Magro Cynthia M, Dyrsen Molly, Kerns Mary Jo
Department of Pathology, New York Presbyterian Hospital/Weill Medical College of Cornell University, New York, NY 10021, USA.
J Cutan Pathol. 2008 Jan;35(1):31-9. doi: 10.1111/j.1600-0560.2007.00770.x.
Dermatomyositis (DM) is a distinctive systemic connective tissue disease whereby the skin defines a cardinal site of involvement. There exists a body of literature, which suggests that a significant component of its clinical manifestations may be related to endothelial cell injury. We have postulated in the past that anti-endothelial cell antibodies may be the defining trigger leading to endothelial cell dysfunction. The primary organs affected by DM are the skin and muscle. A significant albeit rare complication is pulmonary fibrosis, which our recent study postulated to be attributable to an autoimmune endothelialitis.
We describe six patients, four women and two men who ranged in age from 3 to 60 years, and had classic clinical presentations and cutaneous lesions of DM without any supervening clinical changes indicative of cutaneous sclerosis.
Skin biopsies showed cell-poor interface dermatitis with variable dermal mucin and C5b-9 within the cutaneous vasculature. However, at variance with classic DM was the presence of a sclerodermoid tissue reaction, which was of variable depth. All of these patients had severe muscle involvement. One pediatric patient had concomitant significant cutaneous, central nervous system and oral mucosal ischemic infarcts. Significant pulmonary disease ensued in the four adult patients, manifesting as pulmonary fibrosis in two, diffuse alveolar damage in one and diaphragmatic failure in one. In three patients, direct immunofluorescent studies were corroborative of immune-based microvascular injury while Western blot and/or indirect immunofluorescent studies showed anti-endothelial cell antibody activity within the serum of three patients.
The identification of sclerosis in biopsies of skin lesions typical clinically for DM may be a harbinger for more severe autoimmune-based endothelial cell injury phenomenon. One could speculate that its basis may be attributable to elevated serum levels of the natural fibrogenic factor, transforming growth factor beta, which in turn is released from damaged endothelium.
皮肌炎(DM)是一种独特的系统性结缔组织疾病,皮肤是主要受累部位。有大量文献表明,其临床表现的一个重要组成部分可能与内皮细胞损伤有关。我们过去曾推测,抗内皮细胞抗体可能是导致内皮细胞功能障碍的决定性触发因素。DM主要影响的器官是皮肤和肌肉。一种严重但罕见的并发症是肺纤维化,我们最近的研究推测这可归因于自身免疫性内皮炎。
我们描述了6例患者,4名女性和2名男性,年龄在3至60岁之间,具有DM的典型临床表现和皮肤病变,且无任何提示皮肤硬化的后续临床变化。
皮肤活检显示细胞稀少的界面性皮炎,伴有不同程度的真皮粘蛋白和皮肤血管内的C5b - 9。然而,与经典DM不同的是,存在不同深度的硬皮病样组织反应。所有这些患者都有严重的肌肉受累。一名儿科患者同时伴有明显的皮肤、中枢神经系统和口腔黏膜缺血性梗死。4名成年患者出现严重肺部疾病,2例表现为肺纤维化,1例为弥漫性肺泡损伤,1例为膈肌衰竭。3例患者的直接免疫荧光研究证实了基于免疫的微血管损伤,而蛋白质印迹和/或间接免疫荧光研究显示3例患者血清中有抗内皮细胞抗体活性。
在临床上典型的DM皮肤病变活检中发现硬化可能是更严重的基于自身免疫的内皮细胞损伤现象的先兆。可以推测其基础可能归因于天然促纤维化因子转化生长因子β血清水平升高,而该因子又从受损内皮细胞释放。