Pulmonary veno-occlusive disease
Pulmonary veno-occlusive disease (PVOD) is considered an uncommon variant of primary pulmonary hypertension (PPH) that preferentially affects the postcapillary pulmonary vasculature. It is still controversial if this condition and pulmonary capillary haemangiomatosis (PCH) are varied expressions of the same condition or different entities.
It is thought to account for ~5-10% of cases initially considered to be idiopathic PAH 2.
It is rare but can potentially affect all age groups with no geographic predilection. The majority of affected patients are under 50 years of age 1.
- in the pediatric population, both sexes are equally affected
- in the adult population, the ratio of male to female patients is approximately 2:1
Its presentation can be similar to other forms of pulmonary arterial hypertension such as progressive dyspnea, cough, fatigue and also hemoptysis.
Pulmonary capillary wedge pressure (PCWP) is usually normal due to patchy involvement. This is in contrast to the elevated pressures commonly obtained in patients with obstructed or stenotic larger pulmonary veins, mitral stenosis or left ventricular failure 4.
It is characterized by extensive occlusion of pulmonary veins by fibrous tissue in a patchy distribution. This may be loose and edematous or dense and sclerotic 7.
PVOD is still considered an idiopathic disease but innumerable associated conditions have been reported in the medical literature, which include 2,4:
- connective tissue disease
- HIV infection
- pulmonary Langerhans cell histiocytosis
- peripheral blood stem cell transplantation
- bone marrow transplantation 3
- after radiation therapy
- after chemotherapy
- including treatment with bleomycin, cisplatin, vincristine, carmustine, and mitomycin 4
A recent discovery has suggested a biallelic mutation in the EIF2AK4 gene as a cause of heritable form 9.
In general, imaging features can be non-specific and a definitive diagnosis often requires a lung biopsy 1.
Usually demonstrates nonspecific features of pulmonary hypertension, such as an enlarged pulmonary trunk and main pulmonary arteries and prominent heart right chambers.
Reported HRCT chest findings include 1,2,4,9:
- regions of ground-glass opacities, which can be
- diffuse multifocal 1,4
- perihilar 4
- patchy 4
- centrilobular 2,4: most cases 8,9
- smooth interlobular septal thickening
- mediastinal lymph node enlargement 9
- pleural effusions
- enlarged central pulmonary arteries
- mosaic pattern of lung attenuation
- normal caliber pulmonary veins
The normal appearances of the heart left chambers in the setting of these pulmonary findings favors that the transudation of fluid into the lung interstitium is possibly PVOD related.
PVOD pulmonary arteriographic findings include 4:
- enlarged central pulmonary arteries
- subtle narrowing of the distal arterial branches
- no arterial filling defects
- heterogeneous contrast blush in the parenchymal phase
- prolonged lung circulation time
- normal or small left atrium
Treatment and prognosis
Pulmonary veno-occlusive disease generally carries a poor prognosis (some report a 72% mortality at one year from diagnosis 1). Lung transplantation is the treatment of choice 2.
It is important to note that vasodilators commonly used to treat patients with primary pulmonary hypertension, such as calcium-channel blockers 1, epoprostenol (PGI2) 1 or prostacyclin 6 can lead to disastrous outcomes (severe pulmonary edema) in patients with pulmonary veno-occlusive disease.
History and etymology
The first description of the condition is thought to have been first dreported by J Hora (German physician) et al. in 1934 1. The term "pulmonary veno-occlusive disease" was thought to have been coined by Heath et.al in 1966 9.
Possible differential considerations include
- 1. Holcomb BW, Loyd JE, Ely EW et-al. Pulmonary veno-occlusive disease: a case series and new observations. Chest. 2000;118 (6): 1671-9. doi:10.1378/chest.118.6.1671 - Pubmed citation
- 2. Montani D, Price LC, Dorfmuller P et-al. Pulmonary veno-occlusive disease. Eur. Respir. J. 2009;33 (1): 189-200. doi:10.1183/09031936.00090608 - Pubmed citation
- 3. Troussard X, Bernaudin JF, Cordonnier C et-al. Pulmonary veno-occlusive disease after bone marrow transplantation. Thorax. 1984;39 (12): 956-7. doi:10.1136/thx.39.12.956 - Free text at pubmed - Pubmed citation
- 4. Frazier AA, Franks TJ, Mohammed TL et-al. From the Archives of the AFIP: pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis. Radiographics. 27 (3): 867-82. doi:10.1148/rg.273065194 - Pubmed citation
- 5. Swensen SJ, Tashjian JH, Myers JL et-al. Pulmonary venoocclusive disease: CT findings in eight patients. AJR Am J Roentgenol. 1996;167 (4): 937-40. AJR Am J Roentgenol (abstract) - Pubmed citation
- 6. Resten A, Maitre S, Humbert M et-al. Pulmonary hypertension: CT of the chest in pulmonary venoocclusive disease. AJR Am J Roentgenol. 2004;183 (1): 65-70. AJR Am J Roentgenol (full text) - Pubmed citation
- 7. Mandel J, Mark EJ, Hales CA. Pulmonary veno-occlusive disease. Am. J. Respir. Crit. Care Med. 2000;162 (5): 1964-73. doi:10.1164/ajrccm.162.5.9912045 - Pubmed citation
- 8. Matsushita K, Kanna M, Yazawa T et-al. Long-term survivor with pulmonary veno-occlusive disease. Circulation. 2012;125 (12): e503-6. Circulation (full text) - doi:10.1161/CIRCULATIONAHA.111.088450 - Pubmed citation
- 9. David Montani, Edmund M. Lau, Peter Dorfmüller, Barbara Girerd, Xavier Jaïs, Laurent Savale, Frederic Perros, Esther Nossent, Gilles Garcia, Florence Parent, Elie Fadel, Florent Soubrier, Olivier Sitbon, Gérald Simonneau, Marc Humbert. Pulmonary veno-occlusive disease. (2016) European Respiratory Journal. 47 (5): 1518. doi:10.1183/13993003.00026-2016 - Pubmed