Management of Vasculitis in IgA Nephropathy Patient on Enalapril, Dapagliflozin, and Febuxostat
Immediate Action: Determine Vasculitis Type and Discontinue Causative Medication
The first critical step is to immediately discontinue febuxostat, as it is the most likely culprit for drug-induced vasculitis in this clinical scenario, while continuing enalapril and dapagliflozin which are beneficial for IgA nephropathy. 1
Diagnostic Assessment Required
Determine if this is drug-induced vasculitis versus IgA vasculitis (IgAV) - the distinction fundamentally changes management, as drug-induced vasculitis requires only medication withdrawal while IgAV may require immunosuppression 1, 2
Obtain ANCA testing immediately - high-titre MPO ANCA positivity or dual MPO and PR3 ANCA positivity strongly suggests drug-induced rather than idiopathic vasculitis 2
Assess for life-threatening or organ-threatening manifestations - specifically evaluate for renal involvement (rising creatinine, active urinary sediment with RBC casts), pulmonary involvement (hemoptysis, infiltrates), or other major organ involvement 1
Perform skin biopsy if cutaneous vasculitis is present - leukocytoclastic vasculitis on biopsy supports drug-induced etiology 2
Treatment Algorithm Based on Vasculitis Severity
If Limited Cutaneous Vasculitis Without Organ Involvement
Discontinue febuxostat immediately and observe without immunosuppression - drug withdrawal alone is often sufficient for drug-induced leukocytoclastic vasculitis and typically leads to prompt resolution 2
Add systemic corticosteroids only if signs of incipient skin necrosis develop - prednisolone 1 mg/kg/day (maximum 60 mg/day) 2
Do NOT use cyclophosphamide or rituximab - these are inappropriate for drug-induced vasculitis and expose patients to unnecessary toxicity 2
If Organ-Threatening or Life-Threatening Vasculitis
If there is renal involvement, pulmonary involvement, or other organ-threatening manifestations, initiate cyclophosphamide plus high-dose corticosteroids immediately - this suggests true IgA vasculitis rather than drug-induced disease 1
Administer intravenous methylprednisolone 500-1000 mg daily for 3 days, followed by oral prednisone 1 mg/kg/day 3
Start cyclophosphamide 2 mg/kg daily for 3-6 months as first-line remission induction therapy 4, 5
Consider rituximab 375 mg/m² weekly for 4 weeks as alternative if cyclophosphamide is contraindicated 4, 5
Add plasmapheresis if serum creatinine ≥500 μmol/L (5.7 mg/dL) due to rapidly progressive glomerulonephritis, or for severe diffuse alveolar hemorrhage 4, 3
Medication Management Strategy
Continue Beneficial IgA Nephropathy Medications
Continue enalapril (ACE inhibitor) as it provides essential RAS blockade - this should be maintained irrespective of hypertension if proteinuria >0.5 g/day 4
Continue dapagliflozin (SGLT2 inhibitor) as it reduces proteinuria and slows eGFR decline - recent evidence demonstrates efficacy in IgA nephropathy patients even after corticosteroid treatment 6, 7
Replace Febuxostat for Gout Management
Switch to allopurinol once vasculitis has resolved - start at low dose (≤100 mg daily, lower if CKD present) and titrate to target serum uric acid <6 mg/dL 1
Test for HLA-B*5801 allele before starting allopurinol in patients of Southeast Asian descent or African American to prevent severe hypersensitivity reactions 1
Provide mandatory gout flare prophylaxis with colchicine (0.5-1 mg daily, dose-adjusted for renal function) for at least 6 months when initiating allopurinol 1
Never combine allopurinol with febuxostat - they have redundant mechanisms and increase toxicity without therapeutic benefit 1
Alternative Antihypertensive Options if Needed
If additional blood pressure control is required, add calcium channel blocker (amlodipine 2.5-10 mg daily) or thiazide diuretic (chlorthalidone 12.5-25 mg daily) - these are not associated with vasculitis and are effective first-line agents 1
Infection Prophylaxis During Immunosuppression
If immunosuppressive therapy is initiated, provide trimethoprim-sulfamethoxazole prophylaxis - use 800/160 mg on alternate days or 400/80 mg daily for Pneumocystis jiroveci prevention 4, 3
Administer pneumococcal vaccine to patients with nephrotic syndrome and/or CKD 4
Ensure influenza vaccine for patient and household contacts 4
Screen for tuberculosis, hepatitis B, hepatitis C, HIV, and syphilis before initiating immunosuppression 4
Critical Monitoring Parameters
Monitor renal function, urinalysis, and inflammatory markers (CRP, ESR) weekly initially, then monthly until complete resolution 1
Assess for hematuria magnitude and persistence - this has prognostic value in IgA nephropathy and IgA vasculitis 4
Evaluate urine sediment for erythrocyte morphology, red cell casts, and acanthocytes routinely 4
Target proteinuria reduction to <1 g/day as a surrogate marker of improved kidney outcome 4
Critical Pitfalls to Avoid
Do not confuse drug-induced leukocytoclastic vasculitis with ANCA-associated vasculitis requiring aggressive immunosuppression - this is the most dangerous error and leads to unnecessary cyclophosphamide or rituximab exposure 2
Do not combine ACE inhibitors with ARBs or renin inhibitors - this combination is potentially harmful without additional benefit 1
Do not use azathioprine, mycophenolate mofetil, calcineurin inhibitors, or rituximab for IgA nephropathy itself - these are not recommended except in the specific context of rapidly progressive disease or clinical trials 4