What is the diagnosis and treatment approach for a patient with pulmonary veno occlusive disease?

Pulmonary Veno-Occlusive Disease: Diagnosis and Treatment

Patients with suspected or confirmed pulmonary veno-occlusive disease (PVOD) must be referred immediately to a lung transplantation center, as this is the only curative therapy for a disease with dismal prognosis and no established effective medical treatment. 1

Diagnosis

Clinical Presentation

PVOD presents with dyspnea on exertion and fatigue that is clinically indistinguishable from idiopathic pulmonary arterial hypertension (IPAH), but several key features help differentiate it 2:

• Higher male predominance compared to other forms of PAH 2
• Digital clubbing (unusual in other PAH forms) 2
• Bi-basal crackles on lung auscultation (unusual in other PAH forms) 2
• Higher tobacco exposure compared to PAH patients 3

Diagnostic Testing Algorithm

High-resolution CT scanning is the investigation of choice and can establish diagnosis with high probability when combined with clinical findings, avoiding the need for hazardous lung biopsy in most cases 2:

• Subpleural thickened septal lines 2
• Centrilobular ground-glass opacities (contrasting with panlobular distribution in IPAH) 2
• Mediastinal lymphadenopathy 2
• The combination of all three findings is 100% specific for PVOD with 66% sensitivity 2

Pulmonary function testing reveals distinctive patterns 2:

• Markedly lower diffusion capacity for carbon monoxide (DLCO) compared to other PAH forms 2
• More severe hypoxemia at rest 2, 3

Bronchoalveolar lavage demonstrates occult alveolar hemorrhage 2:

• Significantly elevated cell count 2
• Higher percentage of hemosiderin-laden macrophages 2
• Markedly elevated Golde score 2

Genetic testing for bi-allelic EIF2AK4 mutations can confirm heritable PVOD without histological confirmation 1, 4

Right heart catheterization shows 2:

• Elevated pulmonary artery pressures similar to IPAH 2
• Normal pulmonary capillary wedge pressure (pathological changes occur in small venules, not larger veins) 2, 1
• Lower mean systemic arterial pressure compared to PAH 3

Critical Diagnostic Pitfall

Vasoreactivity testing may precipitate acute pulmonary edema and should be performed with extreme caution 2

Treatment Approach

Immediate Management

Refer to lung transplantation center immediately upon diagnosis - this is a Class I, Level C recommendation 2, 1:

• PVOD has substantially worse prognosis than IPAH with median survival approximately 1 year without transplantation 1, 5
• Lung transplantation is the only curative therapy 2, 1
• No reports of disease recurrence post-transplant 2

Medical Management Principles

All PVOD patients must be managed exclusively at centers with extensive experience in pulmonary hypertension - this is a Class IIa, Level C recommendation 2, 1:

PAH-specific vasodilators, particularly prostanoids, must be used with extreme caution or avoided due to high risk of life-threatening pulmonary edema 2, 1:

• In one series, 43.8% of PVOD patients developed pulmonary edema after initiating PAH-specific therapy (median 9 days after treatment) 3
• Pulmonary edema occurred with intravenous epoprostenol, oral bosentan, and calcium channel blockers 3
• The presence of characteristic CT findings correlates with risk of pulmonary edema with epoprostenol therapy 2
• No clinical, functional, or hemodynamic characteristics predict which patients will develop pulmonary edema 3

Despite these risks, there are reports of sustained clinical improvement in individual patients treated cautiously with these medications 2. Patients must be fully informed about the risks before any trial of PAH-specific therapy 2.

Supportive Care

Oxygen therapy for severe hypoxemia (PVOD patients are typically more hypoxemic than other PAH forms) 1

High-dose diuretics to manage fluid retention and pulmonary congestion 1

Inotropic support (such as dobutamine) may be required for hemodynamic stabilization in severe cases 1

Contraindications

Atrial septostomy may be considered but is usually limited by severe baseline hypoxemia 2

Pathophysiology

The disease involves extensive and diffuse occlusion of pulmonary venules and veins with intimal and adventitial fibrosis 2, 1:

• Luminal occlusion can be solid or eccentric with medial thickening 2
• Large amounts of hemosiderin in alveolar macrophages and type II pneumocytes 2
• Engorged and prominent capillary vessels 2
• Pulmonary arterioles show remodeling with medial hypertrophy and intimal fibrosis 2
• Plexiform lesions and fibrinoid arteritis are NOT present (distinguishing feature from other PAH forms) 2
• Pulmonary interstitium shows edema and may progress to interstitial fibrosis 2