What is the best course of treatment for a patient with steroid-dependent (nephrotic syndrome requiring ongoing steroid treatment) nephrotic syndrome experiencing a complicated relapse with varicella (chickenpox) infection?

Management of Steroid-Dependent Nephrotic Syndrome with Varicella Infection

In a child with steroid-dependent nephrotic syndrome who develops varicella, immediately discontinue all immunosuppressive therapy, initiate intravenous acyclovir at 800 mg four times daily (or 20 mg/kg per dose four times daily for children under 40 kg) for 5 days, and restart immunosuppression only after complete resolution of the varicella infection. 1

Immediate Management of Active Varicella

Discontinue Immunosuppression

• Stop all corticosteroids and steroid-sparing agents immediately upon diagnosis of varicella in an immunocompromised child with nephrotic syndrome, as continuing immunosuppression during active viral infection significantly increases morbidity and mortality risk. 2, 3
• Live vaccines are contraindicated in children receiving immunosuppressive agents, and active varicella represents a severe complication requiring cessation of all immunosuppression. 2

Antiviral Therapy

• Administer intravenous acyclovir as the preferred route for immunocompromised patients with varicella, using 800 mg four times daily for adults and children over 40 kg, or 20 mg/kg per dose four times daily (80 mg/kg/day) for children under 40 kg, for a total duration of 5 days. 1
• Intravenous acyclovir is specifically indicated for varicella-zoster infections in immunocompromised patients, making it the appropriate choice over oral formulations in this clinical scenario. 1
• Following completion of IV therapy, transition to oral acyclovir may be considered if clinical improvement is evident and the patient can tolerate oral medications. 3

Prophylaxis for Future Exposures

• For non-immune children on immunosuppressive agents who have close contact with varicella infection, administer varicella zoster immune globulin if available, as this provides passive immunity and may prevent or attenuate infection. 2

Restarting Immunosuppression After Varicella Resolution

Timing of Reinitiation

• Wait until complete resolution of all varicella lesions (all crusted over) and the child is clinically well before restarting any immunosuppressive therapy, typically 2-3 weeks after onset of rash. 3
• Monitor for secondary bacterial infections or other complications before resuming immunosuppression.

Treatment of Nephrotic Syndrome Relapse During or After Varicella

If the patient remains in remission during varicella infection:

• Resume the previous maintenance regimen of steroid-sparing agents once varicella has completely resolved. 4, 5
• For steroid-dependent nephrotic syndrome, glucocorticoid-sparing agents should be prescribed to prevent relapses rather than continuation with glucocorticoid treatment alone. 2

If relapse occurs during or after varicella:

• Once varicella is fully resolved, treat the relapse with daily prednisone at 60 mg/m² (maximum 60 mg/day) until remission for at least 3 consecutive days, then transition to alternate-day prednisone at 40 mg/m² for at least 3 months. 5
• Complete remission is defined as urine protein <200 mg/g or trace/negative on dipstick for 3 consecutive days. 5

Selection of Steroid-Sparing Agent

First-Line Options for Steroid-Dependent Disease

The 2025 KDIGO guidelines no longer distinguish between first-line and alternative agents, but provide guidance based on disease pattern. 2

For steroid-dependent nephrotic syndrome, preferred options include:

• Mycophenolate mofetil at 1200 mg/m²/day in two divided doses for at least 12 months, as most children will relapse when MMF is stopped. 2, 5
• Rituximab (1-4 doses based on current trials), which has shown favorable response in large pediatric clinical trials since 2012. 2
• Calcineurin inhibitors (cyclosporine 3-5 mg/kg/day or tacrolimus) continued for a minimum of 12 months. 2, 5
• Oral cyclophosphamide at 2 mg/kg/day for 8-12 weeks (maximum cumulative dose 168 mg/kg), though this is used to a lesser extent in steroid-dependent disease. 2, 5

Important Considerations

• Ensure the child is in remission with glucocorticoids prior to initiating glucocorticoid-sparing agents, and continue glucocorticoids for 2 weeks following initiation of such agents. 2
• In children with complicated forms of steroid-dependent nephrotic syndrome, mycophenolate mofetil after rituximab can decrease the risk of treatment failure. 2
• The choice depends on route preference (intravenous vs oral), monitoring capability, side effect tolerance, and disease pattern. 4

Monitoring and Prevention

Infection Prevention Strategies

• Administer pneumococcal vaccination to all children with nephrotic syndrome. 2
• Give annual influenza vaccination to the child and household contacts. 2
• Defer live vaccines until prednisone dose is below 1 mg/kg daily (or 20 mg/day) or 2 mg/kg on alternate days (or 40 mg on alternate days). 2
• Immunize healthy household contacts with live vaccines to minimize infection transfer risk, but avoid direct exposure of the immunosuppressed child to gastrointestinal, urinary, or respiratory secretions of vaccinated contacts for 3-6 weeks after vaccination. 2

Varicella Vaccination in Remission

• Varicella vaccination with live, attenuated vaccine is safe and effective in children with steroid-sensitive nephrotic syndrome who are in remission and off immunosuppressive agents, with 85% seroconversion rates. 6
• Vaccination should only be administered when the child meets the criteria for live vaccine administration (low-dose or no steroids, no other immunosuppressive agents). 2, 6

Ongoing Monitoring

• Monitor urine protein daily using dipstick or spot urine protein-to-creatinine ratio to assess treatment response. 5
• Regularly assess kidney function, especially in patients receiving calcineurin inhibitors, as nephrotoxicity is a significant concern. 4
• Monitor for agent-specific side effects: neutropenia with levamisole, hemorrhagic cystitis with cyclophosphamide, and nephrotoxicity with calcineurin inhibitors. 4
• Consider kidney biopsy if there is decreasing kidney function in children receiving calcineurin inhibitors or late failure to respond to therapy. 2, 4

Critical Pitfalls to Avoid

• Never continue immunosuppression during active varicella infection in an immunocompromised patient, as this dramatically increases mortality risk. 3
• Do not restart immunosuppression until all varicella lesions are completely crusted and the patient is clinically well. 3
• Avoid giving a second course of alkylating agents (cyclophosphamide or chlorambucil) due to cumulative gonadal toxicity; use alternative steroid-sparing agents for subsequent treatment needs. 4
• Do not taper steroids prematurely; continue for at least 3 months on alternate-day dosing after achieving remission in steroid-dependent patients. 5
• Verify medication adherence before escalating therapy or declaring treatment failure. 5