Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by the immune system mistakenly attacking the body’s own tissues. It can affect virtually any organ, leading to a broad spectrum of clinical manifestations. In this post, we’ll explore the pathophysiology, clinical presentation, diagnosis, and management of SLE in detail.
What is SLE?
SLE is a type III hypersensitivity autoimmune disorder where immune complexes (antigen-antibody) deposit in tissues and trigger inflammation. The disease affects women more commonly than men, especially during childbearing years, with a 10:1 female to male ratio. The term “lupus” originates from the Latin word for wolf due to the classic facial rash that mimics a wolf bite.
Etiology: Why Does SLE Happen?
1. Genetic Factors
- HLA-DR2, HLA-DR3
- Complement deficiencies (C1q, C4, C2)
2. Environmental Triggers
- UV light exposure
- Smoking
- EBV infection
- Silica dust
3. Hormonal Influence
- Estrogen: Explains female predominance.
4. Drugs
- Hydralazine, Procainamide, Isoniazid (Drug-induced lupus)
Pathophysiology of SLE
When environmental triggers damage cells in genetically susceptible individuals, nuclear antigens (DNA, histones) are released. These act as autoantigens, leading to the production of autoantibodies.
- Immune complexes form and deposit in tissues.
- Complement system is activated → inflammation.
- Complement deficiency → impaired clearance of immune complexes → persistent inflammation.
Clinical Features of SLE
SLE is known for its relapsing-remitting course and systemic involvement:
✅ Constitutional:
- Fatigue, fever, weight loss
✅ Musculoskeletal:
- Symmetrical non-erosive arthritis (MCP & PIP joints)
✅ Dermatologic:
- Malar rash (butterfly rash): Spares nasolabial folds
- Discoid rash: Leaves scars
- Photosensitivity
- Alopecia (non-scarring)
- Painless oral ulcers
- Raynaud’s phenomenon
- Periungual telangiectasias
✅ Hematologic:
- Anemia, leukopenia, thrombocytopenia
✅ Renal:
- Lupus nephritis (proteinuria, hematuria)
✅ Cardiopulmonary:
- Pleuritis, pericarditis, myocarditis
- Libman-Sacks endocarditis
- Pulmonary hypertension
✅ Neurologic:
- Seizures, psychosis, cognitive dysfunction (lupus cerebritis)
Diagnosis of SLE
🔬 Initial Screening:
- ANA (Anti-nuclear antibody): Most sensitive (98%)
🔬 Specific Antibodies:
- Anti-dsDNA: Correlates with disease activity & nephritis
- Anti-Smith (Sm): Most specific
🔬 Other Investigations:
- Complement levels (↓ C3, C4)
- ESR ↑, CRP (less specific)
- Urinalysis (proteinuria, hematuria)
- CBC (cytopenias)
🔬 False-Positive VDRL/RPR
Due to antiphospholipid antibodies
🔬 Antiphospholipid Syndrome Workup:
- Anti-cardiolipin
- Anti-β2 glycoprotein
- Lupus anticoagulant
🩺 Classification Criteria:
2019 EULAR/ACR: Point-based system; ANA positivity (≥1:80) is mandatory; ≥10 points confirms SLE.
Treatment Strategy
🧴 General Measures
- Sun protection (SPF ≥50)
- Smoking cessation
- Aerobic exercise
- Regular cardiovascular risk assessment
🧾 Drug Overview
| Severity | First-line | Add-ons |
|---|---|---|
| Mild | Hydroxychloroquine | NSAIDs ± low-dose steroids |
| Moderate | Hydroxychloroquine + Oral Steroids | Immunosuppressants (e.g. Methotrexate, Mycophenolate) |
| Severe | IV Steroids (Methylprednisolone) | Maintenance: Hydroxychloroquine + Immunosuppressants (e.g. Cyclophosphamide) |
💡 Key Notes:
- Hydroxychloroquine is the cornerstone of long-term therapy.
- Biologics (e.g., belimumab, rituximab) for refractory cases.
- Always rule out latent TB before initiating immunosuppressive treatment.
- Eye screening needed after 5 years on hydroxychloroquine.
Special Scenarios
🔶 Lupus Nephritis:
- Biopsy for diagnosis
- High-dose IV steroids + Mycophenolate/Cyclophosphamide
🔶 Neonatal Lupus:
- Caused by maternal anti-Ro/La (SSA/SSB) antibodies
- Associated with congenital heart block
🔶 Drug-Induced Lupus:
- Associated with anti-histone antibodies
- Reversible upon stopping the offending agent
Summary Mnemonic – “SOAP BRAIN MD”
| Letter | Manifestation |
|---|---|
| S | Serositis |
| O | Oral ulcers |
| A | Arthritis |
| P | Photosensitivity |
| B | Blood disorders |
| R | Renal |
| A | ANA |
| I | Immunologic |
| N | Neurologic |
| M | Malar rash |
| D | Discoid rash |
Conclusion
Systemic Lupus Erythematosus is a complex, systemic autoimmune condition with multi-organ involvement. Prompt recognition of symptoms, accurate diagnostic testing, and early initiation of tailored treatment are essential to improve prognosis and quality of life.
