What is systemic lupus erythematosus (SLE)?

What is Lupus (Systemic Lupus Erythematosus)

Systemic lupus erythematosus (SLE) is a chronic multisystemic autoimmune disease where the immune system loses tolerance and produces autoantibodies against nuclear antigens, leading to immune complex deposition and chronic inflammation that can damage virtually any organ system in the body. 1

Fundamental Disease Mechanism

The core pathophysiology involves three interconnected processes:

• Loss of immunological tolerance where the body's immune system fundamentally fails to distinguish self from non-self, resulting in pathogenic autoantibody production that occurs in virtually all patients 1
• Autoantibody production against nuclear antigens (particularly anti-double-stranded DNA and anti-Smith antibodies) that form immune complexes 1, 2
• Immune complex deposition that activates complement, recruits inflammatory cells, and causes subsequent tissue damage throughout the body 1

The disease results from an interaction between genetic susceptibilities (including MHC polymorphisms) and environmental triggers (particularly viral infections) that precipitate disease onset 1

Who Gets Lupus

• Women are disproportionately affected, comprising approximately 90% of all SLE patients, with peak onset during childbearing years 1, 3
• Racial and ethnic disparities are profound: Latin American, North American Mestizo, African descendants, and Native Americans develop lupus earlier, experience more severe disease manifestations, accumulate greater organ damage, and have higher mortality rates compared to other populations 1
• Approximately 3.4 million people worldwide have been diagnosed with SLE 3

Clinical Manifestations Across Organ Systems

The disease can affect multiple organ systems simultaneously or sequentially:

• Mucocutaneous manifestations include lupus-specific rashes (malar "butterfly" rash, discoid lesions), photosensitivity, mouth ulcers, and alopecia 1, 2
• Musculoskeletal symptoms present as arthritis, joint pain, and myalgia, often among the earliest complaints 1, 2
• Renal involvement (lupus nephritis) develops in approximately 40% of patients, with an estimated 10% progressing to end-stage kidney disease after 10 years 3
• Hematologic abnormalities include cytopenias (thrombocytopenia, leukopenia, autoimmune hemolytic anemia) 4, 1
• Cardiovascular, pulmonary, and neuropsychiatric manifestations can occur, contributing to significant morbidity 1
• Constitutional symptoms such as fever and profound fatigue are common 1, 2

Diagnostic Approach

The 2019 EULAR/ACR classification criteria are 96.1% sensitive and 93.4% specific for SLE, requiring both clinical manifestations and immunologic abnormalities 1, 3:

Clinical features (weighted within each domain):

• Fever, cytopenia, characteristic rash, arthritis, serositis, and proteinuria 1

Immunologic markers that define the disease:

• Anti-double-stranded DNA (anti-dsDNA) antibodies 1, 3
• Anti-Smith (anti-Sm) antibodies 1, 3
• Hypocomplementemia (low complement levels) 1, 3
• Antiphospholipid antibodies 1
• Anti-Ro/SSA and anti-La/SSB antibodies 1

Disease Course and Prognosis

• The disease course remains highly variable with unpredictable flares and remissions 2
• Mortality remains unacceptably high despite therapeutic advances, with patients in certain populations succumbing primarily to disease activity and/or infections 1
• Comorbidities significantly impact outcomes, including infections, cardiovascular disease, osteoporosis, metabolic complications, and malignancy 1
• The burden of disease remains high despite substantial advances in diagnosis and management 2