Stanford Vasculitis Clinic:

Infrequently Asked Questions about Uncommon Diseases

Vasculitis, a group of uncommon diseases characterized by inflammation of the blood vessels, caught the attention of Cornelia Weyand, MD, when she was an immunology and rheumatology fellow at Stanford in the 1980s. Her study of the specialty took her to the Mayo Clinic in Rochester, Minnesota, which gave her access to a large population of vasculitis patients. Weyand returned to Stanford in 2010 as a professor of immunology and rheumatology and started a vasculitis clinic while continuing a wide-ranging research program. During a recent interview, Weyand shared insights about the disease and the clinic, taking us from the time of the Vikings to current-day China.

To begin with, what is vasculitis?

No organ in the body can function without blood supply, which is why blood vessels have a life-sustaining function. Nature has protected blood vessels from inflammatory attacks, but in some patients this protective shield — what we call the immune privilege — fails, and they develop inflammatory disease of blood vessels. When there is an inflammatory attack on the large blood vessels — the aorta or its major branches — it creates a clinically critical situation.

Patients diagnosed with vasculitis and inflammatory blood vessel disease have abnormalities in their immune system. The immune system no longer respects the immune privilege of a blood vessel. In these patients the immune system breaks through that immune privilege and sends inflammatory cells into the blood vessel. Depending on the size of that blood vessel, the vessel responds differently. Either it becomes damaged and then the consequence is bleeding, or it becomes occluded and then the consequence is lack of oxygen and tissue breakdown.

Inflammation of the aorta is most frequently caused by a disease entity called giant cell arteritis (inflammation of an artery). A variant of that disease is Takayasu arteritis, and we have assembled probably the largest cohort in the country of patients with that diagnosis. Other forms of vasculitis are GPA (granulomatosis with polyangiitis), MPA (microscopic polyangiitis), and Churg-Strauss vasculitis.

CORNELIA WEYAND, MD (right), works to re-educate the immune system of a patient with vasculitis.

How did the clinic get started?

During my time as a young faculty at the Mayo Clinic I had an opportunity to see many patients with vasculitis in Minnesota. That’s because one of the vasculitides — giant cell arteritis — is a Viking disease. When Scandinavian immigrants — descendants from Vikings — came to the United States, they settled in Minnesota and brought the disease with them. That allowed me to develop a research program and clinical expertise that came with me to Stanford in 2010.

Stanford has had a prominent position in cardiovascular disease for half a century. When they began to do heart transplants here, it fueled the development of an outstanding vascular pathology program. Likewise, that our radiologists are so extraordinarily good is a legacy of the development of that prominence in cardiovascular disease.

Because this disease is systemic in nature, but it affects localized organs like the eyes, ears, and nerves, there is a need for expertise in many different areas, which Stanford has.

I took advantage of those areas of expertise and began the multidisciplinary clinic that we have today. This is truly a clinic that not every medical center can have because of the varied expertise required. Our clinic is one of only a few in the nation, and several hundred patients come here on an annual basis.

How are we treating patients with this disease?

Because vasculitis has a component of systemic inflammation, patients with vasculitis often have fevers, weight loss, fatigue, and diffuse aches and pains that are difficult to pinpoint.

All of our patients are chronically sick, so management requires treatment by us over many years. We attempt to inhibit inflammation, but even more so, we attempt to re-educate the immune system of the patient so that when they come out of their therapeutic phase, their immune system is not going to repeat how it has acted in the past.

You refer to the multidisciplinary character of the clinic. Can you say more?

When we are managing patients with these diseases, we almost always work very closely with different specialists, particularly those in cardiology and cardiovascular disease. We have a particular expertise at Stanford in large vessel vasculitis, which is vasculitis of the aorta and its immediate branches. There is a very close connection between the Vasculitis Clinic and the Center for Marfan Syndrome and Related Aortic Disorders, which is run by cardiologist David Liang, MD, PhD, because that center is focused on failure of the aorta. Patients with inflammatory disease of the aorta may need surgery, so we work very closely with our colleagues in cardiothoracic surgery as well.

For diagnostic purposes, we need expertise from two directions — pathology and radiology. We also work very closely with the eye center, ENT, and neurovascular surgery because patients with inflammatory blood vessel disease often have trouble with their eyes, sinuses, ears, and nerves.

What research is the clinic involved in?

Another important component of the clinic is an associated research program. We are studying which abnormalities in our patients’ immune systems induce these diseases, how we can detect them, and what the mechanisms of the disease are. We also want to know what the immune system is doing wrong to cause inflammation of the aorta or another blood vessel. And we are looking at which type of immunomodulatory therapies can be used so we can stop the immune system from acting the wrong way.

A unique aspect of our research involves a bioengineered mouse that does not have an immune system of its own but serves as a proxy for our patients. We engraft a human blood vessel into the mouse and then we transfuse the blood of our patient, which gives the mouse the immune system of our patient. That way, we can study in the mouse how that patient’s immune system would respond to therapy. That has been an extremely valuable tool for us to examine vasculitis. It is also an excellent example of personalized medicine offered at Stanford: We build a model system that is personalized for one individual to capture the unique aspects of disease and therapeutic responsiveness.

We have published a series of papers having to do with the humanized mouse model, including one that appeared in the July 31, 2018 issue of Circulation Research, which featured an image from that paper on its cover.

What about the future?

A disease that I mentioned earlier — Takayasu arteritis — was originally described in Japan. It’s a disease that is more frequent in young Asian women, and Japanese scientists are seeking collaboration with Stanford in how to diagnose and manage these patients.

While the United States has had an unparalleled ascent in biomedicine, many groups in the world are now participating in the research of vasculitis, from the bench to the bedside. Physician scientists in Shanghai have become important collaboration partners for us. They take care of many patients with vasculitis, and we will work closely with them in exploring the underlying immune defects, diagnostic criteria, and treatment guidelines for diseases that occur in their population, and vasculitis is one of them.