丙硫氧嘧啶致抗中性粒细胞胞质抗体相关血管炎研究进展

Research progress in antineutrophil cytoplasmtic antibody associated small vessel vasculitis due to propylthiouracil

丙硫氧嘧啶 （PTU） 致抗中性粒细胞胞质抗体 （ANCA） 相关血管炎（AAV）（PTU-AAV）占抗甲状腺药物所致血管炎的80%～90%，可累及呼吸、肾脏、皮肤、肌肉、神经、胃肠和五官等系统，临床表现为发热、乏力、体重下降、肌肉关节疼痛、紫癜样皮损、血尿、结膜炎，严重时可致肺泡出血、急性肾衰竭甚至危及生命，实验室检查血清ANCA阳性。PTU与髓过氧化物酶（MPO）相互作用可能是PTU-AAV的发生机制之一。长期使用PTU可能是诱发AAV的高危因素，血清抗MPO抗体阳性率、滴度以及亲和力也可能与PTU-AAV的发生有关。PTU-AAV的诊断：（1）有小血管炎临床症状，与应用PTU有明确的时间关系；（2） ANCA呈阳性或滴度升高；（3） 组织活检显示小血管有炎性反应与坏死，肾穿刺活检为局灶节段纤维素样坏死和/或新月体性肾小球肾炎；（4）可除外其他可能引起血管炎的疾病，如感染和肿瘤。及时停用PTU及联合应用糖皮质激素与细胞毒药物是治疗PTU-AAV的主要方法。PTU-AAV的预后与小血管受损范围密切相关，其总体预后优于原发性小血管炎。

Antineutrophil cytoplasmic antibody （ANCA） associated small vessel vasculitis （AAV） induced by propylthiouracil （PTU） accounted for 80%-90% of vasculitis due to anti hyperthyroidism drugs. AAV is the disease which involved the systems of respiration, kidney, skin, muscle, nerve, stomach and intestine and ophthalmology and otorhinolaryngology. The clinical manifestations of AAV include fever, weakness, weight loss, myalgia and arthralgia, purpuric skin injury, hematuresis, conjunctivitis, pulmonary alveolar hemorrhage, and acute renal failure, can be even life-threatening. Laboratory examination showed positive ANCA. The mechanism of AAV induced by PTU may be related to interaction of PTU and myeloperoxidase （MPO）. Long-term use of PTU may be the high risk factor in AAV. Serum anti-MPO antibody positive, anti-MPO antibody titer and the affinity to MPO antibody may be also related to PTU-AAV. The diagnostic code of PTU-AAV include （1） appearance of clinical symptoms of small vessel vasculitis and have the specific relationship between symptoms and medication time; （2） ANCA test show positive or titer elevating; （3） tissue biopsy shows inflammatory reaction and necrosis in small vessels, and renal needle biopsy shows focal segmental necrosis of cellulose and /or crescentic glomerulonephritis; （4） other diseases which may induce vasculitis, such as infection and tumor can be excluded. The main treatments for AAV are withdrawal of PTU timely and rational combination of steroids and cytotoxic drugs. The prognosis of PTU-AAV is closely related to the damage range in small vessels. The overall prognosis of PTU-AAV is better than that of primary small vessel vasculitis.