methimazole and Anti-Neutrophil-Cytoplasmic-Antibody-Associated-Vasculitis

The aim of this review was to delineate the characteristics of antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis associated with antithyroid drugs (ATD). A PubMed search was made for English language articles using the search terms antithyroid drugs AND ANCA OR ANCA-associated vasculitis.. The literature includes approximately 260 case reports of ANCA-associated small-vessel vasculitis related to ATD, with 75% of these associated with thiouracil derivatives (propylthiouracil [PTU]) and 25% with methyl-mercapto-imidazole derivatives (MMI/TMZ). The prevalence of ANCA-positive cases caused by ATD varied between 4% and 64% with PTU (median 30%), and 0% and 16% with MMI/TMZ (median 6%). Young age and the duration of ATD therapy were the main factors contributing to the emergence of ANCA positivity. Before ATD therapy initiation, the prevalence of ANCA-positive patients was 0-13%. During ATD administration, 20% of patients were found to be positive for ANCA. Only 15% of ANCA-positive patients treated with ATD exhibited clinical evidence of vasculitis, corresponding to 3% of all patients who received ATD. Clinical manifestations of ANCA-associated vasculitis related to ATD were extremely heterogeneous. When vasculitis occurred, ATD withdrawal was usually followed by rapid clinical improvement and a favorable prognosis.. ANCA screening is not systematically recommended for individuals on ATD therapy, particularly given the decreasing use of PTU in favor of TMZ/MMI. Particular attention should be given to the pediatric population with Graves' disease who receive ATD, as well as patients treated with thiouracil derivatives and those on long-term ATD therapy.

Topics: Age Factors; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antithyroid Agents; Humans; Hyperthyroidism; Methimazole; Prevalence; Propylthiouracil; Time Factors

A 63-year-old woman suddenly developed central retinal artery occlusion following a slight fever while being treated with methimazole (MMI) for hyperthyroidism. She was diagnosed to have anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) based on increased inflammatory reactions with positive myeloperoxidase-ANCA in the serum. Her visual acuity remained low despite immediate treatment with corticosteroids and cyclophosphamide after cessation of MMI, which may have played a role in the pathogenesis of AAV. Central retinal artery occlusion is a rare manifestation of AAV; however, it is important with regard to the possibility of serious sequelae.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Anticoagulants; Antithyroid Agents; Dalteparin; Female; Humans; Hyperthyroidism; Immunosuppressive Agents; Methimazole; Middle Aged; Retinal Artery Occlusion

Propylthiouracil (PTU) is recommended as a first-line antithyroid drug (ATD) during first trimester organogenesis in pregnancy because recent evidence suggests that methimazole (MMI) may be associated with congenital anomalies. However, PTU more commonly causes myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which usually occurs during prolonged treatment, compared with MMI. We report a case of MPO-ANCA-associated vasculitis in a 35-year-old woman with Graves'disease. Although her thyroid function could be maintained euthyroid by MMI, her ATD was switched to PTU because she wished to become pregnant. The patient presented with flu-like symptoms 8 days after starting PTU and developed hemoptysis and dyspnea at 22 days. Her MPO-ANCA titer was 21 ELISA units (EUs) before PTU treatment but increased to 259 EUs at 22 days after PTU treatment. Her clinical condition improved with the discontinuation of PTU and with immunosuppressive therapy. This case indicated that MPO-ANCA vasculitis occurred within several weeks after the initiation of PTU and that this side effect could be caused by the change from MMI to PTU. Thus, our clinical observation suggests that patients treated with PTU should be carefully monitored for MPO-ANCA titers and variable manifestations of MPO-ANCA-associated vasculitis regardless of the period of administration.

Topics: Abnormalities, Drug-Induced; Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Peroxidase; Pregnancy; Pregnancy Complications; Propylthiouracil