What is the treatment approach for a patient with IgA vasculitis, considering the severity of symptoms and potential organ involvement, such as impaired renal function?

Treatment of IgA Vasculitis

For mild IgA vasculitis with isolated skin manifestations, supportive care with NSAIDs and rest is sufficient, but for severe disease with renal involvement (proteinuria >1g/day, declining GFR, or crescentic glomerulonephritis) or life-threatening gastrointestinal complications, initiate high-dose glucocorticoids (prednisone 1 mg/kg/day) immediately, and add cyclophosphamide or rituximab for organ-threatening disease. 1, 2

Disease Severity Stratification

The treatment approach must be tailored to disease severity and organ involvement:

• Mild disease includes isolated palpable purpura, arthralgias, and self-limited gastrointestinal symptoms without organ dysfunction 3, 1
• Severe disease is defined by life- or organ-threatening manifestations: severe glomerulonephritis with declining renal function, hemorrhagic gastrointestinal involvement with bleeding or perforation risk, or extensive skin necrosis 2, 1
• Renal involvement occurs more frequently in adults (30-60%) compared to children and carries worse prognosis, with 10-30% progressing to end-stage renal disease 4, 1

Treatment Algorithm by Disease Severity

Mild, Self-Limited Disease

• Supportive care only for uncomplicated purpura and arthralgias without organ involvement 3, 1
• NSAIDs for symptomatic relief of joint pain 1
• Monitor for progression with serial urinalysis, serum creatinine, and blood pressure 4

Common pitfall: Failing to monitor for renal involvement—check urinalysis weekly for the first month, as nephritis can develop after initial presentation 4

Moderate Disease with Minor Organ Involvement

For persistent symptoms or minor renal involvement (microscopic hematuria, proteinuria <1g/day):

• Colchicine 0.6-1.2 mg daily as first-line steroid-sparing agent 1, 5
• Dapsone 50-100 mg daily as alternative 1, 5
• Short-course glucocorticoids (prednisone 0.5 mg/kg/day for 2-4 weeks with taper) for persistent purpura or arthralgias 1

Severe Disease with Organ-Threatening Manifestations

Induction therapy for severe glomerulonephritis (proteinuria >1g/day, declining GFR, crescentic changes on biopsy) or life-threatening gastrointestinal involvement:

• High-dose glucocorticoids: Prednisone 1 mg/kg/day (maximum 80 mg) or IV methylprednisolone 500-1000 mg daily for 3 days in critical cases 1, 2
• Plus cyclophosphamide: 2 mg/kg/day oral (maximum 200 mg) or IV pulse 0.6 g/m² every 2-4 weeks 2, 1
• OR rituximab: 375 mg/m² weekly for 4 weeks or 1000 mg on days 1 and 15, particularly for refractory cases with 91% remission rates 2, 1

Critical consideration: While these recommendations are extrapolated from ANCA-associated vasculitis and IgA nephropathy protocols (as no specific RCTs exist for severe IgAV), this approach is supported by case series and expert consensus 3, 1

Maintenance Therapy

After achieving remission (typically 3-6 months):

• Azathioprine 1-2 mg/kg/day for at least 18 months 2, 1
• OR mycophenolate mofetil 2 g/day in divided doses as glucocorticoid-sparing alternative 2, 1
• Glucocorticoid taper: Maintain high-dose for minimum 1 month, then gradual taper over 6-12 months 1
• Rituximab has shown efficacy in reducing relapse frequency and achieving long-term remission 1

Renal-Specific Management

For IgAV nephritis, treatment follows IgA nephropathy protocols:

• ACE inhibitors or ARBs for all patients with proteinuria >0.5 g/day for renoprotection 4, 5
• Glucocorticoids alone may be insufficient for severe glomerulonephritis in adults—combination immunosuppression is typically required 4, 5
• Kidney biopsy should be performed when renal involvement is suspected to guide treatment intensity based on histologic severity 4

Adjunctive Therapies and Prophylaxis

Mandatory supportive measures for patients on immunosuppression:

• Pneumocystis prophylaxis: Trimethoprim-sulfamethoxazole for all patients receiving cyclophosphamide 6
• Bone protection: Calcium, vitamin D, and bisphosphonates for all patients on glucocorticoids 6
• Mesna with cyclophosphamide to prevent hemorrhagic cystitis 7
• Antiemetics routinely with IV cyclophosphamide 7

Refractory Disease Options

For patients not responding to initial therapy:

• Intravenous immunoglobulin (IVIG): 2 g/kg over 5 days for persistent low-level activity 6, 1
• Plasma exchange: Consider for rapidly progressive glomerulonephritis with dialysis requirement or severe crescentic disease 1
• Rituximab: Highly effective (91% remission) for refractory cases, particularly in reducing glucocorticoid burden 2, 1
• Calcineurin inhibitors (cyclosporine A, tacrolimus): Promising results as steroid-sparing agents 1

Key Clinical Pitfalls

• Adult IgAV is not benign: Unlike children, adults have 3-fold higher risk of severe renal involvement and worse long-term outcomes 3, 4
• Don't delay treatment: Severe gastrointestinal involvement can rapidly progress to perforation or ischemia—early aggressive therapy is critical 2
• Monitor for infection: Treatment-related complications including secondary hypogammaglobulinemia and opportunistic infections are significant causes of morbidity 2
• Long-term follow-up essential: Up to one-third of adults with IgAV nephritis progress to end-stage renal disease, requiring years of monitoring 4