Pulmonary veno-occlusive disease (PVOD) and/ or pulmonary capillary hemangiomatosis (PCH)
My doctor says I have PVOD. What is this?
As the name suggests Pulmonary veno-occlusive disease (PVOD) uniquely involves the small veins of the lung circulation more than the small arteries. The veins become blocked with scar tissue that is not normally present.
Sometimes PVOD occurs in patients affected by connective tissue diseases like scleroderma, or patients infected with the human immunodeficiency virus (HIV). PVOD also occurs in patients who received some cancer chemotherapy medications or a bone marrow transplant or in individuals who inhaled organic solvent vapors. PVOD also can be inherited. Inherited PVOD is currently known to be caused by mutations in a gene called Eukaryotic translation Initiation Factor 2 Alpha Kinase 4 (EIF2AK4). When the gene, EIF2AK4, does not have a mutation, it produces a protein (also called EIF2AK4) that helps cells respond when they should repair themselves.
The exact number of people with PVOD is currently unknown, but it is known to be a very rare disease. Many scientists believe that PVOD occurs about 5-10 times less often than pulmonary arterial hypertension (PAH), which makes it an extremely rare disease. This means that PVOD occurs in approximately one to two patients per 10 million people.
The diagnosis of PVOD can be very challenging, even for medical specialists. Clues to the diagnosis can be found in the patient’s history. These clues include a history of exposure to organic solvents such as trichloroethylene, exposure to certain chemotherapeutic agents (used to treat cancer) such as cyclophosphamide or mitomycin or a diagnosis of PVOD/PCH in another family member.
There are a few tests that can be used to look for evidence of PVOD. Lung (pulmonary) function tests often show a distinct pattern, with normal or nearly normal lung volumes and a severe reduction in carbon monoxide gas transfer (“DLCO”). Certain features of a computed tomography scan (often referred to as a CT scan) of the chest can increase a doctor’s suspicion that PVOD is present. These include observations on the chest CT scan of (1) “centrilobular ground-glass opacities,” which are hazy spots in the airspaces of the lungs; (2) thickened lines in the lungs called “septal lines”; and (3) abnormally large lymph nodes in the mediastinum (called “mediastinal lymphadenopathy.”)
Confirmation of the diagnosis of PVOD usually requires examination of lung tissue by a pathologist. However, a lung biopsy may carry too much risk for many patients with advanced pulmonary hypertension. In this situation doctors often depend upon the chest CT and pulmonary function tests to make a presumptive diagnosis of PVOD. Doctors can test for EIF2AK4 mutations. For some patients, identification of EIF2AK4 mutations known to cause PVOD confirms the diagnosis of PVOD or PCH without a lung biopsy.
A diagnosis of PVOD has important therapeutic implications. First, PAH-specific therapies such as epoprostenol are generally not as effective as they are for the treatment of PAH; and they may even be harmful if given to a patient with PVOD. In some patients, PAH therapies like epoprostenol can cause rapid accumulation of fluid in the lungs (“pulmonary edema.”) Currently, the best treatment for PVOD is lung transplantation.
My doctor says I have PCH. What is this?
Pulmonary capillary hemangiomatosis (PCH) is a disease which mainly affects the lung capillaries (tiny vessels found between arteries and veins of the lungs.) The capillaries overgrow (or “proliferate”) in the lung tissue. The diagnosis can be made when pathologists see capillary overgrowth in a lung biopsy specimen. However, just like PVOD, lung biopsy often poses too much risk for patients with advanced pulmonary hypertension; forcing the doctor to make a provisional diagnosis of PCH.
Although the original descriptions of PCH and PVOD identified each as a unique pathologic condition, evidence that these two conditions overlap continues to accumulate. The evidence includes very similar results of pulmonary function tests, similar abnormalities on chest CT scans; and observations that the pathologic changes of PVOD and PCH often co-exist in the same patient. Like PVOD, mutations in the gene EIF2AK4 have been shown to cause PCH in some families. Also, like PVOD, PAH therapies, like epoprostenol, may cause the lungs to accumulate fluid rapidly (pulmonary edema). At present, lung transplantation is the most effective therapy for patients with PCH; just as it is for PVOD.