Dyslipoproteinemia in pediatric systemic lupus erythematosus

Abstract

Patients with systemic lupus erythematosus are at increased risk for premature atherosclerosis. We examined one possible etiologic factor, dyslipoproteinemia, both before and after corticosteroid therapy. We identified 2 distinct patterns of dyslipoproteinemia. One is attributable to active disease; the other is attributable, in part, to corticosteroid therapy. The dyslipoproteinemia of active disease consists of depressed high density lipoprotein cholesterol and apoprotein A-I with elevated very low density lipoprotein cholesterol and triglyceride, while the dyslipoproteinemia after corticosteroid therapy consists of increased total cholesterol, very low density lipoprotein cholesterol, and triglyceride. The possible pathophysiologic mechanisms responsible for these patterns, as well as the possible roles in premature atherosclerosis seen in systemic lupus erythematosus patients, are discussed.Premature atherosclerosis and its sequelae, myocardial infarction and cerebrovascular accident, have recently been recognized as complications of systemic lupus erythematosus (SLE) (1-7). Possible etiologies include dyslipoproteinemia, vasculitis, hypertension, and increased tendency for thrombosis associated with the presence of circulating anticoagulant (1-8).Dyslipoproteinemia is common in adult SLE patients (9); however, the relationships of disease activity, diet, corticosteroid therapy, and concurrent renal, liver, and pancreatic disease have not been studied well. To differentiate the roles of corticosteroids and disease activity in the dyslipoproteinemia of SLE, we studied newly diagnosed pediatric patients both before and after high-dose systemic prednisone therapy. PATIENTS AND METHODSPatients. Ten successive pediatric patients (younger than 21 years of age) newly diagnosed as having SLE were enrolled after informed consent was obtained. Nine fulfilled the requirements of the American Rheumatism Association revised diagnostic criteria (10). The other (patient 5) had anticardiolipin, high-titer speckled antinuclear, anti-Smith, and anti-double-stranded DNA antibodies, circulating lupus anticoagulant, hypocomplementemia, and recurrent pulmonary emboli. He was not treated with corticosteroids. Eight patients underwent percutaneous renal biopsy prior to therapy. Results are shown in Table 1. In all 10 patients at diagnosis, and in 8 patients at 4-8 weeks after institution of 1-2 mg/kg/day of prednisone, fasting plasma lipid profiles (see below) were obtained. Dietary intake was quantified by 3-day diet record, and this was supplemented with 24-hour recall

The complex nature of the interaction between disease activity and therapy on the lipid profile in patients with pediatric systemic lupus erythematosus

“…Similar to previous studies, we found that total cholesterol levels were frequently abnormal both at the time of diagnosis and over the course of the disease (25,41). The percentage of patients with abnormal levels was only slightly higher at time of presentation than at other times and remained relatively constant in subsequent years.…”

“…A previous study of 10 newly diagnosed pediatric patients with SLE described the active SLE pattern of increased levels of triglycerides and VLDL cholesterol with depressed levels of HDL cholesterol and apolipoprotein A-I. Following the initiation of steroid therapy, levels of total cholesterol, LDL cholesterol, and HDL cholesterol rose, with lesser increases in the levels of VLDL cholesterol and triglycerides (25). …”

“…These data suggest that factors intrinsic to SLE itself, especially at the time of diagnosis, are likely the major factor in the development of dyslipoproteinemia in patients with pediatric SLE. However, corticosteroid treatment had a modifying effect (17,18,25,41).…”

“…Although both traditional and nontraditional factors are important in the development of premature atherosclerosis in patients with SLE, dyslipoproteinemia, which is present in 30-73% of adult patients with SLE, plays a role in the development of atherosclerosis (2,10,(17)(18)(19)(20)(21)(22)(23)(24). To date, there have been few comprehensive lipid studies in pediatric patients with SLE (5,6,16,(25)(26)(27).…”

“…One pattern, characterized by elevated chylomicrons, triglycerides, and very low-density lipoprotein (VLDL) cholesterol levels and decreased levels of high density lipoprotein (HDL) cholesterol, has been referred to as the active SLE profile (19,25,28). The second pattern, seen with high-dose steroid therapy, is characterized by an increase in total cholesterol levels, which is not seen in the active lipid profile (5,10,17,22,29,30).…”