I'm Aware That I'm Rare: Steven D. Nathan, MD
Dr. Steven D. Nathan discusses sarcoidosis and how it can be complicated by the development of pulmonary hypertension.Steven D. Nathan, MD, is a member of several professional medical associations, including the American Thoracic Society, the American College of Chest Physicians, and the International Society for Heart and Lung Transplantation. Dr. Nathan is board certified in internal medicine, pulmonary diseases, and critical care medicine.
My name is Dr. Steven Nathan. I’m the medical director of the Advanced Lung Disease Program and Medical Director of the lung transplant program at Inova Fairfax Hospital in Falls Church, Virginia.
Today I’m going be talking to you about a lung condition called sarcoidosis that can be complicated by the development of pulmonary hypertension.
There is an intersection between lung disease and pulmonary hypertension. If you look at the WHO classification of pulmonary hypertension, we have (WHO) Groups 1, 2, 3, 4, & 5, the two where we have drugs approved are Group 1 PAH and Group 4 CTEPH, group two is pulmonary hypertension due to heart disease, Group 3 is pulmonary hypertension due to lung disease where we have no PH drugs proven to be effective therefore no drugs approved in this area of pulmonary hypertension. And then in Group 5, we have various miscellaneous conditions.
Sarcoidosis is a condition that we see fairly frequently in our program. It is primarily a lung disease. It’s a disease characterized by what we term “non-caseating” granulomas. These “non-caseating” granulomas can occur anywhere within the body. So it’s a systemic disease but the most common local for these noncaseating granulomas is in the lungs.
Now it is a disease that’s likely more prevalent in African Americans also certain pockets in Europe like in Ireland. In the Scandinavian countries, I believe, there’s a higher prevalence of sarcoidosis. It is a disease that is somewhat unpredictable in that it is prone to spontaneous resolution in many cases. The lungs tend to invariably be involved in upwards of about I’d say 90 percent of cases, even if patients are asymptomatic. Frequently, if you do a lung biopsy, you’ll see these “non-caseating” granulomas, so they can just be sitting there without having any pathophysiologic consequence.
However, in some patients they will develop lung disease. There are various stages of lung disease. We talk about skating stage 1 through 4, with stage 4 being less common fortunately because those are the patients who go on to develop progressive fibro-cavitary lung disease and estimated about 20% of patients who have pulmonary sarcoidosis will go onto stage 4 fibrocystic lung disease.
Now pulmonary hypertension can complicate any form of diffuse parenchymal lung disease including sarcoidosis and sarcoidosis tends to have a higher prevalence of pulmonary hypertension than some of the other lung conditions that we deal with. For example, idiopathic pulmonary fibrosis, COPD, the prevalence of PH tends to be high in sarcoidosis because it appears that it’s more than the lung disease itself and the destructive changes happening in the lung parenchyma. The “non-caseating” granulomas that characterize sarcoidosis can affect the pulmonary vasculature primarily giving essentially a pulmonary vasculitis which can lead to pulmonary hypertension. Albeit, this is a rare cause of pulmonary hypertension in the context of sarcoidosis.
Sarcoidosis is also unique because one of the characteristic features is that you can get mediastinal lymphadenopathy. That means the lymph nodes in the mid-chest region can enlarge. It’s fairly characteristic for sarcoidosis. In some cases these can go on to develop fibrosis, can have essentially a fibrosing mediastinitis which is just fibrosis of the mediastinum which is the central part of the thoracic anatomical structures. The downstream consequences of this is that these can involve the vessels and can cause mechanical obstruction of the pulmonary vessels leading to pulmonary hypertension.
So sarcoid can result in pulmonary hypertension which may be multi-factorial. The main reason is the parenchyma lung disease and the lung destruction that occurs, but also the changes in the mediastinum, the granulomatous vasculitis, that I mentioned, as well, can all lead to pulmonary hypertension. And for this reason, even though it’s primarily lung disease, sarcoidosis is categorized in Group 5 in terms of the world health organization classification of pulmonary hypertension.
If you look at patients with advanced pulmonary sarcoidosis, for example patients who have progressive disease requiring transplantation, about 70 to 80 percent of these patients will have complicating pulmonary hypertension. We know that pulmonary hypertension complicating any lung disease portends a worse outcome — including sarcoidosis. It’s been shown in numerous studies that those patients who have complicating pulmonary hypertension have significantly worse functional status as well as a higher propensity for moralities. Therefore it does portend a poorer prognosis.
The big question and the looming question out there for which we don’t have an answer is even though we know that pulmonary hypertension associated with lung disease including sarcoidosis is associated with worse outcomes, and even though we have multiple medications that can treat pulmonary hypertension, what we don’t know is whether treating the pulmonary hypertension of sarcoidosis or any other lung disease for that matter will result in improved outcomes. There have been a number of studies, mostly small series retrospective reviews that have looked at this issue and the data specifically in sarcoid is a little bit conflicting. There are some ongoing studies in sarcoidosis looking at treating the PH of sarcoidosis as a way of improving patient outcomes, but we don’t have any definitive data as yet.
Most patients will present with sarcoid first with pulmonary hypertension being discovered down the road once they have a well-established sarcoidosis and usually in the context of stage 4 sarcoidosis although it can occur in stage 2 and 3, as well. When to be suspicious that a patient with sarcoidosis might be developing pulmonary hypertension is a good question that is probably multi-factorial in answer. In other words, in many different things that might clue one in to the presence of complicating pulmonary hypertension. For example, if a patient has dyspnea that’s out of proportion to the lung parenchymal abnormalities or out of proportion to what the PFTs look like. If the patient is requiring oxygen as significant de saturation, has a limited six minute walk test — these are all clues to the presence of pulmonary hypertension.
Another clue might be to look at the CT itself and look at the size of the pulmonary artery and if the pulmonary artery to aorta ratio is greater than one, than this might suggest underlying pulmonary hypertension. The best screening tool for pulmonary hypertension in any case is echocardiogram and the echo might show evidence of pulmonary hypertension, it might show evidence of right ventricular dysfunction. It’s an important point to make that echo is not the diagnostic gold standard, of course the diagnostic gold standard remains right heart catheterization, in sarcoidosis patients as it is in patients with group 1 PAH.
If you have a patient with sarcoidosis, there are expert centers around the country and especially if you suspect that they are developing pulmonary hypertension, then they probably warrant referral to a pulmonary hypertension comprehensive care center for further evaluation and discussion with regards to treatment options.My name is Dr. Stephen Nathan and I’m certainly aware that I am quite rare.
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