Case Presentation: Introduction: Hydralazine is an adjunctive antihypertensive medication that is associated with antineutrophil cytoplasmic antibody (ANCA) – associated vasculitis. Kidney involvement usually comprises a pauci-immune, necrotizing glomerulonephritis with crescents. We describe a rare case of hydralazine induced ANCA positive vasculitis with acute tubulointerstitial nephritis and without glomerular involvement.
Case Report: A 74 year old Caucasian male with history of uncontrolled hypertension on hydralazine presented with acute onset malaise, hematuria, and blood tinged sputum. On physical examination, lower extremity edema with skin ecchymosis on right thigh and abdomen was noted. He remained hemodynamically stable. Lab work up revealed pancytopenia, and elevation of serum creatinine (4mg/dl; baseline unknown). Urinalysis showed proteinuria, dysmorphic red blood cells, and no red cell casts. Serology showed myeloperoxidase (MPO) positive high ANCA titers; positive anti-histone antibodies, positive cryoglobulins, and negative antinuclear antibodies. Renal biopsy revealed acute tubulointerstitial nephritis. Light microscopy examination after staining with H&E, PAS, trichrome, trichrome methanamine silver, and Jones silver showed no segmental sclerosis, crescents or areas of necrosis. Immunofluorescence exam showed traces of positivity for IgA, IgM, C3, C1q, Kappa and lambda. Infectious work up, and hepatitis B & C panel were negative. Bone marrow biopsy was normal. He received pulse dose of steroids, and induction therapy with rituximab (375 mg/m2 IV q weekly doses) and then followed by oral prednisone 60mg daily. Upon discharge, his creatinine was stabilized at 2mg/dl.
Five days later after his initial discharge, he was readmitted with worsening of hemoptysis. Lab work up revealed markedly elevated serum creatinine (5.58 mg/dl), hypokalemia (2.9 Meq/l), and persistent pancytopenia. Computed tomographic scan of chest revealed patchy areas of reticulation with ground glass opacities. Bronchoscopy exam revealed presence of diffuse alveolar hemorrhage. Subsequently, he was started on renal replacement therapy for worsening kidney functions.
With two months of follow up, he remains on hemodialysis and maintenance oral prednisone therapy.
Discussion: Hydralazine-induced ANCA vasculitis is a rare occurrence with pulmonary renal syndrome being the most severe presentation. A review by Yokogawa and Vivino described 37 published cases of hydralazine induced ANCA-associated vasculitis (AAV) with kidney involvement. Diagnostic features include the presence of high titer of anti-MPO-ANCA, positive anti-histone antibodies, and the lack of immunoglobulin and complement deposition. Our case fulfills above features with positive MPO-ANCA and anti-histone antibodies. Renal involvement in AAV is characterized by focal segmental crescentic and/or necrotizing glomerulonephritis. Mononuclear tubulointerstitial infiltrates have been noted in literature but these have usually been described in conjunction with glomerulitis which was not seen in this case. The mechanism of tubulointerstitial injury in ANCA-associated vasculitis is not clear. We report a case of hydralazine induced ANCA vasculitis with acute tubulointerstitial nephritis which has not been reported in the literature thus far.
Conclusions: We report a case of hydralazine induced ANCA vasculitis with acute tubulointerstitial nephritis which has not been reported in the literature thus far.