---
TOPIC 2: SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
Introduction
Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune connective tissue
disease characterized by the production of a wide variety of autoantibodies directed against
nuclear, cytoplasmic, and cell surface antigens, leading to immune complex deposition and
inflammation in multiple organs. It follows a relapsing–remitting course and can range from mild
mucocutaneous involvement to life-threatening renal, neurological, or hematological disease.
SLE predominantly affects young women of childbearing age, with a striking female-to-male
ratio of approximately 9:1, highlighting the role of hormonal influences in disease pathogenesis.
The disease shows wide clinical heterogeneity, making diagnosis challenging and requiring a
high index of suspicion.
---
Epidemiology
Prevalence: 20–150 per 100,000 population
Female predominance (especially during reproductive years)
More common and severe in:
Asians
Africans
Hispanics
Onset usually between 15–45 years
Childhood-onset SLE tends to be more severe
---
Etiology
The etiology of SLE is multifactorial, involving a complex interaction between genetic
predisposition, environmental triggers, hormonal influences, and immune dysregulation.
1. Genetic Factors
Strong familial association
Increased concordance in monozygotic twins
Associated genes:
HLA-DR2, HLA-DR3
Complement deficiencies (C1q, C2, C4)
Genetic predisposition leads to defective immune tolerance
2. Environmental Factors
Ultraviolet (UV) light exposure
Viral infections (e.g., Epstein–Barr virus)
Drugs:
Hydralazine
Procainamide
Isoniazid
Smoking
3. Hormonal Factors
Female predominance suggests estrogen involvement
Disease flares during pregnancy or postpartum period
---
Pathogenesis
SLE results from loss of self-tolerance, leading to autoantibody production and immune
complex-mediated tissue damage.
Defective Immune Regulation
Impaired clearance of apoptotic cells
Increased exposure of nuclear antigens
Activation of autoreactive B and T cells
Autoantibody Production
Anti-dsDNA
Anti-Smith (anti-Sm)
Anti-phospholipid antibodies
Immune Complex Deposition
Circulating immune complexes deposit in:
Kidneys
Skin
Joints
Blood vessels
Complement activation leads to inflammation and tissue injury
---
Pathology
General Pathological Features
Immune complex deposition
Vasculitis
Chronic inflammation
Renal Pathology (Lupus Nephritis)
Most serious manifestation
Classified by ISN/RPS classification:
Class I: Minimal mesangial
Class II: Mesangial proliferative
Class III: Focal lupus nephritis
Class IV: Diffuse lupus nephritis (most severe)
Class V: Membranous
Class VI: Advanced sclerosing
---
Clinical Features
SLE is often described as a disease with “100 faces” due to its diverse manifestations.
General Symptoms
Fatigue
Fever
Weight loss
Malaise
---
Musculoskeletal System
Symmetrical polyarthritis
Non-erosive arthritis
Commonly involves small joints
Jaccoud’s arthropathy (reducible deformities)
---
Cutaneous Manifestations
Malar Rash
Butterfly-shaped rash
Spares nasolabial folds
Photosensitive
Discoid Rash
Chronic scarring lesions
Common on scalp and face
Photosensitivity
Exacerbation of rash after sun exposure
Oral Ulcers
Painless
Common on hard palate
---
Renal Manifestations
Proteinuria
Hematuria
Red cell casts
Hypertension
Nephrotic syndrome in severe cases
---
Hematological Manifestations
Anemia:
Anemia of chronic disease
Autoimmune hemolytic anemia
Leukopenia
Lymphopenia
Thrombocytopenia
---
Neurological Manifestations
Seizures
Psychosis
Cognitive dysfunction
Peripheral neuropathy
Stroke (often due to antiphospholipid syndrome)
---
Cardiovascular Manifestations
Pericarditis (most common)
Myocarditis
Libman–Sacks endocarditis
Accelerated atherosclerosis
---
Pulmonary Manifestations
Pleuritis
Pleural effusion
Interstitial lung disease
Pulmonary hypertension
---
Gastrointestinal Manifestations
Mesenteric vasculitis
Hepatitis
Pancreatitis (rare)
---
Investigations
Laboratory Investigations
Autoantibodies
Antinuclear Antibody (ANA)
Highly sensitive (>95%)
Not specific
Anti-dsDNA
High specificity
Correlates with disease activity
Associated with lupus nephritis
Anti-Smith (Anti-Sm)
Highly specific
Low sensitivity
Anti-Phospholipid Antibodies
Lupus anticoagulant
Anti-cardiolipin
Associated with thrombosis and pregnancy loss
---
Complement Levels
Low C3 and C4 during active disease
Useful for monitoring disease activity
---
Other Laboratory Findings
Elevated ESR
Normal or mildly raised CRP
Urinalysis abnormalities
Direct Coombs test positivity
---
Diagnostic Criteria
2019 EULAR/ACR Classification Criteria
Entry criterion: Positive ANA
Weighted scoring system including:
Clinical domains
Immunological domains
Score ≥10 confirms classification as SLE
---
Differential Diagnosis
Rheumatoid arthritis
Dermatomyositis
Systemic sclerosis
Mixed connective tissue disease
Drug-induced lupus
Antiphospholipid syndrome
---
Management
General Principles
Individualized treatment
Control disease activity
Prevent organ damage
Manage comorbidities
---
Non-Pharmacological Management
Sun protection
Patient education
Regular monitoring
Vaccinations (non-live)
---
Pharmacological Management
1. NSAIDs
For mild musculoskeletal symptoms
Use with caution due to renal involvement
---
2. Antimalarials
Hydroxychloroquine is cornerstone therapy
Reduces flares
Improves survival
Retinal toxicity (regular eye exams required)
---
3. Corticosteroids
Used for moderate to severe disease
Oral or intravenous (methylprednisolone pulses)
Long-term side effects limit prolonged use
---
4. Immunosuppressive Drugs
Used in severe organ involvement.
Azathioprine
Mycophenolate mofetil
Cyclophosphamide (especially lupus nephritis)
Methotrexate (for arthritis)
---
5. Biological Therapy
Belimumab (anti-BAFF antibody)
Rituximab (off-label)
---
Lupus Nephritis Management
Renal biopsy guides treatment
Induction therapy:
High-dose steroids
Cyclophosphamide or mycophenolate
Maintenance therapy:
Azathioprine or mycophenolate
---
Complications
Chronic kidney disease
Cardiovascular disease
Infections
Osteoporosis
Pregnancy complications
---
Prognosis
10-year survival >90% with modern therapy
Poor prognostic factors:
Renal involvement
CNS disease
High anti-dsDNA titers
Low complement levels
---
Conclusion
Systemic lupus erythematosus is a complex autoimmune disease with diverse clinical
manifestations and variable prognosis. Early diagnosis, regular monitoring, and a
multidisciplinary approach are essential for optimal management. Advances in immunology and
targeted therapies have significantly improved survival and quality of life for patients with SLE.
---