For her first 40 years, physician Madeline Brown 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, an autoimmune disorder.

By early 2020, she started struggling with new symptoms and couldn’t get off the sofa. Bouts of brain fog made it nearly impossible 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 doctor who could provide some answers: rheumatologist Brit Adler. 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, which is housed within the Department of Physical Medicine and Rehabilitation, is unique in including a rheumatologist, an ophthalmologist, a pediatrician and rehabilitation therapists on the multidisciplinary clinical team. Given patients’ varied needs, the program also offers access to Johns Hopkins experts in cardiology, hyperhidrosis (excessive sweating), neurology, medical genetics and gastroenterology.

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

“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.”

Tae Chung, director and founder of the Johns Hopkins POTS Program, concurs. “It’s a very disabling condition,” he says, “and currently there is no known cure.” What can complicate diagnosis and treatment, Chung notes, is the heterogenous nature of the syndrome.

“We think about 40% of patients with POTS develop it after some type of acute infection, including chronic Lyme disease or long COVID,” says Chung, while the majority — about 50% — have POTS that is caused by an autoimmune disorder, including lupus, Sjögren’s syndrome or celiac disease. Then, there is a small portion of patients, estimated at about 10%, who are perfectly healthy but develop POTS after a traumatic brain injury or in the months after having a baby, notes Chung, an associate professor of neurology and of physical medicine and rehabilitation.

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.”

Given the varied causes and symptoms experienced by those with POTS, patients can struggle for months or even years, seeing specialist after specialist to no avail, Chung says. He notes that the average patient sees several different physicians before getting a POTS diagnosis.

When new patients do find their way to the Johns Hopkins POTS Program, Chung and the physician team often start by assessing them on the tilt table. Patients 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 involves expanding blood volume, “to return more blood to the heart and increase cardiac output,” Chung says. “This typically requires a combination of drug therapy (to improve circulation or lower fast heart rate), physical therapy and dietary modifications,” including increasing a patient’s fluid and salt intake to expand blood volume and improve blood flow.

While aerobic exercise is crucial on the treatment front, Chung says, patients with POTS have an extreme intolerance for exercise, so physical therapy efforts must start very slowly.

Fin Mears is one of four physical therapists in the Johns Hopkins POTS Program. “Early on, we’re not focused on getting patients faster or stronger; our exercise is just designed to increase their tolerance for everyday activities, such as taking a shower or washing the dishes,” he says. “When some patients start out, they can either comb their hair or take a shower. They can’t do both. They live with constant malaise and are completely exhausted.”

While healthy patients see their heart rates quickly return to normal after exertion, patients with “classic” POTS often experience continued elevated heart rate or their heart rate starts to decrease after exertion but then jumps and stays elevated, he explains. “Either way, they don’t get that heart rate recovery, and they feel awful,” says Mears.

 He works with patients so that they exert themselves just enough — even if for only a few minutes — to achieve normal heart rate recovery. “In general, since most patients with POTS have trouble with fluid distribution, we typically start exercises either lying down or sitting in a supported position,” he says. “We’re trying to take gravity out of the equation.

“When we get to where the patient can show me good heart rate recovery, we repeat the exercise over and over, with the goal being to retrain the cardiovascular system to turn itself on and turn itself off,” says Mears.

Patients whose POTS developed in the wake of COVID-19 or another infectious disease often present with different symptoms. For these patients, the slightest activity can leave them exhausted, “huffing and puffing, with fast, shallow breathing” — either alone or in combination with rapid heart rate, Mears says. With these patients, he focuses on techniques, such as blowing bubbles through a straw into a glass of water, to slow their breathing, encouraging deeper breaths and long, slow exhalations. 

Because the going is slow, physical therapy can stretch over many months, even years, before patients with POTS see noticeable improvement.

When they do, it’s incredibly gratifying, says Mears. “I had one patient who was completely homebound as a teen. She had to walk with the support of a cane, and she had no tolerance for activity. But she was remarkably compliant with her exercise program, and after a couple of years, she was able to return to school. She eventually went to nursing school and got a boyfriend. She was just ecstatic. She had gotten her life back.”

An Emerging Field

The overarching goal of the core POTS team at Johns Hopkins — which includes two nurse practitioners, four physical therapists, ophthalmologist Sezen Karakus and physical rehabilitation specialists Pegah Dehghan and Christina Kokorelis, in addition to Chung and Adler — is to give patients back as much function as possible.

While some patients with POTS do recover fully, Chung says it’s more common for the disease to wax and wane, causing flares over time. Many patients must see multiple specialists to manage concurring conditions, such as digestive problems or chronic headaches.

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

In their research at Johns Hopkins, Chung and Adler are pushing to gain a better understanding of the 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,” says Adler.

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

“Our program at Johns Hopkins has been at the vanguard of clinical trials for POTS,” says Chung, who has served as lead principal investigator for two recent trials that examined drugs aimed at improving outcomes for patients with post-COVID POTS, one of which was a multicenter phase 2 trial. “We have a couple more clinical trials scheduled to start in a few months,” he adds.

“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.”

Trying to Stay Positive

Brown, too, holds out hope for scientific breakthroughs that will help her live better with POTS. She is grateful for the care she is receiving from Adler through the Johns Hopkins POTS Program and praises nurse practitioner Beth Clark (see sidebar) for her empathy and compassion. After Brown’s initial POTS diagnosis, she says, “Beth really took the time to explain it all to me, while simultaneously really ‘seeing’ me as a human being going through something life-altering, unpredictable and, in truth, terrifying.”

Unremitting brain fog forced Brown to give up her medical practice in 2021 (“That was a tough transition; I really based a lot of my identity on being a doctor,” she says.) and today, she remains mostly homebound. But she has gained a few more active hours each day, thanks to a new medication Adler prescribed within the past year. “It’s given me enough new mental clarity and energy to get dinner made or tidy up the kitchen,” Brown says. And she and her husband have started traveling again, taking cruises where she can use a scooter to move around the ship.

“I am only 48, and I really try to stay positive,” Brown says. “I had a 20-year career in medicine, and I helped a lot of people. I am fortunate to have a wonderful husband, and we’ve gotten to live in many different places together. There are so many people out there who didn’t get those chances or who have things so much worse than I do.”