What is the initial treatment for Systemic Lupus Erythematosus (SLE) in pediatric patients?

Initial Treatment for Pediatric Systemic Lupus Erythematosus (SLE)

The initial treatment for pediatric SLE should include hydroxychloroquine as the cornerstone therapy for all patients, combined with glucocorticoids and additional immunosuppressive agents based on disease severity and organ involvement. 1

First-Line Medications for All Pediatric SLE Patients

• Hydroxychloroquine is recommended for all pediatric SLE patients regardless of disease severity or organ involvement, at a dose not exceeding 5 mg/kg real body weight 1
• Hydroxychloroquine improves outcomes by reducing renal flares and limiting accrual of renal and cardiovascular damage 1, 2
• Regular ophthalmological screening should be performed at baseline, after 5 years, and yearly thereafter to monitor for retinal toxicity 1

Treatment Based on Disease Severity

Mild Disease

• For mild disease manifestations, hydroxychloroquine alone may be sufficient, with low-dose glucocorticoids (prednisone <7.5 mg/day) added for symptom control 1

Moderate to Severe Disease

• For moderate to severe disease, add glucocorticoids at doses dependent on disease severity 3
• Initial treatment may include three consecutive pulses of intravenous methylprednisolone (500-750 mg/day for 1-3 days), followed by oral prednisone 0.5 mg/kg/day for up to 4 weeks 3
• Taper prednisone to ≤7.5 mg/day by 3-6 months to minimize long-term toxicity 3, 4

Organ-Threatening Disease (Lupus Nephritis)

• For lupus nephritis (occurring in approximately 40% of pediatric SLE patients), add immunosuppressive agents to glucocorticoids 3, 2
• For class III, IV, or V lupus nephritis, use high-dose glucocorticoids (prednisone 1-2 mg/kg/day, maximum 60 mg/day) plus either mycophenolate mofetil (MMF) or cyclophosphamide (CYC) 3
• MMF is preferred over cyclophosphamide for pediatric patients due to better safety profile, particularly regarding gonadal toxicity 3, 5
• For maintenance therapy after induction, MMF or azathioprine (AZA) is recommended over cyclophosphamide 3

Adjunctive Therapies

• Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers are indicated for patients with proteinuria (UPCR >50 mg/mmol) or hypertension 3, 1
• Statins should be considered for persistent dyslipidemia (target LDL-cholesterol 2.58 mmol/liter) 3
• Immunizations with non-live vaccines should be administered according to age-appropriate schedules 3
• Consider calcium and vitamin D supplementation, especially with chronic glucocorticoid use 3

Treatment Goals and Monitoring

• Treatment should aim for complete remission or low disease activity in all organ systems 3
• For lupus nephritis, aim for at least partial remission (≥50% reduction in proteinuria to subnephrotic levels and serum creatinine within 10% from baseline) by 6-12 months 3
• Regular monitoring is essential, with visits scheduled every 2-4 weeks for the first 2-4 months after diagnosis or flare 1
• Assessment should include body weight, blood pressure, serum creatinine, eGFR, serum albumin, proteinuria, urinary sediment, complement levels, and anti-dsDNA antibody levels 3, 1

Refractory Disease Options

• For patients with inadequate response to standard therapy, consider belimumab as add-on treatment 1, 6
• In pediatric patients with SLE, belimumab has shown efficacy in reducing disease activity and severe flares 6
• For organ-threatening disease refractory to standard immunosuppressives, rituximab may be considered 1

Important Considerations for Pediatric SLE

• Pediatric SLE often presents with more severe manifestations than adult-onset disease, with higher rates of lupus nephritis (43% vs 26.4%), hematological disorders, and mucocutaneous manifestations 7
• Medication adherence is critical to preventing disease flares, particularly with hydroxychloroquine 3, 1
• Cost and availability issues may favor azathioprine over mycophenolate mofetil in some regions 3
• Rare adverse reactions to specific glucocorticoid formulations may occur; alternative preparations can be used if necessary 8

By following this treatment algorithm, clinicians can optimize outcomes for pediatric SLE patients while minimizing treatment-related toxicity.