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BACKGROUND

Systemic lupus erythematosus (SLE) is a chronic, potentially serious systemic autoimmune disease. It is characterized biochemically by the presence of autoantibodies; in particular, antibodies directed against nuclear antigens. SLE is a heterogeneous disease in that clinical manifestations can vary significantly from patient to patient, ranging from mild presentations to severe organ dysfunction. Morbidity and mortality rates have improved dramatically over the past few decades due to advances in therapy.

EPIDEMIOLOGY

SLE primarily affects women of childbearing age, including adolescents, with a female:male ratio of 4-5:1. Approximately 10% to 20% of SLE is diagnosed before adulthood. Female predominance is less pronounced, with younger age of onset. It is extraordinarily rare for SLE to present before the age of 5 years, and female:male ratio is essentially equal in this group. Children tend to have more severe disease as compared with adults, with increased rates of nephritis and long-term morbidity.

Overall prevalence rates in the United States are estimated at 40 to 150 per 100,000, with a trend toward increasing prevalence over time. Non-Caucasian populations are more significantly affected, with higher prevalence in Asians, Hispanics, and African-Americans. African-American and Hispanic groups also have higher morbidity and mortality as compared with Caucasian patients.

PATHOPHYSIOLOGY

The pathogenesis of SLE is complex and remains inadequately understood. Immune abnormalities have been described on multiple levels involving both the innate and adaptive immune systems. From the innate immune perspective, dysregulated apoptosis and clearance of cellular debris lead to improper antigen presentation and increased production of proinflammatory cytokines. Loss of self-tolerance allows the development of autoreactive T and B cells that mediate tissue damage.

Immune abnormalities in SLE are affected by genetic, hormonal, and environmental influences. Polymorphisms in many immune-related genes have been described in SLE patients, including STAT4, PTPN22, and IRF5. In most patients, variations in multiple genes are thought to contribute to the development of lupus. There are also rare cases of monogenic SLE developing in children. Examples include deficiencies in complement (especially C1q and C4) and mutations in TREX1, a gene encoding an exonuclease involved in DNA repair and apoptosis.

Hormonal influences are suggested by the strong female predominance in SLE. Flares of disease triggered by pregnancy or exogenous estrogen administration have been well described. However, the exact mechanisms by which sex hormones interact with the immune system are not known.

Environmental triggers, particularly viral infections, are also thought to affect SLE. One example is Epstein-Barr virus (EBV), which infects B cells leading to B cell activation and proliferation. In one study of pediatric SLE patients, more than 99% had prior seroconversion to EBV as compared to 70% in age-matched controls.

Drug-induced lupus can present in identical fashion to SLE; common triggers include hydralazine, procainamide, and minocycline. Anti-histone antibodies are often observed in these patients. Symptoms generally ...

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