Para médicos · reumatologia
Resumos de artigos, podcasts e newsletters sobre Arterite de Células Gigantes, para atualização médica.
A newsletter destaca a revisão do índice de dano (SDI) no Lúpus Eritematoso Sistêmico, que busca maior precisão clínica ao remover itens de atividade inflamatória e incluir critérios de gravidade. Além disso, apresenta novos guidelines da EULAR para vasculites e polimialgia reumática, e discute evidências recentes sobre terapias biológicas e inibidores de fosfodiesterase em doenças autoimunes.
Objectives To describe imaging features of 18F-FDG positron emission tomography/computed tomography (PET/CT) of polymyalgia rheumatica (PMR) and evaluate their ability to distinguish PMR in elderly patients presenting with myalgia. Methods Ninety-three elderly patients (male 29, female 64, age 66.3 ± 8.7 years) with myalgia underwent 18F-FDG PET/CT for suspected PMR. Based on final clinical diagnosis, clinical data of PMR patients and other subjects were compared. Diagnostic efficacy of 2012 EULAR/ACR classification criteria was assessed. PET/CT findings were reviewed to define PMR-related metabolic patterns. An imaging score algorithm was developed to discriminate PMR from rheumatoid arthritis (RA), the most common alternative diagnosis. The score algorithm’s diagnostic performance was validated in the cohort. Results Based on final clinical diagnosis, 44 (47.3%) patients were PMR and 49 (52.7%) were other rheumatic disorders. PMR often presented with fever and hip pain and was absent of other joint involvement. The EULAR/ACR classification criteria reached a maximum accuracy of 55.3%. PET/CT consistently demonstrated PMR-related uptake in the interspinous bursae, pubic tendon entheses, and ischial tuberosity bursae; some patients showed giant-cell arteritis (GCA) through abnormal vascular uptake. An 8-item PET/CT score (1 point per criterion) of ≥ 4 distinguished PMR from RA, with 95.5% sensitivity, 85.2% specificity, and 91.5% accuracy. For the entire cohort, a score ≥ 5 achieved 84.1% sensitivity, 94.8% specificity, and 88.2% accuracy. Conclusion 18F-FDG PET/CT outperformed the EULAR/ACR criteria for early and accurate diagnosis of PMR in elderly individuals with myalgia. Key Points • FDG PET/CT assists in the diagnosis of PMR. • FDG PET/CT achieves higher diagnostic accuracy for PMR than the 2012 EULAR/ACR criteria. • Eight-item PET/CT score distinguishes PMR from RA with 91.5 % accuracy in elderly myalgia.
A newsletter apresenta os resultados do estudo REPLENISH, que valida o secuquinumabe como uma nova opção biológica para a polimialgia reumática, dobrando as taxas de remissão sustentada. São discutidos também novos insights do EULAR 2026, incluindo a distinção entre entesófitos inflamatórios e mecânicos, o valor prognóstico do fator reumatoide na GEPA e o potencial das fibras dietéticas em melhorar a resposta clínica ao metotrexato na artrite reumatoide.
Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely related chronic inflammatory conditions. Glucocorticoids remain the cornerstone of treatment for both conditions, as they rapidly control inflammation and also reduce the risk of ischaemic complications in GCA. However, glucocorticoid therapy is often prolonged and associated with substantial treatment-related morbidity. In addition, many patients experience relapses during glucocorticoid maintenance therapy and can accrue vascular damage. Advances in understanding the immunopathology of GCA and PMR have led to the development of targeted therapies, particularly agents inhibiting the IL-6 pathway and, more recently, Janus kinase (JAK) signalling. IL-6 receptor inhibitors reduce the risk of disease relapse and allow for reduction in glucocorticoid use in both GCA and PMR, and JAK inhibition enables glucocorticoid sparing and lowers the risk of relapse in GCA. Optimal management of GCA and PMR requires close monitoring, careful assessment of disease activity and treatment-related toxicity, as well as individualized therapeutic strategies. Ongoing research continues to refine treatment algorithms and could help to define therapeutic targets across GCA and PMR. Emerging therapeutic options and evolving treatment algorithms reflect the dynamic and patient-centred nature of advancements in GCA and PMR management.
OBJECTIVE: Imaging biomarkers for disease activity are urgently needed in giant cell arteritis (GCA). Whether 18F-fluorodeoxyglucose positron emission tomography (PET) can be used to follow disease activity in those with large vessel vasculitis (LV-GCA) is still unclear. We aimed to determine how often large vessel inflammation improves or becomes radiographically-quiescent on follow up PET in patients with LV-GCA who clinically improve on treatment. METHODS: MEDLINE, EMBASE, CINAHL, Scopus, and Cochrane Library were searched from inception through February 29, 2024. Studies describing patients with active LV-GCA on baseline PET, with a follow up PET scan repeated after escalating immunosuppression, and an assessment of clinical disease activity were included. Meta-analysis of the pooled sensitivity of 1) improved PET for clinical improvement and, 2) normalized PET for clinical remission in treated GCA patients was performed, with subgroup analysis of tocilizumab (TCZ)-treated patients. RESULTS: Of 3131 unique references, 25 studies were included. The pooled sensitivity of improved vascular FDG uptake on follow up PET for clinical improvement of GCA was 0.95 (95% CI 0.82-1.00), and the pooled sensitivity of normalized vascular FDG uptake on follow up PET for clinical remission was 0.53 (95% CI 0.34-0.72). In TCZ-treated patients, the pooled sensitivity of improvement and normalization of follow up PET was 1.00 (95% CI 0.99-1.00) and 0.78 (95% CI 0.50-0.97), respectively. CONCLUSION: Follow up PET images improved in most (95%) patients with LV-GCA who clinically improved on treatment but LVV became radiographically quiescent in only 53%. Better responses were seen in those receiving TCZ.
A newsletter destaca que a hidroxicloroquina não previne a progressão para artrite reumatoide em pacientes anti-CCP positivos e que a plasmaférese deve ser reservada como terapia de resgate em miosites graves. Além disso, discute o benefício do AAS na redução de eventos isquêmicos na arterite de células gigantes, apesar do aumento do risco hemorrágico, e explora a relação entre tofacitinibe e microbiota na espondiloartrite.
A newsletter discute a necessidade de ajustar os pontos de corte dos índices CDAI e SDAI para a realidade brasileira, visando uma identificação mais precisa da remissão na artrite reumatoide e evitando o sobretratamento. Além disso, revisa as diretrizes de rastreio para doença pulmonar intersticial associada à AR e destaca o potencial condroprotetor da metformina em pacientes diabéticos com osteoartrite.
OBJECTIVES: Cough is an underrecognized and atypical manifestation of giant cell arteritis (GCA), which may lead to diagnostic delay. Literature on cough in GCA is limited and lacks comprehensive data on clinical relevance. The aim of this study was to assess the frequency of cough at diagnosis in GCA patients and to compare clinical characteristics between those with and without cough. METHOD: Consecutive patients diagnosed with GCA between 2000 and 2020 and followed for ≥ 12 months at the University Hospitals Leuven (Belgium) were included retrospectively. RESULTS: We included 398 GCA patients, of whom 72 (18%) reported cough. Patients with cough were slightly younger (69.8 vs 72.3 years, p = 0.019), more frequently had constitutional symptoms (94% vs 73%, p < 0.001), and less often had polymyalgia rheumatica (26% vs 50%, p < 0.001) or permanent visual loss (3% vs 19%, p < 0.001). They had higher C-reactive protein (86 vs 68 mg/L, p = 0.003) and erythrocyte sedimentation rate (80 vs 67 mm/h, p = 0.036), and lower haemoglobin (11.3 vs 11.8 g/dL, p = 0.008) and albumin (36.7 vs 38.4 g/L, p = 0.013). Positron emission tomography total vascular score (10 vs 5, p = 0.009) was higher in GCA patients with cough. Although time to first relapse was shorter (10 vs 13 months, p = 0.018), relapse probability [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.82-1.61, p = 0.420] and the probability of discontinuing glucocorticoids were similar (HR 1.10, 95% CI 0.80-1.50, p = 0.563). CONCLUSION: GCA patients with cough may represent a distinct phenotype associated with systemic inflammation and large-vessel involvement. Further prospective studies with standardized cough assessment are needed to clarify the role of
Giant cell arteritis (GCA) is a systemic vasculitis that predominantly affects mediumand large-sized arteries. Delayed diagnosis may result in irreversible blindness or stroke. Temporal artery biopsy (TAB), historically regarded as the diagnostic gold standard, has limited sensitivity (40-70%) due to the segmental distribution of inflammatory lesions and carries risks of procedural complications and diagnostic delay. This systematic review aims to:(1) compare the diagnostic accuracy of non-invasive imaging modalities with TAB;(2) assess the prognostic value of imaging findings; and(3) evaluate the implementation of imaging-first clinical pathways. In accordance with the PRISMA 2020 statement, PubMed and Embase,were searched for high-impact studies (n = 36) addressing diagnostic accuracy, guideline updates, and the effectiveness of the fast-track clinic (FTC) model. Colour Doppler ultrasound (CDUS) demonstrating the "halo sign" achieved a pooled sensitivity of 88-93%. Accordingly, the 2022 ACR/EULAR classification criteria assign CDUS findings diagnostic weight equivalent to a positive TAB. High-resolution MRI enables quantitative evaluation of cranial arterial wall thickening and contrast enhancement. 18F-FDG PET/CT is particularly useful for assessing systemic inflammatory burden and identifying large-vessel involvement associated with higher relapse risk, while CT angiography (CTA) delineates structural vascular damage. Implementation of FTC pathways reduces diagnostic latency to 24-72 hours and lowers the risk of permanent visual loss by 60-80%. Non-invasive, multimodal imaging has redefined the diagnostic paradigm of GCA. By enabling accurate diagnosis and risk stratification, it informs personalized management strategies. Future directions should emphasize standardized acquisition protocols and artificial intelligence-assisted analysis to reduce operator dependence and further enhance early detection.
Diabetes mellitus (DM) is characterized by persistent hyperglycemia due to impaired insulin secretion, action, or both. Glucocorticoid-induced DM (GIDM) is a clinically significant subtype, especially in rheumatology, where glucocorticoids (GCs) are widely used for the management of autoimmune rheumatic diseases (ARDs). GCs increase gluconeogenesis, reduce insulin sensitivity, impair β-cell function, and alter adipokines and hypothalamic signaling, promoting hyperglycemia. Oral GCs carry the greatest risk, though intra-articular and intramuscular injections can also cause dysglycemia. Risk factors include older age, higher body mass index (BMI) and central adiposity, hypertriglyceridemia, family history of DM, higher GC dose and treatment duration, and disease activity. In non-ARD populations, GIDM occurs in 15–52% of GC-treated individuals, while in ARDs, rates vary by disease. In Systemic lupus erythematosus, occurrence ranges from 10–26% and, beyond classic metabolic risk factors, higher disease activity and damage scores, higher GC doses, and mycophenolate mofetil are associated with increased risk, whereas hydroxychloroquine seems to be protective. In Rheumatoid arthritis, true incidence remains uncertain, though GC dose, especially > 10 mg/day, and prolonged duration correlate with increased risk. In Polymyalgia rheumatica and Giant cell arteritis, GIDM increases dose-dependently, with an occurrence of 6% and 13%, respectively. Evidence for other ARDs is limited. Management of GIDM should be guided by a multidisciplinary approach, aiming for a personalized therapeutic strategy. This review summarizes current knowledge on the mechanisms, epidemiology, and risk factors of GIDM in ARDs, aiming to raise awareness within the rheumatology community, highlight key gaps in the literature, and outline implications for future research.
Despite being the cornerstone of induction therapy in Giant Cell Arteritis (GCA), glucocorticoisz (GCs) often fail to achieve sustained disease control and are associated with substantial morbidity, while evidence supporting the broader use of intravenous methylprednisolone (MP) pulses beyond high-risk patients remains limited and conflicting. We aimed to evaluate the effectiveness and safety of MP as induction therapy in newly diagnosed GCA. Retrospective, observational, multicentre study of patients with newly diagnosed GCA according to the 2022 ACR/EULAR classification criteria, comparing induction treatment with either MP or oral GCs. The primary outcome was time to remission. The effect of MP on time to remission was estimated using inverse probability weighted regression adjustment (IPWRA). A total of 206 patients were included; 116 (56.3%) received MP. Patients in the MP group more frequently had ischemic symptoms at onset. Overall, 196 patients (95.1%) achieved remission with a median time of 8.6 weeks (p = 0.287). IPWRA analysis showed that MP was associated with a shorter time to remission (average treatment effect, ATE: −14.2 weeks; 95% CI − 20.5 to − 7.8, p < 0.001). In adjusted Weibull regression, MP was associated with a higher hazard of remission (HR 2.44; 95% CI 1.66–3.59, p < 0.001). Patients treated with MP had a significantly lower median cumulative prednisone dose (733 vs. 1,902 mg; p < 0.001) and lower average daily prednisone dose until remission (13.6 vs. 30 mg; p < 0.001). At 3 months, the MP group required lower daily and cumulative prednisone doses and had fewer cases of diabetes mellitus and osteoporosis. In this real-world multicentre cohort, MP during induction were associated with faster remission and significant glucocorticoid sparing without increased short-term toxicity. These findings
Arthritis &amp;Rheumatology, Volume 78, Issue 3, Page 774-777, March 2026.
Objective This study aims to characterize pathogenic somatic mutations in patients with autoinflammatory or autoimmune diseases lacking disease‐causing germline mutations, explore their contribution to disease pathogenesis and progression, and evaluate their implications for diagnosis and targeted therapy. Methods We performed a systematic analysis of somatic mutations in a selected panel of 185 immune‐related genes in 2,912 patients with autoinflammatory or autoimmune diseases, recruited from 41 medical centers across China, who were previously negative for germline mutations based on whole‐exome sequencing. Results We identified both previously reported and novel somatic mutations in genes such as UBA1 , KRAS , and NLRP3 . Pathogenic somatic mutations in TNFAIP3 were discovered first in patients with autoinflammatory diseases. The pathogenic somatic mutation detection rate was 1.35% in adults and 0.97% in children, emphasizing the importance of genetic diagnosis and novel gene discovery for somatic mutations. In addition, somatic mutations in Ras‐related genes were identified in seven patients, and 39 clonal hematopoiesis–associated mutations were identified in 36 adult patients. Moreover, myeloid cells harboring somatic mutations expanded during disease flare and reduced during remission. Disregarding the dynamic elevation of the variant allele fraction during disease progression led to therapeutic failure. Conclusion This study delineated the genetic landscape of pathogenic somatic mutations underlying autoinflammatory and autoimmune diseases, offering valuable insights for genetic diagnosis and targeted therapies.
Objective Large vessel‐vasculitis (LVV) accounts for up to 70% of patients with giant cell arteritis (GCA). Stenotic involvement in GCA‐LVV remains largely unknown. The purpose of this study was to assess the long‐term outcome and prognosis of GCA with stenotic LVV. Methods This was a retrospective multicenter study of 3,149 patients with GCA, including 198 (6.3%) with stenotic LVV. Hierarchical clustering on principal components was performed on baseline arterial localizations and logistic regression assessed factors associated with vascular complications. Results Stenotic LVV affected mostly the subclavian artery (63%), the carotid artery (58%), vertebral artery (37%), and axillary artery (33%), followed by the femoral artery (30%) and mesenteric arteries (13%). Stroke (31%) was the main complication, followed by limb ischemia (21%), myocardial infarction (4%), and mesenteric ischemia (2%). Cumulative incidence of vascular complications was 13.1% (95% confidence interval [CI] 8.9–18.3), 17.3% (95% CI 12.3–22.9), and 19.5% (95% CI 14.3–25.4), at 1, 5, and 10 years, respectively. Hierarchical clustering analysis identified three clusters among which cluster 1 (n = 123; 62%) included older patients with more arteritic anterior ischemic optic neuropathy ( P = 0.04), vertebral artery stenosis, and a higher mortality rate ( P < 0.044). In multivariate analysis, age at diagnosis (hazard ratio [HR] 1.06, 95% CI 1.03–1.10; P = 0.0004) and vertebral involvement (HR 1.87, 95% CI 1.03–3.40; P = 0.039) were significantly associated with higher risk of vascular complication. Conclusion Stenotic LVV accounts for less than 10% of GCA and is associated with poor vascular prognosis. image
Immune-mediated cochleovestibular dysfunction has gained recognition as an important yet frequently overlooked entity in recent decades. These disorders-ranging from isolated inner-ear syndromes to cochleovestibular manifestations of systemic autoimmune diseases-exhibit humoral or cellular immune attacks on inner-ear structures, commonly accompanied by microvascular injury and inflammatory cascades. Despite increasing awareness, the precise pathophysiological mechanisms remain incompletely understood for most conditions, and diagnostic and therapeutic approaches vary considerably. This narrative review summarizes current evidence on immune-mediated cochleovestibular disorders, dividing them into two main categories (1): primary Isolated disorders (delayed endolymphatic hydrops, bilateral vestibulopathy, and Ménière's disease with established or suspected autoimmune features) (2) cochleovestibular manifestations of rheumatologic diseases (systemic lupus erythematosus, multiple sclerosis, autoimmune thyroid disease, Behçet's disease, Vogt-Koyanagi-Harada disease, psoriasis, Cogan's syndrome, Susac syndrome, Sarcoidosis, Rheumatoid arthritis, Necrotizing vasculitides with polyangiitis and Giant cell arteritis). We examine their clinical features, proposed immune and microvascular mechanisms, diagnostic evaluation, and current management strategies, with particular emphasis on immunomodulatory and immunosuppressive therapies. Systemic corticosteroids at high doses are the primary treatment for most of these disorders, though the ideal duration, tapering protocols, and indications for steroid-sparing medications differ significantly across various syndromes. Evidence supporting many adjunctive therapies is limited or conflicting, underscoring the need for higher-quality clinical trials. Early recognition and prompt immunomodulatory treatment can often reverse or stabilize symptoms in immune-mediated cochleovestibular dysfunction. This review offers a clinically oriented synthesis of current evidence, elucidating the complex immunological underpinnings and the corresponding therapeutic landscape of these disorders. By integrating otologic and rheumatologic perspectives, we aim to heighten awareness, promote earlier diagnosis, and inform more effective treatment of patients presenting with vertigo, hearing loss, or imbalance suggestive of immune-mediated inner-ear pathology.
Antineutrophil cytoplasmic autoantibody-associated vasculitides can be classified by clinical phenotype or antineutrophil cytoplasmic autoantibody specificity, with overlapping yet distinct characteristics. Transcriptomic analyses of kidney biopsies from 2 French antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) cohorts revealed a pronounced type I interferon signature in microscopic polyangiitis (microscopic polyangiitis/myeloperoxidase-AAV) compared with granulomatosis with polyangiitis (granulomatosis with polyangiitis/proteinase 3-AAV). Among biopsies with high interferon scores, 66% were myeloperoxidase-AAV and 28% proteinase 3-AAV. The interferon score was associated with decreased kidney survival. These findings highlight AAV patient heterogeneity and support targeted treatment approaches.
Purpose of review The aim of this review is to describe the substantial advances that have been made in the past 2 years on new treatment options in eosinophilic granulomatosis with polyangiitis (EGPA). Recent findings The therapeutic scenario in EGPA has been recently broadened by the publication of the results from the multicenter, double-blind randomized MANDARA trial, which proved the noninferiority of benralizumab to another anti-interleukin-5 (IL-5) drug, mepolizumab, for the induction of remission in patients with EGPA. A few real-world studies have confirmed these results. Furthermore, the first randomized controlled trial exploring the efficacy of rituximab (anti-CD20) in induction of remission of EGPA was recently published. Targeting other molecular pathways did not always show adequate control of systemic manifestations of EGPA, with only limited evidence of effectiveness from small case series. Interestingly, cases of EGPA onset in severe asthma patients treated with monoclonal antibodies were described. Summary Biological drug therapy targeting IL-5 consolidated its role in the management of EGPA, becoming the cornerstone of the treatment of this rare disease. Future guidelines should consider these recent findings to improve the management of EPGA. Notably, while selective IL-5 targeting is highly effective for remission maintenance, its role in inducing remission in EGPA remains to be fully established. Rituximab was non-superior to standard therapy in induction of remission in patients with EGPA, demonstrating a similar rate of response. The role of other targeted therapies, albeit promising in some cases, remains a matter of debate.
This study aimed to develop and validate a risk stratification scale for unfavourable outcomes in adult patients with IgA vasculitis nephritis (IgAVN). The derivation cohort in this study was constructed using the existing prognosis data from adult IgAVN cohorts. We extracted the risk factors and their hazard ratios. Only statistically significant risk factors were included in our final risk stratification scale. Then this study validated the risk stratification scale in an external cohort of Chinese patients. The performance of the risk stratification scale was evaluated by the receiver operating characteristic (ROC), calibration, decision, and Kaplan-Meier curves. Ten cohorts involving 1,814 adult patients with IgAVN were included in this meta-analysis. Serum albumin (ALB), estimated glomerular filtration rate (eGFR), endocapillary hypercellularity (E1), and tubular atrophy/interstitial fibrosis (T1/2) were included in the risk stratification and scored according to their weightings (maximum score: 6.5). An external cohort comprising 133 patients was used to validate the risk stratification scale. The area under the curve (AUC) value of the scoring scale was 0.88 (95%CI: 0.78-0.99), with a sensitivity of 0.79 (95%CI: 0.49-0.95) and specificity of 0.89 (95%CI: 0.82-0.94), at a cut-off value of 3. The calibration, decision, and Kaplan-Meier curves further confirmed the robust performance of the risk stratification scale. In this study, we established a simple and practical tool to identify adult IgAVN patients at high risk of unfavourable outcomes. Reasonable use of the risk stratification scale can help make early clinical decisions and facilitate the development of precision medicine.
Systemic autoimmune and chronic inflammatory rheumatic diseases predominantly affect childbearing women. These women are at greater risk for pregnancy complications stemming from both the underlying disease and the treatments required to manage it. This cross-sectional study aimed to assess the prevalence of effective contraceptive use across a wide range of diseases including systemic lupus, systemic sclerosis, Sharp syndrome, Sjögren’s disease, rheumatoid arthritis, and spondyloarthritis. We conducted a questionnaire-based study targeting women aged 18–45 years with any of the aforementioned diseases. The data were collected from July 2023 to July 2024. A standardized self-report questionnaire, specifically developed for this study, was used to assess gynecological follow-up and reproductive health. Additional clinical data were extracted from patients’ electronic medical records. Descriptive statistics were used to analyze contraception use across different risk groups, including those on teratogenic treatments and those at increased maternal or fetal obstetric risk. 143 patients were included; among those not trying to conceive, 63% used effective contraception. This rate is lower than the 72% reported for the general population in France in 2016. Among previously pregnant patients, 33% experienced an unplanned pregnancy, highlighting the impact of contraceptive failure. There was no difference between patients on teratogenic treatments, those with increased maternal or fetal obstetric risk, and other patients. This study emphasizes the urgent need for improved education and gynecological management of young women with rheumatic diseases in France. Specific educational programs and enhanced gynecological follow-ups are necessary to address this critical gap. This study was registered with ClinicalTrials.gov (NCT05961267), first posted on the 24th of July, 2023, and in the European database (ID-RCB 2023-A01207-38).
Glucocorticoid therapy is prescribed for a variety of inflammatory conditions and is associated with severe adverse effects. A glucocorticoid withdrawal syndrome (GWS) may occur after prolonged glucocorticoid treatment-with or without biochemical glucocorticoid-induced adrenal insufficiency (GIAI). Previously, GWS was not considered an entity, probably due to the overlap between symptoms of GWS and GIAI. The Addison's disease-specific quality of life questionnaire (AddiQoL-30) is a validated tool for quantifying symptoms of adrenal insufficiency resembling GWS. In the present study, we test the hypothesis that patients with a low AddiQoL-30 score and/or low cortisol response to a short Synacthen test (SST), after cessation of prednisolone treatment, may benefit from low-dose hydrocortisone therapy without increasing the risk of metabolic and cardiovascular disease during prolonged cortisol exposure. REPLACE is a multi-centre, double-blinded, placebo-controlled randomised controlled trial in patients with polymyalgia rheumatica or giant cell arteritis after cessation of prednisolone treatment. Criteria for randomisation are an AddiQoL-30 score ≤85 and/or plasma cortisol response to SST, 30-min p-cortisol >100 and 85; and (2) patients with a SST-stimulated cortisol ≤100 nmol/L. The study is conducted in accordance with the Declaration of Helsinki, registered at the Clinical Trials Information System (CTIS: 2024-513822-53-00) and Clinicaltrials.gov (NCT05193396), and publications will be in accordance with the recommendations of the International Committee of Medical Journal Editors. The trial is monitored by local independent Good Clinical Practice units and overseen by the Danish Data Protection Agency (journal no. 21/27119), the Regional Committees on Health Research Ethics for Southern Denmark (project ID: S-20210076), the Danish Patient Safety Authority and the Danish Medicines Agency. NCT05193396.
In chronic kidney disease (CKD), anaemia develops and evolves as kidney dysfunction progresses. The treatment of anaemia is described in clinical practice guidelines (CPGs), which are designed to report the most relevant evidence for clinical practice in disease management. This study will analyse CPGs for transparency, methodological quality and quality of recommendations for their implementation over time, and also compare recommendations for the treatment of anaemia outlined in these documents. CPGs will be identified by conducting a systematic search of the data sources CINAHL, Embase, MEDLINE, Scielo, Scopus, ProQuest, Trip Database, Virtual Health Library, Web of Science, and guidelines on websites, published between January 2009 and December 2025. Three reviewers will, independently, evaluate the methodological quality of the guidelines using the Appraisal of Guidelines for REsearch and Evaluation II (AGREE-II) tool and the quality of recommendations using the AGREE - Recommendations Excellence tool. The treatment recommendations for anaemia in CKD will be summarised and compared. Results will be presented in tables and descriptive statistics will be compiled for all domains of the tools. This is a literature-based study and, therefore, no ethical approval will be required. Results of the study can be submitted for publication in high-impact, peer-reviewed scientific journals, and also presented at national and international conferences. CRD42024629656.
Abstract Stroke represents a major complication in Takayasu arteritis (TA). We aimed to determine clinical characteristics and neurological outcomes in TA patients with stroke compared to those without. We retrospectively analyzed 35 patients (27F/8 M) with documented stroke to 50 consecutive patients (47F/3 M) without stroke followed by the Istanbul University-Cerrahpasa Medical Faculty. Demographic data, clinical manifestations, arterial involvement patterns, treatments, and neurological outcomes were evaluated. Disability was assessed using the Expanded Disability Status Scale (EDSS), Barthel Index, and Modified Rankin Scale. Mean age at diagnosis among patients with stroke and non-stroke was similar (38.5 ± 10.7 vs. 35.6 ± 11.6 years). The mean age at stroke was 43.1 ± 10.3 years. Patients with stroke were more likely to be male (22.9% vs. 6.0%, p = 0.023). Strokes were predominantly ischemic (91.4%), affecting anterior circulation (82.8%) with left hemisphere predominance (72.4%). Internal carotid artery (ICA) involvement was significantly associated with stroke (right ICA: 51.4% vs 18.0%, p = 0.001; left ICA: 37.1% vs 18.0%, p = 0.047), while abdominal aorta involvement seemed to be protective (20.0% vs 42.0%, p = 0.028). Male gender (OR = 5.70, p = 0.038) and any ICA involvement (OR = 5.98, p = 0.004) were identified as independent predictors of stroke. Importantly, 40% experienced stroke as the initial TA manifestation. Among those developing stroke after TA diagnosis, 85.7% were already receiving immunosuppression and 47.6% antiplatelet therapy. Stroke patients demonstrated significant disability (mean EDSS: 3.63 ± 3.36 vs 0.02 ± 0.14, p < 0.001) and 11.4% mortality, median 5 years after stroke. Male patients and those with ICA involvement face the highest risk for stroke in TA. Long-term consequences are devastating with increased mortality, severe disability
Color duplex ultrasound (CDUS) is increasingly used to assess disease activity in large-vessel giant cell arteritis (LV-GCA), but its role in long-term monitoring and relapse prediction remains unclear. We aimed to evaluate dynamic changes in ultrasound findings during follow-up and their prognostic value for relapse. In this retrospective longitudinal study, 43 newly diagnosed LV-GCA patients from a fast-track clinic underwent serial color duplex ultrasound (CDUS) of temporal, axillary, subclavian, and carotid arteries during follow-up. Several semiquantitative ultrasound indices were assessed. The validated OMERACT GCA Ultrasonography Score (OGUS) included temporal and axillary arteries, while two extended indices, OGUS-10LV and OGUS-12LV, were specifically developed for this study to include subclavian and carotid arteries, respectively. Halo count indices (HC8, HC10, HC12) represented the number of arteries showing a halo sign. Patients were stratified by relapse status, and the predictive value of early ultrasound changes was tested using receiver operating characteristic (ROC) analysis. Relapse occurred in 26 of 43 patients (60.5%), within 24 months (mean 10.2 ± 5.7). Non-relapsing patients showed progressive OGUS indices reductions, with differences at 9 months for OGUS and 6 months for OGUS-10LV/12LV. Values < 1 from month 6 were consistently observed only in non-relapsing patients. HC normalization (no halo in any arteries) occurred earlier in non-relapsing patients (HC8: 18 vs. 24 months; HC10: 18 vs. 30; HC12: 36 vs. not reached). ROC analysis identified ΔOGUS-12LV ≤ 0.07 at 6 months as the optimal cutoff for predicting relapse at 12 months (AUC 0.944). OGUS and its extended variants demonstrate sensitivity to change and prognostic value in LV-GCA. Early dynamic changes predict relapse, while delayed HC normalization characterizes relapsing patients. These findings support imaging remission as a meaningful endpoint and CDUS
Abstract Objectives Rituximab (RTX) is a standard maintenance therapy for ANCA-associated vasculitis. Its efficacy in Japan remains unclear, where microscopic polyangiitis (MPA) predominates and clinical characteristics differ from Western-dominated RCT populations. Methods Japanese patients with MPA or granulomatosis with polyangiitis (GPA) enrolled in a nationwide registry were included. Exposure was RTX use during maintenance therapy. The primary endpoint was major relapse-free survival at 104 weeks. The secondary endpoint was any relapse-free survival (major or minor) at 104 weeks. Baseline differences were adjusted using inverse probability of treatment weighting (IPTW) based on key demographic and disease-related covariates. Results A total of 389 patients were analyzed, with 85 in the RTX group. The RTX group included a higher proportion of GPA cases (37/85 vs. 74/304), resulting in baseline imbalance. After IPTW, no major relapses were observed in the RTX group, whereas the major relapse-free survival at 104 weeks was 94.8% in the non-RTX group. The RTX group showed significantly higher any relapse-free survival at 104 weeks (95.4% vs. 83.3%; HR for any relapse, 0.27; 95% CI, 0.09–0.74; p = 0.02). Conclusions Our findings suggest that RTX may be an effective option for remission maintenance in Japanese patients with MPA or GPA.
Objective Ear, nose and throat (ENT) manifestations are common in ANCA‐associated vasculitis (AAV). There is unmet need for drugs to target these manifestations. Granuloma formation is characteristic of proteinase 3 (PR3)‐AAV. In a zebrafish model, niclosamide inhibits PR3‐induced granuloma formation. We hypothesised that intranasal niclosamide would reduce AAV‐associated ENT symptoms. Methods PROTECT‐V was a randomised, double‐blind, placebo‐controlled platform trial evaluating pre‐exposure prophylaxis agents against COVID‐19 infection. This sub‐analysis includes patients from a single centre, with AAV, enrolled into the intranasal niclosamide arm. Clinical data were retrospectively collected for nine months before, during, and nine months after treatment. Researchers were blinded to treatment allocation. Results Of thirty‐two (14 niclosamide; 18 placebo) patients, 11 (34%) were female; median age was 69 years (IQR 59‐75). Median prior AAV disease duration was 5.4 years (IQR 1.9‐13.1); 19 (59%) had active disease in the year prior to treatment. Median treatment exposure was 200 days (IQR 109‐251). During treatment, ENT symptoms were identified in 1/14 (7%) of the niclosamide group compared with 7/18 (39%) of the placebo group (p = 0.04). No significant difference between groups was found in the nine months before or after treatment. Among PR3‐ANCA‐positive patients, 0/10 in the niclosamide group compared to 5/9 (56%) in the placebo group had ENT symptoms during treatment. Conclusion These data are a signal of potential clinical effect on ENT manifestations in AAV. They support a role for the IL6/STAT3 pathway in AAV; intranasal niclosamide or other drug candidates in this pathway warrant further evaluation.
Aortitis associated with giant cell arteritis (GCA) is a severe manifestation, potentially leading to aneurysms and aortic dissection. Tocilizumab (TCZ) has demonstrated efficacy in the treatment of GCA, both intravenously or subcutaneously administered. However, pivotal studies did not specifically evaluate aortic involvement, and no comparison of intravenous (IV) versus subcutaneous (SC) TCZ has been performed in patients with GCA-related aortitis. The objective of this study was to compare the effectiveness of TCZ according to the administration route in patients with GCA-associated aortitis under clinical practice conditions. This was a multicenter observational study including 196 patients diagnosed with GCA-associated aortitis by imaging and treated with TCZ. Patients were grouped by administration route: IV or SC. GCA was diagnosed following the 1990 American College of Rheumatology criteria, temporal artery biopsy, and/or vascular imaging. Aortitis was identified using 18F-fluorodeoxyglucose positron emission tomography/computed tomography scan. Main outcomes included EULAR remission, clinical and imaging remission, absence of systemic inflammation, and glucocorticoid-sparing effect. Of 196 patients (148 women; mean age 69.8 ± SD 9.4 years), 110 received IV TCZ and 86 SC TCZ. Baseline clinical characteristics and markers of inflammation were comparable between groups. The glucocorticoid-sparing effect was similar. At 24-month follow-up, EULAR-defined remission was significantly more frequent in the SC group (83.3% vs 80.6%; P < 0.05). However, rates of imaging remission and absence of systemic inflammation were comparable between treatment arms. In this real-world cohort of GCA-associated aortitis, SC TCZ showed slightly greater effectiveness than IV TCZ in achieving EULAR-defined remission, whereas no significant differences were observed between both routes regarding imaging remission.
FDG-PET/CT offers high diagnostic accuracy in research settings for GCA, a systemic medium-large vessel vasculitis (M-LVV). We aimed to analyse its diagnostic performance in a real-world clinical setting. We audited all patients investigated with FDG-PET/CT for suspected new onset GCA between July 2019 and March 2022, at a single tertiary institution in Australia. Data was collected from patient and physician questionnaires, and scan reports describing FDG activity in cranial, supra-aortic, aortic and infra-aortic vascular territories, and the overall interpretation of the scan. The gold standard comparator in analysis was the unblinded treating physician's clinical diagnosis at a minimum of 6 months after the scan. One hundred thirty-five patients had an FDG-PET/CT as part of routine care in the investigation of suspected GCA. Forty-four (32.6%) patients had a clinical diagnosis of M-LVV. Thirty-five (26%) scans were reported as positive, 27 (20%) equivocal and 73 (54%) negative for active M-LVV. Diagnostic performance of FDG-PET/CT was dependent on the treatment of equivocal scans in binary analysis, with sensitivity ranging from 77.3 to 90.9% and specificity ranging from 75.8 to 98.9%. In cases with a clinical diagnosis of M-LVV, the supra-aortic territory was metabolically active in 31 (70.5%) and three had metabolic activity isolated to either the cranial or aortic regions. Combined cranial and large vessel FDG-PET/CT shows good diagnostic performance for GCA in a real-world setting. The supra-aortic territory was most commonly active in patients with M-LVV, yet assessment of all territories was required to maximise scan performance. Key Points • FDG-PET/CT has good diagnostic performance for GCA in the real-world setting. • Assessment of both cranial and large vessels is necessary to maximise FDG-PET/CT performance. • Equivocal FDG-PET/CT scans (20% of cases) can
To explore how appropriate different intervals between monitoring blood tests are considered in relation to the risk of clinically significant adverse drug reactions in adults prescribed conventional synthetic DMARDs (csDMARDs) for ≥1 year for systemic autoimmune rheumatic diseases (SARD). A RAND/UCLA Appropriateness Method consensus study was undertaken. Members of the BSR csDMARD guideline working group who manage adults with SARD participated. Experts rated the extent to which intervals between blood tests were appropriate using Likert-type scales with responses from 1 (totally inappropriate) to 9 (totally appropriate) for nine scenarios with 5-year predicted risk of discontinuing treatment due to abnormal monitoring blood tests from 5% to 25%. Median score and the number that voted 1-3 (inappropriate), 4-6 (unsure) and 7-9 (appropriate) were calculated for every interval in each scenario. Scenarios for which agreement could not be reached in the first round were recirculated, enclosing individual round 1 response and the panel median score. Consensus that an interval was appropriate for a scenario was reached where the median panel score was ≥7 and up to six experts rated 10% over 5 years, respectively. A threshold to aid risk-stratified monitoring during established csDMARD treatment was agreed for adults with SARD.
Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a small vessel vasculitis characterized by eosinophilia, asthma, and ear, nose, throat (ENT) involvement. Although glucocorticoids (GCs) are effective in controlling symptoms, relapses and GC dependence are common. The aim of this study was to develop predictive models for vasculitis relapse and GC‐dependent asthma and/or ENT symptoms. Methods This multicenter European retrospective cohort study included EGPA patients fulfilling the 2022 ACR/EULAR criteria. Using the PMSAMPSIZE algorithm, we developed two multivariable prediction models: one for vasculitis relapse and another for GC‐dependent asthma and/or ENT symptoms at 2 years. Internal validation was performed using bootstrapping. Results A total of 809 patients were followed for a median of 72 months (interquartile range, IQR 37‐115). Vasculitis relapse occurred in 228 patients with a 12‐year cumulative incidence of 41.2% (95% CI 36.3‐46.8). GC‐dependent asthma and/or ENT symptoms were observed in 66.4% at 2 years. Predictors of vasculitis relapse included age (nonlinear), GC‐dependent asthma before EGPA diagnosis (hazard ratio, HR 1.57), arthralgia (HR 1.27), myocarditis (HR 1.74), peripheral neuropathy (HR 1.39), MPO‐ANCA (HR 1.56), and baseline eosinophil count (nonlinear). Predictors of GC‐dependent asthma and/or ENT symptoms included older age (odds ratio, OR 0.98 per year), GC‐dependent asthma at diagnosis (OR 1.50), chronic sinusitis (OR 1.78), and baseline eosinophil count (OR 0.70 per 10 9 /L). Conclusion Using a large EGPA cohort, we developed predictive models for vasculitis relapse and GC‐dependent asthma and/or ENT symptoms. These tools may help guide treatment decisions. Prospective external validation in the current therapeutic era is warranted.
To assess the performance of the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA) in a multicenter cohort in Eastern China and compare it against the 1990 ACR and 2017 mepolizumab in relapsing or refractory EGPA (MIRRA) criteria. EGPA patients diagnosed between January 2018 and March 2025 were included in the study, and the diagnosis by "an expert panel" was used as the gold standard. The sensitivity, specificity, positive/negative predictive value (PPV, NPV), accuracy and receiver operating characteristic (ROC) curves of three sets of classification criteria (1990 ACR, 2017 MIRRA and 2022 ACR/EULAR) were evaluated. A total of 96 EGPA patients and 163 controls including 91 cases of other types of vasculitis and 72 cases of eosinophilic disorders were enrolled. 2022 ACR/EULAR classification criteria had the highest sensitivity of 87.5% and accuracy of 94.2% compared with 1990 ACR and 2017 MIRRA criteria. However, the specificity (98.2%) was slightly lower than that of the 1990 ACR and 2017 MIRRA criteria in the entire control. Thirty-five patients (36.5%) fulfilled all three criteria. The most sensitive item was eosinophilia (eosinophil ratio > 10% or count ≥ 1 × 109/L), with a sensitivity of 90.6%, followed by eosinophil ratio > 10% (89.6%) and eosinophil count ≥ 1 × 109/L (82.3%). The most specific item was vascular wall eosinophils (98.6%). The 2022 ACR/EULAR classification criteria demonstrated significant improvement in sensitivity and accuracy while maintaining a relatively high level of specificity. It is noticing that these criteria should not be used for the diagnosis of EGPA. Key Points • 2022 ACR/EULAR EGPA classification criteria were validated in a cohort of China. • 2022 ACR/EULAR criteria had higher sensitivity and accuracy compared to 1990 ACR criteria and 2017
Guselkumab, a monoclonal antibody, selectively targets the p19 subunit of interleukin-23. This randomised, double-blind, placebo-controlled, phase 2 study evaluated guselkumab vs placebo for the treatment of giant cell arteritis (GCA). Patients ≥50 years of age with new-onset or relapsing GCA were randomised 2:1 to guselkumab or placebo. Both arms received background glucocorticoid (GC) therapy, with a protocol-defined taper through week 26. The primary endpoint was the proportion of patients achieving GC-free remission at week 28. Thirty-five patients were randomised to receive guselkumab and 18 to receive placebo. All patients were White, 70% were female, and the mean age was 71.5 years; 60% had new-onset and 40% had relapsing GCA. At week 28, 40% (14/35) and 33% (6/18) of patients in the guselkumab and placebo groups, respectively, achieved GC-free remission (P = .64), whereas 31% (11/35) and 39% (7/18) had experienced a GCA flare or discontinued due to worsening GCA. Median time to first GCA flare through week 28 was not estimable (NE) in the guselkumab group (90% CI: 27.7-NE) and 29.7 weeks (90% CI: 20.1-NE) in the placebo group (P = .64). Through week 60, 97% (34/35) and 94% (17/18) of patients in the guselkumab and placebo groups, respectively, had adverse events (AEs); the most common AEs, aside from worsening of GCA (49% and 56%, respectively), were COVID-19 infection (23% and 28%) and headache (17% and 39%). The study's primary endpoint (GC-free remission) was not met; results do not support the use of guselkumab in the treatment of GCA.
Abstract Objectives To examine contemporary trends in mortality due to granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in Europe. Methods We utilised publicly available data from Eurostat on deaths recorded with GPA or MPA as the underlying cause of death for the period 2011–2021. Crude and standardised mortality rates (SMRs) were calculated for each country and linear regression used to determine changes in mortality rates over time. Crude mortality rate was also stratified by age and sex. To investigate the association between geography and mortality rate, the SMR for each country was displayed on a choropleth map and plotted against the country’s latitude. Results Our analysis of 29 European countries showed a stable mortality rate due to GPA and MPA between 2011–2021, but rising age at death median age-band 70–74 at the start and 75–79 at the end of the study period. There were differences between countries with the highest mortality rate in Denmark (SMR 31.03 per 10 million) and the lowest in Romania (SMR 0.77 per 10 million). Mortality rates were higher in adults aged over 80 years and there were more deaths in men compared with women. A latitudinal gradient in SMR was seen in GPA but not MPA, with the highest mortality rates in Scandinavia. Conclusion Despite major advances in disease management, our results show that deaths due to GPA and MPA were stable over the last decade, indicating an ongoing need to improve the treatment of these diseases.
Giant cell arteritis (GCA) is a chronic inflammatory disease that primarily affects medium and large arteries, predominantly in individuals over 50 years of age. Delayed diagnosis and treatment can result in severe complications, including irreversible vision loss. Conventional diagnostic pathways, often involving temporal artery biopsy, can lead to significant delays. Fast-track clinics (FTC) have been developed to expedite diagnosis and treatment, potentially improving patient outcomes. This meta-analysis aimed to compare the effectiveness of FTC and conventional practice (CP) in managing GCA. A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Relevant studies that compared FTC and CP in GCA management were retrieved from the MEDLINE, Cochrane, and Embase databases. Inclusion criteria required studies to report at least one of the following outcomes: visual disturbances, permanent sight loss, biopsy rates, or median days to diagnosis. The QUADAS-2 tool was used to assess the study quality and bias risk. Statistical analyses included pooled odds ratios (OR) with 95% confidence intervals (CI), heterogeneity assessment using the I2 statistic, and a random-effects model to account for study variability. Funnel plots were used to assess the publication bias. Three studies included 348 patients (173 in the FTC group and 175 in the CP group). FTC implementation was linked to decreased permanent sight loss (8.09% vs. 24.57%, OR: 0.31; p<0.001) and visual disturbances (20.23% vs. 32.57%, OR: 0.58; p=0.04), and use of temporal artery biopsy was lower in the FTC group (47.40% vs. 65.14%, OR: 0.19; p=0.49). The median number of days to diagnosis was slightly lower in the FTC group (57.6 vs. 58.3 d), although the difference was not statistically significant (OR: 0.96; p=0.83). Fast-track clinics
Abstract Objectives To clarify the clinical characteristics of patients with ocular involvement in giant cell arteritis (GCA). Methods This was an observational, single-centre, retrospective study of patients with GCA treated at Juntendo University Hospital between January 2012 and July 2023. The study involved 71 patients, including 21 with ocular involvement: 10 had fundus findings such as anterior ischemic optic neuropathy or central retinal artery occlusion (6 with permanent vision loss), and 11 without fundus findings. The demographic and clinical features of GCA were compared between patients with and without ocular involvement. Results The temporal artery was found to be affected more frequently in cases with ocular involvement than in those without on positron emission tomography/computed tomography (P=0.013) and vascular ultrasound (P=0.02). The average number of signs and symptoms observed before diagnosis was higher in patients with ocular involvement than in those without (P<0.001). The period from the appearance of ocular involvement to therapy initiation was shorter in patients with fundus findings than in those without (8.2 vs. 73.8 days; P=0.032). Conclusions Early imaging and early consultation with an ophthalmologist are important, as ocular involvement with fundus findings tended to occur earlier in GCA patients than without fundus findings.
Polyarteritis Nodosa is a rare necrotizing vasculitis with a broad and variable clinical presentation, driven by its ability to affect multiple organs and systems. This heterogeneity influences disease severity, relapse risk, and mortality, highlighting the prognostic importance of its diverse manifestations. This systematic review and meta-analysis synthesize the available evidence to define the clinical profile of Polyarteritis Nodosa and highlight key prognostic factors. A systematic search of electronic databases was conducted to identify studies reporting clinical manifestations and outcomes of patients diagnosed with Polyarteritis Nodosa. Pooled prevalence summary estimates were calculated using R software, including subgroup analyses by age group. Case Fatality Rate was calculated to determine the clinical severity of the manifestations. Across adult and pediatric groups, the most common manifestations were fever (~ 52%), myalgia (~ 53%), and cutaneous involvement (~ 56%). Age significantly moderated the prevalence of fever, arthralgia, hypertension, and peripheral neuropathy. Several symptoms were frequently observed among patients who experienced relapse, particularly cutaneous involvement (~ 66%) and myalgia (~ 64%). While cardiac involvement was associated with higher case fatality, gastrointestinal manifestations accounted for a greater proportion of reported deaths overall. Total mortality was approximately 13%, relapse occurred in about 27% of patients, while roughly 65% of patients achieved remission. This systematic review with meta-analysis provides crucial information to clinical physicians, regarding the clinical profile and the prognostic factors of Polyarteritis Nodosa. Thus, these insights could guide management strategies and increase the survival and remission rate of these patients. PROSPERO: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251249274 .
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a monogenic disease of adulthood characterised by treatment-refractory systemic inflammation and progressive bone marrow failure. VEXAS syndrome is caused by acquired mutations in the UBA1 gene that are restricted to haematopoietic cells. Men aged 50 years or older are particularly susceptible to VEXAS syndrome, with prevalence estimates of approximately one in 4000 men. Perturbation of UBA1, the master enzyme of cellular ubiquitination, promotes myeloid-driven inflammation that is difficult to control with medications other than glucocorticoids. Cytokine-directed therapies (ie, IL-6 and JAK inhibitors) might temporise symptoms and allow glucocorticoid reduction. Hypomethylating agents (ie, azacytidine) can induce clinical and molecular remission in some patients, but are associated with substantial toxicities. Haematopoietic cell transplant might be effective treatment in patients who are suitable candidates. The discovery of VEXAS syndrome highlights the potential role of somatic mutations in complex inflammatory diseases.
Vasculitis often poses a significant burden on individuals, their families and the health care system. Understanding its epidemiology can aid in facilitating timely interventions. We present a province-wide population study comparing the 1) incidence of vasculitis amongst farmers, rural-non farmers and urban residents, 2) the use of health services and 3) all-cause mortality rates across the three cohorts. The groups were randomly selected on the basis of provincial health data. Criteria for ascertaining vasculitis cases included either one hospital admission, two physician visits within a 2-year interval, or two ambulatory care visits within 2 years related to the vasculitis diagnosis. Descriptive statistics were used to compare the incidence rates. A total sample size of 302,089, with 5437 vasculitis cases. Farmers had the highest incidence of all types of vasculitis (109.8/100,000 person-years (PY)), followed by rural non-farmers (93.1/100,000 PY) and urbanites (71.7/100,000 PY). Age at diagnosis was higher among farmers (66.2 years) compared to rural non-farmers (64.5 years) and urbanites (63.9 years). Polymyalgia rheumatica (PMR) accounted for 47% of cases, followed by Arteritis Unspecified (15%) and small-vessel vasculitis (14%). Within the farming population, a higher percentage of males had positive cases of vasculitis compared to other populations. Rural non-farmer population had the highest use of health care services and unadjusted non-injury mortality rate (31.8/100,000 PY), followed by rural farmers (25.4/100,000 PY) and urban residents (23.8/100,000 PY). Our province-wide study revealed that farmers face the highest incidence rates of vasculitis as well as the second highest burden of disease in terms of healthcare service needs and mortality. Key PointsAQ • There is a notable variation in the incidence rates of vasculitis among farmers, rural and urban residents with the farming population showing the highest incidence rate across most
Ocular manifestations frequently occur in ANCA-associated vasculitides (AAV). Orbital inflammatory disease (OID) is a subset with limited management guidelines. This systematic review evaluated interventions for AAV-OID. We searched Embase, MEDLINE, Web of Science, ClinicalTrials.gov, and Cochrane Central without language or date restrictions for clinical trials, case-control studies, observational studies, and case series (≥5 patients) of adults treated for AAV-OID. Included studies reported therapy type and clinical response after ≥1 month. The primary outcome was clinical response, defined as any improvement in signs or symptoms, up to and including remission. Secondary outcomes included remission, relapse, sustained remission (>6 months), and serious adverse events. Two reviewers independently screened records and appraised studies using the Newcastle-Ottawa Scale (NOS). A qualitative synthesis and meta-analysis of proportions were performed using a random effects model. Of 1001 studies screened, 18 met inclusion criteria (277 patients; 14 retrospective cohorts, 4 case series). Most (17/18) had NOS scores ≥5. Thirteen studies included rituximab (RTX), 10 cyclophosphamide, 7 RTX + another immunosuppressant (IS), 11 conventional IS, and 7 surgical therapies. Most studies involved refractory/relapsing cases. In 4 RTX monotherapy series, 95% (95 %CI 89-100%, p < 0.001) had a clinical response and 84% (95%CI 72-95%, p < 0.001) achieved remission at 6 months. Our results suggest high remission rates of OID with RTX but highlight the need for high-quality prospective studies examining treatments for AAV-OID.
Stroke presentation differs between GCA and TAK, with predominant vertebrobasilar involvement in GCA. Carotid involvement is more frequent in TAK and often requires vascular procedures. These differences are crucial for appropriate management.
A newsletter aborda estratégias terapêuticas para reduzir a carga cumulativa de corticoides na arterite de células gigantes e alerta para a osteopatia induzida por metotrexato como causa de fraturas de insuficiência. Também discute o papel prognóstico de telômeros curtos na doença pulmonar intersticial da artrite reumatoide e a segurança comparável entre inibidores da JAK e anti-TNF.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody-associated vasculitis causing multi-organ damage and long-term disability. Various treatments including IL-5-targeting agents and other biologics have recently emerged, prompting regular updates of clinical practice guidelines. This scoping review and systematic review (SR) aimed to evaluate the efficacy and safety of rituximab and benralizumab in EGPA. A scoping review was conducted to identify relevant clinical questions, followed by an SR of trials published between December 2018 and July 2023. Studies comparing rituximab or benralizumab with standard treatments were included. Risk of bias (RoB) was assessed using RoB 2 and quality of evidence was rated using GRADE. One randomised controlled trial (RCT; n = 105) comparing rituximab with conventional therapy, showed a 180-day remission rate of 63.5% vs. 60.4% (risk ratio 1.05, 95% CI 0.78-1.42), with very low certainty due to serious RoB and imprecision. Another RCT compared benralizumab with mepolizumab, showing similar rates of remission (58.6% vs. 55.7%), relapse (30%), and glucocorticoid tapering, with low certainty owing to imprecision. Rituximab showed no clear benefit over conventional therapy, whereas benralizumab demonstrated comparable efficacy and safety to mepolizumab. However, evidence remains limited, and further EGPA-specific trials are needed.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis in which cardiac involvement is a primary cause of mortality. Complete heart block presenting as Adams-Stokes syndrome is a rare but critical complication. Notably, to our knowledge, EGPA initially manifesting as Adams-Stokes syndrome has not been previously documented, based on a comprehensive review of the literature. We report a 27-year-old female presenting with recurrent syncope and seizures. Laboratory tests revealed significant eosinophilia (49.5%), and cardiac workup confirmed third-degree atrioventricular block. A diagnosis of EGPA was established based on the 2022 ACR/EULAR criteria (score=13). Emergency treatment involved temporary pacing and methylprednisolone pulse therapy, followed by mepolizumab induction. Sinus rhythm recovered within 24 hours. During a two-month follow-up, the patient maintained remission with normalized eosinophil counts and improved cardiac function. This case highlights the importance of including EGPA in the differential diagnosis of unexplained high-grade heart block and supports the efficacy of early immunosuppressive therapy in reversing life-threatening cardiac complications.
Systemic sclerosis (SSc) is an autoimmune disease characterized by autoantibody production, fibrosis, and vasculopathy. The coexistence of ANCA-associated vasculitides (AAV) in SSc is rare and poorly characterized, with limited data on the impact of treatments, particularly high-dose glucocorticoids (GCs), on both conditions. This study aimed to describe the clinical phenotype, management, and outcomes of patients with overlapping SSc and AAV. We conducted a multicenter retrospective study in 18 French centers, including patients who met the 2013 ACR/EULAR criteria for SSc and the 2022 ACR/EULAR criteria for AAV. Clinical, biologic, and radiologic data were collected. We included 30 patients (median age 51.5 years, 83% female). SSc preceded AAV in all cases; 27% had diffuse cutaneous SSc, while 73% had limited cutaneous SSc. Anti-Scl70 antibodies were detected in 50%, and interstitial lung disease (ILD) was present in 80%, predominantly with a fibrosing non-specific interstitial pneumonia pattern (54%). AAV was microscopic polyangiitis in 90%, with MPO-ANCA positivity in 93%. Renal involvement was common (76%), with a median serum creatinine of 170 μmol/l (IQR 120-361) and proteinuria of 2 g/g (IQR 0.9-2.3). All patients received GCs in combination with cyclophosphamide (50%) or rituximab (47%). No cases of scleroderma renal crisis were observed. SSc manifestations, including ILD and skin involvement, remained stable during follow-up. AAV, predominantly microscopic polyangiitis with MPO-ANCA, can occur in SSc, particularly in patients with fibrosing ILD and anti-Scl70. Standard vasculitis treatments appear to be effective and do not worsen outcomes in SSc.
To evaluate the utility of magnetic resonance imaging (MRI)-guided muscle biopsy (MB) in diagnosing small- to medium-vessel vasculitis. We retrospectively included patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) or polyarteritis nodosa (PAN) between April 2020 and March 2025 who underwent MRI and MB. The primary outcome was the diagnostic sensitivity of MRI-guided MB for AAV and PAN. The secondary outcome was the diagnostic sensitivity for PAN alone. MB was considered positive when it demonstrated either necrotizing vasculitis or non-necrotizing vasculitis. Eighteen patients who underwent MRI and MB were included: 11 patients had AAV and 7 had PAN. The median interval between MRI and MB was 3.5 days. The mean Birmingham Vasculitis Activity Score was 13.6. Muscle pain was observed in 11 patients; however, none of the patients exhibited elevated creatine kinase levels. The sensitivity of MB for diagnosing AAV and PAN was 83.3% (15/18; 95% confidence intervals [CI] 58.6-96.4%), whereas that for PAN alone was 85.7% (6/7; 95% CI 42.1-96.3%). No biopsy-related complications were observed. There were no apparent differences in clinical characteristics between the MB-positive and MB-negative groups. MRI-guided MB may represent a diagnostic option for small- to medium-vessel vasculitis, even in patients without muscle pain or when other suitable biopsy sites are unavailable. Although this was a small exploratory retrospective single-center study, these findings should be validated in larger multicenter prospective studies.
Rapid progressive glomerulonephritis (RPGN) is a severe complication of microscopic polyangiitis (MPA), leading to end-stage renal disease (ESRD). However, biomarkers for assessing the disease severity have not been elucidated in MPA-RPGN. The aim in this exploratory hypothesis-generating study was to identify serum biomarkers associated with renal disease severity and prognosis in patients with MPA. This study enrolled 73 patients with MPA. We measured 16 serum biomarker profiles, and compared them between patients with MPA with RPGN and those without RPGN. We identified biomarkers with higher levels in MPA with RPGN and evaluated their associations with progression to ESRD. Five kidney biopsy specimens were examined by haematoxylin and eosin staining and immunostaining to evaluate the biomarker expressions. Of the 73 patients, 30 patients (41.1%) had RPGN on admission. Initial serum M-CSF levels and TNF-a levels were significantly higher in patients with MPA with RPGN than those without RPGN. Among them, serum M-CSF levels significantly correlated with glomerular and renal tubular damage markers. The 5-year ESRD-progression rate was significantly higher in patients with initial serum M-CSF ≥ 416.95 pg/ml than in patients with serum M-CSF < 416.95 pg/ml (P = 0.0002). Immunohistochemical staining showed enhanced M-CSF expression in glomerular capillary endothelial cells and tubular epithelial cells in cases with severe glomerular and tubular damage. CD163-positive macrophages showed high infiltration into the periglomerular and peritubular areas in the sclerotic group. The serum M-CSF level may serve as a biomarker that reflects RPGN severity and predicts progression to ESRD in patients with MPA. M-CSF-inducing CD163 + macrophages might contribute to the pathogenesis of RPGN in MPA. The online version contains supplementary material available at 10.1186/s13075-025-03718-1.
To investigate the concordance between organ involvement at diagnosis and relapse in granulomatosis with polyangiitis and factors associated with new disease features at relapse. Data from a national database of newly diagnosed patients was analysed. Clinical features were recorded at diagnosis and relapse, grouped by organ system. ORs and HRs were used to assess associations between baseline features and first relapse. Factors independently associated with new organ involvement at relapse were identified using multivariable logistic regression. Among 795 patients (median follow-up 3.5 years), 394 (50%) relapsed; organ involvement at relapse was available for 376 patients. Relapses most often affected ear, nose and throat (ENT), lungs and kidneys. Organ involvement at diagnosis was associated with a higher likelihood of relapse in the same organ: eyes (OR 6.69), lungs (OR 3.35), kidneys (OR 3.58), nervous system (OR 2.90), and mucocutaneous (OR 4.53). Major manifestations associated with a higher likelihood of recurrence were scleritis, pachymeningitis, subglottic stenosis and worsening renal function. For 56% of patients, the first relapse affected only the initially involved organs. Of the 165 patients with new organ manifestations, these were rarely isolated (n=34) and usually occurred alongside involvement of at least one previously affected organ (n=131). In multivariable analysis, systemic, ENT and lung manifestations at diagnosis were associated with a lower risk of new organ disease at relapse. Although new features can still emerge, organ involvement at diagnosis is associated with a higher likelihood of relapse in the same organ.
VEXAS syndrome is a rare, adult-onset autoinflammatory disorder caused by somatic mutations in the UBA1 gene. Patients may present with symptoms similar to IgG4-related disease (IgG4-RD) or systemic vasculitis. We report the case of a 70-year-old man who presented with periorbital swelling, fever, and elevated serum IgG4. However, a biopsy of the lacrimal gland did not show histological evidence of IgG4-RD. Consecutively, the patient developed progressive pulmonary infiltrations, bicytopenia and leukocytoclastic vasculitis. Chest-CT showed organizing pneumonia, which was histologically proven by transbronchial lung cryobiopsy (TBLC), again excluding IgG4-RD. PET/CT revealed hypermetabolic bone marrow and bone marrow aspiration biopsy showed vacuolization of granulocytic precursor cells. Finally, genetic testing for UBA1 mutation confirmed the diagnosis of VEXAS syndrome. Treatment with ruxolitinib in addition to steroids, led to temporary stabilization but long-term prognosis was unfavorable. This case highlights the importance of considering VEXAS syndrome a relevant differential diagnosis of vasculitis and IgG4-RD in men. Furthermore, we present valuable insights into the pathophysiology of VEXAS through transmission electron microscopy (TEM) of TBLC samples.
BACKGROUND: To assess a combination of novel color Doppler ultrasound (CDUS), greyscale ultrasound (GSUS), and oscillometric indices of macroangiopathy and (CV) risk in patients with giant cell arteritis (GCA). Additionally, to explore the relationships between these imaging markers and both patient-specific and disease-related characteristics, as well as traditional CV risk factors. METHODS: CDUS was performed to evaluate arterial compliance markers, specifically the resistance (RI) and pulsatility (PI) indices, in both the common (CCA) and internal carotid artery (ICA) of GCA patients and healthy controls. GSUS examinations were conducted to measure carotid intima-media-thickness (cIMT), identify plaques, and quantify cumulative carotid calcification surface. Oscillometry was utilized to determine aortic stiffness via carotid-femoral pulse-wave velocity (cfPWV). RESULTS: Sixty-six GCA patients and 93 healthy subjects were included. Patients showed significantly higher cfPWV (padj <0.001), cIMT (padj =0.037), CCA-PI (padj =0.009), CCA-RI (padj=0.019), and plaque-area (p < 0.001) compared with controls. cfPWV correlated with traditional CV risk factors, like age (rho = 0.330, p < 0.009), mean-arterial-pressure (rho = 0.257, p = 0.044), and cholesterol (rho = 0.318, p = 0.017). CCA-PI and -RI were lower in patients receiving immunosuppressive therapy [1.5 (1.33–2.04) vs. 1.95 (1.72–2.29); 0.74 (0.68–0.82) vs. 0.80 (0.76–0.85), both; p < 0.05], and CCA-RI was predicted by erythrocyte-sedimentation-rate (rho = 0.343, p = 0.044). cIMT correlated with age (r = 0.619, p < 0.001) and plaque area (rho = 0.305, p = 0.047). CONCLUSION: GCA patients demonstrated increased carotid pulsatility, resistance, atherosclerosis, and aortic stiffness compared to controls. Moreover, key predictors of impaired CV and cerebrovascular surrogates were identified. The combined assessment of CDUS and GSUS could provide a more thorough evaluation of the arterial tree, thereby enhancing the overall assessment of macroangiopathy. TRIAL REGISTRATION: DRKS00031470.
Acute anterior ischaemic optic neuropathy (AION) is a feared ischaemic complication of giant cell arteritis (GCA). However, distinguishing arteritic AION (A-AION) from its non-arteritic counterpart (NA-AION), which accounts for approximately 90% of cases, can be challenging. Rapid initiation of glucocorticoids is essential to prevent irreversible vision loss in GCA but is unnecessary in NA-AION. This study evaluated the use of orbital MRI in differentiating A-AION from NA-AION. In this prospective single-centre study, patients >50 years who had recent-onset AION were enrolled between June 2021 and October 2024. The final diagnosis of GCA was confirmed after comprehensive assessments and ≥6 months follow-up. Orbital MRIs were independently evaluated by two experienced radiologists blinded to the clinical diagnosis. Of the 18 patients analysed, nine had A-AION (two with bilateral involvement), while nine had NA-AION. MRI demonstrated differences between the groups, notably in contrast enhancement of the ophthalmic artery (72.7% vs 22.2%; p=0.07), perineural fat (90.9% vs 22.2%; p=0.005) and retrobulbar fat (100% vs 11.1%; p<0.001). The most discriminative MRI feature was retrobulbar fat enhancement, achieving 100% (95% CI 72 to 100) sensitivity and 89% (95% CI 52 to 100) specificity. Bilateral orbital enhancement was identified in more than half of the unaffected contralateral eyes in A-AION patients. These results suggest that orbital MRI may help clinicians rapidly differentiate between A-AION and NA-AION to provide the most appropriate treatment.
The proportion of patients with giant cell arteritis (GCA)-related large vessel vasculitis (LVV) treated with tocilizumab (TCZ) who achieve a complete metabolic response on repeated 18 F-fluorodeoxyglucose positron emission tomography (18FDG-PET)-CT (PET/CT) is unknown. We conducted a retrospective multicentre study that enrolled patients with GCA-related LVV demonstrated on PET/CT, who were treated with TCZ and underwent at least one repeated PET/CT. The primary endpoint was the proportion of patients with vascular extinction on repeated PET/CT during or after TCZ treatment (grade 0 or 1 on the visual vascular to liver FDG uptake grading scale). A total of 91 patients (64 women (70%), median age: 69 (54-83) years) were included. Clinical remission and a complete metabolic response on PET/CT were observed in 69 patients (76%). Among these, 30 had discontinued all GCA treatments and had not relapsed after >12 months of follow-up post negative PET/CT; the remaining 39 patients were still treated or had <12 months of follow-up after the negative PET/CT.13 (14%) patients experienced a relapse of LVV on a third PET/CT within 12 months after TCZ discontinuation. During follow-up, an aortic dilation occurred in one (1%) patient with complete metabolic extinction and in four (18%) patients who did not show complete and persisting PET/CT extinction (p=0.006 by log-rank test). This study suggests that TCZ is an interesting therapeutic option for achieving complete metabolic response on PET/CT in patients with GCA-related LVV. The subsequent risk of aortic dilation may be reduced.
To compare fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging to clinical- and laboratory-based assessments of disease activity in a randomized controlled trial (RCT) in giant cell arteritis (GCA). Patients with new-onset or relapsing GCA were randomized to guselkumab or placebo plus tapered glucocorticoids in an international, multicenter RCT. FDG-PET was performed at the baseline visit before randomization and repeated at disease flare or the week-52 visit (clinical remission off glucocorticoids). FDG-PET scans were interpreted as active or inactive by two readers, and the PET Vascular Activity Score was calculated to quantify arterial FDG uptake. FDG-PET findings were compared to clinical assessment, acute phase reactants, and glucocorticoid use at each visit. Baseline FDG-PET scans were interpreted as active vasculitis in 28 (55%) of 51 patients. FDG-PET activity at enrollment was not associated with clinical symptoms, acute phase reactants, or risk of flare. Younger age (70 vs 76 years; P = 0.03) and female sex (89% vs 48%, P < 0.01) were significantly associated with increased FDG-PET activity. There were no differences in prior glucocorticoid dose (median 780 mg) or duration (median 23 days) between patients with baseline active versus inactive FDG-PET scans. FDG-PET scans were active in 17 of 21 (81%) patients during clinical flare and in 14 of 20 (70%) patients at week 52. Subsets of patients had persistently active (n = 21) or inactive (n = 9) PET scans at all time points, independent of clinical assessment. Vascular FDG-PET activity may be discordant with clinical assessment, particularly in subsets of patients with GCA. Imaging-based outcome measures should remain exploratory in future therapeutic trials.
To compare measures of diagnostic accuracy of cranial, contrast-enhanced 3 T 2D T1-fatsat black-blood (T1fs-BB) MRI and ultrasound of the temporal arteries (TA) for suspected giant cell arteritis (GCA). To evaluate the influence of cardiovascular risk (CVR). Retrospective, single centre study with patients ≥50 years, evaluated for GCA with both MRI and ultrasound. Diagnostic reference: expert diagnosis ≥6 months. Patients were categorized into two CVR-categories. TA segments were re-rated on a scale from 0 to 3 for MRI. Ultrasound grading used halo/compression signs and intima media thickness (IMT) cut-offs using the compressed method. A total of 44 patients included: 74 (51.4%) with GCA and 70 (48.6%) without. In total, 54 (37.5%) had high to very high CVR. Binary agreement between MRI and ultrasound: 79.2% to 83.3% for patient level and 84.7% to 85.0% for segment level. MRI had a sensitivity of 87.8% (78.5-93.5%) and a specificity of 87.1% (77.3-93.1%). Ultrasound IMT cut-offs had a sensitivity of 86.5% (76.9-92.5%) and a specificity of 74.3% (63.0-83.1%); OMERACT signs 87.8% (78.5-93.5%) and 72.9% (61.5-81.9%). While in the high to very high CVR subgroup, MRI preserves its diagnostic accuracy, specificity drops considerably for ultrasound. For the total population T1fs-BB-MRI outperformed ultrasound due to its higher specificity. For patients without high to very high CVR, both modalities perform comparably. In patients with high to very high CVR, MRI has better diagnostic accuracy. Different IMT cut-offs and liberal use of confirmatory tests seem justified for patients with high CVR.
To determine the prevalence, characteristics, and clinical significance of subclinical polymyalgia rheumatica (PMR) in patients with apparently isolated giant cell arteritis (GCA). Single-centre retrospective cohort study including 168 patients with newly diagnosed GCA who underwent 18F-FDG PET-CT at diagnosis. Patients were classified into clinical PMR, subclinical PMR, or pure GCA based on PET findings and clinical symptoms. FDG uptake was assessed at predefined typical PMR sites, and only sites with grade ≥2 uptake were considered positive. Subclinical PMR was defined as FDG uptake involving either bilateral periarticular shoulders or bilateral trochanteric bursae or ischial regions, plus uptake at one additional typical PMR site. PET findings consistent with subclinical PMR were observed in 56% (57/102) of patients with apparently isolated GCA at diagnosis. A substantial proportion of these patients fulfilled different proposed PET-based diagnostic criteria for PMR.Patients with GCA and subclinical PMR showed less extensive musculoskeletal FDG uptake than those with GCA and clinical PMR but greater large-vessel involvement than pure GCA, particularly in the thoracic aorta (p= 0.023), abdominal aorta (p= 0.0001), and supra-aortic trunks (p= 0.007). Compared with pure PMR, they displayed a milder and more localized inflammatory pattern, mainly affecting the shoulder and pelvic girdles. No significant differences were observed across groups in cranial manifestations, severe ischaemic events, systemic inflammation, or relapse rates. Subclinical PMR findings are frequently detected by PET-CT in patients with apparently isolated GCA, supporting the concept of a GCA-PMR spectrum disease.
To integrate evidence-based data with expert opinion to provide guidance for the diagnosis, follow-up and treatment of giant cell arteritis (GCA). A systematic literature review (SLR) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. To structure the key clinical questions, the task force employed the Population, Intervention, Comparison Outcome (PICO) format. The Oxford system was subsequently applied to grade the quality of the evidence and determine the strength of each recommendation. This guideline provides 16 recommendations. We recommend the use of methotrexate in addition to glucocorticoids as first-line treatment in all patients with GCA without ischaemic symptoms. We recommend leflunomide, azathioprine and mycophenolate mofetil as alternatives in these patients if methotrexate is not tolerated. We recommend tocilizumab in GCA patients with ischaemic symptoms or with refractoriness to at least one conventional immunosuppressive. We also recommend upadacitinib as an alternative to tocilizumab in patients with low cardiovascular risk. To our knowledge, our recommendations are the first recommending upadacitinib as an alternative treatment option for the treatment of GCA. The large RCTs assessing and comparing new effective options are still required in GCA. Assessment of the value of conventional immunosuppressives, which are more cost-effective options compared to biologic agents, is another research area in GCA treatment especially for developing countries. Upadacitinib seems to be a promising option in GCA. However, more real-life experience is needed to assess the safety of upadacitinib in the elderly population with especially high cardiovascular risk.
Assessing disease activity in giant cell arteritis (GCA) remains challenging, as existing clinical, laboratory and imaging biomarkers lack specificity. This proof-of-concept study explored the diagnostic potential of vascular adhesion protein-1 (VAP-1) targeting [68Ga]Ga-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) DOTA-sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) positron emission tomography-CT (PET/CT) as an inflammation-specific molecular imaging biomarker in newly diagnosed and relapsing GCA. Patients with newly diagnosed GCA underwent [68Ga]Ga-DOTA-Siglec-9 PET/CT and vascular ultrasound. Tracer uptake (SUVmean/SUVmax) was quantified in aortic, supra-aortic and extravascular (shoulder/hip) regions and compared with relapsing patients. Levels of soluble VAP-1 (sVAP-1) and matrix metalloproteinase (MMP)2/MMP3/MMP9 were measured in patients and controls as potential biomarkers related to vascular inflammation. Eight patients with newly diagnosed GCA were compared with eight relapsing patients, alongside eight controls. Imaging revealed a positive association between ultrasound-assessed subclavian artery intima-media thickness and tracer uptake (r=0.67, p=0.035). Prednisolone exposure was inversely associated with vascular uptake across various vascular regions, with SUVmean showing a stronger overall negative association than SUVmax (SUVmean r=-0.51, p=0.043; SUVmax r=-0.62, p=0.010). Levels of sVAP-1 were reduced in newly diagnosed GCA compared with relapsing patients (p=0.0145) and controls (p=0.0446), and inversely associated with MMP2 (r=-0.56, p=0.037) and MMP9 (r=-0.47, p=0.089). Notably, MMP2 and MMP3 were negatively associated with vascular uptake (eg, aortic arch: r=-0.59, p=0.027). This first-in-human study demonstrates that [68Ga]Ga-DOTA-Siglec-9 PET/CT detects vascular inflammation in GCA and shows attenuation with prednisolone exposure. Reduced sVAP-1 levels and inverse associations between MMP2/MMP3 and tracer uptake support a functional VAP-1/MMP axis underlying the imaging signal. Our findings further position [68Ga]Ga-DOTA-Siglec-9 PET/CT as a promising potential molecular imaging biomarker in GCA.
The objective of this registry-based cohort study was to evaluate longitudinal associations between disease activity measures and patient-reported outcomes (PROs) in GCA, and to assess whether specific PRO domains reflect clinically active disease. Among all GCA patients registered in NorVas up to 12 December 2024, we selected patients who: (i) fulfilled the ACR 1990 classification criteria for GCA, (ii) had two PROs recorded at least once, and (iii) were included in NorVas at the time of diagnosis. HRQoL was assessed by RAND-12, using the physical (PCS) and mental (MCS) composite scores as outcomes. Visual analogue scales were used to assess pain, fatigue and global disease assessment. The association between the PROs and disease activity were evaluated using linear mixed effects models. We assessed the PROs over time and the difference in PROs between active and inactive disease. We included 256 patients in the study with a median of three observations each, and a total of 1003 observations. All examined PROs showed a significant difference between active and inactive disease at baseline. Statistically and clinically significant differences were retained during follow-up for RAND-12-PCS (11.19 [95% CI: 5.67, 16.71]), pain (-12.64 [95% CI: -18.58, -6.70]) and global assessment (-9.92 [95% CI: -15.48, -4.35]). Our study demonstrates a consistent association between PROs and disease activity in GCA, most pronounced for the physical component of HRQoL, pain and global assessment. Patients with active disease showed statistically and clinically significant differences in PRO scores compared with those in remission, both at baseline and throughout follow‑up. While no single PRO domain can replace formal disease activity assessment, patterns across pain, fatigue and patient global measures may signal active disease and warrant clinical reassessment. Taken together, these
Patients on low-dose prednisolone may develop adrenal insufficiency causing reduced health-related quality of life (HRQoL) and increased risk of adrenal crisis. This study examines whether supplemental hydrocortisone during mild to moderate stress improves HRQoL in patients with polymyalgia rheumatica/giant cell arteritis (PMR/GCA) with adrenal insufficiency on low-dose prednisolone. A multicentre, randomised, double-blinded, placebo-controlled, clinical trial including patients with PMR/GCA receiving ongoing prednisolone ≤5 mg/day. Eligible patients undergo an adrenocorticotropic hormone (ACTH) test, and 250 patients with a stimulated cortisol<420 nmol/L (biochemical adrenal insufficiency) are randomised 1:1 to supplemental hydrocortisone or placebo during mild to moderate stress ('sick-days') for 6 months or until daily prednisolone is stopped. The goal is 200 patients completing ≥3 months intervention period. Patients continue prednisolone tapering according to PMR/GCA guidelines. In the event of severe stress (risk of adrenal crisis), patients receive open-label hydrocortisone treatment. 95 patients with stimulated cortisol ≥420 nmol/L serve as control group. The primary outcome is HRQoL measured as fatigue using ecological momentary assessments (EMA) of the General Fatigue scale from the Multidimensional Fatigue Inventory-20, five times daily in situations of stress ('sick-days'). EMA will be administered via a smartphone application 'EMA live'. Differences in mean fatigue scores during sick-days between hydrocortisone and placebo will be analysed using mixed models for repeated measures. Secondary outcomes include daily smartphone-based symptom reporting, additional HRQoL questionnaires, adrenal crises, adverse effects from glucocorticoid excess, serial ACTH tests and biomarkers of adrenal insufficiency. The study is approved by the Ethics Committee of the Capital Region of Denmark and the Danish Medicines Agency. Recruitment began June 2022. The last patient's last visit is expected in 2026. Results will be disseminated via peer-reviewed publication and conference presentations. EudraCT:2021-002528-18, CTIS:2024-518272-30-00, NCT05435781.
Giant cell arteritis is a relapsing large-vessel vasculitis affecting the aorta and its branches. It is the most common vasculitis in persons 50 years of age and older. Vision loss occurs in 18% of patients and is preventable with prompt recognition, evaluation, and treatment. Large-artery complications include stenosis, aortic aneurysms, or dissections. Glucocorticoid therapy is effective, but nearly 50% of patients experience relapse. Tocilizumab and upadacitinib are efficacious glucocorticoid-sparing therapies. Patients require long-term monitoring for aortic aneurysms, a late disease complication, even after therapy is discontinued.
GCA is the most common vasculitis after 50 years of age, responsive to steroids with frequent relapses. Our objective was to evaluate clonal haematopoiesis of indeterminate potential (CHIP) as a risk factor for relapse in GCA. We prospectively analysed CHIP in a monocentric cohort of recently diagnosed GCA patients. CHIP was defined as a variant in a gene implicated in myeloid malignancies with allele frequency >2% detected in peripheral blood mononuclear cells by next-generation sequencing. Relapses were defined as GCA related signs or symptoms and/or inflammatory syndrome attributable to GCA after remission induction. The primary outcome was relapse occurring within 12 months of GCA induction treatment. We included 40 patients with 20 women (50%) of median age 73 years [67-80]. At diagnosis, 16 (40%) patients had ophthalmic involvement and 23 (57%) patients had large vessel involvement. CHIP was detected in 18 (45%) patients. During a median follow-up of 26 [14-45] months, 17 (42%) patients relapsed at 12 months. In multivariate analysis, baseline factors independently associated with GCA relapse at month 12 were ophthalmologic involvement at diagnosis (OR 4.02, 95% CI [1.19-13.56], P < 0.025) and the presence of CHIP (OR 9.94, 95% CI [2.98-33.17], P = 0.0002). The presence of CHIP is associated with GCA relapses in this exploratory cohort. Further studies are needed to confirm these findings.
Thoracic aortic aneurysms (TAA) are predominantly degenerative. Non-infectious inflammatory aortitis, including giant cell arteritis (GCA), Takayasu arteritis and clinically isolated aortitis (CIA), represents a less understood aetiology with poorly characterised growth patterns. While GCA is linked to higher TAA risk, preoperative growth data for inflammatory TAA are scarce. This study compares growth rates in histologically proven inflammatory aortitis. We conducted a retrospective case-control study, including patients with histologically proven aortitis and matched controls with degenerative TAA. Cases and controls were matched for age, sex, surgical year and procedure type. Aneurysm growth rate (mm/month) was calculated from serial imaging. This study included 23 patients with histologically confirmed aortitis (13 GCA, 9 CIA) and 42 matched controls with degenerative TAA. The mean growth rate was significantly higher in the aortitis group (0.177±0.01 mm/month; 2.12 mm/year) compared with controls (0.039±0.02 mm/month; 0.47 mm/year), representing a 4.5-fold acceleration (p<0.001). Among inflammatory etiologies, CIA demonstrated faster growth (0.338±0.06 mm/month; 4.06 mm/year) than GCA (2.1 mm/year; p<0.01). Patients with CIA more frequently required Bentall procedures (33% vs 0%, p=0.047). No differences were observed in baseline demographics, cardiovascular risk factors or baseline aortic diameters between groups. Histologically, 70% of aortitis cases exhibited granulomatous inflammation. Inflammatory aortitis is associated with a 4.5-fold faster preoperative TAA growth rate compared with degenerative aneurysms, with CIA exhibiting two times the growth rate of GCA. Prospective studies are warranted to validate these results and optimise surveillance and management strategies for this high-risk population.