What is pulmonary veno-occlusive disease?
In pulmonary veno-occlusive disease (PVOD), scar-like tissue gradually narrows and blocks the small veins and venules that carry oxygen-rich blood from the lungs back to the heart. Blood backs up in the lung circulation, pressure rises in the pulmonary arteries, and the right side of the heart has to work harder to pump blood through the lungs.
PVOD is classified within the pulmonary arterial hypertension group in the ESC/ERS pulmonary hypertension guidelines, as a form with features of venous and capillary involvement. It overlaps closely with pulmonary capillary haemangiomatosis, and many experts now regard the two as different appearances of the same disease. It is ultra-rare, affecting only a small number of people per million, and it is frequently first diagnosed as ordinary pulmonary arterial hypertension.
Symptoms of PVOD
Symptoms develop gradually and are similar to those of other forms of pulmonary hypertension:
- Breathlessness on exertion: the most common first symptom, slowly worsening over months.
- Tiredness and reduced exercise capacity.
- Chest discomfort, light-headedness or fainting during exertion.
- Ankle swelling and abdominal fullness as the right heart begins to fail.
- Low oxygen levels: often more marked than in typical pulmonary arterial hypertension, particularly on walking.
Some patients have a dry cough, and occasionally small amounts of blood in the sputum. Clubbing of the fingers may be seen.
Causes and risk factors
Several causes are recognised:
- Inherited PVOD: changes in both copies of the EIF2AK4 gene cause a heritable form, often in younger adults and sometimes in brothers and sisters. Because both copies must be affected, it is more common where parents are related by blood, which is relevant in some families in India.
- Chemotherapy: particularly alkylating agents such as mitomycin C and cyclophosphamide.
- Occupational exposure: organic solvents, especially trichloroethylene.
- Smoking.
- Connective tissue disease: particularly systemic sclerosis, where venous involvement may coexist with arterial disease.
- Bone marrow transplantation.
In many people no clear cause is found.
How PVOD is diagnosed
Lung biopsy is avoided because it carries a high risk of bleeding in pulmonary hypertension. Diagnosis instead rests on a combination of tests that, taken together, point to venous rather than purely arterial disease.
| Test | What it shows |
|---|---|
| Echocardiography | Raised estimated pulmonary pressure and strain on the right heart |
| Right heart catheterisation | Confirms pre-capillary pulmonary hypertension. The wedge pressure is usually normal despite venous disease |
| High-resolution CT chest | The characteristic triad of centrilobular ground-glass nodules, thickened septal lines and enlarged mediastinal lymph nodes |
| Lung function tests | A markedly reduced gas transfer (DLCO), often lower than expected |
| Six-minute walk test with oximetry | Exercise capacity and the degree of oxygen desaturation |
| Genetic testing | EIF2AK4 mutations, which confirm heritable PVOD without biopsy |
| Bronchoalveolar lavage (selected cases) | Occult bleeding with haemosiderin-laden macrophages |
The CT changes can be mistaken for interstitial lung disease, heart failure or infection, so an experienced reading in the context of pulmonary hypertension is important.
Treatment of PVOD
Cautious use of pulmonary hypertension drugs
The medicines used in pulmonary arterial hypertension (endothelin receptor antagonists, phosphodiesterase-5 inhibitors, riociguat, and prostacyclin pathway drugs) relax the arteries. In PVOD the blockage lies downstream in the veins, so increased flow into the lungs can cause fluid to leak into the air spaces (pulmonary oedema). These drugs may still help some patients, but they are started at low doses, increased slowly and monitored closely, preferably in a specialist pulmonary hypertension setting.
Supportive care
Long-term oxygen therapy corrects low oxygen levels, diuretics control fluid retention, and anticoagulation is decided individually. Vaccinations, careful exercise, and avoidance of pregnancy, which carries a very high risk, are discussed openly.
Lung transplantation
Lung transplantation is the only treatment that can cure PVOD. Because the disease tends to progress faster than pulmonary arterial hypertension and responds less well to drugs, referral to a transplant centre is advised at the time of diagnosis in suitable patients. Care is coordinated with cardiology and the transplant team.
Outlook and follow-up
PVOD is a serious condition that usually progresses over a few years. Regular review with walk tests, echocardiography, blood markers of heart strain and oxygen assessment helps judge when to step up treatment or proceed to transplant listing. Relatives of patients with heritable PVOD can be offered genetic counselling. For patients in Hyderabad, assessment is available at Apollo Hospitals, Financial District, with onward referral to transplant services when needed.
When to seek urgent care
Seek emergency help if you have sudden worsening of breathlessness, breathlessness at rest or when lying flat, frothy or blood-stained sputum, fainting, chest pain, or rapidly increasing leg swelling. Any of these, particularly soon after starting or increasing a pulmonary hypertension medicine, may indicate pulmonary oedema or right heart failure.
Frequently asked questions
How is PVOD different from pulmonary arterial hypertension?
Both cause high pressure in the lung arteries, but in PVOD the main blockage is in the small veins. This means standard pulmonary hypertension drugs can cause fluid to build up in the lungs, the disease often progresses faster, and early referral for lung transplantation is recommended.
Do I need a lung biopsy to confirm PVOD?
Usually not. Biopsy is risky in pulmonary hypertension. The diagnosis is made from the combination of right heart catheterisation, CT findings, very low gas transfer, low oxygen levels and, where present, an EIF2AK4 gene mutation.
Is PVOD inherited?
Some cases are caused by mutations in both copies of the EIF2AK4 gene and can affect brothers and sisters. Genetic counselling and testing can be offered to the family when a mutation is found.
Can I take pulmonary hypertension medicines?
Some patients benefit, but these medicines must be started carefully at low doses with close monitoring for pulmonary oedema. This should be supervised by a team experienced in pulmonary hypertension.
Is there a cure for PVOD?
Lung transplantation is currently the only curative treatment. Medicines, oxygen and diuretics help symptoms and can act as a bridge to transplantation.
Why was I first told I had another lung condition?
PVOD is ultra-rare and its CT appearance can resemble interstitial lung disease, heart failure or infection, while its pressure findings resemble pulmonary arterial hypertension. Delayed or revised diagnosis is common.
Related conditions and procedures
Consult Dr. Gogineni Ratnakara Rao
Apollo Hospitals, Financial District: Monday to Saturday, 8:30 AM to 5:00 PM. Anything in Lung Clinic, Chanda Nagar: Monday to Saturday (Thursday closed), 6:00 PM to 9:00 PM.