Susan Manzi | Professor of Medicine and Chair, Medicine Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA; Medical Director, Lupus Foundation of America
Citation: AMJ Rheumatol. 2025; https://doi.org/10.33590/rheumatolamj/EDDZ4435
Often termed “the great mimicker,” lupus presents as many things, from fatigue and rashes to severe organ impairment. What strategies can clinicians employ to enhance early and accurate diagnosis?
I always say that you have to think of lupus to diagnose it. There are a few facts that may help. Lupus tends to impact young women (aged 15–45 years), and 90% of those living with lupus are women, though keep in mind that it can impact men, older individuals, and children. It is four times more common in people of color (Black, Hispanic, and Native American populations). Common features include profound fatigue, rashes (often made worse with sun exposure), hair loss, joint pain (often with swelling and stiffness in the morning), chest pain due to fluid that develops around the heart and lungs (pericarditis and pleuritis), seizures and premature strokes, and heart attacks (especially in young people with no traditional risk factors). They also include kidney disease, causing potential kidney failure requiring dialysis or kidney transplant. Many patients may also experience changes in their blood counts, low white blood cells, red blood cells, and platelets. Although some patients with lupus can have mild symptoms, many have life-threatening conditions. Because lupus can present in so many different ways, the diagnosis can be challenging.
Your work on cell-bound complement activation products (CB-CAP) has been trailblazing in this field. How do you envision these biomarkers transforming clinical practice in lupus diagnosis and monitoring?
One of the major issues with lupus is accurate and timely diagnosis. The sooner we can identify and treat the disease, the less likely it is that there will be serious complications. Since lupus can go undiagnosed for years, having improved diagnostic tests to increase the likelihood of identifying those with lupus earlier is essential. Our research program has focused on developing new diagnostic tests for lupus and other autoimmune diseases. We discovered that people with lupus have higher levels of CB-CAPs (proteins that bind to blood cells in the circulation), and that they can improve the diagnosis of lupus by nearly 33%. These tests have been licensed and commercialized by Exagen Inc., a company based in Vista, California, USA, and are now available to physicians across the country. The tests may also help physicians monitor the disease once the diagnosis is made. Since lupus can flare at times with increased periods of inflammation and activity, close monitoring to prevent or treat the flares becomes important. Our research team continues to develop new and improved blood tests to diagnose and monitor lupus.
What steps can healthcare providers take to improve awareness and care for male patients with lupus, given males may experience more severe manifestations?
Recognizing that men can get lupus is the first step. Even though most are women, when men do develop lupus, the disease tends to be more severe, with more central nervous system disease and kidney disease. We also see that men of color are more commonly impacted, but all men are at risk, particularly young men.
The Addressing Lupus Pillars for Health Advancement (ALPHA) project identified key barriers in lupus care. How can clinicians integrate the findings from this initiative to enhance patient outcomes?
By educating providers (those that deliver healthcare), including doctors, advanced practice providers, and nurses, as well as patients seeking healthcare regarding lupus. You have to think of lupus to diagnose it, and having information about common features allows both the providers and the patients to ask the question: “Could this be lupus?” I am a big believer in empowering the public with enough information to be their own advocates in their own healthcare. Ask questions and be informed.
With the approval of therapies like anifrolumab and belimumab, what are the most significant takeaways from recent clinical trials? How can clinicians integrate these into their practice, and how will these directly impact patient outcomes?
This is one of the most exciting times for those living with lupus. We have had more FDA-approved treatments for lupus in the past decade than we had for 60 years before that, and there are more in the pipeline. These new agents are also designed specifically for lupus and targeted to the immune mechanisms that are most relevant to lupus.
As Medical Director for the Lupus Foundation of America (LFA), one of your key roles has been in policy advocacy. What legislative initiatives should healthcare professionals be aware of to better support patients with lupus?
I encourage everyone to lean in and get involved with advocacy. Now, more than ever, we need the voices of those impacted by lupus and those of us that care for people living with lupus. One of our top priorities is supporting lupus research at the federal level. The LFA had successfully advocated for research funding earmarked for lupus through the Department of Defense (DoD) years ago, which amounted to 10 million USD a year. This was a major breakthrough. With more and more women joining the military, the number struggling with lupus has risen.
A number of high-impact research initiatives were supported through this grant mechanism until this year, when the program was put on hold. This and other funding cuts threaten to slow down the pipeline of new treatments or steps toward a cure for lupus.
We also need to advocate for access to treatment. We may have new biologic therapies that are highly effective, but many people cannot access or afford them. We are here to change that.
