What is systemic lupus erythematosus (SLE) and what are its symptoms?

What is Systemic Lupus Erythematosus (SLE)?

Systemic lupus erythematosus 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

Disease Pathophysiology

• SLE results from a fundamental failure of immunological tolerance, leading to pathogenic autoantibody production present in virtually all patients 1
• Genetic factors (including MHC polymorphisms) and environmental triggers (particularly viral infections, UV light exposure, and hormonal factors) interact to precipitate disease onset 1, 2
• Immune complex deposition activates complement, recruits inflammatory cells, and causes subsequent tissue damage in affected organs 1, 3
• The disease is inherited in a polygenic manner in most patients, though rare single-gene complement deficiencies are strongly associated with SLE 2

Who Gets Lupus?

• The disease predominantly affects women during childbearing years, with approximately 90% of patients being female 1, 4
• 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
• Approximately 3.4 million people worldwide have received a diagnosis of SLE 4

Clinical Manifestations and Symptoms

Mucocutaneous Manifestations

• Characteristic skin rashes including malar (butterfly) rash, discoid lesions, and photosensitive rashes 5, 4
• Oral or nasal ulcers 4

Musculoskeletal Symptoms

• Arthritis affecting multiple joints, typically non-erosive 5, 4
• Joint pain and swelling 3, 6

Renal Involvement

• Proteinuria indicating lupus nephritis, which develops in approximately 40% of SLE patients 5, 4
• An estimated 10% of people with lupus nephritis develop end-stage kidney disease after 10 years 4

Neuropsychiatric Manifestations

• Seizures or psychosis representing severe neurological involvement 5
• Cognitive dysfunction and other neuropsychiatric symptoms 2

Cardiopulmonary Manifestations

• Serositis including pleuritis and pericarditis 5, 4
• Pulmonary involvement occurs in 20% to 90% of patients, with pleural involvement being the most common pulmonary manifestation 5
• Interstitial lung disease is rare (1% to 15% of patients) but associated with poor prognosis 5

Hematologic Abnormalities

• Cytopenia including anemia, thrombocytopenia, and leukopenia 5, 4
• Autoimmune hemolytic anemia 7

Constitutional Symptoms

• Fever without other identifiable cause 4
• Debilitating fatigue 2, 6

Respiratory Symptoms (When Present)

• Dyspnea, chest pain, reduced exercise tolerance, cough, and hemoptysis should prompt evaluation for underlying lung disease 5

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, 4

Clinical Features to Evaluate

• Fever, cytopenia, characteristic rash, arthritis, serositis, and proteinuria 1, 8
• New clinical signs including rashes, arthritis, serositis, neurological manifestations and seizures/psychosis 5

Essential Laboratory Tests

• Complete blood count to assess for cytopenias 5, 8
• Serum creatinine, proteinuria, and urinary sediment to evaluate renal involvement 5, 8

Immunologic Markers

• Anti-double-stranded DNA (anti-dsDNA) antibodies - highly specific for SLE 5, 1
• Anti-Smith (anti-Sm) antibodies - highly specific for SLE 5, 1
• Hypocomplementemia (low serum C3/C4) indicating active disease 5, 1
• Antiphospholipid antibodies 5, 1
• Anti-Ro/SSA and anti-La/SSB antibodies 5, 1
• Anti-U1-RNP antibodies (associated with increased ILD risk) 5

Additional Diagnostic Studies

• Brain MRI and renal biopsy may add prognostic information in selected patients 5
• Chest radiography and pulmonary function tests at baseline 5

Disease Course and Prognosis

• SLE runs a highly variable clinical course characterized by remissions and flares 5
• The disease can range from relatively mild to life-threatening 9
• Multiple organ involvement patterns affect mortality and quality of life 8
• Increased risk for premature cardiovascular disease and infections due to both disease and immunosuppressive therapy 2
• The 10-year mortality has improved with modern treatment approaches 2

Important Comorbidities

SLE patients are at increased risk for certain comorbidities due to the disease and/or its treatment. 5

These include:

• Infections (urinary-tract infections and others) requiring high index of suspicion 5, 8
• Atherosclerosis and premature cardiovascular disease 5, 2
• Hypertension and dyslipidemia 5
• Diabetes 5
• Osteoporosis and avascular necrosis 5, 8
• Malignancies (especially non-Hodgkin's lymphoma) 5