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Objective: Takayasu arteritis (TA) leads to stenotic disease. Aneurysmal lesions are rarer. This study assessed the main characteristics of aneurysmal disease in a Canadian cohort of patients with TA., Methods: This monocentric retrospective study included patients with TA followed at the Mount Sinai Hospital Vasculitis Clinic in Toronto. Diagnosis of TA was based on clinical findings and/or satisfied the 1990 American College of Rheumatology classification criteria., Results: Seventy-four patients were included. At any time, aneurysmal disease was found in 23 (31%) patients. Median disease duration was 9.0 (IQR 7.0-19.0) years. Prior hypertension ( P = 0.02), fever ( P = 0.04), and seizure disorders ( P = 0.03) were more common. Limb claudication was less frequent ( P = 0.01). Persistent and/or new aneurysms were demonstrated in 22/23 patients at follow-up. Thoracic aorta aneurysm (13/22) was most common, followed by abdominal aorta (8/22), subclavian (7/22), and carotid (6/22) artery disease. Aortic valve regurgitation was more frequent (9/23 vs 3/48; P = 0.001). Twenty-one patients had been treated with glucocorticoids (median 6.1 years [IQR 3.7-8.1]). Methotrexate, azathioprine, and leflunomide were repeatedly used. Infliximab (7/23) was used more often ( P = 0.04), whereas tocilizumab was received by only 4 patients with aneurysmal disease ( P = 0.01). Patients with aneurysms suffered more frequent relapses (2.0 [IQR 0.0-4.0] vs 1.0 [IQR 0.0-2.0], P = 0.04)., Conclusion: Aneurysmal disease was found in a significant proportion of patients with TA. Given that aneurysms may carry a risk of rupture, and are associated with a higher rate of relapse, this finding should be reported systematically in TA studies., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: In 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aims to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence., Methods: A needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014 to September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a 2-step modified Delphi procedure to reach > 80% consensus on the inclusion, wording, and grading of each new and revised recommendation., Results: Eleven new and 16 revised recommendations were created and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary material for practical use was revised to reflect the updated recommendations., Conclusion: The 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts., (Copyright © 2021 by the Journal of Rheumatology.)

Objective: Takayasu arteritis (TA) is a rare large-vessel vasculitis that puts patients at high risk of developing severe ischemic events (SIE). Outcomes for TA patients with SIE are poorly understood. We aim to describe the characteristics of TA patients experiencing SIE., Methods: All TA patients with at least 1 followup visit seen between 1988 and 2015 were included from 3 academic centers in Ontario, Canada. Diagnosis was based on American College of Rheumatology criteria, physician opinion, and vascular imaging. SIE were defined as cerebrovascular accident (CVA), acute coronary syndrome (ACS), ischemic cardiomyopathy, ischemic blindness, and/or ischemic bowel or limb requiring surgery., Results: Of the 52 patients with TA included in the study, 51 (98%) were female and 22 (42%) were of European descent. The mean age was 31 (SD 12) at the time of diagnosis and the followup time was 6 years (SD 5). Fifteen (29%) experienced an SIE: 5 CVA, 5 ACS, 1 ischemic cardiomyopathy, and 4 limb ischemia. Thirteen out of 15 SIE (87%) occurred at or before diagnosis. Patients with SIE were more likely than those without SIE to be started on corticosteroids combined with immunosuppressants (p = 0.04) and antiplatelet agents (p = 0.004). Outcomes including disease activity and damage scores were similar between patients with and without SIE., Conclusion: SIE are common in patients with TA and occur early in the disease. With aggressive treatment, patients with SIE had a favorable prognosis.

Objective: We evaluated potential circulating biomarkers of disease activity in giant cell arteritis (GCA), Takayasu arteritis (TA), polyarteritis nodosa (PAN), and eosinophilic granulomatosis with polyangiitis (EGPA)., Methods: A panel of 22 serum proteins was tested in patients enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies of GCA, TA, PAN, or EGPA. Mixed models were used for most analyses. A J48 classification tree method was used to find the most relevant markers to differentiate between active and inactive GCA., Results: Tests were done on 418 samples from 152 patients (60 GCA, 29 TA, 26 PAN, 37 EGPA), during both active vasculitis and remission. In GCA, these showed significant (p < 0.05) differences between disease states: B cell-attracting chemokine 1 (BCA)-1/CXC motif ligand 13 (CXCL13), erythrocyte sedimentation rate (ESR), interferon-γ-induced protein 10/CXC motif chemokine 10, soluble interleukin 2 receptor α (sIL-2Rα), and tissue inhibitor of metalloproteinase-1 (TIMP-1). In EGPA, these showed significant increases during active disease: granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF, interleukin (IL)-6, IL-15, and sIL-2Rα. BCA-1/CXCL13 also showed such increases, but only after adjustment for treatment. In PAN, ESR and matrix metalloprotease (MMP)-3 showed significant differences between disease states. Differences in biomarker levels between diseases were significant for 11 markers and were more striking (all p < 0.01) than differences related to disease activity. A combination of lower values of TIMP-1, IL-6, interferon-γ, and MMP-3 correctly classified 87% of samples with inactive GCA., Conclusion: We identified novel biomarkers of disease activity in GCA and EGPA. Differences of biomarker levels between diseases, independent of disease activity, were more apparent than differences related to disease activity. Further studies are needed to determine whether these serum proteins have potential for clinical use in distinguishing active disease from remission or in predicting longer-term outcomes.

Objective: The Patient Reported Outcome Measurement Information System (PROMIS) is a collection of item banks of self-reported health. This study assessed the feasibility and construct validity of using PROMIS instruments in vasculitis., Methods: Data from a multicenter longitudinal cohort of subjects with systemic vasculitis were used. Instruments from 10 PROMIS item banks were selected with direct involvement of patients. Subjects completed PROMIS instruments using computer adaptive testing (CAT). The Medical Outcomes Study Short Form-36 (SF-36) was also administered. Cross-sectional construct validity was assessed by calculating correlations of PROMIS scores with SF-36 measures and physician and patient global scores for disease activity. Longitudinal construct validity was assessed by correlations of between-visit differences in PROMIS scores with differences in other measures., Results: During the study period, 973 subjects came for 2306 study visits and the PROMIS collection was completed at 2276 (99%) of visits. The median time needed to complete each PROMIS instrument ranged from 40 to 55 s. PROMIS instruments correlated cross-sectionally with individual scales of the SF-36, most strongly with subscales of the SF-36 addressing the same domain as the PROMIS instrument. For example, PROMIS fatigue correlated with both the physical component score (PCS; r = -0.65) and with the mental component score (MCS; r = -0.54). PROMIS physical function correlated strongly with PCS (r = 0.81) but weakly with MCS (r = 0.29). Weaker correlations were observed longitudinally between change in PROMIS scores with change in PCS and MCS., Conclusion: Collection of data using CAT PROMIS instruments is feasible among patients with vasculitis and has some cross-sectional and longitudinal construct validity.

Objective: Involvement of intracranial arteries in giant cell arteritis (GCA) is rare. We describe the neurologic complications of intracranial GCA (IC GCA) and available treatment options., Methods: We describe 5 IC GCA cases from 3 Canadian vasculitis centers and review the literature. We searched English-language publications reporting similar patients meeting American College of Rheumatology (ACR) criteria for GCA and having intracranial artery involvement diagnosed by autopsy, magnetic resonance angiography, computed tomography angiography, or conventional angiography., Results: All 5 cases of IC GCA met ACR criteria for GCA; 4 cases had a temporal artery biopsy that was consistent with GCA. All cases experienced cerebrovascular accident(s). Arteritis involved the following vessels: intracranial internal carotid (n = 1), vertebrobasilar arteries (n = 1), or both (n = 3). All cases received aspirin and oral prednisone (preceded by intravenous methylprednisone in 3 cases), combined with an immunosuppressant in 4 cases. All patients survived; 2 had complete neurological recovery, 3 had residual neurologic sequelae. The literature review included 42 cases from 28 publications. The clinical features of the reported cases were similar to those of our 5 cases. However, mortality was 100% in untreated cases (n = 2), 58% in those treated with corticosteroid alone (n = 31), and 40% in those treated with corticosteroid and an immunosuppressant (n = 10)., Conclusion: IC GCA appears to be associated with neurologic complications and mortality. In some cases corticosteroid alone was not sufficient to prevent neurologic complications. The role of additional immunosuppressive agents needs further investigation.

Objective: The Canadian Vasculitis research network (CanVasc) is composed of physicians from different medical specialties and researchers with expertise in vasculitis. One of its aims is to develop recommendations for the diagnosis and management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada., Methods: Diagnostic and therapeutic questions were developed based on the results of a national needs assessment survey. A systematic review of existing non-Canadian recommendations and guidelines for the diagnosis and management of AAV and studies of AAV published after the 2009 European League Against Rheumatism/European Vasculitis Society recommendations (publication date: January 2009) until November 2014 was performed in the Medline database, Cochrane library, and main vasculitis conference proceedings. Quality of supporting evidence for each therapeutic recommendation was graded. The full working group as well as additional reviewers, including patients, reviewed the developed therapeutic recommendations and nontherapeutic statements using a modified 2-step Delphi technique and through discussion to reach consensus., Results: Nineteen recommendations and 17 statements addressing general AAV diagnosis and management were developed, as well as appendices for practical use, for rheumatologists, nephrologists, respirologists, general internists, and all other healthcare professionals more occasionally involved in the management of patients with AAV in community and academic practice settings., Conclusion: These recommendations were developed based on a synthesis of existing international guidelines, other published supporting evidence, and expert consensus considering the Canadian healthcare context, with the intention of promoting best practices and improving healthcare delivery for patients with AAV.

Objective: To determine frequency and outcomes of granulomatosis with polyangiitis (GPA)-related cardiac disease in a North American GPA cohort., Methods: Analysis was done of all patients in the Vasculitis Clinical Research Consortium Longitudinal Study of GPA. Demographic and clinical characteristics of patients with and without GPA-related cardiac involvement were compared., Results: Of 517 patients with GPA, 3.3% had cardiac involvement. No differences were observed between patients with or without cardiac involvement in terms of demographics, antineutrophil cytoplasmic antibody positivity, or relapse rate., Conclusion: Cardiac involvement in GPA is rare and heterogeneous. In this cohort, cardiac involvement was not associated with a higher rate of relapse or premature death.

Objective: Systemic necrotizing vasculitides (SNV) are associated with more frequent subclinical atherosclerosis, suggesting that SNV might be associated with a higher risk of major cardiovascular events (MCVE). We aimed to identify factors predictive of MCVE in patients with SNV., Methods: Patients in remission from SNV were assessed for CV risk factors and subclinical atherosclerosis. MCVE was defined as myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, and/or death from CV causes. MCVE-free survival curves were compared using the log-rank test., Results: Forty-two patients were followed for 7.1±2.6 years. Eight patients (18.9%) had MCVE. The respective 5- and 10-year MCVE rates were 9.5% and 26.8%. National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III)-defined high-risk status [hazard ratio (HR) 5.02 (95% CI: 1.17-27.4), p=0.03], BMI>30 kg/m2 [HR 4.84 (95% CI: 1.46-116), p=0.02], and plaque detection in the abdominal aorta (p=0.01) were significantly associated with MCVE. SNV characteristics, corticosteroid maintenance therapy, and C-reactive protein>5 mg/l were not associated with MCVE. Plaque in the aorta was significantly associated with high-risk status (p<0.001), while BMI and high-risk status were independent variables. Thus, a BMI>30 kg/m2 and/or a high-risk status were strongly associated with MCVE (p=0.004). Carotid intima-media thickness (IMT) identified patients with early MCVE and was correlated with the time to MCVE (r2=0.68, p=0.01)., Conclusion: These results suggest that factors associated with a higher MCVE risk in patients with SNV are NCEP/ATP III-defined high-risk status and BMI>30 kg/m2. Carotid IMT could help identify patients with SNV at risk of early MCVE.

Objective: The effect of systemic sclerosis (SSc) on bone density is not well understood. Through systematic review of the literature, the objectives of this study were to synthesize data about the prevalence of low bone mineral density (BMD), risk factors for low BMD, and occurrence of fracture and fracture-related mortality in SSc., Methods: A search was conducted of MEDLINE (1948-2012), Evidence Based Medicine Reviews (1991-2012), EMBASE (1980-2012), and CINAHL (1981-2012). Abstracts were screened to identify studies that evaluated low BMD in patients with SSc. Two investigators independently used a standardized form to abstract prevalence of osteopenia and osteoporosis (OP); risk factors for low BMD, BMD measurements, frequency of fracture, and fracture-related mortality., Results: Screening of 1032 citations identified 19 articles. Fifteen studies compared patients with SSc to controls. Most patients were white, female (prevalence 74%-100%), and postmenopausal (prevalence 45.9%-100%). The prevalence of low BMD and OP was 27%-53.3% and 3%-51.1%, respectively. Ten studies reported a lower BMD in patients with SSc compared to matched controls, whereas 2 studies reported no difference. Candidate risk factors for low BMD in SSc include family history of OP, age, menopause, diffuse subtype, presence of internal organ involvement, low vitamin D levels, and calcinosis. However, the studies supporting these factors were conflicting. Fracture rate ranged between 0% and 38%. No study reported OP-related fracture mortality., Conclusion: The data suggest that patients with SSc are at risk of low BMD and fracture, especially when other risk factors for OP are present. The interaction of SSc manifestations, traditional OP risk factors, and clinically relevant outcomes is complex and warrants further research.

Objective: (1) To describe a series of adults assessed for suspected primary angiitis of the central nervous system (PACNS) and their final diagnosis; (2) to describe and compare presenting features of PACNS and reversible cerebral vasoconstriction syndrome (RCVS); and (3) to evaluate the specificity of the presenting features of RCVS., Methods: Patients evaluated at our institution between 2000 and 2008 for a possible CNS vasculitis and investigated by conventional angiography and/or brain biopsy were retrospectively analyzed. The inclusion criteria were a clinicoradiological presentation and cerebral angiography and/or brain biopsy raising the hypothesis of isolated cerebral vasculitis; and absence of identifiable etiology at the time of conventional angiogram and/or brain biopsy., Results: Among 58 cases evaluated, 37 met the inclusion criteria and 33 were included in the study. Thirteen patients had RCVS. Thunderclap headaches, the absence of a focal neurological deficit, a convexal subarachnoid hemorrhage and/or normal brain parenchyma on magnetic resonance imaging, and "string of beads" appearance on conventional angiography had high diagnostic value. Six patients had other noninflammatory vascular disorders (intracranial atherosclerosis, cryptogenic embolism, and genetic vasculopathy). Six patients had infection or malignancy. Eight patients were diagnosed with PACNS; their clinical presentation and disease course were heterogeneous. Brain biopsy was performed in 3 cases (positive in 1)., Conclusion: RCVS is an important differential diagnosis of CNS vasculitis. Its particular presentation should allow rapid identification in order to avoid pointless investigations and treatment. The frequent lack of histological proof and heterogeneous presentation of PACNS illustrated the nosological uncertainties of this label.

Objective: To evaluate the efficacy compared to the relapse risk and tolerance of systematic rituximab (RTX) infusions as maintenance therapy for patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), who entered remission taking conventional immunosuppressants or RTX., Methods: A retrospective study of the main clinical characteristics, outcomes, and RTX tolerance of patients who had received ≥ 2 RTX maintenance infusions in our center, regardless of induction regimen, between 2003 and 2010., Results: We identified 28 patients [4 MPA and 24 GPA; median age 55.5 yrs (range 18-78); 17 (60%) males] who received a median of 4 (range 2-10) RTX maintenance infusions, with median followup of 38 months (range 21-97) since diagnosis or last flare. None experienced a RTX infusion-related adverse event; 15 patients (among the 21 with available data) had hypogammaglobulinemia (predominantly IgM) prior to their last RTX maintenance infusion; 3 had infectious events (1 cutaneous abscess, 1 otitis, 1 fatal H1N1 flu). Two patients suffered pulmonary relapses shortly before a planned RTX maintenance infusion (both had increased antineutrophil cytoplasmic antibody levels and 1 had CD19+ lymphocyte reconstitution)., Conclusion: Rituximab maintenance therapy was well tolerated but did not completely prevent relapses and persistent "grumbling" disease. These preliminary results remain to be confirmed by a randomized controlled trial currently in progress.

Objective: To study the frequency and characteristics of patients with Wegener's granulomatosis (WG) strictly and persistently localized to one organ., Methods: Retrospective analysis of the French Vasculitis Study Group (FVSG) WG cohort., Results: Sixteen patients (3.2% of the cohort) were identified who had isolated lung nodules, ear-nose-throat, or ocular involvement that did not progress to systemic disease (median followup, 58 mo) over the period of observation. Ten received first-line therapy with cyclophosphamide, which was effective in 4. Cotrimoxazole alone achieved remission in one, combined with corticosteroids in 3. Eight required subsequent treatments because of first-line failure or relapse., Conclusion: Strictly and persistently localized WG is uncommon. Optimal treatment remains to be determined.

Objective: To investigate brain involvement in patients with systemic sclerosis (SSc)., Methods: Sixty-three patients with SSc fulfilling the American College of Rheumatology and/or Leroy and Medsger criteria were retrospectively studied, including 30 (47.6%) with limited cutaneous and 27 (42.9%) with diffuse cutaneous SSc. Forty-one patients underwent computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain, 11 patients only CT scan, and the remaining 11 patients only MRI. Cerebral vasculopathy on MRI and CT scan was defined as absent or mild (score < 1), moderate (1 or= 2) on a 4-point scale (0 to 3)., Results: Cerebral vasculopathy was identified on CT scan in 22 patients (moderate in 12 and severe in 10) and on MRI in 38 patients (moderate in 28 and severe in 10). Patients with severe cerebral vasculopathy seen on MRI were more likely to have pulmonary arterial hypertension (PAH; p = 0.003) and showed a tendency to have scleroderma renal crisis (SRC; p = 0.25, test for trend p = 0.097). A similar association was found between severe cerebral vasculopathy seen on CT scan and PAH (p = 0.026) or SRC (p = 0.04). After adjusting for age and hypertension, severe cerebral vasculopathy was still associated with increased risk of severe vascular manifestations [odds ratio (OR) 32, 95% confidence interval (CI) 3.45-297, p = 0.002 for CT scan; OR 26, 95% CI 1.71-394, p = 0.019 for MRI]., Conclusion: Severe cerebral vasculopathy is associated with severe vascular manifestations in SSc patients. SSc patients with severe vascular complications should undergo neuroradiological imaging assessment of brain involvement.

Objective: To evaluate the effects and safety of 6-month intravenous cyclophosphamide (CYC) followed by 18-month oral azathioprine (AZA) therapy in patients with systemic sclerosis (SSc) and worsening interstitial lung disease (ILD)., Methods: All patients presented with ILD and worsened forced vital capacity (FVC) and/or total lung capacity of more than 10% and/or DLCO of more than 15% during the previous year. Treatment was 6 monthly pulses of 0.6 g/m(2) CYC followed by oral AZA for 18 months on disease stabilization or improvement. The endpoint was the rate of percentage change in pulmonary function tests (PFT) after 6 and 24 months., Results: Twenty-seven patients with SSc (20 females) were recruited. Age and disease duration before CYC therapy were (mean +/- SD) 49.4 +/- 15 years and 75.5 +/- 87.8 months, respectively. Mean baseline FVC was 67% +/- 19% of predicted value. At 6 months, in 7 (26%) patients disease was improved, in 12 (44%) stabilized, and in 8 (30%) worsened. Among the 19 (70%) responders, 15 received AZA and 4 declined. Twenty-three completed 2-year followup, 3 died, and one dropped out. Six (22.2%) had improved, 8 (29.6.%) were stable, and 13 (48.2%) had worsened. Evolution of the slope of FVC (in % per year) varied from -15.5 prior to treatment to +3 (p = 0.004) at 6 months and to +1 (p < 5 x 10(-5)) at 24 months., Conclusion: Intravenous CYC followed by oral maintenance immunosuppressive therapy for worsening ILD was well tolerated and was associated with stable or improved PFT in 70% and 51.8% of SSc patients at 6 months and 2 years, respectively.

Objective: To determine the prevalence and characteristics of moderate to severe pulmonary hypertension (PH) in patients with systemic sclerosis (SSc) with and without interstitial lung disease (ILD)., Methods: We retrospectively studied clinical and functional characteristics of 197 consecutive patients with SSc who had undergone a screening echocardiography to detect PH., Results: Moderate to severe PH was suspected in 36 patients (18.3%) and confirmed in 32 who underwent right heart catheterization. The prevalence of PH did not differ between patients with limited and patients with diffuse cutaneous SSc. PH was detected in 12/67 (17.9%) patients without ILD vs 24/110 (21.8%) patients with ILD (p not significant). In patients with ILD, a lower PaO2 appeared as the unique independent factor significantly associated with PH, regardless of the extent of fibrosis. In 3 patients out of 9 (33.3%) with ILD and significantly restrictive disease, PH was out of proportion to the degree of fibrosis. In patients with no ILD, a higher grade of dyspnea appeared as the unique independent factor associated with PH. In patients with no ILD, altered DLCO was the sole indicator of the pulmonary function tests associated with PH (best cutoff value 72%). DLCO correlated with systolic pulmonary arterial pressure only in patients with no ILD., Conclusion: Prevalence of moderate to severe PH was similar in SSc patients with and those without ILD. In patients with ILD, a lower PaO2 was the unique independent indicator associated with PH. In some patients with severe ILD, PH was out of proportion to the degree of fibrosis. A linear correlation between DLCO and systolic pulmonary arterial pressure was observed only in patients without ILD. All these indicators should assist identification of patients with or without ILD requiring diagnostic procedures for PH before annual screening.

Objective: Investigators have reported significant seasonal variations of onset of Wegener's granulomatosis (WG), but those data were not confirmed by others. We reexamined the hypothesis of a seasonal pattern of onset of WG., Methods: We conducted telephone interviews with 59 patients with newly diagnosed WG fulfilling the American College of Rheumatology criteria. Patients were identified having been enrolled from 2001 to 2004 by French hospitals in 2 multicenter therapeutic trials. The interviews investigated precisely how and when their disease had appeared to establish an index date, defined as the year and month of the first symptom(s) attributable to WG. Once telephone interviews had been completed, index dates were also retrieved from medical records., Results: Among the 59 patients interviewed, 14 (24%) were unable to specify an exact month of WG onset. Based on the remaining 45 "informative" patients, the month of onset distribution varied significantly (p = 0.03, exact goodness-of-fit chi-square test), notably with a higher onset rate in August (p = 0.001). Seasonal distributions also differed significantly (p = 0.01), with an increased rate of summer onset (June-August) (p = 0.001). Index dates extracted from medical files showed that onset was also more frequent in summer (p = 0.01)., Conclusion: Our results confirm the seasonality in onset of WG, but unlike previous reports indicating an increase in winter, instead suggest that this vasculitis preferentially appears in summer. These findings might support an allergic mechanism in the pathogenesis of WG.