What are the diagnostic criteria and treatment options for systemic lupus erythematosus (SLE)?

Diagnosing and Managing Systemic Lupus Erythematosus (SLE)

The diagnosis of SLE requires documentation of multisystem involvement and the presence of antinuclear antibodies, with treatment centered on hydroxychloroquine as cornerstone therapy for all patients. 1, 2

Diagnostic Criteria for SLE

The 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology classification criteria are the most current standard for SLE diagnosis, with 96.1% sensitivity and 93.4% specificity 3. These include:

Clinical Manifestations

• Mucocutaneous: Lupus-specific rashes, photosensitivity, oral/nasal ulcers, alopecia, discoid lesions 1, 4
• Musculoskeletal: Joint pain with inflammatory features, symmetric arthritis 1, 5
• Hematologic: Anemia, leukopenia, lymphopenia, thrombocytopenia 1
• Cardiovascular: Pericarditis, myocarditis, Libman-Sacks endocarditis 1
• Neuropsychiatric: Headaches, cognitive dysfunction, seizures, psychosis, peripheral neuropathy 1
• Renal: Proteinuria (indicating possible lupus nephritis) 3
• Constitutional: Fever, fatigue 4, 3

Laboratory Findings

• Positive ANA: Present in nearly all SLE cases but not specific; requires clinical context 2, 5
• SLE-specific autoantibodies: Anti-dsDNA, anti-Sm 1, 3
• Complement levels: Low C3, C4 1, 3
• Antiphospholipid antibodies: Associated with increased thrombotic risk 1, 4

Important: ANA testing should be reserved for patients with unexplained multisystem inflammatory disease, not for nonspecific symptoms like fatigue alone 5

Treatment Approach for SLE

First-Line Therapy

• Hydroxychloroquine (200-400 mg daily, not exceeding 5 mg/kg/day) for all SLE patients 1, 3
  • Requires baseline and periodic ophthalmologic examinations
  • Can be continued during pregnancy
  • Associated with significant reduction in mortality 3

Additional Therapies Based on Disease Severity

For Moderate to Severe Disease:

• Immunosuppressive agents:
  • Azathioprine
  • Mycophenolate mofetil
  • Cyclophosphamide (for severe manifestations) 3

For Lupus Nephritis:

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

Recently FDA-Approved Biologics:

• Belimumab: For active SLE and lupus nephritis
• Anifrolumab: For active SLE
• Voclosporin: For lupus nephritis 3

For Refractory Disease:

• Rituximab: Particularly effective for hematologic manifestations
• Extended course IV cyclophosphamide: For severe refractory disease 1

Special Considerations

Antiphospholipid Antibody Positive Patients:

• Require anticoagulation or antiplatelet therapy
• Anticoagulation may be superior for secondary prevention of arterial events 1

Monitoring Requirements:

• Active disease: Every 1-3 months
• Stable disease: Every 6-12 months
• Parameters to monitor: Renal function, proteinuria, complete blood count, complement levels, anti-DNA antibodies 1

Preventive Measures:

• Osteoporosis prophylaxis with calcium and vitamin D
• Sun protection and UV light avoidance
• Cardiovascular risk management:
  • Blood pressure target <130/80 mmHg
  • LDL target <100 mg/dl 1

Treatment Goals

The primary goals of SLE management are:

1. Achieve remission or low disease activity
2. Prevent organ damage
3. Optimize quality of life 1, 4, 3

Caution: Despite advances in treatment, SLE mortality remains unacceptably high, and access to newer expensive medications may be restricted in different regions 4