What is the typical treatment for Systemic Lupus Erythematosus (SLE)?

Treatment of Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine at ≤5 mg/kg real body weight is mandatory foundational therapy for all SLE patients unless contraindicated, as it reduces disease activity, prevents flares, and improves survival. 1, 2

Foundation Therapy (Required for All Patients)

• Hydroxychloroquine must be prescribed at a dose not exceeding 5 mg/kg of real body weight to minimize retinal toxicity risk while maintaining therapeutic benefit 1, 2, 3
• Ophthalmological screening is mandatory at baseline, after 5 years of therapy, then yearly thereafter using visual fields examination and/or spectral domain-optical coherence tomography 1, 2
• Photoprotection with sunscreens prevents cutaneous flares and should be recommended universally 1, 2
• Low-dose aspirin should be given to patients with antiphospholipid antibodies, those receiving corticosteroids, or those with cardiovascular risk factors 1, 2
• Calcium and vitamin D supplementation is required for all patients on long-term glucocorticoids to prevent osteoporosis 1, 2

Glucocorticoid Management Algorithm

For acute flares, initiate with intravenous methylprednisolone pulse therapy (250-1000 mg daily for 1-3 days) to provide immediate therapeutic effect and enable lower starting doses of oral steroids. 1, 2, 4

• Following IV pulse therapy, start oral prednisone at 0.5-1 mg/kg/day depending on severity (never exceed 60 mg/day, as higher doses do not improve outcomes and accelerate damage accrual) 1, 4
• Aggressively taper glucocorticoids with a goal of <7.5 mg/day prednisone equivalent for chronic maintenance, and withdraw completely when possible to prevent organ damage 1, 2
• Prompt initiation of immunosuppressive agents expedites glucocorticoid tapering and discontinuation 2

Common Pitfall: Prolonged high-dose glucocorticoid therapy (>7.5 mg/day) leads to significant organ damage, infections, osteoporosis, avascular necrosis, and increased mortality. Always add steroid-sparing immunosuppressive agents early. 1, 5

Immunosuppressive Therapy Selection

When hydroxychloroquine plus glucocorticoids are insufficient, or when glucocorticoids cannot be tapered below 7.5 mg/day, add immunosuppressive agents based on organ involvement: 1, 2

• Methotrexate for skin and joint manifestations 1, 2
• Azathioprine for maintenance therapy, particularly suitable for women contemplating pregnancy 1, 2
• Mycophenolate mofetil for renal and non-renal manifestations (except neuropsychiatric disease) 1, 2
• Cyclophosphamide for severe organ-threatening disease, especially renal, cardiopulmonary, or neuropsychiatric manifestations 1, 2, 4

Organ-Specific Treatment Protocols

Lupus Nephritis

Kidney biopsy is essential before initiating therapy—failure to perform biopsy leads to suboptimal therapy selection. 1, 2

• Induction therapy: Mycophenolate mofetil OR low-dose IV cyclophosphamide (both have the best efficacy/toxicity ratio; low-dose cyclophosphamide is preferred over high-dose due to comparable efficacy and lower gonadotoxicity) 1, 2
• Maintenance therapy: Mycophenolate mofetil OR azathioprine 1, 2
• Target at least partial remission within 6-12 months 1

Neuropsychiatric Lupus

Treatment depends on the underlying pathophysiological mechanism: 1, 2

• For inflammatory/immune-mediated mechanisms: High-dose intravenous methylprednisolone PLUS cyclophosphamide (response rate 95% vs 54% with methylprednisolone alone, p=0.03) 1, 4
• For thrombotic/embolic mechanisms: Anticoagulation with warfarin (target INR 2.0-3.0 for first venous thrombosis; 3.0-4.0 for arterial or recurrent thrombosis) 1, 2
• Rituximab is an alternative for refractory cases, but has lower quality evidence 4

Hematological Manifestations

• For significant thrombocytopenia: Initial pulse IV methylprednisolone followed by moderate/high-dose glucocorticoids combined with immunosuppressive agents (azathioprine, mycophenolate mofetil, or cyclosporine) 1, 2
• IVIG may be considered in the acute phase or with inadequate response to glucocorticoids 2
• For refractory cases: rituximab or cyclophosphamide 2

Cutaneous Manifestations

• First-line therapy includes topical glucocorticoids, topical calcineurin inhibitors, and hydroxychloroquine 1, 2

Biologic Therapies for Refractory Disease

When patients have inadequate response to standard therapy (hydroxychloroquine, glucocorticoids, and immunosuppressives), consider biologics: 1, 2

• Belimumab (anti-BAFF antibody) is FDA-approved for active extrarenal SLE in patients receiving standard therapy, and for active lupus nephritis 1, 6
• Anifrolumab (anti-type 1 interferon receptor) is FDA-approved for moderate-to-severe extrarenal SLE 1
• Voclosporin is FDA-approved for lupus nephritis 1
• Rituximab may be considered for refractory cases, particularly hematological manifestations and organ-threatening disease with intolerance or contraindications to standard immunosuppressive agents 1, 2

Critical Monitoring and Comorbidity Management

• Use validated activity indices (such as SELENA-SLEDAI) at each visit 1, 2
• Monitor anti-dsDNA, C3, C4, complete blood count, creatinine, proteinuria, and urine sediment regularly 1, 2
• SLE patients have 5-fold increased mortality risk—screen aggressively for infections, cardiovascular disease, hypertension, diabetes, dyslipidemia, osteoporosis, avascular necrosis, and malignancies (especially non-Hodgkin lymphoma) 1, 2

Common Pitfall: NSAIDs should only be used judiciously for limited periods in patients at low risk for complications (renal disease, cardiovascular disease, or on anticoagulation). 1

Pregnancy Considerations

• Safe medications during pregnancy: Prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin 1, 2
• Contraindicated medications: Mycophenolate mofetil, cyclophosphamide, and methotrexate 1, 2
• When using cyclophosphamide in reproductive-age patients, counsel about gonadal toxicity and fertility preservation options 4