For her first 40 years, physician Madeline Brown, M.D., enjoyed an active lifestyle. When she wasn’t seeing patients or teaching medical residents, she and her physician husband loved hiking and skiing near their Colorado home, and traveling the globe.

But that all began to change for her in 2018. “I started developing bad skin rashes and extreme photosensitivity to sun and experiencing joint pain and weakness in my muscles to the point that I couldn’t hold positions in yoga,” she recalls. After visiting her local rheumatologist, she was diagnosed with dermatomyositis, which is marked by muscle weakness and a skin rash, and Sjögren's syndrome.

By early 2020, she started struggling with new symptoms and couldn’t get off the sofa. Bouts of brain fog made it difficult for her to focus. Her joints ached horribly and episodes of searing nerve pain became the norm. She felt so dizzy that it was difficult to stand up.

“I’m a doctor, so I knew there was something wrong with me. I went from being completely healthy to basically being bedridden,” Brown says. “But when I went to different doctors, I had trouble getting them to take my symptoms seriously.”

Eventually, in June 2022, Brown landed at Johns Hopkins and found a rheumatologist who could provide some answers: Brit Adler, M.D. After examining Brown and running a series of tests including a “tilt table test,” which monitors the heart and nervous system’s response to changes in position, Adler told her patient, “I think a lot of the weakness and brain fog you are experiencing is coming from something called POTS, or postural orthostatic tachycardia syndrome.” Adler was about to join the clinical team in the POTS Program at Johns Hopkins. Brown, who by then lived in Pennsylvania, jumped at the opportunity to be treated by Adler and her team.

“For me, the stars aligned perfectly,” says Brown. “Dr. Adler is so smart and so easy to talk to, and the fact that she was transitioning to the POTS clinic — that was exactly what I needed.”

Largely Ignored Until Now

Currently, there are only a few POTS programs at hospitals around the country. Among them, the Johns Hopkins POTS Program is unique in including a rheumatologist on the multidisciplinary clinical team, which is housed within the Department of Physical Medicine and Rehabilitation. Given patients’ varied needs, the program also offers access to experts in cardiology, hyperhidrosis (excessive sweating), neurology, adolescent medicine and physical therapy.

Adler, who completed her rheumatology fellowship in the Johns Hopkins Division of Rheumatology and joined the faculty in 2018, first saw patients in the Myositis Center and focused her basic research on scleroderma. It was while completing a research project on autonomic dysfunction in scleroderma that she was introduced to POTS and its symptoms, and the profound impact POTS has on patients’ quality of life.

“I started looking for these symptoms when evaluating patients in my general rheumatology clinic, and I discovered that POTS is incredibly common and often overlooked,” she says. “I saw an opportunity to make a meaningful impact by focusing my clinical care and research pursuits on POTS. I hope to utilize my background in rheumatology to identify different subgroups of patients with POTS whose mechanisms of disease are immune-mediated and may respond to immune treatments.”

The syndrome most frequently impacts women between the ages of 15 to 50 years. Many come in with symptoms including fast heart rate, lightheadedness and fainting, brain fog, and muscle pain and weakness.

“While POTS has been around for decades, it’s largely been ignored by our medical system. Historically, the response has been to dismiss these symptoms as being due to women’s ‘anxiety,’ and to them being ‘overwhelmed.’” Adler says. “But many of these patients are very sick. They are young, and the vast majority have had to cut back on school or work, or even take a medical leave because of their symptoms.”

Adler’s role as a rheumatologist in the POTS clinic is critical: She is finding that many patients diagnosed with POTS have overlapping autoimmune disorders, which can be debilitating and further complicate treatment. Some patients come in with Sjögren's syndrome or dermatomyositis. Other patients have scleroderma, lupus, chronic Lyme disease or celiac disease.

Says Adler, “I am also seeing a lot of overlap with Ehlers-Danlos syndrome (EDS),” an inherited group of disorders that affect connective tissues in the body, causing hypermobility and potentially life-threatening complications. “We still don’t understand why EDS puts patients at risk of developing POTS,” she says. “It’s a big area of research.”

But what’s really driven an “explosion” in POTS cases, Adler says, has been the COVID-19 pandemic. Before COVID-19, an estimated 500,000 to 3 million patients in the United States were believed to suffer from POTS. Since the pandemic, that number has risen dramatically.

“We’ve seen a large increase in patients who develop POTS after COVID-19,” she says. “There just aren’t enough doctors to evaluate and treat them. It’s a huge public health problem.”

A Very Heterogenous Syndrome

Patients with POTS can struggle for months or even years, seeing specialist after specialist to no avail, Adler says.

When new patients do find their way to Adler at the Johns Hopkins POTS Program, she usually starts by assessing them on the tilt table. They lie flat as the table is lifted from a horizontal position to almost upright, while their heart rate and blood pressure are monitored. Many (though not all) patients with POTS will experience an increase in heart rate when upright, and/or feel lightheaded or faint. Some will also experience weakness, fatigue, sweating or nausea.

The problem in some cases appears to lie in the sympathetic vasomotor system. When a healthy patient stands up, the blood pools in the legs due to gravity; the blood vessels are supposed to squeeze and pump the blood up to the brain where it needs to go. “But in some cases of POTS, that fails to happen. The blood vessels fail to constrict and patients get blood pooling in their legs,” Adler explains.

Treatment for POTS often begins with making lifestyle changes, Adler explains. These include increasing fluid and salt intake to expand blood volume and improve blood flow to prevent dizziness and fatigue; the use of compression stockings; and physical therapy, which is aimed at building muscle strength and improving conditioning for better blood circulation.

But lifestyle changes alone are often not sufficient. “A number of my patients need to take medications to improve their circulation or lower their fast heart rate,” she says. “Our goal is to give people their function back — and we are able to do that in many cases.” While some of her patients do recover fully, she says it’s more common for the disease to wax and wane, causing flares over time, and many patients must see multiple specialists to manage concurring conditions.

Finding the right medication plan can be a trial-and-error affair, Adler says, undoubtedly due to the fact “that POTS is a very heterogenous syndrome.” She’s seen some perfectly healthy patients who have developed POTS after a head injury, and others in the months after having a baby. “The causes could be infectious — such as COVID or chronic Lyme — or POTS may have an origin in autoimmune dysfunction, such as lupus or Sjögren's syndrome. And then there are potential nonimmune causes, like concussions or EDS.”

“There’s probably dozens of different causes of POTS,” says Adler, “and we don’t have a biopsy or single diagnostic test to guide us.”

An Emerging Field

In her research, Adler is pushing to gain a better understanding of the immunologic basis of POTS in distinct subgroups of patients.

Given the heterogenous causes of the syndrome, “there is a lot of work to be done to identify subsets of patients who behave similarly or have a similar underlying trigger,” Adler says, which will ultimately enable doctors to fine-tune treatments based on an individual’s disease course and related illnesses. A person who develops POTS after COVID-19, for example, will probably require a different treatment plan than someone like Brown, whose POTS arose in the wake of her autoimmune disorders. “We suspect that distinct clinical and laboratory biomarkers may associate with different POTS subgroups, and this is an active area of investigation by our group,” Adler says.

She is working closely with infectious disease specialist John Aucott, M.D., director of the Johns Hopkins Lyme Disease Research Center, to examine how POTS develops after Lyme disease, in addition to after COVID-19.

One key to finding answers that will benefit all patients with POTS, Adler says, lies in building a clinical database and biobank of patient samples (blood, urine and saliva) that will enable clinical researchers like her to parse varied causes and patterns of progression — work that she has already begun at Johns Hopkins — and to launch clinical trials to better understand the effectiveness of various treatments for different subgroups of patients.

“Despite how common POTS is, there have been few longitudinal studies that look at long-term outcomes,” Adler says. “We are at the forefront of this emerging field, which has become a hot area of study since the pandemic. It is a very exciting time for research,” she says. “For too long, doctors dismissed patients with POTS. It’s very clear at this point that POTS is something very real and I am hopeful that we will start to unravel this complex disease.”

Related Reading

Dysautonomia following Lyme disease: a key component of post-treatment Lyme disease syndrome? Front in Neurol, 2024, PMID: 38390594.

Color changes in the feet: a sign of autonomic symptoms in systemic sclerosis. Rheumatology (Oxford), 2024, PMID: 39302703.

Symptoms of autonomic dysfunction in systemic sclerosis assessed by the COMPASS-31 questionnaire. J Rheumatol, 2018, PMID 29907667.