What is the initial treatment for adult IgA (Immunoglobulin A) vasculitis?

Initial Treatment for Adult IgA Vasculitis

For adult IgA vasculitis, initiate treatment with high-dose glucocorticoids at 1 mg/kg/day (maximum 60-80 mg/day) as first-line therapy, with the addition of immunosuppressive agents reserved for severe organ-threatening manifestations, particularly renal involvement. 1

Disease Severity Assessment

The treatment approach depends critically on disease severity at presentation:

• Severe disease includes life- or organ-threatening manifestations such as glomerulonephritis with rapidly declining renal function (creatinine >300 µmol/L or >3.4 mg/dL), severe gastrointestinal involvement with bleeding or perforation risk, or pulmonary hemorrhage 2
• Non-severe disease presents with isolated cutaneous purpura, arthralgias, or mild gastrointestinal symptoms without organ dysfunction 1, 3

Glucocorticoid Therapy Protocol

Initial Dosing

• Start with prednisone 1 mg/kg/day (maximum 60-80 mg/day) for adults with severe manifestations 2, 1
• For weight-based dosing: patients <50 kg receive 50 mg/day, 50-75 kg receive 60 mg/day, and >75 kg receive 75 mg/day in week 1 2
• Maintain this high dose for approximately one month before initiating taper 4

Tapering Schedule

The evidence supports a structured, gradual taper over 4-5 months 2:

• Weeks 2-4: Reduce to 20-30 mg/day depending on body weight 2
• Months 2-3: Target 15-20 mg/day 4
• Months 4-5: Achieve 5 mg/day 2, 4
• Beyond 6 months: Attempt complete withdrawal if disease remains in remission 4

Critical pitfall: Tapering glucocorticoids too quickly leads to disease flare and should be avoided 4. The median time to achieve 10 mg/day in major trials is 19 weeks, and 7.5 mg/day by 21 weeks 2.

Immunosuppressive Therapy for Severe Disease

Indications for Adding Immunosuppression

Add immunosuppressive agents when patients present with:

• Glomerulonephritis with proteinuria >1 g/day despite 3-6 months of optimized supportive care 2
• Rapidly progressive renal dysfunction (creatinine >300 µmol/L or requiring dialysis) 2
• Severe gastrointestinal manifestations with bleeding or perforation risk 1, 3
• Steroid-refractory disease after appropriate glucocorticoid trial 4, 1

First-Line Immunosuppressive Options

Cyclophosphamide remains the traditional choice for severe organ-threatening disease 2, 1:

• Oral: 2 mg/kg/day (maximum 200 mg/day) for 3-6 months, with dose reduction for age (1.5 mg/kg/day if >60 years, 1.0 mg/kg/day if >70 years) 2
• Intravenous: 15 mg/kg every 2 weeks for 3 doses, then every 3 weeks for at least 3 additional doses 2
• Reduce dose by 0.5 mg/kg/day (oral) or 2.5 mg/kg (IV) if GFR <30 ml/min/1.73 m² 2

Important caveat: One randomized trial in adults with IgA vasculitis and renal involvement showed cyclophosphamide did not improve renal outcomes or patient survival, highlighting the controversy in this area 5. However, it remains recommended based on extrapolation from ANCA-associated vasculitis data 2.

Rituximab is emerging as an effective alternative 1, 6:

• Dose: 375 mg/m² weekly for 4 weeks or 1,000 mg on days 1 and 15 2
• A multicenter study of 22 adults with IgA vasculitis showed 90.9% achieved remission with rituximab, with significant reductions in proteinuria, inflammatory markers, and glucocorticoid requirements 6
• Particularly useful for patients with refractory/relapsing disease or contraindications to cyclophosphamide 6, 5

Alternative Immunosuppressive Agents

For patients intolerant of cyclophosphamide or with less severe disease 1:

• Mycophenolate mofetil: 2,000-3,000 mg/day in divided doses 2, 1
• Azathioprine: 1-2 mg/kg/day 2
• Calcineurin inhibitors (cyclosporine A, tacrolimus): Favorable results as glucocorticoid-sparing agents 1

Supportive Care Measures

Infection Prophylaxis

• Pneumocystis jirovecii prophylaxis with trimethoprim/sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) for all patients receiving cyclophosphamide or rituximab with high-dose glucocorticoids 2
• Alternatives if contraindicated: dapsone or atovaquone 2

Bone Protection

• Consider bone protection therapy for all patients on prolonged glucocorticoid treatment 4

Renal-Specific Management

• ACE inhibitors or ARBs for blood pressure control and proteinuria reduction in patients with proteinuria >1 g/day 2
• Target blood pressure <125/75 mm Hg if proteinuria >1 g/day 2

Treatment for Non-Severe Disease

For patients with isolated cutaneous purpura, arthralgias, or mild symptoms without organ involvement 1, 3:

• Symptomatic treatment alone may be sufficient, as spontaneous remission can occur 3, 5
• Colchicine, dapsone, or methotrexate can control minor manifestations 1
• Close monitoring for development of renal involvement is essential, as nephritis can appear later in the disease course 7, 3

Special Considerations and Monitoring

Disease Monitoring

• Structured clinical assessment with urinalysis at each visit rather than relying on laboratory markers alone 2
• Monitor for proteinuria progression, as up to one-third of adults may progress to end-stage renal disease 7, 3

Refractory Disease

• Patients with disease refractory to standard therapy require thorough reassessment and should be managed at or referred to centers with vasculitis expertise 2
• Consider plasma exchange for severe renal involvement (creatinine >300 µmol/L) or diffuse alveolar hemorrhage, though evidence is limited 2

Key distinction from pediatric disease: Adult IgA vasculitis has a more severe course with higher frequency of glomerulonephritis (occurring in most adults vs. minority of children) and greater risk of progression to end-stage renal disease, necessitating more aggressive treatment approaches 7, 1, 3.