What is Systemic Lupus Erythematosus (SLE)?
Systemic lupus erythematosus (SLE) is a chronic multisystem 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
Fundamental Pathophysiology
The disease results from a fundamental failure of immunological tolerance, leading to pathogenic autoantibody production present in virtually all patients 1. The mechanism involves:
- Immune dysregulation: Autoantibodies form immune complexes that deposit in tissues, activate complement, recruit inflammatory cells, and cause subsequent tissue damage 1, 2
- Genetic susceptibility: MHC polymorphisms increase susceptibility to autoimmune reactions 2
- Environmental triggers: Viral infections (particularly herpes family viruses) can precipitate disease onset through lymphocyte activation 2
Clinical Presentation
SLE has variable presentation, course, and prognosis 3. The disease can be:
- Multisystem involvement: Affecting mucocutaneous, musculoskeletal, renal, cardiovascular, pulmonary, neuropsychiatric, and hematologic systems 1, 4
- Occasionally limited: Restricted to one or few organs 3
- Variable severity: Ranging from mild rashes and arthritis to life-threatening organ damage 4
Diagnosis
SLE is diagnosed on clinical grounds in the presence of characteristic serological abnormalities 3. The 2019 EULAR/ACR classification criteria are 96.1% sensitive and 93.4% specific, requiring both clinical manifestations and immunologic abnormalities 1, 5:
Clinical Features (weighted within each domain):
- Fever 1
- Cytopenia 1, 5
- Characteristic rash 1, 5
- Arthritis 1, 5
- Serositis 1
- Proteinuria (indicating potential lupus nephritis) 1, 5
Immunologic Markers:
- Anti-double-stranded DNA (anti-dsDNA) antibodies 1, 5
- Anti-Smith (anti-Sm) antibodies 1, 5
- Hypocomplementemia 1, 5
- Antiphospholipid antibodies 1
- Anti-Ro/SSA and anti-La/SSB antibodies 1
Epidemiology
- Gender predominance: Approximately 90% of patients are female, predominantly during childbearing years 1, 5
- Ethnic disparities: Latin American, North American Mestizo, African descendants, and Native Americans develop lupus earlier, experience more severe disease, higher disease activity, greater organ damage accumulation, and higher mortality rates 1
- Global burden: Approximately 3.4 million people worldwide have received a diagnosis of SLE 5
Prognosis and Complications
- Lupus nephritis: Approximately 40% of patients develop lupus nephritis, with an estimated 10% progressing to end-stage kidney disease after 10 years 5
- Mortality: Infections represent 25-50% of global mortality, with more than 20% of hospitalizations due to infections 2
- Treatment goals: Long-term patient survival, prevention of organ damage, and optimization of health-related quality of life 3, 1