The Mighty Logo

I'm Aware That I'm Rare: Stephen Mathai, MD (Part 1)

The most helpful emails in health
Browse our free newsletters

Dr. Stephen Mathai is an Associated Professor of medicine at the Johns Hopkins University School of Medicine. His areas of clinical expertise include pulmonary disease and critical care medicine. His research interests include scleroderma-associated pulmonary hypertension, idiopathic pulmonary fibrosis and pulmonary complications of connective tissue disease. Dr. Mathai discusses how scleroderma increases your risk of the development of pulmonary hypertension.


My name is Steve Mathai. I’m a pulmonologist at Johns Hopkins School of Medicine, and my clinical and research interests are in pulmonary hypertension and specifically in scleroderma associated disease.

Today I’d like to talk with you about scleroderma and pulmonary hypertension, how scleroderma increases your risk of the development of pulmonary hypertension and how therapies might be different for pulmonary hypertension associated with this disease compared to other diseases.

Scleroderma is an autoimmune diseases of really unknown origin. It is a relatively uncommon disease when compared to other rheumatologic disease like lupus or rheumatoid arthritis, but the unique aspect of scleroderma and why it’s so relative and pertinent to patients when we think about pulmonary hypertension is that the risk of developing pulmonary hypertension is much higher in patients with scleroderma than in other connective tissues diseases. So, these connective tissue diseases, which I’ve mentioned include lupus, rheumatoid arthritis, Sjogren’s syndrome, these are all diseases that can be associated with pulmonary hypertension, but much more rarely than in scleroderma.

On average, we think about 10 to 15 percent of patients with scleroderma will go onto to develop pulmonary hypertension. And while that is significantly increased a proportion compared to other connective tissue diseases, it offers a couple of instructive things regarding the evaluation of pulmonary hypertension and the potential for understanding better the develop of pulmonary hypertension. So, I think it’s a very useful disease state to focus on clinically because we can learn a lot about the disease as having a particular group of patients who are at risk for developing the disease.

Scleroderma is a multi-organ disease, a systemic disease, so similar to diseases like lupus and rheumatoid arthritis that affect multiple organ systems, scleroderma affects the heart, the lungs, skin, the kidneys, and the muscles. And therapy is often directed at those particular organs. So, for instance, when someone has progressive skin disease, and scleroderma is characterized by this hardening of the skin, and that’s actually the origins of the word scleroderma are from the Greek, which translates roughly to hard skin. So, you have thickening and hardening of the skin. Immunosuppressions, medications that suppress the immune system, can sometimes help slow down or even stop the progressive thickening of the skin that occurs with scleroderma.

Similarly, if there is evidence of muscle involvement, the muscle inflammation and weakness known as myositis, which can complicate scleroderma, sometimes immunosuppressive medications are used to suppress that and to treat that particular complication. Scarring in the lungs. If there is active scarring in the lungs, there’s a process of inflammation going on in the lungs, sometimes immunosuppressive medications are recommended for that.

The caveat to all of this, though, is that pulmonary hypertension in scleroderma is not responsive to immunosuppressive medications. So, we kind of view that a little bit differently. If someone has progressive lung disease, skin disease, or myositis, or if they have kidney disease, there are specific algorithms for treatment that might be useful to improve those particular complications of scleroderma. But for pulmonary hypertension, we treat it more like we treat pulmonary hypertension as in patients who have idiopathic pulmonary arterial hypertension or other forms of pulmonary arterial hypertension. We tend to treat both disease states at the same time, and because the modes and methods of treatment differ between pulmonary hypertension and scleroderma, I think it’s reasonable to view those as treating those disease states concurrently.

So, I typically am not seeing patients who are recently diagnosed with scleroderma. It’s more at the referral stage from rheumatologists who are more likely to see patients with diseases like scleroderma. But at our center, and we have a very scleroderma center at Hopkins, which is why I have a particular interest and clinical experience with patients with scleroderma, but the providers at our scleroderma center do discuss this with their patients and mention the risk of development of pulmonary hypertension and other complications that can be associated with scleroderma.

So, patients with scleroderma are at risk for other diseases that can affect the heart and lungs, such as interstitial lung disease, which is a progressive fibrotic lung disease, or a scarring of the lung tissue, that can lead to shortness of breath and actually can also lead to pulmonary hypertension as a consequence of this progressive fibrotic process of the lungs. There are other possibilities and other ways that pulmonary hypertension can develop in scleroderma as well. The process of scleroderma and the pathogenesis of how the disease progresses can also affect the heart independent of the lungs and cause the heart to become more stiff, and the function can be impaired with that. And shortness of breath can result from that process as well.

I think there are many aspects of scleroderma that can lead to not only the symptoms of shortness of breath, but also pulmonary hypertension and therefore it’s important to be aware of this particular complication in patients with this disease. As a part of that, it is commonly recommended, both in clinical practice guidelines and in just clinical practice that patients who have scleroderma undergo yearly evaluations for the presence or development of pulmonary hypertension. And where that comes into play is usually at the level of the rheumatologist or the primary care physician who is evaluating the patient before they develop these symptoms, like shortness of breath, that might indicate the development of pulmonary hypertension.

These screening tests include pulmonary function tests, or breathing tests, and these breathing tests include not only measurements of lung volumes and lung capacity, but also a measurement of the ability of oxygen to get from the air into your bloodstream, known as the diffusing capacity. And this relationship between the lung capacity, the volumes of air that the lungs have, and the relationship between this measurement called the diffusing capacity are very important because this ratio of these two numbers can be used to predict the development of pulmonary hypertension in patients with scleroderma.

If there’s an abnormal finding on the pulmonary function test, often patients will undergo echocardiograms as another screening tool to determine whether or not there’s development of pulmonary hypertension or suggestion of the development of pulmonary hypertension. And if those two tests come back abnormal, then often patients are referred to either a cardiologist or pulmonologist for evaluation and consideration of right heart catheterization.

The one thing to be aware of is that while there can be treatments for these complications of scleroderma that I mentioned, interstitial lung disease, the myositis, the kidney disease, and the skin disease, those treatments tend to center around either immunosuppressive therapies or a specific therapy for someone who has a renal involvement or kidney involvement, which involves a medication called angiotensin converting enzyme inhibitor, which is a commonly used blood pressure medication. But those medications don’t treat the pulmonary hypertension complication of scleroderma. So, you have to be pretty aware of that and cognizant of that so you don’t fall into the fall sense of security, “Oh, I’m treating the lung disease, or I’m treating the myositis, I’m treating the scleroderma, therefore my pulmonary hypertension is being treated.” Because it’s two separate avenues for treatment, two separate methods.

This is a good opportunity then to talk about the way we treat pulmonary hypertension when it is in the presence of scleroderma, and talk a little bit about the history of that. Up until recently, in a recent study that’s come out, the general concept and general feeling about treatment of scleroderma associated with pulmonary hypertension was that we would approach it the same way as we do other forms of pulmonary arterial hypertension and treat patients with any of the available therapies. And that’s based upon in a clinical experience of using the same medications that we have used to treat idiopathic pulmonary arterial hypertension and other forms of pulmonary arterial hypertension, but recognizing some of the differences in response.

So, typically patients with scleroderma associated pulmonary arterial hypertension have had a more, or I should say, a less robust response to pulmonary vasodilator therapy than patients with idiopathic pulmonary arterial hypertension, for instance. And that’s been borne out through multiple different studies. But I think that newer studies suggest that aggressive initial therapy with combination of therapy involving phosphoesterase inhibitors and endothelin receptor antagonists might actually be particularly effective in patients with scleroderma associated pulmonary hypertension. A recent subgroup analysis of a clinical trial looking at a combination of these two classes of drugs really suggested a similar response in the scleroderma associated PAH group compared to the idiopathic PAH group, which is something that hasn’t really been demonstrated previously. So, I think there’s reason for some optimism that therapies that have been shown to be effective in idiopathic PAH and other forms of PAH in combination actually might be as effective in the scleroderma PAH population.

That being said, I’ve spent a lot of time talking about how the underlying scleroderma and the autoimmune disease is really important and how that can not only influence the development of pulmonary hypertension and the treatments that we target for scleroderma might be a little bit different than what we think about for pulmonary arterial hypertension in other forms. I think it’s really important to note that there are clinical trials now focusing just on scleroderma PAH patients, and I think that’s really valuable because we understand that while there are many similarities with regards to pulmonary arterial hypertension, between idiopathic patients and the scleroderma associated PAH patients, I think understanding that the scleroderma might be a risk factor for the development of pulmonary hypertension and how that contributes to the development of pulmonary hypertension is something that needs to be examined more and studied more.

And currently there are clinical trials now focused on patients with scleroderma associated PAH to see if there are pathways in the immune system that might be abnormal and therefore could be targeted with specific therapies against the immune system to either improve pulmonary hypertension or even prevent the development of pulmonary hypertension. I think that’s an exciting arena in research in pulmonary arterial hypertension that we are currently delving into.

My name is Stephen Mathai, and I am aware that I’m rare.

Learn more about pulmonary hypertension at Never miss an episode with the phaware® podcast app. Follow us on facebook, twitter, instagram, youtube & linkedin @phaware #phaware #phawareMD #scleroderma

Originally published: November 21, 2017
Want more of The Mighty?
You can find even more stories on our Home page. There, you’ll also find thoughts and questions by our community.
Take Me Home