Limb arteries involvement assessed by FDG/PET CT at diagnosis of giant cell arteritis and risk of relapse: An observational study.

INTRODUCTION: Steroids and anti-IL6 biotherapy are highly effective in obtaining remission in patients with giant cell arteritis (GCA) but the risk of relapses remains high. We aimed to identify predictors of relapse in GCA. METHODS: All consecutive patients admitted with a new diagnosis of GCA - according to the 2022 American College of Rheumatology/EULAR (ACR/EULAR) classification criteria - between May 2011 and May 2022 were eligible for this study. The primary outcome was the GCA relapse rate over the 36-months follow up. Factors associated with the primary outcome and time to first relapse were analyzed. RESULTS: One hundred and eight patients (74 [69-81] years, 64.8% women) with a new diagnosis of GCA were studied. GCA was biopsy-proven in 65 (60.2%) cases. Ninety-eight (90.7%) FDG/PET CT scans performed at diagnosis were available for review. All patients received steroids given for 21.0 [18.0-28.5] months, associated with methotrexate (n=1, 0.9%) or tocilizumab (n=2, 1.9%). During a median follow-up of 27.5 [11.4-35.0] months, relapse occurred in 40 (37%) patients. Multivariable Cox regression model, including general signs, gender, aortic wall thickness, FDG uptake in arterial wall and IV steroid pulse as covariates, showed that both general signs (HR 2.0 [1.0-4.0, P<0.05) and FDG uptake in limb arteries (HR 2.7 [1.3-5.5], P<0.01) at diagnosis were associated with GCA relapse. CONCLUSION: FDG uptake in limb arteries at diagnosis is a predictor of relapse in newly diagnosed GCA.

N-Terminal pro-Brain Natriuretic Peptide is a biomarker for cardiovascular damage in systemic lupus erythematous: a cross-sectional study.

OBJECTIVES: Prediction models based on traditional risk factors underestimate cardiovascular (CV) risk in systemic lupus erythematosus (SLE). In a large sample of unselected SLE patients, we investigated cross-sectional associations of NT-proBNP with cardiovascular damage (CVD). METHODS: Serum NT-proBNP was measured in SLE patients enrolled in the MUHC Lupus Clinic registry. Serum were collected between March 2022 and April 2023 at annual research visits. The primary outcome was CVD identified on the SLICC Damage Index. Factors associated with CVD and NT-proBNP levels were determined. RESULTS: Overall, 270 SLE patients (female 91%, median age 50.7 [1st quartile- 3rd quartile : 39.6-62.1] years) were analyzed for the primary outcome. Among them, 33 (12%) had CVD. The ROC curve for NT-proBNP demonstrated strong associations with CVD (AUC 0.78, 95% CI 0.69-0.87) with a threshold of 133 pg/ml providing the best discrimination for those with/without CVD. Hypertension (OR 3.3, 95% CI 1.2-9.0), dyslipidaemia (OR 3.6, 95% CI 1.3-9.6) and NT-proBNP > 133 pg/ml (OR 7.0, 95% CI, 2.6-19.1) were associated with CVD in the multivariable logistic regression model. Increased NT-proBNP levels were associated with age (OR 4.2, 95% CI 2.2-8.3), ever smoking (OR 1.9, 95% CI 1.0-3.5), reduced eGFR (4.1, 95% CI 1.3-13.1), prior pericarditis/pleuritis (OR 2.5, 95% CI 1.4-4.5) and aPL antibodies (OR 2.6, 95% CI 1.4-4.9). CONCLUSION: NT-proBNP is a biomarker for CV damage in SLE. The novel associations of NT-proBNP levels with prior pericarditis/pleuritis and aPL antibodies suggest new avenues for research to better understand what drives CV risk in SLE.

Improving Human Papillomavirus-Related Cervical Cancer Screening in Patients With Systemic Lupus Erythematosus.

Women with systemic lupus erythematosus (SLE), especially when exposed to immunosuppressive drugs, are at higher risk of human papillomavirus (HPV)-related cervical cancer.1 A recent study has shown that cervical cancer screening (CCS) coverage is worryingly low in this population.2.

Musculoskeletal Tuberculosis: New Insights on Diagnosis Strategy and Treatment.

BACKGROUND/ OBJECTIVE: Skeletal tuberculosis (TB) is rare. We aimed to report on diagnostic strategy and treatment of skeletal TB. METHODS: In this multidisciplinary single-center medical records review study, all adult patients admitted between January 2009 and December 2019 with microbiologically proven skeletal TB were included. Demographic, medical history, laboratory, imaging, pathologic findings, treatment, and follow-up data were extracted from medical records. RESULTS: Among 184 patients identified with TB, 21 (16 women, 42 years [27, 48 years]) had skeletal involvement. Skeletal TB included spondylitis (n = 11), lytic bone lesions (n = 7), sacroiliitis (n = 5), arthritis (n = 3), osteitis (n = 2), and diffuse muscle abscesses without bone lesion (n = 1). Lytic lesions involved both axial and peripheral skeleton at multiple sites in most cases. 18F-fluorodeoxyglucose positron emission tomography was performed in 13 patients and helped to detect multifocal asymptomatic lesions and to target biopsy. All patients were treated with anti-TB therapy for 7 to 18 months. Fifteen patients (71.4%) received steroids as an adjunct therapy. Eleven patients needed an orthopedic immobilization corset, and 3 patients underwent surgery. All patients clinically improved under treatment, but 2 relapsed over a median follow-up of 24 months (12-30 months). No patient died or suffered long-term disabilities. CONCLUSION: Our study emphasizes the diversity of skeletal involvement in TB. 18F-fluorodeoxyglucose positron emission tomography scanner at diagnosis is key to assess the extension of skeletal involvement and guide extraskeletal biopsy. Neurological complications might be prevented by adding corticosteroids to anti-TB therapy.

Clonal haematopoiesis of indeterminate potential and cardiovascular events in systemic lupus erythematosus (HEMATOPLUS study).

OBJECTIVE: The detection of somatic mutations among the genes of myeloid cells in asymptomatic patients-defining clonal haematopoiesis of indeterminate potential (CHIP)-is associated with a predisposition to cardiovascular events (CVEs) in the general population. We aimed to determine whether CHIP was associated with CVEs in SLE patients. METHODS: The study is an ancillary study of the randomized, double-blind, placebo-controlled, multicentre PLUS trial conducted from June 2007 through August 2010 at 37 centres in France, involving 573 SLE patients. The search for somatic mutations by high-throughput sequencing of 53 genes involved in clonal haematopoiesis was performed on genomic DNA collected at PLUS inclusion. CHIP prevalence was assessed in SLE and in a retrospective cohort of 479 patients free of haematological malignancy. The primary outcome was an incident CVE in SLE. RESULTS: Screening for CHIP was performed in 438 SLE patients [38 (29-47) years, 91.8% female]. Overall, 63 somatic mutations were identified in 47 patients, defining a CHIP prevalence of 10.7% in SLE. Most SLE patients (78.7%) carried a single mutation. Most variants (62.5%) were located in the DNMT3A gene. CHIP frequency was related to age and to age at SLE diagnosis, and was associated with a lower frequency of aPLs. CHIP occurred >20 years earlier (P < 0.00001) in SLE than in controls. The detection of CHIP at inclusion was not found to be associated with occurrence of CVEs during follow-up [HR = 0.42 (0.06-3.21), P = 0.406]. CONCLUSION: The prevalence of CHIP is relatively high in SLE for a given age, but was not found to be associated with incident CVEs. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT05146414.

Acute myocarditis revealing autoimmune and inflammatory disorders: Clinical presentation and outcome.

BACKGROUND: Acute myocarditis (AM) may be the heralding manifestation of autoimmune and inflammatory disorders (AIID). We aimed to describe the clinical presentation and outcome of patients with AM revealing AIID. METHODS: All consecutive adult patients with AM admitted in a department of Cardiology (Bichat Hospital, Paris, France) from January 2011 to January 2019 were included. Diagnosis of AM was based on clinical manifestations, elevated Troponin, myocardial inflammation on CMR and no evidence for coronary artery disease. AIID were classified using international criteria. RESULTS: Two-hundred and eighteen (35.3 [26.4-47.1] years, 75.2% males) patients with AM were included. Overall, AM revealed AIID in 15 (6.9%), including systemic lupus erythematosus (n = 3), adult onset Still's disease (n = 3), sarcoidosis (n = 2), mixed connective tissue disease (n = 1), anti-Jo1 syndrome (n = 1), eosinophilic granulomatosis with polyangiitis (n = 1), antiphospholipid syndrome (n = 1), reactive arthritis (n = 1), Graves' disease (n = 1) and Crohn's colitis (n = 1). Left ventricular ejection fraction (LVEF) at onset was <30% in 5 (33.3%) patients with AIID. All but 2 patients with AIID were treated with steroids, immunosuppressive and/or immunomodulatory drugs and LVEF normalized in all by the end of follow-up. By comparing patients with AIID to patients with idiopathic AM (n = 203), multivariable analysis showed that pericardial effusion, lack of chest pain and high CRP level at onset were independently associated with AIID. CONCLUSION: Acute myocarditis revealing AIID may be life-threatening at the acute phase but has an overall good prognosis under specific treatment. Pericardial effusion and CRP level at admission suggest an AIID as the cause for AM.

Efficacy and safety of TNF-α antagonists and tocilizumab in Takayasu arteritis: multicentre retrospective study of 209 patients.

OBJECTIVE: To assess the safety and the efficacy of TNF-α antagonists and tocilizumab in patients with Takayasu arteritis (TAK). METHODS: A total of 209 patients with TAK [median age 29 years (interquartile range 7-62)], 186 (89%) females] were included. They received either TNF-α antagonists [n = 132 (63%) with 172 lines; infliximab (n = 109), adalimumab (n = 45), golimumab (n = 8), certolizumab (n = 6) and etanercept (n = 5)] or tocilizumab [n = 77 (37%) with 121 lines; i.v. and s.c. in 95 and 26 cases, respectively]. RESULTS: A complete response at 6 months was evidenced in 101/152 (66%) patients on TNF-α antagonists and 75/107 (70%) patients on tocilizumab. Age ≥30 years [odds ratio 2.09 (95% CI 1.09, 3.99)] was associated with complete response, whereas vascular signs [OR 0.26 (95% CI 0.1, 0.65)], baseline prednisone ≥20 mg/day [OR 0.51 (95% CI 0.28, 0.93)] were negatively associated with the complete response to TNF-α antagonists or tocilizumab. During a median follow-up of 36 months, 103 relapses were noted. Supra-aortic branches and thoracic aorta involvement [HR 2.44 (95% CI 1.06, 5.65) and 3.66 (1.18, 11.4), respectively] and systemic signs at baseline [HR 2.01 (95% CI 1.30, 3.11)] were significantly associated with relapse. The cumulative incidence of treatment discontinuation and relapse were similar in TNF-α antagonists and tocilizumab. Fifty-eight (20%) adverse effects occurred on biologic targeted therapies [37 (21%) on TNF-α antagonists and 21 (17%) on tocilizumab (P = 0.4), respectively]. CONCLUSION: This large multicentre study shows high efficacy of biologic targeted treatments in refractory TAK. Efficacy, relapse and drug retention rate were equivalent with TNF-α antagonists and tocilizumab.

Patients of 75 years and over with ANCA-associated vasculitis have a lower relapse risk than younger patients: A multicentre cohort study.

BACKGROUND: Little is known about antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in older patients. We aim to study relapse risk of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in patients diagnosed after 75 years and compare it with those of patients aged 65-75 years. METHODS: Data from AAV patients aged ≥65 years were extracted from the French Vasculitis Study Group (FVSG) database and from a call for observation to FVSG members. Cox and Fine-Gray models were used to assess relapse risk, taking death into account either as a censoring or a competing event, respectively. RESULTS: The analysis included 219 patients aged ≥75 years (median 79) and 80 patients aged 65-75 years (median 70), of those 155 had GPA (52%), 136 MPA (45%), with 95 (32%) anti-proteinase 3 positivity and 179 (61%) anti-myeloperoxidase. Patients aged ≥75 years had a lower relapse risk in multivariate analysis (cause-specific hazards ratio [CSHR] 0.54, 95% CI [0.33-0.89], p = 0.016, Cox model; subdistribution hazard ratio [SHR] 0.46, 95% CI [0.29-0.74], p = 0.001, Fine-Gray model) after taking into account vasculitis type. Patients aged ≥75 years had a lower probability of being treated for remission maintenance with a combination of glucocorticoids and immunosuppressants (vs. glucocorticoids alone, HR 0.28, 95% CI [0.11-0.68], p = 0.005) after adjusting to Five Factor Score, although relapse-free survival was significantly longer when receiving such combination (CSHR 0.40, 95% [CI 0.24-0.67], p < 0.001). CONCLUSIONS: AAV patients ≥75 years have a lower relapse risk than patients aged 65-75 years despite a lower probability of having received maintenance therapy with a combination of glucocorticoids and immunosuppressants, but they still benefit from such treatment regimen.

Clinical spectrum, outcome and management of immune thrombocytopenia associated with myelodysplastic syndromes and chronic myelomonocytic leukemia.

Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are associated with systemic inflammatory or autoimmune diseases in 10-20 % of cases. Among them, immune thrombocytopenia (ITP) has been reported but large studies assessing this association are missing. Whether such patients have a particular phenotype and require particular management is unclear. This study analyzes the clinical spectrum, outcome and therapeutic management of patients with ITP associated with MDS or CMML, in comparison (i) to patients with primary ITP without MDS/CMML and (ii) to patients with MDS/CMML without ITP. Forty-one MDS/CMML-associated ITP patients were included, with chronic ITP in 26 (63%) patients, low-risk myelodysplasia in 30 (73%) patients and CMML in 24 (59%) patients. An associated autoimmune disease was noted in 10 (24%) patients. In comparison to primary ITP patients, MDS/CMML-associated ITP patients had a higher occurrence of severe bleeding despite similar platelet counts at diagnosis. First-line treatment consisted of glucocorticoids (98%) and intravenous immunoglobulin (IVIg) (56%). Response achievement with IVIg was more frequent in primary ITP than in MDS/CMML-associated ITP patients. Response rates to second-line therapies were not statistically different between primary ITP and MDS/CMMLassociated ITP patients. Ten percent (n=4) of patients with MDS/CMML-associated ITP had multirefractory ITP versus none in primary ITP controls. After a median follow-up of 60 months, there was no difference in overall survival between MDS/CMML-associated ITP and primary ITP patients. Leukemia-free-survival was significantly better in MDS/CMMLassociated ITP patients than in MDS/CMML without ITP MDS/CMML-associated ITP have a particular outcome with more severe bleeding and multirefractory profile than primary ITP, similar response profile to primary ITP therapy except for IVIg, and less progression toward acute myeloid leukemia than MDS/CMML without ITP.

A 29-Year-Old Man With an Osteolytic Rib Lesion.

CASE PRESENTATION: A 29-year-old man with no significant medical history presented to the ED with a 4-week history of chest pain. The pain was insidious, located on the right side of the chest, increased by deep breathing, and incompletely alleviated by acetaminophen. The patient had never smoked tobacco. He denied any recent fevers, chills, dyspnea, cough, night sweats, hemoptysis, or history of trauma but had lost at least 8 kg in the past 6 months. The patient was from Morocco and had lived in France for 1 year.

Effects of BAFF Neutralization on Atherosclerosis Associated With Systemic Lupus Erythematosus.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death in systemic lupus erythematosus (SLE). B cells play a key role in the pathogenesis of lupus, and anti-BAFF therapy has been approved for use in SLE. Since mature B cells also promote atherosclerosis, we undertook this study to evaluate, in a mouse model and in SLE patients, whether BAFF neutralization has an atheroprotective effect in SLE. METHODS: The effect of BAFF on atherosclerosis associated with lupus was investigated in the atherosclerosis/lupus-prone apolipoprotein E-knockout D227K mouse model and in a cohort of SLE patients. Mice were treated with a blocking anti-BAFF monoclonal antibody (mAb), while fed a standard chow diet. Carotid plaque and carotid intima-media thickness were assessed by ultrasound at baseline and during follow-up in SLE patients who were asymptomatic for CVD. RESULTS: Anti-BAFF mAb in ApoE-/- D227K mice induced B cell depletion, efficiently treated lupus, and improved atherosclerosis lesions (21% decrease; P = 0.007) in mice with low plasma cholesterol levels but worsened the lesions (17% increase; P = 0.06) in mice with high cholesterol levels. The atheroprotective effect of the BAFF-BAFF receptor signaling inhibition on B cells was counterbalanced by the proatherogenic effect of the BAFF-TACI signaling inhibition on macrophages. In SLE patients, blood BAFF levels were associated with subclinical atherosclerosis (r = 0.26, P = 0.03). Anti-BAFF mAb treatment had a differential effect on the intima-media thickness progression in SLE patients depending on body mass index. CONCLUSION: Depending on the balance between lipid-induced and B cell-induced proatherogenic conditions, anti-BAFF could be detrimental or beneficial, respectively, to atherosclerosis development in SLE.

Temporal Arteritis Revealing Antineutrophil Cytoplasmic Antibody-Associated Vasculitides: A Case-Control Study.

OBJECTIVE: Temporal arteritis (TA) is a typical manifestation of giant cell arteritis (GCA). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are rarely revealed by TA manifestations, leading to a risk of misdiagnosis of GCA and inappropriate treatments. This study was undertaken to describe the clinical, biologic, and histologic presentations and outcomes in cases of TA revealing AAV (TA-AAV) compared to controls with classic GCA. METHODS: In this retrospective case-control study, the characteristics of patients with TA-AAV were compared to those of control subjects with classic GCA. Log-rank test, with hazard ratios (HRs) and 95% confidence intervals (95% CIs), was used to assess the risk of treatment failure. RESULTS: Fifty patients with TA-AAV (median age 70 years) were included. Thirty-three patients (66%) presented with atypical symptoms of GCA (ear, nose, and throat involvement in 32% of patients, and renal, pulmonary, and neurologic involvement in 26%, 20%, and 16% of patients, respectively). Blood samples were screened for ANCAs at the time of disease onset in 33 patients, and results were positive in 88%, leading to a diagnosis of early TA-AAV in 20 patients. The diagnosis of AAV was delayed a median interval of 15 months in 30 patients. Compared to controls with GCA, patients with TA-AAV were younger (median age 70 years versus 74 years), were more frequently men (48% versus 30%), and had high frequencies of atypical manifestations and higher C-reactive protein levels (median 10.8 mg/dl versus 7.0 mg/dl). In patients with TA-AAV, temporal artery biopsy (TAB) showed fibrinoid necrosis and small branch vasculitis in 23% of patients each, whereas neither of these characteristics was evident in controls with GCA. Treatment failure-free survival was comparable between early TA-AAV cases and GCA controls, whereas those with delayed TA-AAV had a significantly higher risk of treatment failure compared to controls (HR 3.85, 95% CI 1.97-7.51; P < 0.0001). CONCLUSION: TA-AAV should be considered diagnostically in cases of atypical manifestations of GCA, refractoriness to glucocorticoid treatment, or early relapse. Analysis of TAB specimens for the detection of small branch vasculitis and/or fibrinoid necrosis could be useful. Detection of ANCAs should be performed in cases of suspected GCA with atypical clinical features and/or evidence of temporal artery abnormalities on TAB.

Management of patients with myocardial tuberculosis: A case series.

BACKGROUND: Myocardial Tuberculosis (MT) is exceedingly rare. We aimed to report on myocardial involvement in tuberculosis (TB). METHODS: All adult patients admitted in a department of Internal Medicine over an 8-year period with microbiologically proven MT were retrospectively reviewed. Demographic, medical history, laboratory, imaging, pathologic findings, treatment, and follow-up data were extracted from medical records. RESULTS: Six patients (4 women, 37.6 [21.3-62.1] years) with MT were identified. MT included cardiac mass (n = 1), coronaritis (n = 1), left ventricle spontaneous rupture (n = 1) and myocarditis (n = 3). Pericardial effusion was associated with myocardial involvement in 2 cases. Four patients presented with acute heart failure. CRP serum level was high in all cases. The mean delay between the first symptoms and TB diagnosis was of 6 [1-44] months. The time from admission to diagnosis was of 18 (9-28) days. No patient had human immunodeficiency virus infection. Fluorodeoxyglucose - positron emission tomography (FDG-PET) detected extra-cardiac asymptomatic Mycobacterium tuberculosis infection localization and guided biopsy in 5 cases. As compared to TB patients without cardiac involvement, patients with MT were younger and more frequently women. All patients received antituberculosis therapy for 7.5 to 12 months associated with steroids for at least 6 weeks. Cardiac surgery was required in all but one patient. No patient died over a median follow-up of 1.2 [0.2-4.4] years. CONCLUSION: Our study emphasizes the clinical spectrum of life-threatening MT. Early diagnosis using FDG-PET imaging to target biopsy in extra-cardiac tissues and combined treatment strategy associating antituberculosis therapy, corticosteroids and surgery prevent complications and death.

A 22-Year-Old Woman With Fever, Palpitations, and a Cardiac Mass.

CASE PRESENTATION: A 22-year-old woman was admitted to our department for fever of unknown origin. The patient reported intermittent fever and nonspecific abdominal pain for several years. Six months before admission she started complaining of palpitations and exertional dyspnea. She had no weight loss, chest pain, headache, or joint complaints. Medical history was unremarkable. She did not consume tobacco, alcohol, or illicit drugs. The patient was from Malia. She had lived in France for 4 years and did not report recent travel.

Osseous sarcoidosis: A multicenter retrospective case-control study of 48 patients.

OBJECTIVE: To describe the clinical presentation, distribution of lesions, treatment, and outcomes of osseous sarcoidosis. METHODS: A French retrospective multicenter study of patients with biopsy-proven sarcoidosis analyzed patients with 1) a biopsy-proven granuloma without caseous necrosis, and either 2) osseous clinical manifestations, or 3) abnormal osseous imaging. Sarcoidosis patients with osseous involvement (cases) were compared with 264 age- and sex-matched sarcoidosis patients with no osseous manifestations (controls). RESULTS: In the osseous sarcoidosis group (n=88), forty-two (48%) patients had osseous-related symptoms involving the axial (69%) and/or appendicular (58%) skeleton. On imaging, the most commonly affected bones were in the spine (52%), pelvis (42%), hands (22%) and femur (19%). Compared with controls, cases had higher rates of mediastinal (93% vs. 47%) and extra-thoracic lymph node involvement (66% vs. 21%), pulmonary (90% vs. 65%) and cutaneous involvement (44% vs. 23%) (all P<0.0001), and hypercalcemia (8.5% vs. 2%, P=0.014). Spleen/liver and gastrointestinal involvement were less frequent in the osseous sarcoidosis group (29% vs. 45%, and 1% vs. 17%, respectively, P<0.0001). Response rates to with glucocorticoids alone, glucocorticoids plus methotrexate or glucocorticoids plus hydroxychloroquine were 23/44 (52%), 9/13 (69%) and 4/6 (67%), respectively. CONCLUSION: In patients with osseous sarcoidosis the spine and pelvis were the most commonly affected bones. Compared with controls, cases with osseous sarcoidosis have higher rates of thoracic and extra-thoracic lymph node involvement, pulmonary and cutaneous involvement, and hypercalcemia. Most patients with osseous sarcoidosis had a good response to glucocorticoids in combination with methotrexate or hydroxychloroquine.

Large-vessel vasculitis diagnosed between 50 and 60 years: Case-control study based on 183 cases and 183 controls aged over 60 years.

BACKGROUND: Age at onset of large-vessel vasculitis (LVV) is commonly used to distinguish giant cell arteritis (GCA) and Takayasu arteritis (TA). However, LVV between age 50 and 60 years may be difficult to classify. METHODS: We conducted a retrospective study including LVV aged between 50 and 60 years at onset (LVV50-60, cases) and compared them to LVV aged over 60 years (LVV>60, controls). LVV was defined histologically and/or morphologically. Controls fulfilled ACR 1990 criteria for GCA or presented isolated aortitis. RESULTS: We included 183 LVV50-60 and 183 gender-matched LVV>60. LVV50-60 had more frequent peripheral limb manifestations (23 vs. 5%), and less frequent cephalic (73 vs. 90%) and ocular signs (17 vs. 27%) than LVV>60. Compared to LVV>60, CT angiography and PET/CT scan were more frequently abnormal in LVV50-60 (74 vs. 38%, and 90 vs. 72%, respectively), with aorta being more frequently involved (78 vs. 47%). By multivariate analysis, absence of cephalic symptoms, presence of peripheral limb ischemia and aorta involvement, and increased CRP level were significantly associated with LVV50-60 presentation compared to LVV>60. At last follow-up, compared to LVV>60, LVV50-60 received significantly more lines of treatment (2 vs. 1), more frequent biologics (12 vs. 3%), had more surgery (10 vs. 0%), and had higher prednisone dose (8.8 vs. 6.5 mg/d) at last follow-up, CONCLUSION: LVV onset between 50 and 60 years identifies a subset of patients with more frequent aorta and peripheral vascular involvement and more refractory disease compared to patients with LVV onset after 60.