[Antineutrophil cytoplasmic antibody associated vasculitis induced by antithyroid agents].

OBJECTIVE

To investigate the significance of antineutrophil cytoplasmic antibody (ANCA) in hyperthyroidism at different stages and treated with different drugs and to investigate the relationship between the ANCA specific target antigens and the clinical manifestations of vasculitis.

METHODS

Two hundred and sixteen patients with hyperthyroidism were divided into four groups: untreated (n = 34), treated with propylthiouracil (PTU) (n = 62), treated with methimazole (MMI) (n = 77), and treated with both PTU and MMI (n = 43). Sera were collected from the 216 patients. Indirect immunofluorescence (IIF) test was used to detect the ANCA and antinuclear antibody (ANA). Antigen-specific ELISA was used to detect the existence of 7 specific target antigens of ANCA: myeloperoxidase (MPO), proteinase 3 (PR3), lactoferrin (LF), human leukocyte elastase (HLE), azurocidin (AZU), cathepsinG (CG), and bactericidal/permeability-increasing protein (BPI) in the sera positive in ANCA and ANA determined by IIF.

RESULTS

The IIF positive rate was 5.9% (2/34) in the untreated group; 22.6% (14/62) in the patients treated with PTU, all IIF-ANCA positive; 6.5% (5/77) in the patients treated with MMI, all IIF-ANA positive; and 27.9% (12/43) in the patients treated with both PTU and MMI, 8 IIF-ANA positive and 3 IIF-ANCA positive. The IIF-ANCA positive rate in the patients receiving PTU was significantly higher than that in the untreated patients (P < 0.017). The IIF-ANA and IIF-ANCA positive rates of the patients treated with PTU were both significantly higher than those of the patients treated with MMI (P < 0.017). Six of the IIF-positive 31 patients administered with drugs (19.4%) had signs and symptoms associated with vasculitis. Of the six patients, 4 were MPO antibody positive (66.7%), 2 were PR3 antibody positive (33.3%), 4 were LF antibody positive, 3 were HLE antibody positive, 3 were AZU antibody positive, and 2 were CG antibody positive. None was anti-BPI antibody positive. Two of the six patients were both anti-MPO and anti-PR3 negative. All MPO-ANCA positive patients had clinical signs and symptoms of vasculitis.

CONCLUSION

PTU is associated with the production of ANCA in patients with hyperthyroidism. PTU induced ANCA is caused by polyclonal activation of B cells. Anti-MPO antibody may be related to the occurrence of clinical vasculitis.