What is the management for systemic lupus erythematosus (SLE)?

Management of Systemic Lupus Erythematosus

All patients with SLE should receive hydroxychloroquine as the foundation of therapy at a dose not exceeding 5 mg/kg real body weight unless contraindicated, combined with the lowest possible glucocorticoid dose (target ≤7.5 mg/day prednisone equivalent for maintenance), with treatment aimed at achieving remission or low disease activity to prevent organ damage and improve survival. 1, 2

Treatment Goals

• The primary objective is achieving remission (absence of clinical activity) or low disease activity, defined as SLEDAI ≤4 with prednisone ≤7.5 mg/day on well-tolerated immunosuppressive agents 1
• Prevention of disease flares, organ damage accrual, and minimization of drug toxicity are essential endpoints that directly impact mortality and quality of life 1
• Complete remission is infrequent, but low disease activity states show comparable rates of halting damage progression 1

Core Pharmacological Management

Hydroxychloroquine (Universal Foundation)

• Hydroxychloroquine must be prescribed to all SLE patients unless contraindicated, as it reduces flares, increases remission rates, reduces organ damage, and improves survival 1, 3, 2, 4
• Dose: 200-400 mg daily (not exceeding 5 mg/kg real body weight) 1, 2
• Ophthalmological screening with visual fields examination and/or spectral domain-optical coherence tomography should begin at baseline, then after 5 years, and yearly thereafter 1

Glucocorticoids (Minimize Aggressively)

• For acute moderate-to-severe flares, use intravenous methylprednisolone pulses (250-1000 mg/day for 1-3 days) to enable lower starting doses of oral prednisone 1, 5
• Oral glucocorticoids can be initiated at doses appropriate to organ involvement severity, but must be tapered rapidly 1
• Chronic maintenance glucocorticoids must be minimized to <7.5 mg/day prednisone equivalent and withdrawn when possible, as prolonged use contributes significantly to organ damage 1, 5
• Prompt initiation of immunomodulatory agents expedites glucocorticoid tapering and discontinuation 1

Immunosuppressive Agents

• For patients not responding to hydroxychloroquine alone or unable to reduce glucocorticoids below acceptable chronic doses, add immunomodulating agents 1:
  • Methotrexate for predominant articular and cutaneous manifestations 1, 3
  • Azathioprine as a steroid-sparing agent 1, 4
  • Mycophenolate mofetil for moderate-to-severe disease or refractory cutaneous manifestations 1, 3, 4
• Immunosuppressive agents should be included in initial therapy for organ-threatening disease 1
• Cyclophosphamide is reserved for severe organ-threatening or life-threatening SLE, and as rescue therapy for patients not responding to other agents 1, 4

Biologic Therapies

• Belimumab is FDA-approved for active SLE (2011) and lupus nephritis (2020), effective for controlling disease activity and preventing severe flares while enabling glucocorticoid reduction 6, 4
• Anifrolumab is FDA-approved for active SLE 4
• Rituximab can be used for refractory or organ-threatening disease 5
• Early inclusion of biologic agents in first-line treatment, particularly in certain patients, may decrease long-term disease burden and organ damage 6

Organ-Specific Management

Cutaneous Manifestations

• First-line: Topical glucocorticoids or calcineurin inhibitors plus hydroxychloroquine 3, 7
• For widespread or severe disease: Add short-term systemic glucocorticoids 7
• Refractory cases: Methotrexate (effective for various cutaneous manifestations), retinoids (for hyperkeratotic/hypertrophic lesions), dapsone (for bullous lupus and urticarial vasculitis), or mycophenolate mofetil 7
• Photoprotection is beneficial for all patients with cutaneous involvement 7

Lupus Nephritis

• Treatment goal: Achieve at least partial remission (≥50% reduction in proteinuria to subnephrotic levels with serum creatinine within 10% of baseline) by 6-12 months 1, 3
• Induction therapy: Mycophenolate mofetil or low-dose intravenous cyclophosphamide combined with glucocorticoids 3, 4
• Voclosporin is FDA-approved specifically for lupus nephritis 4
• Regular monitoring of proteinuria, urinary sediment, and renal function is essential 3, 7
• Reduction of proteinuria to <0.8 g/day is more important than residual hematuria in assessing treatment response 1

Musculoskeletal Manifestations

• Hydroxychloroquine combined with low-dose glucocorticoids for mild-to-moderate arthritis 3
• Methotrexate is particularly effective for articular manifestations 1, 3

Management of Critical Comorbidities

Antiphospholipid Syndrome

• All patients must be screened at diagnosis for antiphospholipid antibodies 1
• Patients with high-risk antiphospholipid antibody profile (persistently positive medium/high titers or multiple positivity) should receive primary prophylaxis with antiplatelet agents, especially if other atherosclerotic/thrombophilic factors are present 1, 7
• For secondary prevention (thrombosis, pregnancy complications), use the same therapeutic approach as primary antiphospholipid syndrome 1

Cardiovascular Disease

• Regular assessment for traditional and disease-related cardiovascular risk factors is mandatory, including persistently active disease, increased disease duration, medium/high titers of antiphospholipid antibodies, renal involvement (especially proteinuria and/or GFR <60 mL/min), and chronic glucocorticoid use 1
• Based on individual cardiovascular risk profile, consider preventative strategies including low-dose aspirin and lipid-lowering agents (statins) 1, 3, 8

Infections

• Assess for general and disease-related infection risk factors: advanced age/frailty, diabetes mellitus, renal involvement, immunosuppressive/biological therapy, and glucocorticoid use 1
• General preventative measures including immunizations, early recognition, and prompt treatment of infection/sepsis are essential 1, 3
• Maintain high index of suspicion with immediate evaluation and diligent follow-up 3, 7

Osteoporosis and Avascular Necrosis

• Monitor and prevent osteoporosis, particularly in patients on chronic glucocorticoids 3
• Calcium and vitamin D supplementation may be necessary 3

Pregnancy Considerations

• Pregnancy can increase SLE disease activity, though flares are usually mild 7
• Patients with lupus nephritis and antiphospholipid antibodies have higher risk of preeclampsia and require closer monitoring 7
• Safe medications during pregnancy: Prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin 3, 7
• Contraindicated during pregnancy: Mycophenolate mofetil, cyclophosphamide, and methotrexate 3, 7

Monitoring Strategy

• Regular monitoring using validated disease activity indices (SLEDAI, BILAG, or ECLAM) 3, 7
• Initial and follow-up evaluation should include clinical signs (skin lesions, arthritis, serositis, neurological manifestations), laboratory tests (complete blood count, serum creatinine, proteinuria, urine sediment), and immunological tests (C3, C4, anti-dsDNA, antiphospholipid antibodies) 3, 7, 8
• Risk factors for higher flare rates include younger age at disease onset, no use of antimalarials, persistent generalized disease activity, and serological activity (anti-dsDNA, low complement) 1

Critical Pitfalls to Avoid

• Never delay hydroxychloroquine initiation—it is the backbone of therapy and improves survival 1, 4
• Avoid prolonged high-dose glucocorticoids—they are a major contributor to organ damage and should be tapered aggressively with early immunosuppressive agent introduction 1, 5
• Do not exceed hydroxychloroquine dose of 5 mg/kg real body weight to minimize retinal toxicity risk 1, 2
• Ensure adherence to drug treatment through patient education, as non-adherence increases flare risk 1