丙基硫氧嘧啶和甲巯咪唑与抗中性粒细胞胞浆抗体相关性血管炎

Study on propylthiouracil,methimazole and antineutropil cytoplasmic antibody-associated vasculitis

目的:研究抗甲状腺药物丙基硫氧嘧啶(PTU)、甲巯咪唑(MMI)与抗中性粒细胞胞浆抗体(ANCA)的关系。方法:收集甲状腺功能亢进患者199例,按用药情况分为4组:初发未治组30例、服用PTU组61例、服用MMI组65例、混合用药组43例。应用间接免疫荧光法(IIF)检测所有患者血清中的P-ANCA和C-ANCA。应用酶联免疫吸附法(ELISA)测定抗MPO抗体及抗PR3抗体。ANCA阳性患者行尿常规、肾功能、血沉、胸片、五管科检查。对于检测时正在服用PTU的AN-CA阳性患者,停用PTU,改用MMI治疗。随访每例ANCA阳性患者的临床表现并监测血清中的ANCA。结果:初发未治组30例患者的血清中无一例检测到ANCA阳性,PTU组中有8/61(13.11%)例P-ANCA阳性,其中3例识别MPO。MMI组中仅1/65(1.53%)例P-ANCA阳性,无一例识别MPO。混合组中7/43(16.28%)例P-ANCA阳性,其中4例识别MPO。PTU组和混合组ANCA阳性率高于初发未治组和MMI组(P<0.05)。16例ANCA阳性患者中7例出现血管炎临床表现。共8例ANCA阳性患者换用MMI后随访1年,6例ANCA转阴,2例仍为阳性。结论:PTU与甲亢患者出现ANCA阳性相关,并导致其中的一部分患者出现血管炎临床表现。PTU引起的ANCA阳性患者在密切监测的情况下可试换用MMI进一步治疗甲亢。

OBJECTIVE To study the relation between antithyroid drugs propyhhiouracil （PTU）, methimazole （MMI） and the occurrence of antineutropil cytoplasmic antibody （ANCA） in sera from patients with primary hyperthyroidism. METHODS One hundred and ninety-nine patients with primary hyperthyroidism, from Jinhua Central Hospital, were enrolled in the current study. They were divided into four groups： untreated patients （n = 30）, patients treated with PTU （n = 61）, patients treated with MMI （n = 65） and patients treated with both PTU and MMI （n = 43）. Indirect immunofluorescence （IIF） assay was used to detect P-ANCA and C-ANCA. Antigen specific ELISAs were used to detect anti-MPO antibody and anti-PR3 antibody in sera from all the patients. Every ANCA-positive patient was screened for urinalysis, renal function, ESR, chest X rays and ophthalmology. Those ANCA-positive patients treated with PTU were informed to change to MMI. ANCA was detected during follow-up. RESULTS Among the untreated patients, none was ANCA positive. Eight sera from patients treated with PTU （13. 11%） were P-ANCA positive, and three of the eight patients had anti-MPO antibodies. Only one （1.53%） was P-ANCA positive in sera from patients treated with MMI. In patients treated with both PTU and MMI, seven （16. 28%） had P-ANCA, and four had anti-MPO antibodies. The prevalences of ANCA in sera from patients treated with PTU and treated with both PTU and MMI were significantly higher than those in MMI group and untreated group, respectively （P〈0. 05）. Seven out of 16 patients with positive ANCA had mild clinical evident ANCA associated vasculitis but without immunosuppressive therapy. Eight patients were followed up for more than one year, serum ANCA changed to negative in six patients and remained positive in two. CONCLUSION PTU might be related to ANCA production in patients with hyperthyroidism. Some patients with positive ANCA developed clinical vasculitis.