Pulmonary hypertension caused by sarcoidosis

Abstract

Pulmonary hypertension is an uncommon complication of sarcoidosis, but in severe pulmonary disease it occurs frequently. It is an important cause of cryptogenic dyspnea in sarcoidosis patients and can occur despite the absence of pulmonary fibrosis. The true prevalence is unknown. With the advent of specific therapies for pulmonary hypertension, there has been a resurgence of interest in the pathophysiology, diagnosis, and treatment of sarcoidosis-associated pulmonary hypertension. This article reviews the status of the current epidemiologic, pathophysiologic, and therapeutic knowledge regarding this entity.

Figure 1. Distribution of granulomas in pulmonary sarcoidosis

Sarcoidosis granulomas are found in a lymphatic distribution, including surrounding the bronchovascular bundle (circled area); the interlobular septae which also contain the pulmonary veins (adjacent to the line); and the subpleural area (arrow). Because of this anatomic orientation, granulomatous inflammation frequently encroaches on the vascular structures, even in the absence of overt fibrosis or vascular wall inflammation (Hematoxylin and eosin).

Figure 2. Granulomatous arteritis in sarcoidosis

2a. Movat pentachrome stain showing granulomas obliterating the internal and external elastic laminae and smooth muscle (arrow) of medium size artery. There is secondary intimal fibroplasia seen in the center of the artery. (Movat pentachrome). 2b. In some cases, only giant cells and mononuclear cell infiltrates may be seen in sarcoidosis-associated arteritis. Arrowhead indicates the vascular lumen. Numerous giant cells may be seen in the vessel wall (Hematoxylin and eosin).

Figure 2. Granulomatous arteritis in sarcoidosis

2a. Movat pentachrome stain showing granulomas obliterating the internal and external elastic laminae and smooth muscle (arrow) of medium size artery. There is secondary intimal fibroplasia seen in the center of the artery. (Movat pentachrome). 2b. In some cases, only giant cells and mononuclear cell infiltrates may be seen in sarcoidosis-associated arteritis. Arrowhead indicates the vascular lumen. Numerous giant cells may be seen in the vessel wall (Hematoxylin and eosin).

Figure 3. Obliteration of pulmonary venous drainage by exuberant granuloma formation

Movat pentachrome stain of an interlobular septum showing extensive fibrosis and obliteration of the venous structures by granulomas. Perivenular distribution of granulomas is typical in sarcoidosis. Arrows indicate compressive granulomas. (Movat pentachrome).

Figure 4. Compression of central pulmonary vascular structures by bulky lymph nodes

Coronal section of thorax of post-mortem specimen from a patient who died from end-stage SAPH. There is extensive hilar compression of the main pulmonary arteries. Arrow denotes the left lower lobe pulmonary artery, which is subtotally occluded by extrinsic compression of calcified lymph nodes that are present throughout the mediastinum. Image reproduced from Farver CF. Chapter 31: Sarcoidosis. In Dail and Hammar’s Pulmonary Pathology, 3rd edition. Editors, Tomashefski, Cagle, Farver, Fraire. Figure 18B. With kind permission of Springer Science and Business Media.