Pulmonary veno-occlusive disease: a paradigm of diagnosis and therapeutic challenges in pulmonary hypertension.

Abstract

Purpose of review: Pulmonary veno-occlusive disease (PVOD) is a rare and life-threatening form of precapillary pulmonary hypertension. This review aims to outline its genetic and environmental risk factors, highlight key diagnostic challenges, and discuss current treatment options.

Recent findings: PVOD can occur sporadically or as a hereditary autosomal recessive condition with biallelic eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) mutations, leading to nearly complete disease penetrance. Known risk factors include specific drug/toxin and environmental exposures, such as mitomycin C and trichloroethylene, respectively. PVOD is characterized by progressive pulmonary venous and capillary remodelling, severe hypoxemia, and right ventricular failure. Diagnosis remains difficult due to overlapping features with pulmonary arterial hypertension (PAH), but high-resolution computed tomography (HRCT) findings, low lung diffusion capacity for carbon monoxide (DLCO), and genetic testing can aid differentiation. Initiation of PAH-approved drugs in patients with PVOD requires careful consideration due to limited evidence of long-term clinical benefits and the high risk of developing pulmonary oedema in this population. Lung transplantation remains the only curative treatment, with posttransplant survival rates comparable to idiopathic PAH.

Summary: PVOD is a progressive and fatal disease requiring early recognition and specific management. Due to its poor prognosis and lack of effective medical therapies, early referral for lung transplantation is crucial. Advances in genetic and molecular research may lead to novel treatment strategies.