Dorfmüller Peter, Humbert Marc, Perros Frédéric, Sanchez Olivier, Simonneau Gérald, Müller Klaus-Michael, Capron Frédérique
Service d'Anatomie et de Cytologie Pathologiques, Centre Hospitalier Universitaire Pitié-Salpêtrière, 47-83, Boulevard de l'Hôpital, F-75651 Paris Cedex 13, France.
Hum Pathol. 2007 Jun;38(6):893-902. doi: 10.1016/j.humpath.2006.11.022. Epub 2007 Mar 21.
Pulmonary arterial hypertension is a severe complication of connective tissue diseases. It is currently well established that pulmonary arterial hypertension associated with connective tissue diseases such as systemic sclerosis is frequently less responsive or even refractory to pulmonary vasodilator therapies. In that setting, pulmonary venoocclusive disease is believed to contribute to treatment failures. We therefore hypothesized that pulmonary arterial hypertension associated with connective tissue diseases may be associated with obstructive lesions of pulmonary veins. Lung samples from 8 patients with pulmonary arterial hypertension associated with connective tissue disease (4 limited systemic sclerosis, 2 systemic lupus erythematosus, 1 mixed connective tissue diseases, and 1 rheumatoid arthritis) were studied by light microscopy and analyzed by immunohistochemistry (5 postmortem samples, 3 explants after lung transplantation). Findings were compared with 29 pulmonary arterial hypertension cases from patients displaying neither connective tissue diseases nor associated conditions. We found that (a) 6 (75%) of 8 patients with pulmonary arterial hypertension associated with connective tissue diseases showed significant obstructive pulmonary vascular lesions predominating in veins/preseptal venules, as compared with 5 (17.2%) of 29 non-connective tissue diseases control pulmonary arterial hypertension; (b) lesions of small muscular arteries were consistently present in pulmonary arterial hypertension associated with connective tissue diseases, showing mostly intimal fibrosis and thrombotic lesions; and (c) 6 of 8 lung samples from patients with pulmonary arterial hypertension associated with connective tissue diseases revealed perivascular inflammatory infiltration. In conclusion, our study highlights the fact that pulmonary arterial hypertension complicating the course of connective tissue diseases may be characterized by a more frequent involvement of pulmonary veins and may thus explain why these patients are less prone to respond to specific pulmonary arterial hypertension treatment as compared with idiopathic pulmonary arterial hypertension.
肺动脉高压是结缔组织病的一种严重并发症。目前已明确，与系统性硬化症等结缔组织病相关的肺动脉高压对肺血管扩张剂治疗常常反应较差甚至无效。在这种情况下，肺静脉闭塞性疾病被认为是治疗失败的原因之一。因此，我们推测与结缔组织病相关的肺动脉高压可能与肺静脉阻塞性病变有关。我们对8例与结缔组织病相关的肺动脉高压患者（4例局限性系统性硬化症、2例系统性红斑狼疮、1例混合性结缔组织病和1例类风湿关节炎）的肺组织样本进行了光学显微镜检查，并通过免疫组织化学进行分析（5例尸检样本，3例肺移植后的外植体）。将结果与29例既无结缔组织病也无相关疾病的肺动脉高压患者的病例进行比较。我们发现：（a）8例与结缔组织病相关的肺动脉高压患者中有6例（75%）表现出明显的阻塞性肺血管病变，主要累及静脉/间隔前小静脉，而29例非结缔组织病对照肺动脉高压患者中只有5例（17.2%）出现这种情况；（b）与结缔组织病相关的肺动脉高压患者中始终存在小肌性动脉病变，主要表现为内膜纤维化和血栓形成病变；（c）8例与结缔组织病相关的肺动脉高压患者的肺组织样本中有6例显示血管周围炎性浸润。总之，我们的研究突出了这样一个事实，即结缔组织病病程中并发的肺动脉高压可能以更频繁累及肺静脉为特征，这也可以解释为什么与特发性肺动脉高压相比，这些患者对特定的肺动脉高压治疗反应较差。
