What is Systemic Lupus Erythematosus (SLE)?

Systemic Lupus Erythematosus (SLE): Definition and Management

Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease characterized by immune complex deposition and vasculopathy that can affect any organ system, with manifestations ranging from skin rashes and joint pain to severe organ damage and increased mortality. 1, 2

Pathophysiology and Epidemiology

SLE results from a complex interplay between:

• Genetic susceptibility and environmental factors
• Dysregulation of both innate and adaptive immune systems
• Type-1 interferon dysregulation as a common denominator 1
• Autoantibody production, particularly against nuclear antigens 2

Key epidemiological features:

• Prevalence: 20-150 cases per 100,000 population 1
• More common in women (approximately 90% of cases) 3
• Higher disease severity and earlier onset in Latin American, African descendants, and Native Americans 1

Clinical Manifestations

SLE can affect virtually any organ system:

1. Mucocutaneous:

   • Lupus-specific rashes
   • Oral ulcers
   • Alopecia
   • Photosensitivity

2. Musculoskeletal:

   • Arthritis/arthralgia
   • Myalgia
   • Myositis

3. Renal:

   • Lupus nephritis (affects ~40% of patients) 3
   • Can progress to end-stage kidney disease

4. Cardiovascular:

   • Pericarditis
   • Myocarditis
   • Accelerated atherosclerosis

5. Pulmonary:

   • Pleural effusion (most common)
   • Interstitial lung disease (1-15% of patients) 1
   • Pneumonitis

6. Neuropsychiatric:

   • Seizures
   • Psychosis
   • Cognitive dysfunction

7. Hematologic:

   • Cytopenias
   • Leukopenia
   • Thrombocytopenia

8. Constitutional:

   • Fatigue
   • Fever
   • Weight loss

Diagnosis

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

• Clinical criteria: Fever, cytopenia, rash, arthritis, proteinuria
• Immunologic criteria: SLE-specific autoantibodies (anti-dsDNA, anti-Sm), low complement levels

Anti-dsDNA antibodies are particularly important for diagnosis and monitoring disease activity, though they lack standardization and can be found in other disorders 1.

Treatment Approach

Overarching Principles

1. All SLE patients should receive antimalarials (hydroxychloroquine) unless contraindicated 1, 3
2. Glucocorticoids should be used at the lowest possible dose for the shortest time 1
3. Treatment goal is to achieve remission or low disease activity as soon as possible 1, 2
4. Preventive care should include photoprotection, osteoporosis prevention, cardiovascular risk management, and infection prevention 1

Medication Options

First-Line:

• Hydroxychloroquine (200-400 mg daily): Cornerstone medication for all SLE patients; reduces mortality, disease activity, and flares 4, 3
  • Requires baseline and periodic ophthalmologic examinations

Second-Line (Based on Organ Involvement):

• Glucocorticoids: Initial dosing 0.25-0.5 mg/kg/day for musculoskeletal manifestations, targeting ≤5 mg/day maintenance 4

• Immunosuppressants:

  • Azathioprine (1-2.5 mg/kg daily): Effective for cutaneous lupus 4
  • Mycophenolate mofetil (0.5-1 g twice daily): Better tolerated than azathioprine in some patients 4
  • Methotrexate (5-15 mg weekly): Preferred for predominant musculoskeletal manifestations 4

For Lupus Nephritis:

• Class III/IV: Methylprednisolone pulses followed by oral prednisone with mycophenolate mofetil or cyclophosphamide 4
• Class V: Prednisone with mycophenolate mofetil 4
• High-risk: High-dose intravenous cyclophosphamide 4

Biologics and Newer Therapies:

• Belimumab: FDA-approved for active SLE and lupus nephritis in adults and children ≥5 years 5, 3
  • Contraindicated during active infections
  • Live vaccines should not be administered during treatment 5
• Anifrolumab: FDA-approved for active SLE 2, 3
• Voclosporin: FDA-approved for lupus nephritis 2, 3
• Rituximab: Considered for refractory cases 4

Monitoring

• Disease activity: SLEDAI-2K tool (scores 0-105, higher scores indicate greater activity) 4
• Laboratory monitoring:
  • Complete blood count every 1-3 months during active disease
  • Anti-dsDNA antibodies and complement levels
  • Renal function tests and urinalysis for kidney involvement 4
• Treatment response:
  • Complete response: proteinuria <0.5 g/g with stable/improved kidney function
  • Partial response: ≥50% reduction in proteinuria to <3 g/g with stable kidney function 4

Non-Pharmacological Interventions

• Physical therapy and exercise: Improves physical function and reduces pain 4
• Patient education and self-management support: Improves quality of life 4
• Psychosocial interventions: Reduces anxiety and depression 4
• Photoprotection: Prevents disease flares 4

Special Considerations

Infections

• Leading cause of morbidity and mortality (25-50% of overall mortality) 1
• Pneumococcal vaccination recommended for all SLE patients 1
• Higher risk of pneumococcal infection (13 times higher than general population) 1

Pregnancy

• Hydroxychloroquine can be continued during pregnancy 4
• Pregnancy registry available for women exposed to belimumab 5
• Retinoids and thalidomide should be avoided due to teratogenicity 4

Comorbidities

• Cardiovascular disease: Monitor and manage risk factors; target BP <130/80 mmHg 4
• Osteoporosis: Implement prevention strategies, especially with glucocorticoid use 1
• Mental health: Monitor for depression and anxiety 4

SLE remains a complex disease requiring vigilant monitoring and personalized treatment approaches to minimize organ damage and improve quality of life.