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To assess challenges to optimal rheumatology care from the perspective of patients served by our institution's rheumatology division.Focus group study of adult rheumatic disease patients who attend clinics at a university teaching hospital in Montreal, Canada.Individuals participated in 1-h focus group discussions concerning their experiences and beliefs regarding rheumatology care. Sessions were recorded and transcripts generated. A thematic analysis approach was used by two individual analyzers.Eighteen patients participated in three focus groups (group one = 8 patients; group two = 5; group three = 5). Eleven patients had systemic lupus erythematosus, 6 had rheumatoid arthritis, and 1 patient had psoriatic arthritis. The average age (standard deviation) was 51.2 (14.0) years, disease duration 23.5 (14.5) years, and in the majority had at least a high school education. All participants were female and 72.2% were Caucasian. Three main themes emerged: theme 1 identified patients' needs for information and support, at diagnosis and throughout the disease trajectory; theme 2 identified barriers to accessing health care: theme 3 identified patients' beliefs regarding improvements needed to optimize their experiences throughout the disease course.Our focus group study not only clarified the needs of rheumatology patients with chronic inflammatory disease, and identified barriers to optimal rheumatology care, but also was a source of recommendations that might improve patient experiences in seeking health care in a rheumatology setting. Limitations include the fact that our participants were all female, and mostly were middle aged, Caucasian and well educated. Regardless, the findings can help inform efforts to improve rheumatology care. Key Points • Our focus group study clarified the needs of chronic inflammatory rheumatic disease, and identified barriers to optimal rheumatology care. • Despite some potential limitations, our work provides recommendations that could improve patient experiences when seeking health care in a rheumatology setting.

There are limited reports of the clinical significance of Raynaud phenomenon (RP) in systemic lupus erythematosus (SLE), with some suggesting RP is associated with less severe lupus. Since most prior studies were small and/or focused on a specific race/ethnic demographic, it is unclear if those results are generalizable. We evaluated whether RP was associated with demographic and clinical factors in a large multiethnic SLE cohort.We studied Montreal General Hospital SLE cohort patients who are followed with standardized annual assessments. We included patients with at least 1 visit across 2011-2018 and assessed demographic and clinical variables (using the 1997 American College of Rheumatology criteria and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) at their first visit. We present multivariate logistics regression analyses of cross-sectional associations between these variables and RP in SLE.Of 489 SLE patients, most were female (n = 445, 91%). Mean age at SLE diagnosis was 31.5 (standard deviation, 13.5) years, and 169 (34.6%) had RP. In our fully adjusted model, female sex (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.07-6.03), White race/ethnicity (OR, 1.85; 95% CI, 1.10-3.17), neurological/neuropsychiatric manifestations (OR, 1.98; 95% CI, 1.10-3.56), and anti-RNP antibodies (OR, 3.03; 95% CI, 1.73-5.38) were positively associated with RP, whereas hemolytic anemia and cellular casts were negatively associated.Over one third of our large multiethnic North American SLE cohort had RP. This study confirmed associations between RP and a specific SLE phenotype.

Although azathioprine (AZA) is the immunosuppressive of choice in SLE pregnancies, no one has evaluated 6-mercaptopurine (6-MP) metabolite levels in this population. Even outside pregnancy, the use of metabolite testing has not been widely applied in SLE.1 AZA is a prodrug that is cleaved to 6-MP, which is converted to the active nucleotides 6-thioguanine (6-TG) and via the enzyme thiopurine methyltransferase (TPMT) to 6-methylmercaptopurine (6-MMP) (figure 1).1 Studies in inflammatory bowel diseases (IBD) established the therapeutic range for 6-TG concentrations between 235 and 450 pmol/8×108 red blood cells (RBC), as higher concentrations are associated with higher risk of myelotoxicity without increased efficacy.1 6-MMP levels >5700 pmol/8×108 RBC are associated with a higher risk of hepatotoxicity.1 Additionally, a subgroup of patients resistant to AZA shunts 6-MP towards the overproduction of 6-MMP, which is reflected in an inability to achieve therapeutic 6-TG levels despite dose escalation.1 In one study, 31% of patients on AZA were identified as ‘shunters’.2 Figure 1 Azathioprine metabolism. AZA, azathioprine; 6-MP, 6-mercaptopurine; 6-TG, 6-thioguanine; 6-MMP, 6-methylmercaptopurine; TPMT, thiopurine methyltransferase. Identifying patients as non-adherent, treatment-refractory or undertreated, as well as identifying drug toxicity, could improve the efficacy and safety of clinical decision-making. As pregnancy is a particularly critical period to optimise disease control and minimise drug toxicity, we evaluated …

OBJECTIVE To determine whether offspring from mothers with systemic lupus erythematosus (SLE), exposed in utero to antimalarials, have an increased risk of ocular anomalies during childhood versus unexposed SLE offspring. METHODS We systematically performed searches of PubMed, Embase, and Web of Science databases for original human data on fetal and/or child ocular outcomes following exposure to antimalarials during pregnancy and/or lactation, from their inception until March 2017. RESULTS A total of 10 cohort studies and 2 randomized controlled trials, ranging in size from 6 to 444 exposed infants studied, and 3 case reports met the inclusion criteria for our systematic review. Collectively, 1,477 infants were studied, 789 of which were exposed to hydroxychloroquine or chloroquine. In all, 563 exposed infants had follow-up visits after delivery (ranging from

Objectives To assess the prevalence of combined hormonal contraceptives (CHCs) in reproductive-age women with SLE with and without possible contraindications and to determine factors associated with their use in the presence of possible contraindications. Methods This observational cohort study included premenopausal women ages 18–45 years enrolled in the SLICC Registry ⩽15 months after SLE onset, with annual assessments spanning 2000–2017. World Health Organization Category 3 or 4 contraindications to CHCs (e.g. hypertension, aPL) were assessed at each study visit. High disease activity (SLEDAI score >12 or use of >0.5 mg/kg/day of prednisone) was considered a relative contraindication. Results A total of 927 SLE women contributed 6315 visits, of which 3811 (60%) occurred in the presence of one or more possible contraindication to CHCs. Women used CHCs during 512 (8%) visits, of which 281 (55%) took place in the setting of one or more possible contraindication. The most frequently observed contraindications were aPL (52%), hypertension (34%) and migraine with aura (22%). Women with one or more contraindication were slightly less likely to be taking CHCs [7% of visits (95% CI 7, 8)] than women with no contraindications [9% (95% CI 8, 10)]. Conclusion CHC use was low compared with general population estimates (>35%) and more than half of CHC users had at least one possible contraindication. Many yet unmeasured factors, including patient preferences, may have contributed to these observations. Further work should also aim to clarify outcomes associated with this exposure.

Objectives Myositis is an infrequent feature of SLE and may often be overlooked. We aimed to estimate the incidence of myositis in SLE, and to determine demographic and clinical factors associated with it. Methods Within our lupus cohort, we identified potential myositis cases using the SLICC Damage Index for muscle atrophy or weakness, the SLEDAI-2K item for myositis, and annually measured serum creatinine kinase. Cases were confirmed through chart review. We performed descriptive analyses of prevalent myositis cases as of January 2000. From that point onward, we studies patients without myositis to determine risk of incident myositis, using cohort analyses adjusted for demographic variables (age, sex, race/ethnicity). Results As of January 2000, there were 5 prevalent myositis cases in our SLE cohort. Among 560 SLE patients with a study visit from January 2000 onward, with no history of myositis at baseline, 5 new cases (4 females, 1 male) were identified over an average follow-up of 8.5 years (incidence 1.05 cases per 1000 person-years). There was a higher proportion of Caucasians in the non-myositis group versus myositis group, with a trend for fewer females in the myositis cases. Arthritis, Raynaud’s phenomenon, and anti-Smith antibodies were common pre-existing features, occurring in all incident myositis cases. In Cox regression analyses adjusting for age, race/ethnicity and sex, non-Caucasian patients had a markedly increased risk of developing myositis. Conclusion We found a low incidence of myositis in our SLE cohort. A cluster of variables, particularly non-Caucasian race/ethnicity, arthritis, Raynaud’s phenomenon, and anti-Smith antibodies were associated with risk of developing myositis in SLE. These variables may aid clinicians in identifying SLE patients at highest risk for this important complication.

Objective.Persistent systemic lupus erythematosus (SLE) disease activity is associated with increased morbidity and mortality. In a multicenter cohort of patients with prevalent SLE, we described persistence, patterns, and predictors of change in disease activity over time.Methods.Based on SLE Disease Activity Index (SLEDAI)-2K scores at cohort entry, patients were classified into 4 groups: low (score < 4; LOW), moderate (4 to < 6; MOD), moderately high (6 to ≤ 10; MHIGH), and very high (> 10; VHIGH). Multivariable linear and longitudinal mixed linear regression models were used to identify predictors of change over time in SLEDAI-2K.Results.There were 2019 participants, with declining followup data over 5 years (1326, 580, 274, 186, and 148 patients, respectively). At cohort entry, mean (± SD) age was 42 (± 17) years, disease duration 11 (± 10) years, and 90% were female. The 4 groups included 44% LOW (n = 891), 20% MOD (n = 400), 22% MHIGH (n = 442), and 14% VHIGH (n = 286); therefore, 36% had clinically important SLE activity. The proportion of patients in the LOW group at entry who moved to a higher activity level varied from 30% (167/557) at 1 year, to 49% (41/83) at 3 years, and 54% (30/56) at 5 years. Among 181 patients with MOD to VHIGH entry activity and 3 years of followup, 116 (64.1%) remained active. In all analyses, only higher SLEDAI-2K at cohort entry remained a significant predictor of higher SLEDAI-2K in subsequent years.Conclusion.Higher SLEDAI-2K at study entry was the single major independent predictor of higher SLEDAI-2K over time, reflecting frequent persistence of active disease, even in patients with longstanding disease. This highlights gaps in the optimal treatment of SLE.

Objective Limited evidence suggests a potentially increased risk of allergic conditions in offspring born to women with systemic lupus erythematosus (SLE). In a large population-based study, we aimed to determine if children born to mothers with SLE have an increased risk of allergic conditions compared to children born to mothers without SLE. Methods Using the Offspring of SLE Mothers Registry, we identified children born live to mothers with SLE and their matched controls, and ascertained the number of allergic conditions (asthma, allergic rhinitis, eczema, urticaria, angioedema, and anaphylaxis) based on ≥1 hospitalization or ≥1 or 2 physician(s) visit(s) with a relevant diagnostic code. We adjusted for maternal age, education, race/ethnicity, obstetrics complications, calendar year of birth, sex of the child, and maternal medication. Results There were 509 women with SLE who had 719 children, while 5,824 matched controls had 8,493 children. The mean ± SD followup period was 9.1 ± 5.8 years. Compared to controls, more children born to mothers with SLE had evidence of allergic conditions (43.9% [95% confidence interval (95% CI) 40.4-47.6] versus 38.1% [95% CI 37.0-39.1]). In multivariate analysis (n = 9,212), children born to mothers with SLE had an increased risk of allergic conditions versus control children (odds ratio 1.35 [95% CI 1.13-1.61]). Conclusion Compared to children from the general population, children born to women with SLE may have an increased risk of allergic conditions. Genetics, shared environmental exposures, as well as in utero exposure to maternal autoantibodies and cytokines may mediate this increased risk.

BackgroundA major systemic lupus erythematosus (SLE) susceptibility locus lies within a common inversion polymorphism region (encompassing 3.8 – 4.5 Mb) located at 8p23. Initially implicated genes includedFAM167A-BLKandXKR6, of whichBLKreceived major attention due to its known role in B-cell biology. Recently, additional SLE risk carried in non-inverted background was also reported.Objective and methodsIn this case –control study, we further investigated the ‘extended’ 8p23 locus (~ 4 Mb) where we observed multiple SLE signals and assessed these signals for their relation to the inversion affecting this region. The study involved a North American discovery data set (~1200 subjects) and a replication data set (> 10 000 subjects) comprising European-descent individuals.ResultsMeta-analysis of 8p23 SNPs, with p < 0.05 in both data sets, identified 51 genome-wide significant SNPs (p < 5.0 × 10−8). While most of these SNPs were related to previously implicated signals (XKR6-FAM167A-BLKsubregion), our results also revealed two ‘new’ SLE signals, includingSGK223-CLDN23-MFHAS1(6.06 × 10−9≤ meta p ≤ 4.88 × 10−8) andCTSB(meta p = 4.87 × 10−8) subregions that are located > 2 Mb upstream and ~ 0.3 Mb downstream from previously reported signals. Functional assessment of relevant SNPs indicated putativecis-effects on the expression of various genes at 8p23. Additional analyses in discovery sample, where the inversion genotypes were inferred, replicated the association of non-inverted status with SLE risk and suggested that a number of SLE risk alleles are predominantly carried in non-inverted background.ConclusionsOur results implicate multiple (known+novel) SLE signals/genes at the extended 8p23 locus, beyond previously reported signals/genes, and suggest that this broad locus contributes to SLE risk through the effects of multiple genes/pathways.

To describe the characteristics of patients receiving belimumab, overall patterns of systemic lupus erythematosus (SLE) care, clinical outcomes, and changes in glucocorticoid dose following 6 months of therapy with belimumab, and healthcare resource utilization in belimumab users in Canadian clinical practice settings. Retrospective multicenter medical chart review study of adult patients with SLE who were prescribed belimumab as part of usual care and who received ≥8 infusions or 6 months of treatment. Primary endpoints included physician-determined overall clinical improvement from baseline, glucocorticoid use, and physician-determined SLE disease severity at Month 6. In total, 52 patients were included in the study. At belimumab initiation, 5.8/76.9/17.3% of patients had mild/moderate/severe SLE, respectively. Oral glucocorticoids were discontinued in 11.4% of patients and 59.1% received a lower dose at Month 6. At Month 6, 80.8/57.7/17.3% of patients had a physician-determined clinical improvement of ≥20/≥50/≥80%, respectively. Sixteen patients had a SLE Disease Activity Index-2K score at both baseline and Month 6, with a mean improvement of 2.6 ± 5.3 from 8.1 ± 3.2 at baseline. No formal disease assessment tool was utilized for 42.3% of study patients at baseline. This study provides the first real-world insights into belimumab use in Canada. It demonstrates significant reduction or discontinuation of glucocorticoid dose in 70.5% of patients and clinically significant improvement following 6 months' belimumab therapy. The high number of patients with no formal disease activity assessments highlights a key care gap in SLE treatment in the real-world setting.

Objective.To develop recommendations for the assessment of people with systemic lupus erythematosus (SLE) in Canada.Methods.Recommendations were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. The Canadian SLE Working Group (panel of Canadian rheumatologists and a patient representative from Canadian Arthritis Patient Alliance) was created. Questions for recommendation development were identified based on the results of a previous survey of SLE practice patterns of members of the Canadian Rheumatology Association. Systematic literature reviews of randomized trials and observational studies were conducted. Evidence to Decision tables were prepared and presented to the panel at 2 face-to-face meetings and online.Results.There are 15 recommendations for assessing and monitoring SLE, with varying applicability to adult and pediatric patients. Three recommendations focus on diagnosis, disease activity, and damage assessment, suggesting the use of a validated disease activity score per visit and annual damage score. Strong recommendations were made for cardiovascular risk assessment and measuring anti-Ro and anti-La antibodies in the peripartum period and conditional recommendations for osteoporosis and osteonecrosis. Two conditional recommendations were made for peripartum assessments, 1 for cervical cancer screening and 2 for hepatitis B and C screening. A strong recommendation was made for annual influenza vaccination.Conclusion.These are considered the first guidelines using the GRADE method for the monitoring of SLE. Existing evidence is largely of low to moderate quality, resulting in more conditional than strong recommendations. Additional rigorous studies and special attention to pediatric SLE populations and patient preferences are needed.

Objective Several autoimmune diseases have familial aggregation and, possibly, common genetic predispositions. In a large population-based study, we evaluated whether children born to mothers with systemic lupus erythematosus (SLE) have an increased risk of rheumatic and nonrheumatic autoimmune diseases versus children born to mothers without SLE. Methods Using the Offspring of SLE Mothers Registry, we identified children born live to SLE mothers and their matched controls, and ascertained autoimmune diseases based on ≥1 hospitalization or ≥2 physician visits with a relevant diagnostic code. We adjusted for maternal age, education, race/ethnicity, obstetric complications, calendar birth year, and sex of child. Results A total of 509 women with SLE had 719 children, while 5,824 matched controls had 8,493 children. The mean ± SD follow-up period was 9.1 ± 5.8 years. Children born to mothers with SLE had a similar frequency of rheumatic autoimmune diagnoses (0.14%; 95% confidence interval [95% CI] 0.01-0.90) versus controls (0.19% [95% CI 0.11-0.32]). There was a trend toward more nonrheumatic autoimmune diseases in SLE offspring (1.11% [95% CI 0.52-2.27]) versus controls (0.48% [95% CI 0.35-0.66]). In multivariate analyses, we did not see a clear increase in rheumatic autoimmune disease (odds ratio [OR] 0.71 [95% CI 0.11-4.82]), but children born to mothers with SLE had a substantially increased risk of nonrheumatic autoimmune disease versus controls (OR 2.30 [95% CI 1.06-5.03]). Conclusion Although the vast majority of offspring have no autoimmune disease, children born to women with SLE may have an increased risk of nonrheumatic autoimmune diseases versus controls. Additional studies assessing offspring through to adulthood would be additionally enlightening.

Objectives To compare physical and mental health-related quality of life (HRQoL) across four systemic autoimmune rheumatic diseases (SARD). Methods Incident subjects enrolled in four SARD cohorts, namely systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA) and idiopathic inflammatory myopathies (IIM) were studied. The outcomes of interest were baseline Short Form Health Survey physical (PCS) and mental (MCS) component summary scores. Multivariate analysis was conducted to determine whether PCS and MCS scores differed across SARD type. Results The study included 118 SLE (93% women, mean age 36 years), 108 SSc (79% women, mean age 55), 64 RA (63% women, mean age 58) and 25 IIM (68% women, mean age 49) subjects. Mean PCS scores were 38.9 ± 12.2 in SLE, 37.1 ± 13.3 in RA, 35.0 ± 13.6 in SSc and 28.0 ± 15.4 in IIM. Mean MCS scores were 45.0 ± 13.3 in RA, 44.4 ± 14.7 in SSc, 40.1 ± 14.3 in SLE and 33.6 ± 18.7 in IIM. SARD type was an independent predictor of HRQoL with, in some cases, the magnitude of the differences reaching one standard deviation (IIM worse PCS scores compared to SLE (β -12.23 [95% CI -18.11, -6.36; p

OBJECTIVE In rheumatoid arthritis (RA), quality indicators (QIs) are tools used to measure process of care. This study aimed to assess performance of selected QIs from the 2004 Arthritis Foundation's QI Set at 2 major sites of a university network of teaching hospitals. METHODS The charts and electronic hospital records of 76 RA patients were audited to determine adherence to QIs. Logistic multivariate regression analyses were performed to investigate potential determinants of nonadherence and propose measures to facilitate better QI compliance, as a potential strategy towards RA care improvement. RESULTS We identified consistent observance of QIs mandating prescription of disease-modifying antirheumatic drug therapy for all patients, drug adjustment with disease activity, prednisone tapering, and bisphosphonate therapy if indicated for patients on glucocorticoids. However, there was either lack of documentation or true inconsistent adherence to QIs dealing with radiograph performance, functional capacity assessment, and screening for hepatitis and tuberculosis before commencement of methotrexate and biologic agents, respectively. For the specific QIs analyzed, we did not find any definite independent associations with the studied variables. CONCLUSIONS Our findings indicate that while there is frequent evidence for adherence to certain RA quality care standards at our centers, there is less compliance to others. Strategies to optimize the performance or documentation of those found most lacking, namely, functional capacity and screening for specific drug contraindications, could improve patient care. Radiographic disease monitoring, while lacking, may represent a move toward other more sensitive methods of RA progression detection, such as joint ultrasound. The inclusion of patient- and physician-derived information could help elucidate the reasons underlying nonadherence.

Objective There is recent evidence to suggest that in utero exposure to maternal antibodies and cytokines is an important risk factor for autism spectrum disorders (ASDs). We aimed to systematically review the risk of ASDs in children born to mothers with rheumatoid arthritis (RA) compared to children born to mothers without RA. Methods We conducted a systematic review of original articles using the electronic databases PubMed, Embase, and Web of Science. Results Our literature search yielded a total of 70 articles. Of the potentially relevant studies retrieved, 67 were excluded for lack of relevance and/or because they did not report original data. Three studies were included in the final analysis. A case–control study found no difference in the prevalence of RA in mothers of children with ASDs versus control mothers. Another case–control study showed a statistically significant 8-fold increase in autoimmune disorders, including RA, in mothers of offspring with ASDs compared to controls. Forty-six percent of offspring with ASDs had a first-degree relative with RA, compared to 26% of controls. And in a population-based cohort study, investigators observed an increased risk of ASDs in children with a maternal history of RA compared to children born to unaffected mothers. These studies had methodologic limitations: none controlled for medication exposures, only 1 controlled for obstetric complications and considered the timing of RA diagnosis in relation to pregnancy, and all but 1 used a case–control study design. Conclusion Observational studies suggest a potentially increased risk of ASDs in children born to mothers with RA compared to children born to mothers without RA, although data are limited.

Objective.Women with systemic lupus erythematosus (SLE) are at risk of osteoporosis (OP) and fractures because of SLE or its treatments. We aimed to determine in women with SLE (1) the prevalence of low bone mass (LBM) in those < 50 years of age and OP in those > 50 years of age; (2) the 10-year absolute fracture risk in those > 40 years of age using the Canadian Fracture Risk Assessment Tool (FRAX); (3) bone quality using hip structural analysis (HSA); and (4) the associations between HSA and age, SLE duration, and corticosteroid exposure.Methods.Women without prior OP fractures were eligible. Bone mineral densities at the hip, spine, and femoral neck were determined using dual-energy x-ray absorptiometry. OP was determined using World Health Organization definitions for participants aged ≥ 50 years (32.8%), and LBM was defined as Z-scores ≤ −2.0 for those aged < 50 years. For those aged ≥ 40 years (63.5%), the 10-year probabilities of a major fracture (FRAX-Major) and hip fracture (FRAX-Hip) were calculated. FRAX-Major ≥ 20% or Hip ≥ 3% was considered high risk. HSA was done in a subgroup (n = 81) of patients.Results.The study group was 271 women. Mean (SD) age was 43.8 (13.1) years and SLE duration was 11.6 (10.4) years. OP was diagnosed in 14.6% and LBM in 8.8%. FRAX-Major ≥ 20% was seen in 9 patients (5.3%), of whom 6 were taking OP medications. FRAX-Hip ≥ 3% occurred in 16 patients (9.4%), of whom 9 were taking OP medications. Buckling ratio at the left hip narrow neck was positively correlated with FRAX-Major, FRAX-Hip, SLE duration, and duration of corticosteroid use.Conclusion.LBM is prevalent in women with SLE who are < 50 years of age. FRAX may identify those at higher risk of fractures while HSA can assess bone structure noninvasively.

Objective. To investigate whether comorbidity as assessed by the Charlson Comorbidity Index (CCI) is associated with mortality in a long-term followup of systemic lupus erythematosus (SLE) patients. Methods. Data were collected from 499 SLE patients attending the Lupus Clinic at the McGill University Health Center, Montreal, Quebec, Canada, and 170 SLE patients from the Department of Rheumatology at Lund University Hospital, Lund, Sweden. This included data on comorbidity, demographics, disease activity, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and antiphospholipid antibody syndrome (APS). Variables were entered into a Cox proportional hazards survival model. Results. Mortality risk in the Montreal cohort was associated with the CCI (hazard ratio [HR] 1.57 per unit increase in the CCI, 95% confidence interval [95% CI] 1.18-2.09) and age (HR 1.04 per year increase in age, 95% CI 1.00-1.09). The CCI and age at diagnosis were also associated with mortality in the Lund cohort (CCI: HR 1.35, 95% CI 1.13-1.60; age: HR 1.09, 95% CI 1.05-1.12). Furthermore, the SDI was associated with mortality in the Lund cohort (HR 1.40, 95% CI 1.19-1.64), while a wide CI for the estimate in the Montreal cohort prevented a definitive conclusion (HR 1.20, 95% CI 0.97-1.48). We did not find a strong association between mortality and sex, race/ethnicity, disease activity, or APS in either cohort. Conclusion. In this study, comorbidity as measured by the CCI was associated with decreased survival independent of age, lupus disease activity, and damage. This suggests that the CCI may be useful in capturing comorbidity for clinical research in SLE. (Less)

Background: Cardiomyopathy in systemic lupus erythematosus (SLE) may be secondary to myocardial inflammation (i.e. myocarditis) or to systemic complications such as hypertension. Symptomatic left ventricular dysfunction is the most common clinical presentation of cardiomyopathy and is potentially life threatening. Identifying the cause is critical as it dictates therapy. Methods: We present three cases of left ventricular failure suggestive of myocarditis in SLE patients followed in the Lupus Clinic of the Montreal General Hospital over a 5-year period. Results: The most frequent presentation is acute onset of a marked reduction of the left ventricular ejection fraction (LVEF). All patients were treated with cardiac support, prednisone, and additional immunosuppressive medications. Improvement of symptoms and LVEF was observed in two of three patients. Conclusion: Myocarditis is a rare, but life-threatening, manifestation of SLE. With immunosuppressive medications and cardiovascular support, the long-term outcome is usually favorable.

Background Systemic lupus erythematosus (SLE) is a chronic disease of unclear etiology, characterized by an overactive immune system and the production of antibodies that may target normal tissues of many organ systems, including the kidneys. It can arise at any age and occurs mainly in women. Objective Our aim was to evaluate the potential influence of particulate matter (PM) air pollution on clinical aspects of SLE. Methods We studied a clinic cohort of SLE patients living on the island of Montreal, followed annually with a structured clinical assessment. We assessed the association between ambient levels of fine PM [median aerodynamic diameter ≤ 2.5 μm (PM2.5)] measured at fixed-site monitoring stations and SLE disease activity measured with the SLE Disease Activity Index, version 2000 (SLEDAI-2K), which includes anti–double-stranded DNA (anti-dsDNA) serum-specific autoantibodies and renal tubule cellular casts in urine, which reflects serious renal inflammation. We used mixed effects regression models that we adjusted for daily ambient temperatures and ozone levels. Results We assessed 237 patients (223 women) who together had 1,083 clinic visits from 2000 through 2007 (mean age at time of first visit, 41.2 years). PM2.5 levels were associated with anti-dsDNA and cellular casts. The crude and adjusted odds ratios (reflecting a 10-μg/m3 increase in PM2.5 averaged over the 48 hr prior to clinical assessment) were 1.26 [95% confidence interval (CI), 0.96–1.65] and 1.34 (95% CI, 1.02–1.77) for anti-dsDNA antibodies and 1.43 (95% CI, 1.05–1.95) and 1.28 (0.92–1.80) for cellular casts. The total SLEDAI-2K scores were not associated with PM2.5 levels. Conclusions We provide novel data that suggest that short-term variations in air pollution may influence disease activity in established autoimmune rheumatic disease in humans. Our results add weight to concerns that pollution may be an important trigger of inflammation and autoimmunity.

The objective of this study was to assess isolated pyuria in an unselected systemic lupus erythematosus sample, and to determine factors potentially associated with this manifestation. We studied patients followed in our lupus clinic, defining isolated pyuria as more than 10 white blood cells per high power field in the absence of hematuria, proteinuria, casts, or bacteriuria. We assessed the effects of various demographic and clinical factors on the occurrence of isolated pyuria, using univariate logistic regression analyses. We also performed multivariate models which included sex, age, race/ethnicity, systemic lupus erythematosus duration, non-renal systemic lupus erythematosus disease activity, systemic lupus erythematosus damage, number of non-renal and renal American College of Rheumatology criteria ever present, pre-existing hypertension, and current drug exposures. Of 264 subjects, 66 were excluded (43 had bacteriuria or a contaminated urine culture and 23 had no concomitant urine culture); 27 of the remaining 198 (13.6%) had isolated pyuria. Sixteen of 27 patients with sterile pyuria had previous American College of Rheumatology criteria for renal involvement (hematuria, casts, and/or proteinuria) compared to 62/171 patients without sterile pyuria (unadjusted odds ratio = 2.55; 95% confidence interval = 1.11-5.85). Our univariate analyses also suggested a trend towards higher non-renal disease activity in patients with isolated pyuria. Independent associations were not evident in adjusted analyses. Isolated pyuria was observed in a significant number of our systemic lupus erythematosus sample. Although the differential diagnosis for isolated pyuria is broad, this manifestation may be correlated with lupus activity even in the absence of hematuria or proteinuria. Lupus (2010) 19, 793-796.

Objective.Pleuritis is a common manifestation and independent predictor of mortality in systemic lupus erythematosus (SLE). We examined the prevalence of pleuritis and factors associated with pleuritis in a multicenter Canadian SLE cohort.Methods.We studied consecutive adults satisfying the American College of Rheumatology (ACR) classification criteria for SLE who had a completed Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) score, at least 1 evaluable extractable nuclear antigen assay, and either a SLE Disease Activity Index (SLEDAI) or a SLE Activity Measure score. Pleuritis was defined as having pleuritis by satisfying the ACR criteria or the SLEDAI. Factors related to pleuritis were examined using univariate and multivariate logistic regression.Results.In our cohort of 876 patients, 91% were women, 65% Caucasian, mean age (± SD) was 46.8 ± 13.5 years, and disease duration at study entry was 12.1 ± 9.9 years; the prevalence of pleuritis was 34% (n = 296). Notably, greater disease duration (p = 0.002), higher SDI score (p ≤ 0.0001), age at SLE diagnosis (p = 0.009), and anti-Sm (p = 0.002) and anti-RNP (p = 0.002) seropositivity were significantly associated with pleuritis. In multivariate analysis with adjustment for disease duration, age at diagnosis, and SDI score, concomitant seropositivity for RNP and Sm were related to a nearly 2-fold greater prevalence of pleuritis (OR 1.98, 95% CI 1.31–2.82).Conclusion.Pleuritis occurred in one-third of this Canadian cohort. Concomitant Sm and RNP seropositivity, greater cumulative damage, longer disease duration, and younger age at SLE disease onset were related to a higher rate of SLE pleural disease.

Objective.Associations between the use of micronutrient supplements (MS) and disease activity, quality of life (QOL), and healthcare resource utilization were studied in a Canadian population of patients with systemic lupus erythematosus (SLE).Methods.QOL was assessed by the Medical Outcomes Study 36-item Short Form. Healthcare resource utilization and disease activity/damage were determined.Results.Of the 259 subjects studied, 53% were MS users and 34% used only calcium/vitamin D. MS users had a higher Systemic Lupus International Collaborating Clinics score and utilized more healthcare resources. Disease activity and QOL were similar between MS users and nonusers.Conclusion.MS are frequently used by patients with SLE and are not associated with concomitant benefit on QOL. MS users utilized more healthcare resources.

Objective To determine polymyalgia rheumatica (PMR) prevalence using population-based administrative data, and to estimate the error associated with case ascertainment approaches when using these databases. Methods Cases were ascertained using physician billing and hospitalization data from the province of Manitoba (population 1.1 million). Focusing on the population age ≥45 years, we compared 3 different case definition algorithms and also used statistical methods that accounted for imperfect case ascertainment to estimate the prevalence and the properties of the ascertainment algorithms. A hierarchical Bayesian latent class regression model was developed that also allowed us to assess differences across patient demographics (sex and region of residence). Results Using methods that account for the imperfect nature of both billing and hospitalization databases, we estimated the prevalence of PMR in women age ≥45 years to be lower in urban areas (754.5 cases/100,000; 95% credible interval [95% CrI] 674.1–850.3) compared with rural areas (1,004 cases/100,000; 95% CrI 886.3–1,143). This regional trend was also seen in men age ≥45 years, where the prevalence was estimated at 273.6 cases/100,000 (95% CrI 219.8–347.6) in urban areas and 380.7 cases/100,000 (95% CrI 311.3–468.1) in rural areas. Billing data appeared more sensitive in ascertaining cases than hospitalization data, and a large proportion of diagnoses was made by physicians other than rheumatologists. Conclusion These data suggest a higher prevalence of PMR in rural versus urban regions. Our approach demonstrates the usefulness of methods that adjust for the imperfect nature of multiple information sources, which also allow for estimation of the sensitivity of different case ascertainment approaches.

Objective To estimate the prevalence of systemic sclerosis (SSc) using population-based administrative data, and to assess the sensitivity of case ascertainment approaches. Methods We ascertained SSc cases from Quebec physician billing and hospitalization databases (covering ∼7.5 million individuals). Three case definition algorithms were compared, and statistical methods accounting for imperfect case ascertainment were used to estimate SSc prevalence and case ascertainment sensitivity. A hierarchical Bayesian latent class regression model that accounted for possible between-test dependence conditional on disease status estimated the effect of patient characteristics on SSc prevalence and the sensitivity of the 3 ascertainment algorithms. Results Accounting for error inherent in both the billing and the hospitalization data, we estimated SSc prevalence in 2003 at 74.4 cases per 100,000 women (95% credible interval [95% CrI] 69.3–79.7) and 13.3 cases per 100,000 men (95% CrI 11.1–16.1). Prevalence was higher for older individuals, particularly in urban women (161.2 cases per 100,000, 95% CrI 148.6–175.0). Prevalence was lowest in young men (in rural areas, as low as 2.8 cases per 100,000, 95% CrI 1.4–4.8). In general, no single algorithm was very sensitive, with point estimates for sensitivity ranging from 20–73%. Conclusion We found marked differences in SSc prevalence according to age, sex, and region. In general, no single case ascertainment approach was very sensitive for SSc. Therefore, using data from multiple sources, with adjustment for the imperfect nature of each, is an important strategy in population-based studies of SSc and similar conditions.

Objective: To estimate the prevalence of polymyositis and dermatomyositis using population-based administrative data, the sensitivity of case ascertainment approaches and patient demographics and these parameters. Methods: Cases were ascertained from Quebec physician billing and hospitalisation databases (approximately 7.5 million beneficiaries). Three different case definition algorithms were compared, and statistical methods were also used that account for imperfect case ascertainment, to generate estimates of disease prevalence and case ascertainment sensitivity. A hierarchical Bayesian latent class regression model was developed to assess patient characteristics with respect to these parameter estimates. Results: Using methods that account for the imperfect nature of both billing and hospitalisation databases, the 2003 prevalence of polymyositis and dermatomyositis was estimated to be 21.5/100 000 (95% credible interval (CrI) 19.4 to 23.9). Prevalence was higher for women and for older individuals, with a tendency for higher prevalence in urban areas. Prevalence estimates were lowest in young rural men (2.7/100 000, 95% CrI 1.6 to 4.1) and highest in older urban women (70/100 000, 95% CrI 61.3 to 79.3). Sensitivity of case ascertainment tended to be lower for older versus younger individuals, particularly for rheumatology billing data. Billing data appeared more sensitive in ascertaining cases in urban (vs rural) regions, whereas hospitalisation data seemed most useful in rural areas. Conclusions: Marked variations were found in the prevalence of polymyositis and dermatomyositis according to age, sex and region. These methods allow adjustment for the imperfect nature of multiple data sources and estimation of the sensitivity of different case ascertainment approaches.

There are few precise or recent estimates of the risk or causes of stillbirths in women with systemic lupus erythematosus (SLE). Thus, we undertook the present study to examine causes of stillbirths in mothers with SLE versus those without SLE.The Offspring of SLE Mothers Registry (OSLER) is a large population-based cohort, identified through Quebec's health care databases (1989-2009), including all women who had ≥1 hospitalization for delivery after SLE diagnosis, and a randomly selected control group of women matched for age and year of delivery. We identified stillbirths and ascertained the cause of death as indicated on death certificates. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated, and multivariate logistic regression analysis was performed to estimate the risk of stillbirth in women with SLE versus controls.In our cohort, 509 women with SLE had 729 births, including 9 stillbirths, while 5,829 matched controls had 8,541 births, including 47 stillbirths. We observed more stillbirths in mothers with SLE than in controls (1.24% versus 0.55%, difference 0.69% [95% CI 0.03, 1.88]). Women with SLE had an increased risk of stillbirth compared to controls (adjusted OR 2.13 [95% CI 1.02, 4.45]). We also observed a trend toward more stillbirths due to placenta-mediated pregnancy complications in mothers with SLE than in controls (44% [95% CI 14, 79] versus 15% [95% CI 6, 28]).Compared to women from the general population, women with SLE have an increased risk of stillbirth. Stillbirths in women with SLE might be more often caused by placenta-mediated pregnancy complications compared to stillbirths in mothers without SLE.

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.

In utero exposure to maternal antibodies and cytokines are potential risk factors for autism spectrum disorders (ASDs). The aim of this study was to determine whether children born to mothers with systemic lupus erythematosus (SLE) have an increased risk of ASD compared to children born to mothers without SLE.The study population was derived from the Offspring of SLE Mothers Registry (OSLER), a large population-based cohort identified through healthcare databases in Quebec (1989-2009) comprising all women who had ≥1 hospitalization for a delivery (stillbirth or live birth) after SLE diagnosis. As general population controls, a randomly selected group of women without SLE was matched ≥4:1 to the mothers with SLE for age and year of delivery. Children born live to mothers with SLE and those born live to matched controls were identified, and a recorded diagnosis of ASD was ascertained for each child. Multivariate analyses were performed to adjust for parents' demographic characteristics, sex, birth order of the child, maternal comorbidities, and obstetric complications.In total, 509 women with SLE had 719 children, and 5,824 matched controls had 8,493 children. Children born to women with SLE were more frequently found to have a diagnosis of ASD compared to controls (frequency of recorded ASDs 1.4% [95% confidence interval (95% CI) 0.8-2.5] versus 0.6% [95% CI 0.5-0.8]), a difference of 0.8% (95% CI 0.1-1.9). The mean age at ASD diagnosis was younger in offspring of SLE mothers (mean 3.8 years, 95% CI 1.8-5.8) compared to offspring of controls (mean 5.7 years, 95% CI 4.9-6.5). In primary multivariate analysis, SLE offspring had a substantially increased risk of ASD compared to controls (odds ratio 2.19, 95% CI 1.09-4.39).Compared to children from the general population, children born to women with SLE have an increased risk of ASD, although, in absolute terms, it represents a rare outcome. These hypothesis-generating data provide direction for additional studies of maternal autoimmunity and ASD risk.

Therapeutic approaches in systemic lupus erythematosus (SLE) have evolved over the last few decades, but their impact on prevention of organ damage is unknown. The objective of this study was to compare new cumulative damage in SLE patients across different calendar periods. Patients from a large SLE cohort were divided into two subcohorts; the first diagnosed and followed between 1978 and 1988 (cohort #1, n = 100) and the second between 1989 and 1999 (cohort #2, n = 51). Initial Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) scores, and changes in scores over the observation intervals, were compared for the two groups. Logistic regression estimated adjusted odds ratios (OR) comparing damage accrual between the two cohorts. Medication exposures were noted. Baseline characteristics were similar between the two groups. At first assessment, the adjusted OR for a SLICC/ACR DI score ≥1 was 1.79 (95% CI 0.82, 3.88) for cohort #1 versus cohort #2. At the end of the observation interval, the adjusted OR for a SLICC/ACR DI score ≥1 was 1.22 (0.58, 2.55) for cohort #1 versus cohort #2. The adjusted OR for accruing damage over the observation interval in cohort #1 versus cohort #2 was 0.94 (0.39, 2.44). Increased medication exposure was evident for cohort #2 compared to cohort #1. Despite increased therapeutic measures used for patients in more recent periods, our data do not establish a clear difference in damage accrual. This emphasizes the need for strategies to effectively treat lupus-specific manifestations, while minimizing side effects and comorbidities.

Objective. We have shown that SLE patients in Canada and the UK incurred 20% and 13% lower health costs than those in the US, respectively, but did not experience worse outcomes as expressed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. We now compare change in quality of life in these patients. Patients and methods. Seven hundred and fifteen SLE patients (Canada 231, US 269, UK 215) completed the SF-36 annually over four years. The annual change in the SF-36 Physical and Mental Component Summary (PCS and MCS) scores over the course of the study were summarized by estimating a linear trend for each individual patient using hierarchical modelling. Cross-country comparison of the slopes in the PCS and MCS scores was then performed using simultaneous regressions. Results. The estimated mean annual changes (95% credible interval [CrI]) in the PCS scores in Canada, the US, and the UK were 0.18 (� 0.07, 0.43), � 0.05 (� 0.27, 0.17), and 0.03 (� 0.20, 0.27), respectively; the mean annual changes in the MCS scores were 0.15 (� 0.04, 0.34), 0.23 (0.09, 0.37), and 0.08 (� 0.10, 0.27), respectively. Regression results showed that the mean annual changes in PCS and MCS scores did not substantially differ across countries. Conclusion. Quality of life remained stable across countries. Despite Canadian and British patients incurring lower health costs, on average, patients experienced similar changes in physical and mental well-being.

Objectives The authors aim to calculate the number of live births, before and after systemic lupus erythematosus (SLE) diagnosis, in women diagnosed during their reproductive years and to compare this with general population rates. Methods The authors identified women with SLE using Quebec administrative databases (1 January 1994 to 31 December 2003). The authors determined the number of live births, and calculated the standardised incidence ratio (SIR) of observed to expected live births. Results 1334 women with SLE were identified. Overall, the number of live births over the interval (559) was below that which would be expected (708) (SIR 0.79; 95% CI 0.73 to 0.86). Compared with the general population, live births were substantially lower after SLE diagnosis (SIR 0.62; 95% CI 0.55 to 0.70) than before diagnosis (SIR 1.01; 95% CI 0.90 to 1.13). Conclusion After diagnosis, women with SLE have substantially fewer live births than the general population.

Objective To examine the association between anti-Ro antibodies, namely anti-Ro60/SS-A and anti-Ro52/TRIM21, together and separately, and a prolonged QT interval corrected for heart rate (QTc) in systemic sclerosis (SSc) patients. Methods A total of 689 SSc patients enrolled in a multicenter cohort study underwent a 12-lead resting EKG at baseline. The QTc interval was measured, and a QTc ≥ 440ms was considered prolonged. Detailed clinical data and sera of these patients were collected and positivity for anti-Ro60/SS-A and anti-Ro52/TRIM21 antibodies was determined using an addressable laser bead immunoassay (ALBIA). Results QTc prolongation was common in this SSc cohort (25%). In a univariate analysis, Ro antibodies, together or separately, were not associated with prolongation of the QTc interval [mean difference in QTc in anti-Ro antibody positive versus negative subjects was −2.2ms ( p = 0.5748), in anti-Ro60/SS-A antibody positive versus negative subjects was 1.3ms ( p = 0.8616), and in anti-Ro52/TRIM21 antibody positive versus negative subjects was −3.3ms ( p = 0.4106)]. In a multivariate logistic regression analysis adjusting for possible confounders, there was no association between prolonged QTc and anti-Ro antibodies [odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.45, 1.22], anti-Ro60/SS-A antibodies (OR = 1.57, 95% CI: 0.72, 3.41), and anti-Ro52/TRIM21 antibodies (OR = 0.76, 95% CI: 0.46, 1.26). However, in both univariate and multivariate analyses, QTc prolongation was associated with longer disease duration, greater disease severity, and the presence of anti-RNA polymerase III antibodies. Conclusions QTc prolongation is common in SSc, although anti-Ro antibodies do not seem to be associated with it as is the case in systemic lupus erythematosus. The reasons for this difference as well as the cause of abnormalities in cardiac repolarization in SSc will require additional studies.

Children born to women with systemic lupus erythematosus seem to have a potentially increased risk of neurodevelopmental disorders compared to children born to healthy women. Recent experimental data suggest in utero exposure to maternal antibodies and cytokines as important risk factors for neurodevelopmental disorders. Interestingly, women with systemic lupus erythematosus display high levels of autoantibodies and cytokines, which have been shown, in animal models, to alter fetal brain development and induce behavioral anomalies in offspring. Furthermore, subjects with systemic lupus erythematosus and neurodevelopmental disorders share a common genetic predisposition, which could impair the fetal immune response to in utero immunologic insults. Moreover, systemic lupus erythematosus pregnancies are at increased risk of adverse obstetrical outcomes and medication exposures, which have been implicated as potential risk factors for neurodevelopmental disorders. In this article, we review the current state of knowledge on neurodevelopmental disorders and their potential determinants in systemic lupus erythematosus offspring.

Objective.To estimate systemic autoimmune rheumatic disease (SARD) prevalence across 7 Canadian provinces using population-based administrative data evaluating both regional variations and the effects of age and sex.Methods.Using provincial physician billing and hospitalization data, cases of SARD (systemic lupus erythematosus, scleroderma, primary Sjögren syndrome, polymyositis/dermatomyositis) were ascertained. Three case definitions (rheumatology billing, 2-code physician billing, and hospital diagnosis) were combined to derive a SARD prevalence estimate for each province, categorized by age, sex, and rural/urban status. A hierarchical Bayesian latent class regression model was fit to account for the imperfect sensitivity and specificity of each case definition. The model also provided sensitivity estimates of different case definition approaches.Results.Prevalence estimates for overall SARD ranged between 2 and 5 cases per 1000 residents across provinces. Similar demographic trends were evident across provinces, with greater prevalence in women and in persons over 45 years old. SARD prevalence in women over 45 was close to 1%. Overall sensitivity was poor, but estimates for each of the 3 case definitions improved within older populations and were slightly higher for men compared to women.Conclusion.Our results are consistent with previous estimates and other North American findings, and provide results from coast to coast, as well as useful information about the degree of regional and demographic variations that can be seen within a single country. Our work demonstrates the usefulness of using multiple data sources, adjusting for the error in each, and providing estimates of the sensitivity of different case definition approaches.

Objective Systemic lupus erythematosus is an inflammatory autoimmune disease associated with high morbidity and unacceptable mortality. A major challenge for persons with lupus is coping with their illness and complex care. Our objective was to identify the informational and resource needs of persons with lupus, rheumatologists, and allied health professionals treating lupus. Our findings will be applied toward the development of an innovative web-based technology, the Lupus Interactive Navigator (LIN™), to facilitate and support engagement and self-management for persons with lupus. Methods Eight focus groups were conducted: four groups of persons with lupus ( n = 29), three groups of rheumatologists ( n = 20), and one group of allied health professionals ( n = 8). The groups were held in British Columbia, Ontario, and Quebec. All sessions were audio-recorded and transcribed verbatim. Qualitative analysis was performed using grounded theory. The transcripts were reviewed independently and coded by the moderator and co-moderator using 1) qualitative data analysis software developed by Provalis Research, Montreal, Canada, and 2) manual coding. Results Four main themes emerged: 1) specific information and resource needs; 2) barriers to engagement in health care; 3) facilitators of engagement in health care; and 4) tools identified as helpful for the self-management of lupus. Conclusion These findings will help guide the scope of LIN™ with relevant information topics and specific tools that will be most helpful to the diverse needs of persons with lupus and their health care providers.

Objectives Hospitalization is a major factor in health care costs and a surrogate for worse outcomes in chronic disease. The aim of this study was to determine the frequency of hospitalization secondary to lupus flare, the causes of hospitalization, and to determine risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). Methods Data were collected as part of the 1000 Canadian Faces of Lupus, a prospective cohort study, where annual major lupus flares including hospitalizations were recorded over a 3-year period. Results Of 665 patients with available hospitalization histories, 68 reported hospitalization related to a SLE flare over 3 years of follow-up. The average annual hospitalization rate was 7.6% (range 6.6–8.9%). The most common reasons for hospitalization were: hematologic (22.1%), serositis (20.6%), musculoskeletal (MSK) (16.2%), and renal (14.7%). Univariate risk factors for lupus hospitalization included (OR [95% CI]; p 25 mm/hr (1.9 [1.1–3.4]), proteinuria >0.5 g/d (4.2 [1.9–9.3], and SLAM-2 score (1.1 [1.0–1.2]). After multivariate regression only BMI, number of ACR criteria, and psychosis were associated with hospitalization for lupus flare. Conclusions The mean annual rate of hospitalization attributed to lupus was lower than expected. Hematologic, serositis, MSK and renal were the most common reasons. In a regression model elevated BMI, more ACR criteria and psychosis were associated with hospitalization.

To examine the association between smoking and cutaneous involvement in systemic lupus erythematosus (SLE).We analyzed data from a multicenter Canadian SLE cohort. Mucocutaneous involvement was recorded at the most recent visit using the Systemic Lupus Erythematosus Disease Activity Index 2000 Update (rash, alopecia, and oral ulcers), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (alopecia, extensive scarring, and skin ulceration), and the ACR revised criteria for SLE (malar rash, discoid rash, photosensitivity, and mucosal involvement). Multivariate logistic regression models were used to estimate the independent association between mucocutaneous involvement and cigarette smoking, age, sex, ethnicity, lupus duration, medications, and laboratory data.In our cohort of 1,346 patients (91.0% women), the mean ± SD age was 47.1 ± 14.3 years and the mean ± SD disease duration was 13.2 ± 10.0 years. In total, 41.2% of patients were ever smokers, 14.0% current smokers, and 27.1% past smokers. Active mucocutaneous manifestations occurred in 28.4% of patients; cutaneous damage occurred in 15.4%. Regarding the ACR criteria, malar rash was noted in 59.5%, discoid rash in 16.9%, and photosensitivity in 55.7% of patients. In the multivariate analysis, current smoking was associated with active SLE rash (odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.07, 2.48]). Having ever smoked was associated with ACR discoid rash (OR 2.36 [95% CI 1.69, 3.29]) and photosensitivity (OR 1.47 [95% CI 1.11, 1.95]), and with the ACR total cutaneous score (OR 1.50 [95% CI 1.22, 1.85]). We did not detect any associations between previous smoking and active cutaneous manifestations. No association was found between smoking and cutaneous damage or mucosal ulcers. No interaction was seen between smoking and antimalarials.Current smoking is associated with active SLE rash, and ever smoking with the ACR total cutaneous score. This provides additional motivation for smoking cessation in SLE.

Objective.To produce evidence on the longitudinal evolution of risk factors for coronary heart disease (CHD) in patients with systemic lupus erythematosus (SLE).Methods.Based on data for 115 patients from the Montreal General Hospital Lupus Clinic (1971–2003) and for 4367 control subjects from the Framingham Offspring Study (1971–1994), we investigated the temporal evolution of total serum cholesterol, systolic blood pressure (SBP), body mass index (BMI), blood glucose, and estimated risk for CHD (reflecting the balance of changes in different risk factors). In analyses limited to patients with SLE, we assessed the effect of SLE duration on each risk factor, adjusting for age, calendar time, sex, baseline level of the risk factor, and medication use. Next, we assessed how the adjusted difference in the values of the risk factors between SLE and controls changes over time.Results.Among patients with SLE, longer disease duration was independently associated with higher SBP and blood glucose levels. Compared with controls, these patients appeared to have accelerated rates of increase in total cholesterol, blood glucose, and overall estimated CHD risk. The rate of increase in BMI was lower in patients with SLE than in controls.Conclusion.Elevated CHD risk in patients with SLE appears to be at least partially mediated by accelerated increases in some CHD risk factors, longitudinal trajectories of which increasingly diverge over time from those of population controls.

Objectives The (ever) prevalence of neuropsychiatric systemic lupus erythematosus (NPSLE) can vary widely depending on the definition used. We determined the prevalence of NPSLE in 1000 Faces of Lupus , a large multicenter Canadian cohort. Methods Adults enrolled at 10 sites who satisfied the American College of Rheumatology (ACR) classification for systemic lupus erythematosus (SLE) were included. NPSLE was defined as (i) NPSLE by ACR classification criteria (seizures or psychosis), (ii) ACR, SLEDAI (seizure, psychosis, organic brain syndrome, cranial nerve disorder, headache, and cerebrovascular accident (CVA)), SLAM (CVA, seizure, cortical dysfunction, and headache), and SLICC (cognitive impairment, psychosis, seizures, CVA, cranial or peripheral neuropathy, and transverse myelitis) with and (iii) without minor nonspecific NPSLE manifestations (including mild depression, mild cognitive impairment, and electromyogram-negative neuropathies), and (iv) by ACR and SLEDAI neuropsychiatric (NP) indexes alone. Factors associated with NPSLE were explored using regression models. Results Cohort size was 1253, with mean disease 12 ± 10 years, mean age 41 ± 16 years, and 86% female. Subgroup size was dependent on the specific definition of NPSLE. Prevalence of NPSLE was 6.4% in group (i), n = 1253 ( n = 80); 38.6% in group (ii), n = 681( n = 263); 28.7% in group (iii), n = 586 ( n = 168); and 10.2% in group (iv), n = 1125 ( n = 115). In univariate analysis, Aboriginals had a nearly 2-fold increase in frequency of NPSLE in all groups. Education level and income were not associated with NPSLE ( P = 0.32 and 0.03, respectively). As well, number of ACR criteria, SLAM, age at diagnosis, disease duration, and gender were not associated with NPSLE. Anti-Ro was significantly associated in groups (i) and (iv) and antiphospholipid antibodies (aPL) were increased in groups (i), (ii), and (iii); however, this lost significance when thromboembolic events were excluded from SLICC, SLEDAI, and SLAM indexes. In group (iv), absence of anti-Sm was significant. In multivariate analysis, anti-Ro and aPL (i) and anti-Ro+ and lack of anti-Sm (iv) were significant. NPSLE was not increased in those with +anti-DNA, La, or ribonucleoprotein (RNP), lupus anticoagulant (LAC), or anticardiolipin (aCL) antibody. Conclusions The prevalence and factors associated with NPSLE varied depending on the definition used, was highest in Aboriginals, and may be higher if +anti-Ro or aPL are present. SLAM and SLICC include mild subjective disease manifestations, which contributed to a 10% higher prevalence of NPSLE compared to a more strict definition. NPSLE may be less in this database than other publications as its overall prevalence may be decreasing, or because of selection bias inherent to those who enter an observational cohort. NPSLE was associated with aPL and often anti-Ro and varied by ethnicity.

Objectives. To determine the prevalence of echocardiographic abnormalities and identify associated clinical and laboratory features in a large systemic lupus erythematosus (SLE) cohort. Methods. Patients fulfilling ACR criteria for SLE underwent a transthoracic echocardiogram (TTE) between January 2005 and June 2006. Variables used as potential correlates included age, sex, ethnicity, lupus duration, lupus disease activity (SLEDAI), cumulative damage (SLICC/ACR damage index (DI)), arterial hypertension, diabetes, current smoking, medication use and laboratory data. Multivariate logistic regression was used to examine the association between TTE abnormalities and potential determinants. Results. For the 217 subjects with a TTE performed during the study, the main abnormalities were of the mitral valve (37.3%) and included thickening (25.4%) and insufficiency (25.8%). Other findings included pulmonary artery pressure (PAP) ≥ 30 mm Hg (10.1%), pericardial effusion (4.6%), hypokinesis (2.8%), and aortic insufficiency (3.7%). In multivariate analysis, mitral insufficiency was associated with the use of corticosteroids (OR 2.90; 95%CI 1.42–5.94) and hypokinesis with angiotensin-converting enzyme inhibitors (12.89; 1.06–157.18). Elevated PAP was associated with age (1.04; 1.01–1.07) and with DI (1.20; 1.01–1.42). Conclusion. Valvular abnormalities are frequent in patients with SLE, with mitral valve lesions occurring in over one third. TTE screening may be indicated in patients with SLE, especially for those with identified risk factors such as corticosteroid use.

A growing body of evidence suggests that auto-antibodies to heat-shock protein 60 (anti-Hsp60) constitute an important nontraditional risk factor for cardiovascular disease (1). Immunity to the Hsp60 family has been implicated in endothelial cell stress/activation and the development of atherosclerosis (2). Heat-shock proteins show considerable sequence homology among species, and immune reactions to Hsp60 in infections by microorganisms that express Hsp65 have been widely described (3). Anti-Hsp65 antibodies, induced in response to these pathogens, can cross-react with self Hsp60 expressed on endothelial cells (4–7). Elevated levels of anti-Hsp60 have been associated with progression and severity of atherosclerosis (8–15), with vasculitis in systemic autoimmune diseases (16), and with thrombotic events in the context of systemic lupus erythematosus (SLE) and lupus anticoagulant (LAC) positivity (17). Moreover, anti-Hsp60 from SLE patients were shown to bind to the surface of endothelial cells and induce apoptosis in these cells (17). We have recently demonstrated that anti-Hsp60 enhance thrombus formation and promote endothelial changes in an in vivo murine model of carotid artery injury (18), supporting the notion that these autoantibodies have a prothrombotic role. Based on these findings and others reported in the current literature, we hypothesized that individuals with circulating anti-Hsp60 might be at risk for vascular events. We further hypothesized that anti-Hsp60 might increase the risk of vascular events in individuals with known thrombovascular risk factors, such as antiphospholipid antibodies (aPL). Antiphospholipid antibodies (LAC, anticardiolipin antibody [aCL], and anti–β2-glycoprotein I [anti-β2GPI]) are associated with thrombovascular events (19–21), but it remains unclear why clinical events occur in only some individuals with aPL. Our findings demonstrate that the presence of anti-Hsp60 itself is associated with an increased risk of arterial, but not venous, vascular events. We further show that anti-Hsp60 confer a risk of arterial vascular events in aPL-positive individuals but not in aPL-negative individuals.

Objective To examine whether anti-Ro/SSA antibodies are associated with an increased risk of corrected QT (QTc) prolongation, and to study the stability of this relationship over time. Methods Patients fulfilling the American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE) were invited to undergo a 12-lead resting electrocardiogram (EKG) in the pilot phase of our project, performed between February 2002 and March 2005. The same study population was used to perform a second similar analysis with a larger sample between April 2005 and May 2007. Multivariate logistic regression models were fit to estimate the cross-sectional association between anti-Ro/SSA and other demographic and clinical variables on QTc prolongation. The other potentially associated factors examined included age, sex, disease duration, lupus activity (Systemic Lupus Erythematosus Disease Activity Index 2000 update), damage (Systemic Lupus International Collaborating Clinics/ACR Damage Index), potassium and magnesium levels, and medications with the potential to prolong the QTc interval. Results Cross-sectional analysis of the pilot data (n = 150 patients) showed an association of prolonged QTc with the presence of anti-Ro/SSA (adjusted odds ratio [OR] 12.6; 95% confidence interval [95% CI] 2.3, 70.7). In the second larger study (n = 278), the association was replicated, with a narrower 95% CI (adjusted OR 5.1; 95% CI 1.5, 17.4). In the 118 patients with 2 EKG assessments, the results were consistent over time. Conclusion Anti-Ro/SSA was associated with QTc prolongation in both our pilot data and a larger SLE cohort sample. Patients positive for anti-Ro/SSA may benefit from EKG testing and appropriate counseling should be considered for those identified with QTc prolongation.

Objective Multiple disease-related factors may limit the number of children born to women with systemic lupus erythematosus (SLE). We calculated live births in women with SLE and compared this with general population rates. Methods We studied women with SLE from a subset of centers participating in the Systemic Lupus International Collaborating Clinics Prospective Inception Cohort Study of SLE. Women diagnosed as having SLE before age 50 years were included. Using age, calendar-period, and country-specific general population birth rates, we calculated the standardized incidence ratio (SIR) of observed to expected live births. We also performed a multivariate analysis with the SIR as the dependent variable to explore potential predictors of live births. Results A total of 339 women with SLE were studied. The number of live births over the interval (n = 313) was substantially below that which would be expected (n = 479; SIR 0.65, 95% confidence interval [95% CI] 0.58–0.73). In the multivariate analyses, black race/ethnicity (SIR 1.47, 95% CI 1.08–2.00) and being married or living common-law (SIR 2.04, 95% CI 1.52–2.74) were associated with increased live births (relative to what would be expected). There were trends for fewer live births in women exposed to cyclophosphamide (SIR 0.88, 95% CI 0.56–1.38) and in those with high disease activity (mean SLE Disease Activity Index 2000 update score ≥5; SIR 0.82, 95% CI 0.54–1.25). Conclusion Overall, we found that women with SLE have fewer live births compared with the general population. Marital status, race/ethnicity, and possibly clinical factors may mediate this effect.

Objective.Little information exists regarding the economic burden related to inflammatory myopathies. Our objective was to estimate health services costs in a large, unselected, population-based sample of patients with inflammatory myopathies.Methods.We identified subjects with polymyositis and dermatomyositis from administrative healthcare databases (covering all beneficiaries, about 7.5 million) in Quebec province, Canada. Average estimates of health services costs (physician visits, diagnostic tests and procedures, outpatient surgeries and procedures, acute care hospitalizations) for 2003 were calculated by multiplying health service use levels by the appropriate unit prices, determined from government fee schedules and other sources. Multiple linear regression analyses were performed to establish whether specific factors (age, sex, disease duration, region of residence, socioeconomic status, type of myositis, disease severity) were associated with cost.Results.We identified 1102 subjects with inflammatory myopathy from January 1, 1989, to January 1, 2003. About two-thirds were women (68.9%); average age at case ascertainment was 57.4 years (SD 18.4). The average cost of all reimbursed health services, in 2008 Canadian dollars, was $4099 per patient (SD $9639). Costs increased with age, and were highest early in the disease course. Greater disease severity (defined as the need for prior hospitalization for myositis) was also a strong predictor of both physician costs and total costs.Conclusion.These results indicate significant economic burden related to inflammatory myopathies, with important demographic predictors. Our estimates suggest that the health services costs in inflammatory myopathies may equal, or exceed, those of other serious diseases, such as rheumatoid arthritis and systemic sclerosis.

Objective.To determine the prevalence of restless legs syndrome (RLS) in women with systemic lupus erthythematosus (SLE), and to compare this to a rheumatic disease sample without SLE.Methods.Unselected consecutive female patients were SLE were recruited from a lupus clinic. A RLS questionnaire based on 4 criteria, validated by the International Restless Legs Syndrome Study Group, was administered during a face-to-face interview. Smoking history and height and weight data were collected. Similar methods were used to determine RLS prevalence in a comparator group of women with rheumatic diseases other than SLE. Controls were frequency-matched by age group (in 5-year age bands) to SLE subjects. Controls were otherwise unselected.Results.We recruited 33 women with SLE and 32 controls. Twelve of 33 female SLE subjects scored positively for RLS (37.5%; 95% CI 22.9, 54.7) compared to 4 of 32 controls (12.5%; 95% CI 5.0, 28.1). Multivariate logistic regression showed that adjusted for age, obesity, and smoking, women with SLE were more likely to have RLS than the female controls (adjusted odds ratio 6.61, 95% CI 1.52, 28.77). In our multivariate analyses of all rheumatic patients, including SLE, the adjusted OR for obesity and RLS was 5.14 (95% CI 1.07, 24.6).Conclusion.These novel data indicate that RLS is more prevalent in women with SLE than in controls. Although obesity was a significant risk factor for RLS in our sample, the predictive covariates examined were limited.

Objective.To evaluate factors affecting therapeutic approaches used in clinical practice for the management of systemic lupus erythematosus (SLE), in a multicenter cohort.Methods.We combined data from 10 clinical adult SLE cohort registries in Canada. We used multivariate generalized estimating equation methods to model dichotomized outcomes, running separate regressions where the outcome was current exposure of the patient to specific medications. Potential predictors of medication use included demographic (baseline age, sex, residence, race/ethnicity) and clinical factors (disease duration, time-dependent damage index scores, and adjusted mean SLE Disease Activity Index-2K scores). The models also adjusted for clustering by center.Results.Higher disease activity and damage scores were each independent predictors of exposure to nonsteroid immunosuppressive agents, and for exposure to prednisone. This was not definitely demonstrated for antimalarial agents. Older age at diagnosis was independently and inversely associated with exposure to any of the agents studied (immunosuppressive agents, prednisone, and antimalarial agents). An additional independent predictor of prednisone exposure was black race/ethnicity (adjusted RR 1.46, 95% CI 1.18, 1.81). For immunosuppressive exposure, an additional independent predictor was race/ethnicity, with greater exposure among Asians (RR 1.39, 95% CI 1.02, 1.89) and persons identifying themselves as First Nations/Inuit (2.09, 95% CI 1.43, 3.04) than among whites. All of these findings were reproduced when adjustment for disease activity was limited to renal involvement.Conclusion.Ours is the first portrayal of determinants of clinical practice patterns in SLE, and offers interesting real-world insights. Further work, including efforts to determine how differing clinical approaches may influence outcome, is in progress.

There is growing interest in developing tools and methods for the surveillance of chronic rheumatic diseases, using existing resources such as administrative health databases. To illustrate how this might work, we used population-based administrative data to estimate and compare the prevalence of systemic autoimmune rheumatic diseases (SARDs) across three Canadian provinces, assessing for regional differences and the effects of demographic factors. Cases of SARDs (systemic lupus erythematosus, scleroderma, primary Sjogren’s, polymyositis/dermatomyositis) were ascertained from provincial physician billing and hospitalization data. We combined information from three case definitions, using hierarchical Bayesian latent class regression models that account for the imperfect nature of each case definition. Using methods that account for the imperfect nature of both billing and hospitalization databases, we estimated the over-all prevalence of SARDs to be approximately 2–3 cases per 1,000 residents. Stratified prevalence estimates suggested similar demographic trends across provinces (i.e. greater prevalence in females-versus-males, and in persons of older age). The prevalence in older females approached or exceeded 1 in 100, which may reflect the high burden of primary Sjogren’s syndrome in this group. Adjusting for demographics, there was a greater prevalence in urban-versus-rural settings. In our work, prevalence estimates had good face validity and provided useful information about potential regional and demographic variations. Our results suggest that surveillance of some rheumatic diseases using administrative data may indeed be feasible. Our work highlights the usefulness of using multiple data sources, adjusting for the error in each.

To evaluate the association between cigarette smoking and cutaneous damage in systemic lupus erythematosus (SLE).Our study was performed in SLE clinic registry cohort patients, all of whom fulfilled revised American College of Rheumatology criteria for SLE; patients are followed prospectively with annual assessments that include collection of demographic variables, smoking history, disease activity (SLE Disease Activity Index version 2000, SLEDAI-2K), medications, and damage scores (Systemic Lupus International Collaborating Clinics/ACR Damage Index). Cumulative cutaneous damage scores were used for the primary analyses. Logistic and logit regression models were performed to examine potential associations between current smoking and cutaneous damage, controlling for age, sex, race, lupus disease duration, antimalarial or immunosuppressant use, and anti-DNA and anti-SSA antibody status.Of our sample (N = 276), 92% were women and 73.7% were Caucasian; the mean age was 45.1 years, mean disease duration 13.5 years, and 17.5% were current smokers. In the regression analyses, current cigarette smoking was associated with total cutaneous damage (OR 2.73, 95% CI 1.10, 6.81) and with scarring (OR 4.70, 95 CI 1.04, 21.2). In additional analyses, current smoking was also associated with active lupus rash (OR 6.18, 95% CI 1.63, 23.3).Current cigarette smoking may be associated with cutaneous damage and active lupus rash in SLE, suggesting another reason to emphasize smoking cessation in patients with SLE.