Ohta K, Shimizu M, Yokoyama T, Ohta K, Nakai A, Seno A, Kasahara Y, Yachie A, Fujieda M, Koizumi S
Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
Clin Nephrol. 2007 Nov;68(5):315-21. doi: 10.5414/cnp68315.
We report a 16 year-old girl with propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-positive glomerulonephritis combined with Henoch-Schönlein purpura nephritis (HSPN) and antiphospholipid syndrome (APS).
The patient had Graves' disease and had been treated with PTU for about 6 years. She complained of arthralgia, epigastralgia, purpura of the lower extremities, anemia, and abnormal urinalysis. Lupus anticoagulant was positive. Additionally, a high level of anti-myeloperoxidase (MPO) antibodies (IgG) and a low level of coagulation factor XIII were recognized. She had several complications including lung bleeding, lacuna infarctions of the right frontal and parietal brain lobes, and deep vein thrombosis of the left lower extremity. We studied tissue histology and carried out MPO-ANCA subtype analysis by immunofluorescence and flow cytometry and MPO-ANCA epitope analysis.
Histologically, purpura showed leukocytoclastic vasculitis with perivascular depositions of IgA and complement C3. Renal biopsy showed necrotizing glomerulonephritis with crescents and mesangial IgA deposits. Notably, IgG, IgM, and IgA ANCA were detected in the patient's serum by flow cytometry and immunofluorescence. We diagnosed an overlap syndrome of ANCA-positive vasculitis, HSPN, and APS. A change in the reactivity of MPO-ANCA from recognition of only the Hg epitope in the C-terminal region to recognition of multiple MPO epitopes was accompanied by a remission of symptoms.
This report may provide a very rare description of an overlap syndrome of PTU-induced ANCA vasculitis, HSPN, and APS in which not only IgG ANCA but also IgA and IgM ANCA were found. Epitope analysis may be a useful marker for disease-monitoring of PTU-induced ANCA-positive vasculitis. This case may provide insight into the pathological mechanism underlying each of these diseases.
我们报告一名16岁女孩，患有丙硫氧嘧啶（PTU）诱导的抗中性粒细胞胞浆抗体（ANCA）阳性肾小球肾炎，合并过敏性紫癜性肾炎（HSPN）和抗磷脂综合征（APS）。
该患者患有格雷夫斯病，接受PTU治疗约6年。她主诉关节痛、上腹部疼痛、下肢紫癜、贫血及尿液分析异常。狼疮抗凝物阳性。此外，还检测到高水平的抗髓过氧化物酶（MPO）抗体（IgG）和低水平的凝血因子 XIII。她出现了多种并发症，包括肺出血、右侧额叶和顶叶脑叶腔隙性梗死以及左下肢深静脉血栓形成。我们研究了组织病理学，并通过免疫荧光和流式细胞术进行MPO-ANCA亚型分析以及MPO-ANCA表位分析。
组织学上，紫癜表现为白细胞破碎性血管炎，伴有血管周围IgA和补体C3沉积。肾活检显示为坏死性肾小球肾炎伴新月体形成及系膜IgA沉积。值得注意的是，通过流式细胞术和免疫荧光在患者血清中检测到IgG、IgM和IgA ANCA。我们诊断为ANCA阳性血管炎、HSPN和APS重叠综合征。MPO-ANCA反应性从仅识别C末端区域的Hg表位转变为识别多个MPO表位，同时症状缓解。
本报告可能提供了关于PTU诱导的ANCA血管炎、HSPN和APS重叠综合征的极为罕见的描述，其中不仅发现了IgG ANCA，还发现了IgA和IgM ANCA。表位分析可能是监测PTU诱导的ANCA阳性血管炎病情的有用标志物。该病例可能有助于深入了解这些疾病各自的病理机制。
