing availability of disease-modifying therapies for inborn errors of metabolism, rheumatologists must be able to recognize these disorders, particularly in patients with atypical features or treatment-refractory disease.

With new insights into damage accrual, new outcome measures and new therapies emerging, treatment for lupus nephritis (LN) has evolved over the last years. Although a greater proportion of patients shows clinical responses, treatment reduction and withdrawal remain challenging. While immunosuppressive therapy has relevant side effects, relapses pose the risk of long-term kidney function impairment. Unlike other autoimmune kidney diseases, LN lacks a unique biomarker or biomarker profile clearly reflecting disease activity. Here, we review definitions of remission, LN immunosuppressant withdrawal studies and new biomarkers correlated with disease activity. These factors can help to identify patients who can be safely withdrawn from immunosuppression reducing risk of infection, cardiovascular side effects, toxicity and damage accrual.

Digital vasculopathy (a spectrum of Raynaud's phenomenon, digital ulceration and critical ischaemia) is one of the most characteristic manifestations of systemic sclerosis (SSc). It is an area of unmet need with a major impact on quality of life: current treatments are only poorly effective. SSc-related digital vasculopathy is a result of structural as well as functional change at the level of both the microcirculation and the digital artery, explaining its severity. This review begins with a brief description of digital vasculopathy, followed by its assessment in the clinical setting, relevant to both diagnosis and monitoring of SSc. Outcome measures of Raynaud's phenomenon and of digital ulcers are then discussed, focusing on recent advances. These outcome measures are a 'hot topic' because reliable patient-reported and laboratory-based outcome measures will facilitate much needed clinical trials. Finally, some of the emerging non-invasive technologies which are providing new insights into pathophysiology are briefly described.

SSc is a rare rheumatological disease associated with significant morbidity and mortality. Despite significant recent international clinical trial activity, the yield of approved compounds has been disappointingly low. Our aim was to identify and prioritize potential 'druggable' targets with insights from human genetics, by integrating the available evidence with publicly available bioinformatics sources relevant for SSc drug development.

Glucocorticoids (GCs) are the cornerstone of polymyalgia rheumatica (PMR) treatment, but the optimal tapering strategy remains unclear. This systematic review aimed to explore the impact of published GC tapering strategies on remission, flare rates, GC discontinuation, cumulative GC doses and patient-reported outcomes (PROs).

Peripheral manifestations (peripheral arthritis/enthesitis/dactylitis) are frequent in axial spondyloarthritis (axSpA) yet, understudied. We (i) evaluated the assessment/reporting of peripheral manifestations in trials of biological or targeted synthetic DMARDs (b/tsDMARDs) for axSpA and peripheral SpA (pSpA), and (ii) synthesized the efficacy of b/tsDMARDs on these manifestations.

Articular cartilage is crucial for joint function; however, it has limited regenerative capacity when damaged, a hallmark of many rheumatic diseases. Non-invasive imaging is essential for early diagnosis, therapeutic monitoring and prognostication. MRI remains the reference standard, offering detailed assessment of both morphological and compositional cartilage changes. Technological advances, including high-resolution and compositional MRI techniques such as T2 mapping, T1ρ, delayed gadolinium-enhanced MRI of cartilage, sodium imaging, diffusion imaging and ultra-short echo-time imaging, enable early detection of matrix alterations that precede structural breakdown. CT arthrography, although it involves radiation, serves as a valuable alternative when MRI is contra-indicated, offering high performance in the detection and evaluation of cartilage surface lesions. Emerging modalities, such as ultrasonography and PET, offer additional functional insights but are currently limited in scope. Artificial intelligence is poised to transform cartilage imaging through accelerated acquisition, automated segmentation, improved interpretation and enhanced efficiency, with growing clinical adoption. Advanced cartilage imaging will probably have an increasingly important role in clinical rheumatology, particularly for the optimization of individualized management of cartilage pathology.

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.