Case Presentation: An 87-year-old female with stage 4 chronic kidney disease, hypertension, and heart failure presented with concern for acute kidney injury based on outpatient laboratory studies. She had sought prior care for worsening fatigue, lightheadedness, productive cough, and decreased urine output. Lab results revealed a creatinine of 4.4 mg/dL (baseline 1.7 mg/dL) and potassium of 5.6 mEq/L, prompting her hospital admission.On arrival, she reported several days of worsening exertional dyspnea. Medications included torsemide, sacubitril-valsartan, carvedilol, hydralazine, amlodipine, atorvastatin, aspirin, phenytoin, pantoprazole, nitroglycerin, and fluoxetine. She was afebrile with blood pressure of 162/79 and otherwise normal vitals and unremarkable physical exam. Chest x-ray significant for interstitial and alveolar opacities. Laboratory results included elevated ESR (90 mm/hr) and CRP (35 mg/L). Urinalysis was notable for 3+ blood, RBCs >50, and proteinuria. Chest CT revealed ground-glass opacities.Subsequent labs revealed elevated anti-dsDNA (26), MPO (91), PR3 (138), and ANA (1/160 homogenous) and indeterminate ANCA. Nephrology was consulted for kidney biopsy, which showed necrotizing crescentic glomerulonephritis consistent with ANCA vasculitis. Electron micrograph findings showed evidence for both lupus and pauci-immune glomerulonephritis. Hydralazine and phenytoin were stopped due to concern for drug-induced nephritis. High dose glucocorticoid was initiated after renal biopsy and rituximab initiated thereafter. Her hospital course was complicated by hemorrhagic shock from perinephric hematoma, which lead to hemodialysis initiation. She was eventually discharged to skilled nursing facility, and had several readmissions for associated dyspnea, fatigue and elevated volume status. The patient was transitioned to hospice and expired five months after her initial admission.
Discussion: Hydralazine is a common antihypertensive, but has the serious side effect of drug induced lupus (DIL) and the more rare ANCA vasculitis (1, 2). Research has shown slow acetylators and patients with HLA-DR4 antigens have an increased risk of DIL (3). These markers are not always easy to detect. Other case reports of DIL and/or ANCA vasculitis show diverse presentations of this condition, including acute hypoxemic respiratory failure and UTI (1), nephrotic syndrome, acute kidney injury (4), and/or weight loss (5). Several patients had an underlying fatigue and/or generalized weakness for weeks prior to presentation (1, 5, 6); weakness was noted in all reviewed case reports with overlapping syndromes. While prognosis of hydralazine-induced lupus is generally favorable, mortalities have been reported (7, 8).
Conclusions: Hospitalists should consider drug-induced lupus and/or ANCA vasculitis in patients with fatigue, respiratory symptoms, and acute kidney injury while on hydralazine, even if the drug was initiated years prior. High index of suspicion is needed to recognize this potential complication of hydralazine due to often nonspecific presenting symptoms. Early diagnosis and discontinuation of hydralazine are crucial to prevent progression to renal failure and death.