Diagnosis and management of pulmonary veno-occlusive disease

ABSTRACTIntroduction Pulmonary veno-occlusive disease (PVOD) is an orphan disease and uncommon etiology of pulmonary arterial hypertension (PAH) characterized by substantial small pulmonary vein and capillary involvement.Areas covered PVOD, also known as 'PAH with features of venous/capillary involvement' in the current ESC/ERS classification.Expert opinion In recent years, particular risk factors for PVOD have been recognized, including genetic susceptibilities and environmental factors (such as exposure to occupational organic solvents, chemotherapy, and potentially tobacco). The discovery of biallelic mutations in the EIF2AK4 gene as the cause of heritable PVOD has been a breakthrough in understanding the molecular basis of PVOD. Venous and capillary involvement (PVOD-like) has also been reported to be relatively common in connective tissue disease-associated PAH (especially systemic sclerosis), and in rare pulmonary diseases like sarcoidosis and pulmonary Langerhans cell granulomatosis. Although PVOD and pulmonary arterial hypertension (PAH) exhibit similarities, including severe precapillary PH, it is essential to differentiate between them since PVOD has a worse prognosis and requires specific management. Indeed, PVOD patients are characterized by poor response to PAH-approved drugs, which can lead to pulmonary edema and clinical deterioration. Due to the lack of effective treatments, early referral to a lung transplantation center is crucial.KEYWORDS: Pulmonary veno-occlusive diseasepulmonary hypertensionEIF2AK4chemotherapysolventspulmonary edematransplantation Article highlights PVOD, also known as 'PAH with features of venous/capillary involvement' in the current ESC/ERS classification, is an uncommon etiology of PAH characterized by substantial small pulmonary vein and capillary involvement.Risk factors for PVOD include genetic susceptibilities (biallelic EIF2AK4 mutations) and exposure to occupational organic solvents, chemotherapy, and potentially tobacco.Significant venous/capillaries involvement has been also reported complicating connective tissue diseases (systemic sclerosis, interstitial lung disease associated with anti-synthetase syndrome) or respiratory diseases (sarcoidosis, pulmonary Langerhans cell granulomatosis).Several distinctive features can help differentiate PVOD from PAH: the combination of very low DLCO, resting hypoxemia, severe desaturation during exercise, and radiological signs on HRCT.PVOD is associated with a poor prognosis and a limited response to PAH-approved drugs, which can result in pulmonary edema and clinical deterioration.Declaration of interestD Montani has received speaker fees from Bayer, Janssen and MSD, consultancy fees from Acceleron, Janssen and MSD, and research grants from Acceleron, Janssen, and MSD. A Boucly has received compensation for scientific symposia from Janssen and MSD, speaker fees from Janssen, MSD, AOPHealth, and Ferrer, and research grants from Acceleron, Janssen, and MSD. A Beurnier has received speaker fees from AstraZeneca and Sanofi Aventis. O Sitbon has received speaker fees from AOPHealth, Janssen, Ferrer, and MSD, consultancy fees from Acceleron, Altavant, AOPHealth, Ferrer, Gossamer Bio, Janssen, and MSD, research grants from Acceleron, AOPHealth, Janssen, and MSD, and has served as an advisory board member for Altavant, Gossamer Bio, Janssen, and MSD. M Humbert has received speaker fees from Janssen and MSD, consultancy fees from Acceleron, Aerovate, Altavant, AOPHealth, Bayer, Chiesi, Ferrer, Janssen, MSD, MorphogenIX, Shou Ti, Tiakis, and United Therapuetics, research grants from Acceleron, AOPHealth, Janssen, MSD, and Shou Ti, and has served as an advisory board member for Acceleron, Altavant, Janssen, MSD, and United Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to discloseAdditional informationFundingThis paper was not funded.