What is the treatment approach for a 7-year-old child with Febrile Recurrent Neutrophilic Skin (FRNS) using Mycophenolate Mofetil (MMF)?

Treatment of a 7-Year-Old Child with Frequently Relapsing Nephrotic Syndrome (FRNS) Using Mycophenolate Mofetil (MMF)

Mycophenolate mofetil (MMF) is recommended as an effective corticosteroid-sparing agent for children with FRNS at a starting dose of 1200 mg/m²/day given in two divided doses for at least 12 months, as most children will relapse when MMF is stopped. 1

Initial Approach to MMF Therapy

• MMF should be initiated at a dose of 1200 mg/m²/day (approximately 600 mg/m² twice daily) with a maximum dose of 1 g twice daily 1, 2
• MMF should be combined with a tapering dose of alternate-day prednisone during the initial phase of treatment to maintain remission while transitioning to MMF 2
• MMF therapy should be continued for a minimum of 12 months to maximize effectiveness in preventing relapses 1

Rationale for Using MMF in FRNS

• MMF is suggested by KDIGO guidelines as an appropriate corticosteroid-sparing agent for children with FRNS who develop steroid-related adverse effects 1
• MMF has a favorable side-effect profile compared to alkylating agents (cyclophosphamide, chlorambucil) and calcineurin inhibitors (cyclosporine, tacrolimus) 1
• MMF has been shown to significantly reduce relapse rates in children with FRNS from one episode every 2 months before treatment to one every 14.7 months after treatment 2

Monitoring and Follow-up During MMF Therapy

• Regular monitoring of complete blood count is necessary to detect potential bone marrow suppression 3
• Monitor for gastrointestinal side effects (diarrhea, nausea, abdominal pain), which are the most common adverse events 2, 4
• Assess renal function periodically, although MMF does not cause nephrotoxicity like calcineurin inhibitors 1
• Continue to monitor for proteinuria to evaluate treatment response 1

Expected Outcomes with MMF Treatment

• Approximately 75% of children with FRNS remain in remission throughout 6 months of MMF therapy 2
• MMF therapy can reduce relapse rates by up to 74% during the treatment period 5
• Some patients (approximately 25%) may maintain long-term remission for 18-30 months after stopping MMF 2
• The relapse-preventing effect typically diminishes after MMF discontinuation 5

Infection Prevention During Immunosuppressive Therapy

• Ensure pneumococcal vaccination is up-to-date 1
• Provide annual influenza vaccination to the child and household contacts 1
• Defer live vaccines until prednisone dose is below 1 mg/kg daily or 2 mg/kg on alternate days 1
• Live vaccines are contraindicated while the child is receiving MMF 1
• Following close contact with varicella infection, administer varicella zoster immune globulin if the child is non-immune 1

When to Consider Alternative Therapies

• If the child fails to maintain remission despite adequate MMF dosing, consider:
  • Calcineurin inhibitors (cyclosporine 4-5 mg/kg/day or tacrolimus 0.1 mg/kg/day) 1, 4
  • Levamisole 2.5 mg/kg on alternate days (if available) 1
  • Alkylating agents only if other options have failed (cyclophosphamide 2 mg/kg/day for 8-12 weeks, maximum cumulative dose 168 mg/kg) 1
• Consider rituximab only in steroid-dependent cases with frequent relapses despite optimal combinations of prednisone and corticosteroid-sparing agents 1, 5

Common Pitfalls and Caveats

• Do not use MMF as monotherapy initially; always combine with a tapering course of steroids 2
• Do not discontinue MMF prematurely (before 12 months), as this significantly increases risk of relapse 1, 5
• Avoid azathioprine as a corticosteroid-sparing agent in FRNS as it is not recommended 1
• Be aware that MMF may have reduced bioavailability when taken with food; consistent administration with respect to meals is important 3
• Consider kidney biopsy if there is late failure to respond following initial response to corticosteroids or if there is suspicion of a different underlying pathology 1

MMF represents an effective second-line therapy for children with FRNS with a favorable safety profile compared to other immunosuppressive agents, making it a valuable option for long-term management of this challenging condition 1, 2, 4.