Awareness, misconceptions grow about POTS and mast cell activation syndrome

POTS and mast cell activation syndrome, or MCAS, have gained unprecedented attention in recent years, fueled by social media, long COVID research and online speculation that has sometimes outpaced the science. 

The increased visibility has helped many people recognize symptoms and seek medical care. However, researchers at the University of Mississippi Medical Center say it has also fueled misconceptions about two complex disorders that can be difficult to diagnose. 

"My biggest concern is the overdiagnosis of both conditions based on anecdotal reports, mostly on social media," said Dr. Gailen Marshall, the R. Faser Triplett Sr. MD Chair in Allergy and Immunology, director of the Division of Clinical Immunology and vice chair for research in the Department of Medicine at UMMC. "That can lead patients to demand testing that ultimately produces inaccurate diagnoses."

Marshall says symptoms such as dizziness, rapid heartbeat, brain fog, hives and chronic gastrointestinal problems can have many causes.

"It's important to remember that association does not prove causation," he said. "Proper diagnosis requires a careful medical history, physical examination and appropriate laboratory studies." 

Although POTS and MCAS are distinct conditions, they often produce similar symptoms. 

POTS, or postural orthostatic tachycardia syndrome, affects the autonomic nervous system, which regulates heart rate and blood pressure. When someone with POTS stands, the heart rate rises abnormally fast – often exceeding 120 beats per minute – causing dizziness, fatigue, nausea, shortness of breath and the "brain fog" many patients describe. 

Dr. Douglas A. Wolfe, professor of medicine in the Division of Cardiovascular Diseases and director of UMMC's Cardiac Autonomic Disorders Clinic, said the condition occurs because the body struggles to maintain normal blood flow after standing. 

"When a healthy person stands, blood vessels tighten to keep blood flowing to the brain," Wolfe said. "In POTS, that response is impaired, so blood pools in the lower body and the heart compensates by beating much faster." 

MCAS is an immune disorder in which mast cells become overly active, releasing chemicals that trigger allergic-type reactions throughout the body. 

Symptoms may include recurrent anaphylaxis, hives, skin flushing, nausea, vomiting, abdominal cramping, constipation and diarrhea. 

Ironically, mast cells normally play an important protective role. 

"Their primary function is defending against certain parasite infections, but they also contribute to wound healing, blood vessel formation and detoxifying some insect venoms," Marshall said. "Problems arise when those cells become overactive." 

Because both disorders mimic many other illnesses, patients often spend years searching for answers. 

Researchers are also trying to understand why the conditions sometimes occur together. 

Current studies suggest that 20 percent to 40 percent of patients with POTS also have MCAS, with similar percentages seen in patients diagnosed with MCAS. 

"There is considerable interest in determining whether there are commonalities that might help patients with either – or both – conditions," Marshall said. "But association does not prove causation."  

Diagnosing POTS involves documenting abnormal heart-rate changes while ruling out other conditions that can produce similar symptoms, Wolfe said. 

MCAS requires three key findings: symptoms consistent with mast cell activation, laboratory evidence of elevated mast cell activity and improvement with medications such as antihistamines. 

POTS is diagnosed most often in women, accounting for about 75 percent to 85 percent of cases, typically between ages 15 and 50. 

MCAS also affects women more frequently, with symptoms often beginning between ages 21 and 30. Although diagnosis historically took many years, Marshall says increasing physician awareness is helping patients receive answers much sooner.  

Researchers have also observed more cases of both disorders among patients with long COVID, suggesting inflammation may play an important role. 

At UMMC, Marshall and colleagues are studying whether POTS and MCAS contribute to long COVID symptoms and are investigating new therapies aimed at reducing inflammation. While neither condition has a cure, many patients experience significant improvement with individualized treatment. 

Wolfe said treatment for POTS often begins with increasing fluids and sodium intake, wearing compression garments and following a structured exercise program. Depending on the patient's needs, medications such as fludrocortisone, midodrine, beta blockers or ivabradine may be prescribed to improve blood flow, increase blood volume or control a rapid heart rate.  

For MCAS, treatment typically includes antihistamines, mast cell-stabilizing medications such as cromolyn, and in some cases corticosteroids, Marshall said. He also advises physicians to remain open to revisiting a diagnosis if treatment isn't working. "If treatment isn't working, it's important to ask why and consider whether another diagnosis or treatment approach may be more appropriate." 

As researchers continue to explore the relationship between POTS, MCAS and long COVID, both physicians hope greater scientific understanding – not social media speculation – will lead to earlier diagnoses and more effective, personalized treatments.

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