What is the optimal treatment approach for a patient with IgA (Immunoglobulin A) vasculitis?

Treatment of IgA Vasculitis in Adults

For adults with IgA vasculitis, treatment should be stratified by disease severity: supportive care alone for self-limited cutaneous disease, glucocorticoids (prednisolone 1 mg/kg/day, maximum 60-80 mg) for severe skin or gastrointestinal manifestations, and glucocorticoids combined with immunosuppressive agents (cyclophosphamide, rituximab, or mycophenolate mofetil) for severe IgA vasculitis nephritis with risk factors for progression to end-stage renal disease. 1, 2, 3

Disease Severity Stratification and Initial Assessment

IgA vasculitis (IgAV) in adults differs fundamentally from pediatric disease, with higher frequency of glomerulonephritis (IgAV nephritis) and greater risk of progression to end-stage renal disease (10-30% of affected adults) compared to children. 1, 2

Immediately assess for organ-threatening manifestations:

• Obtain urinalysis for hematuria, proteinuria, and red cell casts; measure serum creatinine and estimate GFR to detect nephritis early. 2, 3
• Evaluate for gastrointestinal bleeding, severe abdominal pain, or intussusception, which represent principal causes of morbidity in adults. 2
• Baseline proteinuria >1-1.5 g/day, impaired renal function at presentation, and renal biopsy findings of interstitial fibrosis, sclerotic glomeruli, or fibrinoid necrosis predict long-term progression to ESRD. 2

Treatment Algorithm by Disease Severity

Self-Limited Cutaneous Disease Without Organ Involvement

For isolated palpable purpura without systemic manifestations, supportive care with symptomatic treatment is sufficient, as disease course is usually benign and self-limiting. 4, 5, 1

• Colchicine, dapsone, or methotrexate can control minor cutaneous or articular manifestations as glucocorticoid-sparing agents. 1

Severe Cutaneous or Gastrointestinal Manifestations

Initiate glucocorticoids (prednisolone 1 mg/kg/day, maximum 60-80 mg/day) for severe skin manifestations with incipient necrosis or severe gastrointestinal complications including bleeding or severe abdominal pain. 6, 1, 2

• Taper glucocorticoids to maintenance dose of 10 mg/day or less during remission, with gradual reduction after 6-18 months depending on response. 6

IgA Vasculitis Nephritis (Severe Renal Involvement)

For proliferative glomerulonephritis or IgAV nephritis with risk factors for progression (proteinuria >1 g/day, impaired baseline renal function), combine glucocorticoids with immunosuppressive therapy following recommendations adapted from ANCA-associated vasculitis and IgA nephropathy management. 5, 1, 3

Induction therapy options (3-6 months):

• Glucocorticoids plus cyclophosphamide (2 mg/kg/day for 3-6 months) for severe glomerulonephritis. 1, 3
• Glucocorticoids plus rituximab (375 mg/m² weekly for 4 weeks) has demonstrated efficacy in reducing relapse frequency and achieving long-term remission. 1
• Glucocorticoids plus mycophenolate mofetil has shown favorable results as an alternative immunosuppressive agent. 1, 3

Maintenance therapy (minimum 18-24 months following remission):

• Calcineurin inhibitors (cyclosporine A or tacrolimus) or mycophenolate mofetil serve as glucocorticoid-sparing maintenance agents. 1
• Azathioprine or methotrexate can be used for maintenance following cyclophosphamide induction. 6

Refractory or Life-Threatening Disease

For patients failing to achieve remission or with life-threatening manifestations:

• Plasma exchange therapy combined with immunosuppression can be useful in difficult and life-threatening situations. 1
• Intravenous immunoglobulin (IVIG) may achieve remission in refractory cases, but measure serum immunoglobulin levels first as selective IgA deficiency may cause anaphylaxis. 6, 1
• Switch from cyclophosphamide to rituximab or vice versa if initial therapy fails. 6

Critical Pitfalls to Avoid

Do not confuse IgA vasculitis with ANCA-associated vasculitis (AAV), as they are distinct entities despite some overlapping treatment approaches. IgAV is characterized by IgA1-dominant immune deposits, whereas AAV involves ANCA antibodies. 4, 5

Do not delay treatment waiting for biopsy results if clinical presentation strongly suggests severe IgAV nephritis, particularly with rapidly declining GFR or nephritic syndrome. 6

Recognize that absence of correlation between initial presentation and long-term renal outcome makes management challenging—patients with severe presentation may experience spontaneous remission, while those with mild symptoms may progress to ESRD. 2

Monitor for disease relapse during follow-up, as IgAV characteristically relapses; rituximab has shown particular efficacy in reducing relapse frequency and lowering cumulative glucocorticoid burden. 1

Evidence Quality and Controversies

High-quality evidence for treatment of severe IgAV in adults is lacking, with most recommendations extrapolated from pediatric studies, IgA nephropathy trials, or ANCA-associated vasculitis guidelines. 2, 3

Controversy exists regarding whether corticosteroids or immunosuppressive agents improve long-term renal outcome in proliferative glomerulonephritis, as prospective randomized controlled trials are needed to analyze benefit-risk ratios. 2, 3

Emerging therapies with encouraging preliminary results include TRF-budesonide, B-cell-directed therapy, SGLT-2 inhibitors, endothelin receptor antagonists, and complement pathway inhibitors, but these require further research before routine clinical use. 1