Antineutrophil cytoplasmic antibody-associated vasculitis in a patient with polycythemia vera after long-term hydroxyurea treatment

Hydroxyurea is an antineoplastic agent commonly used to treat chronic myeloproliferative disorders. Rare side eff ects such as vasculitic ulcerations were reported in the 1970s [1], but the major pathogenic mechanism was ill-defi ned. According to our knowledge, no patient with antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis under hydroxyurea treatment has been reported to date. A 74-year-old man was admitted because of lower gastrointestinal hemorrhage. Gastroscopy mucosal biopsies displayed chronic atrophic gastritis primarily in the gastric antrum. Mucosal biopsy samples from colonic ulcers showed no signs of granulation tissue, neutrophil infi ltration, necrosis, or thrombus in the lumen of small vessels. Colonoscopy showed several round, superfi cial ulcers about 0.1 – 0.2 cm in diameter at the transverse colon and rectum. Selective arteriography found no bleeding or atherosclerotic stenosis in the mesenteric and gastroduodenal arteries. F-18 fl udeoxyglucose whole-body positron emission tomography showed no abnormal physiological isotope uptake. Previously diagnosed with polycythemia vera 28 years ago, he had been treated with hydroxyurea 1.0 0.5 g/day for 12 years, with a stable white blood count and hemoglobin level. Interferon therapy was initiated in this patient in the early 1990s, but was not well tolerated, and was abandoned after several months. Aphthous ulcers had occurred more than three times a year for about 7 years. Upon admission he had a high fever and diarrhea 3 – 4 days a week which could not be controlled by antibiotics. Ear, nose, and throat examination was normal except for rampant caries. A peripheral blood smear revealed 74% neutrophils, 1.0% basophils, 9.4% lymphocytes, and 3.0% eosinophils. Stool bacterial culture found no pathogens. Bone marrow examination showed no signs of acute myelogenous leukemia. In the third week, three scrotum ulcers of 0.5 – 1.0 cm in diameter were detected (Figure 1). Tests for herpes simplex virus type II (HSV-II)-immunoglobulin M (IgM), HSV-II-IgG, anti-human immunodefi ciency virus, rapid plasma regain, and Treponema pallidum particle agglutination assay for syphilis were all negative. Repeated immunologic studies revealed positive results for antinuclear autoantibodies (1.41, reference range: 0 – 1), ANCAs specifi c for proteinase 3 (PR3-ANCA), and ANCAs specifi c for myeloperoxidase (MPO-ANCA), by both enzyme-linked immunosorbent assay and indirect immunofl uorescence. A skin pathergy test was negative. Hydroxyurea was changed to cyclophosphamide (CTX)