What is the initial treatment for a systemic lupus (SLE) flare?

Initial Treatment for Systemic Lupus Erythematosus Flares

The initial treatment for a systemic lupus (SLE) flare should be adjusted according to the severity of organ involvement, with glucocorticoids as the cornerstone therapy, combined with hydroxychloroquine and potentially additional immunosuppressive agents depending on organ involvement. 1

Treatment Algorithm Based on Flare Severity

Non-Organ-Threatening Flares

1. First-line therapy:

   • Hydroxychloroquine (HCQ) 5 mg/kg/real body weight daily for all patients 1
   • Oral prednisone 0.5 mg/kg/day (maximum 30 mg/day) 2
   • Goal: Taper prednisone to ≤7.5 mg/day within 3-6 months 1, 2

2. Adjunctive therapy:

   • Short-term NSAIDs for patients at low risk for complications 2
   • Topical agents (glucocorticoids, calcineurin inhibitors) for skin manifestations 1

Organ-Threatening Flares

1. Initial therapy:

   • Intravenous methylprednisolone pulses (250-1000 mg/day for 1-3 days) 1, 2
   • Followed by oral prednisone 0.5 mg/kg/day 2
   • Hydroxychloroquine (continue or initiate) 1

2. Add immunosuppressive agents based on organ involvement:

   • For nephritis: Mycophenolate mofetil (target 2-3 g/day) or low-dose intravenous cyclophosphamide 1
   • For severe organ-threatening disease: Cyclophosphamide 1
   • For neuropsychiatric manifestations: High-dose glucocorticoids plus immunosuppressants 1, 2

Specific Organ Involvement Considerations

Renal Disease (Lupus Nephritis)

• Class III/IV nephritis: Methylprednisolone pulses followed by oral prednisone with mycophenolate mofetil or cyclophosphamide 1
• Class V nephritis: Prednisone with mycophenolate mofetil 1, 2
• High-risk patients (reduced GFR, fibrous crescents, fibrinoid necrosis): Consider high-dose intravenous cyclophosphamide 1
• Monitor proteinuria: Goal is <0.5-0.7 g/24 hours by 12 months 1

Hematological Disease

• Acute thrombocytopenia: High-dose glucocorticoids (including IV methylprednisolone) and/or intravenous immunoglobulin 1

Skin Disease

• First-line: Topical agents, antimalarials, and/or systemic glucocorticoids 1
• For non-responsive cases: Add methotrexate, retinoids, dapsone, or mycophenolate 1

Neuropsychiatric Disease

• Inflammatory manifestations: Glucocorticoids and immunosuppressive agents 1
• Atherothrombotic/aPL-related manifestations: Antiplatelet/anticoagulants 1

Monitoring Response and Adjusting Therapy

1. Early response indicators:

   • Improvement in proteinuria with GFR stabilization by 3 months 1
   • At least 50% reduction in proteinuria by 6 months 1
   • Clinical signs (rashes, arthritis, serositis, neurological manifestations) 2
   • Laboratory parameters (CBC, renal function, urinalysis, C3/C4, anti-dsDNA) 2

2. If inadequate response:

   • For refractory disease: Consider rituximab 1
   • For persistent disease activity despite standard therapy: Consider belimumab 1, 3

Important Considerations and Pitfalls

• Steroid minimization: Aim to reduce prednisone to <7.5 mg/day as quickly as possible to prevent long-term complications 1, 2, 4
• Hydroxychloroquine importance: HCQ is associated with reduced mortality and should be continued long-term 1, 5
• Immunosuppressive initiation timing: Early initiation can expedite glucocorticoid tapering 1
• Monitoring for complications: Regular assessment for infections, hypertension, hyperglycemia, osteoporosis, and other steroid-related complications 4
• Avoid premature treatment changes: In nephrotic-range proteinuria, allow 6-12 months for recovery before changing therapy 1

The treatment approach should balance immediate disease control with prevention of long-term damage from both the disease and its treatments, with the ultimate goals of achieving remission or low disease activity and preventing flares in all organs 1, 6.