Pulmonary veno-occlusive disease (PVOD) is a rare and severe pulmonary vascular disease characterized by widespread fibrotic obstruction of post-capillary pulmonary vessels (small pulmonary veins and venules), accompanied by secondary changes in pulmonary capillaries (capillary congestion, sometimes proliferation overlapping with PCH) and pulmonary arteries (intimal thickening). The vascular obstruction increases pulmonary venous resistance, causing post-capillary congestion, alveolar capillary leakage, and pre-capillary pulmonary hypertension that clinically resembles PAH.
Etiology overlaps with PCH—biallelic EIF2AK4 mutations cause autosomal recessive familial PVOD/PCH (often clinically indistinguishable), sporadic cases (majority), associations with chemotherapy (cyclophosphamide, mitomycin C, bleomycin, BCNU/CCNU, dasatinib), bone marrow and stem cell transplantation, autoimmune diseases (especially systemic sclerosis), HIV infection, and certain occupational exposures (organic solvents). The shared genetic and clinical features have led to combined classification under WHO Group 1' (PVOD/PCH).
Clinical presentation: progressive dyspnea, fatigue, severe hypoxemia disproportionate to right heart catheterization findings, syncope, and right heart failure. Key distinguishing features from PAH: significantly reduced DLCO (<55% predicted), characteristic HRCT findings (centrilobular ground-glass opacities, smooth interlobular septal thickening, mediastinal lymphadenopathy, occasional pleural effusions), normal-to-low pulmonary capillary wedge pressure (<15 mmHg, distinguishing from postcapillary PH due to left heart disease), and paradoxical worsening of pulmonary edema with PAH-targeted vasodilators (epoprostenol, ambrisentan, sildenafil) due to increased pulmonary blood flow into obstructed veins. Right heart catheterization shows pre-capillary PH pattern. Lung biopsy is rarely performed due to bleeding risk—diagnosis is usually presumptive based on HRCT and clinical features. Treatment: lung transplantation is the only definitive treatment; bridging medical therapy includes diuretics, oxygen, and cautious vasodilator therapy under close monitoring (some patients benefit modestly without pulmonary edema). Prognosis is poor with median survival of 12-24 months without transplantation.