Dialysis-associated systemic fibrosis (Nephrogenic fibrosing dermopathy) -: Study of inflammatory cells and transforming growth factor β1 expression in affected skin
Dialysis-associated systemic fibrosis (Nephrogenic fibrosing dermopathy) -: Study of inflammatory cells and transforming growth factor β1 expression in affected skin
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DOI：
10.1002/art.20362
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发表时间：
2004-08-01
影响因子：
--
通讯作者：
Shanahan, JC
中科院分区：
文献类型：
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作者：
Jiménez, SA;Artlett, CM;Shanahan, JC
目标。肾源性纤维化皮肤病（NFD）是一种新发现的发生在终末期肾脏疾病（ESRD）患者中的皮肤纤维化疾病。本研究的目的是描述9例新发病例的临床和组织病理学特征，并对感染皮肤的炎症细胞和转化生长因子β 1 （tgfβ 1）的表达进行表征。临床和实验室评估，包括血清学和肺功能研究，对9例长期透析患者（8例血液透析；1例腹膜透析）进行了不同病因的ESRD。组织病理学检查皮肤、筋膜、横纹肌、肺和心脏。使用特异性单克隆抗体对炎症细胞进行免疫表型分析。原位杂交法检测TGFbeta1的表达。所有患者均表现出类似系统性硬化症和弥漫性筋膜炎的皮肤特征，并伴有多关节严重的活动能力丧失和屈曲挛缩。6例患者表现为腿部、大腿和前臂肌肉木质硬化。6例肺部受累患者中有5例在肺功能测试中一氧化碳扩散能力降低。6例患者红细胞沉降率和/或c反应蛋白水平明显升高。4例患者存在低滴度的抗核抗体。组织病理学研究表明，除真皮外，纤维化过程还影响皮下组织、筋膜、横纹肌、肺和心肌。病变皮肤和肌肉中CD68+/factor XIIIa+树突状细胞大量增加，TGFbeta1表达增加。我们的研究结果表明，NFD的纤维化过程不仅影响真皮层，还影响皮下组织、筋膜和其他器官，包括横纹肌、心脏和肺。因此，我们认为这是一个全身性纤维化过程，我们建议透析相关的全身性纤维化是一个更好的术语。
Objective. Nephrogenic fibrosing dermopathy (NFD) is a newly recognized cutaneous fibrotic disorder occurring in individuals with end-stage renal disease (ESRD). The aim of the present study was to describe the clinical and histopathologic features of 9 new cases and to characterize the inflammatory cells and expression of transforming growth factor beta1 (TGFbeta1) in affected skin.Methods. Clinical and laboratory assessments, including serology and pulmonary function studies, were performed in 9 patients undergoing long-term dialysis (8 hemodialysis; 1 peritoneal dialysis) for ESRD of diverse etiologies. Skin, fascia, striated muscles, lungs, and heart were examined by histopathology. Inflammatory cells were characterized by immunophenotyping using specific monoclonal antibodies. TGFbeta1 expression was determined by in situ hybridization.Results. All patients displayed cutaneous features resembling both systemic sclerosis and diffuse fasciitis, with severe loss of motion and flexion contractures in multiple joints. Six patients displayed woody induration of the muscles of the legs, thighs, and forearms. Five of the 6 patients with lung involvement had a reduced diffusion capacity for carbon monoxide on pulmonary function testing. Marked elevations of the erythrocyte sedimentation rate and/or C-reactive protein level were found in 6 patients. Antinuclear antibodies were present at low titers in 4 patients. Histopathologic studies indicated that in addition to the dermis, the fibrotic process affected the subcutaneous tissue, fascia, striated muscles, lungs, and myocardium. Large numbers of CD68+/factor XIIIa+ dendritic cells and increased expression of TGFbeta1 were found in affected skin and muscle.Conclusion. Our findings indicate that the fibrotic process of NFD affects not only the dermis, but also the subcutaneous tissues, fascia, and other organs, including striated muscles, heart, and lungs. We therefore believe this is a systemic fibrosing process, and we suggest that dialysis-associated systemic fibrosis would be a better term for the condition.