Combined ANCA-associated vasculitis and lupus syndrome following prolonged use of hydralazine: a timely reminder of an old foe

Abstract

A 55-year-old woman with type II diabetes and resistant hypertension presented to her GP in July 2008 complaining of lethargy, breathlessness, and joint pains. In 2007, based upon a positive antinuclear antibody test (ANA) in the context of pancytopenia, arthralgia, and a persistent malar rash, she had been diagnosed with systemic lupus erythematosis (SLE) by her referring hospital. Her regular medications were perindopril 4 mg daily, amlodipine 5 mg daily, atenolol 100 mg daily, and hydralazine 25 mg twice daily which she had started in 2005. She had remained on hydralazine, despite the diagnosis of SLE, treatment of which was limited to intra-articular corticosteroid injections. In July 2008 she was referred to our renal unit with acute kidney injury (AKI). Upon arrival, examination revealed a malar rash, and a soft systolic murmur. The remainder of the examination was unremarkable. Her blood pressure was 163/81 and she was afebrile. Laboratory investigations confirmed AKI with a serum creatinine of 300 lmol/L, (previously 148 lmol/L in May 2008, and 82 lmol/L in March 2008). Full blood count revealed pancytopenia, and her blood film showed rouleaux formation with occasional spherocytes. ANA remained positive, and she had now developed high titres of serum anti neutrophil cytoplasmic antibodies of the anti-myeloperoxidase subtype (p-ANCA), which were previously negative (See Table 1). Despite immediate cessation of hydralazine and appropriate rehydration, over the following days, her clinical condition deteriorated. A widespread, florid vasculitic rash developed, accompanied by arthralgia, intermittent pyrexia, and a rising serum creatinine. Her symptoms and immunological profile were consistent with hydralazine-induced SLE (although renal involvement in this setting is unusual). However, the presence of serum ANCA and the florid vasculitic rash also made ANCA-associated vasculitis (AAV) a likely diagnosis. Since these two conditions were potentially therapeutically distinct, she underwent renal and skin biopsies, and a bone marrow aspirate and trephine. The renal biopsy confirmed the diagnosis of AAV with pauci-immune crescentic glomerulonephritis, occurring alongside hydralazineinduced lupus syndrome, complicated by autoimmune pancytopenia, the underlying cause of which was attributed to prolonged use of hydralazine. She was treated with three intravenous pulses of methylprednisolone (500 mg) and five sessions of plasma exchange—3 L exchanges with 1.5 L 5% human albumin solution and 1.5 L fresh frozen plasma (FFP). She required three sessions of haemodialysis and, following recovery of her white cell N. Sangala R. W. Lee C. Horsfield D. J. A. Goldsmith (&) Renal and Histopathology Departments, Kings Health Sciences, London 0207-188-5708, UK e-mail: David.goldsmith@gstt.nhs.uk