What is Systemic Lupus Erythematosus (SLE)?

Systemic Lupus Erythematosus (SLE)

Systemic Lupus Erythematosus (SLE) is a chronic multisystemic autoimmune disease characterized by immune complex deposition and vasculopathy that can affect any organ system in the body, with manifestations ranging from mild skin and joint involvement to severe, life-threatening organ damage. 1

Definition and Pathophysiology

• SLE is a prototypic autoimmune disease characterized by the presence of autoantibodies directed against nuclear antigens, leading to immune complex formation and deposition in various tissues 1
• The pathogenesis involves a complex interplay between genetic susceptibility and environmental factors, resulting in dysregulation of both innate and adaptive immune responses 2
• Type-1 interferon dysregulation is a common denominator in the disease process 2
• The disease leads to chronic inflammation in target organs including skin, joints, kidneys, heart, lungs, and the nervous system 1

Epidemiology

• SLE affects approximately 3.4 million people worldwide 3
• Prevalence ranges from 20 to 150 cases per 100,000 population 2
• Approximately 90% of patients with SLE are female 3
• The disease disproportionately affects Latin American, African descendants, and Native American populations, who tend to develop lupus earlier and experience more severe disease 2

Clinical Manifestations

SLE can affect multiple organ systems, with common manifestations including:

• Constitutional symptoms: fever, fatigue, weight loss 1
• Mucocutaneous: lupus-specific rashes, photosensitivity, oral ulcers, alopecia 1
• Musculoskeletal: arthritis, arthralgia, myalgia 1
• Renal: lupus nephritis (affects approximately 40% of patients) 3
• Neuropsychiatric: seizures, psychosis, cognitive dysfunction, peripheral neuropathy 2
• Cardiovascular: pericarditis, myocarditis, accelerated atherosclerosis 2
• Pulmonary: pleuritis, pneumonitis, pulmonary hypertension 2
• Hematologic: cytopenias (leukopenia, thrombocytopenia, anemia) 2

Diagnosis

While there are no universally accepted diagnostic criteria for SLE, the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria are commonly used, with 96.1% sensitivity and 93.4% specificity 3:

• Clinical criteria include fever, cytopenia, rash, arthritis, serositis, and renal involvement 3
• Immunological criteria include SLE-specific autoantibodies (anti-dsDNA, anti-Sm) and low complement levels 3
• Anti-dsDNA antibodies are relatively specific for SLE and can be useful for monitoring disease activity and treatment response 2

Management Principles

• The primary therapeutic goal is to achieve remission or low disease activity as soon as possible after diagnosis and maintain it long-term 4
• Treatment should focus on preventing organ damage, minimizing medication side effects, and improving quality of life 4
• Management should be tailored to the specific organ manifestations and disease severity 2
• All patients should receive antimalarials (primarily hydroxychloroquine) unless contraindicated 2, 4
• Glucocorticoids should be prescribed at the lowest possible dose and for the shortest period of time 2
• Immunosuppressive agents are added for moderate to severe disease or specific organ involvement 3

Pharmacological Treatment

First-line therapy:

• Antimalarials (hydroxychloroquine): Standard of care for all SLE patients, associated with significant reduction in mortality 3
• Glucocorticoids: For acute flares, at lowest effective dose and shortest duration 2

Additional therapies based on disease severity:

• Immunosuppressants: Azathioprine, mycophenolate mofetil, methotrexate for moderate disease 2, 3
• Cyclophosphamide: For severe manifestations, particularly nephritis 3
• Biologics: Belimumab (approved for active SLE and lupus nephritis), anifrolumab (for active SLE), and voclosporin (for lupus nephritis) 3

Monitoring and Follow-up

• Regular assessment should include clinical signs (skin lesions, arthritis, serositis, neurological manifestations), laboratory tests (CBC, creatinine, proteinuria, urinalysis), and immunological markers (C3, anti-dsDNA) 4
• Validated disease activity indices should be used to monitor disease activity and detect flares 4
• For lupus nephritis, monitoring should include renal biopsy (when indicated), urine sediment analysis, proteinuria, and kidney function tests 4

Management of Comorbidities

SLE patients are at increased risk for:

• Infections: Leading cause of morbidity and mortality, accounting for 25-50% of overall mortality 2
• Cardiovascular disease: Accelerated atherosclerosis due to chronic inflammation 4
• Osteoporosis: Related to chronic inflammation and glucocorticoid use 4
• Malignancies: Particularly non-Hodgkin lymphoma 4

Special Considerations

Pregnancy:

• Pregnancy may increase disease activity, though flares are usually mild 2
• Patients with lupus nephritis and antiphospholipid antibodies have higher risk of preeclampsia 2
• Medications safe during pregnancy include prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin 2
• Mycophenolate mofetil, cyclophosphamide, and methotrexate must be avoided during pregnancy 2

Antiphospholipid Syndrome:

• Low-dose aspirin may be considered for primary prevention of thrombosis and pregnancy loss 2
• Long-term anticoagulation with oral anticoagulants is effective for secondary prevention of thrombosis 2
• Estrogen-containing medications increase thrombosis risk and should be avoided 2

Preventive Measures

• Photoprotection is beneficial for patients with cutaneous manifestations 2
• Pneumococcal vaccination is recommended due to high risk of pneumococcal infection (13 times higher than general population) 2
• Lifestyle modifications including smoking cessation, weight control, and exercise should be encouraged 2