What is the treatment for severe IgA (Immunoglobulin A) vasculitis with nephritis?

Treatment of Severe IgA Vasculitis with Nephritis

For severe IgA vasculitis with nephritis, the recommended treatment is a combination of high-dose glucocorticoids and cyclophosphamide, with consideration of plasma exchange in cases with rapidly progressive glomerulonephritis or serum creatinine >500 μmol/L (5.7 mg/dL). 1, 2

Initial Assessment and Treatment Approach

• Treatment should be initiated without delay, even if kidney biopsy results are pending, especially in patients with rapidly deteriorating renal function 1, 3
• Patients with IgA vasculitis with nephritis should ideally be managed at centers with experience in vasculitis management 1, 3
• Kidney biopsy is strongly recommended to confirm diagnosis and assess severity of nephritis when feasible 1

Induction Therapy

Glucocorticoids

• Initial therapy typically includes IV methylprednisolone (500-1000 mg/day for 1-3 days) followed by oral prednisone 3
• Oral prednisone should be started at 0.8-1 mg/kg/day (maximum 60-75 mg/day) with gradual tapering according to clinical response 1, 2
• A reduced-dose glucocorticoid regimen may be considered to minimize toxicity while maintaining efficacy, with a target of 5-7.5 mg/day by 3-5 months 1

Cyclophosphamide

• Cyclophosphamide is the preferred immunosuppressive agent for severe IgA vasculitis with nephritis 1, 2, 4
• Dosing options:
  • Oral cyclophosphamide: 1.5-2 mg/kg/day (maximum 200 mg/day) 3, 2
  • Intravenous cyclophosphamide: 15 mg/kg as pulses at weeks 0,2,4,7,10, and 13 1, 3
• Treatment duration should be tailored to individual response, with an average duration of 12-18 weeks until plateau of response 2

Plasma Exchange

• Consider plasma exchange for patients with:
  • Rapidly progressive glomerulonephritis 1
  • Serum creatinine >500 μmol/L (5.7 mg/dL) 1
  • Severe diffuse alveolar hemorrhage (if present) 1

Maintenance Therapy

• After achieving remission (typically 3-6 months), transition from cyclophosphamide to a less toxic maintenance agent 1, 3
• Recommended maintenance options include:
  • Azathioprine (1-2 mg/kg/day) as first-line maintenance therapy 1
  • Mycophenolate mofetil (up to 1g twice daily) for patients intolerant to azathioprine 1, 5
  • Methotrexate (initially 0.3 mg/kg/week, maximum 25 mg/week) if GFR >60 ml/min/1.73m² 1
• Maintenance therapy should be continued for at least 18-24 months following induction of sustained remission 1
• Low-dose glucocorticoids (5-7.5 mg/day) should be continued during maintenance therapy 1, 2

Alternative Therapies for Refractory Disease

• For patients not responding to cyclophosphamide and glucocorticoids:
  • Rituximab may be considered as an alternative immunosuppressive agent 1, 5, 4
  • Intravenous immunoglobulin can be useful in difficult cases 5
  • Calcineurin inhibitors (cyclosporine A, tacrolimus) have shown favorable results as glucocorticoid-sparing agents 5, 4

Supportive Care and Monitoring

• Implement prophylaxis against Pneumocystis jirovecii pneumonia with trimethoprim-sulfamethoxazole 1, 3
• Consider osteoporosis prophylaxis with calcium, vitamin D, and bisphosphonates 3
• Regular monitoring should include:
  • Renal function tests and urinalysis 1, 3
  • Complete blood counts to monitor for drug toxicity 3
  • Inflammatory markers 3
  • ANCA levels (if initially positive) 1, 3

Prognosis and Long-term Considerations

• Long-term prognosis is heavily dependent on the presence and severity of nephritis 6, 7
• Up to one-third of adult patients with IgA vasculitis nephritis may progress to end-stage renal disease 6, 5
• Early aggressive treatment with cyclophosphamide and glucocorticoids has been shown to improve outcomes in severe cases with crescentic changes 2
• Persistent hematuria may indicate ongoing disease activity, while resolution followed by recurrence suggests relapse 3

Common Pitfalls to Avoid

• Do not delay treatment while waiting for biopsy results in patients with clinical presentation compatible with severe IgA vasculitis and evidence of nephritis 1, 3
• Do not withhold treatment based solely on unfavorable histologic findings, as kidney recovery can occur even with advanced damage 3
• Do not underestimate the importance of monitoring for drug toxicity, especially with cyclophosphamide 3
• Do not discontinue maintenance therapy too early, as this increases risk of relapse 1