Pulmonary veno-occlusive disease: illustrative cases and literature review

Abstract

Pulmonary veno-occlusive disease (PVOD), also known as "pulmonary arterial hypertension (PAH) with overt features of venous/capillary involvement", is a rare cause of PAH characterised by substantial small pulmonary vein and capillary involvement, leading to increased pulmonary vascular resistance and right ventricular failure. Environmental risk factors have been associated with the development of PVOD, such as occupational exposure to organic solvents and chemotherapy, notably mitomycin. PVOD may also be associated with a mutation in the EIF2AK4 gene in heritable forms of disease. Distinguishing PVOD from PAH is critical for guiding appropriate management. Chest computed tomography typically displays interlobular septal thickening, ground-glass opacities and mediastinal lymphadenopathy. Life-threatening pulmonary oedema is a complication of pulmonary vasodilator therapy that can occur with any class of PAH drugs in PVOD. Early referral to a lung transplant centre is essential due to the poor response to therapy when compared with other forms of PAH. Histopathological analysis of lung explants reveals microvascular remodelling with typical fibrous veno-occlusive lesions. This review covers the main features distinguishing PVOD from PAH and two clinical cases that illustrate the challenges of PVOD management.

FIGURE 1

Computed tomography and histopathological images of patient 1 at diagnosis (2009) (a and b) and at the time of lung transplantation (2017) (c and d). a) In 2009, chest computed tomography revealed mild nonspecific ground-glass opacities and interlobular septal thickening, without lymph node enlargement (not shown). c) In 2017, ground-glass opacities and interlobular septal thickening are more pronounced. b) Lung histology in 2009 (surgical biopsy, haematoxylin and eosin staining) and d) in 2017 (lung transplant, haematoxylin and eosin–saffron staining) are shown. In b), pulmonary microcirculation (scale bar = 50 µm) shows extensive thickening of the intima (arrow) with subtle venous remodelling (asterisk). d) Subtotal obliteration of septal veins is confirmed in the explanted lung in 2017 (asterisk) with patchy capillary congestion and proliferation (arrow) and more extensive remodelling of the microcirculation (zoom-in panel; scale bar = 50 µm).

FIGURE 2

Computed tomography images of patient 2, a) at diagnosis and b) 2 weeks later.