What are the diagnosis and management approaches for Systemic Lupus Erythematosus (SLE)?

Diagnosis and Management of Systemic Lupus Erythematosus (SLE)

Diagnosis

SLE diagnosis should be based on a combination of characteristic clinical findings and serological abnormalities, with particular attention to multi-organ involvement patterns that affect mortality and quality of life. 1, 2

Key Diagnostic Elements:

• Clinical manifestations to evaluate include:

  • Skin lesions (discoid lesions, malar rash)
  • Arthritis
  • Serositis (pleuritis, pericarditis)
  • Neurological manifestations (seizures, psychosis)
  • Renal involvement 3

• Laboratory tests essential for diagnosis:

  • Complete blood count (anemia, thrombocytopenia)
  • Renal function (serum creatinine, proteinuria, urinary sediment)
  • Immunological markers (anti-dsDNA, anti-C1q, anti-Ro/SSA, anti-La/SSB, antiphospholipid antibodies, anti-RNP, serum complement C3/C4) 3, 1

• Confirmatory testing for specific organ involvement:

  • Brain MRI for neuropsychiatric manifestations
  • Renal biopsy for lupus nephritis 3

Management Approach

Foundation of Treatment:

• Hydroxychloroquine should be prescribed for all SLE patients unless contraindicated, as it reduces flares, increases remission rates, and reduces organ damage even in lupus nephritis. 1, 4

  • Dose should not exceed 5 mg/kg real body weight
  • Regular ophthalmological screening (baseline, after 5 years, then yearly) 1

• Glucocorticoids:

  • Use at lowest effective dose (target <7.5 mg/day prednisone equivalent for maintenance)
  • Aim for rapid tapering and eventual withdrawal when possible
  • Short-term systemic glucocorticoids for flares 3, 1, 4

Treatment Algorithm by Disease Severity:

1. Mild to moderate SLE without major organ involvement:

   • Hydroxychloroquine as baseline therapy
   • Low-dose glucocorticoids for symptom control
   • Methotrexate for predominant articular and cutaneous manifestations 1, 4

2. Moderate to severe SLE with major organ involvement:

   • Mycophenolate mofetil or low-dose intravenous cyclophosphamide combined with glucocorticoids
   • Consider mycophenolate mofetil/calcineurin inhibitor combination for nephrotic-range proteinuria 2, 4

3. Refractory disease:

   • Belimumab for patients with persistently active disease despite standard therapy
   • Rituximab may be considered for cases unresponsive to standard therapies 1, 5

Specific Organ Manifestations:

• Cutaneous manifestations:

  • First-line: Topical glucocorticoids and hydroxychloroquine
  • Second-line: Methotrexate, retinoids (for hyperkeratotic lesions), dapsone (for bullous lupus) 1

• Lupus nephritis:

  • Goal: Achieve at least partial remission (≥50% reduction in proteinuria to subnephrotic levels with serum creatinine within 10% of baseline) within 6-12 months
  • Treatment with mycophenolate mofetil or cyclophosphamide plus glucocorticoids 2, 5

• Neuropsychiatric lupus:

  • Immunosuppressive therapy for inflammatory manifestations
  • Anticoagulation for thrombotic events 3, 2

Management of Comorbidities:

• Cardiovascular risk:

  • Regular assessment and management of atherosclerosis risk factors
  • Consider low-dose aspirin for primary prevention in patients with antiphospholipid antibodies 3, 1, 4

• Infection risk:

  • High index of suspicion for infections
  • Prompt evaluation and diligent follow-up
  • Vaccination according to guidelines (avoid live vaccines during immunosuppression) 3, 1

• Bone health:

  • Monitor and prevent osteoporosis and avascular necrosis
  • Calcium, vitamin D supplementation as needed 1, 4

Pregnancy Considerations:

• Pregnancy can increase SLE disease activity, though flares are usually mild
• Patients with lupus nephritis and antiphospholipid antibodies have higher risk of preeclampsia
• Safe medications during pregnancy include prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin
• Avoid mycophenolate mofetil, cyclophosphamide, and methotrexate 1, 2

Monitoring

• Regular monitoring of disease activity using validated indices (BILAG, ECLAM, or SLEDAI)
• Monitor clinical manifestations, laboratory tests, and immunological markers
• For lupus nephritis: Regular assessment of proteinuria, urinary sediment, and renal function 1, 2, 4

Common Pitfalls and Caveats

• Delayed diagnosis due to heterogeneous presentation - maintain high index of suspicion for multi-system symptoms in young women 6
• Discontinuation of hydroxychloroquine - should be maintained long-term in all patients unless contraindicated 1, 4
• Overuse of glucocorticoids - aim for lowest effective dose and rapid tapering 1, 4
• Undertreatment of comorbidities - cardiovascular disease and infections are major causes of mortality 3, 6
• Inadequate monitoring during pregnancy - requires close surveillance, especially with history of lupus nephritis or antiphospholipid antibodies 1, 2