Definition of Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a complex multisystemic autoimmune disease characterized by loss of immune tolerance, production of autoantibodies against nuclear antigens, immune complex deposition, and chronic inflammation affecting multiple organ systems. 1
Core Pathophysiologic Features
The disease fundamentally represents a failure of immunological tolerance, leading to pathogenic autoantibody production that is present in virtually all patients. 1, 2 This process involves:
- Autoantibody formation against nuclear components, particularly anti-double-stranded DNA (anti-dsDNA) and anti-Smith (anti-Sm) antibodies 1, 3
- Immune complex deposition in tissues with subsequent complement activation 1, 2
- Recruitment of inflammatory cells and resulting tissue damage across multiple organ systems 1
Clinical Characteristics
SLE presents as a multisystem disease that can affect virtually any organ, though it may occasionally be limited to one or few organs at presentation. 4 The disease is diagnosed on clinical grounds in the presence of characteristic serological abnormalities. 4
Key affected systems include:
- Mucocutaneous manifestations (characteristic rashes, photosensitivity, mouth ulcers, alopecia) 1, 3
- Musculoskeletal involvement (arthritis, joint pain, myalgia) 1, 3
- Renal disease (proteinuria, lupus nephritis in approximately 40% of patients) 1, 5
- Hematologic abnormalities (cytopenias, thrombocytopenia, anemia) 1
- Neuropsychiatric manifestations (seizures, psychosis) 4, 1
- Cardiovascular and pulmonary complications 1
Epidemiologic Profile
The disease predominantly affects women during their childbearing years, with approximately 90% of patients being female. 1, 5 Approximately half a million people in Europe and a quarter of a million in the USA have SLE. 4
Populations at higher risk include:
- Latin American, North American Mestizo, African descendants, and Native Americans, who develop lupus earlier with more severe disease, higher activity, greater organ damage accumulation, and higher mortality rates 1
Disease Course
SLE runs a highly variable clinical course characterized by remissions and flares. 4 The disease can take a chronic or relapsing-remitting course, with presentations ranging from mild rashes and arthritis to debilitating fever, fatigue, and severe life-threatening organ involvement. 6
Diagnostic Framework
The 2019 EULAR/ACR classification criteria are 96.1% sensitive and 93.4% specific for SLE, requiring both clinical manifestations and immunologic abnormalities. 1, 5 These criteria systematically evaluate:
Clinical features (weighted within each domain):
Immunologic markers:
- Anti-dsDNA antibodies 1, 3
- Anti-Sm antibodies 1, 3
- Hypocomplementemia 1, 3
- Antiphospholipid antibodies 1, 3
- Anti-Ro/SSA and anti-La/SSB antibodies 1
Etiologic Factors
The development of SLE involves an interaction between genetic susceptibilities and environmental triggers. 1 Genetic factors include MHC polymorphisms, while environmental triggers particularly include viral infections that can precipitate disease onset. 1, 2