Notes on Systemic Lupus Erythematosus (SLE) Lecture

Introduction to SLE

• SLE is an autoimmune disease mediated by autoantibodies and immune complexes.
• It targets nearly all organs and is chronic, commonly affecting women during reproductive years.

Pathophysiology

• Involves genetic, epigenetic, immunological, hormonal, and environmental factors.
• Environmental factors (e.g., UV light, infections, smoking) may trigger SLE.
• Damaged cells undergo apoptosis; improper clearance leads to exposure of nuclear material.
• Complement proteins (C1, C2, C3, C4) deficiencies impair apoptotic cell clearance.
• Antigen-presenting cells pick up nuclear materials, leading to immune system sensitization.

Immune Response and Antibody Production

• Antigen-presenting cells activate T-helper cells, primarily T-helper 2, favoring antibody production.
• B cells activate and proliferate into plasma cells, producing autoantibodies towards self-antigens.
• Autoantibodies, such as ANA, target nuclear proteins and form immune complexes.
• Immune complexes cause inflammation and organ damage through complement activation.

Characteristics and Symptoms

• Flare-ups due to immunologic memory and exposure to antigens.
• Symptoms include fatigue, myalgia, weight loss, fever, butterfly rash, sensitivity to light.
• Neurological: cognitive impairment, headaches, seizures.
• Pulmonary: fibrosis, vasculitis, pleuritis.
• Cardiovascular: pericardial disease, myocarditis, hypertension.
• Renal: lupus nephritis leading to potential renal failure.
• Gastrointestinal: non-specific pain, nausea, hepatomegaly.
• Hematological: anemia, leukopenia.
• Musculoskeletal: arthritis, arthralgia, osteoporosis.

Risk Factors and Diagnosis

• More common in women (15-40 years) due to hormonal influence.
• Diagnostic tests: full blood count, kidney function tests, urine tests, serological markers (ANA, anti-dsDNA, etc.).
• Special attention to potential drug-induced lupus.

Management of SLE

• General management: avoid UV exposure, vitamin D/calcium supplements, lifestyle changes (weight loss, smoking cessation).
• Pharmacological treatments:
  • Calcineurin inhibitors (e.g., tacrolimus) suppress T-cell activity.
  • Mycophenolate and azathioprine reduce B/T lymphocyte activity.
  • Belimumab inhibits B-cell survival.
  • Glucocorticoids reduce inflammation.
  • Anti-hypertensives manage blood pressure.

Complications

• Osteoporosis due to low vitamin D, renal impairment, steroid use.
• Antiphospholipid syndrome and increased risk of non-Hodgkin lymphoma.