SLICC Damage Index Research Articles

AB0390 Suicidal ideation in patients with systemic lupus erythematosus: prevalence and risk factors

ObjectivesTo study the prevalence of suicidal ideation in patients with SLE and its associated risk factorsMethodsConsecutive patients who fulfilled 34 ACR criteria for SLE were recruited for a questionnaire study...

AB0645 Suicidal ideation in patients with systemic lupus erythematosus: Incidence and relationship with anxiety/depression score, disease activity and organ damage

ObjectivesTo study the incidence of suicidal ideation in patients with SLE and its relationship with anxiety/depression score, disease activity and organ damageMethodsConsecutive patients who fulfilled the ACR criteria for SLE...

THU0332 Use and Reasons for Non-Use of Antimalarial Drugs in a Dutch Cohort of Patients with Systemic Lupus Erythematosus

BackgroundAntimalarials (AMs) have been demonstrated to reduce disease activity and prevent damage accrual in SLE. Recent guidelines advice to prescribe AMs in all patients with SLE. However, AM related retinopathy...

SAT0204 Predictors for SLE flares: Baseline disease activity and demographic characteristics from the bliss trials’ combined placebo groups

BackgroundPredicting which SLE patients are at increased risk for clinically meaningful flares may be useful in making management decisions.ObjectivesTo identify demographic and disease-related predictors for flares.MethodsBaseline demographic and SLE-related disease...

THU0279 Prednisone Therapy is an Independent Cause of Damage Attributable to Steroids in Systemic Lupus Erythematosus

BackgroundThe effect of glucocorticoids on organ damage in lupus has been suggested in previous studies, with some relations described with specific domains. Ideal prednisone doses have not yet been described.ObjectivesTo...

SP0139 Predictors for Outcome of Juvenile SLE

Approximately 20% of patients withy systemic lupus erythematosus (SLE) have disease which begins in childhood. Several series have reported that childhood-onset SLE (cSLE) is often more severe than adult disease...

THU0262 Off-Label Use of Rituximab for SLE in Europe: A Comparison to Patients Treated with Conventional Immunosuppressive Medications

BackgroundRituximab (Mabthera; RTX) has not been approved for use in SLE, but uncontrolled observations have suggested efficacy in some patients and the medication can be used off-label in many European...

Neuropsychiatric damage in Systemic Lupus Erythematosus: Possible protective role of medications.

Objective: To examine the possible role of medications in the occurrence of neuropsychiatric damage in patientswith systemic lupus erythematosus (SLE). Material and methods: SLE patients from the LUMINA (Lupus inMinorities: Nature vs. Nurture) cohort (ACR criteria, ≥ 16 years of age at enrollment and ≤5 years of diseaseduration) were studied. Time-to-neuropsychiatric damage [defined according with the Systemic Lupus CollaboratingClinics (SLICC) Damage Index (SDI): neurocognitive impairment or psychosis, seizures, cranial or peripheralneuropathy, stroke or surgical resection not due to malignancies and transverse myelitis] was examined by univariableand multivariable Cox regression analyses. Propensity score analyses were done to further determine the possibleprotective role of hydroxychloroquine in neuropsychiatric damage occurrence. Results: Six-hundred and thirtytwopatients were studied. Age, Caucasian ethnicity, disease activity over time, diabetes and abnormal illness-relatedbehaviors were associated with a shorter time-to-the occurrence of neuropsychiatric damage whereas photosensitivity,anemia, Raynaud’s phenomenon, hydroxychloroquine and a medium dose of prednisone were associated with alonger time. Although the direction of the association remained the same by propensity score analyses(hydroxychloroquine), significance was no longer evident. Conclusions: Our data suggest a possible protectiverole of hydroxychloroquine and moderate doses of prednisone in the occurrence of neuropsychiatric damage inpatients with SLE. (Rev. Neuropsiquiatría 2008; 71: 51-57).

Measuring therapeutic adherence in systemic lupus erythematosus with electronic monitoring

We used an electronic monitoring system to quantify adherence to prescribed oral therapies by patients with systemic lupus erythematosus (SLE). Participants were included from a larger longitudinal study cohort of 110 patients recruited from publicly-funded rheumatology clinics, 78 of whom agreed to have their SLE drug therapy electronically monitored for two years with the Medication Events Monitoring System (MEMS®, AARDEX Group). Adherence was determined as the percentage of days (weeks for methotrexate) the patient took the medication as prescribed by the physician. Collected data included SLEDAI; SLICC damage index for SLE (SDI); medical outcome study social support survey (MOS-SSS); Center for Epidemiologic Studies depression scale (CESD); and quality of life (SF-12). Ninety percent of the cohort was female, 45% were Hispanic, and 49% were African-American. Mean age was 36.3 years, disease duration was 5.9 years, SLEDAI score was 3.2, and SDI score was 0.9. Adherence was 62% for all drugs combined and did not differ significantly for individual medications. Patients with more depression (p < 0.02), and higher number of pills taken daily (p < 0.02) were more likely to be non-adherent. Only one-fourth of the patients had an average adherence of ≥80%; these patients had a better mental component score (SF-12) at 24 months than non-adherent patients (p < 0.01). Electronic monitoring demonstrated that only one-fourth of the patients had an adherence rate ≥80%. Polypharmacy and depression were associated with non-adherence.

Familial Mediterranean fever gene (MEFV) mutations as a modifier of systemic lupus erythematosus

The objective of this study was to assess the prevalence of the Mediterranean FeVer (MEFV) gene mutations in systemic lupus erythematosus (SLE) patients and their effect on organ involvement, as well as disease activity and severity. The frequencies of three familial Mediterranean fever-related MEFV gene mutations (M694V, V726A and E148Q) were investigated in 70 SLE patients. Organ involvement, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were correlated with mutation carriage. Eleven of 70 patients (15.7%) were found to carry an MEFV mutation. A single patient harbored two mutations, E148Q and V726A, without overt familial Mediterranean fever while the rest were heterozygous carriers. Four of the 11 carried an M694V mutation, four carried V726A and two carried E148Q. The majority of MEFV mutation carriers were Sephardic while non-carriers were mainly of Ashkenazi origin (72.7% vs. 45.7% and 47.4% vs. 9.1%, respectively, p = 0.02). SLE onset was significantly earlier in MEFV carriers (27.6 ± 9.7 vs. 38.2 ± 15.5 years, in carriers vs. non-carriers, p = 0.02). Hematologic and serologic parameters were comparable among mutation carriers and non-carriers. Febrile episodes were more common among MEFV mutation carriers (45.4% vs. 15.2%, p = 0.035) and there was a trend for excess episodes of pleuritis as well (54.5% vs. 23.7%, p = 0.06 in carriers vs. non-carriers, respectively). The frequency of secondary anti-phospholipid antibody syndrome was equivalent among the groups. Conversely, compound urinary abnormalities and renal failure was not observed among MEFV carriers yet was present in 33.4% and 18.6% of non-carriers (p = 0.027 and 0.19, respectively). SLICC damage index and SLEDAI activity index did not differ significantly between the groups. MEFV mutation carriage appears to modify the SLE disease phenotype in that it contributes to an excess of inflammatory manifestations such as fever and pleuritis on the one hand, while thwarting more severe renal involvement on the other.

Biologics use in sle in 23 centers – data from the international registry for biologics in SLE

Backgroundand objectivesThere is only one biologic agent approved for use in SLE, but some are used off-label in various settings. To obtain information systematically regarding this, members of the SLICC...

Neuropsychiatric lupus in children

Results There were 120 children with SLE followed during the study period: 93 female (77.5%, M:F 3.4:1); 61 Hispanic (50.8%) and 34 African-American (28.3%). NPSLE affected 15 children (12.5%). Cognitive dysfunction was the most common manifestation, followed by significant headache, seizures, psychosis, and focal neurologic signs. NPSLE was diagnosed in the first year in 10/15 patients (67%). Abnormalities of brain magnetic resonance imaging were encountered in 10 patients (67%). Children with NPSLE had a significantly greater number of co-morbidities (end-stage renal disease, thrombocytopenia, and pancreatitis) than unaffected children with SLE (p<0.05). NPSLE was associated with a higher SLEDAI at diagnosis and the presence of anti-Smith antibodies (p<0.05). All patients received high-dose corticosteroid and cyclophosphamide. NPSLE was associated with the occurrence of major infections, as well as a higher SLICC damage index, and mortality (p<0.05). Conclusions In this cohort NPSLE was associated with co-morbidities, major infections, and higher damage scores.

Age related clinical presentation and laboratory parameters in juvenile SLE: a Hungarian multicenter study

Results Female:Male ratio was 9:1 in both groups. The most common initial manifestations as butterfly rash occured in 60%/62%, cytopenias 60%/57%, kidney involvement 47%/43%, serositis 27%/23%, in the pre/postpubertal group. Arthritis was significantly more common in the older group (57%/77%). General symptomes like fever 47%/57%, weight loss 23%/30%, increased infection rate 20%/13% were also similar in the two age groups, as did ANA, anti-dsDNA, anti-Sm, anti-SSA, anti-SSB positivity and low C3 and C4 levels. Anti-RNP antibody was more common in the younger ages (33%/10%). Mean SLEDAI score was 12 in both groups. Zero SLICC damage index is significantly more common (68%/43%) in the older group after comparable follow-up period.

Risk Factors for Clinical Coronary Heart Disease in Systemic Lupus Erythematosus: The Lupus and Atherosclerosis Evaluation of Risk (LASER) Study

Accelerated atherosclerosis and premature coronary heart disease (CHD) are recognized complications of systemic lupus erythematosus (SLE), but the exact etiology remains unclear and is likely to be multifactorial. We hypothesized that SLE patients with CHD have increased exposure to traditional risk factors as well as differing disease phenotype and therapy-related factors compared to SLE patients free of CHD. Our aim was to examine risk factors for development of clinical CHD in SLE in the clinical setting. In a UK-wide multicenter retrospective case-control study we recruited 53 SLE patients with verified clinical CHD (myocardial infarction or angina pectoris) and 96 SLE patients without clinical CHD. Controls were recruited from the same center as the case and matched by disease duration. Charts were reviewed up to time of event for cases, or the same "dummy-date" in controls. SLE patients with clinical CHD were older at the time of event [mean (SD) 53 (10) vs 42 (10) yrs; p < 0.001], more likely to be male [11 (20%) vs 3 (7%); p < 0.001], and had more exposure to all classic CHD risk factors compared to SLE patients without clinical CHD. They were also more likely to have been treated with corticosteroids (OR 2.46; 95% CI 1.03, 5.88) and azathioprine (OR 2.33; 95% CI 1.16, 4.67) and to have evidence of damage on the pre-event SLICC damage index (SDI) (OR 2.20; 95% CI 1.09, 4.44). There was no difference between groups with regard to clinical organ involvement or autoantibody profile. Our study highlights the need for clinical vigilance to identify modifiable risk factors in the clinical setting and in particular with male patients. The pattern of organ involvement did not differ in SLE patients with CHD events. However, the higher pre-event SDI, azathioprine exposure, and pattern of damage items (disease-related rather than therapy-related) in cases suggests that a persistent active lupus phenotype contributes to CHD risk. In this regard, corticosteroids and azathioprine may not control disease well enough to prevent CHD. Clinical trials are needed to determine whether classic risk factor modification will have a role in primary prevention of CHD in SLE patients and whether new therapies that control disease activity can better reduce CHD risk.

Work disability in systemic lupus erythematosus is prevalent and associated with socio-demographic and disease related factors

Our objectives were to examine the prevalence of work disability (WD) and factors associated with job loss in systemic lupus erythematosus (SLE) in a large, multi-centered Canadian sample to determine the current prevalence of WD and identify the contribution of disease activity, damage, and co-morbidities with respect to WD in this cohort. Cross-sectional data on WD status from the 1000 Canadian Faces of Lupus database (a multi-center multi-ethnic cohort of SLE patients) along with clinical measures (number of ACR criteria ever, SLICC Damage Index, SLAM, SLEDAI, SF-36 and Charlson Co-morbidity Index scores), demographic features (age, sex, high school education, household income, marital status, disease duration, employment status) and co-morbidities (including self-reported fibromyalgia, arthralgias, depression and fatigue) were used in bivariate and logistic regression analyses. The 1137 SLE patients had a mean age of 50 years (SE 0.75) and mean disease duration was 18 years (SE 0.70); 19.09% were work disabled and 49.78% were employed. Those with WD were more likely than non-WD SLE patients to have: a higher number of ACR criteria for SLE; not completed high school; older age; single marital status; a lower household income; longer disease duration; higher SLICC Damage Index and SLAM scores; lower SF-36 PCS and SF-36 MCS scores; less vigorous activity per week; and fibromyalgia, arthralgias, fatigue and depression (p < 0.05). This contemporary rate of WD is lower than many past reports. Socio-demographic factors, co-morbidities (fibromyalgia and fatigue) and disease related factors were strongly associated with WD. We cannot determine cause and effect as the study was cross-sectional.

Predictors of cardiovascular damage in patients with systemic lupus erythematosus: data from LUMINA (LXVIII), a multiethnic US cohort

To determine the features predictive of atherosclerotic cardiovascular damage in patients with SLE. SLE LUMINA (LUpus in MInorities: NAture vs nurture) patients (n = 637), aged >or=16 years, disease duration <or=5 years at baseline (T0), of African-American, Hispanic and Caucasian ethnicity were studied. Atherosclerotic cardiovascular damage was defined by the following items of the SLICC Damage Index (SDI) cardiovascular domain: angina or coronary artery by pass surgery, myocardial infarction and/or congestive heart failure; factors associated with its occurrence were examined by univariable and multivariable regression analyses. Forty-three (6.8%) of 637 patients developed cardiovascular damage over a mean +/- S.D. total disease duration of 6.6 +/- 3.6 years. Nearly 90% of the patients were women with a mean +/- s.d. age of 36.5 (12.6) years; all ethnic groups were represented. By multivariable analyses, after adjusting for the cardiovascular manifestations present, age [odds ratio (OR) = 1.06; 95% CI 1.03, 1.09], male gender (OR = 3.57; 95% CI 1.35, 9.09) SDI at baseline (OR = 1.28; 95% CI 1.09, 1.50) and CRP levels [highest tertile (OR = 2.63; 95% CI 1.17, 5.91)] were associated with the occurrence of cardiovascular damage, whereas the number of years of education was negatively associated with such outcome (OR = 0.85; 95% CI 0.74, 0.94). Our data suggest that atherosclerotic cardiovascular damage in SLE is multifactorial; traditional (age, gender) and disease-related factors (CRP levels, SDI at baseline) appear to be important contributors to such an occurrence. Tight control of the inflammatory process must be achieved to prevent it.

Renal damage is the most important predictor of mortality within the damage index: data from LUMINA LXIV, a multiethnic US cohort

Damage accrual in SLE has been previously shown to be an independent predictor of mortality. We sought to discern which SLICC Damage Index (SDI) domains are the most important predictors of survival in SLE. SLE patients (ACR criteria), age > or =16 years, disease duration < or =5 years at enrolment, of African-American, Hispanic or Caucasian ethnicity were studied. Disease activity was assessed using the SLAM-Revised (SLAM-R) at diagnosis. Damage was ascertained using the SDI at the last visit. The SDI domains associated with time to death (and interaction terms) were examined by univariable and multivariable Cox proportional hazards regression analyses; those significant in the multivariable analyses were added to the final two models (with and without poverty) that included other variables known to be associated with shorter survival. A total of 635 SLE patients were studied of whom 97 (15.3%) have died over a mean (s.d.) total disease duration of 5.7 (3.7) years. Patients were predominantly women [570 (89.8%)]; their mean (s.d.) age was 36.5 (12.6) years; 126 (19.8%) had developed renal damage, 62 (9.3%) cardiovascular, 48 (7.8%) pulmonary and 34 (5.4%) peripheral vascular damage. When excluding poverty from the multivariable model, the renal domain of the SDI was independently associated with a shorter time to death (hazard ratio = 1.65; 95% CI 1.03, 2.66). The renal domain of the damage index is associated with a shorter time to death when poverty, a strong predictor of this outcome, is removed from the model. Preventing renal damage in lupus patients has long-term prognostic implications.

Systemic Lupus Erythematosus in a Multiethnic US Cohort (LUMINA): LXI. Value of C-Reactive Protein as a Marker of Disease Activity and Damage

To determine whether C-reactive protein (CRP) measured by a high sensitivity (hs) assay is a surrogate marker of disease activity and damage in systemic lupus erythematosus (SLE). Five hundred eighty-eight patients with SLE participating in a multiethnic cohort (Hispanic, African American, and Caucasian) were studied. Disease activity was measured with the Systemic Lupus Activity Measure-Revised (SLAM-R) and damage with the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI). hs-CRP was measured by immunometric assay. Disease activity and hs-CRP were measured at enrollment and damage accrual at last visit. The association of hs-CRP with the SLAM-R and SDI was examined by univariable (Pearson's correlation) and multivariable (linear regression) analyses. The association of hs-CRP and each individual domain of the SLAM-R and SDI was examined by Spearman's correlation. hs-CRP was associated with the SLAM-R in the univariable (r = 0.35, p < 0.001) and multivariable (t = 7.11, coefficient beta = 0.27, p < 0.001) analyses. It also correlated with the constitutional, eye, pulmonary, gastrointestinal, neuromotor, and laboratory domains of the SLAM-R. hs-CRP was associated with the SDI (r = 0.12, p = 0.004) in the univariable analysis but not in the multivariable analysis. When the individual domains of the SDI were analyzed, hs-CRP correlated with the renal, pulmonary, cardiovascular, musculoskeletal, and diabetes domains. hs-CRP was associated with disease activity but not with overall damage accrual; however, it correlated with specific domains of the damage index. hs-CRP may be useful to monitor the course of the disease and predict its intermediate outcome, but longitudinal studies with serial hs-CRP measurements are necessary to define its clinical value.

Initial and accrued damage as predictors of mortality in Brazilian patients with systemic lupus erythematosus: a cohort study

The aim of this study was to investigate whether initial and accrued organ damage measured by Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI) predicts mortality in cohort of Brazilian patients with systemic lupus erythematosus (SLE). One hundred and five outpatients with SLE were enrolled from July 2000 to March 2001; their demographics, disease manifestations, interventions and quantified disease activity (SLEDAI) were obtained. SDI was measured at baseline and at the end of follow-up. Initial and accrued SDI prognostic values for mortality were investigated by multivariate Cox survival analysis and Kaplan-Meyer survival curves. After a median follow-up of 6.3 years, 19 patients died due to disease activity, end-organ failure, cardiovascular events, cancer and infection. Deceased patients had longer disease duration and greater initial and final SDI than survivors had. After adjustment for age, sex and disease duration, both initial and final SDI >/= 3 points were independent predictors of mortality, with hazard ratios (HRs) of 3.0 (1.1-8.2) and 4.7 (1.6-14.5), respectively. Damage accrual during follow-up was the strongest predictor of death (HR: 5.1, 2.0-13.0). Renal and pulmonary damages were the main predictors of increased mortality risk. In conclusion, baseline and accrued damage increase mortality risk in Brazilian patients with SLE. Measures to prevent damage development and progression are urgent to reduce the mortality of patients with SLE.

Expression of Reversion-inducing Cysteine-rich Protein with Kazal Motifs in Peripheral Blood Mononuclear Cells from Patients with Systemic Lupus Erythematosus: Links to Disease Activity, Damage Accrual and Matrix Metalloproteinase 9 Secretion

We studied the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) on peripheral blood mononuclear cells (PBMCs), the serum concentration of matrix metalloproteinase 9 (MMP-9) and the MMP-9 secretion ability of PBMCs in patients with systemic lupus erythematosus (SLE), and clinical features were assessed. Compared with PBMCs from healthy donors, PBMCs from SLE patients expressed less RECK protein and mRNA but secreted more MMP-9. The serum concentration of MMP-9 was, however, lower in SLE patients than in healthy donors. The level of RECK protein was inversely associated with the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI) and MMP-9 secretion in SLE, but no relationship was found between serum MMP-9 concentration and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). In conclusion, the level of RECK protein expressed in PBMCs could be used to predict organ or system damage in SLE and this might help in developing new therapies for SLE targeted at MMP-9.