Investigations and Management of Systemic Lupus Erythematosus (SLE)
Diagnostic Investigations
Diagnose SLE using a combination of characteristic clinical findings and serological abnormalities, focusing on multi-organ involvement patterns that directly impact mortality and quality of life. 1
Essential Clinical Manifestations to Evaluate
- Skin lesions (malar rash, discoid lesions, photosensitivity) 1
- Arthritis (non-erosive, involving two or more peripheral joints) 1
- Serositis (pleuritis, pericarditis) 1
- Neurological manifestations (seizures, psychosis, peripheral neuropathy) 1
Required Laboratory Tests
- Complete blood count (assess for cytopenias: leukopenia, lymphopenia, thrombocytopenia, hemolytic anemia) 1
- Renal function (serum creatinine, eGFR) 1
- Urinalysis (proteinuria, urinary sediment with cellular casts) 1, 2
Immunological Markers
- Anti-nuclear antibody (ANA) - screening test 1
- Anti-double-stranded DNA (anti-dsDNA) - disease-specific 1, 2
- Anti-Smith (anti-Sm) - highly specific 3
- Complement levels (C3, C4) - assess disease activity 1, 2
- Anti-Ro/SSA and anti-La/SSB - important for pregnancy planning 2
- Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) - assess thrombosis risk 2, 3
Specialized Testing
- Renal biopsy for lupus nephritis (has independent predictive value for clinical outcome) 2
Management Approach
All SLE patients should receive hydroxychloroquine unless contraindicated, as it reduces flares, increases remission rates, and reduces organ damage even in lupus nephritis. 1, 2
First-Line Universal Treatment
Hydroxychloroquine (Cornerstone of Therapy)
- Dose: 200-400 mg daily, not exceeding 5 mg/kg actual body weight 1, 2, 4
- Monitoring: Ophthalmological screening at baseline, after 5 years, then yearly thereafter to detect retinal toxicity 2, 4
- Rationale: Reduces disease activity, prevents flares, and is safe during pregnancy 1, 2
Photoprotection
Treatment Algorithm by Disease Severity
Mild to Moderate SLE (No Major Organ Involvement)
- Hydroxychloroquine 200-400 mg daily 1
- Low-dose glucocorticoids (prednisone ≤7.5 mg/day for maintenance) 1
- Topical glucocorticoids for localized cutaneous manifestations 1, 2
Moderate to Severe SLE (Major Organ Involvement)
For Lupus Nephritis
- Induction therapy: Mycophenolate mofetil OR low-dose intravenous cyclophosphamide PLUS glucocorticoids 1
- Goal: Achieve at least partial remission within 6-12 months 1
- Belimumab 10 mg/kg IV on Days 0,14,28, then every 28 days (FDA-approved for lupus nephritis; 43% achieved primary efficacy renal response at Week 104 vs 32% placebo) 5
- Monitoring: Regular assessment of proteinuria, urinary sediment, and renal function 1
For Cutaneous Manifestations
- First-line: Topical glucocorticoids + hydroxychloroquine 2, 4
- Second-line (refractory): Methotrexate (effective for various cutaneous manifestations) 1, 2, 4
- Third-line: Mycophenolate mofetil for refractory cutaneous disease 2, 4
- Specialized options: Dapsone for bullous lupus/urticarial vasculitis; retinoids for hyperkeratotic lesions 2, 4
For Neuropsychiatric Lupus
- Immunosuppressive therapy and anticoagulation may be necessary 1
Glucocorticoid Management Strategy
Minimize glucocorticoids to less than 7.5 mg/day prednisone equivalent for chronic maintenance and withdraw when possible. 1, 2
- For widespread/severe disease: Short-term systemic glucocorticoids to expedite control 2
- Steroid-sparing approach: Prompt initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate mofetil) expedites glucocorticoid tapering 2
Biologic Therapy
Belimumab (BENLYSTA)
For active SLE despite standard therapy:
- IV dosing: 10 mg/kg at 2-week intervals for first 3 doses, then every 4 weeks 5
- Subcutaneous dosing (adults): 200 mg once weekly 5
- Efficacy: 49% achieved SLE Responder Index vs 42% placebo 5
- Consider prophylactic premedication for infusion reactions 5
For lupus nephritis:
- IV dosing: 10 mg/kg on Days 0,14,28, then every 28 days 5
- Subcutaneous dosing: 400 mg (two 200-mg injections) once weekly for 4 doses, then 200 mg once weekly 5
Monitoring Disease Activity
Perform regular monitoring using validated activity indices (BILAG, ECLAM, or SLEDAI) to detect flares and assess treatment response. 1, 2
Monitoring Frequency
Parameters to Monitor
- Clinical manifestations (skin lesions, arthritis, serositis, neurological symptoms) 1, 2
- Laboratory tests (CBC, renal function, complement levels, anti-dsDNA) 1, 2, 4
- For lupus nephritis: Proteinuria, urinary sediment, renal function 1, 2
Management of Comorbidities
Cardiovascular Disease Prevention
- Regular assessment of atherosclerosis risk factors (hypertension, dyslipidemia, diabetes) 1, 2
- Low-dose aspirin for primary prevention in patients with antiphospholipid antibodies 1, 2
Infection Prevention
- High index of suspicion for infections due to immunosuppression 1, 2, 5
- Vaccination according to guidelines (avoid live vaccines during BENLYSTA treatment) 1, 5
- Consider interrupting BENLYSTA if new infection develops 5
Bone Health
- Calcium and vitamin D supplementation 1
- Monitoring and prevention of osteoporosis and avascular necrosis 1
Thrombosis Prevention (Antiphospholipid Antibody Positive)
- Primary prevention: Low-dose aspirin 1, 2
- Secondary prevention: Long-term oral anticoagulation 2
- Avoid estrogen-containing medications (increases thrombosis risk) 2
Pregnancy Considerations
Pregnancy can increase SLE disease activity, though flares are usually mild. 2
Safe Medications During Pregnancy
Contraindicated During Pregnancy
High-Risk Pregnancies
- Patients with lupus nephritis and antiphospholipid antibodies have higher risk of preeclampsia and require closer monitoring 1, 2
- Mothers with anti-Ro and/or anti-La antibodies can affect the fetus (neonatal lupus, congenital heart block) 2
Critical Pitfalls to Avoid
Depression and Suicidality
- Assess for depression and suicide risk before initiating BENLYSTA 5
- Monitor during treatment and instruct patients to report new/worsening depression or suicidal thoughts 5
Progressive Multifocal Leukoencephalopathy (PML)
- Evaluate patients with new neurological symptoms for PML 5
- Suspend BENLYSTA if PML suspected until excluded; discontinue if confirmed 5