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Sasha Bernatsky,
Rosalind Ramsey-Goldman,
Jeremy Labrecque,
Lawrence Joseph,
Jean-Francois Boivin,
Michelle Petri,
Asad Zoma,
Susan Manzi,
Murray B Urowitz,
Dafna Gladman, [......],
Jean-Luc Senécal,
Michel Zummer,
Janet E Pope,
Stephanie Ensworth,
Hani El-Gabalawy,
Timothy McCarthy,
Lene Dreyer,
John Sibley,
Yvan St Pierre,
Ann E Clarke
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ABSTRACT: OBJECTIVE: To update estimates of cancer risk in SLE relative to the general population. METHODS: A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. RESULTS: Across 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person-years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin's lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61-0.88), endometrial (SIR 0.44, 95% CI 0.23-0.77), and possibly ovarian cancers (0.64, 95% CI 0.34-1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23). CONCLUSION: These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL, and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing.
Journal of Autoimmunity 02/2013; · 7.37 Impact Factor
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Zahi Touma,
Dafna D Gladman,
Anne Mackinnon,
Simon Carette,
Mahmoud Abu-Shakra,
Anca Askanase,
Ola Nived, John G Hanly,
Carolina Landolt-Marticorena,
Lai-Shan Tam,
Sergio Toloza,
Mandana Nikpour,
Claire Riddell,
Amanda Steiman,
Lihi Eder,
Amir Haddad,
Claire Barber,
Murray B Urowitz
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ABSTRACT: OBJECTIVE: To describe the development of the Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 (S2K RI-50) Website (www.s2k-ri-50.com) and to assess satisfaction with its training and examination modules among rheumatologists and rheumatology fellows. METHODS: The development of the Website occurred in 3 phases. The first was a deployment phase that consisted of preparing the site map along with its content. The content included the S2K RI-50 training manual, the tests and corresponding question bank, and the online adaptive training module, along with the extensive site testing. The second phase included the participation of rheumatologists and trainees who completed the Website modules. The third was a quality assurance phase in which an online survey was developed to determine the satisfaction level of its users. Further modifications were implemented per participants' recommendations. RESULTS: The site has been online since it was registered in September 2010. Fourteen rheumatologists and rheumatology trainees from different centers reviewed and completed the material contained in the Website. The survey revealed acceptance among rheumatologists for the Website's content, design, and presentation. The Website was rated as user-friendly and useful in familiarizing investigators with the S2K RI-50. After completion of the training and examination modules, participants reported a suitable level of preparation to implement the S2K RI-50 in clinical trials and research settings in a timely manner. CONCLUSION: The Website includes training and examination modules that familiarize rheumatologists with the S2K RI-50 and assesses their competence to use the index. This prepares them for the use of the S2K RI-50 in clinical trials and research settings.
The Journal of Rheumatology 11/2012; · 3.69 Impact Factor
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Ben Parker,
Murray B Urowitz,
Dafna D Gladman,
Mark Lunt,
Sang-Cheol Bae,
Jorge Sanchez-Guerrero,
Juanita Romero-Diaz,
Caroline Gordon,
Daniel J Wallace,
Ann E Clarke, [......],
Meggan Mackay,
Manuel Ramos-Casals,
Raymond F van Vollenhoven,
Kenneth C Kalunian,
Guillermo Ruiz-Irastorza,
Sam Lim,
Diane L Kamen,
Christine A Peschken,
Murat Inanc,
Ian N Bruce
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ABSTRACT: BACKGROUND: The metabolic syndrome (MetS) may contribute to increased cardiovascular risk in systemic lupus erythematosus (SLE). We aimed to examine the association of demographic factors, lupus phenotype and therapy exposure with the presence of MetS. METHODS: The Systemic Lupus International Collaborating Clinics Registry for Atherosclerosis inception cohort enrolled recently diagnosed (<15 months) SLE patients from 30 centres across 11 countries from 2000. Clinical, laboratory and therapeutic data were collected according to a standardised protocol. MetS was defined according to the 2009 consensus statement from the International Diabetes Federation. Univariate and backward stepwise multivariate logistic regression were used to assess the relationship of individual variables with MetS. RESULTS: We studied 1686 patients, of whom 1494 (86.6%) had sufficient data to determine their MetS status. The mean (SD) age at enrolment and disease duration was 35.2 years (13.4) and 24.1 weeks (18.0), respectively. MetS was present at the enrolment visit in 239 (16%). In backward stepwise multivariable regression analysis, higher daily average prednisolone dose (mg) (OR 1.02, 95% CI 1.00 to 1.03), older age (years) (OR 1.04, 95% CI 1.03 to 1.06), Korean (OR 6.33, 95% CI 3.68 to 10.86) and Hispanic (OR 6.2, 95% CI 3.78 to 10.12) ethnicity, current renal disease (OR 1.79, 95% CI 1.14 to 2.80) and immunosuppressant use (OR 1.81, 95% CI 1.18 to 2.78) were associated with MetS. CONCLUSIONS: Renal lupus, higher corticosteroid doses, Korean and Hispanic ethnicity are associated with MetS in SLE patients. Balancing disease control and minimising corticosteroid exposure should therefore be at the forefront of personalised treatment decisions in SLE patients.
Annals of the rheumatic diseases 09/2012; · 8.11 Impact Factor
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Michael Mahler,
Todd Parker,
Carol L Peebles,
Luis E Andrade,
Andreas Swart,
Yvette Carbone,
David J Ferguson,
Danilo Villalta,
Nicola Bizzaro, John G Hanly,
Marvin J Fritzler
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ABSTRACT: OBJECTIVE: Antinuclear antibodies (ANA) are a serological hallmark of systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE). While a number of ANA patterns detected by indirect immunofluorescence (IIF) have diagnostic significance, autoantibodies producing the dense fine speckled (DFS) pattern have been reported to be more prevalent in healthy individuals than in SARD. METHODS: Sequential samples submitted for ANA testing were screened for anti-DFS antibodies by IIF (n = 3263). Samples with the DFS pattern were tested for anti-DFS70/lens epithelium-derived growth factor (LEDGF) antibodies by ELISA and by a novel chemiluminescence assay (CIA, Quanta Flash DFS70). Sera from patients with various diseases and healthy individuals were tested for anti- DFS70/LEDGF antibodies by CIA. A cohort of 251 patients with SLE was used to analyze serological and clinical associations of anti-DFS70 antibodies. RESULTS: The frequency of anti-DFS antibodies by IIF was 1.62%. The prevalence of anti- DFS70/LEDGF antibodies as detected by CIA in the different cohorts was 8.9% in healthy individuals, 2.8% in SLE, 2.6% in rheumatoid arthritis, 4.0% in asthma, 5.0% in interstitial cystitis, 1.7% in Graves' disease, and 6.0% in Hashimoto's thyroiditis. Of note, the prevalence of anti- DFS70/LEDGF antibodies was significantly higher in healthy individuals compared to patients with SARD (p = 0.00085). In SLE results, anti-DFS70/LEDGF antibodies were not significantly associated with clinical features or other autoantibodies typically found in SLE. Only 1/7 SLE sera showed anti-DFS70/LEDGF, but no other autoantibody reactivity. CONCLUSION: "Monospecific" anti-DFS70/LEDGF antibodies may represent a biomarker for differentiating SARD from non-SARD individuals, but there is a need for a reliable assay to ensure reactivity to DFS70.
The Journal of Rheumatology 09/2012; · 3.69 Impact Factor
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ABSTRACT: We examined the association between responses on a screening questionnaire and objective performance on a computer-administered test of cognitive abilities in systemic lupus erythematosus (SLE).
The Cognitive Symptom Inventory (CSI) and Hospital Anxiety and Depression Scales (HADS) questionnaires were compared in patients with SLE or rheumatoid arthritis (RA). The Automated Neuropsychological Assessment Metrics (ANAM) was used to evaluate cognitive performance in patients with SLE. Efficiency of performance was measured by "throughput" (number of correct responses per minute) and "inverse efficiency" (response speed/proportion of correct responses). Linear regression was applied to log-transformed CSI scores to examine their associations with ANAM scores and other factors.
Patients with SLE (n = 68) or RA (n = 33) were similar in age, sex, ethnicity, and education status (p > 0.05). Patients with SLE had higher total CSI scores (33.6 ± 10.5 vs 29.4 ± 6.8, respectively; p = 0.041) and attention/concentration subscale CSI scores (15.7 ± 5.3 vs 13.3 ± 3.4; p = 0.016) compared to patients with RA. In patients with SLE there was a positive association between CSI scores and neuropsychiatric (NP) events at the time of testing (p = 0.0006), HADS anxiety (p < 0.0001), and depression (p < 0.0001) scores. After adjustment for age, education, disease duration, and NP events at the time of testing, there was no significant association (p > 0.05) between ANAM and CSI scores in patients with SLE. The results were similar using either "throughput" or "inverse efficiency" or the number of impaired ANAM subscales after adjustment for simple reaction time.
The CSI self-report questionnaire of cognitive symptoms does not reliably screen for efficiency of cognitive processing in patients with SLE. Rather, cognitive complaints reported in the CSI are influenced by the presence of anxiety and depression.
The Journal of Rheumatology 06/2012; 39(7):1371-7. · 3.69 Impact Factor
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Michelle Petri,
Ana-Maria Orbai,
Graciela S Alarcón,
Caroline Gordon,
Joan T Merrill,
Paul R Fortin,
Ian N Bruce,
David Isenberg,
Daniel J Wallace,
Ola Nived, [......],
Kristjan Steinsson,
Andrew G Franks,
Lisa Sigler,
Suhail Hameed,
Hong Fang,
Ngoc Pham,
Robin Brey,
Michael H Weisman,
Gerald McGwin,
Laurence S Magder
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ABSTRACT: The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE.
The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. The SLICC group validated the classification criteria in a new validation sample of 690 new expert-rated patient scenarios.
Seventeen criteria were identified. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (49 versus 70; P = 0.0082) and had greater sensitivity (94% versus 86%; P < 0.0001) and equal specificity (92% versus 93%; P = 0.39). In the validation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (62 versus 74; P = 0.24) and had greater sensitivity (97% versus 83%; P < 0.0001) but lower specificity (84% versus 96%; P < 0.0001).
The new SLICC classification criteria performed well in a large set of patient scenarios rated by experts. According to the SLICC rule for the classification of SLE, the patient must satisfy at least 4 criteria, including at least one clinical criterion and one immunologic criterion OR the patient must have biopsy-proven lupus nephritis in the presence of antinuclear antibodies or anti-double-stranded DNA antibodies.
Arthritis & Rheumatism 05/2012; 64(8):2677-86. · 7.87 Impact Factor
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The American Journal of dermatopathology 04/2012; 34(7):770-1. · 1.30 Impact Factor
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John G Hanly,
Murray B Urowitz,
Li Su,
Caroline Gordon,
Sang-Cheol Bae,
Jorge Sanchez-Guerrero,
Juanita Romero-Diaz,
Daniel J Wallace,
Ann E Clarke,
Em Ginzler, [......],
Rf van Vollenhoven,
Kenneth C Kalunian,
Guillermo Ruiz-Irastorza,
Sam Lim,
Diane L Kamen,
Christine A Peschken,
Murat Inanc,
Chris Theriault,
Kara Thompson,
Vernon Farewell
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ABSTRACT: The aim of this study was to describe the frequency, attribution, outcome and predictors of seizures in systemic lupus erythematosus (SLE).
The Systemic Lupus International Collaborating Clinics, or SLICC, performed a prospective inception cohort study. Demographic variables, global SLE disease activity (SLE Disease Activity Index 2000), cumulative organ damage (SLICC/American College of Rheumatology Damage Index (SDI)) and neuropsychiatric events were recorded at enrolment and annually. Lupus anticoagulant, anticardiolipin, anti-β(2) glycoprotein-I, antiribosomal P and anti-NR2 glutamate receptor antibodies were measured at enrolment. Physician outcomes of seizures were recorded. Patient outcomes were derived from the SF-36 (36-Item Short Form Health Survey) mental component summary and physical component summary scores. Statistical analyses included Cox and linear regressions.
The cohort was 89.4% female with a mean follow-up of 3.5±2.9 years. Of 1631 patients, 75 (4.6%) had ≥1 seizure, the majority around the time of SLE diagnosis. Multivariate analysis indicated a higher risk of seizures with African race/ethnicity (HR (CI): 1.97 (1.07 to 3.63); p=0.03) and lower education status (1.97 (1.21 to 3.19); p<0.01). Higher damage scores (without neuropsychiatric variables) were associated with an increased risk of subsequent seizures (SDI=1:3.93 (1.46 to 10.55); SDI=2 or 3:1.57 (0.32 to 7.65); SDI≥4:7.86 (0.89 to 69.06); p=0.03). There was an association with disease activity but not with autoantibodies. Seizures attributed to SLE frequently resolved (59/78 (76%)) in the absence of antiseizure drugs. There was no significant impact on the mental component summary or physical component summary scores. Antimalarial drugs in the absence of immunosuppressive agents were associated with reduced seizure risk (0.07 (0.01 to 0.66); p=0.03).
Seizures occurred close to SLE diagnosis, in patients with African race/ethnicity, lower educational status and cumulative organ damage. Most seizures resolved without a negative impact on health-related quality of life. Antimalarial drugs were associated with a protective effect.
Annals of the rheumatic diseases 04/2012; 71(9):1502-9. · 8.11 Impact Factor
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The American Journal of dermatopathology 03/2012; 34(7):755-6. · 1.30 Impact Factor
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ABSTRACT: The presence of anti-nuclear antibodies (ANA) is a hallmark of systemic autoimmune rheumatic diseases (SARD). The indirect immunofluorescence (IIF) assay on HEp-2 cells is a commonly used test for the detection of ANA and was recently recommended as the screening test of choice by a task force of the American College of Rheumatology. However, up to 20% of serum samples from healthy individuals (HI) have been reported to have a positive ANA test, the majority of which are directed to the dense fine speckles 70 (DFS70) antigen. Even more important, the DFS IIF pattern has been reported in 33% of ANA positive HI, but not in ANA positive SARD sera. Since the intended use of the ANA HEp-2 test is to aid in the diagnosis of SARD, the reporting of anti-DFS70 antibodies and their associated pattern (DFS) as a positive test, significantly reduces the specificity and the positive likelihood of the ANA test. This has significant implications for diagnostic algorithms involving the detection of ANA. We summarize the current knowledge of anti-DFS70 antibodies and their impact on ANA testing. We also suggest a test algorithm which considers the DFS pattern and the presence of anti-DFS70 antibodies. In addition, we describe a novel method based on immunoadsorption of anti-DFS70 antibodies, which increases the specificity of the ANA HEp-2 test for SARD and which has the potential to overcome a significant limitation of the ANA HEp-2 assay.
Autoimmunity reviews 11/2011; 11(9):642-5. · 6.37 Impact Factor
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Nature Reviews Rheumatology 08/2011; 7(10):564-5. · 8.39 Impact Factor
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ABSTRACT: To examine the validity of case definitions for systemic autoimmune rheumatic diseases [SARD; systemic lupus erythematosus (SLE), systemic sclerosis (SSc), myositis, Sjögren's syndrome, vasculitis, and polymyalgia rheumatica] based on administrative data, compared to rheumatology records.
A list of rheumatic disease diagnoses was generated from population-based administrative billing and hospitalization databases. Subjects who had been seen by an arthritis center rheumatologist were identified, and the medical records reviewed.
We found that 844 Nova Scotia residents had a diagnosis of one of the rheumatic diseases of interest, based on administrative data, and had had ≥ 1 rheumatology assessment at a provincial arthritis center. Charts were available on 824 subjects, some of whom had been identified in the administrative database with > 1 diagnosis. Thus a total of 1136 diagnoses were available for verification against clinical records. Of the 824 subjects, 680 (83%) had their administrative database diagnoses confirmed on chart review. The majority of subjects who were "false-positive" for a given rheumatic disease on administrative data had a true diagnosis of a similar rheumatic disease. Most sensitivity estimates for specific administrative data-based case definitions were > 90%, although for SSc, the sensitivity was 80.5%. The specificity estimates were also > 90%, except for SLE, where the specificity was 72.5%.
Although health administrative data may be a valid resource, there are potential problems regarding the specificity and sensitivity of case definitions, which should be kept in mind for future studies.
The Journal of Rheumatology 05/2011; 38(8):1612-6. · 3.69 Impact Factor
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Evelyne Vinet,
Ann E Clarke,
Caroline Gordon,
Murray B Urowitz, John G Hanly,
Christian A Pineau,
David Isenberg,
Anisur Rahman,
Daniel Wallace,
Graciela S Alarcón,
Ian Bruce,
Michelle Petri,
Mary Ann Dooley,
Kenneth Kalunian,
Peter Maddison,
Cynthia Aranow,
Ronald van Vollenhoven,
Sasha Bernatsky
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ABSTRACT: 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.
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.
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).
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.
Arthritis care & research. 03/2011; 63(7):1068-72.
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ABSTRACT: The term 'cocaine-induced pseudovasculitis' was coined to encompass a constellation of clinical and laboratory findings which mimics a systemic vasculitis but lacks confirmatory evidence of vasculitis on biopsy. Antineutrophil cytoplasmic antibodies reacting with human neutrophil elastase (HNE) have been reported to distinguish the cocaine-related syndrome from a true autoimmune vasculitis. Published cases of retiform purpura related to cocaine use are rare and an etiologic role for levamisole, a common adulterant of cocaine, has been postulated. We describe two female patients aged 39 and 49 years with cocaine-related retiform purpura, mainly affecting the legs. The initial clinical and serological profile in case 1 led to a suspicion of anti-phospholipid syndrome and in case 2 to Wegener's granulomatosis with an unexplained associated neutropenia. Skin biopsies revealed a mixed pattern of leukocytoclastic vasculitis and microvascular thrombosis in case 1 and pure microvascular thrombosis in case 2. Identification of anti-HNE antibodies in both patients linked their disease to cocaine. The mixed vasculopathic pattern in case 1 and the associated neutropenia in case 2, both known adverse effects of levamisole, point to this as the true etiologic agent. Urine toxicology shortly after a binge of cocaine use in each case was positive for levamisole.
Journal of Cutaneous Pathology 12/2010; 37(12):1212-9. · 1.56 Impact Factor
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ABSTRACT: The performance of immunoassays for the detection of autoantibodies is of critical importance to the diagnosis and assessment of patients with systemic lupus erythematosus (SLE). Our objective was to compare 3 multiplexed assays for measurement of multiple autoantibodies and their association with global disease activity, active nephritis and cumulative organ damage in systemic lupus erythematosus (SLE). Stored sera, clinical and laboratory data from the enrollment visit of a long-term lupus registry were used. Autoantibodies were measured using the BioPlex 2200 ANA screen (Bio-Rad), QuantaPlex ENA8 (INOVA Diagnostics) and recomLine ANA/ENA (Mikrogen). The analytes included dsDNA, chromatin, ribosomal P protein, SS-A/Ro60, Ro52, SS-B/La, Sm, U1-RNP, centromere B, topoisomerase 1 and Jo-1 (histidyl tRNA synthetase). Global SLE disease activity was measured by the SLE disease activity index (SLEDAI) and cumulative organ damage by the SLICC/ACR damage index (SDI). One hundred ninety two patients (87% female; 91% Caucasian; mean disease duration 8.8years) were studied. Agreement between the 3 assays varied from 70% to 99% (Cohen's kappa: 0.04-0.88). There were significant associations between SLEDAI scores (excluding anti-dsDNA) and ANA (INOVA, Mikrogen), anti-dsDNA (Bio-Rad, Mikrogen), anti-chromatin (Bio-Rad, INOVA), anti-Ro (Mikrogen), anti-Sm and anti-U1-RNP (all 3 immunoassays) (p=0.002-0.05). Concurrent lupus nephritis was associated with anti-dsDNA (Bio-Rad (p=0.017) or Bio-Rad and Mikrogen together (p=0.015)). There was no significant association between autoantibodies and SDI scores. The overall agreement between assays for the detection of autoantibodies was reasonable. The greatest discordance (70-83%) occurred with those autoantibodies most strongly associated with global SLE disease activity (ANA, anti-dsDNA, anti-chromatin and anti-Sm). Furthermore, there were differences between assays in their associations with global SLE disease activity and lupus nephritis.
Journal of immunological methods 06/2010; 358(1-2):75-80. · 2.35 Impact Factor
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Karen H Costenbader,
Munther Khamashta,
Silvia Ruiz-Garcia,
Maria Teresa Perez-Rodriguez,
Michelle Petri,
Jennifer Elliott,
Susan Manzi,
Elizabeth W Karlson,
Tabitha Turner-Stokes,
Bonnie Bermas, [......], John G Hanly,
Timothy S Shaver,
Robert S Katz,
Eliza Chakravarty,
Paul R Fortin,
Martha L Sanchez,
Jigna Liu,
Kaleb Michaud,
Graciela S Alarcón,
Frederick Wolfe
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ABSTRACT: The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) is a validated instrument for assessing organ damage in systemic lupus erythematosus (SLE). Trained physicians must complete it, thus limiting utility where this is impossible.
We developed and pilot tested a self-assessed organ damage instrument, the Lupus Damage Index Questionnaire (LDIQ), in 37 SLE subjects and 7 physicians. After refinement, 569 English-speaking SLE subjects and 14 rheumatologists from 11 international SLE clinics participated in validation. Subjects and physicians completed the instruments separately. We calculated sensitivity, specificity, Spearman's correlations, and agreement using the SDI as the gold standard. Six hundred five SLE participants in the community-based National Data Bank for Rheumatic Diseases (NDB) study completed the LDIQ and we assessed correlations with outcome and disability measures.
The mean LDIQ score was 3.3 (range 0-16) and the mean SDI score was 1.5 (range 0-9). The LDIQ had a moderately high correlation with the SDI (Spearman's r = 0.50, P < 0.001). Specificities of individual LDIQ items were >80%, except for neuropathy. Sensitivities were variable and lowest for damage, with <1% prevalence. Agreement between the SDI and LDIQ was >85% for all but neuropathy, reduced renal function, deforming arthritis, and alopecia. In the NDB, the LDIQ correlated well with the comorbidity index (r = 0.45), the Short Form 36 physical component scale (r = 0.43), the Medical Research Council dyspnea scale (r = 0.40), disability (r = 0.37), and the Systemic Lupus Erythematosus Activity Questionnaire score (r = 0.37).
The metric properties of the LDIQ are good compared with the SDI. It has construct validity and correlations with health assessments similar to the SDI. The LDIQ should allow expansion of SLE research. Its ultimate value will be determined in longitudinal studies.
Arthritis care & research. 04/2010; 62(4):559-68.
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ABSTRACT: Computerized neuropsychological testing may facilitate screening for cognitive impairment in systemic lupus erythematosus (SLE). This study was undertaken to compare patients with SLE, patients with rheumatoid arthritis (RA), and patients with multiple sclerosis (MS) with healthy controls using the Automated Neuropsychological Assessment Metrics (ANAM).
Patients with SLE (n = 68), RA (n = 33), and MS (n = 20) were compared with healthy controls (n = 29). Efficiency of cognitive performance on 8 ANAM subtests was examined using throughput (TP), inverse efficiency (IE), and adjusted IE scores. The latter is more sensitive to higher cognitive functions because it adjusts for the impact of simple reaction time on performance. The results were analyzed using O'Brien's generalized least squares test.
Control subjects were the most efficient in cognitive performance. MS patients were least efficient overall (as assessed by TP and IE scores) and were less efficient than both SLE patients (P = 0.01) and RA patients (P < 0.01), who did not differ. Adjusted IE scores were similar between SLE patients, RA patients, and controls, reflecting the impact of simple reaction time on cognitive performance. Thus, 50% of SLE patients, 61% of RA patients, and 75% of MS patients had impaired performance on >or=1 ANAM subtest. Only 9% of RA patients and 11% of SLE patients had impaired performance on >or=4 subtests, whereas this was true for 20% of MS patients.
ANAM is sensitive to cognitive impairment. While such computerized testing may be a valuable screening tool, our results emphasize the lack of specificity of slowed performance as a reliable indicator of impairment of higher cognitive function in SLE patients.
Arthritis & Rheumatism 02/2010; 62(5):1478-86. · 7.87 Impact Factor
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ABSTRACT: Autoantibodies are central to the diagnosis and assessment of systemic lupus erythematosus (SLE). A recent technique for the measurement of autoantibodies utilizes addressable laser bead immunoassay technology (BioPlex 2200) which permits the simultaneous detection of multiple autoantibodies and improved efficiency due to the shorter time to perform the assay and low volume of test samples and reagents. In the current study we have compared this technique to more traditional measures of autoantibody detection. The clinical and laboratory data and stored serum samples from the enrollment visit into a long-term lupus registry at a single academic medical center were used. Sera were examined for a panel of autoantibodies using the BioPlex ANA screen. The results were compared to the historical data on autoantibody profiles using indirect immunofluorescence (IIF) and ELISA. The association with global and organ specific SLE disease activity (nephritis) was also examined. The study consisted of 192 patients who were predominantly female (87%) and Caucasian (91%) with mean disease duration of 8.8 years. The frequency of ANA and anti-dsDNA by IIF and ELISA was 81.3% and 46.6% respectively and was higher than that found with BioPlex (75.5% and 31.8%). The latter detected a higher proportion of patients with autoantibodies to Sm (7.5% vs 16.7%), RNP (21.8% vs 24.0%), Ro (37.4% vs 41.7) and La (13.9% vs 23.4%). Overall agreement between assays varied between 71.4% and 92.5%. Additional autoantibodies identified by BioPlex were anti-chromatin antibodies which were similar in frequency to anti-dsDNA antibodies (33.9% and 31.8% respectively). There was a low frequency of anti-ribosomal P (6.8%), anti-Scl-70 (5.2%), anti-centromere B (3.7%) and anti-Jo-1 (0.5%). Several autoantibodies revealed significant associations with SLEDAI scores but in a multivariate analysis the only autoantibodies that approached statistical significance were anti-Sm (p=0.094) measured by ELISA and anti-dsDNA (p=0.082) measured by BioPlex. There was no association between any of the autoantibodies regardless of the method of detection and cumulative organ damage scores. Fifty-three patients (27.6%) had lupus nephritis of which 17 (32%) had active nephritis at the time of autoantibody determination. There was no significant association between a positive ANA (IIF) and any autoantibodies detected by ELISA with either the cumulative occurrence of lupus nephritis or active nephritis. In contrast, there was an association between BioPlex detected anti-dsDNA with the cumulative occurrence of nephritis (p=0.074) which reached statistical significance with active nephritis at the time of antibody testing (p=0.012). This was confirmed by multivariate analysis (p=0.047). These results suggest reasonable agreement between the detection of lupus autoantibodies by ELISA and BioPlex. The latter demonstrated a better correlation with lupus nephritis.
Journal of immunological methods 10/2009; 352(1-2):147-52. · 2.35 Impact Factor
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ABSTRACT: To determine if a hospital rheumatology consultation service improves diagnostic accuracy and adherence to treatment recommendations for gout.
This was a retrospective, single-center, case-control study of consecutive hospitalized patients with gout. Demographic, diagnostic, and treatment variables were compared in patients with and without a rheumatology consultation (controls). American College of Rheumatology (ACR) preliminary criteria for the classification of acute gout and the European League Against Rheumatism (EULAR) recommendations were used to determine diagnostic accuracy. Adherence to EULAR drug management recommendations and Quality Indicators for treatment were compared between groups.
In total, 138 patients were studied. The mean (SD) age was 71.3 (13.4) years and 70% were men. Forty-eight (35%) patients had gout on admission, 90 (65%) during their hospital stay, and 8 (6%) had multiple attacks. A total of 79 (57%) patients had a rheumatology consultation. These patients had more joints involved (p < 0.001), more frequent synovial fluid analysis (p < 0.001), and fulfilled ACR classification criteria more frequently than those who did not have a rheumatology consultation (65% vs 37%; p = 0.002). Intraarticular corticosteroid use was more common (44% vs 12%; p < 0.001) in patients who were seen by rheumatology. In contrast, colchicine was used more frequently in controls (63% vs 40%; p = 0.006). Patients seen by rheumatology were more likely to use nonsteroidal antiinflammatory drugs or colchicine for gout prophylaxis while titrating allopurinol to target (p = 0.033).
A rheumatology consultation service for hospitalized patients with gout significantly improved the diagnostic accuracy and adherence to established guidelines for short and longterm treatment.
The Journal of Rheumatology 07/2009; 36(8):1699-704. · 3.69 Impact Factor
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ABSTRACT: To prospectively examine neuropsychiatric (NP) events and their association with health related quality of life (HRQOL) over time in patients with systemic lupus erythematosus (SLE).
In an observational cohort study from a single academic center, NP events and their attribution were identified at enrollment and at annual assessments for up to 7 years. NP events were characterized using the American College of Rheumatology case definitions; other variables were global SLE disease activity and cumulative organ damage. The outcomes of NP events were recorded and self-report HRQOL was measured with the mental (MCS) and physical (PCS) component summary scores of the Medical Outcomes Study Short Form-36.
There were 209 patients, 88% female and 92% Caucasian, with a mean (standard deviation) age of 43.7 (13.8) years. Followup was available in 175/209 (84%) patients. There were 299 NP events in 132/209 (63%) patients over a mean followup of 3.6 (2.5) years. Thirty-one percent of NP events in 54 patients were attributed to SLE. Multivariate analysis indicated lower MCS scores in patients with NP events compared to those without events (p < 0.001) regardless of attribution. The group means for PCS scores were significantly lower in patients with NP events (p < 0.001) regardless of attribution. There was no association between HRQOL and cumulative organ damage, nor between NP events and the progression of organ damage.
The association of lower HRQOL with NP events over time, which is independent of progression in cumulative organ damage, emphasizes the persistent negative effect of NP events in the lives of patients with SLE.
The Journal of Rheumatology 06/2009; 36(7):1449-59. · 3.69 Impact Factor
