Study of Flare Assessment in Systemic Lupus Erythematosus Based on Paper Patients.

OBJECTIVE: To determine the level of agreement of disease flare severity (distinguishing severe, moderate, and mild flare and persistent disease activity) in a large paper-patient exercise involving 988 individual cases of systemic lupus erythematosus. METHODS: A total of 988 individual lupus case histories were assessed by 3 individual physicians. Complete agreement about the degree of flare (or persistent disease activity) was obtained in 451 cases (46%), and these provided the reference standard for the second part of the study. This component used 3 flare activity instruments (the British Isles Lupus Assessment Group [BILAG] 2004, Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] flare index [SFI] and the revised SELENA flare index [rSFI]). The 451 patient case histories were distributed to 18 pairs of physicians, carefully randomized in a manner designed to ensure a fair case mix and equal distribution of flare according to severity. RESULTS: The 3-physician assessment of flare matched the level of flare using the 3 indices, with 67% for BILAG 2004, 72% for SFI, and 70% for rSFI. The corresponding weighted kappa coefficients for each instrument were 0.82, 0.59, and 0.74, respectively. We undertook a detailed analysis of the discrepant cases and several factors emerged, including a tendency to score moderate flares as severe and persistent activity as flare, especially when the SFI and rSFI instruments were used. Overscoring was also driven by scoring treatment change as flare, even if there were no new or worsening clinical features. CONCLUSION: Given the complexity of assessing lupus flare, we were encouraged by the overall results reported. However, the problem of capturing lupus flare accurately is not completely solved.

Deciphering systemic lupus erythematosus-associated serum biomarkers reflecting apoptosis and disease activity.

Systemic lupus erythematosus (SLE) is a severe chronic inflammatory autoimmune connective tissue disease. Despite major efforts, SLE remains a poorly understood disease with unpredictable course, unknown etiology and complex pathogenesis. Apoptosis combined with deficiency in clearing apoptotic cells is an important etiopathogenic event in SLE, which could contribute to the increased load of potential autoantigen(s); however, the lack of disease-specific protein signatures deciphering SLE and the underlying biological processes is striking and represents a key limitation. In this retrospective pilot study, we explored the immune system as a specific sensor for disease, in order to advance our understanding of SLE. To this end, we determined multiplexed serum protein expression profiles of crude SLE serum samples, using antibody microarrays. The aim was to identify differential immunoprofiles, or snapshots of the immune response modulated by the disease, reflecting apoptosis, a key process in the etiology of SLE and disease activity. The results showed that multiplexed panels of SLE-associated serum biomarkers could be decoded, in particular reflecting disease activity, but potentially the apoptosis process as well. While the former biomarkers could display a potential future use for prognosis, the latter biomarkers might help shed further light on the apoptosis process taking place in SLE.

Differences in body structure and function between patients with systemic lupus erythematosus and healthy individuals, with particular reference to joint hypermobility.

OBJECTIVES: To explore differences in body structure and function in systemic lupus erythematosus (SLE) patients and controls, with particular reference to joint hypermobility, and to evaluate the usefulness of the Brighton criteria for diagnosing joint hypermobility syndrome (JHS) in SLE. METHOD: Female SLE patients were, according to age group, consecutively invited to participate in the study. Controls were healthy females matched for age. All individuals were examined by a physician according to the Brighton criteria, and by an occupational therapist and a physiotherapist to obtain the Beighton scores, overall joint mobility, and manifestations in body structure and function. RESULTS: Sixteen (23%) SLE patients and 19 (27%) controls had a Beighton score ≥ 4 (non-significant, ns), and 39 (55%) individuals in the SLE group and 22 (31%) in the control group satisfied the Brighton criteria for JHS (p < 0.01). Many individuals in both groups exceeded the normative values for joint mobility in joints other than those included in the Beighton score. Stratifying for a Beighton score ≥ 4 vs. < 4, there were no significant differences in body structure or body function constituting JHS either in the SLE patients or in the controls. CONCLUSIONS: Although the presence of joint hypermobility in SLE patients was frequent, we could not verify that this caused excess manifestations in addition to the SLE symptoms.

Cardiovascular events prior to or early after diagnosis of systemic lupus erythematosus in the systemic lupus international collaborating clinics cohort.

OBJECTIVE: To describe the frequency of myocardial infarction (MI) prior to the diagnosis of systemic lupus erythematosus (SLE) and within the first 2 years of follow-up. METHODS: The systemic lupus international collaborating clinics (SLICC) atherosclerosis inception cohort enters patients within 15 months of SLE diagnosis. MIs were reported and attributed on a specialised vascular event form. MIs were confirmed by one or more of the following: abnormal ECG, typical or atypical symptoms with ECG abnormalities and elevated enzymes (≥2 times upper limit of normal), or abnormal stress test, echocardiogram, nuclear scan or angiogram. Descriptive statistics were used. RESULTS: 31 of 1848 patients who entered the cohort had an MI. Of those, 23 patients had an MI prior to SLE diagnosis or within the first 2 years of disease. Of the 23 patients studied, 60.9% were female, 78.3% were Caucasian, 8.7% black, 8.7% Hispanic and 4.3% other. The mean age at SLE diagnosis was 52.5±15.0 years. Of the 23 MIs that occurred, 16 MIs occurred at a mean of 6.1±7.0 years prior to diagnosis and 7 occurred within the first 2 years of follow-up. Risk factors associated with early MI in univariate analysis are male sex, Caucasian, older age at diagnosis, hypertension, hypercholesterolaemia, family history of MI and smoking. In multivariate analysis only age (OR=1.06 95% CI 1.03 to 1.09), hypertension (OR=5.01, 95% CI 1.38 to 18.23), hypercholesterolaemia (OR=4.43, 95% CI 1.51 to 12.99) and smoking (OR=7.50, 95% CI 2.38 to 23.57) remained significant risk factors. CONCLUSIONS: In some patients with lupus, MI may develop even before the diagnosis of SLE or shortly thereafter, suggesting that there may be a link between autoimmune inflammation and atherosclerosis.

Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis.

OBJECTIVE: A high level of galectin-3-binding protein (G3BP) appears to distinguish circulating cell-derived microparticles in systemic lupus erythematosus (SLE). The aim of this study is to characterize the population of G3BP-positive microparticles from SLE patients compared to healthy controls, explore putative clinical correlates, and examine if G3BP is present in immune complex deposits in kidney biopsies from patients with lupus nephritis. METHODS: Numbers of annexin V-binding and G3BP-exposing plasma microparticles from 56 SLE patients and 36 healthy controls were determined by flow cytometry. Quantitation of microparticle-associated G3BP, C1q and immunoglobulins was obtained by liquid chromatography tandem mass spectrometry (LC-MS/MS). Correlations between microparticle-G3BP data and clinical parameters were analyzed. Co-localization of G3BP with in vivo-bound IgG was examined in kidney biopsies from one non-SLE control and from patients with class IV (n = 2) and class V (n = 1) lupus nephritis using co-localization immune electron microscopy. RESULTS: Microparticle-G3BP, microparticle-C1q and microparticle-immunoglobulins were significantly (P < 0.01) increased in SLE patients by LC-MS/MS. Three G3BP-exposing microparticle populations could be discerned by flow cytometry, including two subpopulations that were significantly increased in SLE samples (P = 0.01 and P = 0.0002, respectively). No associations of G3BP-positive microparticles with clinical manifestations or disease activity were found. Immune electron microscopy showed co-localization of G3BP with in vivo-bound IgG in glomerular electron dense immune complex deposits in all lupus nephritis biopsies. CONCLUSIONS: Both circulating microparticle-G3BP numbers as well as G3BP expression are increased in SLE patients corroborating G3BP being a feature of SLE microparticles. By demonstrating G3BP co-localized with deposited immune complexes in lupus nephritis, the study supports cell-derived microparticles as a major autoantigen source and provides a new understanding of the origin of immune complexes occurring in lupus nephritis.

Anti-C1q antibodies in systemic lupus erythematosus.

OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. RESULTS: Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8-4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7-5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2-5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9-6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5-5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3-4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8-38.4, p < 0.01). CONCLUSIONS: Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.

Hand function and performance of daily activities in systemic lupus erythematosus: a clinical study.

This clinical study was performed to investigate hand problems in individuals with systemic lupus erythematosus (SLE) in comparison with healthy controls, and to explore problems in the performance of daily activities related to these hand problems, in order to objectify findings from a previous mail survey. We also investigated whether a simple hand test could detect hand problems in SLE. All individuals, 71 with SLE and 71 healthy controls, were examined for manifestations in body structures and body functions of the hands with a study-specific protocol. The simple hand test was performed by all the individuals and the arthritis impact measurement scale (AIMS 2) questionnaire was completed by the SLE individuals. In the SLE group, 58% had some kind of difficulty in the simple hand test, compared with 8% in the control group. Fifty percent of the SLE individuals experienced problems in performing daily activities due to hand deficits. Pain in the hands, reduced strength and dexterity, Raynaud's phenomenon and trigger finger were the most prominent body functions affecting the performance of daily activities. Deficits in hand function are common in SLE and affect the performance of daily activities. The simple hand test may be a useful tool in detecting hand problems.

Changes in quality of life in the first 5 years of disease in a multicenter cohort of patients with systemic lupus erythematosus.

OBJECTIVE: The Medical Outcomes Study Short Form 36 (SF-36) is recommended to assess quality of life (QOL) in systemic lupus erythematosus (SLE). The aim of the current study was to assess QOL over time in the first 5 years of a multicenter inception cohort of patients with SLE. METHODS: An inception SLE cohort was assembled according to a standardized protocol between 2000 and 2012. In addition to clinical and laboratory assessments, patients completed the SF-36 at yearly intervals. Only patients who had ≥5 completed QOL questionnaires were included in these analyses. Generalized estimating equation models were run separately for each of the 8 subscales and for the physical and mental component summary scores, adjusting for repeated measures by patients. RESULTS: A total of 495 patients were included. The mean ± SD disease duration at the first visit was 5.3 ± 4.1 months. The mean ± SD age at enrollment was 35.8 ± 13.2 years. All 8 subscales and the 2 summary scores showed improvement in the first 2 years from enrollment. Between years 2 and 5, none of the subscales or summary scores showed any change. Minimum clinically important improvement was achieved by 35-56% of the patients and was influenced by demographic and disease factors. CONCLUSION: Unlike late-stage lupus, where QOL is stable over time, in patients with early disease, all subscales improve in early followup up to 2 years. Therefore, the SF-36 may be a sensitive outcome measure in early disease in patients with SLE.

An observational study of outcome in SLE patients with biopsy-verified glomerulonephritis between 1986 and 2004 in a defined area of southern Sweden: the clinical utility of the ACR renal response criteria and predictors for renal outcome.

OBJECTIVES: To test the utility of the World Health Organization (WHO) and International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria for lupus nephritis (LN) in systemic lupus erythematosus (SLE) and the American College of Rheumatology renal response criteria (ACR-RRC) for renal follow-up in an observational cohort. METHOD: All 52 biopsy-verified cases of LN during 19 years were identified, and glomerular filtration rate (GFR), serum creatinine, proteinuria, haematuria, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and complement were retrieved at diagnosis of nephritis, after 6 and 12 months, and at the latest visit. Forty-five renal biopsies were available for re-evaluation with the ISN/RPS criteria. Outcome was defined by the ACR-RRC and the final GFR. RESULTS: The mean follow-up time was 9 years; complete renal response (CRR) was achieved in 11 cases, end-stage renal disease (ESRD) in four, and nephrotic syndrome (NS) in one. The final GFR decreased with increasing age at biopsy (p < 0.01) and with interstitial manifestations added to the ISN/RPS classification (p < 0.05). The final GFR correlated with the decrease of proteinuria or casts and actual serum creatinine after 6 months of treatment (all p < 0.05). The outcome defined by ACR-RRC correlated with the nephrological components of SLEDAI-2K after 6 months of therapy (p < 0.01) and with the presence of antibodies to C1q at biopsy (p < 0.05). CONCLUSIONS: Renal outcome is correlated with the response to treatment after 6 months and with the addition of interstitial changes to the ISN/RPS classification, which might add useful information for prediction. The ACR-RRC offers a defined alternative to categorize renal response.

Breast cancer in systemic lupus erythematosus.

OBJECTIVE: Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries. METHODS: Information on age, SLE duration, cancer date, and histology was available. We analyzed information on histological type and performed multivariate logistic regression analyses of histological types according to age, SLE duration, and calendar year. RESULTS: We studied 180 breast cancers in the SLE cohort. Of the 155 cases with histology information, 11 were referred to simply as 'carcinoma not otherwise specified'. In the remaining 144 breast cancers, the most common histological type was ductal carcinoma (n = 95; 66%) followed by lobular adenocarcinoma (n = 11; 8%), 15 cancers were of mixed histology, and the remaining ones were special types. In our regression analyses, the independent risk factors for lobular versus ductal carcinoma was age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01-1.14] and for the 'special' subtypes it was age (OR 1.06, 95% CI 1.01-1.10) and SLE duration (OR 1.05, 95% CI 1.00-1.11). CONCLUSIONS: Generally, up to 80% of breast cancers are ductal carcinomas. Though our results are not definitive, in the breast cancers that occur in SLE, there may be a slight decrease in the ductal histological type. In our analyses, age and SLE duration were independent predictors of histological status.

Low diagnostic and predictive value of anti-dsDNA antibodies in unselected patients with recent onset of rheumatic symptoms: results from a long-term follow-up Scandinavian multicentre study.

OBJECTIVES: To verify the diagnostic accuracy of anti-double-stranded DNA (anti-dsDNA) antibodies detected by the Crithidia luciliae immunofluorescence test (CLIFT) in a cohort of unselected patients, referred to a rheumatologist due to recent onset of rheumatic symptoms. METHOD: A total of 1073 consecutive patients were screened for anti-nuclear antibodies (ANAs). Serum samples from 292 ANA-positive and 292 matching ANA-negative patients were tested three times for anti-dsDNA antibodies, using two different CLIFT kits (ImmunoConcepts(®) and Euroimmun(®)). An initial clinical diagnosis was made by rheumatologists unaware of the results. The diagnoses were updated after a median follow-up of 4.8 years. RESULTS: CLIFT was positive at least once in 60 patients but only 23 patients were CLIFT positive in all of the assays. Diagnosis of systemic lupus erythematosus (SLE) was made initially in 65 patients, of whom 24 (37%) were CLIFT positive. Many other diagnoses were observed among the CLIFT-positive patients. Overall, 16 (5.5%) ANA-negative patients were CLIFT positive. After approximately 5 years, the diagnosis of SLE remained unchanged in 63 patients (23 CLIFT positive) and altered in only two (one CLIFT positive). Among the 36 CLIFT-positive patients who were not diagnosed with SLE at study entry, only one developed SLE during the follow-up period. CONCLUSIONS: CLIFT was not reliable as a diagnostic tool in unselected patients with rheumatic symptoms. ANAs were of little value as a screening test before the CLIFT analysis. CLIFT had surprisingly low positive predictive value (PPV) for the diagnosis of SLE despite its high specificity. For non-SLE patients, being CLIFT positive poses little risk of developing SLE within 5 years.

Contribution of IKBKE and IFIH1 gene variants to SLE susceptibility.

The type I interferon system genes IKBKE and IFIH1 are associated with the risk of systemic lupus erythematosus (SLE). To identify the sequence variants that are able to account for the disease association, we resequenced the genes IKBKE and IFIH1. Eighty-six single-nucleotide variants (SNVs) with potentially functional effect or differences in allele frequencies between patients and controls determined by sequencing were further genotyped in 1140 SLE patients and 2060 controls. In addition, 108 imputed sequence variants in IKBKE and IFIH1 were included in the association analysis. Ten IKBKE SNVs and three IFIH1 SNVs were associated with SLE. The SNVs rs1539241 and rs12142086 tagged two independent association signals in IKBKE, and the haplotype carrying their risk alleles showed an odds ratio of 1.68 (P-value=1.0 × 10(-5)). The risk allele of rs12142086 affects the binding of splicing factor 1 in vitro and could thus influence its transcriptional regulatory function. Two independent association signals were also detected in IFIH1, which were tagged by a low-frequency SNV rs78456138 and a missense SNV rs3747517. Their joint effect is protective against SLE (odds ratio=0.56; P-value=6.6 × 10(-3)). In conclusion, we have identified new SLE-associated sequence variants in IKBKE and IFIH1, and proposed functional hypotheses for the association signals.

Increased C1q, C4 and C3 deposition on platelets in patients with systemic lupus erythematosus--a possible link to venous thrombosis?

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have an increased risk of developing vascular diseases (VD) such as myocardial infarction, stroke and venous thrombosis, which can only partly be explained by traditional risk factors. The role of platelets in this process has not been extensively studied. Platelet activation supports complement binding to the platelet surface, and increased C4d has been seen on platelets in SLE patients as well as in non-rheumatic patients with stroke. In this study we investigated in vivo platelet deposition of the classical complement pathway components C1q, C4d and C3d in relation to VD in SLE patients. Furthermore, the ability of serum to support in vitro complement deposition on fixed heterologous platelets was analyzed. METHODS: Blood from 69 SLE patients and age- and sex-matched healthy individuals was collected in sodium-citrate tubes and platelets isolated by centrifugation. Complement deposition on platelets was detected by flow cytometry. RESULTS: We could demonstrate that SLE patients had increased C1q, C3d and C4d deposition on platelets as compared to healthy controls (p < 0.0001). SLE patients with a history of venous thrombosis had increased complement deposition on platelets as compared to SLE patients without this manifestation (p < 0.05). In vitro studies demonstrated that serum from patients with lupus anticoagulant, venous thrombosis or antiphospholipid antibody syndrome supported increased platelet C4d deposition in vitro as compared to SLE patients without these manifestations (p < 0.05). Our data support the hypothesis that platelet activation and the subsequent complement deposition on platelets are central in the development of venous thrombosis in SLE. CONCLUSIONS: Altogether we suggest that complement deposition on platelets could reflect important pathogenetic events related to the development of venous thrombosis in SLE and might be used as a marker for venous thrombosis in SLE.

Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort.

OBJECTIVE: We describe disease activity, damage, and the accrual of key autoantibodies in an inception systemic lupus erythematosus (SLE) cohort. METHODS: The Systemic Lupus International Collaborating Clinics (SLICC) International Research Network, comprising 27 centers from 11 countries, has followed an inception cohort of SLE patients yearly according to a standardized protocol. Of these patients, 298 were followed for a minimum of 5 years and constitute the study population. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K) and damage was assessed using the SLICC/American College of Rheumatology Damage Index (SDI). Antinuclear antibody (ANA), anti-DNA, and anticardiolipin antibody (aCL) levels and lupus anticoagulant were assessed yearly. Descriptive statistics were generated and repeated-measures general linear models were used to evaluate SLEDAI-2K and SDI over time between whites and nonwhites. RESULTS: Of the 298 patients, 87% were women, 55% were white, 12% were African American, 14% were Asian, 16% were Hispanic, and 2% were categorized as "other." At enrollment, the mean age was 35.3 years, the mean SLEDAI-2K score was 5.9, and the mean disease duration was 5.5 months. Mean SLEDAI-2K scores decreased in the first year and then remained low. SLEDAI-2K scores were significantly lower at each year in whites compared to nonwhites. Mean SDI scores increased progressively over 5 years; there was no significant difference between whites and nonwhites. As expected, ANA positivity was high and anti-DNA positivity was relatively low at enrollment, and both increased over 5 years. Although lupus anticoagulant increased slightly over 5 years, aCL positivity did not. CONCLUSION: Disease activity in newly diagnosed patients decreases over their first 5 years, while damage increases. Antibody positivity ran variable courses over this period.

Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus.

OBJECTIVE: Neuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events. METHODS: Patients with a recent SLE diagnosis were assessed prospectively for up to 10 years for neuropsychiatric events using the American College of Rheumatology case definitions. Decision rules of graded stringency determined whether neuropsychiatric events were attributable to SLE. Associations between the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant (LA), anticardiolipin, anti-ß(2) glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. RESULTS: Disease duration at enrolment was 5.4 ± 4.2 months, follow-up was 3.6 ± 2.6 years. Patients were 89.1% female with mean (±SD) age 35.2 ± 13.7 years. 495/1047 (47.3%) developed one or more neuropsychiatric event (total 917 events). Neuropsychiatric events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrolment 21.9% of patients had LA, 13.4% anticardiolipin, 15.1% anti-ß(2) glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. LA at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (HR 2.54, 95% CI 1.08 to 5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR 3.92, 95% CI 1.23 to 12.5, p=0.02). Other autoantibodies did not predict neuropsychiatric events. CONCLUSION: In a prospective study of 1047 recently diagnosed SLE patients, LA and anti-ribosomal P antibodies are associated with an increased future risk of intracranial thrombosis and lupus psychosis, respectively.

Systemic lupus erythematosus and cardiac risk factors: medical record documentation and patient adherence.

This study explores patients' knowledge of cardiac risk factors (CRFs), analyses how information and advice about CRFs are documented in clinical practice, and assesses patient adherence to received instructions to decrease CRFs. Systemic lupus erythematosus (SLE) patients with ≥ 4 ACR criteria participated through completing a validated cardiovascular health questionnaire (CHQ). Kappa statistics were used to compare medical records with the self-reported CHQ (agreement) and to evaluate adherence. Two hundred and eleven (72%) of the known patients with SLE participated. The mean age of the patients was 55 years. More than 70% of the SLE patients considered hypertension, obesity, smoking and hypercholesterolaemia to be very important CRFs. The agreement between medical record documentation and patients' reports was moderate for hypertension, overweight and hypercholesterolaemia (kappa 0.42-0.60) but substantial for diabetes (kappa 0.66). Patients' self-reported adherence to advice they had received regarding medication was substantial to perfect (kappa 0.65-1.0). For lifestyle changes in patients with hypertension and overweight, adherence was only fair to moderate (kappa 0.13-0.47). Swedish SLE patients' awareness of traditional CRFs was good in this study. However, the agreement between patients' self-reports and medical record documentation of CRF profiles, and patients' adherence to medical advice to CRF profiles, could be improved.

Association of the Charlson comorbidity index with mortality in systemic lupus erythematosus.

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.

Autoantibodies in systemic lupus erythematosus: comparison of historical and current assessment of seropositivity.

Systemic lupus erythematosus (SLE) is characterized by multiple autoantibodies and complement activation. Recent studies have suggested that anti-nuclear antibody (ANA) positivity may disappear over time in some SLE patients. Anti-double-stranded DNA (dsDNA) antibody titers and complement levels may vary with time and immunosuppressive treatment, while the behavior of anti-extractable nuclear antigen (ENA) over time is less well understood. This study sought to determine the correlation between historical autoantibody tests and current testing in patients with SLE. Three hundred and two SLE patients from the ACR Reclassification of SLE (AROSE) database with both historical and current laboratory data were selected for analysis. The historical laboratory data were compared with the current autoantibody tests done at the reference laboratory and tested for agreement using percent agreement and Kappa statistic. Serologic tests included ANA, anti-dsDNA, anti-Smith, anti-ribonucleoprotein (RNP), anti-Ro, anti-La, rheumatoid factor (RF), C3 and C4. Among those historically negative for immunologic markers, a current assessment of the markers by the reference laboratory generally yielded a low percentage of additional positives (3-13%). However, 6/11 (55%) of those historically negative for ANA were positive by the reference laboratory, and the reference laboratory test also identified 20% more patients with anti-RNP and 18% more with RF. Among those historically positive for immunologic markers, the reference laboratory results were generally positive on the same laboratory test (range 57% to 97%). However, among those with a history of low C3 or C4, the current reference laboratory results indicated low C3 or C4 a low percentage of the time (18% and 39%, respectively). ANA positivity remained positive over time, in contrast to previous studies. Anti-Ro, La, RNP, Smith and anti-dsDNA antibodies had substantial agreement over time, while complement had less agreement. This variation could partially be explained by variability of the historical assays, which were done by local laboratories over varying periods of time. Variation in the results for complement, however, is more likely to be explained by response to treatment. These findings deserve consideration in the context of diagnosis and enrolment in clinical trials.

SF-36 summary and subscale scores are reliable outcomes of neuropsychiatric events in systemic lupus erythematosus.

OBJECTIVE: To examine change in health-related quality of life in association with clinical outcomes of neuropsychiatric events in systemic lupus erythematosus (SLE). METHODS: An international study evaluated newly diagnosed SLE patients for neuropsychiatric events attributed to SLE and non-SLE causes. The outcome of events was determined by a physician-completed seven-point scale and compared with patient-completed Short Form 36 (SF-36) health survey questionnaires. Statistical analysis used linear mixed-effects regression models with patient-specific random effects. RESULTS: 274 patients (92% female; 68% Caucasian), from a cohort of 1400, had one or more neuropsychiatric event in which the interval between assessments was 12.3 ± 2 months. The overall difference in change between visits in mental component summary (MCS) scores of the SF-36 was significant (p<0.0001) following adjustments for gender, ethnicity, centre and previous score. A consistent improvement in neuropsychiatric status (N=295) was associated with an increase in the mean (SD) adjusted MCS score of 3.66 (0.89) in SF-36 scores. Between paired visits when the neuropsychiatric status consistently deteriorated (N=30), the adjusted MCS score decreased by 4.00 (1.96). For the physical component summary scores the corresponding changes were +1.73 (0.71) and -0.62 (1.58) (p<0.05), respectively. Changes in SF-36 subscales were in the same direction (p<0.05; with the exception of role physical). Sensitivity analyses confirmed these findings. Adjustment for age, education, medications, SLE disease activity, organ damage, disease duration, attribution and characteristics of neuropsychiatric events did not substantially alter the results. CONCLUSION: Changes in SF-36 summary and subscale scores, in particular those related to mental health, are strongly associated with the clinical outcome of neuropsychiatric events in SLE patients.

An assessment of disease flare in patients with systemic lupus erythematosus: a comparison of BILAG 2004 and the flare version of SELENA.

AIMS: To compare the British Isles Lupus Assessment Group (BILAG) 2004, the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) flare index (SFI) and physician's global assessment (PGA) in assessing flares of disease activity in patients with systemic lupus erythematosus (SLE). METHODS: Sixteen patients with active SLE were assessed by a panel of 16 rheumatologists. The order in which the patients were seen was randomised using a 4×4 Latin square design. Each patient's flare status was determined at each assessment using the BILAG 2004 activity index; the SFI and a PGA. A group of five specialists designated each patient into severe, moderate, mild or no flare categories. RESULTS: The rate of complete agreement (95% CI) of the four individual examining physicians for any flare versus no flare was 81% (55% to 94%), 75% (49% to 90%) and 75% (49% to 90%) for the BILAG 2004 index, SELENA flare instrument and PGA, respectively. The overall agreement between flare defined by BILAG 2004 and the SFI was 81% and when type of flare was considered was 52%. Intraclass correlation coefficients (95% CI), as a measure of internal reliability, were 0.54 (0.32 to 0.78) for BILAG 2004 flare compared with 0.21 (0.08 to 0.48) for SELENA flare and 0.18 (0.06 to 0.45) for PGA. Severe flare was associated with good agreement between the indices but mild/moderate flare was much less consistent. CONCLUSIONS: The assessment of flare in patients with SLE is challenging. No flare and severe flare are identifiable but further work is needed to optimise the accurate 'capture' of mild and moderate flares.