Share ThisEditor's Update: This article was first published December 14, 2021. It was most recently reviewed and updated April 26, 2023.
In our Ask a Doc series, we sit down with physicians and other clinical experts, including those at Allegheny Health Network (AHN), for a chat on an important health topic. In this post, we talk about lupus with Dr. Susan Manzi, who has dedicated much of her career to researching and treating the disease.
If you have questions about lupus, Susan Manzi, MD, MPH, is one of the best people you could ask for answers.
Chair of the Allegheny Health Network (AHN) Medicine Institute, Dr. Manzi was instrumental in establishing AHN’s Autoimmunity Institute. She is recognized internationally for research regarding premature cardiovascular disease in systemic lupus erythematosus and in identifying biomarkers for lupus diagnosis, monitoring, and stratification. In addition to being director of the AHN Lupus Center of Excellence, Dr. Manzi is medical director for the Lupus Foundation of America, and previously served as chair of the foundation’s board of directors.
She took time to talk with us about lupus, including some of the advances in treatment and research around this challenging autoimmune disease.
Kendyl Ferrara: For people who already have some understanding of what lupus is, what are the biggest gaps or misunderstandings that they still tend to have about this disease?
Dr. Susan Manzi: People tend to think lupus is a mild disease that just causes occasional joint pain and skin rashes, and don’t always realize that it is a chronic disease with no cure, that it is potentially fatal, and that it can cause significant disability.
Two other things people may not know are that lupus tends to affect young women between the ages of 15 and 45, and it impacts women of color more commonly.
Kendyl Ferrara: What does living with lupus look like on a day-to-day basis?
Dr. Susan Manzi: I would say it’s unpredictable — lupus patients will often use that word. I’ve heard patients say that a diagnosis of cancer might even be easier since at least there is a chance of a cure with many cancers. Individuals with lupus tend to have periods of flaring, where disease activity increases significantly, and then it might calm down for a while. It means living in a constant state of uncertainty, and people will often share that they can’t plan ahead because of the unpredictability. It’s very frustrating.
Caitlan Rossi: What are the challenges in diagnosing lupus?
Dr. Susan Manzi: Lupus is the great mimicker — it can look like anything. So it's a strange situation where it's both under-diagnosed and over-diagnosed. Under the umbrella of lupus, we will see one person come in with fatigue, rash, hair loss and joint pain; the next can walk in the door with chest pain and a premature heart attack; another will be a 30-year-old with a stroke; another has kidney disease. It could always be lupus. We don't have one blood test that says you have the disease. Lacking a test that says yes or no, adding in all the different ways the disease can present, and all the different specialists that may see these patients, it can be very hard to get a handle on lupus.
Caitlan Rossi: How can studying lupus teach us about other autoimmune diseases?
Dr. Susan Manzi: Lupus is what they call the prototypical autoimmune disease. Inflammatory bowel disease affects the gut, autoimmune thyroid affects the thyroid gland, multiple sclerosis affects the brain. But lupus is indiscriminate. It’s an important disease to study because it can affect the brain, the heart, the kidney, the lungs, the skin, the joints.
Genetically, autoimmune diseases share similar backgrounds. Most have a genetic predisposition, so you inherit genes that may or may not put you at risk for developing one of these conditions. Think about identical twins with the exact same genes. If one twin has lupus, the chance of the other twin getting lupus is the flip of a coin. If we can solve for the genes that predispose someone to lupus, we’re going to find many commonalities with the other autoimmune diseases.
Kendyl Ferrara: What are the treatment options for someone living with lupus?
Dr. Susan Manzi: It really depends on the person. Lupus is a spectrum disease, and it’s been said that lupus patients are like snowflakes: no two are alike. For people whose symptoms are mild, primarily joint pain and skin rashes, treatment could include non-steroidal anti-inflammatories (NSAIDs) such as Ibuprofen, Naproxen and topical creams. Hydroxychloroquine, which is an anti-malaria medication, is often prescribed for patients with mild lupus activity, as it can bring down inflammation in the body.
Then we get into more potent immunosuppressives. With lupus, for unknown reasons, the immune system starts targeting itself as if it were an invader. To treat this, we need to quiet the immune system and alert it to stop. Sometimes we use steroids to calm the immune system, such as prednisone. Other options include certain chemotherapy drugs and biologic medications.
Another important point is that some people with lupus become very sick. For example, people with lupus may suffer strokes and need to be on blood thinners, or develop heart disease. Some people with lupus develop kidney disease and require dialysis.
Caitlan Rossi: Are there any parallels or lessons about autoimmunity between COVID-19 and lupus?
Dr. Susan Manzi: Patients with severe COVID were, in a way, experiencing problems related to autoimmunity. It wasn’t necessarily the virus itself that made people unable to breathe or gave them blood clots, it was the viral infection triggering a major immune response that mistakenly targeted “self.” So we were using the same drugs to quiet the immune system down and prevent that ongoing attack.
It seems counterintuitive, because you would think the immune system should stay on high alert to keep attacking that virus. But the virus may come and go, and meanwhile the immune system has taken on a life of its own and has to be shut down to stop it from attacking other parts of the body. It’s fascinating because you realize how important the immune system is in any disease.
Kendyl Ferrara: The AHN Autoimmunity Institute was created to improve care and treatment for people living with autoimmune diseases. How is the institute’s approach helpful for people living with lupus?
Dr. Susan Manzi: With lupus in particular, any or all organ systems can be impacted. Before the Autoimmunity Institute, patients would have to see multiple specialists in different locations. The Autoimmunity Institute brings all those specialists under one roof. Whoever you need to see — gastroenterologist, cardiologist, behavioral health specialist, pharmacist — we’re pulling that team together and they will have expertise in autoimmune diseases. We also go beyond just the medical treatment to provide support in areas like anxiety, depression, medication affordability, diet and nutrition.
It is highly unique to have all specialists in one place and be able to provide patients with everything they need to navigate this condition. This also leads to better communication between clinicians — we can walk right down the hallway to consult with the appropriate colleague. Overall, the entire care experience is much less fragmented than it normally is for people with lupus.
The Autoimmunity Institute takes this model of integrated care to address not only lupus but more than 100 autoimmune diseases impacting people from across the country. We have seen patients from 34 states seeking an opinion about diagnosis and management of their autoimmune disease.
At the same time, we have a very strong research program, so patients are also assured of having access to the latest treatments and best approaches in diagnosing and managing the disease. That research also helps study autoimmunity across the board. We have all of these practitioners working together to figure out why people get these diseases. What are the genetic triggers? What are the risk factors that take a person from being at risk to developing the disease?
Dr. Manzi was instrumental in helping to establish the first-of-its-kind AHN Autoimmunity Institute.
Kendyl Ferrara: Dr. Manzi, you have been involved with much of the research driving new treatments for lupus, including biologic medications. Could you explain a bit about how the newer treatments work?
Dr. Susan Manzi: The immune system is quite complicated. Simplifying it a bit, there are two types of white blood cells, B-cells and T-cells, that typically communicate with one another when an invader, like bacteria, enters the body. So, these cells “see” the invader, communicate, and mount a response in the form of antibodies. With lupus, the immune system sees the body itself as the invader, and there is miscommunication between B-cells and T-cells. One way to understand the biologic treatments is that they halt the communication between B-cells and T-cells that signal the system to attack, and thus reduce disease activity.
Kendyl Ferrara: In 2021, Saphnelo was approved by the Food and Drug Administration (FDA) as a treatment option for lupus. Can you talk a little about that?
Dr. Susan Manzi: Saphnelo is an agent that targets type 1 interferon receptors on immune blood cells. Type 1 interferons cause inflammation in the body and are often increased in people with lupus. If we can block the binding of interferon with its receptor, we can reduce inflammation and organ damage due to lupus.
Saphnelo is given once a month, via IV infusion. It’s a promising treatment option for many people, but it hasn’t been evaluatp>ed or recommended for individuals with severe active lupus kidney disease or central nervous system lupus.
Kendyl Ferrara: Are there other new treatments that you hope to see approved soon?
Dr. Susan Manzi: So, in 2011, a drug called Belimumab, which targets B-cells, was the first drug approved by the FDA for lupus treatment specifically in over 60 years. Since then, we just had Saphnelo approved in 2021 by the FDA. There are large gaps in time between new drug treatment advancements. However, with the research being conducted in recent years, there is more of a pipeline of potential new treatments specific to lupus, and as they prove their effectiveness in trials, I am hopeful that they will be approved in a shorter period of time.
Kendyl Ferrara: Could you talk a little about the focus of your research, and also your involvement with the Lupus Foundation, which helps support research and also provides resources for individuals and families?
Dr. Susan Manzi: My research career has been focused on investigating the reason why young women with lupus develop premature heart disease, and on developing new blood tests to diagnose lupus and autoimmune diseases.
I serve as the Lupus Foundation’s medical director, and have been on its medical scientific advisory committee. I also served as chair of the board of directors. The foundation’s website, Lupus.org, is the source of truth for people seeking information regarding lupus and a great resource for finding support groups. There is information all over the Internet about lupus, but getting accurate information is critical, and that’s what can be found at Lupus.org.
About 9 out of every 10 lupus cases are women, and rates are also higher among people of color.
Kendyl Ferrara: What motivated you to become so heavily involved in doing research?
Dr. Susan Manzi: Physicians impact patients one at a time, but with research you can make discoveries that can reach thousands. One big challenge with lupus is that most people go years without getting an accurate diagnosis. By developing new blood tests that better diagnose lupus, we can help people worldwide, and that wouldn’t happen without a commitment to research.
Kendyl Ferrara: In a previous article, you shared the story of a young woman who passed from a lupus-related cardiac event as part of what drives your work. What other factors shaped your career?
Dr. Susan Manzi: Reflecting back on what led me down this path to becoming a rheumatologist, I found the immune system so fascinating and complex. If I ask you to point to your brain, or your heart or kidney, you would know where to point. But can you point to your immune system? Probably not, because it is everywhere — your blood cells, your lymph nodes. The immune system is the most intricate system, and it is critical to keeping you well and healthy. If it gets weakened, you end up sick. But you also don’t want it to become too overactive, because then you develop one or more of the roughly 100 different autoimmune diseases.
What fascinated me about lupus specifically is that patients are so young and they can be so sick. There is a pediatric form of lupus — children as young as 5 or 6 years of age. Many of the patients that I see are women in their 20s and 30s. It didn’t seem right that this disease could be so damaging for people so young. Dedicating my career to improving the lives of these patients has been rewarding. I’ve loved every minute of it — I love helping our patients and also being part of the emerging science behind the disease.
Dr. Manzi is currently Professor of Medicine and Chair of the Medicine Institute at Allegheny Health Network, Pittsburgh, PA. Dr. Manzi received her MD from the University of Pittsburgh School of Medicine. Read more
She completed her medical Internship and Residency at Duke University Medical Center, after which she completed her Fellowship in Rheumatology at UPMC, and received her Masters of Public Health (MPH) from the University of Pittsburgh Graduate School of Public Health.
Dr. Manzi is recognized internationally as a pioneer in the investigation of premature cardiovascular disease in systemic lupus erythematosus and in the discovery of biomarkers for lupus diagnosis, monitoring and stratification. She has published over 250 scientific reports and book chapters and is inventor of the cell-bound complement activation products (CB- CAPs) technology platform for which she holds more than 20 patents. Her research program has received multi-million dollar support from many organizations including the NIH, the Department of Defense, the Lupus Foundation of America and the Arthritis Foundation.
Dr. Manzi has served on Advisory Boards for the Food and Drug Administration and more than 20 pharmaceutical and biotech companies and has chaired or served on numerous NIH study sections and data safety monitoring boards. She has served as Chair of the Board of Directors of the Lupus Foundation of America and currently serves as its Medical Director. Dr. Manzi has been recognized by the NIH for her outstanding mentorship of medical students, residents, graduate students and faculty.
Watch Dr. Manzi discussing some of the latest research on lupus:
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