What is the recommended treatment for a patient experiencing a lupus flare?

Treatment of Lupus Flare

Lupus flares should be treated by adjusting ongoing therapies (glucocorticoids and immunosuppressive agents) to higher doses, switching medications, or adding new therapies, with the specific regimen determined by the severity of organ involvement. 1

Initial Assessment and Stratification

Before initiating treatment, assess flare severity by evaluating:

• Clinical manifestations: Type and number of organ systems involved (mucocutaneous, musculoskeletal, renal, neuropsychiatric, hematologic, cardiopulmonary) 1
• Laboratory markers: Complete blood count, serum creatinine, proteinuria, urinary sediment, complement levels (C3/C4), anti-dsDNA antibodies 1, 2
• Disease activity indices: SELENA-SLEDAI score to quantify severity 3

Treatment Algorithm Based on Flare Severity

Mild to Moderate Flares (Non-Organ Threatening)

Start with oral prednisone 0.5 mg/kg/day (maximum 40 mg) combined with hydroxychloroquine. 2

• Hydroxychloroquine is mandatory for all lupus patients unless contraindicated, as it reduces flare frequency, prevents organ damage, and improves survival 1
• Dose hydroxychloroquine at ≤5 mg/kg actual body weight daily 1
• Add or increase immunosuppressive agents if the patient cannot taper glucocorticoids below acceptable chronic doses 1
  • First-line options: methotrexate, azathioprine, or mycophenolate mofetil 1
  • Mycophenolate mofetil 2-3 g/day is preferred for patients with renal involvement 1, 4

Severe Flares (Organ-Threatening or Life-Threatening)

Begin with intravenous methylprednisolone pulses 250-750 mg daily for 1-3 days, followed by oral prednisone. 1, 2

• Oral prednisone dosing after IV pulses: 2
  • Reduced-dose: 0.5-0.6 mg/kg/day (max 40 mg) for weeks 0-2
  • Moderate-dose: 0.6-0.7 mg/kg/day (max 50 mg) for weeks 0-2
  • High-dose: 0.8-1.0 mg/kg/day (max 80 mg) for weeks 0-2
• Taper prednisone to <7.5 mg/day by end of 3 months 1
• Immediately add immunosuppressive therapy to enable glucocorticoid tapering 1

Active Lupus Nephritis Flares (Class III/IV ± V)

Combine glucocorticoids with one of the following first-line regimens: 1, 2

1. Mycophenolate mofetil 2-3 g/day for 6 months (preferred option) 1
2. Low-dose intravenous cyclophosphamide 500 mg every 2 weeks × 6 doses (total 3 g over 3 months) 1
3. Belimumab plus mycophenolate or cyclophosphamide for patients with repeated kidney flares or high progression risk 2, 3
4. Mycophenolate plus calcineurin inhibitor (tacrolimus) when eGFR >45 mL/min/1.73 m² and nephrotic-range proteinuria present 1, 2

For maintenance therapy after initial response:

• Continue mycophenolate mofetil 1-2 g/day if used for induction 1, 4
• Azathioprine is an alternative if pregnancy is contemplated or cost is prohibitive 1
• Total duration of immunosuppression should be at least 36 months 4

Pure Class V Lupus Nephritis

Use mycophenolate mofetil 2-3 g/day as first choice. 1

• Alternative options include cyclophosphamide or calcineurin inhibitors (especially tacrolimus) as monotherapy or combined with mycophenolate 1

Neuropsychiatric Lupus Flares

Major neuropsychiatric manifestations of inflammatory origin require immunosuppressive therapy. 1

• This includes optic neuritis, acute confusional state/coma, cranial or peripheral neuropathy, psychosis, and transverse myelitis/myelopathy 1
• Diagnostic workup should mirror that for the general population with similar symptoms 1

Monitoring During Flare Treatment

Assess patients every 2-4 weeks during the first 2-4 months of treatment. 2

Monitor the following parameters:

• Blood pressure 2
• Serum creatinine and eGFR 2
• Serum albumin 2
• Proteinuria quantification (spot urine protein/creatinine ratio or 24-hour collection) 2
• Urinary sediment 2
• Complement levels (C3, C4) 2
• Anti-dsDNA antibodies 2

Treatment response definitions for lupus nephritis: 4

• Complete response: Proteinuria <0.5 g/g with stable/improved kidney function within 6-12 months 4
• Partial response: ≥50% reduction in proteinuria to <3 g/g with stable/improved kidney function 4
• Switch therapy if: No improvement within 3-4 months, no partial response after 6-12 months, or no complete response after 2 years 4

Critical Pitfalls to Avoid

Never abruptly discontinue glucocorticoids in patients on chronic therapy, as this triggers withdrawal symptoms mimicking true flares (45% flare rate with abrupt discontinuation versus 20% with continuation). 2

Avoid prolonged high-dose glucocorticoids (>7.5 mg/day prednisone equivalent) beyond 4-6 months, as this significantly increases organ damage accrual and morbidity. 1, 2

Do not exceed hydroxychloroquine dose of 5 mg/kg actual body weight to minimize retinal toxicity risk. 1

Limit lifetime cyclophosphamide exposure to <36 g to reduce malignancy and fertility risks. 1

Essential Adjunctive Measures

Continue or initiate the following supportive therapies during flares: 2

• ACE inhibitors or ARBs for proteinuria or hypertension 2
• Calcium and vitamin D supplementation with glucocorticoid therapy 2
• Pneumocystis jirovecii prophylaxis when prednisone >20 mg/day for >1 month combined with other immunosuppression 2
• Low-dose aspirin for cardiovascular risk reduction and during pregnancy in high-risk patients 1
• Lifestyle modifications: smoking cessation, weight control, exercise, UV light protection 1

Refractory Disease Management

For non-responding or refractory flares, consider: 1

• Rituximab for persistent disease activity despite standard therapies 1, 4
• Belimumab as add-on therapy (reduces severe flare risk by 49-64%) 3
• Cyclophosphamide as rescue therapy for severe organ-threatening disease 1, 4
• "Multitarget" regimen combining mycophenolate with calcineurin inhibitor (tacrolimus) 1

Before declaring refractory disease, assess medication adherence and measure drug levels where available. 1