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 3
- Anti-double-stranded DNA (anti-dsDNA) - disease-specific, correlates with activity 1, 2
- Anti-Smith (anti-Sm) - highly specific for SLE 3
- Complement levels (C3, C4) - low levels indicate active disease 1, 2
- Anti-Ro/SSA and anti-La/SSB - associated with neonatal lupus risk 2
- Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) - thrombosis and pregnancy loss risk 2, 3
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
Universal First-Line Treatment
- Hydroxychloroquine 200-400 mg daily (not exceeding 5 mg/kg actual body weight) for all patients 1, 2, 4
- Ophthalmological screening: baseline, after 5 years, then yearly to monitor for retinal toxicity 2, 4
- Photoprotection: strict sun avoidance and comprehensive UV protection measures 2, 4
Glucocorticoid Strategy
- Target maintenance dose: <7.5 mg/day prednisone equivalent 1, 2
- Use the lowest effective dose to minimize long-term complications (osteoporosis, avascular necrosis, infections, cardiovascular disease) 1
- Prompt initiation of immunomodulatory agents expedites glucocorticoid tapering 2
Treatment Algorithm by Disease Severity
Mild to Moderate SLE (No Major Organ Involvement)
- Hydroxychloroquine + low-dose glucocorticoids 1
- For predominant articular and cutaneous manifestations: add methotrexate 1, 2
Moderate to Severe SLE (Major Organ Involvement)
- Mycophenolate mofetil OR low-dose intravenous cyclophosphamide + glucocorticoids 1
- Consider early biologic therapy (belimumab) to control disease activity, prevent flares, and reduce glucocorticoid exposure 5
Organ-Specific Management
Cutaneous Manifestations
First-line approach: topical glucocorticoids (fluocinonide 0.05% cream for localized lesions) + hydroxychloroquine. 2, 4
Second-line options for refractory disease:
- Methotrexate - effective for various cutaneous manifestations 2, 4
- Mycophenolate mofetil - for refractory cutaneous disease 2, 4
- Retinoids (acitretin) - for hyperkeratotic/hypertrophic lesions 2, 4
- Dapsone - particularly effective for bullous lupus and urticarial vasculitis 2, 4
For widespread or severe disease, add short-term systemic glucocorticoids, then taper aggressively 2
Lupus Nephritis
Goal: achieve at least partial remission within 6-12 months. 1
Treatment:
- Mycophenolate mofetil OR cyclophosphamide + glucocorticoids for induction 1
- Belimumab 10 mg/kg IV added to standard therapy significantly increases complete and partial renal response rates at 52 and 104 weeks 6
- Regular monitoring: proteinuria, urinary sediment, renal function 1, 2
- Renal biopsy has independent predictive value for clinical outcome 2
Neuropsychiatric Lupus
- Immunosuppressive therapy based on severity 1
- Anticoagulation if antiphospholipid antibody-mediated 1
Comorbidity Management
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, prompt evaluation, and diligent follow-up 1, 2
- Vaccination according to guidelines (avoid live vaccines during immunosuppression) 1
- Consider interrupting BENLYSTA if new infection develops 6
Bone Health
- Calcium and vitamin D supplementation 1
- Monitor for osteoporosis and avascular necrosis (glucocorticoid-related complications) 1, 2
Thrombosis Prevention
- In patients with antiphospholipid antibodies and prior thrombosis: long-term anticoagulation with oral anticoagulants 2
- Avoid estrogen-containing medications (increase thrombosis risk) 2
Pregnancy Considerations
Pregnancy can increase SLE disease activity, though flares are usually mild. 2
High-Risk Populations
- Lupus nephritis patients - higher preeclampsia risk, require closer monitoring 1, 2
- Antiphospholipid antibody-positive patients - higher risk of pregnancy loss and thrombosis 1, 2
Safe Medications During Pregnancy
Contraindicated Medications During Pregnancy
Disease Monitoring
Regular monitoring using validated disease activity indices (BILAG, SLEDAI) is mandatory. 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 at each visit 1, 2
Critical Pitfalls to Avoid
- Do not delay hydroxychloroquine initiation - it is the cornerstone of therapy for all patients 1, 2
- Avoid chronic high-dose glucocorticoids - target <7.5 mg/day to prevent cumulative organ damage 1, 2
- Screen for depression and suicidality before and during BENLYSTA treatment 6
- Assess for progressive multifocal leukoencephalopathy (PML) if new neurological symptoms develop during immunosuppression 6
- The first five years after diagnosis are crucial for prognosis - aggressive early treatment prevents long-term organ damage 5