Systemic lupus erythematosus (SLE), the “disease with a thousand faces” , is an autoimmune disease characterized by the production of autoantibodies to nuclear antigens in association with a broad spectrum of clinical manifestations. SLE has an estimated prevalence of about 10–150 per 100,000 persons and a female:male ratio of around 9:1 (see section 1.6) . The peak incidence is between the ages of 15 and 40, and SLE is therefore considered to be one of the most common autoimmune diseases of women of childbearing age. However, SLE can affect all age groups, from infants to geriatric patients (see Chapter 7). The exact etiology and pathogenesis of SLE remain unknown, but involves complex multifactorial interactions between genetic, epigenetic, hormonal and environmental factors (Figure 1.1) that eventually result in a loss of self-tolerance. The disease can affect almost any tissue or organ system (see Chapter 3), and has a variable course and severity that can range from mild to potentially fatal. A broad spectrum of autoantibodies can be found in SLE patients, and are often associated with specific clinical features. Antinuclear antibodies (ANA) are found in 98% of patients, but are non-specific. Conversely, antibodies to double-stranded DNA (dsDNA), anti-Sm, or anti-nucleosome are highly specific (see section 4.2). Three main patterns of disease activity have been identified, including a remitting-relapsing disease course characterized by flares and periods of remission, chronically active disease, and long quiescence . Organ damage, which can occur in relation with disease activity or even in patients without obvious symptoms, is the main predictor of morbidity and mortality. There has been a significant reduction in mortality of SLE patients over the last decades, with many studies reporting 5-year survival rates exceeding 95%. While infections and cardiovascular morbidity are the main causes of death, SLE itself can still cause death today (see Chapter 7).