What is the treatment for a lupus flare?

Treatment of Lupus Flares

The treatment of a lupus flare requires prompt intervention with glucocorticoids as the primary therapy, with dosing tailored to the severity of the flare, while simultaneously initiating or adjusting immunosuppressive agents to allow for steroid tapering and prevention of future flares. 1, 2

Initial Assessment and Treatment Algorithm

Step 1: Assess Severity of Flare

• Mild to Moderate Flare:

  • Musculoskeletal symptoms
  • Mild cutaneous manifestations
  • No major organ involvement

• Severe Flare:

  • Lupus nephritis
  • Neuropsychiatric manifestations
  • Severe hematologic abnormalities
  • Other major organ involvement

Step 2: Glucocorticoid Therapy Based on Severity

For Mild to Moderate Flares:

• Initial therapy: Low-to-moderate dose oral prednisone (0.25-0.5 mg/kg/day) 2
• Target lowest effective dose (≤5 mg/day) for shortest duration possible
• Consider short-term prednisone boost (30 mg/day for 2 weeks, 20 mg/day for 1 week, 10 mg/day for 1 week) for serologically active patients showing increased anti-dsDNA and complement activation 3

For Severe Flares:

• Initial therapy: Methylprednisolone pulse therapy (500-1000 mg IV daily for 3 days) followed by oral prednisone 2, 4
• Low-dose pulse methylprednisolone (≤1500 mg over 3 days) has been shown to be effective with fewer infectious complications compared to high-dose pulses 4
• Oral prednisone starting at 0.5-1 mg/kg/day after pulse therapy

Immunosuppressive Therapy

For Maintenance/Prevention After Flare:

• First-line options:
  • Mycophenolate mofetil (MMF): 750-1000 mg twice daily 1
  • Mycophenolic acid: 540-720 mg twice daily 1
  • Azathioprine
  • Hydroxychloroquine: Fundamental for all SLE patients regardless of severity 2

For Severe Lupus Nephritis (Class III/IV):

• Methylprednisolone pulses followed by oral prednisone with:
  • Mycophenolate mofetil or
  • Cyclophosphamide (500-750 mg/m² monthly) 2

For Refractory Cases:

• Belimumab
• Rituximab
• Voclosporin (for lupus nephritis)
• Anifrolumab 1, 2

Glucocorticoid Tapering Strategy

1. Aim to reduce prednisone to ≤7.5 mg/day by the end of initial treatment phase 1
2. Continue tapering to lowest possible dose during maintenance
3. Consider discontinuation after complete clinical renal response maintained for ≥12 months 1

Important: Recent evidence shows significantly increased flare rates when prednisone is discontinued completely compared to maintaining a low dose of 5 mg daily 1. Withdrawal should be undertaken with caution and careful monitoring.

Duration of Immunosuppressive Therapy

• Total duration of immunosuppression (initial + maintenance) should be ≥36 months for proliferative lupus nephritis 1
• Maintain MMF doses until achieving complete response before tapering 1
• Glucocorticoids should be withdrawn before immunosuppressive agents 2

Monitoring and Adjustment

• Assess disease activity at each visit using validated indices (SLEDAI-2K)
• Monitor laboratory parameters: CBC, anti-dsDNA antibodies, complement levels, renal function, urinalysis
• Switch therapy if:
  • No improvement within 3-4 months
  • No partial response after 6-12 months
  • No complete response after 2 years 2

Common Pitfalls and Caveats

1. Prolonged glucocorticoid exposure leads to significant organ damage and morbidity - aim for the lowest effective dose and shortest duration 1, 5

2. Discontinuing hydroxychloroquine can lead to increased flares - maintain as background therapy even during remission 2

3. Inadequate immunosuppression during steroid tapering increases risk of flare - ensure appropriate maintenance therapy 1

4. Abrupt glucocorticoid withdrawal after long-term use may cause withdrawal symptoms that mimic disease flares 1

5. Overlooking serologic changes in clinically stable patients - consider preemptive short-term steroid treatment in patients with rising anti-dsDNA and complement activation to prevent severe flares 3

6. Excessive methylprednisolone dosing increases infection risk - low-dose pulse therapy (≤1500 mg over 3 days) can be as effective as high-dose with fewer serious infections 4