Dominique Ibañez

Difference in disease features between childhood‐onset and adult‐onset systemic lupus erythematosus

OBJECTIVE To investigate potential differences between childhood-onset and adult-onset systemic lupus erythematosus (SLE). METHODS An inception cohort with childhood-onset SLE (n = 67) was compared with an inception cohort with adult-onset SLE (n = 131), each of whom was diagnosed between 1990 and 1998 and followed up until February 1999. Prospective information included data on medications, laboratory markers, and disease activity and damage as measured by the SLE Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), respectively. RESULTS Eighty-five percent of patients with childhood-onset SLE and 88% of patients with adult-onset SLE were female; the mean duration of followup was 3.2 and 3.5 years, respectively. On average, the children had more-active disease than did the adults at the time of diagnosis and during followup. There was a higher incidence of renal disease in those with childhood-onset SLE (78% versus 52% in adults; P = 0.0005), and the adjusted mean SLEDAI renal score was higher in the children than in the adults (2.37 versus 0.82; P < 0.0001). Treatment with steroids (97% versus 72%; P < 0.0001) and immunosuppressive drugs (66% versus 37%; P = 0.0001) was used significantly more often in children with SLE. Four adult patients with SLE, but none of the children, died during the followup. At the end of the followup, the mean SDI scores in those with childhood-onset SLE were higher than those with adult-onset SLE (1.70 versus 0.76; P = 0.008). CONCLUSION Children with childhood-onset SLE have more active disease at presentation and over time than do adults with SLE, especially active renal disease. Compared with adults with SLE, children receive more intensive drug therapy and accrue more damage, often related to steroid toxicity.

Changing Patterns in Mortality and Disease Outcomes for Patients with Systemic Lupus Erythematosus

Objective Survival of patients with systemic lupus erythematosus (SLE) has improved significantly, but new morbidities have emerged, leading to altered patterns of outcome in this disease. We examined changes in mortality and other outcomes over time in a large SLE cohort. Methods A group of 1241 patients from the University of Toronto Lupus Clinic followed prospectively were divided into 4 entry cohorts — 1: 1970–1978, 2: 1979–1987, 3: 1988–1996, 4: 1997–2005. These cohorts were followed through four 9-year calendar periods defined over the same intervals. Both cohort and calendar effects were assessed for the following outcomes: mortality (standardized mortality ratio; SMR), disease activity over time (adjusted mean SLEDAI; AMS), cumulative damage (Systemic Lupus International Collaborating Clinics Damage Index; SDI), coronary artery disease (CAD), and osteonecrosis (ON). Cox regression models were used to further investigate mortality and the influence on it of the disease-related factors. Results Over the 36-year period of the study, 211 deaths occurred. The overall SMR in the first and last decades were 12.60 (95% CI: 9.13, 17.39) and 3.46 (95% CI: 2.71, 4.40) respectively. When SMR were stratified by the entry cohort and calendar period, there is evidence of a calendar-period effect but no cohort effect. The AMS decreased over the decades, while SDI, CAD, and ON increased. There were significant detrimental effects for male sex, CAD, AMS, SDI, and use of immunosuppressive drugs and significant protective effects for use of antimalarials and the effect of calendar period on mortality. Conclusion Our study demonstrates improved survival in patients with SLE over a 36-year period. Disease-related variables included in the model are important factors for mortality in this SLE cohort, but could not completely explain the trend of improved survival over calendar period observed.

Vitamin D insufficiency in a large female SLE cohort.

The objective of this study was to determine the vitamin D status and its relationship with disease and therapy features and with bone mineral density in women with systemic lupus erythematosus. Non-pregnant systemic lupus erythematosus women with dual-energy X-ray absorptiometry and vitamin D measurements performed between May 1 2005 and August 31 2006 were studied. In each patient, the lowest T-score of the first dual-energy X-ray absorptiometry scan during the study period was used. In postmenopausal women, a T-score ≥1.0 standard deviation was considered normal, between -1.0 and -2.5 standard deviations osteopenia and ≤2.5 standard deviations osteoporosis; in premenopausal women a T-score ≥2.5 standard deviations was normal and ≤2.5 standard deviations defined as reduced bone density. 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were determined at the time of dual-energy X-ray absorptiometry. A 25-hydroxyvitamin D level of <80 nmol/L was defined as sub-optimal and a level <40 nmol/L as deficient. Demographic and clinical variables were investigated for association with vitamin D levels by univariate and multivariate analyses. One-hundred and twenty-four systemic lupus erythematosus women had dual-energy X-ray absorptiometry scans and vitamin D assays performed during the study period. Sub-optimal 25-hydroxyvitamin D levels were found in 82 (66.7%) and deficient 25-hydroxyvitamin D levels in 22 (17.9%) patients. The disease-related features examined at the time of vitamin D assays or bone mineral density showed no correlation with vitamin D levels by univariate analyses. Neither 25-hydroxyvitamin D nor 1,25-dihydroxyvitamin D was associated with bone mineral density status among these patients. A multivariate logistic regression model identified season, cumulative glucocorticoid exposure, and serum creatinine as being associated with 25-hydroxyvitamin D levels, whereas ethnicity, glucocorticoid exposure, and serum creatinine were associated with 1,25-dihydroxyvitamin D levels. In conclusion, sub-optimal vitamin D status is common in women with systemic lupus erythematosus and is related to season, cumulative glucocorticoid dose, and serum creatinine.

Atherosclerotic vascular events in a multinational inception cohort of systemic lupus erythematosus

To describe vascular events during an 8‐year followup in a multicenter systemic lupus erythematosus (SLE) inception cohort and their attribution to atherosclerosis.

NEW STONE FORMATION: A COMPARISON OF EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY AND PERCUTANEOUS NEPHROLITHOTOMY

PURPOSE There is theoretical concern that stone recurrence rates may be higher following extracorporeal shock wave lithotripsy (ESWL) compared to other techniques because of residual stone debris. MATERIALS AND METHODS We documented all new stone formations in 298 consecutive patients who initially achieved a stone-free status following ESWL for renal calculi less that 2 cm in largest dimension, and compared the findings to those of 62 patients treated with percutaneous nephrolithotomy without ultrasonic fragmentation. Stone-free status was assessed by a centrally reviewed plain abdominal film and renal tomograms at 3 months. A plain abdominal film was repeated at 12 and 24 months to detect recurrence. RESULTS New stones formed in 22.2% of patients after ESWL and 4.2% after percutaneous nephrolithotomy at 1 year (p = 0.004), and in 34.8% versus 22.6%, respectively, at 2 years (p =0.190). Furthermore, more new stones recurred in the lower and mid calices compared to baseline location in the ESWL group (chi-square <0.0001), which was not observed in the percutaneous nephrolithotomy group. CONCLUSIONS Our data support a trend toward higher stone recurrence rates in ESWL treated patients, which may be due to microscopic sand particles migrating to dependent calices and acting as a nidus for new stone formation.

Pulmonary hypertension in systemic lupus

Pulmonary arterial hypertension (PAH) has devastating consequences in the rheumatic diseases; however, the prevalence in lupus is not well delineated. We searched the University of Toronto lupus database to ascertain the first echocardiogram ordered at their physician’s discretion between 1995 and 2002. We reviewed the echocardiogram reports for right ventricular systolic pressure (RVSP), valvular disease, and atrial and ventricular function. The PAH was defined as RVSP ≥40 mmHg. Patients were divided into three groups: RVSP ≥40 mmHg, RVSP 1/4 30-39 mmHg and RVSP, 30 mmHg. We analysed potential associations between presence of PAH and lupus including disease activity, organ involvement and anticardiolipin antibodies, both at the time of and any time prior to echocardiography. In total, 129 patients underwent echocardiography. Nine patients’ echocardiogramswere not obtainable, and three patients were excluded from analysis, as their visit was more than six months from the date of echocardiography. Sixteen patients (14%) had RVSP ≥40 mmHg, 43 (37%) patients had RVSP of 30-39, and 60 (51%) patients had RVSP, 30 mmHg. There was no statistical difference in disease activity, organ involvement or serology among all three groups. In conclusion, the prevalence of PAH (RVSP ≥40 mmHg) on first echocardiogram ordered at physician discretion in our cohort was 14%. An RVSP of 30-39 mmHg was found in 37% of patients. Although abnormal, the clinical significance of this finding is unknown. Disease activity, organ involvement and anti-cardiolipin antibodies were not associated with PAH. Further research is needed to identify the mechanism, response to immunosuppression and impact on quality of life in these patients.

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

We describe disease activity, damage, and the accrual of key autoantibodies in an inception systemic lupus erythematosus (SLE) cohort.

Frequency and determinants of flare and persistently active disease in systemic lupus erythematosus

OBJECTIVE Selection of flare as the primary outcome variable in systemic lupus erythematosus (SLE) clinical trials fails to capture patients with persistently active disease (PAD). We sought to elucidate the frequency and determinants of flare and PAD. METHODS Prospectively collected data from the Toronto Lupus Cohort were used to determine the incidence of flare and PAD in 2004 and 2005. Flare was defined as an increase in SLE Disease Activity Index 2000 update (SLEDAI-2K) score of >/=4 from the previous visit. PAD was defined as a SLEDAI-2K score of >/=4, excluding serology alone, on >/=2 consecutive visits. Data from 1, 2, and 3 years prior were used to model flare and PAD in 2004. Model properties were tested for prediction of flare and PAD in 2005. RESULTS One-third of the patients had >/=1 flare, whereas nearly half experienced PAD in a given year. Nearly 60% of the patients had episodes of flare or PAD per year. At least 25% of patients had PAD without achieving the definition of flare. In the best-fitting model, predictors of PAD in 2004 were SLEDAI-2K score at the start of the outcome interval and prior cutaneous or musculoskeletal disease activity. This model gave 79% correct prediction of PAD in 2005. In contrast, flare prediction models performed poorly. CONCLUSION Persistent activity is a common disease state in SLE and should be an outcome variable in SLE clinical trials. Our PAD prediction model may aid prognostication and selection of patients for inclusion in clinical trials.

The effect of lupus nephritis on pregnancy outcome and fetal and maternal complications.

Objective. To evaluate the effect of lupus nephritis on pregnancy with respect to fetal outcome, maternal complications, and lupus activity. Methods. All pregnancies seen between 1970 and 2003 in the Lupus Clinic were evaluated for the 3 outcomes. Renal disease was defined as the presence of nephrotic syndrome, dialysis, renal transplant, serum creatinine > 120 mmol/l, proteinuria, sterile hematuria and pyuria, or the presence of casts. Fetal complications were evaluated in pregnancies resulting in either live births or stillbirths. Generalized estimating equations were used to test for differences in outcomes between pregnancies with and without the presence of active renal disease. Repeated measures adjustments were made in the model for multiple pregnancies in the same mother. Results. There were 193 pregnancies in 104 women. Of these, 81 occurred in the presence of active renal disease during the study period, defined as 6 months prior to conception until the date of pregnancy outcome. One hundred twelve pregnancies were defined as nonrenal. No statistical difference was found in pregnancy outcome. Fetal complications were not different between the 2 groups with the exception of low birth weight and congenital malformations, which were observed more frequently in the renal group. Pregnancy-induced hypertension was more frequent in pregnancies with renal disease. Lupus flares were also more likely to occur in pregnancies with renal disease compared to those without. Conclusion. Lupus nephritis in pregnancy does not lead to worsened pregnancy or fetal outcomes. Active renal disease, however, is associated with pregnancy-induced hypertension, as well as a flare of lupus activity during pregnancy.

Accumulation of coronary artery disease risk factors over three years: Data from an international inception cohort

OBJECTIVE To examine the accumulation of risk factors over 3 years in a multicenter, international inception cohort of patients with systemic lupus erythematosus (SLE). METHODS The Systemic Lupus International Collaborating Clinics registry for atherosclerosis comprises 27 centers from 11 countries. An inception cohort of 935 patients with SLE was assembled, according to a standardized protocol, from 2000 to 2006 to study risk factors for atherosclerosis. Both classic and other coronary artery disease (CAD) risk factors were collected at entry and through 3 years of followup. Therapy was documented over the 3 years. The Framingham 10-year risk factor profile was calculated for each patient at year 1 and year 3. RESULTS A total of 278 patients from the inception cohort were followed for 3 years and constituted the population for this study. At enrollment a substantial number of patients already demonstrated several risk factors for CAD, both classic and other. All risk factors increased from enrollment over the 3 years of followup. Treatment of hypertension and hypercholesterolemia also increased over 3 years, but less so for hypercholesterolemia. The Framingham 10-year CAD risk profile was higher in men than in women both at entry and at 3 years, and remained unchanged over the 3 years. Corticosteroid use increased only slightly over 3 years, but use of antimalarials and immunosuppressive agents increased to a greater extent. CONCLUSION Patients with SLE should be monitored for CAD risk factors from the time of diagnosis and appropriate treatment should be instituted early.