Systemic Lupus Erythematosus Management

Foundation Therapy - Universal for All SLE Patients

Hydroxychloroquine is the cornerstone of SLE treatment and should be prescribed to all patients unless contraindicated, as it reduces disease activity, prevents flares, and improves survival. 1, 2, 3

Dosing: Maximum 5 mg/kg of actual body weight daily (typically 200-400 mg daily) to minimize retinal toxicity risk 1, 2, 3
Ophthalmologic monitoring: Baseline examination, repeat after 5 years, then yearly thereafter 1, 2
Administration: Take with food or milk; do not crush or divide tablets 3

Additional Universal Measures

Photoprotection: Sunscreen use is mandatory to prevent cutaneous flares 1, 2
Low-dose aspirin: For patients with antiphospholipid antibodies, those receiving corticosteroids, or those with cardiovascular risk factors 1, 2
Calcium and vitamin D supplementation: Required for all patients on long-term glucocorticoids 1, 2

Glucocorticoid Strategy - Minimize and Withdraw

The goal is to use glucocorticoids at the lowest effective dose for the shortest duration, targeting chronic maintenance below 7.5 mg/day prednisone equivalent and complete withdrawal when possible. 1, 2

Acute Flare Management

Intravenous methylprednisolone pulses provide immediate therapeutic effect and enable lower starting oral doses 1, 2
Initial oral dosing: 0.5-1 mg/kg/day prednisone depending on severity, followed by aggressive tapering 2

Chronic Maintenance

Target: Less than 7.5 mg/day prednisone equivalent 1, 2
Ultimate goal: Complete withdrawal to prevent organ damage 1, 2

Immunosuppressive Therapy - When to Add

Add immunomodulating/immunosuppressive agents when patients fail to respond to hydroxychloroquine alone or in combination with glucocorticoids, or when glucocorticoids cannot be reduced below acceptable chronic doses. 1

Agent Selection by Manifestation

Methotrexate: Skin and joint manifestations 1, 2
Azathioprine: Maintenance therapy, particularly suitable for women contemplating pregnancy 1, 2
Mycophenolate mofetil: Renal and non-renal manifestations (except neuropsychiatric disease) 1, 2
Cyclophosphamide: Severe organ-threatening disease (especially renal, cardiopulmonary, or neuropsychiatric) 1, 2

Organ-Specific Treatment Algorithms

Lupus Nephritis

Kidney biopsy is mandatory before initiating therapy to guide treatment selection. 1, 2

Induction Therapy

First-line options: Mycophenolate mofetil OR low-dose cyclophosphamide 1, 2
Low-dose cyclophosphamide is preferred over high-dose due to comparable efficacy and lower gonadotoxicity 1
Target: At least partial remission within 6-12 months 2

Maintenance Therapy

Options: Mycophenolate mofetil OR azathioprine 1, 2

Neuropsychiatric Lupus (NPSLE)

Treatment depends on the underlying pathophysiological mechanism - inflammatory versus thrombotic. 1, 2

Inflammatory/Immune-Mediated Mechanisms

High-dose intravenous methylprednisolone PLUS cyclophosphamide 1, 2
Evidence: Response rate of 18/19 patients versus 7/13 with methylprednisolone alone (p=0.03) 1

Thrombotic/Embolic Mechanisms

Anticoagulation with warfarin 1, 2
Target INR: 2.0-3.0 for first venous thrombosis; 3.0-4.0 for arterial or recurrent thrombosis 1

Combined Mechanisms

Use both immunosuppressive and anticoagulant/antithrombotic therapy 1

Hematological Manifestations (Significant Thrombocytopenia)

Initial therapy: Pulse intravenous methylprednisolone 1, 2
Followed by: Moderate/high-dose glucocorticoids combined with immunosuppressive agents (azathioprine, mycophenolate mofetil, or cyclosporine) 1, 2
IVIG: Consider in acute phase or with inadequate response to glucocorticoids 1
Refractory cases: Rituximab or cyclophosphamide 1, 2

Cutaneous Manifestations (Including Discoid Lupus)

First-line: Potent topical corticosteroids (e.g., fluocinonide 0.05% cream) PLUS hydroxychloroquine 200-400 mg daily 4
Strict photoprotection is mandatory 4
Second-line for refractory disease: Methotrexate, mycophenolate mofetil, retinoids (acitretin), or dapsone (particularly for bullous lupus) 4

Biologic Therapies for Refractory Disease

Consider biologics when patients have inadequate response to standard therapy. 1, 2

FDA-Approved Biologics

Belimumab (anti-BAFF antibody): Approved for active extrarenal SLE (patients ≥5 years old receiving standard therapy) and active lupus nephritis 1, 5
- IV dosing: 10 mg/kg at 2-week intervals for first 3 doses, then every 4 weeks 5
- SC dosing for adults with SLE: 200 mg once weekly 5
- SC dosing for lupus nephritis: 400 mg (two 200-mg injections) once weekly for 4 doses, then 200 mg once weekly 5
Anifrolumab (anti-type 1 interferon receptor): Approved for moderate-to-severe extrarenal SLE 1, 2
Voclosporin: Approved for lupus nephritis 1, 2
Rituximab: May be considered for refractory cases, particularly hematological manifestations 1, 2

Monitoring and Comorbidity Prevention

SLE patients have a 5-fold increased mortality risk, requiring aggressive screening and prevention strategies. 1, 2

Disease Activity Monitoring

Use validated activity indices at each visit (BILAG or SLEDAI) 1, 2, 4
Laboratory monitoring: Anti-dsDNA, C3, C4, complete blood count, creatinine, proteinuria, and urine sediment 1, 2, 4
Frequency when inactive: Every 6-12 months 4
Frequency during active disease or medication adjustments: More frequent 4

Comorbidity Screening

Infections: Maintain high index of suspicion as immunosuppression increases risk 1, 2, 4
Cardiovascular disease, hypertension, diabetes, dyslipidemia: Screen aggressively 1, 2
Osteoporosis and avascular necrosis: Monitor in patients on chronic glucocorticoids 2
Malignancies: Particularly non-Hodgkin lymphoma 1

Pregnancy Considerations

Safe medications during pregnancy: Prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin 1, 2, 4

Contraindicated medications: Mycophenolate mofetil, cyclophosphamide, methotrexate, and thalidomide 2, 4

Critical Pitfalls to Avoid

NSAIDs: Use judiciously for limited periods only in patients at low risk for complications 2
Failure to perform kidney biopsy: Leads to suboptimal therapy selection for lupus nephritis 2
Exceeding hydroxychloroquine dose of 5 mg/kg actual body weight: Increases retinal toxicity risk 1, 2
Prolonged high-dose glucocorticoid use: Causes organ damage; aggressive tapering is essential 1, 2
Live vaccines: Should not be given concurrently with belimumab or other immunosuppressive therapy 5
Ignoring depression and suicidality risk: Assess before and monitor during treatment, particularly with belimumab 5

What are the treatment options for Systemic Lupus Erythematosus (SLE) management?

Help us tailor your experience