Lang S M, Astner S, Fischer R, Schiffl H, Huber R M
Department of Medicine, University of Munich, Federal Republic of Germany.
Wien Klin Wochenschr. 1998 Oct 16;110(19):691-4.
In May 1984 a 58-year-old woman presented with a broad spectrum of clinical symptoms including malaise, arthralgia, hemoptysis and dyspnea, proteinuria and hematuria and a vasculitic necrotizing rash. Bronchial biopsies revealed subglottic granulomatous lesions and renal biopsies showed necrosis, extracapillary proliferation and crest formation, confirming the diagnosis of Wegener granulomatosis. Positive c-ANCA and anti-proteinase 3 subfraction (anti-PR3) titers were first analysed in 1991. Clinical remission was achieved by standard immunosuppressive therapy and renal function was stabilised. Several minor relapses were treated with pulsed intravenous cyclophosphamide but the symptoms could not be completely controlled. Eight years after the onset of disease, a dramatic increase in anti-PR3 titers was observed (34438 U/ml, normal range < 10, ELISA), followed 3 months later by a clinically apparent relapse. Immunosuppressive therapy was reinstituted without clinical improvement. At this point plasmapheresis resulted in an amelioration of clinical symptoms as well as a reduction in anti-PR3 titers. Concomitant immunosuppressive therapy was administered with oral corticosteroids. Forty days later anti-PR3 titers increased, reaching 75000 U/ml twelve months later, however this time without associated clinical symptoms. During the following months the patient had a further transient deterioration of pulmonary and renal function due to secondary bacterial infection which was successfully treated with antibiotics. A nephritic sediment was not present during these episodes. Curiously, the anti-PR3 titers have remained excessively elevated for the last three years.
1984年5月，一名58岁女性出现了一系列广泛的临床症状，包括不适、关节痛、咯血、呼吸困难、蛋白尿、血尿以及血管炎性坏死性皮疹。支气管活检显示声门下肉芽肿性病变，肾活检显示坏死、毛细血管外增生和新月体形成，确诊为韦格纳肉芽肿。1991年首次检测到抗中性粒细胞胞浆抗体（c-ANCA）和抗蛋白酶3亚组分（抗PR3）滴度呈阳性。通过标准免疫抑制治疗实现了临床缓解，肾功能得以稳定。多次轻微复发采用脉冲静脉注射环磷酰胺治疗，但症状无法完全控制。疾病发作八年后，观察到抗PR3滴度急剧升高（34438 U/ml，ELISA法正常范围<10），3个月后出现明显的临床复发。重新开始免疫抑制治疗，但临床症状并无改善。此时，血浆置换使临床症状得到改善，抗PR3滴度降低。同时给予口服皮质类固醇进行免疫抑制治疗。40天后，抗PR3滴度再次升高，12个月后达到75000 U/ml，但此次无相关临床症状。在接下来的几个月里，患者因继发细菌感染导致肺和肾功能进一步短暂恶化，经抗生素治疗成功。这些发作期间未出现肾炎性沉渣。奇怪的是，抗PR3滴度在过去三年一直异常升高。
