SCIENTIFIC
Hydralazine-Induced Vasculitis Causing Pulmonary- Renal Syndrome : Two Cases and a Literature Review
AUTHORS : Mark Radow , MD
R . Scott Morehead , MD
Division of Pulmonology and Critical Care Medicine , West Virginia University School of Medicine , Charleston Area Medical Center
CASE PRESENTATION
CASE 1 A 76-year-old woman with atrial fibrillation , diastolic heart failure , chronic obstructive pulmonary disease , hypertension , and chronic kidney disease was hospitalized with dyspnea and symptomatic anemia . She denied fever , cough , hemoptysis , and sputum production . Home medications included tramadol , fluticasone-salmeterol inhaler , omeprazole , clonidine , amlodipine , metoprolol , and hydralazine .
Upon presentation , the patient was afebrile , normotensive , and her oxygen saturation was 96 % on ambient air . Her examination was unremarkable except for left-sided inspiratory rales and a right pleural effusion . Laboratory results revealed anemia , elevated inflammatory markers , microscopic hematuria , and renal failure ( Table 1 ). Chest radiograph and computed tomography ( CT ) revealed bilateral airspace disease and a right pleural effusion ( Figure 1 A and B ).
Despite a blood transfusion and furosemide administration , she became hypoxic and required tracheal intubation . Thoracentesis yielded a transudate with negative cytology . Bronchoscopy with sequential bronchoalveolar lavages ( BAL ) yielded fluid consistent with diffuse alveolar hemorrhage ( DAH ) and pulmonary-renal syndrome was ultimately diagnosed .
Serology results were consistent with hydralazine-induced , anti-neutrophil cytoplasmic antibody ( ANCA ) -associated vasculitis ( Table 1 ) and hydralazine usage was discontinued . High-dose intravenous ( IV ) methylprednisolone and plasma exchange
ABSTRACT
INTRODUCTION Hydralazine has been used to treat hypertension for several decades , but its use has been limited due to side effects , principally drug-induced lupus . Nevertheless , prescriptions for hydralazine have increased in the last decade . Anti-neutrophil cytoplasmic antibody ( AN- CA ) -associated vasculitis is a less appreciated
were administered , followed by rituximab infusion . Her inflammatory markers and airspace disease on chest radiograph improved , resulting in successful liberation from mechanical ventilation . However , the patient subsequently developed abdominal pain four days after extubation , prompting an abdominal radiograph that revealed free intraperitoneal air . Emergent surgical exploration revealed sigmoid diverticulitis with perforation requiring resection and colostomy formation . The patient died four hours after returning to the intensive care unit .
CASE 2 A 72-year-old woman with coronary artery disease , hypertension , diabetes mellitus , diastolic heart failure , prior curative lobectomy for carcinoid tumor , and chronic kidney disease was hospitalized due to angioedema of her tongue two weeks after starting lisinopril . She described dyspnea for several prior months but denied cough , sputum production , and hemoptysis . Home medications included cyclobenzaprine , escitalopram , insulin , omeprazole , oxcarbazepine , rosuvastatin , trazodone , clonidine , carvedilol , hydrochlorothiazide , losartan , and hydralazine .
Upon presentation , the patient was afebrile , normotensive , and her oxygen saturation was 97 % on ambient air . Her examination was unremarkable except for edema of the tongue . Laboratory results revealed anemia , elevated inflammatory markers , microscopic hematuria , and renal failure ( Table 1 ). Chest radiograph and CT revealed bilateral airspace disease ( Figure 1 C and D ). but more severe side effect of hydralazine use . Here we present two cases of pulmonary-renal syndrome due to hydralazine-induced ANCA-associated vasculitis and a medical literature review of this topic . This report underscores the importance of prompt recognition and treatment of this condition .
The angioedema improved within 24 hours of IV methylprednisolone , IV diphenhydramine , and fresh frozen plasma transfusion . The following morning , however , the patient developed worsening dyspnea and new hemoptysis . Empiric antibiotics and IV furosemide were given , but tracheal intubation was ultimately required . Sequential BALs revealed fluid consistent with DAH .
Hydralazine was discontinued , and the patient ’ s serology was consistent with a diagnosis of hydralazine-induced ANCA-associated vasculitis ( Table 1 ). After three days of high-dose IV methylprednisolone and plasma exchange , the patient improved and was successfully extubated . Rituximab infusion was started prior to discharge . At a three-month follow up appointment , supplemental oxygen was no longer required , but she remained dialysis dependent .
DISCUSSION
Drug-induced vasculitis is important to recognize because of the discontinue of the suspected drug is the first step in management . Many drugs may produce vasculitis , and reported clinical manifestations range from a benign , self-limited rash to life threatening organ involvement . 1 Pulmonary-renal syndrome is a small-vessel vasculitis that causes DAH and rapidly progressive glomerulonephritis . Primary ANCA-associated vasculitis ( e . g . granulomatosis with polyangiitis ) and anti-glomerular basement membrane disease account for 68-95 % of cases . 2 Drug-induced vasculitis uncommonly causes this complication , with hydralazine and
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