ARTHRITIS & RHEUMATISM Vol. 42, No. 2, February 1999, pp 384–388 © 1999, American College of Rheumatology ALTERNATING ANTINEUTROPHIL CYTOPLASMIC ANTIBODY SPECIFICITY Drug-Induced Vasculitis in a Patient with Wegener’s Granulomatosis HYON K. CHOI, PETER A. MERKEL, JAN WILLEM COHEN TERVAERT, ROBERT M. BLACK, ROBERT T. MCCLUSKEY, and JOHN L. NILES We describe a patient who presented with Wege- ner’s granulomatosis associated with antineutrophil cytoplasmic antibodies (ANCA) directed against pro- teinase 3 (PR3) with a cytoplasmic immunofluorescence pattern (cANCA), whose ANCA type changed to antimy- eloperoxidase antibodies with a perinuclear immunoflu- orescence pattern (pANCA) when treated with propyl- thiouracil, and changed back to anti-PR3 antibodies with cANCA after the medication was discontinued. The patient developed flares of vasculitis symptoms associ- ated with rises in either type of ANCA. Tests for antimyeloperoxidase ANCA were repeatedly negative before the drug was started, strongly implicating the drug as the cause of the episode. This case demonstrates that patients with idiopathic ANCA-positive vasculitis may quickly develop a superimposed drug-associated ANCA-positive vasculitis. Iatrogenic vasculitis should be suspected when a patient with idiopathic vasculitis with one type of ANCA develops the other type of ANCA. Tests for circulating antineutrophil cytoplasmic antibodies (ANCA) with specificity for myeloperoxidase (MPO) or proteinase 3 (PR3) are of considerable value in the diagnosis of the spectrum of vasculitis that in- cludes Wegener’s granulomatosis (WG), microscopic polyangiitis, the Churg-Strauss syndrome, idiopathic ne- crotizing and crescentic glomerulonephritis, and related or overlapping forms of vasculitis. These antibodies can be detected by indirect immunofluorescence, using ethanol-fixed human neutrophils as substrate: antibodies to PR3 produce a cytoplasmic pattern of staining (cANCA) and antibodies to MPO antibodies produce a perinuclear or nuclear pattern (pANCA). Almost all patients with such antibodies have only one or the other of these 2 types of ANCA; very few patients have both, and usually, one type is of marginal titer (1–4). The triggers that induce ANCA-positive vasculi- tis are largely unknown. In some cases, however, the disease appears to be induced by medications. Among the medications that have been associated with ANCA- positive vasculitis (5), hydralazine (6–8) and propylthio- uracil (9–11) have been reported most often. This report gives the first description of a case of alternating ANCA types associated with propylthioura- cil therapy in a patient with preexisting cANCA/anti- PR3–positive WG and provides compelling evidence of a causal role of propylthiouracil. CASE REPORT A 25-year-old man presented in May 1989 with malaise, fever, arthralgias, epistaxis, nasal congestion, hemoptysis, and hematuria with red blood cell casts. Biopsy of his nasal mucosa revealed necrotizing granu- lomatous vasculitis, and open-lung biopsy demonstrated alveolar capillaritis. Immunofluorescence ANCA testing was positive for cANCA, and anti-PR3 antibodies were present at a titer of 48 units (normal 5) by enzyme- linked immunosorbent assay (ELISA) using highly puri- fied antigen. Tests for anti-MPO antibodies were nega- tive (12). The titers and types of ANCA throughout the subsequent course and their relationship to therapy and disease manifestations are depicted in Figure 1. Hyon K. Choi, MD, Peter A. Merkel, MD, MPH, Robert T. McCluskey, MD, John L. Niles, MD: Massachusetts General Hospital, Boston, Massachusetts; Jan Willem Cohen Tervaert, MD, PhD: Uni- versity Hospital Groningen, Groningen, The Netherlands; Robert M. Black, MD: St. Vincent Hospital, Worcester, Massachusetts. Address reprint requests to Hyon K. Choi, MD, Arthritis Unit, Bulfinch 165, Massachusetts General Hospital, Fruit Street, Boston, MA 02114. Submitted for publication April 16, 1998; accepted in revised form July 14, 1998. 384