What is the treatment for a patient experiencing a lupus flare-up?

Treatment of Lupus Flare

For a lupus flare without major organ involvement, initiate oral prednisone at 0.5-0.6 mg/kg/day (maximum 40 mg/day) combined with an immunosuppressive agent like mycophenolate mofetil (MMF) 2-3 g/day, then rapidly taper steroids to ≤7.5 mg/day by 8-12 weeks. 1, 2

Severity-Based Treatment Algorithm

Mild-to-Moderate Flares (No Major Organ Involvement)

Initial Therapy:

• Start oral prednisone 0.5-0.6 mg/kg/day (maximum 40 mg/day) 1
• Add antimalarials (hydroxychloroquine ≤5 mg/kg real body weight) if not already on them 3, 2
• Consider adding immunosuppressive agents early to enable rapid steroid taper 1, 2

Steroid-Sparing Immunosuppression:

• First-line: Mycophenolate mofetil 2-3 g/day 1, 2
• Alternatives: Azathioprine 2 mg/kg/day or methotrexate 3
• NSAIDs may be used judiciously for short periods in low-risk patients 3

Tapering Strategy:

• Reduce prednisone to ≤7.5 mg/day by 8-12 weeks 1
• Aim for complete glucocorticoid discontinuation after maintaining clinical response for ≥12 months, but only with gradual tapering 1

Severe or Organ-Threatening Flares

Induction Therapy:

• IV methylprednisolone pulses 250-500 mg/day for 3 days 1, 2
• Transition to oral prednisone 0.5-0.6 mg/kg/day (maximum 40 mg/day) 1
• Combine with immunosuppression immediately to minimize cumulative steroid exposure 1

Immunosuppressive Options:

• Lupus nephritis (Class III/IV): MMF 2-3 g/day OR low-dose IV cyclophosphamide 3, 1, 2
• Pure membranous nephritis (Class V): MMF 3 g/day for 6 months with prednisone 0.5 mg/kg/day 3
• Neuropsychiatric lupus (inflammatory origin): Immunosuppressive therapy for optic neuritis, acute confusional state, cranial/peripheral neuropathy, psychosis, transverse myelitis 3

Maintenance Therapy

Duration and Agents:

• Continue maintenance immunosuppression for ≥36 months total duration in proliferative lupus nephritis 1, 2
• MMF: Reduce to 750-1000 mg twice daily (2 g/day) for maintenance 3, 2
• Azathioprine: 2 mg/kg/day as alternative, especially if pregnancy contemplated 3
• Maintain low-dose prednisone 5-7.5 mg/day during maintenance phase 3

Refractory Disease Management

Treatment Escalation:

• Switch from MMF to cyclophosphamide, or vice versa, if lack of response 3
• Rituximab: Consider for persistent disease activity or inadequate response to standard therapy 2, 4
• Belimumab: Add to triple immunosuppressive regimen (with glucocorticoids and MMF or reduced-dose cyclophosphamide) for repeated kidney flares or high progression risk 2, 4, 5
• Calcineurin inhibitors (voclosporin, tacrolimus, cyclosporine): Consider for preserved kidney function with nephrotic-range proteinuria 2, 4

Monitoring Response

Assessment Timeline:

• Schedule visits every 2-4 weeks for first 2-4 months after diagnosis or flare 3
• Assess response at 6 months before major treatment changes, unless clear worsening at 3 months (≥50% increase in proteinuria or creatinine) 1
• Lifelong monitoring every 3-6 months thereafter 3

Response Definitions:

• Complete response: Proteinuria <0.5 g/g, stable/improved kidney function, resolution of extrarenal manifestations 2
• Partial response: ≥50% reduction in proteinuria to <3 g/g with stable/improved kidney function 4

Laboratory Monitoring:

• CBC, serum creatinine, eGFR, serum albumin, proteinuria, urinary sediment 3
• Serum C3/C4, anti-dsDNA antibodies 3
• Anti-phospholipid antibodies and lipid profile at baseline and intermittently 3

Adjunctive Therapies

Mandatory Considerations:

• Hydroxychloroquine: Recommended for all SLE patients (unless contraindicated) to reduce renal flares and limit damage accrual 3, 2
• ACE inhibitors/ARBs: For proteinuria (UPCR >50 mg/mmol) or hypertension 3
• Calcium/vitamin D supplementation: To prevent steroid-induced osteoporosis 3
• Low-dose aspirin: In patients with antiphospholipid antibodies 3
• Statins: For persistent dyslipidemia (target LDL <100 mg/dL) 3

Lifestyle Modifications:

• Photo-protection for skin manifestations 3
• Smoking cessation, weight control, exercise 3

Critical Pitfalls to Avoid

Steroid-Related:

• Prolonged high-dose glucocorticoids cause significant organ damage and mortality 2, 6
• Rapid steroid taper before 6 months significantly increases relapse risk 1
• Abrupt withdrawal in patients on long-term therapy may cause withdrawal symptoms mimicking disease flare 2
• Some patients require maintenance >10 mg/day despite guidelines suggesting lower doses 1

Treatment Duration:

• Immunosuppression withdrawal too early increases relapse risk—maintain for at least 36 months in proliferative lupus nephritis 1, 2
• Assess for relapse versus chronic damage before escalating therapy; consider repeat kidney biopsy if uncertain 1, 2

Monitoring:

• Patients with low mycophenolic acid exposure have higher flare risk; consider therapeutic drug monitoring in selected cases 2
• Screen for infections vigilantly, as immunosuppression decreases ability to fight infections 5

Special Populations

Pregnancy:

• Safe medications: Prednisolone, azathioprine, hydroxychloroquine, low-dose aspirin 3
• Switch from MMF to azathioprine at least 3 months prior to conception 3
• Monitor closely for pre-eclampsia, especially with lupus nephritis or antiphospholipid antibodies 3