Autoantibody flares are important drivers of pathology in systemic lupus erythematosus (SLE), highlighting the pivotal role of B cells in initiating and propagating chronic autoimmunity. Although autoreactive specificities are a normal feature of the naive B cell repertoire, these cells are normally suppressed by layered tolerance checkpoints that limit inappropriate activation. Autoimmune-prone environments can lower these tolerance thresholds, rendering naive autoreactive B cells more sensitive to aberrant cues. Cytokines and other microenvironmental signals shape tissue niches that direct autoreactive B cells towards either germinal-centre or extrafollicular differentiation pathways. Germinal centres support the entry, selection and diversification of autoreactive B cells, with T cell help sustaining these repertoires. By contrast, naive autoreactive B cells entering the extrafollicular pathway exhibit an attenuated requirement for cognate T cell help and strong dependence on complement and TLR signalling. Emerging evidence continues to refine our understanding of germinal-centre and extrafollicular responses as complementary sources of autoreactive effector cells. With this progress, investigations into the origin, development, longevity and tissue dynamics of autoreactive memory B cells as chronic sources of autoantibodies are warranted. Although broad B cell depletion therapies have yielded benefit, a key challenge now is developing precision strategies that selectively target pathogenic B cell subsets.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women of childbearing age. As the prevalence of SLE rises, and advances since the 1960s have substantially improved survival and quality of life, the number of women with SLE who become pregnant is steadily increasing. Although pregnancy is feasible for most patients with well-controlled SLE, pregnancy remains challenging for both women with SLE and clinicians because the risk of maternal complications and adverse fetal outcomes is higher than that in the general population. Moreover, the increased risk of pregnancy complications persists in subsequent pregnancies in women with SLE, whereas in healthy women this risk decreases owing to the development of maternal-fetal immune tolerance. During pregnancy and the postpartum period, women remain at risk of disease flares and other complications, particularly those with active disease at conception, a history of lupus nephritis, antiphospholipid syndrome or recent medication withdrawal. Important knowledge gaps persist regarding the mechanisms underlying these complications and the safety of treatment during conception, pregnancy and lactation. Preconception counselling, assessment of risk factors for adverse outcomes, pregnancy planning, timely medication adjustment and multidisciplinary management are essential to improve the maternal and fetal outcomes in women with SLE.

Glucocorticoids remain a cornerstone in treating inflammatory rheumatic musculoskeletal diseases due to their rapid, potent anti-inflammatory effects. However, their long-term use carries well known risks, such as their cumulative toxicity, leading to international consensus that glucocorticoids should be given at the lowest effective dose and for the shortest duration, and discontinued whenever clinically feasible. In rheumatoid arthritis, systemic lupus erythematosus, and polymyalgia rheumatica, modern guidelines recommend short-term glucocorticoid use as bridging therapy at the lowest effective dose, often feasible through concomitant disease-modifying antirheumatic drugs or immunomodulatory or suppressive agents. However, registry and cohort data show chronic glucocorticoid therapy (>6 months) remains common. Contributing factors include difficult-to-treat disease, flares during tapering, limited access to glucocorticoid-sparing therapies, reluctance by physicians or patients to discontinue, barriers to implementing guideline-based care, and other barriers. However, new evidence indicates that, when clinically necessary, longer-term glucocorticoid therapy with very low doses (<5 mg/day), under careful monitoring, might offer an acceptable safety profile, although cumulative risks persist. In patients with unmet therapeutic needs, rational strategies combining disease-modifying antirheumatic drugs with very low-dose glucocorticoids might improve outcomes, reduce the frequency and severity of disease flares in diseases amenable to glucocorticoid therapy while maintaining toxicity within acceptable limits, and help to overcome the ceiling effect in rheumatoid arthritis. This Review summarises current recommendations, highlights the gap between guidelines and clinical practice, and discusses optimal approaches for glucocorticoid reduction, discontinuation, and potential safe long-term low-dose use, focusing on rheumatoid arthritis, systemic lupus erythematosus, and polymyalgia rheumatica.

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.