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Reports of mortality risks among individuals with giant cell arteritis (GCA) have been mixed. Our aim was to evaluate all-cause mortality among individuals with GCA relative to the general population over time.We performed a population-based study in Ontario, Canada using health administrative data. We studied a cohort of 22,677 GCA patients ages ≥50 years that was identified using a validated case definition (with 81% positive predictive value, 100% specificity). General population comparators were residents ages ≥50 years without GCA. Deaths were ascertained from vital statistics. Annual crude, age- and sex-standardized, and age- and sex-specific all-cause mortality rates were determined for individuals with and without GCA between 2000 and 2018. Standardized mortality ratios (SMRs) were estimated.Age- and sex-standardized mortality rates were significantly higher for GCA patients than comparators, and trending to increase over time with 50.0 deaths per 1,000 GCA patients in 2000 (95% confidence interval [95% CI] 34.0-71.1) and 57.6 deaths per 1,000 GCA patients in 2018 (95% CI 50.8-65.2), whereas mortality rates in the general population significantly declined over time. The annual SMRs for GCA patients generally increased over time, with the lowest SMR occurring in 2002 (1.22 [95% CI 1.03-1.40]) and the highest in 2018 (1.92 [95% CI 1.81-2.03]). GCA mortality rates were more elevated for male patients than female patients.Over a 19-year period, mortality rates were increased among GCA patients relative to the general population, and more premature deaths were occurring in younger age groups. The relative excess mortality for GCA patients did not improve over time.

Objective.Rheumatoid arthritis (RA) is more common in females, and although the cause of RA is unknown, it is characterized by the production of autoantibodies. The aims of this study were to determine whether RA-associated autoantibodies are more often found in females than males and to identify factors that influence the relationship between sex and seropositivity.Methods.Databases were searched and studies of RA (N ≥ 100) were included if they reported proportion of seropositive patients with RA by sex. Metaanalyses and metaregression were conducted using the random-effects model. Covariates regressed were smoking, age, BMI, Health Assessment Questionnaire–Disability Index (HAQ-DI), and the Disease Activity Score in 28 joints (DAS28).Results.Eighty-four studies with a total of 141,381 subjects with rheumatoid factor (RF) seropositivity and 95,749 subjects with anticitrullinated protein antibody (ACPA) seropositivity met inclusion criteria. The mean age of participants ranged from 37 to 68 years and the proportion of female subjects ranged from 9% to 92%. Results indicated that females were less likely than males to be seropositive: odds ratio (OR) 0.84 [95% CI 0.77–0.91] for RF and OR 0.88 [95% CI 0.81–0.95] for ACPA. BMI, smoking, mean age, DAS28, and HAQ-DI did not affect the relationship between sex and seropositivity.Conclusion.Although studies report that females have higher RA disease activity than males and that seropositivity predicts worse outcomes, females were less likely to be seropositive than males.

ObjectiveIn 2020, the Canadian Vasculitis Research Network (CanVasc) published their updated recommendations for the management of ANCA-associated vasculitides (AAV). The current addendum provides further recommendations regarding the use of avacopan in AAV based on a review of newly available evidence.MethodsAn updated systematic literature review on avacopan (formerly, CCX168) using Medline, Embase, and the Cochrane Library was performed for publications up to September 2022. New recommendations were developed and categorized according to the EULAR grading levels, as done for previous CanVasc recommendations. A modified Delphi procedure and videoconferences were used to reach ≥80% consensus on the inclusion, wording and grading of each recommendation.ResultsThree new recommendations were developed. They focus on avacopan therapy indication and duration, as well as timely glucocorticoid tapering.ConclusionThese 2022 addended recommendations provide rheumatologists, nephrologists and other specialists caring for patients with AAV with guidance for the use of avacopan, based on current evidence and consensus from Canadian experts.

Objective: Antibodies to citrullinated and homocitrullinated (also known as carbamylated) proteins, specific for rheumatoid arthritis (RA), are associated with cardiovascular disease (CVD). Immune ...

Objective To estimate trends in the incidence and prevalence of GCA over time in Canada. Methods We performed a population-based study of Ontario health administrative data using validated case definitions for GCA. Among Ontario residents ≥50 years of age we estimated the annual incidence and prevalence rates between 2000 and 2018. We performed sensitivity analyses using alternative validated case definitions to provide comparative estimates. Results Between 2000 and 2018 there was a relatively stable incidence over time with 25 new cases per 100 000 people >50 years of age. Age-standardized incidence rates were significantly higher among females than males [31 cases (95% CI: 29, 34) vs 15 cases (95% CI: 13, 18) per 100 000 in 2000]. Trends in age-standardized incidence rates were stable among females but increased among males over time. Incidence rates were highest among those ≥70 years of age. Standardized prevalence rates increased from 125 (95% CI 121, 129) to 235 (95% CI 231, 239) cases per 100 000 from 2000 to 2018. The age-standardized rates among males rose from 76 (95% CI 72, 81) cases in 2000 to 156 (95% CI 151, 161) cases per 100 000 population in 2018. Between 2000 and 2018, the age-standardized rates among females similarly increased over time, from 167 (95% CI 161, 173) to 304 (95% CI 297, 310) cases per 100 000 population. Conclusion The incidence and prevalence of GCA in Ontario is similar to that reported in the USA and northern Europe and considerably higher than that reported for southern Europe and non-European populations.

Rheumatoid arthritis (RA) is a systemic musculoskeletal disease where immune dysregulation and subsequent autoimmunity induce significant synovial joint inflammation and damage, causing pain and disability. RA disease onset is promoted through multifaceted interactions between genetic and environmental risk factors. However, the mechanisms of disease onset are not completely understood and disease-specific treatments are yet to be developed. Current RA treatments include nonspecific disease-modifying antirheumatic drugs (DMARDs) that suppress destructive immune responses and prevent damage. However, DMARDs are not curative, and relapses are common, necessitating lifelong therapy in most patients. Additionally, DMARD-induced systemic immunosuppression increases the risk of serious infections and malignancies. Herein, we review the current understanding of RA disease pathogenesis, with a focus on T and B cell immune tolerance breakdown, and discuss the development of antigen-specific RA therapeutics that aim to restore a state of immune tolerance, with the potential for disease prevention and reduction of treatment-associated adverse effects.

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 Metabolic syndrome (MetS) prevalence in early rheumatoid arthritis (ERA) is conflicting. The impact of sex, including menopause, has not been described. We estimated the prevalence and factors associated with MetS in men and women with ERA. Methods A cross‐sectional study of the Canadian Early Arthritis Cohort (CATCH) was performed. Participants with baseline data to estimate key MetS components were included. Sex‐stratified logistic regression identified baseline variables associated with MetS. Results The sample included 1543 participants; 71% were female and the mean age was 54 (SD 15) years. MetS prevalence was higher in men 188 (42%) than women 288 (26%, P < 0.0001) and increased with age. Frequent MetS components in men were hypertension (62%), impaired glucose tolerance (IGT, 40%), obesity (36%), and low high‐density lipoprotein cholesterol (36%). Postmenopausal women had greater frequency of hypertension (65%), IGT (32%), and high triglycerides (21%) compared with premenopausal women (P < 0.001). In multivariate analysis, MetS was negatively associated with seropositivity and pulmonary disease in men. Increasing age was associated with MetS in women. In postmenopausal women, corticosteroid use was associated with MetS. Psychiatric comorbidity was associated with MetS in premenopausal women. MetS status was not explained by disease activity or core RA measures. Conclusion The characteristics and associations of MetS differed in men and women with ERA. Sex differences, including postmenopausal status, should be considered in comorbidity screening. With this knowledge, the interplay of MetS, sex, and RA therapeutic response on cardiovascular outcomes should be investigated.

OBJECTIVE. Only a few small case series, case reports, and one small clinical trial suggested some benefit of leflunomide (LEF) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and other vasculitides. We analysed the clinical efficacy and tolerability of LEF in a large cohort of patients with various vasculitides. METHODS. This was a retrospective analysis of patients who received LEF for treatment of their vasculitis enrolled in the Vasculitis Clinical Research Consortium (VCRC) Longitudinal Study and in 3 additional centres from the Canadian vasculitis research network (CanVasc). RESULTS. Data for 93 patients were analysed: 45 had granulomatosis with polyangiitis (GPA), 8 microscopic polyangiitis (MPA), 12 eosinophilic granulomatosis with polyangiitis (EGPA), 14 giant-cell arteritis (GCA), 9 Takayasu’s arteritis (TAK), and 5 polyarteritis nodosa (PAN). The main reason for initiation of LEF was active disease (89%). LEF was efficacious for remission induction or maintenance at 6 months for 62 (67%) patients (64% with GCA, 89% with TAK, 80% with PAN, 69% with GPA, 75% with MPA, 33% with EGPA); 20% discontinued LEF before achieving remission because of persistent disease activity. Overall, 22 adverse events (gastrointestinal symptoms being the most common) led to drug discontinuation in 18 (19%) patients, of which 12 stopped LEF before month 6, before showing any benefit in 8/12 of these patients. CONCLUSION. Leflunomide can be an effective therapeutic option for various vasculitides, especially for non-severe refractory or relapsing ANCA-associated vasculitis or large-vessel vasculitis. No new safety signals for LEF were identified in this population.

Rheumatoid Arthritis (RA) is more common and severe in women compared to men. Both women and men with RA express autoantibodies to post-translationally modified antigens, including citrullinated and homocitrullinated proteins or peptides. These autoantibodies are strongly linked with the HLA-DR4 gene. The objective of this study was to determine sex differences in immune responses to homocitrullinated antigens. We used a humanized animal model of RA, DR4-transgenic mice and immunized them with a homocitrullinated peptide called HomoCitJED. Immune responses in these mice were measured for splenocyte proliferation by tritiated thymidine incorporation, serum autoantibody production by ELISA and cytokine levels by multiplex. We found that T cell and antibody responses to homocitrullinated antigens were similar in male and female mice. However, we found sex differences in serum cytokine profiles with female mice having higher ratio of IL-1α to IL-5, suggesting imbalances in immune regulation. This is the first study to report that immune responses to homocitrullinated antigens can be differentiated by sex., Highlights • Splenocyte proliferation and antibody responses in DR4tg mice immunized with a homocitrullinated peptide were similar for females and males. • The cytokine profile of homocitrullinated peptide-immunized DR4tg mice was differentiated by sex: females had a higher ratio of IL-1α to IL-5. • Anti-homocitrullinated peptide splenocyte and antibody responses were more frequent in DR4tg than wild-type B6 mice.

OBJECTIVE To compare the clinical features, efficacy and safety of treatment regimens, and outcomes of childhood- and adult-onset Takayasu arteritis (TAK). METHODS The study was designed as a retrospective cohort study comparing patients with childhood-onset TAK (from 1986 onward) to patients with adult-onset TAK (from 1988 onward) who were followed up until 2014 or 2015 at 4 centers in Ontario, Canada. Demographic, clinical, laboratory, and angiographic features, treatment regimens, and outcomes were recorded throughout the course of the disease. Disease activity and damage scores were completed retrospectively. RESULTS Twenty-nine children and 48 adults (median age at diagnosis 12.1 years and 31.2 years, respectively) were included. A lower predominance of females was observed among the childhood-onset TAK cohort (76% versus 100% of patients with adult-onset TAK; P < 0.01), and children had a shorter delay to diagnosis (median 6.0 months versus 12.2 months for adults; P = 0.03). The distribution of vascular involvement was also different, with children having significantly more aortic and renal artery involvement and a higher frequency of arterial hypertension. Relapses in the first year after diagnosis were common both in children (39%) and in adults (28%). Two children, but no adults, died. CONCLUSION Childhood-onset TAK has a lower female predominance and a higher frequency of aortic and renal involvement compared to adult-onset TAK. Relapses and disease burden were high in both groups, corroborating the need for careful monitoring of disease activity and aggressive therapeutic management.

Objective.Antibodies that target citrullinated protein/peptide (ACPA) and homocitrullinated/carbamylated protein/peptide (AHCPA) are associated with rheumatoid arthritis (RA). The relationship between ACPA and AHCPA remains unclear. We examined the expression and cross-reactivity of these antibodies using citrulline- and homocitrulline-containing synthetic peptides, CitJED and HomoCitJED, respectively, which have equal numbers of citrulline or homocitrulline residues on the same peptide backbone.Methods.Serum from healthy subjects (n = 51) and patients with RA (n = 137), systemic lupus erythematosus (SLE; n = 37), and psoriatic arthritis (PsA; n = 37) were screened for IgG anti-CitJED and anti-HomoCitJED antibodies by ELISA. Cross-reactivity of these antibodies was examined by inhibition with various concentrations of CitJED and HomoCitJED.Results.Out of 137 patients with RA, antibodies to CitJED and HomoCitJED were detected in 69 (50%) and 78 (57%), respectively. Anti-CitJED and HomoCitJED antibodies were 77% concordant and their levels were strongly correlated [Spearman correlation coefficient (rs) = 0.6676]. Sera from 25/27 patients (93%) with RA were inhibited by both CitJED and HomoCitJED with equal or higher affinity for the cognate (homologous) peptide.Conclusion.Antibodies to CitJED and HomoCitJED frequently occurred in RA, but were not found in SLE or PsA, suggesting that these antibodies are specific to RA. Cross-reactivity between anti-HomoCitJED and anti-CitJED antibodies suggests that ACPA and AHCPA are derived from the same B cell population and both may contribute to the pathogenesis of RA.

Aberrant macrophage polarization is a major contributor to the onset and progression of atherosclerosis. Despite this, macrophage polarization during in early stages of human atherosclerotic disease is poorly understood. Using transcriptomic analysis of macrophages recovered from early-stage human atherosclerotic lesions, we have identified a unique gene expression profile dissimilar to that observed in later stages of disease that is characterized by upregulation of the hematopoietic transcription factor GATA2. GATA2 overexpressionin vitrorecapitulated defects observed in patient macrophages, including deficiencies in the uptake and processing of apoptotic cells, and in the catalysis of atherogenic protein modifications, with GATA2 knockdown abrogating these defects. Our data describe a previously unreported macrophage differentiation state present in early atheroma formation and identifies GATA2 as a driver of macrophage functional defects during the early stages of atherosclerosis in humans.

Background Prevalence studies of metabolic syndrome (MetS) in early rheumatoid arthritis (ERA) are sparse and estimates are variable. Differences by sex and menopausal status have not been formally assessed. Objectives We estimated prevalence and factors associated with MetS in ERA patients treated in routine practice settings. Variations by sex, and by menopausal status were also examined. Methods Cross-sectional data were analyzed from patients meeting 1987 or 2010 ACR/EULAR RA criteria enrolled in the Canadian Early Arthritis Cohort (CATCH) from January 2007-March 2017. CATCH is a prospective multicenter observational study of patients diagnosed and treated for early inflammatory arthritis (symptoms Results The sample included 1543 participants; 71% were female and mean(SD) age was 54 (15) years. 476 (31%) of the total sample met criteria for MetS. Participants with MetS were older, more frequently past smokers and reported more comorbid conditions, including cardiovascular disease (CVD) (p Conclusion Approximately 1 in 3 ERA patients met crietria for MetS. Though men had a higher prevalence of MetS and individual MetS components, post-menopausal women had a similar MetS profile as men, and should equally be considered high risk for CVD development. Characteristics and associations with MetS differed in men and women suggesting sex-specific variations are important considerations for comorbidity screening and surveillance of CVD outcomes in ERA. Reference [1] Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15(7):539-53. Acknowledgement Sponsors: Amgen & Pfizer-Founding sponsors 2007+; AbbVie 2011+; Medexus 2013+;EliLilly2016+, Merck Canada 2017+, Hoffmann-LaRoche & Janssen Biotect 2011-2016, UCB & BMS 2011-2018, Sanofi-Genzyme 2016-2017. Disclosure of Interests Bindee Kuriya Consultant for: Advisory Board Member: Abbvie, Sanofi Genzyme, Eli Lilly, Pfizer Canada, Roche, Orit Schieir: None declared, Marie-France Valois: None declared, Janet Pope Consultant for: Eli Lilly and Company, Gilles Boire Grant/research support from: Investigator-initiated studies: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Pfizer, Consultant for: Advisory boards: Amgen, BMS, Celgene, Eli Lilly, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Louis Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Speakers bureau: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Glen Hazlewood : None declared, Carter Thorne Grant/research support from: Investigator-initiated studies: Amgen, Pfizer. RCTs: Abbvie, Celgene, CaREBiodam, Novartis, Pfizer, Consultant for: Advisory board: Abbvie, Amgen, Celgene, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi. Consultant: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Diane Tin: None declared, CArol Hitchon Grant/research support from: Pfizer, UCB (unrelated studies), Susan J. Bartlett Consultant for: Pfizer, UCB, Lilly, Novartis, Merck, Jansen, Abbvie, Edward Keystone Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, Consultant for: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, UCB., Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Lillian Barra: None declared

Introduction Rheumatoid arthritis is frequently associated with hypertension, which has been shown to increase the risk of cardiovascular disease in these patients. The aim of this systematic review was to explore demographic, behavioural or clinical factors including medication use, associated with incident hypertension in rheumatoid arthritis. Methods MEDLINE and Scopus were searched for eligible studies that longitudinally investigated incident hypertension or changes in blood pressure (BP) in rheumatoid arthritis patients. Publications were screened by two reviewers according to predetermined inclusion and exclusion criteria. The quality of included studies was assessed via the Newcastle Ottawa Scale and Cochrane Risk of Bias Tool. Results Fourteen studies were deemed eligible and included in this review. The proportion of female subjects ranged from 12 to 87% and the mean age ranged from 47 to 61 years. Regular exercise was associated with a decrease in systolic BP, p = 0.021. Methotrexate was associated with decreased risk of hypertension in two studies. LEF was associated with increased BP in two studies. COX-2 inhibitors were associated with systolic BP and diastolic BP variability (p = 0.009, 0.039, respectively) in one study. Prednisone was found to increase BP and risk of hypertension in three studies. The risk of hypertension in patients taking biologic disease modifying anti-rheumatic drugs (DMARDs) is unclear as some studies report increased BP while others report no difference for biologic compared to conventional DMARDs. Conclusion Despite limited longitudinal studies exploring this topic, methotrexate and exercise were shown to protect against risk of hypertension in RA patients, while prednisone and COX-2 inhibitors may increase risk of hypertension.

Introduction: This study evaluated the prevalence and progression of subclinical carotid artery atherosclerosis in active rheumatoid arthritis (RA). Methods: Carotid arteries of RA patients were scanned using 3D ultrasound at baseline and 24 weeks for total plaque area, vessel wall volume, and intima-media thickness (IMT), as well as arterial stiffness measured using pulse wave velocity. Variables related to inflammation, lipids and cardiovascular (CV) risk were assessed for associations with plaque progression. Of 195 screened patients, 31 met inclusion criteria (66 Swollen joint count (SJC) plus 68 Tender joint count (TJC)≥8 OR SJC plus TJC≥4 with elevated acute phase reactants) and were enrolled (27 female; mean age 59.3±9.8years). Patients using lipid lowering drugs and uncontrolled comorbidities were excluded. Results: Atherosclerotic plaque occurred in 35% and arterial wall hypertrophy (IMT≥0.6mm) in 86% of patients. Most (68%) had an abnormal lipid profile characterized by reduced HDL and/or increased total cholesterol/HDL index, which was adversely affected by disease activity. Stepwise binary logistic regression analysis showed that Framingham risk score (OR=1.155, 95%CI:1.002-1.332, p=0.046) and ESR (OR=1.148, 95%CI:1.015-1.299, p=0.028) predicted plaque burden most strongly. Plaque progression was significantly associated with baseline higher hsCRP, ESR, and heavy smoking, but only hsCRP predicted plaque growth in multivariate regression analysis (p=0.004); and hsCRP was related to higher disease activity (r=0.443, p=0.016), LDL (r=0.544, p=0.007), and smoking (r=0.384, p=0.04). Conclusion: RA-related inflammation contributed to augmented CV burden in RA and might mediate its effect on atherosclerosis through hsCRP and modulation of the traditional CV risk factors, such as dyslipidemia.

Background Primary Central Nervous System Vasculitis (PCNSV) remains a diagnostic challenge due to its variable and non-specific clinical manifestations. In part, the clinical heterogeneity of PCNSV may be a consequence of the modalities used for diagnosis; accordingly, there may be different subtypes of PCNSV based on whether the diagnosis was attained by biopsy or cerebral angiography. Objective To examine the frequency of symptoms, laboratory, and radiological features associated with PCNSV, and to identify distinct clinical features between biopsy and angiography defined PCNSV. Methods We conducted a systematic review of articles published in the English language from 1991 to 2019 that met all diagnostic criteria of PCNSV. Results We identified 55 studies, reporting on 907 PCNSV cases. Median age was 45 (IQR 50–36), and 53% were women. Biopsy compared to angiography defined PCNSV had a higher percentage of cognitive impairment, and seizures on initial presentation, and were more likely to have a subacute or progressive onset, abnormal CSF profile, small vessel involvement on angiography, and tumor-like lesions and gadolinium enhancement on MRI. Angiography defined PCNSV were more likely to have an acute onset, focal weakness and visual impairment on initial presentation, medium vessel involvement on angiography, and infarcts on MRI. Brain biopsy was diagnostic of PCNSV in 71% of cases, and demonstrated an alternative diagnosis in 37% of cases, the most common being infection (19%) and lymphoproliferative disease (18%). Conclusions This study provides further evidence that there are distinct clinical features between biopsy and angiography defined PCNSV, which may aid in selecting patients for appropriate invasive tests.

Background:Individuals with giant cell arteritis (GCA) are at increased risk of serious morbidity including cardiovascular disease and stroke. Yet the risk of mortality among individuals with GCA have produced conflicting reports1.Objectives:Our aim was to evaluate excess all-cause mortality among individuals with GCA relative to the general population over time.Methods:We performed a population-based study in Ontario, Canada, using health administrative data among all individuals 50 years and older. Individuals with GCA were identified using a validated case definition (81% PPV, 100% specificity). All Ontario residents aged 50 and above who do not have GCA served as the General Population comparators. Deaths occurring in each cohort each year were ascertained from vital statistics. Annual crude and age/sex standardized all-cause mortality rates were determined for individuals with and without GCA between 2000 and 2018. Standardized mortality ratios (SMRs) were calculated to measure relative excess mortality over time. Differences in mortality between sexes and ages were also evaluated.Results:Population denominators among individuals 50 years and older with GCA and the General Population increased over time with 12,792 GCA patients and 5,456,966 comparators by 2018. Annual standardized mortality rates among the comparators steadily declined over time and were significantly lower than GCA morality rates (Figure). Annual GCA mortality rates fluctuated between 42-61 deaths per 1000 population (with overlapping confidence intervals) during the same time period. SMRs for GCA ranged from 1.28 (95% CI 1.08,1.47) at the lowest in 2002 to 1.96 (95% CI 1.84, 2.07) at the highest in 2018. GCA mortality rates and SMRs were highest among males and younger age groups.Conclusion:Over a 19-year period, mortality has remained increased among GCA patients relative to the general population. GCA mortality rates were higher among males and more premature deaths were occurring at younger age groups. In our study, improvements to the relative excess mortality for GCA patients over time (mortality gap) did not occur. Understanding cause-specific mortality and other factors are necessary to inform contributors to premature mortality among GCA patients.References:[1]Hill CL, et al. Risk of mortality in patients with giant cell arteritis: a systematic review and meta-analysis. Semin Arthritis Rheum. 2017;46(4):513-9.Figure.Acknowledgments: :This study was supported by a CIORA grantDisclosure of Interests:Lillian Barra: None declared, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB, Priscila Pequeno: None declared, Jodi Gatley: None declared, Jessica Widdifield: None declared

Atherosclerosis is an inflammatory disease involving formation of lipid-rich lesions within the arteries. Macrophages clear apoptotic cells that accumulate within these lesions. Defective apoptotic cell clearance is a hallmark of advanced atherosclerotic disease, yet mechanisms that drive this defect are poorly understood. In this study, we identify the hematopoietic transcription factor GATA2 as a novel regulator of macrophage-mediated apoptotic cell clearance. Macrophages were isolated by laser capture microdissection from atherosclerotic lesions in aortic tissue obtained from patients undergoing open heart surgery. Gene expression profiling was performed on these macrophages by microarray, with macrophages derived from peripheral blood monocytes used as a control. We found approximately 3,000 genes to be differentially expressed in aortic punch macrophages, with enrichment in pathways involved in apoptotic cell clearance. In particular, we identified upregulation of GATA2. Mutations in GATA2 have previously been associated with increased risk of coronary artery disease and we found that overexpression of GATA2 in vitro resulted in decreased ability of macrophages to both internalize and degrade apoptotic cells. Conversely, GATA2 downregulation is sufficient to abrogate oxLDL-induced defective apoptotic cell clearance. Atherosclerotic macrophages exhibit dysregulated expression of genes involved in apoptotic cell clearance and upregulation of GATA2. Recapitulation of GATA2 overexpression is sufficient to impair apoptotic cell clearance in vitro. To our knowledge, we are the first to identify a potential role for GATA2 in driving defective apoptotic cell clearance in atherosclerosis.

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.

Objectives : To study variations in Canadian clinical practice patterns for the management of ANCA-associated vasculitis (AAV) and identify points to consider for the development of national recommendations. Material and Methodology : A 30-item needs assessment questionnaire was sent to all members of the Canadian Vasculitis network (CanVasc), Canadian Rheumatology Association (CRA), Canadian Thoracic Society (CTS) and Canadian Society of Nephrology (CSN). Respondent characteristics, practice patterns, concerns and expectations were analyzed. Results : Among 132 physicians who followed at least 1 vasculitis patient and responded to the survey, 39% stated that they felt confident in their management of AAV. Several variations in practice were observed regarding diagnostic procedure, induction and maintenance treatments and use of biologics; some were due to logistic constraints (difficulties in access to some specific tests, drugs or care; lack of health care coverage for the costs). The top 5 topics for which recommendations are expected involve treatment for remission induction, maintenance, refractory disease, and relapse as well as biologics. Conclusion : Practice variations identified in this needs assessment survey will serve to formulate key questions for the development of CanVasc recommendations.

Background Takayasu's Arteritis (TAK) affects mostly young women and causes significant morbidity. Most patients are refractory to glucocorticoids (GC) or relapse when GC doses are reduced. The objective of this study is to summarize the literature pertaining to the effectiveness of non-GC drugs for the treatment of TAK. Methods MEDLINE and Embase were searched for English-language studies of TAK patients with a sample size >5. Studies were included if the effectiveness of non-GC drugs for the treatment of TAK was reported. Random effects meta-analyses of various effect measures were performed. Results Of the 915 studies identified by the search, 14 of small molecule immunosuppressants (IS) and 25 of biologic therapies were included. Studies had a high risk of bias. Pooled remission rates were similar for both categories of non-GC drugs: 58% (95% CI: 40–74%) and 64% (95% CI: 56–72%), respectively. The relapse rate was 54% (95% CI: 39–68%) for IS therapies and 31% (95% CI: 22–41%) for biologics. Both significantly decreased GC doses and acute phase reactants. Observational studies suggested that anti-TNF agents were more effective than IS at maintaining remission. Randomized-controlled trials (RCTs) of biologics were of small sample size: abatacept was not effective and the trial of tocilizumab was underpowered to detect a difference in time to relapse versus placebo. Serious adverse events were uncommon. Conclusions Non-GC agents were moderately effective in inducing remission in TAK, but relapse rates were high. Larger, better designed studies are required to determine the optimal treatment regimen for TAK.

To the Editor: Giant cell arteritis (GCA) is a large-vessel vasculitis with a predilection for cranial arteries. Based on retrospective studies, GCA is associated with an increased prevalence of traditional cardiovascular (CV) risk factors and CV events, including myocardial infarction and stroke1,2,3,4,5. However, studies regarding management of CV disease (CVD) in GCA are lacking. We report here on CV risk factors and CV complications, and describe physician adherence to guidelines for prevention of CV events in a Canadian population with GCA. We studied a single-center retrospective cohort of patients with GCA assessed at the St. Joseph’s Health Care rheumatology clinic in London, Ontario, by rheumatologists between 2006 and 2015. Patients were identified by diagnostic codes, met American College of Rheumatology classification criteria for GCA, and had at least 1 followup visit. CV complication (CVC) was defined as a composite outcome: any acute coronary syndrome (ACS), stroke, transient ischemic event, or severe peripheral vascular disease (PVD) requiring surgical intervention. Ethics approval was given by … Address correspondence to Dr. L.J. Barra, St. Joseph’s Health Care, 268 Grosvenor St., Room D2-160, London, Ontario N6A 4V2, Canada. E-mail: lillian.barra{at}sjhc.london.on.ca

Infections are common complications of necrotising vasculitis. We aimed to determine the rate of infections in patients with severe necrotising vasculitis treated with cyclophosphamide (CYC) combined with high dose glucocorticoids (GC).Searches of MEDLINE, Embase and Cochrane Library databases (1990 to May 2016) were performed. Inclusion criteria were randomised controlled trials of intravenous (IV) or oral (PO) CYC induction therapy for granulomatosis and polyangiitis (GPA), microscopic poyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and systemic polyarteritis nodosa (PAN). Pooled rates of infectious complications were determined by random effects meta-analyses. Meta-regression was performed to identify variables associated with severe infection.Search results yielded 2636 references; 14 studies with a total of 888 subjects met inclusion criteria. The mean age of participants ranged from 39 to 75 years. Mean cumulative doses of CYC were 2.7 to 50.4 g and of GC were 6 to 13 g. The pooled rate per year per gram of CYC of severe infection was 2.2% (95% CI: 0.9, 5.3%, I2 = 58.7%), any infection was 5.6% (95% CI: 1.8, 16.7%, I2 = 79.1%) and infection-related deaths was 1.7% (95% CI: 0.8, 3.9%, I2 = 0%). By meta-regression, age, creatinine and cumulative GC dose were not significantly associated with the rate of severe infections.The rate of severe infections and infection related mortality in patients with severe necrotising vasculitis treated with CYC + GC induction therapy is high.

Work disability associated with rheumatic diseases accounts for a substantial financial burden. However, few studies have investigated disability among patients with vasculitis. The purpose of this study was to examine the impact of vasculitis on patient employment and income.Patients enrolled in the Vasculitis Clinical Research Consortium (VCRC) Patient Contact Registry, living in the USA or Canada, and followed for1 year post-diagnosis, participated in an online survey-based study.421 patients with different systemic vasculitides completed the survey between June and December 2015. The majority of patients were female (70%) and Caucasian (90%); granulomatosis with polyangiitis (GPA) was the most common type of vasculitis (49%), and the mean age at the time of diagnosis was 53 years. At the time of their diagnosis of vasculitis 76% of patients were working a paid job, 6% were retired, and 2% were on disability. Over the course of their disease, and with a mean follow-up of 8±6.4 years post-diagnosis, 26% of participants became permanently work disabled or had to retire early due to vasculitis. Variables that were independently associated with permanent work disability included work physicality, less supportive work environment, and symptoms such as respiratory disease, pain, and cognitive impairment. Overall, patients reported a mean productivity loss of 6.9% and income was reduced by a median of 45%.Due to their vasculitis, patients frequently suffer substantial limitations in work and productivity, and personal income loss.

Antibodies to proteins/peptides containing citrulline are hallmarks of Rheumatoid Arthritis (RA). These antibodies are strongly associated with the expression of the Shared Epitope (SE). RA patients also generate antibodies to homocitrulline-containing proteins/peptides (also referred to as anti-carbamylated protein antibodies (Anti-CarP)). This study was undertaken to investigate the relationship between homocitrulline and citrulline immune responses using an established mouse model of RA: DR4-transgenic (DR4tg) mice that express the human SE. C57BL/6 (B6) and DR4tg (on a B6 background) mice were immunized subcutaneously with a homocitrullinated peptide (HomoCitJED). Splenic T cell proliferation was evaluated by 3H-thymidine incorporation assay. Antibodies to homocitrullinated and citrullinated antigens were screened by enzyme-linked immunosorbent assay (ELISA). Antibody cross-reactivity was examined by inhibition with HomoCitJED and its citrullinated counterpart peptide, CitJED (the number of homocitrullines in HomoCitJED is equal to the number of citrullines in CitJED). HomoCitJED-immunized DR4tg mice developed early T and B cell responses to HomoCitJED and late responses to CitJED. These mice also developed anti-CCP2 antibodies. In some mice, antibodies to HomoCitJED were also reactive to CitJED. B6 mice immunized with HomoCitJED developed late T and B cell responses to HomoCitJED, but did not generate responses to citrullinated antigens. Unlike DR4tg mice, anti-HomoCitJED antibodies from B6 mice did not react to CitJED. In conclusion, DR4tg mice immunized with HomoCitJED developed immune responses to CitJED, indicating cross-reactivity. CitJED immune responses were dependent on the SE. HomoCitJED responses occurred in the absence of the SE (B6 mice); however, they developed earlier in DR4tg SE-expressing mice.

Objectives Takayasu's arteritis (TAK) is a rare vasculitis affecting the large blood vessels with significant morbidity and mortality from ischemic complications. The objective of this meta-analysis is to determine the proportion of TAK patients with severe ischemic complications. Methods We performed a literature search using MEDLINE, EMBASE and the Cochrane library from database inception to March 2016. We included articles that reported at least one severe ischemic complication. A random effects model with inverse-variance weighting was performed to estimate the pooled proportion of TAK subjects with ischemic complications. Results 35 studies met inclusion criteria, representing 3262 TAK patients. All studies were observational and of low to moderate quality. Mean age at symptom onset or at diagnosis ranged from 10 to 49 years and mean delay from symptom onset to diagnosis ranged from 2 months to 7.6 years. Study follow-up times were from 22 months to 17 years. The majority of studies had >70% female subjects. The pooled prevalence of stroke in TAK was 8.9% (95% CI: 7.0–10.9%) and of MI was 3.4% (95% CI: 2.1–4,8%) at any time during the disease course. There was moderate to severe heterogeneity across the studies (stroke: I 2 =64.9%; M I : I 2 =74.0%). Other ischemic complications were inconsistently reported. Conclusion Stroke and MI are common in TAK patients. Further studies are needed to identify predictors and preventative measures for severe ischemic events in TAK patients.

Objectives : To investigate differences in response to tumor necrosis factor inhibitor treatment (TNFi) in seropositive (rheumatoid factor positive; RF+) versus seronegative (RF-) patients with established RA as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) and pain. Methods : RA patients from an established RA cohort were studied according to rheumatoid factor (RF) status for change in HAQ-DI and pain (0-3 VAS) one year after starting treatment with a TNFi. Results : There were 238 patients treated with TNFi who had follow-up data (178 RF+ and 60 RF-). Disease duration was longer in RF+ vs RF- (12+8 vs 8+8 years) but the proportion of females (82% vs 72%, P=0.7), baseline HAQ-DI (1.44+0.63 vs 1.41+0.63, P=0.8) and pain (1.92+0.67 vs 1.93+0.67, P=0.9) were not different. The mean duration of treatment of first TNFi was 2.8 vs 2.3 years, P=0.1 and 68% of RF+ vs 62% of RF- were still receiving first TNFi at last visit (P=0.5). For patients with data at baseline and one year, the one-year HAQ-DI change was significantly greater in 90 RF+ patients (-0.356) versus 38 RF- patients (-0.126; P=0.04). The mean pain improvement was also greater in 77 RF+ vs 32 RF- patients (-0.725 vs -0.332 respectively; P=0.03). Numbers are small, data are missing and comorbidities, DAS28 and anti-CCP were not collected. Conclusion : Despite limitations in the data, in established RA after failure of DMARDs, RF+ patients may be more responsive to TNFi therapy as measured by changes in HAQ-DI and pain. Innovation : There may be a better response to TNFi in RA if RF positive for function and pain.

Objective: To determine the effectiveness of antiplatelet and/or anticoagulant therapy (AP/AC) at reducing ischemic events in patients with Large Vessel Vasculitis (LVV). Methods: We performed a random effects meta-analysis of studies examining antiplatelet and/or anticoagulant therapy (AP/AC) and ischemic events in Takayasu’s Arteritis (TAK) or Giant Cell Arteritis (GCA). Severe ischemic events were defined as stroke, ischemic ocular manifestations and claudication symptoms. Any ischemic event included jaw claudication in addition to the above manifestations. Results: Seven studies met inclusion criteria: 1 TAK and 6 GCA. The majority of patients (>80%) were treated with ASA and treatment was initiated prior to diagnosis of LVV. Risk of severe and any ischemic event in patients with LVV treated with AP/AC versus no treatment was not significantly different (OR 0.570, 95% CI 0.243, 1.340 and OR 0.594, 95% CI 0.248, 1.421, respectively). For studies with follow-up data (26-76 months), AP/AC was protective for severe ischemic events (OR 0.18, 95% CI 0.04, 0.83). Findings were similar when excluding studies that did not account for potential confounders, such as cardiovascular risk factors. Conclusion: At follow-up, antiplatelet therapy significantly decreases ischemic events in patients with LVV. However, in most cases of GCA, the treatment was initiated prior to the diagnosis of vasculitis. The benefit of initiating anti-platelet therapy at the time of GCA diagnosis remains unclear.

Objective First-degree relatives (FDRs) of rheumatoid arthritis (RA) patients sharing genetic and environmental risk factors for RA may represent a pre-RA state. Since anti–cyclic citrullinated protein/peptide antibodies (ACPAs) appear years before the onset of RA, the purpose of this study was to determine the prevalence of various ACPAs in FDRs of RA patients. Methods We evaluated 88 RA patients, 50 unaffected FDRs, and 20 healthy control subjects. Six different types of ACPAs were determined by enzyme-linked immunosorbent assay. Joint and periodontal disease symptoms were self-reported. Patients and FDRs were HLA typed for the shared epitope (SE) and the RA-protective alleles HLA–DRB*1301/1302. Results FDRs had a high prevalence of ACPAs (48%) as compared to controls (10%). Prevalence of the SE and smoking in FDRs was also high (62% and 49%, respectively). Of all of the ACPAs in the FDRs, 13 of 32 (41%) were of the IgA isotype. The most commonly expressed IgG ACPA targeted citrullinated vimentin, occurring in 20% of FDRs. The FDRs had an average of 1 type of ACPA, whereas the RA patients expressed a median of 5 different ACPAs. The only FDR to later develop RA expressed 4 different ACPAs. Joint and periodontal disease symptoms in the FDRs were significantly associated with smoking (OR 5.714 [95% confidence interval (95% CI) 1.151–28.3] and OR 12.25 [95% CI 2.544–58.99], respectively), but not with ACPAs. Conclusion The rate of ACPA positivity in unaffected FDRs of RA patients with a high prevalence of the SE and smoking was 48%, whereas ACPAs were rare in the healthy controls. ACPAs in the FDRs of RA patients was most commonly of the IgA isotype, but IgG ACPA targeting citrullinated vimentin was also frequently found.

Objective: Cardiovascular disease (CVD) and risk factors for CVD (smoking, hypertension, dyslipidemia and diabetes) are commonly associated with Rheumatoid Arthritis (RA). We aimed to determine the validity of selfreported CVD events and risk factors in the Canadian Early Arthritis Cohort (CATCH). Methods: CATCH is a multicenter inception cohort of patients with early RA. Various co-morbidities and pharmacologic therapies are self-reported at baseline and at each follow-up visit. Using a randomly selected subgroup of subjects enrolled in CATCH from one representative site, we performed a detailed review of their complete medical record to identify diagnoses of CVD events, risk factors and drug therapies. The validity of selfreported variables was determined using the Cohen’s kappa statistic. Results: The validation subgroup (N=141) was similar to the entire CATCH population (N=2626) with respect to baseline demographics and RA disease characteristics. There was very good agreement between self-report and the medical record for cardiovascular or cerebrovascular events (kappa=0.66), as well as for hypertension and diabetes (kappa=0.70 and 0.81, respectively). Subjects tended to under-report dyslipidemia and the reporting of lipid-lowering and antiplatelet/anticoagulant agents was inaccurate compared to the medical record. Conclusion: Self-reported cardiovascular disease, hypertension and diabetes was representative of the medical record suggesting that these self-reported variables are valuable for future studies of this early RA population.

© 2017 Canadian Urological Association. Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) is a systemic necrotizing vasculitis of small- and mediumsized blood vessels, primarily affecting the upper and lower respiratory tracts, as well as the kidneys. Urogenital manifestations of GPA are exceedingly rare and usually respond well to systemic immunosuppressive therapy. Here, we present a case of a 36-yearold female presenting with acute urinary obstruction secondary to urethral GPA involvement in the immediate postpartum period. Special consideration should be given to ruling out malignancy in all patients with a history of GPA and urethral lesions, especially when there is a history of cyclophosphamide treatment.

Objective.In inflammatory arthritis, rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) are believed to be associated with more severe clinical outcomes. Our objective was to determine whether ACPA and RF remain stable in early inflammatory arthritis and whether their trajectories over time or baseline levels predicted clinical outcomes.Methods.The study population consisted of patients enrolled in the Canadian Early Arthritis Cohort Study with baseline and at least 12-month followup values of RF and ACPA. Primary outcomes were Disease Activity Score (DAS) remission and the presence of erosions at 12 and 24 months. Other objectives included swollen joint count, Health Assessment Questionnaire score, and DAS.Results.At baseline, 225/342 (66%) patients were ACPA-positive and 334/520 (64%) were RF-positive. At 24 months, 15/181 (8%) ACPA-positive patients became negative. A larger number of patients changed from ACPA-negative to positive: 13/123 (11%). For RF, fluctuations were more common: 67/240 (28%) reverted from positive to negative and 21/136 (18%) converted from negative to positive. RF and ACPA fluctuations did not predict disease outcomes. Patients who remained ACPA-positive throughout followup were more likely to have erosive disease (OR 3.86, 95% CI 1.68, 8.92).Conclusion.RF and ACPA have the potential to revert and convert during the early course of disease. Fluctuations in RF and ACPA were not associated with clinical outcomes.

The majority of rheumatoid arthritis (RA) patients express anti-citrullinated protein antibodies (ACPA). Unaffected first-degree relatives of RA patients (FDR) also express ACPA, commonly of the IgA isotype. IgG anti-homocitrullinated/carbamylated protein antibodies (AHCPA) have been detected in both RA and FDR. It is unknown whether other isotypes are expressed. We aim to investigate the AHCPA isotype profile in unaffected FDR of RA patients.The enrolled subjects were examined by a rheumatologist. FDR and healthy controls (HC) were excluded if they had swollen joints. Serum AHCPA targeting homocitrullinated fibrinogen was determined using enzyme linked immunoabsorbant assay (ELISA). FDR were genotyped for HLA-DR4 alleles encoding the shared epitope (SE).125 RA (35 probands), 61 FDR and 40 HC were included. 20% of FDR expressed IgG AHCPA, compared to 30% in RA patients and 5% in HC (p=0.0010 for RA vs. HC). Levels of IgG AHCPA in FDR were similar to RA. FDR rarely expressed IgM (8%) and did not express IgA AHCPA. 20% of RA and 13% of HC subjects expressed IgM, but very few expressed IgA AHCPA (7% in both groups). AHCPA expression in FDR was not significantly associated with joint symptoms, smoking or SE.IgG AHCPA is the most commonly expressed isotype in RA and FDR. The significance of IgG AHCPA in FDR is unclear as it was not associated with joint symptoms or other risk factors for RA. Longitudinal studies are needed to determine whether AHCPA is meaningful in populations at risk for RA.

The Canadian Vasculitis research network (CanVasc) is composed of physicians from different medical specialties, including rheumatology and nephrology and researchers with expertise in vasculitis. One of its aims was to develop recommendations for the diagnosis and management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides in Canada. This executive summary features the 19 recommendations and 17 statements addressing general AAV diagnosis and management, developed by CanVasc group based on a synthesis of existing international guidelines, other published supporting evidence and expert consensus considering the Canadian healthcare context.

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.

Published small case series suggest that inflammatory bowel disease [IBD; Crohn's disease (CD) or ulcerative colitis (UC)] and vasculitis co-occur more frequently than would be expected by chance.To describe this association by an analysis of a large cohort of carefully studied patients and through a systematic literature review.Patients with both IBD and vasculitis enrolled in the Vasculitis Clinical Research Consortium (VCRC) Longitudinal Studies, followed in Canadian Vasculitis research network (CanVasc) centers and/or in the University of Toronto's IBD clinic were included in this case series. A systematic literature review of patients with IBD and vasculitis involved a PubMed search through February 2014. The main characteristics of patients with Takayasu arteritis (TAK) and IBD were compared to those in patients with TAK without IBD followed in the VCRC.The study identified 32 patients with IBD and vasculitis: 13 with large-vessel vasculitis [LVV; 12 with TAK, 1 with giant cell arteritis (GCA); 8 with CD, 5 with UC]; 8 with ANCA-associated vasculitis [AAV; 6 granulomatosis with polyangiitis (GPA), 2 with eosinophilic granulomatosis with polyangiitis (EGPA)]; 5 with isolated cutaneous vasculitis; and 6 with other vasculitides. Patients with LVV and AAV were mostly female (18/21). The diagnosis of IBD preceded that of vasculitis in 12/13 patients with LVV and 8/8 patients with AAV. The review of the literature identified 306 patients with IBD and vasculitis: 144 with LVV (133 TAK; 87 with IBD preceding LVV), 19 with AAV [14 GPA, 1 EGPA, 4 microscopic polyangiitis (MPA)], 66 with isolated cutaneous vasculitis, and 77 with other vasculitides. Patients with IBD and TAK were younger and had more frequent headaches, constitutional symptoms, or gastrointestinal symptoms compared to those patients in the VCRC who had TAK without IBD.These findings highlight the risk of vasculitis, especially TAK, in patients with IBD (both CD and UC).