A Case of Hydralazine-Induced ANCA-Associated Vasculitis

Introduction: ANCA vasculitis is a systemic autoimmune disease that results in small-vessel inflammation caused by pathogenic autoantibodies directed against proteinase-3 or myeloperoxidase. Hydralazine is a commonly used antihypertensive which is known to precipitate drug-induced lupus. However, it can also cause a drug induced ANCA vasculitis, which presents with a necrotizing and crescentic glomerulonephritis. We present a case of hydralazine induced ANCA vasculitis. Case Description: A 69-year old female with chronic sinusitis and CKD 3B attributed to HTN, presented for a 3-week history of nausea, vomiting, and poor PO intake. Work up revealed an AKI (Cr 7.8mg/dL from a baseline of 1.6mg/dL), with new onset hematuria, non-nephrotic range proteinuria (UPCR 0.5g), and an elevated ESR. Her antihypertensive regimen included hydralazine, hydrochlorothiazide, and nifedipine. Given concerns for an underlying glomerulonephritis, she underwent a renal biopsy, which showed pauci-immune (ANCA) focal necrotizing and crescentic GN. Anti-histone Ab levels were elevated at 6.1 units and there was dual ANCA positivity (pANCA >1:1280; MPO 254;SP3 49). The patient was started on solumedrol IV for 3 days and transitioned to PO prednisone with a four-month taper. She was also given rituximab 1000mg weekly for two doses, followed by 500mg every four months for maintenance therapy. She initially had improvement in her renal function (Cr 5mg/dL), but unfortunately was re-admitted due to worsening renal function and required initiation of hemodialysis. Discussion: As clinicians, we should always be cognizant of the potential harms of the medications we prescribe. Hydralazine can cause a drug-induced ANCA vasculitis associated with elevated ANA, anti-histone antibodies, and dual ANCA positivity (MPO-ANCA and anti-PR3 antibodies) in one third of patients. Patients who develop these complications should immediately stop the offending agent and receive immunosuppressive therapy. Unfortunately, a literature review shows that 27% of patients progress to ESRD despite treatment, demonstrating the importance of early diagnosis. Nephrologists should keep a high level of suspicion when patients on these medications present with worsening renal function and a nephritic syndrome.