To summarize and critically evaluate recent literature on autoinflammatory syndromes of hidradenitis suppurativa (HS). HS-associated autoinflammatory syndromes traditionally encompass pyoderma gangrenosum (PG), acne, and HS (PASH); pyogenic arthritis, PG, acne, and HS (PAPASH); psoriatic arthritis, PG acne, and HS (PsAPASH); and PG, acne, HS and ankylosing spondylitis (PASS). However, this spectrum continues to expand, with recent literature considering the inclusion of additional autoinflammatory diseases such as HS associated with SAPHO, including synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO); and Hyperimmunoglobulin D Syndrome (HIDS). HS-associated autoinflammatory syndromes are thought to be driven by dysregulation of the innate immune system and the subsequent overexpression of key inflammatory cytokines such as IL-1, and targeted IL-1 therapies have demonstrated particularly brisk and efficacious response. Multiple genes related to follicular keratinization or inflammatory regulation have been implicated, and sequencing methods such as whole-exome sequencing and variant enrichment analysis continue to identify novel genetic variants and are being used to further elucidate genotype-phenotype correlations. HS-associated autoinflammatory syndromes are an evolving spectrum of rare, severe, diseases in which HS coexists with other autoinflammatory conditions, most commonly PASH and related syndromes. They are driven by innate immune dysregulation and pathogenic genetic variants, with whole-exome sequencing aiding diagnosis and genotype–phenotype correlation. Management is often challenging and highly individualized, with targeted biologic therapies such as IL-1 inhibitors showing the most consistent and rapid clinical benefit.
Sexual dysfunction is an underrecognized but clinically relevant manifestation in women with axial spondyloarthritis (axSpA), with significant implications for quality of life. This review aims to provide a comprehensive synthesis of the biological, clinical, and psychosocial mechanisms underlying sexual dysfunction in axSpA, integrating available literature with supportive quantitative evidence. Emerging evidence demonstrates that sexual dysfunction in axSpA is common and multifactorial. Chronic inflammation may contribute to endothelial dysfunction, neuroendocrine alterations, and fatigue, which may indirectly affect physiological components of sexual response. Clinical factors such as pain, functional limitation, and reduced mobility further compromise sexual activity, while psychological burden; including depression, anxiety, and body image disturbance; plays a critical mediating role. Structural changes, including genital atrophy associated with disease duration, may also contribute to persistent dysfunction. Quantitative data from a meta-analysis involving 547 women suggest that there may be lower Female Sexual Function Index scores in patients with axSpA compared to healthy controls, despite the low-to-moderate certainty of evidence. This seems particularly evident in areas such as arousal, lubrication, orgasm, pain, and desire. Sexual dysfunction in women with axSpA appears to involve a complex interplay between inflammatory, physical, psychological, and structural factors. A multidisciplinary approach might be beneficial for improving patient outcomes, and systematic assessment of sexual health should be considered into routine care.
Obesity-induced osteoarthritis (OA) is emerging as a distinct metabolic phenotype fundamentally different from mechanically driven OA. Current therapies largely target downstream joint damage and fail to address underlying adipose–joint pathological interactions. This review synthesises recent advances in understanding how systemic metabolic dysfunction, adipose tissue inflammation, and cellular heterogeneity revealed by single-cell analyses drive OA pathogenesis, and highlights emerging strategies targeting metabolic dysfunction and chronic inflammation. We critically summarised human and experimental studies investigating the role of dysfunctional adipose depots, including visceral, subcutaneous, and infrapatellar fat, in joint degeneration. Mechanistic findings on adipokine signalling, immune activation, and metabolic stress were integrated with recent single-cell insights and therapeutic interventions addressing systemic metabolism and inflammation. Obesity promotes adipose tissue hypertrophy, hypoxia, and inflammatory adipokine secretion, which remodel systemic metabolism and alter the function of joint-resident cells. Crosstalk between adipocytes, macrophages, fibroblasts, and chondrocytes sustains chronic low-grade inflammation, oxidative stress, and extracellular matrix degradation. Single-cell analyses have revealed fibroblast and macrophage subsets that mediate depot-specific inflammatory circuits. Recent findings also point to metabolic modulators (GLP-1 receptor agonists), anti-adipokine agents, and regenerative strategies as promising interventions to modify disease progression. Obesity-induced OA arises from multi-level metabolic and inflammatory crosstalk between adipose and joint tissues. Deciphering adipose–joint crosstalk provides a foundation for precision therapies that address the upstream metabolic and inflammatory drivers of joint degeneration.
Fifteen years after the initial description of type I interferonopathies, this review aims to provide an updated overview of the field by integrating recent genetic and mechanistic advances. It also seeks to outline practical diagnostic approaches and highlight current and emerging targeted therapeutic strategies. Type I interferonopathies are a group of monogenic autoinflammatory diseases caused by inappropriate activation of type I interferon signaling. Multiple pathogenic mechanisms have been identified, including abnormalities in nucleic acid metabolism or sensing, constitutive activation of innate immune pathways, proteasome dysfunction, endosomal Toll-like receptor hyperactivation, and impaired negative regulation of IFNAR signaling. These mechanisms result in overlapping neuroinflammatory, cutaneous, and systemic manifestations, with variable severity and often significant morbidity and mortality. Advances in the understanding of the molecular basis of type I interferonopathies have refined their classification and improved diagnostic strategies. These insights are paving the way for more precise, mechanism-based treatments, offering promising perspectives for patient management despite the persistent severity of these disorders.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides, particularly granulomatosis with polyangiitis and microscopic polyangiitis, are rare but severe systemic diseases frequently requiring intensive care unit (ICU) admission due to life-threatening renal and pulmonary involvement. Despite advances in immunosuppressive therapy, these patients remain at high risk of mortality and end-stage kidney disease, with prognosis driven by organ failure (notably diffuse alveolar haemorrhage [DAH]) and treatment-related complications such as infection. ICU management is complex and relies on rapid diagnosis, aggressive induction therapy, and tailored organ support. Current remission-induction strategies centre on high-dose glucocorticoids combined with cyclophosphamide or rituximab, with growing emphasis on minimizing steroid exposure. Plasma exchange (PLEX), once widely used for severe renal disease and DAH, remains debated, although selected high-risk subgroups may still derive benefit. Optimal management in the ICU requires a multidisciplinary approach, including careful selection of immunosuppressive regimens, individualized use of adjunctive therapies such as PLEX and the management of infectious complications. Advances in supportive care, including lung-protective ventilation, renal replacement therapy, and extracorporeal support, have improved short-term outcomes. However, significant uncertainty persists regarding optimal therapeutic strategies in the critically ill populations, highlighting the need for further research and phenotype-driven approaches.
PURPOSE OF THIS REVIEW: Behçet's syndrome (BS) frequently comes up in the differential diagnosis of many conditions, including but not limited to rheumatological, dermatological, ophthalmological, neurological and gastrointestinal diseases. We present here a summary of what is currently known about this condition and recent published literature that may help in the diagnosis and management of BS patients. RECENT FINDINGS: A better understanding of the pathogenesis of BS may help potentially better treatment options to be developed. New epidemiological studies have shown that BS may not be as rare in certain areas as previously thought. New treatment options and clinical trials are providing both patients and doctors treating BS with more options and potentially better outcomes. New imaging modalities are helping the diagnosis and monitoring of BS patients. Better understanding of pathogenesis and availability of treatment options are helping improve outcomes in BS patients.
Psoriatic arthritis (PsA) is a chronic, immune-mediated inflammatory disease with highly heterogeneous clinical manifestations associated with psoriasis (PsO). The wide variability in presentation, together with the absence of definitive serological biomarkers, makes early diagnosis particularly challenging. This review evaluates the role of ultrasound in identifying and characterising musculoskeletal involvement across the psoriatic disease (PsD) continuum—from asymptomatic PsO to established PsA. Ultrasound can detect subclinical synovitis, enthesitis, peritendonitis, tenosynovitis, bursitis, and structural damage in PsD. Evidence highlights its value in the early identification of musculoskeletal changes in patients with PsO who are at risk of progressing to PsA, with important implications for disease interception and prevention. Additional applications include differential diagnosis; assessment of enthesitis and distinction between inflammatory and non-inflammatory disease; and monitoring of therapeutic response, including in refractory disease. Ultrasound also demonstrates prognostic utility by detecting subclinical inflammation, predicting flares and future structural damage, and supporting personalized treatment strategies. Standardized ultrasound scoring systems and emerging methods for evaluating small hand entheses and dactylitis are also discussed. Ultrasound is an important tool for early detection, prognostic assessment, and management guidance in PsA, offering potential to prevent disease progression and inform precision medicine approach.
The purpose of this review was to identify and characterize the diverse risks and benefits of glucocorticoid use in the perioperative period in patients with rheumatic diseases. Glucocorticoids increase the risk of surgical site infection, wound dehiscence, pneumonia, unplanned intubation and readmissions. The risk of perioperative adrenal insufficiency is rare. Guidelines specifically for knee and hip arthroplasties do not recommend stress dosing of steroids. Continuation of home doses of glucocorticoids is adequate for most patients. Stress dosing of glucocorticoids should be reserved for patients with biochemically confirmed adrenal dysfunction or are receiving supraphysiologic doses of glucocorticoids going for moderate to high-risk surgeries.
Systemic lupus erythematosus (SLE) patients are complex with multisystem organ involvement and often organ damage due to the disease and its treatment. This review aims to shed light on surgical outcomes in SLE patients and how these can be optimized in the perioperative setting. SLE patients often require various surgical procedures as a direct result of their disease. Several studies, the majority orthopedic, have reported the often-increased incidence of infectious, thrombotic, hemorrhagic and other postoperative outcomes in SLE patients compared to controls, as well as the role of lupus activity, severity, comorbidities, and glucocorticoids (GC) in predicting poor outcomes. Unfortunately, most publications are limited by retrospective design, small numbers or lack of granular information on lupus activity and its treatment. Nevertheless, recent guidelines for the treatment of SLE and the perioperative management of immunosuppressive therapies (IST) in patients with rheumatic diseases undergoing hips/knee arthroplasty have been published and have filled an important gap in the management of these patients. Achievement of remission or low lupus activity by escalating IST and GC taper to prednisone doses ≤ 5-7.5 mg/day is recommended in general and in the perioperative setting. Severe SLE patients actively treated for organ involvement may be allowed to continue IST perioperatively, but others may withhold IST. Careful multidisciplinary planning of elective surgeries, considering disease activity, severity, and comorbidities, as well as prudent perioperative GC, IST and anticoagulant management, should optimize outcomes in SLE patients. Large prospective studies of SLE patients undergoing common surgeries should facilitate further progress.
IgG4-related disease (IgG4-RD) is a chronic immune-mediated fibroinflammatory condition characterized by tumefactive lesions in multiple organs. Although glucocorticoids remain the cornerstone of therapy, high relapse rates and treatment-related toxicity have prompted the development of steroid-sparing strategies and targeted therapies. This review summarizes current evidence on pharmacological and non-pharmacological management of IgG4-RD and proposes a practical treatment approach based on available data and clinical experience. Glucocorticoids continue to be the first-line therapy for remission induction, achieving high initial response rates; however, relapses are common, particularly after tapering or withdrawal. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as mycophenolate mofetil, leflunomide, azathioprine, and methotrexate, are frequently used as steroid-sparing agents, although comparative evidence remains limited. B-cell targeted therapies have emerged as key treatment options. Rituximab has demonstrated high efficacy as first-line therapy and in refractory or relapsing disease, and is widely used despite remaining off-label in most regions. More recently, the anti-CD19 monoclonal antibody inebilizumab became the first therapy approved for IgG4-RD following the MITIGATE trial, which showed reduced disease flares and increased rates of glucocorticoid-free remission. Additional emerging therapies include obinutuzumab, obexelimab, CAR-T cell therapy, and cytokine-targeted agents such as dupilumab and tocilizumab, although evidence for most remains limited. Management of IgG4-RD requires an individualized approach based on disease severity, organ involvement, relapse risk, patient’s comorbidities and preferences, and access to therapies. B-cell-directed therapies and other targeted agents are emerging as key components of treatment and may enable more effective and steroid-sparing disease control.
Patients with interstitial lung disease (ILD) are at elevated risk of postoperative pulmonary complications (PPCs), including acute exacerbation, which carry high mortality. Surgical decision-making in this population requires careful preoperative risk stratification, medical optimization, and tailored intra- and postoperative management. This review summarizes current evidence to guide perioperative care for patients with ILD. The ARISCAT (Assess Respiratory Risk in Surgical Patients in Catalonia) risk index is widely used for PPC prediction but likely underestimates risk in ILD. Recent studies highlight the high prevalence of comorbid obstructive sleep apnea in ILD, supporting the need for routine screening. Updated American College of Rheumatology guidelines inform perioperative antirheumatic drug management, while International Society for Heart and Lung Transplantation consensus recommendations guide care of patients with pulmonary hypertension and right heart failure, a common comorbid condition. Emerging evidence suggests that perioperative antifibrotic therapy is safe and may reduce the risk of acute exacerbation, although further investigation is needed. Regional anesthesia can be a feasible alternative to general anesthesia when possible, for further risk mitigation in this patient population. Intraoperative lung-protective ventilation and use of the lowest oxygen concentration that maintains safe oxygen saturation remain critical, while judicious fluid management, postoperative extubation to high-flow nasal cannula or noninvasive ventilation, early mobilization, and multimodal analgesia may further reduce PPC risk. Perioperative management of ILD patients is complex due to heightened vulnerability to PPCs. Current evidence supports adapting general perioperative strategies while incorporating disease-specific considerations. As therapeutic advances extend survival, further prospective studies are needed to establish evidence-based perioperative guidelines for this high-risk group.
The purpose of this review is to provide details of the STOP Gout trial, among the first randomized, blinded studies to compare allopurinol with febuxostat using a treat-to-target strategy. In addition to details of its design and trial results, this review summarizes findings from pre-planned and other analyses, as well as an associated biorepository that has enabled the identification of biomarkers impacted by highly effective urate-lowering therapy (ULT). In addition to primary trial findings demonstrating the non-inferiority of allopurinol to febuxostat in flare prevention and the achievement of serum urate goals, data generated from the STOP Gout trial have provided additional insights that have included: 1) the relative efficacy and safety of both allopurinol and febuxostat in participants with stage 3 chronic kidney disease; 2) patient factors associated with the achievement of serum urate goals; 3) the frequency and determinants of mobilization flares during the early phases of treat-to-target treatment; 4) the heightened risk of flare following discontinuation of anti-inflammatory prophylaxis; 5) limited persistence of ULT following transitions back to real-world care; 6) rapid gains in health-related quality of life accompanying highly effective ULT that pre-date reductions in flare risk; and 7) the positive effects of urate-lowering on measures of systemic inflammation and other circulating biomarkers. In addition to informing the comparative efficacy and safety of allopurinol and febuxostat, STOP Gout and the resources generated from this trial have enabled research that has further informed our understanding of gout and its management.
This review aims to provide clinicians with a practical framework for distinguishing idiopathic inflammatory myopathies (IIMs) from their numerous non–immune-mediated mimics, including hereditary, toxic, metabolic, and endocrine myopathies, by integrating clinical, serologic, imaging, electrophysiologic, and histopathologic clues. IIMs represent a heterogeneous group of immune-mediated muscle diseases. Despite major advances in antibody discovery, imaging, and classification criteria, accurate diagnosis remains challenging because many non-immune-mediated myopathies can mimic IIMs. Such resemblance may lead to misdiagnosis, delay in genetic evaluation, prolonged exposure to offending agents in toxic myopathy, and unnecessary treatment with immunosuppressive therapy that carries significant adverse effects. The temporal course of weakness, pattern of muscle involvement, presence of extramuscular manifestations, and ancillary testing offer important diagnostic clues, but none are pathognomonic when interpreted in isolation. We introduce the mnemonic “MYOSITIS” to summarize key diagnostic red flags that should raise concern for mimicking disorders: Myopathic motor unit potentials without fibrillation potentials, Young age of symptom onset or positive family history, Onset atypical for IIMs, Seronegative or weakly positive myositis specific autoantibodies, Iatrogenic causes, Treatment refractoriness, Irregular weakness patterns, and Systemic features. Recognizing these pitfalls and adopting an integrated diagnostic approach that combines clinical pattern recognition with selective use of serologic, imaging, and genetic testing can help clinicians differentiate true IIMs from their mimics and ensure timely, accurate diagnosis and optimal patient management.
Behçet’s disease (BD) is a multisystemic inflammatory disorder in which treatment decisions are largely driven by the pattern and severity of organ involvement. This review provides a practical, organ-based overview of current therapeutic strategies for severe and refractory BD, with an emphasis on treatment selection and timing in routine clinical practice. Recent evidence supports an upfront, intensive treatment approach for life-threatening or damage-prone organ involvement, particularly neurological, vascular, and ocular disease, where delays in inflammation control are closely associated with irreversible damage. Anti–tumour necrosis factor agents form the core of therapy in these settings, supported by the strongest disease-specific data, while other biologic and targeted therapies are increasingly used in refractory cases. In contrast, mucocutaneous and articular manifestations predominantly affect quality of life and are commonly managed with stepwise strategies. Colchicine remains a widely used first-line treatment in routine practice and provides effective control of mucocutaneous and joint manifestations in a substantial proportion of patients, with escalation to additional systemic or targeted therapies guided by persistence, refractoriness, and patient burden. Importantly, treatment responses vary across organ systems, and benefit in one domain cannot be assumed to translate to others, reinforcing the need for organ-specific treatment planning. Optimal management of BD depends on matching treatment intensity to organ-specific risk, prioritising early aggressive therapy for major organ involvement while adopting proportionate, stepwise approaches for non–life-threatening disease. Improved outcomes are likely to be achieved through timely recognition of patients at risk of progression and early use of appropriately targeted therapies to prevent irreversible organ damage.
Behçet's syndrome (BS) frequently comes up in the differential diagnosis of many conditions, including but not limited to rheumatological, dermatological, ophthalmological, neurological and gastrointestinal diseases. We present here a summary of what is currently known about this condition and recent published literature that may help in the diagnosis and management of BS patients. A better understanding of the pathogenesis of BS may help potentially better treatment options to be developed. New epidemiological studies have shown that BS may not be as rare in certain areas as previously thought. New treatment options and clinical trials are providing both patients and doctors treating BS with more options and potentially better outcomes. New imaging modalities are helping the diagnosis and monitoring of BS patients. Better understanding of pathogenesis and availability of treatment options are helping improve outcomes in BS patients.
This review recognizes gout as an autoinflammatory disease rather than a solely metabolic condition. It provides an overview of autoinflammatory diseases, the NOD-, LRR, and pyrin domain-containing protein 3 (NLRP3) inflammasome, and how soluble and crystalline forms of uric acid (UA) act as inflammatory triggers, prompting NLRP3 inflammasome formation and activation. It also highlights the genetics associated with the autoinflammatory features of gout and discusses NLRP3 inflammasome-targeted treatments. Autoinflammatory diseases result from hyperactivity of the innate immune system, and the NLRP3 inflammasome complex, an innate immune sentinel and nonspecific sensor of cellular perturbation, is the initiator and key participant in gouty inflammation. Both the soluble and crystalline forms of UA act as inflammatory triggers, leading to the formation and activation of the NLRP3 inflammasome further promoting caspase 1-dependent release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. Intracellular soluble UA also induces endothelial nitric oxide synthase dysfunction, oxidative stress, and inflammation. These mechanisms explain UA’s important role in promoting inflammatory pathways in patients. Gout is now recognized as a disease rooted in innate immune dysregulation, with uric acid-driven activation of the NLRP3 inflammasome. Integrating the autoinflammatory perspective highlights the opportunities for developing targeted treatments. Emerging therapies focused on NLRP3 inhibition coupled with urate-lowering strategies may offer a better approach for managing gout flares.
Takayasu arteritis (TAK) is a chronic, large-vessel vasculitis disproportionately affecting young women. The consequences of vascular inflammation include stenotic and occlusive disease with resultant end organ ischemia and dysfunction impacting quality of life. In this review, we highlight the recent advances in the assessment of disease activity and damage and treatment of TAK. Distinguishing disease activity from vascular damage in patients with TAK is challenging. The PET Vascular Activity Score (PETVAS) and Vasculitis Activity using MR and PET Vasculitis Activity using MR and PET (VAMP) hold promise. Composite scores such as the TAK Integrated Disease Activity Index (TAIDAI) combine information from prevalent clinical features and FDG-PET. For damage assessment, the validation of the Large Vessel Vasculitis Index of Damage (LVVID) in patients with TAK and reports of serum biomarkers of fibrosis are important advances. The usual practice for treating patients with TAK is to combine glucocorticoids with DMARDs. Recent studies have shown the effectiveness of methotrexate or mycophenolate mofetil (alone or in combination), secukinumab, tofacitinib, and baricitinib while confirming the role of tumor necrosis factor alpha inhibitors or tocilizumab in the management of TAK. Vascular interventions are reserved for vascular damage or ischemia of major organs threatening their function or affecting the quality of life. Advances in the assessment of disease activity and damage using composite tools hold promise to improve the management of patients with TAK. More high-quality trials are required to better inform the evidence base for treating patients with TAK.
