Abstract：
Idiopathic Systemic Capillary Leak Syndrome (ISCLS), also known as Clarkson\'s Syndrome, is due to primary fluid and protein leak across capillaries that leads to an accumulation of interstitial fluids and cardiovascular collapse from intravascular hypovolemia. Viral infections are a putative trigger of these episodes. ISCLS is typically associated with a monoclonal gammopathy. Here we present four patients with idiopathic systemic capillary leak syndrome. The cohort consists of three men and one woman who range in age from 55 to 72 years old. All of the patients had a monoclonal gammopathy. Two patients had viral triggers. Biopsies of normal skin were examined throughout all phases of the disease. During an acute attack, we identified perivascular mixed CD4+ and CD8+ T cell lymphocytic infiltrates in the superficial dermis. We observed significant microvascular deposits of C5b-9 and upregulation of type I interferon signaling in endothelium along with reduced serum levels of complement during very active disease. We also identified deposits of immunoglobulin along the dermal epidermal junction mirroring the monoclonal immunoglobulin isotype implicated in each patient. During a post treatment recovery or mild disease phase there was reduced inflammation and decreased amounts of C5b-9 and type I interferon expression. Sudden onset capillary leak syndrome reflects enhanced endothelial cell permeability as a unique form of endothelial injury mediated by the combined effects of complement pathway activation and upregulation of type I interferon signaling on endothelium.
摘要：
特发性系统性毛细血管渗漏综合征(ISCLS),也被称为克拉克森综合症,是由于毛细血管中的原发性液体和蛋白质渗漏，导致间质液积聚和血管内血容量不足引起的心血管塌陷。病毒感染是这些发作的假定触发因素。ISCLS通常与单克隆丙种球蛋白病有关。在这里，我们介绍了四名特发性系统性毛细血管渗漏综合征患者。该队列由三名男性和一名女性组成，年龄从55岁到72岁不等。所有患者均患有单克隆丙种球蛋白病。两名患者有病毒触发因素。在疾病的所有阶段检查正常皮肤的活检。在急性发作期间，我们在真皮浅层发现了血管周围混合的CD4+和CD8+T淋巴细胞浸润.我们观察到在非常活跃的疾病期间，内皮中C5b-9的显着微血管沉积和I型干扰素信号的上调以及补体的血清水平降低。我们还确定了沿真皮表皮交界处的免疫球蛋白沉积物，反映了每位患者所涉及的单克隆免疫球蛋白同种型。在治疗后恢复或轻度疾病阶段,炎症减少,C5b-9和I型干扰素表达量减少。突发性毛细血管渗漏综合征反映了增强的内皮细胞通透性，它是由补体途径激活和I型干扰素信号上调对内皮的联合作用介导的内皮损伤的一种独特形式。
