Described as a form of pulmonary arterial hypertension (PAH), pulmonary veno-occlusive disease (PVOD) is a pathological process involving small veins in the pulmonary circulation, and is estimated to encompass about 5-10% of cases previously diagnosed as idiopathic PAH [1] [2] [3] [4]. Several risk factors have been established, including male gender and increased exposure to tobacco smoke [3] [5]. The disease is marked by an elevation of pressure inside the pulmonary vessels that could eventually result in right ventricular failure [2] [5]. The clinical presentation of pulmonary veno-occlusive disease is strikingly similar to PAH with severe exertional dyspnea as one of the main symptoms. Some authors observed hemoptysis and occult alveolar hemorrhage in a small but significant number of patients [2] [3] [4]. Symptoms may rapidly progress within a short period of time after administration of standard PAH therapy. Although considered a subtype of PAH, PVOD resistance to standard PAH therapy and more pronounced risk for cardiorespiratory insufficiency are distinctive characteristics of the disease.

• Fatigue

  Clinical presentation is non-specific, including dyspnoea, cough and fatigue. Diagnosis of PVOD is typically based on high clinical suspicion with a definitive diagnosis confirmed by histology. [ncbi.nlm.nih.gov]

  Progressively worsening dyspnea and signs of heart failure such as fatigue and blood pressure changes are manifestations of PVOD. [symptoma.com]

  It is believed to be associated with blood cancers, such as leukemia and lymphoma, and bone marrow transplantation and chemotherapy Common signs and symptoms of Pulmonary Veno-Occlusive Disease are shortness of breath, coughing-up blood, fatigue, and [dovemed.com]

  Shortness of breath (dyspnea) and tiredness (fatigue) during exertion are the most common symptoms of this condition. [ghr.nlm.nih.gov]

• Pathologist

  It is important that both clinician and pathologist be aware of this entity; otherwise, elastic tissue stains may not be performed and the diagnosis missed. [ncbi.nlm.nih.gov]

  Ideally this should be in a multidisciplinary clinical setting with input from respiratory physicians, rheumatologists, cardiologists, radiologists and pathologists with experience in pulmonary vascular disease, as well as specialised nurses and paramedical [em-consulte.com]

• Recurrent Pulmonary Embolism

  Chest roentgenogram finding suggesting postcapillary pulmonary hypertension is a clue to a diagnosis and differentiates this from two other causes of clinical primary pulmonary hypertension, that is, recurrent pulmonary embolism and plexogenic pulmonary [ncbi.nlm.nih.gov]

  Secondary thromboembolic events are common and may be the only clinical evidence of a tumor at presentation, with clinical features similar to those of recurrent pulmonary embolism. [doi.org]

• Sudden Infant Death Syndrome

  Clinical and gross autopsy findings on a 3-month-old infant were consistent with the sudden infant death syndrome. However, on histologic examination pulmonary veno-occlusive disease was found. [ncbi.nlm.nih.gov]

• Infectious Mononucleosis

  This case report is about a patient with PVOD, whose first symptoms of the disease occurred after infectious mononucleosis. [ncbi.nlm.nih.gov]

• Dyspnea

  The patient was a 21-year-old male who complained of dyspnea with hypoxemia followed by loss of consciousness. The abnormalities in chest CT and echocardiography were compatible with a diagnosis of PVOD. [ncbi.nlm.nih.gov]

  Progressively worsening dyspnea and signs of heart failure such as fatigue and blood pressure changes are manifestations of PVOD. [symptoma.com]

• Cough

  Clinical presentation is non-specific, including dyspnoea, cough and fatigue. Diagnosis of PVOD is typically based on high clinical suspicion with a definitive diagnosis confirmed by histology. [ncbi.nlm.nih.gov]

  Fatigue on exertion Fainting Coughing up blood Difficulty breathing while lying flat Exams and Tests The health care provider will examine you and ask about your medical history and symptoms. [leehealth.org]

  It is believed to be associated with blood cancers, such as leukemia and lymphoma, and bone marrow transplantation and chemotherapy Common signs and symptoms of Pulmonary Veno-Occlusive Disease are shortness of breath, coughing-up blood, fatigue, and [dovemed.com]

  Clinical Case Female, 51 years of age, ex-smoker, working as a gardener, seen in another center for progressive dyspnea and dry cough which began 8 months previously. Initial spirometry showed severe obstructive disease. [archbronconeumol.org]

• Exertional Dyspnea

  A 58-year-old woman was referred to our hospital with a chief complaint of exertional dyspnea. [ncbi.nlm.nih.gov]

  The clinical presentation of pulmonary veno-occlusive disease is strikingly similar to PAH with severe exertional dyspnea as one of the main symptoms. [symptoma.com]

  Case report A 53-year-old woman with no history of smoking became aware of the onset of exertional dyspnea in early June, 2011. Her symptoms gradually increased, and were accompanied by a dry cough. [omicsonline.org]

  The clinical manifestations are nonspecific and may include exertional dyspnea (60% of all cases), fatigue, angina, syncope, and cor pulmonale ( 1, 14 ). [doi.org]

• Painful Cough

  cough, hemoptysis or syncope. 16, 20, 22 Physical exam findings are typically nonspecific and consistent with that of pulmonary hypertension. [nature.com]

  Some patients suffer from chest pain, cough (which is often nonproductive), cyanosis, and, rarely, syncope [ 5, 7 ]. Hemoptysis occurred in 8 out of 20 patients in a case series [ 5 ] but in only 1 out of 24 patients in another series [ 6 ]. [karger.com]

• Dyspnea at Rest

  At 68 years of age, she was urgently admitted to our hospital because of severe dyspnea at rest. A chest x-ray showed bilateral pulmonary artery enlargement ( Figure 1 ). [circ.ahajournals.org]

• Failure to Thrive

  In infants, the disease is initially observed as feeding difficulty and/or failure to thrive, often accompanied by mild respiratory distress. Two of the infants died suddenly. [ncbi.nlm.nih.gov]

• Cyanosis

  As the condition worsens, affected individuals can develop a bluish tint to the skin (cyanosis), chest pains, fainting spells, and an accumulation of fluid in the lungs ( pulmonary edema ). [ghr.nlm.nih.gov]

  The exam may reveal: Increased pressure in the neck veins Clubbing of the fingers Bluish coloration of the skin due to lack of oxygen ( cyanosis ) Swelling in the legs Your provider may hear abnormal heart sounds when listening to the chest and lungs [mountsinai.org]

  Common signs and symptoms associated with Pulmonary Venoocclusive Disease include: Shortness of breath on exertion Fatigue Cyanosis (bluish skin discoloration) Hemoptysis (coughing-up blood) Syncope (fainting) in later stages How is Pulmonary Veno-Occlusive [dovemed.com]

• Neglect

  As in PAH, progressive dyspnoea on exertion is the most frequent symptom, although it is often neglected by the patients, leading to frequent delay in establishing the diagnosis. [doi.org]

• Forgetful

  When clinicians encounter patients with interstitial lung disease, they should not forget the possibility of PVOD and should be alert for emerging pulmonary hypertension. [ncbi.nlm.nih.gov]

The diagnosis of pulmonary veno-occlusive disease (PVOD) may be difficult to attain solely on clinical grounds, but the importance of a detailed patient history and a proper physical examination must not be overlooked. Physicians should obtain a meticulous personal history since PVOD has been associated with human immunodeficiency virus (HIV) infection, sarcoidosis, Langerhans cell granulomatosis, and connective tissue diseases [5]. During the physical examination, auscultation of the lungs and the heart can provide valuable clues, such as systolic murmurs (which may point to tricuspid regurgitation) and crackles [2]. Many studies have proposed that the diagnosis of pulmonary veno-occlusive disease is ideally made by obtaining a biopsy of the lungs with subsequent histopathological examination [2] [3] [5] [6], but the numerous risks of this procedure advocate the use of non-invasive studies, most important being arterial blood gases and imaging procedures. Pulse oximetry and pulmonary function tests confirm hypoxemia and a low diffusing capacity for carbon monoxide (CO) respectively, whereas high-resolution computed tomography (HRCT), described as a very useful imaging study for the diagnosis of PVOD, reveals centrilobular ground-glass opacities, thickening of the septa, and enlargement of lymph nodes [1] [2] [7].

• Lymphocytic Infiltrate

  Cases with PCH also all showed a mild interstitial lymphocytic infiltrate but there was no venulitis or infarction. [ncbi.nlm.nih.gov]

  infiltrates, lymphocytic venulitis or leukocytoclastic vasculitis may be associated with interstitial fibrosis. 16, 22 Role of vascular injury and endothelial dysfunction The endothelium plays a dynamic role in maintaining normal microvascular blood [nature.com]

1. Montani D, Lau EM, Dorfmüller P, et al. Pulmonary veno-occlusive disease. Eur Respir J. 2016;47(5):1518-1534.
2. Montani D, Price LC, Dorfmuller P, et al. Pulmonary veno-occlusive disease. Eur Respir J. 2009;33(1):189-200.
3. Montani D, Achouh L, Dorfmüller P, et al. Pulmonary veno-occlusive disease: clinical, functional, radiologic, and hemodynamic characteristics and outcome of 24 cases confirmed by histology. Medicine (Baltimore). 2008;87(4):220-233.
4. Rabiller A, Jais X, Hamid A, et al. Occult alveolar haemorrhage in pulmonary veno-occlusive disease. Eur Respir J 2006;27:108–113.
5. Montani D, O'Callaghan DS, Savale L, et al. Pulmonary veno-occlusive disease: recent progress and current challenges. Respir Med. 2010;104(Suppl 1):S23-32.
6. Porres-Aguilar M, Al-Bayati I, Porres-Muñoz M, et al. Pulmonary veno-occlusive disease as a cause of pulmonary arterial hypertension. Proceedings Proc (Bayl Univ Med Cent). 2015;28(3):350-352.
7. Resten A, Maitre S, Humbert M, et al. Pulmonary hypertension: CT of the chest in pulmonary veno-occlusive disease. Am J Roentgenol. 2004;183:65–70.