Earl D Silverman

SickKids, Toronto, Ontario, Canada

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Publications (325)1509.78 Total impact

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    ABSTRACT: Objectives Determine if longer disease duration negatively impacts carotid intima-media thickness (CIMT), flow-mediated dilation (FMD) and pulse wave velocity (PWV) in a cohort of childhood-onset systemic lupus erythematosus patients (cSLE). To compare CIMT, FMD and PWV in cSLE with those in healthy children and explore determinants of vascular measurements in cSLE.Methods Cross-sectional analysis performed on a prospective longitudinal cSLE cohort at latest follow-up. Clinical and laboratory data were collected for cSLE patients. CIMT, FMD and PWV were measured in cSLE and healthy children using standardized protocols. Correlations between disease duration and the three vascular tests were performed. Vascular data in cSLE were compared with healthy children. Multivariable linear regression was used to identify determinants of CIMT, FMD and PWV in cSLE.Results cSLE patients (N=149) and healthy controls (N=178) were enrolled. Median age of cSLE was 17.2 (interquartile range [IQR] 15.7-17.9) years and disease duration was 3.2 (IQR 1.8-4.9) years. Median age of healthy children was 14.7 (IQR 13.1-15.9) years. Longer disease duration correlated with worse FMD (r = -0.2; p = 0.031) in cSLE. cSLE had smaller (better) CIMT, higher (better) FMD and similar PWV compared with healthy controls. Linear regression analysis explained < 24% of cSLE vascular tests variability, suggesting that other variables should be explored as important determinants of CIMT, FMD and PWV.Conclusions In this cohort of 149 cSLE, patients did not have worse CIMT, FMD or PWV than healthy controls. Longer disease duration was associated with worse FMD, suggesting progressive endothelial dysfunction over time. This article is protected by copyright. All rights reserved.
    Arthritis and Rheumatology 09/2015; DOI:10.1002/art.39423
  • E. Jaeggi · F. Golding · C. Laskin · J.C. Kingdom · E. Silverman · N. Kan
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    Su B · Capecchi M · Lung K · Manlhiot C · Yan YQ · Liu L · Cui R · Jaeggi ET · Silverman ED · Hamilton EM
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    Tsang W · Silverman E · Cui R · Su B · Wu X · Hamilton R
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    Su B · Capecchi M · Lung K · Manlhiot C · Yan YQ · Liu L · Cui R · Jaeggi ET · Silverman ED · Hamilton EM
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):92.1-92. DOI:10.1136/annrheumdis-2015-eular.3512 · 10.38 Impact Factor
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    ABSTRACT: Background The systemic autoimmune rheumatic diseases (SARD; Systemic Lupus Erythematosus, Rheumatoid Arthritis, Sjogren's Disease, Systemic Sclerosis) are proposed to have a prolonged period of pre-clinical autoimmunity culminating in clinical disease. Evidence from disease-specific studies (e.g., SLE, RA) suggests that the pre-clinical phase is marked by the accrual of immunological abnormalities such as pathogenic auto-antibodies (auto-Ab). Little is known about the cellular derangements that accompany the transition from benign to pathological autoimmunity. Abnormalities in T cell subsets including invariant NKT (iNKT) and T follicular helper (TFH) cells are implicated in the development of systemic autoimmunity. Both a decrease in iNKT cells and an increase in TFH cells are found in patients with established SARD. Objectives To determine if T cell abnormalities associated with SARD are present in pre-clinical autoimmunity. Methods Patients (n=87) who were ANA+ (titer ≥1:160) and healthy controls (HC, n=37) were recruited. Patients were stratified into clinical subsets: (1) no defining SARD symptoms (n=24); (2) undifferentiated connective tissue disease (UCTD, n=17), one or more SARD defining symptom; and (3) early SARD (n=46), fulfilling ACR criteria for a SARD diagnosis. Patients were immunosuppressive and steroid naïve. PBMCs were isolated over a Ficoll gradient, stained with combinations of fluorescently labeled antibodies and analyzed by flow cytometry. ANA titer and auto-Ab profile were determined. Results A statistically significant decrease in the proportion of iNKT cells (CD3+Vα24Jα18 TCR+) was found for all ANA+ patients relative to HC (p=0.0001). Similar results were found for each patient subset when compared to HC; ANA+ asymptomatic (p=0.001), UCTD (p=0.02) and SARD (p=0.001), with no differences amongst groups. The proportion of TFH (CD4+CXCR5highPD-1high) cells was significantly elevated (p=0.01) in patients versus HC. While the proportion of TFH cells was similar between asymptomatic ANA+ patients and HC, there was a significant expansion of TFH in UCTD as compared to both groups (p=0.02 and p=0.04, respectively). SARD patients had a non-significant trend to increased proportions of TFH as compared to UCTD. Patients (n=50) with higher ANA titers (≥1:640) had a significant increase (p=001) in TFH when compared to individuals (n=13) with lower ANA levels (1:160). A positive correlation (p<0.0001) between the proportion of TFH and the number of auto-Abs within the patient population was found. No significant differences were noted in the iNKT or TFH cell proportions between SARD patients stratified by specific disease diagnosis. Conclusions A decrease in the iNKT cell subset is present at the earliest phase of pre-clinical autoimmunity (asymptomatic ANA+) suggesting that loss of this T cell subset contributes to a breach of tolerance to nuclear antigens. In contrast, increases in the TFH compartment appear to parallel the onset of clinical symptoms and accrual of auto-Abs. These results suggest that an incremental development of T cell abnormalities marks the progression towards clinically significant autoimmunity. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):421.1-421. DOI:10.1136/annrheumdis-2015-eular.4052 · 10.38 Impact Factor
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    ABSTRACT: Background Patients with systemic autoimmune rheumatic diseases (SARD) often have a prolonged pre-clinical phase during which they are anti-nuclear antibody (ANA)+ but lack clinical symptoms. It has been proposed that progression from asymptomatic autoimmunity to clinical disease is accompanied by immunologic changes that could be used as predictors of disease development. Elevated levels of interferon (IFN)-induced gene expression, termed the IFN signature, are found in several SARD conditions, and IFNs appear to play an important role in disease pathogenesis. Objectives To determine whether ANA+ individuals who lack sufficient symptoms for a SARD diagnosis share the IFN-signature. Methods ANA+ individuals who: 1) lacked clinical symptoms of SARD (ANS); 2) had a least one clinical symptom of SARD (Undifferentiated Connective Tissue Disease, UCTD); or 3) had a recently diagnosed SARD (Systemic Lupus Erythematosus, SLE; Sjogren's Disease, SjD; Scleroderma, SSc; Mixed Connective Tissue Disease, MCTD; Dermatomyositis, DM) were recruited from clinics at UHN/MSH hospitals. None of the patients were on corticosteroids or DMARDs with the exception of hydroxychloroquine. Healthy controls (HC) were also recruited. RNA was prepared from blood archived in Tempus tubes. Expression of 5 IFN-induced genes was quantified by Nanostring, normalized to expression of housekeeping genes, and summed to generate an IFN5 score. ANAs and levels of specific autoantibodies were measured by the hospital laboratory. Results To date we have measured the IFN signature on 95 individuals (21 HC, 21 ANS, 16 UCTD, 22 SjD, 7 SSc, 6 SLE, 1 MCTD, 1 DM). There was a trend to higher mean IFN score in all groups as compared to HC (mean ± SD: HC 7,071±6,321; ANS 27,245±36,037; UCTD 27,624±24,827; SSc 34,940±40,940; SjD 61,877±33,404; SLE 62,769±50,233; MCTD/DM 97,716±24,973), which achieved statistical significance for ANS, UCTD, SjD, and SLE (corrected p=0.044, 0.003, <0.0001, 0.0075, respectively). Using a cutoff of 2 SD above the mean of HC as indicative of an elevated IFN5 score; 8/21 ANS, 8/16 UCTD, 3/7 SSc, 18/22 SjD, 5/6 SLE, and 2/2 MCTD/DM participants had elevated IFN levels. Marked elevations of the IFN5 score were seen in a subset of ANS and UCTD participants, which could not be attributed to recent infection. Although there was a significant correlation between the ANA titer (p=0.002) and IFN5 score for all ANA+ individuals, this was not seen in the ANS or UCTD subsets of this population. However the IFN5 score was positively correlated with the number of different ANA specificities present in the UCTD subset (p=0.048) and all ANA+ individuals (p<0.0001). Within the ANS subset, there was a strong correlation between the presence of anti-Ro/La antibodies with 6/8 IFN5 high as compared to 1/13 IFN low individuals being antibody positive (p=0.003). Conclusions An IFN signature is seen in a subset of ANA+ individuals prior to a confirmed diagnosis of SARD and appears to correlate with the type and number of specific ANAs rather than onset of clinical disease. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):98.1-98. DOI:10.1136/annrheumdis-2015-eular.5017 · 10.38 Impact Factor
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    ABSTRACT: Objective To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis ( pcJIA). Methods This three-part, randomised, placebocontrolled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) <30 kg; 8 mg/kg for BW ≥30 kg). At week 16, patients with ≥JIA-American College of Rheumatology (ACR) 30 improvement entered the 24- week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab. Results In part 1, 188 patients received tocilizumab (<30 kg: 10 mg/kg (n=35) or 8 mg/kg (n=34); ≥30 kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: -0.21; 95% CI -0.35 to -0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIAACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY). Conclusions Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis.
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    ABSTRACT: To describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis (JIA) and to identify clinical features associated with an increased risk of flare. We studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment. Probability of first flare was calculated with Kaplan-Meier methods, and associated features were identified using Cox regression. 1146 children were followed up a median of 24 months after attaining inactive disease. We observed 627 first flares (54.7% of patients) with median active joint count of 1, physician global assessment (PGA) of 12 mm and duration of 27 weeks. Within a year after attaining inactive disease, the probability of flare was 42.5% (95% CI 39% to 46%) for any flare and 26.6% (24% to 30%) for a significant flare. Within a year after stopping treatment, it was 31.7% (28% to 36%) and 25.0% (21% to 29%), respectively. A maximum PGA >30 mm, maximum active joint count >4, rheumatoid factor (RF)-positive polyarthritis, antinuclear antibodies (ANA) and receiving disease-modifying antirheumatic drugs (DMARDs) or biological agents before attaining inactive disease were associated with increased risk of flare. Systemic JIA was associated with the lowest risk of flare. In this real-practice JIA cohort, flares were frequent, usually involved a few swollen joints for an average of 6 months and 60% led to treatment intensification. Children with a severe disease course had an increased risk of flare. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the rheumatic diseases 05/2015; DOI:10.1136/annrheumdis-2014-207164 · 10.38 Impact Factor
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    ABSTRACT: Systemic lupus erythematosus (SLE) is characterized by increased cardiovascular risk in adult-onset and childhood-onset SLE (cSLE). Type I interferons (IFNs) appear to play a prominent role in premature vascular damage in adult SLE, at least in part, by inducing impairments in the phenotype and function of endothelial progenitor cells (EPCs), thereby hampering vascular repair. It is not clear if EPC dysfunction is present in cSLE in association with a type I IFN signature. Phenotype and numbers of EPCs were quantified in patients with cSLE, juvenile idiopathic arthritis (JIA), and matched healthy controls (HC). In a separate cohort of cSLE subjects, markers of subclinical atherosclerosis and endothelial dysfunction were quantified using standardized protocols, and analyzed for associations with type I IFN serum activity. EPC numbers and function were significantly decreased in cSLE as compared to JIA and HC. cSLE serum impaired HC EPC differentiation into mature endothelial cells, an effect blocked by type I IFN pathway inhibition. Type I IFN serum activity was not significantly associated with subclinical atherosclerosis and endothelial function in cSLE. As in adults, cSLE is characterized by phenotypic and functional EPC abnormalities, likely triggered by type I IFNs. While cross-sectional analysis detected no global association between type I IFN signatures and vascular measures of subclinical atherosclerosis, longitudinal assessments are needed to evaluate if progression of vascular damage in cSLE is associated with type I IFNs as in the adult population. This article is protected by copyright. All rights reserved. © 2015 American College of Rheumatology.
    Arthritis and Rheumatology 04/2015; 67(8). DOI:10.1002/art.39149
  • E V Rozenblyum · D M Levy · U Allen · E Harvey · D Hebert · E D Silverman
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    ABSTRACT: Cytomegalovirus (CMV) is a beta-herpesvirus and antibodies to this virus are common in patients with systemic lupus erythematosus (SLE). However, few studies have examined the relationship between CMV infection and SLE. Our objectives were: 1) to determine the prevalence of CMV infection at the time of SLE diagnosis, and 2) to determine the risk factors for CMV infection. A database review of 670 patients with pediatric SLE (pSLE) seen over a 20-year period identified seven patients with a CMV infection detected at the time of diagnosis of SLE. CMV was diagnosed by serology, urine and bronchoalveolar lavage. Clinical manifestations, laboratory findings, virology studies and treatments were reviewed. CMV infection was detected in seven patients at the time of SLE diagnosis (1.04% of total cohort): six were female: mean age was 13 years. Predominant features included non-Caucasian ethnicity (p < 0.01 as compared to total SLE cohort), persistent fevers on prednisone in seven and nephrotic syndrome in four. Laboratory findings included: anemia in seven, lymphopenia in five, elevated liver enzymes in four, with anti-dsDNA and anti-RNP antibodies present in six and five, respectively. Six patients received ganciclovir and CMV hyperimmune globulin (Cytogam®) with the continuation of prednisone during CMV treatment. Six of seven fully recovered without sequelae (one without treatment) but one patient died with active CMV infection. There were 1.04% of patients with pSLE who developed CMV infection. All were of non-Caucasian ethnicity. Persistent fever despite prednisone, with concomitant anemia, may be additional clues to CMV infection in pSLE. We suggest all patients have routine testing for CMV immunity at initial presentation of pSLE. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    Lupus 01/2015; 24(7). DOI:10.1177/0961203314565443 · 2.20 Impact Factor
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    ABSTRACT: Objective: To evaluate the influence of ethnicity on self-reported health-related quality of life (HRQOL) in the Canadian childhood-onset systemic lupus erythematosus (cSLE) population. Methods: Patients with cSLE at 4 pediatric centers were consecutively enrolled. Sociodemographics and multiple disease activity measures were collected. The Child Health Questionnaire (CHQ) was administered and analyzed by ethnicity. Results: We enrolled 213 cSLE patients, and complete data from 196 patients with the following ethnicities were analyzed: white (33%), Asian (32%), South Asian (16%), African American (11%), Latino/Hispanic (5%), and Aboriginal (4%). Compared to healthy children, cSLE patients rated their HRQOL significantly more poorly in 9 of 10 individual domains, and in 4 of 10 domains when compared to a cohort of juvenile arthritis patients. Within the cSLE cohort, CHQ scores were lower in 5 of 10 domains in white patients versus nonwhite ethnicities (P < 0.05 for each). Physical summary scores were lower for white patients compared to the other ethnicities aggregated together (mean ± SD 46.0 ± 11.9 versus 50.4 ± 10.1; P = 0.009); however, psychosocial summary scores were similar among the groups (mean ± SD 40.5 ± 14.6 versus 42.8 ± 12.7; P = 0.26). Disease activity measures, including the Systemic Lupus Erythematosus Disease Activity Index 2000, the Systemic Lupus Activity Measure, Revised, and physician global visual analog scale, were similar across ethnicities. However, patient-reported Systemic Lupus Erythematosus Activity Questionnaire symptom scores were greater in patients of white ethnicity compared to those of Asian ethnicity (mean ± SD 8.2 ± 5.8 versus 4.5 ± 4.7; P = 0.004). Conclusion: The self- and parent-reported health status of Canadian cSLE patients differed across ethnicities, with white patients reporting lower HRQOL despite similar and overall low disease activity.
    12/2014; 66(12). DOI:10.1002/acr.22363
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    ABSTRACT: Objective: Prognosis studies examine outcomes and/or seek to identify predictors or factors associated with outcomes. Many prognostic factors have been identified in systemic lupus erythematosus (SLE), but few have been consistently found across studies. We hypothesized that this is due to a lack of rigor of study designs. This study aimed to systematically assess the methodologic quality of prognosis studies in SLE. Methods: A search of prognosis studies in SLE was performed using MEDLINE and Embase, from January 1990 to June 2011. A representative sample of 150 articles was selected using a random number generator and assessed by 2 reviewers. Each study was assessed by a risk of bias tool according to 6 domains: study participation, study attrition, measurement of prognostic factors, measurement of outcomes, measurement/adjustment for confounders, and appropriateness of statistical analysis. Information about missing data was also collected. Results: A cohort design was used in 71% of studies. High risk of bias was found in 65% of studies for confounders, 57% for study participation, 56% for attrition, 36% for statistical analyses, 20% for prognostic factors, and 18% for outcome. Missing covariate or outcome information was present in half of the studies. Only 6 studies discussed reasons for missing data and 2 imputed missing data. Conclusion: Lack of rigorous study design, especially in addressing confounding, study participation and attrition, and inadequately handled missing data, has limited the quality of prognosis studies in SLE. Future prognosis studies should be designed with consideration of these factors to improve methodologic rigor.
    10/2014; 66(10). DOI:10.1002/acr.22322
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    ABSTRACT: To determine the most effective immunosuppressive therapy for the longterm management of proliferative lupus nephritis (PLN) based on the outcome of renal failure. A systematic review of randomized controlled trials (RCT) was conducted. MEDLINE and EMBASE were searched. RCT designed to examine the maintenance treatment effectiveness of immunosuppressive agents for PLN were included. A Bayesian network metaanalysis of 2-arm and 3-arm trials was used. A skeptical prior assumption was used in sensitivity analysis. Four immunosuppressive agents were evaluated: cyclophosphamide (CYC), azathioprine (AZA), mycophenolate mofetil (MMF), and prednisone alone. The outcome of interest was renal failure during the study period, defined by serum creatinine (sCr) > 256 μmol/l, doubling of sCr from baseline, and/or endstage renal disease. The OR (95% credible interval) of developing renal failure at 2-3 years was 0.72 (0.11, 4.49) for AZA versus CYC, 0.32 (0.04, 2.25) for MMF versus CYC, 2.40 (0.22, 36.94) for prednisone alone versus CYC, and 0.45 (0.11, 1.48) for MMF versus AZA. The probability (95% credible interval) of developing renal failure at 2 years as expected for each agent was 6% (0.7%, 24%) for MMF, 12% (2%, 37%) for AZA, 16% (5%, 33%) for CYC, and 31% (5%, 81%) for prednisone alone. After applying a skeptical prior in the Bayesian analysis, there was no evidence of benefit for 1 therapy over another. Although the data suggest that MMF may be superior to other treatments for the maintenance treatment of PLN, the evidence is not conclusive.
    The Journal of Rheumatology 09/2014; 41(10). DOI:10.3899/jrheum.140050 · 3.19 Impact Factor
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    ABSTRACT: Key Clinical Message Systemic lupus erythematosus should be included in the differential diagnosis of every adolescent with pancytopenia. An accurate diagnosis with the appropriate therapy is vital and can cause lasting reversal of this condition. Systemic lupus erythematosus should be included in the differential diagnosis of every adolescent with pancytopenia. An accurate diagnosis with the appropriate therapy is vital and can cause lasting reversal of this condition.
    09/2014; 2(6). DOI:10.1002/ccr3.123
  • E.N. Kelly · R Sananes · C Chiu‐Man · E.D. Silverman · E Jaeggi
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    ABSTRACT: Objective: To determine the impact of prenatal exposure to maternal anti-Ro antibodies, slow fetal heart rate, and/or prolonged dexamethasone therapy for immune-mediated congenital atrioventricular heart block (CAVB) on the cognitive and academic performance of these children at school age. Methods: We performed a prospective, blinded assessment of the cognitive functioning of 3 cohorts of children ages 6-16 years with in utero exposure to maternal anti-Ro antibodies in the following groups: no CAVB and no prenatal dexamethasone treatment (n = 14), CAVB without prenatal treatment (n = 10), and CAVB with prenatal dexamethasone treatment (n = 16). Domains assessed included intelligence, visual perceptual and visual motor skills, auditory and visual attention, verbal learning and memory, visual memory, executive function, and behavior. Results: All cohorts scored within the normal range and were not significantly different in terms of intelligence scores, verbal comprehension, perceptional reasoning, working memory, and processing speed. For children with CAVB who were treated prenatally, there were no significant associations between the neurocognitive function scores, the minimal fetal heart rate (range 47-80 beats per minute), and either the duration (range 2-15 weeks) or dosage (range 56-824 mg) of dexamethasone therapy. Conclusion: CAVB and transplacental treatment with dexamethasone was not associated with neurocognitive impairment in school-age children. Larger numbers of children are needed to validate our observation, and assessment of other cognitive abilities is warranted.
    Arthritis and Rheumatology 08/2014; 66(8). DOI:10.1002/art.38675
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    ABSTRACT: Background: Studies of paediatric patients with membranous lupus nephritis (MLN) have yielded variable results, mostly due to the inclusion of mixed, i.e. proliferative nephritis. The aim of this study was to describe clinical and laboratory findings at the diagnosis of paediatric non-proliferative MLN, report the outcome and identify predictors of remission. Methods: A single-center cohort study of consecutive children diagnosed with non-proliferative MLN was performed. Clinical and laboratory measures and treatment regimens were obtained in prospective standardized assessments. Renal outcome was measured by renal parameters and steroid requirement. Predictors for remission and time to remission were determined. Results: A total of 30 children were identified with a median follow-up time 4.1 years. Of 21 patients followed for more than 2 years, 19 (90 %) achieved clinical remission, and 16 (76 %) achieved a state of maintained clinical remission on low-dose prednisone. Three patients developed proliferative nephritis on subsequent renal biopsy. Lower albumin at the time of biopsy was correlated with a lower rate of remission and longer time to remission. Conclusions: Among our paediatric patient cohort the outcome of non-proliferative MLN in systemic lupus erythematosus was good. The majority of patients did not require aggressive immunosuppressive treatment to reach a stable disease state on low-dose steroid treatment.
    Pediatric Nephrology 07/2014; 30(1). DOI:10.1007/s00467-014-2908-2 · 2.86 Impact Factor
  • 69th Annual Meeting of the Canadian-Rheumatology-Association (CRA); 07/2014
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    ABSTRACT: Objective To describe clinical outcomes of juvenile idiopathic arthritis (JIA) in a prospective inception cohort of children managed with contemporary treatments. Methods Children newly diagnosed with JIA at 16 Canadian paediatric rheumatology centres from 2005 to 2010 were included. Kaplan–Meier survival curves for each JIA category were used to estimate probability of ever attaining an active joint count of 0, inactive disease (no active joints, no extraarticular manifestations and a physician global assessment of disease activity <10 mm), disease remission (inactive disease >12 months after discontinuing treatment) and of receiving specific treatments. Results In a cohort of 1104 children, the probabilities of attaining an active joint count of 0 exceeded 78% within 2 years in all JIA categories. The probability of attaining inactive disease exceeded 70% within 2 years in all categories, except for RF-positive polyarthritis (48%). The probability of discontinuing treatment at least once was 67% within 5 years. The probability of attaining remission within 5 years was 46–57% across JIA categories except for polyarthritis (0% RF-positive, 14% RF-negative). Initial treatment included joint injections and non-steroidal anti-inflammatory drugs for oligoarthritis, disease-modifying antirheumatic drugs (DMARDs) for polyarthritis and systemic corticosteroids for systemic JIA. Conclusions Most children with JIA managed with contemporary treatments attain inactive disease within 2 years of diagnosis and many are able to discontinue treatment. The probability of attaining remission within 5 years of diagnosis is about 50%, except for children with polyarthritis.
    Annals of the Rheumatic Diseases 05/2014; 74(10). DOI:10.1136/annrheumdis-2014-205372 · 10.38 Impact Factor

Publication Stats

9k Citations
1,509.78 Total Impact Points


  • 1989–2015
    • SickKids
      • • Division of Rheumatology
      • • Division of Cardiology
      • • Department of Diagnostic Imaging
      Toronto, Ontario, Canada
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
    • The University of Calgary
      • Faculty of Medicine
      Calgary, Alberta, Canada
  • 1988–2015
    • University of Toronto
      • • Hospital for Sick Children
      • • Department of Immunology
      • • Department of Paediatrics
      • • Division of Rheumatology
      • • Laboratory Medicine Program
      Toronto, Ontario, Canada
  • 2009
    • University Health Network
      Toronto, Ontario, Canada
    • The University of Chicago Medical Center
      Chicago, Illinois, United States
    • IRCCS Istituto G. Gaslini
      Genova, Liguria, Italy
    • University of Oklahoma Health Sciences Center
      • Department of Pediatrics
      Oklahoma City, Oklahoma, United States
  • 1993–2006
    • Dalhousie University
      • Department of Pediatrics
      Halifax, Nova Scotia, Canada
    • University of Texas Health Science Center at Houston
      • Department of Internal Medicine
      Houston, Texas, United States
  • 1996
    • University of Ottawa
      • Department of Pediatrics
      Ottawa, Ontario, Canada
    • University of Saskatchewan
      • Department of Pediatrics
      Saskatoon, Saskatchewan, Canada
  • 1992–1996
    • Toronto Western Hospital
      Toronto, Ontario, Canada
    • Children's National Medical Center
      • Division of Rheumatology
      Washington, Washington, D.C., United States
    • Baylor College of Medicine
      • Department of Pediatrics
      Houston, TX, United States
  • 1995
    • Stockholm University
      Tukholma, Stockholm, Sweden
  • 1985
    • Stanford University
      Palo Alto, California, United States
    • Stanford Medicine
      Stanford, California, United States
  • 1984
    • Children's Hospital Los Angeles
      Los Angeles, California, United States