Fulminant Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis After 10 Years of Hydralazine Use

Vasculitis, by definition, causes changes in the walls of blood vessels, including thickening, weakening, narrowing, and scarring, leading to inflammation and necrosis of the blood vessel walls. Small-vessel vasculitis is commonly associated with anti-neutrophil cytoplasmic antibodies (ANCA), which activate cytokine-primed neutrophils and monocytes that express ANCA antigens proteinase 3 (PR3) and myeloperoxidase (MPO) on their surface. The continuous injury and inflammation of these small vessels characterized by circulating immune complexes and antinuclear antibodies result in clinical features standard in all types of vasculitis. When a 59-year-old male with a history of heart failure, hypertension (on hydralazine 100 mg every eight hours for more than ten years), diabetes mellitus, and dyslipidemia presented to the hospital, he was complaining of hematuria, intermittent periumbilical abdominal pain, and 40-lb weight loss over four months. Initial evaluation showed symptomatic anemia and large blood cells with proteinuria on urine analysis. During his clinical course, the patient developed a new diffuse purpuric rash. Imaging showed systemic involvement with ground-glass opacities, diffuse alveolar hemorrhage, and peripancreatic inflammatory changes, consistent with small-vessel vasculitis. Immunological tests confirmed ANCA-associated vasculitis, and kidney biopsy showed ANCA-mediated pauci-immune glomerulonephritis supported by the salvage technique used by pronase immunofluorescence, which provides evidence against the glomerular disease of the complex immune type in the setting of MPO-ANCA seropositivity. Despite the withdrawal of hydralazine and prompt initiation of immunosuppressive therapy and alternating sessions of plasmapheresis, the patient succumbed to acute massive pulmonary hemorrhage and subsequent demise. We recommend that patients on the common antihypertensive, hydralazine, should be monitored with non-specific inflammatory markers and, if warranted, with qualitative and quantitative assessment tools to measure inflammatory disease activity for possible complications of hydralazine drug-induced vasculitis or hydralazine ANCA-associated vasculitis (HAAV). Furthermore, cumulative dosages may be a predisposing factor for HAAV to present as a pulmonary-renal syndrome, which can be fulminant and fatal, despite aggressive efforts. Therefore, screening, revisiting therapy, early diagnosis, and prompt discontinuation of the drug are imperative.