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This version published online on June 2, 2009
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2008-2700
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Submitted on December 10, 2008
Accepted on May 26, 2009

Clinical Characteristics of Myeloperoxidase Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Caused by Antithyroid Drugs

Jaeduk Yoshimura Noh*, Shigemitu Yasuda, Shotaro Sato, Masako Matsumoto, Yo Kunii, Yoshihiko Noguchi, Koji Mukasa, Kunihiko Ito, Koichi Ito, Osamu Sugiyama, Hiroshi Kobayashi, Shigeru Nihojima, Masaru Okazaki, and Shunji Yokoyama

Ito Hospital (J.Y.N., S.Y., S.S., M.M., Y.K., Y.N., K.M., K.K. K.K.), Tokyo 150-8308, Japan; Drug Safety Unit (O.S., H.K., S.N., M.O., S.Y.), Chugai Pharmaceutical Co., Ltd., Tokyo 103-8324, Japan

* To whom correspondence should be addressed. E-mail: h-yoshimura{at}ito-hospital.jp..

Context: The clinical characteristics of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis caused by antithyroid drugs are still unclear because most reports describe only a small number of patients.

Objective: The objective was to analyse a large number of patients with MPO-ANCA-associated vasculitis to determine the time of onset, the drug and dose taken, the clinical symptoms, the relationship between the clinical symptoms and the MPO-ANCA titre, and the incidence.

Design: We analysed 92 patients in whom the adverse reaction of MPO-ANCA-associated vasculitis was reported to Chugai Pharmaceutical, a company that markets antithyroid drugs.

Results: Of the 92 patients, 41 (44.6%) had single-organ failure, 32 (34.8%) had two-organ failure, 13 (14.1%) had three-organ failure and two (2.2%) had four-organ failure. The number of organs involved was unknown in the other four patients (4.3%). The median time of onset was 42 months (range: 1 to 372 months) after starting drug treatment. The median dose at onset of MPO-ANCA-associated vasculitis was 15 mg/day (range: 2.5 to 45 mg/day) for methimazole and 200 mg/day (50 to 450 mg/day) for propylthiouracil. The severity and number of organs involved were not correlated with the MPO-ANCA titre. The incidence was between 0.53 and 0.79 patients per 10,000 and the ratio of the estimated incidences for methimazole and propylthiouracil was 1:39.2.

Conclusions: The time of onset of MPO-ANCA-associated vasculitis and the dose at onset varied. The severity and number of organs involved were not correlated with the MPO-ANCA titre, indicating a need for vigilance even when the MPO-ANCA titre is only weakly positive.


Key words: Graves' disease • propylthiouracil • methimazole • myeloperoxidase antineutrophil cytoplasmic antibody




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