Cell-bound complement activation products (CB-CAPs) have high sensitivity and specificity in pediatric-onset systemic lupus erythematosus and correlate with disease activity.

OBJECTIVE: Elevated levels of cell-bound complement activation products (CB-CAPs) (C4d deposition on B lymphocytes (BC4d) and/or erythrocytes (EC4d)) are sensitive and specific in diagnosis and monitoring of adult systemic lupus erythematosus (SLE). Our objective was to evaluate the role of CB-CAPs for diagnosis and monitoring of pediatric-onset SLE (pSLE). METHODS: A prospective cohort study of 28 pSLE and 22 juvenile arthritis patients was conducted. SLE disease activity was determined using a clinical Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) that excluded serologies. Autoantibodies were measured using solid-phase immunoassays, C3 and C4 using immunoturbidimetry, and CB-CAPs using quantitative flow cytometry. Abnormal CB-CAPs were defined as EC4d or BC4d above the 99th percentile for healthy adults (>14 and > 60 net mean fluorescence intensity (MFI), respectively). Performance characteristics of CB-CAPs were assessed using area under the curve (AUC) for receiver operating characteristics. Linear mixed effect models evaluated the correlation between CB-CAPs and clinical SLEDAI over 6 months. RESULTS: BC4d yielded higher AUC (0.91 ± 0.04) than C3 (0.63 ± 0.08) and C4 (0.67 ± 0.08) ( p < 0.05). Abnormal CB-CAPs were 78% sensitive and 86% specific for diagnosis of pSLE (Youden's index = 0.64 ± 0.11). In contrast to BC4d, EC4d levels correlated with clinical SLEDAI ( p < 0.01). CONCLUSION: CB-CAPs (EC4d and BC4d) have higher sensitivity and specificity than low complement in pSLE, and may help with diagnosis of pSLE. EC4d could provide a useful biomarker for disease activity monitoring.

Use of atorvastatin in systemic lupus erythematosus in children and adolescents.

OBJECTIVE: Statins reduce atherosclerosis and cardiovascular morbidity in the general population, but their efficacy and safety in children and adolescents with systemic lupus erythematosus (SLE) are unknown. This study was undertaken to determine the 3-year efficacy and safety of atorvastatin in preventing subclinical atherosclerosis progression in pediatric-onset SLE. METHODS: A total of 221 participants with pediatric SLE (ages 10-21 years) from 21 North American sites were enrolled in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus study, a randomized double-blind, placebo-controlled clinical trial, between August 2003 and November 2006 with 36-month followup. Participants were randomized to receive atorvastatin (n=113) or placebo (n=108) at 10 or 20 mg/day depending on weight, in addition to usual care. The primary end point was progression of mean-mean common carotid intima-media thickening (CIMT) measured by ultrasound. Secondary end points included other segment/wall-specific CIMT measures, lipid profile, high-sensitivity C-reactive protein (hsCRP) level, and SLE disease activity and damage outcomes. RESULTS: Progression of mean-mean common CIMT did not differ significantly between treatment groups (0.0010 mm/year for atorvastatin versus 0.0024 mm/year for placebo; P=0.24). The atorvastatin group achieved lower hsCRP (P=0.04), total cholesterol (P<0.001), and low-density lipoprotein (P<0.001) levels compared with placebo. In the placebo group, CIMT progressed significantly across all CIMT outcomes (0.0023-0.0144 mm/year; P<0.05). Serious adverse events and critical safety measures did not differ between groups. CONCLUSION: Our results indicate that routine statin use over 3 years has no significant effect on subclinical atherosclerosis progression in young SLE patients; however, further analyses may suggest subgroups that would benefit from targeted statin therapy. Atorvastatin was well tolerated without safety concerns.

Early versus later onset childhood-onset systemic lupus erythematosus: Clinical features, treatment and outcome.

The objective of the study was to compare clinical features, treatment and disease outcome in patients with early versus later onset of childhood-onset systemic lupus erythematosus (cSLE). A retrospective matched cohort study of cSLE patients diagnosed between 1988 and 2008 and followed for a minimum of one year was conducted. Thirty-four pre-pubertal cSLE patients with disease onset prior to their 12th birthday were matched by ethnicity and year of diagnosis to 34 pubertal cSLE patients. The most common criteria at diagnosis in both groups were malar rash, arthritis, hematologic manifestations, and renal disease. After a mean follow-up of more than six years, a similar proportion of patients in the two groups were still prescribed corticosteroids (47% and 41%); patients in the early onset group required a significantly higher daily dose (0.6 mg/kg prednisone-equivalent versus 0.2 mg/kg, p < 0.05). There were no significant differences in organ involvement, disease activity and disease damage between the two groups, and severe complications occurred at similar rates. There were a greater number of admissions to the pediatric intensive care unit (PICU) in the early onset group (18 versus 5, p = 0.01), with time-to-event analysis demonstrating a significantly shorter disease duration from diagnosis to first PICU admission in the early onset group (p < 0.001). While a similar proportion of patients in the early and later onset groups required treatment with cyclophosphamide, patients in the early onset group received treatment earlier in their disease course (mean 13.7 versus 19.9 months, p < 0.001). Early onset cSLE leads to earlier and more frequent PICU admission, earlier use of cyclophosphamide, and higher corticosteroid dose at long-term follow-up.

Sulfasalazine therapy for juvenile rheumatoid arthritis.

OBJECTIVE: To determine the safety and therapeutic potential of sulfasalazine (SSZ) in the treatment of a large cohort of patients with juvenile rheumatoid arthritis (JRA). METHODS: All patients who required the addition of a second line agent were offered SSZ and assessed at regular intervals. Thirty patients took SSZ as their sole drug therapy. One hundred thirty-nine patients with an average age of 11.5 yrs (range 1.5-21.8 yrs) took the medication. The duration of symptoms at the start of treatment was 30 mo (1-130 mo). All subtypes of JRA were included in the study group. Patients were treated for a mean of 13 mo (1-42 mo) with 31 mg/kg/day of SSZ. Significant improvement was defined as 50% decrease in the number of joints with active arthritis; or 50% decrease in the number of joints with effusion; or 50% decrease in total degrees of joint contractures; or normalization of an elevated erythrocyte sedimentation rate within 12 months of starting treatment. Data on adverse reactions, remissions, and treatment failure were also collected. RESULTS: One hundred two patients (73%) had significant improvement after starting SSZ. Fifty-six patients (40%) were able to stop all other medication at an average of 9.5 mo. Thirty-nine patients (28%) remitted and discontinued all medication. Twenty-three patients (17%) discontinued the drug for adverse reactions. All reactions resolved completely when the drug was discontinued. CONCLUSION: SSZ is safe and appears to be an effective primary or second line therapy for JRA, and should be studied further in a multi-institutional, placebo controlled study.