In this meta-analysis of international cohorts, current smoking is confirmed as a significant BMD-independent predictor of future fracture with a stronger relationship in men than in women. A causative and reversible effect of smoking on fracture risk is suggested by past smoking having a significantly lower risk than current smoking. In this meta-analysis of international cohorts, the aim was to examine the relationship of current and past smoking with fracture risk to provide an update for future iterations of the FRAX tool. The risk of fracture associated with current and past smoking was estimated using an extended Poisson model applied separately to each of 58 prospective international cohort studies. Covariates included current time since start of follow up, current age, and in an additional model, BMD at the femoral neck. The results of the different studies were merged by using inverse-variance weighted β-coefficients. This analysis included a total of 1,691,024 participants (61.2% women, overall mean age 58.8 years). Current smoking, documented in 12.1% of all participants (15.2% and 10.1% respectively in men and women), was associated with a significantly increased risk of any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and particularly hip fracture in both sexes. The hazard ratio (HR) for fracture was greater in men than in women for all fracture categories [e.g. hip fracture HR (95% confidence interval): 1.78 (1.58-2.00) vs. 1.64 (1.50-1.78)]. Low BMD explained about 19-54% of the increase in risk. When compared with never smoking, past smoking was associated with a significantly lower risk than current smoking [e.g. hip fractures for men, HR in past smokers: 1.08 (1.05-1.12) vs. 1.73, 95%CI (1.46-2.05) in current smokers]. Our results confirm the association between current smoking and increased fracture risk that is partly independent of BMD; these data will be used to inform future iterations of FRAX.
BackgroundLarge language models (LLMs) have demonstrated promising capabilities in medical diagnostic reasoning, yet their performance in specialized clinical domains such as rheumatology remains incompletely characterized. While diagnostic accuracy has been evaluated, critical dimensions including calibration, reasoning quality, and temporal stability have not been systematically assessed across contemporary models.ObjectivesThis study aimed to comprehensively evaluate and compare the diagnostic accuracy, certainty expression, reasoning quality, and hallucination rates of four state-of-the-art LLMs ChatGPT-4, Claude 3.5, DeepSeek-V3, and Gemini 1.5 Pro in complex rheumatologic case scenarios.DesignA cross-sectional, analytical, and comparative study was conducted following STARD and TRIPOD guidelines, adapted for LLM evaluation. Nine complex rheumatologic cases from published case reports were evaluated at three time points (Days 1, 5, and 10) between July 1 and September 18,2025.MethodsStandardized clinical vignettes were submitted to each LLM under controlled experimental conditions. Two blinded senior rheumatologists independently assessed diagnostic accuracy, reasoning quality across five analytical dimensions using Likert scales, and hallucination frequency. Certainty expression and temporal stability were quantified using intraclass correlation coefficients. Correlation analyses examined relationships between reasoning quality and confidence expression.ResultsAll models achieved near-perfect diagnostic accuracy, with ChatGPT, Claude and Gemini correctly identifying the primary diagnosis in 100% of cases and DeepSeek in 88.9%. However, Spearman correlation analysis revealed uniformly weak and non-significant associations between reasoning quality and expressed certainty across all models (ρ range: -0.156 to 0.215, all p>0.05), indicating fundamental miscalibration. ChatGPT demonstrated the highest reasoning score (3.89±0.23) and lowest hallucination rate (7.4%), while Gemini showed the highest hallucination frequency (18.5%). Temporal stability was excellent for ChatGPT (ICC=0.84) and good for DeepSeek (ICC=0.79).ConclusionDespite exceptional diagnostic accuracy, current LLMs exhibit critical limitations in confidence calibration and variable hallucination rates, representing significant barriers to safe clinical deployment in rheumatology.
Autonomous home-based transcranial direct current stimulation (HB-tDCS) is a scalable non-pharmacological intervention for chronic pain, but evidence under fully autonomous use remains limited. To identify factors associated with adherence to fully autonomous HB-tDCS; to characterize the incidence, severity, and timing of adverse events under active and sham stimulation; and to examine if patient and clinical factors, including adverse events and clinical response, are associated with variability in adherence and safety outcomes. Secondary pooled analysis of three double blind, sham-controlled randomized clinical trials. A total of 234 women with fibromyalgia diagnosed according to the 2016 American College of Rheumatology criteria. Participants received a standardized autonomous HB-tDCS protocol (≥20 sessions). The primary outcomes were adherence and safety. We examined associations with adherence and adverse events using generalized linear mixed-effects models, adjusted for demographic, clinical, and psychosocial factors. We also explored whether the burden of adverse events explained the link between treatment allocation and adherence. Overall adherence was 82.6% (95% CI, 81.6-83.6). Adherence rates were similar for the active (84.7%, 95% CI, 83.3-86.0) and sham groups (80.5%, 95% CI, 78.9-82.1). Older age (β = -0.024 sessions/year; 95% CI, -0.040 to -0.008) and greater central sensitization (β = -0.025 per point; 95% CI, -0.040 to -0.010) were associated with lower adherence. Higher depressive symptom severity was linked to higher adherence (β = 0.041 per point; 95% CI, 0.040-0.060). Most participants reported no adverse events (67.0%, 95% CI, 61.0-73.0), with no group differences (χ 2 = 0.04, p = 0.83). Reported events were mostly mild and brief. Active stimulation led to more frequent tingling and erythema. Higher education (β = 0.078; 95% CI, 0.023-0.130) and depressive symptoms (β = 0.037; 95% CI, 0.020-0.050) were associated with more adverse event reports. Greater functional impairment was linked to fewer reported events (β = -0.003; 95% CI, -0.040 to -0.007). Autonomous home-based transcranial direct current stimulation was feasible, safe, and highly adhered to in fibromyalgia, with adherence and safety influenced by clinical and psychosocial factors, supporting scalable implementation in chronic pain.
Systemic lupus erythematosus (SLE) is a disease with few licensed drugs when compared to rheumatoid arthritis, axial spondyloarthropathies, and psoriatic arthritis. We report on results of a systematic literature review of IL-17i in SLE with appraisal of published cases of both efficacy of treatment and the risk of developing new SLE following treatment with IL-17i through investigation of adverse events in the setting of clinical trials of IL-17i in non-SLE indications. We performed a PubMed, EMBASE, and MEDLINE search from inception till 30 June 2025 for case reports of IL-17i-induced SLE. The four EMA-licensed IL-17 inhibitors secukinumab, bimekizumab, brodalumab, and ixekizumab were included for analysis. All four monoclonal antibodies block IL-17A, with bimekizumab having the dual functionality of blocking IL-17A/F. Furthermore, the clinical trial data for secukinumab in psoriasis, psoriatic arthritis, and axial spondylarthritis from inception till 2024 was reviewed for adverse event reporting of new cases of SLE. Both systemic and cutaneous SLE were reported on. We also reported on secukinumab case reports for treating SLE. Clinical efficacy of IL-17i in case reports of active SLE: in the case of patients treated with secukinumab for known active SLE outside of the clinical trial setting (n = 4), the commonest indications for the use of secukinumab were active cutaneous disease and inflammatory arthritis (75%, n = 3), with 25% [n = 1] having lupus nephritis. All four patients had positive serology for ANA and dsDNA. New-onset SLE following IL-17i in the literature: amongst 56 clinical trials for secukinumab, there have been no reports of drug-induced or paradoxical/new-onset SLE following treatment in the reporting periods for each respective trial (n = 13,000). To date, there are no case reports of bimekizumab- or ixekizumab-induced SLE, although there are two case reports for ixekizumab-induced lupus tumidus, which were excluded from the analysis. One case report exists for new-onset SLE in a patient undergoing treatment with brodalumab for psoriasis, and six cases of SLE following initiation of secukinumab were identified. We identified four of the uses of secukinumab in the treatment of SLE. Despite a handful of case reports for paradoxical reactions with IL-17i, they remain a potential therapeutic option in SLE. All patients recovered upon cessation of the offending IL-17i, and generally patients with drug-induced lupus only require symptomatic management and withdrawal of the offending agent. The efficacy of IL-17i for use in SLE remains unclear due to the limited data from case reports. Among the case reports there was heterogeneity in the reporting of disease activity with no standardization or the use of classic disease metrics such as the SLEDAI or DORIS, which can provide its own challenge in appreciating the results and validating the findings. In conclusion, this is an area that deserves further investigation. Translational research is needed to better understand the role of IL-17 in the pathogenesis of SLE. Dedicated studies and trials of clinical efficacy are needed. https://www.crd.york.ac.uk/prospero/, identifier 1338317.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a relapsing, autoantibody-driven disease in which current therapies often fail to achieve durable remission or are limited by cumulative toxicity. Although CD20-directed B-cell depletion has transformed AAV management, persistent autoreactive B-cells and long-lived, tissue-resident plasma cells contribute to refractory disease and relapse. Chimeric antigen receptor (CAR) T-cell therapy offers a mechanistically distinct approach through deep and sustained depletion of pathogenic B-cell lineages and potential "immune reprogramming." Emerging clinical experience in autoimmune diseases, coupled with preclinical models and early case reports in AAV, has demonstrated rapid disease control, marked reductions in ANCA levels, and prolonged immunologic quiescence following CD19 CAR-T therapy. While safety signals in autoimmune populations appear favorable, critical questions remain regarding the durability of response, long-term immunologic consequences, optimal CAR constructs, and patient selection. This review summarizes the immunopathogenic rationale, existing evidence, safety considerations, and future directions for CAR-based therapies in AAV.
Background and Clinical Significance: Multiligamentous knee injuries (MLKIs) are uncommon but severe injuries associated with instability, neurovascular compromise, and long-term functional impairment. Irreducible knee dislocations are a distinct subgroup requiring urgent intervention because soft-tissue interposition may prevent closed reduction and place the limb at risk of skin necrosis and vascular compromise. This report reviews current concepts in MLKI management and presents a complex KD-IV irreducible knee dislocation treated with a staged surgical strategy. Case Presentation: A 56-year-old woman presented 24 h after a skiing injury with a grossly deformed knee, multidirectional instability, and an anteromedial "pucker sign". Magnetic resonance imaging demonstrated a KD-IV injury with complete rupture of the anterior cruciate ligament, posterior cruciate ligament, and medial collateral ligament, associated with capsular disruption and intra-articular soft-tissue interposition causing irreducibility. Urgent open reduction was performed. The first stage included reduction of the incarcerated capsule, capsular repair, and reconstruction of the posteromedial corner and medial collateral ligament using a semitendinosus autograft. Delayed reassessment at 6 months demonstrated satisfactory stability, minimal residual anterior laxity, and no subjective instability; therefore, anterior cruciate ligament reconstruction was not performed. At final follow-up, the patient had near-full range of motion, no significant valgus instability, and no arthrofibrosis or vascular complications. Conclusions: Management of MLKIs should be individualized according to reducibility, soft-tissue condition, neurovascular status, and functional demands. Irreducible KD-IV dislocations with a pucker sign require urgent open reduction. In selected patients, staged reconstruction may reduce postoperative stiffness and allow selective omission of cruciate ligament reconstruction when satisfactory functional stability is achieved.
Brief rationale: Osteoporosis management in Italy shows regional inconsistencies. Expert surveys and meetings revealed limited access to anabolic treatments and fragmented care pathways. Significance of the paper: Findings support the need for updated national guidelines to promote equitable care and reduce the burden of osteoporotic fractures. Osteoporosis is a progressive bone disease characterized by reduced bone density and increased fracture risk, significantly affecting quality of life and imposing a substantial burden on healthcare systems. In Italy, managing osteoporosis is a national priority due to the rising incidence of fractures among the aging population. This study evaluates clinical practices in osteoporosis management across Northern, Central, and Southern Italy, focusing on diagnostics, therapies, and access to specialized care. A detailed survey was distributed across multiple centers to evaluate diagnostic, therapeutic, and follow-up practices, along with specialists' perspectives on national guidelines and the challenges in accessing advanced treatments. Following the survey, three regional expert meetings were held to analyze the findings and gain further insight. Findings show widespread use of bone mineral density (BMD) testing and laboratory assessments, with regional differences in the use of fracture risk tools (FRAX, DeFRA) and markers such as CTX. Bisphosphonates, denosumab, and anabolic agents are commonly used; however, significant disparities persist in access to anabolic treatments. The patient journey remains uneven across regions, with challenges in accessing bone specialists, timely diagnosis, and appropriate treatment. In areas lacking structured care pathways, these gaps lead to delayed or suboptimal management. These findings highlight the need for updated, flexible guidelines to support a tailored and equitable approach to osteoporosis care in Italy. Improving access to specialized care and standardizing treatment pathways may enhance outcomes and reduce healthcare costs associated with osteoporosis-related fractures.
Small bowel involvement represents a common and clinically significant manifestation of systemic sclerosis (SSc). Pathogenesis is multifactorial, and diagnosis remains challenging due to non-specific symptoms, limited diagnostic tools, and a lack of standardized management strategies. A systematic search of PubMed and Embase was conducted to identify studies evaluating small bowel involvement in patients with SSc using objective tests and patient tissue. A qualitative synthesis was performed due to the anticipated heterogeneity in study designs, interventions, and outcomes. Of the 24 studies included, 9 (37.5%) evaluated small bowel motor function using manometry, 12 (50%) employed other objective diagnostic methods, and 7 (29.2%) reported histopathological findings. Manometric studies showed a high prevalence of motor abnormalities: absent or impaired phase III complexes (median 50.3%, IQR,22.5%-81%), reduced phase III migration velocity (31.3%, IQR,18%-53%), diminished contraction amplitude (median 62.5%, IQR,40%-75%), and abnormal postprandial responses (median 60.6%, IQR,50%-90%). No correlation was found between esophageal and small bowel involvement when both were assessed by manometry(5 studies). Transit studies (breath tests, capsule endoscopy, and whole-gut scintigraphy) showed variable performance; however, whole-gut scintigraphy identified clinically relevant associations, including a strong link with increased mortality (HR 4.57; 95% CI: 1.58-13.24). Histopathological results identified smooth muscle atrophy, enteric neuropathy, and vascular fibrosis in the pathogenesis of small bowel involvement. In SSc, small bowel involvement is frequent and associated with decreased contractile amplitude and delayed transit time. There is a critical need for standardized diagnostic approaches to enable early recognition and guide management.
As part of a research program examining rheumatology referrals in British Columbia, the Patient Self-Administered Inflammatory Arthritis Detection (SAID) Study evaluated the SAID tool, which contains validated patient-completed questionnaires for identifying and prioritizing individuals with inflammatory arthritis, supporting its utility and feasibility. This article reports the perspectives of participating patients and rheumatologists regarding the SAID tool. A multimethods design was used to collect and analyze patient survey and rheumatologist interview data, with an emphasis on implementation considerations. Ninety-two patients who completed the questionnaires in the Patient SAID Study also provided feedback on their experience. Semistructured interviews were conducted with 3 rheumatologists. Quantitative and qualitative data were analyzed using Microsoft Excel and NVivo to identify usability, relevance, and barriers or enablers to implementing the tool in primary-to-specialist referral. Most patients found the SAID tool easy to log into (85%) and complete (82%). Across diagnostic groups, most (76%) believed it could help their general practitioner assess symptoms but emphasized the need for more nuanced response options and space for elaboration. Rheumatologists viewed the tool as brief, useful, and potentially valuable for triage, especially if integrated at the referral stage. Key barriers included time constraints, false negatives, and lack of integration with electronic medical records. All rheumatologists supported optional implementation led by motivated patients, provided it complemented-not complicated-existing workflows. With targeted modifications and appropriate implementation mechanisms, the SAID tool has the potential to improve the quality of referrals, support triage decision making, and address current gaps in access to rheumatology care within evolving digital health systems.
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.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multisystem involvement and fluctuating activity. Among its many complications, cardiovascular disease (CVD) is a leading cause of morbidity and mortality, with up to 25% of patients affected. Cardiac manifestations, such as pericarditis, myocarditis, and accelerated atherosclerosis, are often underdiagnosed due to their subclinical presentation and lack of standardized screening protocols. This systematic review aims to synthesize current evidence on the incidence, detection, and prognostic challenges of cardiac complications in SLE patients and to identify gaps in current risk stratification and diagnostic methods. A comprehensive literature search was conducted across Ovid, CINAHL, EMBASE, and Web of Science using predefined search terms related to SLE, cardiovascular complications, disease flares, and diagnostic tools (e.g., biomarkers, cardiac MRI). English-language studies published between 2015 and 2025 involving adults (≥18 years) were included. Eligible studies focused on cardiac complications in SLE patients and reported outcomes such as incidence, diagnostic markers, or evidence of underdiagnosis. Exclusion criteria included pediatric populations, non-SLE autoimmune diseases, lack of cardiac outcome data, animal/in vitro studies, non-English papers, reviews, and editorials. Across 31 studies encompassing over 7,000 patients with SLE, cardiac symptoms were frequent, ranging from subclinical abnormalities to life-threatening complications. Case reports highlighted severe manifestations, including cardiac tamponade, myocarditis, cardiogenic shock, and myocardial infarction, often mimicking acute coronary syndromes. Observational and retrospective cohorts demonstrated high rates of pericardial effusion (up to 25%), pulmonary hypertension (15-42%), valvular disease (15-32%), and subclinical myocardial dysfunction detected by advanced echocardiographic or PET modalities. Large-scale cohorts identified lupus myocarditis in 1.7%-9% of patients, strongly associated with higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, hypocomplementemia, and anti-nucleosome antibody positivity. Biomarker studies reported elevated troponin, IL-18, IL-1Ra, and interferon-α as predictors of myocardial injury and adverse outcomes. Mortality data linked poor prognosis to myocarditis, pulmonary hypertension, renal disease, and higher comorbidity indices. Outcomes varied, and patients were treated with diverse therapies, including glucocorticoids, immunosuppressants, biologics, and cardiovascular medications. Collectively, findings underscore that cardiac manifestations in SLE are common, multifactorial, and frequently underdiagnosed, with biomarkers and advanced imaging emerging as valuable tools for early detection. Cardiac complications in SLE are prevalent, diverse, and often underrecognized. This review highlights the critical need for improved diagnostic strategies, including the use of emerging biomarkers and advanced imaging techniques, to enable earlier detection and more accurate risk stratification. Standardizing screening protocols and incorporating cardiovascular assessment into routine SLE management may reduce delays in diagnosis and improve patient outcomes. Further research is essential to develop consensus guidelines for early identification and prognostication of cardiac involvement in SLE.
Takayasu arteritis (TA) is a chronic, immune-mediated vasculitis that primarily affects the large arteries, particularly the aorta and its main branches, leading to stenosis, occlusion, dilation, or aneurysms. Traditional imaging modalities, including computed tomography angiography (CTA), magnetic resonance angiography (MRA), and positron emission tomography/computed tomography (PET-CT), offer valuable diagnostic information; however, their clinical applicability has limitations, including high costs, radiation exposure, and reduced availability. In recent years, contrast-enhanced ultrasound (CEUS) has emerged as a minimally invasive, radiation-free technique capable of detecting vascular wall neovascularization as a potential surrogate imaging marker of TA inflammatory activity. This scoping review, conducted in accordance with the Joanna Briggs Institute (JBI) methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist, aims to synthesize current evidence on the diagnostic and monitoring utility of CEUS in patients with TA and carotid involvement. We systematically searched MEDLINE/PubMed, Scopus, Web of Science, LILACS and EBSCO from inception to May 2025 for original studies of adult patients with TA in whom CEUS was used to assess disease activity. Eighteen studies (8 cross-sectional, 3 cohort, 7 case reports; 631 patients) met the eligibility criteria. Across these studies, CEUS detected arterial wall neovascularization compatible with active inflammation, particularly in the carotid arteries, and demonstrated moderate-to-strong correlations with inflammatory biomarkers, PET-CT findings, and clinical activity scores such as the Indian Takayasu Activity Score (ITAS) and the National Institutes of Health (NIH) criteria. Importantly, CEUS can reveal subclinical or residual inflammation even when clinical symptoms or laboratory markers are absent. Its ability to detect early relapses and monitor therapeutic response has been demonstrated in both observational cohorts and individual case reports. Despite this, substantial heterogeneity in imaging protocols and activity definitions limits comparability across studies and restricts integration into clinical practice. CEUS is a minimally invasive, reproducible, and effective technique for both detecting and monitoring disease activity in TA with carotid vessel involvement, thereby facilitating early and accurate therapeutic decisions. Its future incorporation into clinical practice will require validated scoring systems, harmonized acquisition protocols, and demonstration of added value in treatment decision-making and long-term outcomes.
Rapidly progressive interstitial lung disease (RP-ILD) from anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5) dermatomyositis (DM) is a rare condition associated with up to 63% mortality. Despite aggressive medical treatment, many patients require escalating levels of respiratory support. Extracorporeal membrane oxygenation (ECMO) has emerged as a rescue therapy for these patients, intended as a bridge to lung transplantation. A retrospective chart review was conducted on patients who were treated at our center between 2021 and 2025. Baseline characteristics, treatments, complications, and outcomes are described and presented herein. A literature review was performed to compare our outcomes for patients with anti-MDA5 DM placed on ECMO with those reported elsewhere. The study included 9 patients (5 females and 4 males) with RP-ILD due to anti-MDA5 DM. All patients were treated with high-dose corticosteroids and a variety of other immunosuppressive therapies. Eight patients were placed on veno-venous (V-V) ECMO and one patient was placed on veno-arterialvenous (V-AV) ECMO. All patients were evaluated for lung transplant candidacy. Eight of nine patients were deemed ineligible for lung transplant, most commonly due to severe deconditioning, and died in the ICU. One patient was successfully bridged to bilateral lung transplant after 3 days on ECMO and is currently 30 months post-transplant.A retrospective review of published studies found 79 patients with anti-MDA5 DM induced-RP-ILD requiring ECMO support. Twenty-eight (35.4%) patients were bridged to transplant (average time on ECMO 18 days), 46 (58.2%) died in the ICU (average time on ECMO 28 days), and only 4 (5%) were successfully bridged to recovery (average time on ECMO 44 days). Outcomes for 1 patient were not reported. RP-ILD due to anti-MDA5 DM is associated with a high rate of mortality despite current medical therapies. ECMO as a bridge to recovery is very unlikely (∼5%, 4/79) for these patients; thus, lung transplant should be pursued expeditiously, particularly given the possible association between shorter time on ECMO and successful transplantation. Transfer to an ECMO and lung transplant center is crucial since immunosuppression decisions should be made in a multidisciplinary fashion (lung transplant, rheumatology, etc.) as these decisions can affect lung transplant candidacy.
To seek for the current evidence in support of the adoption of the treat-to-target (T2T) strategy in the management of juvenile dermatomyositis (JDM). A systematic literature review (SLR) was performed to address 14 research questions formulated by the Steering Committee (SC) of the project. MEDLINE, Embase, Cochrane Central, and Web of Science databases were searched for clinical trials, observational studies (retrospective and prospective), case reports of > 2 patients, expert recommendations, and systematic reviews published until March 2023. The protocol for the SLR was registered in PROSPERO (CRD42023421254). Quality assessment was performed according to a modified GRADE approach. A total of 2,714 articles were retrieved from the databases, with an additional 47 identified through citation searching, and 23 flagged by SC members. Of these, 220 were included in the final review. Evidence was strong or moderate for 2 and 22 articles, respectively, and weak for the remaining articles. Although no published study that compared conventional management with a targeted approach was retrieved, useful insights into specific therapeutic endpoints and optimal timing for their achievement that could be considered in designing the T2T strategy for JDM were obtained. This SLR provides a comprehensive overview of the current knowledge that served as the basis for the consensus definition of the overarching principles and recommendations for treating JDM to target.
Established treatments for granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) include the use of immunosuppressive agents for remission induction followed by maintenance therapy. However, patients continue to experience disease progression, organ damage, and adverse events related to current therapies. Avacopan, an oral selective C5a receptor antagonist, was approved by the European Commission in January 2022 for the treatment of adult patients with severe, active GPA or MPA in combination with rituximab (RTX) or cyclophosphamide (CYC). In the pivotal phase 3 ADVOCATE (Avacopan Development in Vasculitis to Obtain Corticosteroid Elimination and Therapeutic Efficacy) study, avacopan was noninferior to prednisone taper in achieving remission at week 26 and superior in sustaining remission at week 52; furthermore, a greater improvement in estimated glomerular filtration rate with avacopan was also observed at week 52. The AvacoStar study will generate data on the benefit and risk and safety profile of avacopan in patients in a real-world context, including in those where treatment may potentially continue beyond 1 year. The primary objective of AvacoStar is to evaluate the incidence of defined medical events of special interest in patients with antineutrophil cytoplasmic antibody-associated vasculitis commencing avacopan. These include liver injury, cardiac safety, serious infections, and malignancy. AvacoStar is a noninterventional, multinational, prospective postauthorization safety study. It will enroll up to 500 patients in Germany and the United Kingdom in 2 groups of approximately 250 participants each: those treated with avacopan (plus a standard of care at local investigators' discretion; usually an RTX- or CYC-based regimen) and a second cohort treated with a CYC- or RTX-based induction regimen without avacopan. Avacopan and the standard of care will be prescribed in the usual manner in accordance with the corresponding summary of product characteristics under the sole decision of the investigator. The treatment decision will fall within current established practice. Eligible participants will be aged ≥18 years with severe, active GPA or MPA as determined by the investigator at the time of commencing avacopan or non-avacopan standard-of-care induction therapy. Patients will be followed for up to 7 years. This study has been enrolling patients since September 11, 2023. The final report is expected in the second half of 2031; interim reports are planned every 24 months after the first patient first visit. The AvacoStar study will be the largest European prospective real-world evidence comparative study conducted to date that evaluates the long-term safety of avacopan in severe, active GPA or MPA. This study is expected to yield important insights on the use of avacopan in severe, active GPA or MPA in a real-world setting.
Patients with systemic sclerosis (SSc) or morphea increasingly inquire about cosmetic procedures, as these conditions often result in disfiguring cutaneous manifestations such as microstomia, thin lips, sclerotic plaques or skin atrophy. Traditionally, rheumatologists prioritize immunosuppression and disease control but often fail to address aesthetic concerns. Among available interventions, hyaluronic acid (HA) fillers offer a minimally invasive approach, yet there is not enough information regarding efficacy and safety in this population. This systematic review aims to discuss current evidence regarding the use of HA fillers in patients with SSc or morphea. A literature search was conducted in PubMed, CENTRAL and clinicaltrials.gov from inception until January 2025. Two independent reviewers examined the studies and extracted data. Data regarding the number of patients, disease type, HA filler particulars, technique, additional treatments, immunosuppression, patient reported or other outcomes and follow-up were extracted. Nineteen studies met the inclusion criteria, consisting of 8 case reports, 7 case series and 4 prospective interventional studies (including one controlled study). Most common areas were the forehead, chin and perioral region. Some studies used adjuvant treatments such as Botox or Platelet-Rich Plasma (PRP). HA fillers were consistently associated with patient satisfaction and good cosmetic results. In patients with SSc, mouth opening improved and microstomia was alleviated. However, one controlled study reported no significant improvement in mouth opening compared to autologous fat grafting. Inactive morphea lesions appeared to be more responsive compared to inflammatory ones. Adverse events were mild with no reports of disease flare. HA fillers appear to be a safe and minimally invasive procedure for addressing both functional and aesthetic concerns of patients with SSc or morphea. Further randomized controlled trials are needed to clarify indications, durability and long-term safety.
VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently defined adult-onset autoinflammatory disorder caused by somatic mutations in the UBA1 gene. This narrative review synthesizes current insights into its epidemiology, pathogenesis, clinical spectrum, diagnostic strategies, and emerging therapeutic approaches, emphasizing data from the French and AIDA registries. We conducted a comprehensive literature search of PubMed, Scopus, and Web of Science databases up to 15 June 2025, using keywords including "VEXAS", "UBA1", "autoinflammatory syndromes", "myelodysplastic syndromes", and "JAK inhibitors". Studies reporting epidemiological data, clinical phenotypes, pathophysiological mechanisms, diagnostic pathways, or therapeutic outcomes were included. Case reports and non-English articles without abstracts were excluded. Since its identification in 2020, more than 300 VEXAS cases have been reported, primarily affecting older males. The clinical phenotypes include relapsing polychondritis, cytopenias, neutrophilic dermatoses, and frequent overlap with myelodysplastic syndromes. Diagnosis is confirmed by detecting somatic mutation in UBA1, most commonly at codon 41. Treatment responses are heterogeneous: corticosteroids are often used initially,but longer-lasting benefits are observed with JAK inhibitors, hypomethylating agents, or hematopoietic stem-cell transplantation. However, therapeutic decision-making remains empirical mainly due to the lack of controlled trials. VEXAS syndrome exemplifies the interface between clonal hematopoiesis and systemic inflammation. Early molecular diagnosis and genotype-informed treatment strategies are critical. Collaborative, prospective studies are urgently needed to refine diagnostic algorithms and optimize therapeutic outcomes.
BACKGROUND Sarcoidosis, a rare multisystem disease characterized by non-caseating granulomas, affects the gastrointestinal system in less than 1% of cases, mainly involving the gastric antrum. Most cases are asymptomatic and are discovered incidentally during endoscopy; fewer than 1% of patients present with symptoms such as gastroesophageal reflux disease (GERD), dyspepsia, or bleeding. The relationship between gastric sarcoidosis and GERD is not well understood, posing diagnostic and treatment challenges that are not fully addressed in the current literature. This report describes a case of incidentally discovered gastric sarcoidosis presenting as GERD that improved without immunosuppressive therapy. To facilitate management, we propose an algorithm for managing GERD symptoms in the context of gastric sarcoidosis. CASE REPORT A 48-year-old man with pulmonary sarcoidosis - in remission for 7 years - presented for endoscopic evaluation of GERD and nonspecific chest pain. Vital signs, physical examination, and routine laboratory results, including a cardiac workup, were unremarkable. Upper gastrointestinal endoscopy revealed grade A esophagitis and a 6-mm antral papule. Histopathologic examination of the biopsy specimen revealed non-caseating granulomas consistent with gastric sarcoidosis. The patient's symptoms improved with escalated proton pump inhibitor therapy; immunosuppression was not required. Rheumatology consultation recommended no additional treatment, given his clinically quiescent disease and improvement in GERD symptoms. CONCLUSIONS This case highlights the diagnostic uncertainty of GERD in the presence of gastric sarcoidosis and emphasizes the importance of personalized, multidisciplinary management.
Generalized morphea, a rare and severe variant of localized scleroderma, is marked by extensive skin involvement with multiple hardened plaques and hyperpigmentation. The pathogenesis of generalized morphea is still unclear, and there is no established therapy. The aim of this article is to present a novel treatment approach for generalized morphea while also conducting a systematic review of previously published cases to summarize and analyze the clinical features and current effective treatment strategies for this condition. We herein describe the case of a 61-year-old male patient with generalized morphea successfully treated with tripterygium glycosides (TG) and hydroxychloroquine (HCQ). The systematic review analyzed a total of 77 patients with generalized morphea, comprising 76 previously reported cases (57 adults and 19 children) and one adult patient from our article. Compared with the adult group, the pediatric group demonstrated significantly higher rates of abnormal antinuclear antibodies (78.9%, p=0.002) and a greater proportion of severe cases (89.5%, p=0.001). Furthermore, systemic glucocorticoid is currently the most frequently used and effective treatment (p=0.016). In the treatment of generalized morphea, the combination of HCQ and TG may represent a potentially useful therapeutic option worthy of further investigation.
Although brain and heart conditions share overlapping risk factors and commonly co-occur, current cardiac and neurologic clinical guidelines are typically produced within specialty silos. The objective of this guideline from a Canadian Cardiovascular Harmonized National Guideline Endeavour (C-CHANGE) panel is to expand on current cardiovascular guidelines to include evidence from the neurologic and mental health literature, with specific recommendations for providers managing comorbid brain and heart conditions. The guideline development panel comprised an Executive Steering Committee; 10 expert subgroups to develop research questions and draft recommendations for specific brain-heart conditions; an Evidence Review Team to ensure the rigour and consistent application of the methodology; and an Implementation Committee to facilitate uptake of the recommendations by clinicians and into electronic medical records. The McMaster Evidence Review and Synthesis Team supported the literature searches and critical appraisal. A panel of people with lived experience of specific conditions and caregivers provided input on patient values and perspectives throughout the guideline development process. Our consensus process followed the Appraisal of Guidelines for Research and Evaluation II framework. We used an established evidence appraisal approach to determine the level of evidence and strength of each recommendation, and adhered to the Guidelines International Network's principles for managing competing interests. We developed 11 recommendations for the management of joint brain and heart diseases. Key recommendations include screening for cognitive decline in atrial fibrillation and depression in coronary artery disease; treatment of depression in coronary artery disease, cognitive impairment in hypertension, and dyslipidemia in stroke; and vaccination to prevent stroke, myocardial infarction, and dementia. We also recommend shared decision-making, including the use of evidence-based decision aids, to support patients with heart-brain diseases. We sought to produce an implementable and actionable guideline for patients with brain and heart comorbidity. It is primarily targeted to primary care providers, but also relevant to help address and individualize subspeciality care and for interprofessional teams caring for patients with joint brain and heart diseases.