What is the recommended treatment for an acute systemic lupus erythematosus flare?

Treatment of Acute Lupus Flare

For an acute SLE flare, immediately administer intravenous methylprednisolone pulse therapy (250-1000 mg daily for 1-3 days) for severe organ-threatening manifestations, or oral prednisone 0.5-1 mg/kg/day for mild-to-moderate flares, while ensuring the patient is on hydroxychloroquine ≤5 mg/kg real body weight and promptly initiating immunosuppressive agents to enable rapid glucocorticoid tapering to <7.5 mg/day within 3-6 months. 1, 2, 3

Immediate Flare Assessment and Stratification

Before initiating treatment, determine flare severity to guide treatment intensity:

• Mild-to-moderate flares include constitutional symptoms, arthritis, rash, or mild serositis without major organ involvement 3
• Severe/organ-threatening flares include active lupus nephritis, neuropsychiatric manifestations, severe cytopenias (thrombocytopenia, hemolytic anemia), cardiopulmonary involvement, or vasculitis 3

Acute Glucocorticoid Management by Severity

Severe/Organ-Threatening Flares

• Administer IV methylprednisolone 250-1000 mg daily for 1-3 consecutive days as pulse therapy 1, 2, 4, 3
• This approach provides immediate therapeutic effect while enabling lower starting doses of oral glucocorticoids 1, 2, 5
• Methylprednisolone pulses are effective for both severe and non-severe manifestations without significant short or long-term toxicity 5, 6
• After pulse therapy, initiate oral prednisone at 0.3-0.5 mg/kg/day (lower than historical 1 mg/kg/day based on recent evidence showing comparable efficacy with reduced toxicity) 4, 6, 7

Mild-to-Moderate Flares

• Initiate oral prednisone 0.5-1 mg/kg/day with tapering over 2-4 weeks 3
• Consider methylprednisolone pulses even for non-severe flares to reduce oral glucocorticoid burden 5, 6

Critical Glucocorticoid Tapering Strategy

• Rapidly taper to ≤7.5 mg/day prednisone within 3-6 months as the primary goal 1, 2, 4, 3
• Target maintenance dose <5 mg/day for long-term therapy 6, 7
• Never maintain chronic glucocorticoid doses >7.5 mg/day as this substantially increases risk of irreversible organ damage, infections, osteonecrosis, and mortality 1, 2, 4, 3

Concurrent Immunosuppressive Therapy

Immediately initiate or optimize immunosuppressive agents to enable glucocorticoid tapering—this is not optional but mandatory for reducing steroid toxicity 1, 2, 3:

• Mycophenolate mofetil for renal and non-renal manifestations (except neuropsychiatric disease) 1, 2, 3
• Azathioprine for maintenance therapy, particularly suitable for women contemplating pregnancy 1, 2
• Methotrexate for skin and joint manifestations 1, 2
• Cyclophosphamide for severe organ-threatening disease, especially renal, cardiopulmonary, or neuropsychiatric manifestations 1, 2, 3

Early introduction of immunosuppressive treatment improves clinical efficacy while reducing glucocorticoid toxicity 7, 8

Hydroxychloroquine: The Non-Negotiable Foundation

• Ensure all patients are on hydroxychloroquine ≤5 mg/kg real body weight (typically 200-400 mg daily) 1, 2, 4, 3
• This is mandatory unless contraindicated, as hydroxychloroquine reduces disease activity, prevents flares, improves survival, and reduces mortality 1, 2, 4, 9
• Universal hydroxychloroquine therapy should be aimed at all SLE patients—this is the backbone therapy that must continue during and after flare management 3, 8

Organ-Specific Flare Management

Lupus Nephritis Flare

• Kidney biopsy is essential before initiating therapy for diagnosis and treatment planning 2, 3
• Induction therapy: IV methylprednisolone pulse followed by oral prednisone PLUS mycophenolate mofetil 2-3 g/day OR low-dose IV cyclophosphamide (500 mg every 2 weeks × 6 doses) 2, 4, 3
• Target partial response by 6 months (≥50% reduction in proteinuria to subnephrotic levels, creatinine within 10% of baseline) 1, 2, 4
• Target complete response by 12 months (proteinuria <0.5-0.7 g/24 hours) 4

Neuropsychiatric Lupus Flare

• For inflammatory/immune-mediated mechanisms: high-dose IV methylprednisolone PLUS cyclophosphamide 2, 3
• For thrombotic/embolic mechanisms: anticoagulation therapy 2
• Aggressively exclude infection before initiating immunosuppressive therapy 4

Hematological Manifestations (Severe Thrombocytopenia)

• High-dose glucocorticoids including IV methylprednisolone pulses 2
• IV immunoglobulin G may be added in the acute phase or with inadequate response 2
• For refractory cases: rituximab or cyclophosphamide 2

Biologic Therapies for Refractory Flares

If inadequate response to standard therapy by 6 months:

• Belimumab (anti-BAFF antibody) for active extrarenal SLE and lupus nephritis 2, 4, 9
• Rituximab for organ-threatening disease refractory to standard immunosuppressive agents 2, 4
• Anifrolumab (anti-type 1 interferon receptor) for moderate-to-severe extrarenal SLE 2, 4, 9
• Voclosporin for lupus nephritis 2, 4, 9

Monitoring During and After Flare

At each visit, assess:

• Validated activity indices (SLEDAI, BILAG) 2, 4, 3
• Anti-dsDNA antibodies and complement levels (C3, C4) 2, 3
• Complete blood count, serum creatinine 3
• Urine protein-creatinine ratio and urine sediment (for renal involvement) 4, 3
• Screen aggressively for infections, as SLE patients have 5-fold increased mortality risk 2, 3

Common Pitfalls to Avoid

• Do not use prolonged high-dose oral glucocorticoids (>7.5 mg/day) as this is the major cause of toxicity and damage accrual in SLE 1, 5, 8
• Do not delay immunosuppressive therapy—early initiation is critical for enabling glucocorticoid tapering 6, 7
• Do not omit hydroxychloroquine—poor adherence is common but this medication is essential for all patients 1, 8
• Do not use high-dose oral prednisone (1 mg/kg/day) as initial therapy—methylprednisolone pulses followed by lower oral doses (0.3-0.5 mg/kg/day) are more effective and less toxic 4, 5, 6