丙基硫氧嘧啶致抗中性粒细胞胞浆抗体阳性患者的临床特点

Clinical characteristics of propylthiouracil (PTU) induced antineutrophil cytoplasmic antibodies positive cases; analysis of a case of PTU induced ANCA positive patients with hyperthyroidism

目的探讨丙基硫氧嘧啶(PTU)导致抗中性粒细胞胞浆抗体(ANCA)阳性病例的临床特点,以提高对PTU导致ANCA阳性血管炎(APV)的认识。方法分析北京协和医院自2000年以来9例因应用PTU导致的ANCA阳性病例临床资料,并进行相关文献复习。结果(1)9例患者发病年龄16～51岁(平均331岁),服用PTU时间3～84个月(平均324个月);(2)6例进行了ANCA靶抗原谱的测定,除抗髓过氧化物酶(MPO)外,均同时存在识别其他抗原的抗体,包括抗蛋白酶3(PR3)、抗人白细胞弹力蛋白酶(HLE)、抗杀菌/通透性增高蛋白(BPI)和抗乳铁蛋白(LF);(3)6例核周型ANCA(pANCA)高滴度阳性(≥1∶1280)的病例临床确诊为APV(均有肾脏受累,其中5例为肾穿刺病理证实),另外3例pANCA低滴度阳性(≤1∶320)的病例无明确血管炎表现;(4)8例患者被发现ANCA阳性后停用PTU,其中1例APV仅停用PTU后病情缓解,另外4例APV同时予糖皮质激素和免疫抑制剂后病情逐渐缓解,而1例继续服用PTU随诊18个月pANCA滴度未升高。结论PTU可引起ANCA阳性,而高滴度pANCA阳性提示APV,其病情与抗体滴度相关;及时停用PTU,根据肾穿刺病理的病变程度确定治疗方案,对改善预后意义重大。

Objective To study the clinical characteristics of propylthiouracil (PTU) induced antineutrophil cytoplasmic antibodies (ANCA) positive cases and increase the awareness of PTU induced ANCA positive vasculitis (APV) Methods The clinical data of nine cases with positive ANCA induced by PTU in Peking Union hospital since 2000 were analyzed and literature review was conducted Results ① Nine patients with hyperthyroidism, at a mean age of 33 1 (16～51), who were treated with PTU for a mean period of 32 4 months (3～84); ② Sera from nine cases were ANCA positive, and autoantibodies from six tested cases could recognize not only MPO, but also PR3, HLE, BPI and LF; ③ Six cases with high titer perinuclear ANGA(pANCA) (≥1∶1280) were diagnosed APV and all had renal involvement (five confirmed by renal biopsies), three cases with low titer pANCA (≤1∶320) had little clinical manifestations of vasculitis; ④ Eight patients stopped taking PTU when positive ANCA were noted One case with APV got remission after stopping PTU, the other three APV were treated with glucocorticosteroid and immunosuppressive agents at meanwhile Only one patient kept taking PTU for eighteen months without an increased titer of ANCA Conclusion PTU could induce production of ANCA High titer of ANCA might suggest existence of APV and the titer would be associated with status of APV Early withdrawal of PTU and administration of glucocorticosteroid and immunosuppressive agents based on renal pathology will greatly improve the prognosis