A 65-year-old male presents with new onset thyrotoxicosis, and he is found to be in atrial fibrillation with rapid ventricular response and is hypotensive. He is currently being treated with propylthiouracil and steroids and awaiting total thyroidectomy for definitive therapy, while his cardiovascular status is optimized. During his hospitalization, he develops massive hemoptysis. He is intubated for airway protection and brought to the ICU where serial bronchoalveolar lavage (BAL) reveals progressively more hemorrhagic specimens with each aliquot. Laboratory analysis reveals a positive antineutrophil cytoplasmic antibody (ANCA) in a cytoplasmic pattern and a positive antiproteinase 3 (anti-PR3) antibody.
Which of the following medications is most associated with drug-induced ANCA vasculitis?
A. FurosemideCorrect Answer: C
This patient exhibits DAH, which occurs because of the accumulation of red blood cells into the alveolar space. It is diagnosed with BAL by observation of progressively more hemorrhagic aliquots. DAH generally presents with dyspnea, hemoptysis, chest infiltrates, and a fall in hemoglobin, though surprisingly, hemoptysis is absent in up to one-third of cases.
New diagnosis of DAH should prompt a diagnostic workup including serologies for the common forms of small-vessel vasculitis. Small-vessel vasculitis is defined as vasculitis that affects vessels smaller than arteries, such as arterioles, venules, and capillaries. ANCAs bind to antigens in neutrophil and monocyte lysosomes and occur in two staining patterns: cytoplasmic (c-ANCA) and perinuclear (p-ANCA). A positive ANCA is seen in granulomatosis with polyangiitis (GPA, formerly known as Wegener granulomatosis), eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome), microscopic polyangiitis (MPA), and renal-limited ANCA vasculitis. Most patients with GPA have a c-ANCA pattern and antibodies to anti-PR3, whereas most patients with EGPAor MPAhave a p-ANCApattern and antibodies to anti-MPO.
Antithyroid drugs, including methimazole and propylthiouracil, are well-known to be associated with the development of ANCA-associated small-vessel vasculitis. Other drugs known to cause small-vessel vasculitis, with or without ANCA positivity, include hydralazine and levamisole (an agent found in adulterated cocaine).
Treatment for DAH secondary to drug-induced ANCA vasculitis includes withdrawal of the offending agent, high-dose corticosteroids, cyclophosphamide, and rituximab. Plasmapheresis is recommended in severe cases.
References: