SHARE Initiative Recommendations for Childhood-Onset Systemic Lupus Erythematosus (cSLE) Treatment
For childhood-onset SLE, treatment should follow immunosuppression regimens similar to adults, with high-dose glucocorticoids plus either mycophenolate mofetil (MMF) or cyclophosphamide (CYC) for induction therapy, followed by MMF or azathioprine (AZA) for maintenance therapy. 1
Initial Assessment and General Management
- Renal biopsy is essential for any child with SLE showing signs of renal involvement (proteinuria ≥0.5 g/24h, especially with glomerular hematuria and/or cellular casts) to guide treatment decisions 1
- Hydroxychloroquine (6.5 mg/kg/day or 400 mg/day, whichever is lower) should be prescribed for all cSLE patients regardless of disease severity or organ involvement 1, 2
- Non-live vaccines should be administered according to standard schedules for all cSLE patients 1
Induction Therapy for Lupus Nephritis
- For class III-IV lupus nephritis, use high-dose glucocorticoids (prednisone 1-2 mg/kg/day, maximum 60 mg/day) plus either MMF or CYC 1
- Initial treatment should include three consecutive pulses of intravenous methylprednisolone (500-750 mg), followed by oral prednisone, with the goal of reducing to ≤10 mg/day by 4-6 months 1
- MMF may be preferred over CYC in certain populations (particularly African-American and Hispanic patients) due to better response rates 1, 3
- In severe cases with adverse prognostic factors (acute deterioration in renal function, substantial cellular crescents, fibrinoid necrosis), higher doses of CYC may be considered 1
Maintenance Therapy
- For maintenance therapy in children who have responded to induction therapy, MMF or AZA is recommended over CYC (weak recommendation based on low certainty evidence) 1
- Maintenance therapy should be continued for at least 3 years 1
- Cost and availability issues may favor AZA in some regions 1
- MMF dosing may require adjustment in children due to different pharmacokinetic effects 1, 3
Treatment of Refractory Disease
- For patients not responding to initial therapy, consider switching from MMF to CYC or vice versa 1
- Rituximab may be considered for refractory cases, either as add-on therapy or monotherapy 1, 4
- Additional options for refractory disease include calcineurin inhibitors (tacrolimus, cyclosporine), intravenous immunoglobulin, or plasma exchange for rapidly progressive glomerulonephritis 1, 3
Special Considerations in Children
- Growth concerns should guide glucocorticoid dosing strategies to minimize exposure 1
- Fertility preservation concerns may favor limiting CYC exposure, especially as patients approach adolescence 1, 3
- Adherence issues may favor intravenous medications in some cases 1, 3
- Psychosocial concerns related to school and peer socialization should be addressed 1
- Co-management by pediatric nephrologists and rheumatologists with expertise in lupus is essential 1
Monitoring
- Regular monitoring should include body weight, blood pressure, serum creatinine, estimated GFR, serum albumin, proteinuria, urinary sediment, serum C3/C4, and anti-dsDNA antibody levels 1
- Spot urine protein-to-creatinine ratio on first morning void is a valid measure for monitoring proteinuria in children 1
- Complete renal response (proteinuria <0.5 g/24h with normal or near-normal renal function) should be achieved preferably by 6 months but no later than 12 months after starting treatment 1
Adjunctive Treatments
- Renin-angiotensin-aldosterone system blockers are recommended for patients with significant proteinuria or hypertension 1, 3
- Cardiovascular risk factors should be managed similarly to patients without SLE 1
- Complications of chronic renal insufficiency should be managed as in patients without SLE 1