[Clinicopathological characteristics of propylthiouracil-induced antineutrophil cytoplasmic antibodies-positive vasculitis and their target antigens: a report of 4 cases and literature review].

OBJECTIVE: To study the clinicopathological manifestations and target antigens of propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA) positive vasculitis. METHODS: Four hospitalized patients with PTU-induced ANCA positive vasculitis in recent two years were studied. Target antigens and antibody titers were investigated with ELISA using seven highly purified known ANCA antigens as solid phase ligands. The known antigens included proteinase 3 (PR3), myeloperoxidase (MPO), human leukocyte elastase (HLE), lactoferrin (LF), cathepsinG (CG), bactericidal/permeability-increasing protein (BPI) and azurocidin (AZU). RESULTS: Four patients with Grave's disease, 2 female and 2 male with a mean age of 30 (11 approximately 57) years who had been treated with PTU for 7 approximately 60 months suffered from ANCA positive vasculitis. All the 4 patients had renal, lung, skin, joint, muscle and hematological involvement. Sera from all the 4 patients were ANCA positive and recognized MPO, LF and CG. Sera from 3 patients recognized HLE and AZU and 2 recognized PR3. None of the sera recognized BPI. The majority of the autoantibodies had high titers >/= 1:25 600. All the sera from 30 patients with Grave's disease and PTU treatment but without vasculitis were ANCA negative. All the 4 patients had pauci- immune glomerular lesions in renal biopsy; 2 had crescentic glomerulonephritis and the remaining 2 had minor glomerular abnormalities. All the 4 patients responded to withdrawal of propylthiouracil; 3 patients were treated with immunosuppressive agents. All the patients achieved clinical remission. However, one patient with crescentic glomerulonephritis was dialysis dependent. After withdrawal of PTU and administration of immunosuppressants, ANCA titres declined, but did not turn to negative in 1-6 months in most of the patients. CONCLUSIONS: PTU can induce ANCA positive vasculitis. The autoantibodies were polyclonal and recognized multiple target antigens of neutrophil cytoplasm. Early withdrawal of PTU and administration of immunosuppressive agents might improve the prognosis.