What is the management approach for Systemic Lupus Erythematosus (SLE)?

Management of Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine is the cornerstone medication for all SLE patients and should be prescribed for every patient with SLE to reduce disease activity, morbidity, and mortality. 1, 2

Disease Assessment and Monitoring

• Use validated tools like SLEDAI-2K to measure disease activity across 9 organ systems 1
• Regular monitoring should include:
  • Complete blood count every 1-3 months during active disease
  • Anti-dsDNA antibodies and complement levels (C3, C4)
  • Serum creatinine, urinalysis, and urine protein/creatinine ratio for renal involvement 1
• Low C3 complement levels are particularly associated with active renal disease and poorer renal survival 1

Treatment Algorithm

First-Line Therapy

• Hydroxychloroquine (200-400 mg daily) for all patients 1, 3, 2
  • Requires baseline and periodic ophthalmologic examinations to screen for retinal toxicity
  • FDA-approved indication for SLE 3
  • Associated with significant reduction in mortality 2

Additional Therapies Based on Disease Manifestations

1. Mild Disease (Constitutional, Mucocutaneous, Musculoskeletal)

   • Glucocorticoids: Low-to-moderate doses (0.25-0.5 mg/kg/day)
   • Target lowest effective dose (≤5 mg/day) for shortest duration 1
   • Consider methotrexate or leflunomide for predominant musculoskeletal manifestations 1

2. Moderate Disease

   • Azathioprine for milder systemic disease 1
   • Mycophenolate mofetil for moderate disease not responding to first-line therapy

3. Severe Disease/Lupus Nephritis

   • Class III/IV lupus nephritis: Methylprednisolone pulses followed by oral prednisone with mycophenolate mofetil or cyclophosphamide 1
   • Class V lupus nephritis: Prednisone with mycophenolate mofetil 1
   • High-risk lupus nephritis: High-dose intravenous cyclophosphamide 1

4. Biologic Therapies for Refractory Disease

   • Belimumab (approved for active SLE and lupus nephritis)
   • Voclosporin (approved for lupus nephritis)
   • Anifrolumab (approved for active SLE) 2

Prevention and Supportive Care

• Cardiovascular Risk Management

  • Blood pressure control (target <130/80 mmHg)
  • Dyslipidemia management 1

• Infection Prevention

  • Screen for HIV, HCV, HBV, and tuberculosis before starting immunosuppressive therapy
  • Administer inactivated vaccines when SLE is inactive, preferably before immunosuppressive therapy
  • Consider recombinant zoster vaccination in patients ≥50 years 1

• Patient Education and Support

  • Photoprotection to prevent flares
  • Aerobic exercise programs to reduce fatigue and depressive symptoms
  • Psychosocial interventions to improve quality of life 1

Special Considerations

• Pregnancy

  • Hydroxychloroquine can be continued during pregnancy
  • Avoid retinoids and thalidomide due to teratogenic effects 1

• Antiphospholipid Antibodies

  • Patients with antiphospholipid antibodies should receive anticoagulation or antiplatelet therapy 1

• Renal Transplantation

  • Consider when lupus activity has been absent or at a low level for at least 3-6 months
  • Superior results with living donor and pre-emptive transplantation 1

Treatment Goals and Monitoring

The primary goal of treatment is to achieve disease remission or low disease activity, defined by minimal symptoms, low levels of autoimmune inflammatory markers, and minimal systemic glucocorticoid requirement 2, 4. This approach reduces disease exacerbations, hospitalizations, and organ damage due to the disease or treatment toxicity.

Common Pitfalls and Caveats

• Overreliance on corticosteroids contributes to long-term organ damage 5
• Hydroxychloroquine non-adherence is associated with increased flares and mortality
• Daily doses exceeding 5 mg/kg of hydroxychloroquine increase the incidence of retinopathy 3
• Up to 45% of patients with lupus nephritis experience renal flares, with risk of doubling serum creatinine at 7.4-8.5% at 5 years 1
• Approximately 40% of people with SLE develop lupus nephritis, and about 10% of these patients develop end-stage kidney disease after 10 years 2

By following this structured approach to SLE management, focusing on disease assessment, appropriate medication selection based on disease severity, and preventive care, clinicians can optimize outcomes for patients with this complex autoimmune disease.