by Dr. Andrew White

There seems to be a growing awareness in the medical and patient community that some patients with postural orthostatic tachycardia syndrome (POTS) also have mast cell activation syndrome (MCAS).  It is not clear at this time what the relationship between POTS and MCAS is or how common this overlap is.  This is an extremely complicated intersection of two poorly understood illnesses, so there are more questions than answers right now.

I’m assuming if you are reading this blog, you understand what POTS is, but the concept of what mast cells do might be more foreign. Mast cells, for the last century, have been understood primarily in the context of allergic disease. They are the central cells in immediate allergic reactions to things like peanuts or bee stings. They secrete histamine and lead to the formation of hives and itchy rashes. More recently, researchers discovered that mast cells have an important role in wound healing, in the regulation of the immune system and in keeping us healthy. These roles are not as well understood.

Mast cells are present throughout most of our body. They can also be paired with neurons (nerve cells), including autonomic nerve fibers. Mast cells secrete up to 200 different chemicals in response to different stimuli. Doctors usually think of mast cell secretion as an “all or nothing” phenomenon. For example, the mast cell is releasing high quantities of histamine, prostaglandins, and leukotrienes at the time of an allergic reaction -OR- the mast cell is resting quietly, doing nothing. However, this is probably not the case as mast cells are constantly interacting with the environment – sensing – reacting. And in some people, this process might not work correctly.

When mast cells cause symptoms and problems in humans, they generally lead to episodes of abdominal pain, cramping, diarrhea, flushing, itching, wheezing, coughing, lightheadedness and potential problems with “brain fog” or other difficulties with memory. Many of these symptoms can be present in other illnesses that have nothing to do with mast cells. But there appears to be a subset of patients with POTS who are found to have a combination of these symptoms and laboratory evidence of problems with their mast cells.

So what tests can be done to determine if the mast cells are misbehaving? The first test that is usually done is a blood test for tryptase. Tryptase is a protein that comes from mast cells and it is usually elevated in two circumstances. The first is after a severe allergic reaction (anaphylaxis) and the second is if you have too many mast cells in your body (mastocytosis). If you have a significantly elevated tryptase, your doctor might recommend a bone marrow biopsy which is usually the definitive test for mastocytosis. Mastocytosis can be a serious illness, but it is different than the problem that most people with MCAS have. In mastocytosis, there are too many mast cells due to a genetic mutation that made one cell start to grow and divide without control. Patients with mastocytosis and MCAS are treated differently.

For most people with POTS, the tryptase level is normal and they don’t have mastocytosis. In these patients we need to look for other clues that their mast cells are not functioning normally. There are many different chemicals that come out of mast cells and can be measured. Substances like histamine, prostaglandins and leukotrienes are usually measured in a 24 hour urine sample. If the symptoms fit and the patient has evidence of making too much of a mast cell chemical, many physicians are then willing to diagnose MCAS and move on to treatment.

Although different diagnostic criteria are published, a commonly used strategy to diagnose patients is to use all three of the following:

1. Symptoms consistent with chronic/recurrent mast cell release
   a. Recurrent abdominal pain, diarrhea, flushing, itching, nasal congestion, coughing,  chest tightness, wheezing, lightheadedness (usually a combination of some of these   symptoms is present)
2. Laboratory evidence of mast cell mediator (N-methyl histamine, prostaglandin D2 or 11-beta- prostaglandin F2 alpha, leukotriene E4 and others)
3. Improvement in symptoms with the use of medications that block or treat elevations in these mediators

A word of caution about laboratory testing… many of the labs that can be ordered need to be sent on ice. If the labs are drawn at a facility that does not understand what is necessary, the samples may come back falsely normal. Testing is ideally going to be abnormal immediately after a flare up of symptoms. It would make sense to wait for testing on a “bad day.” There are several labs that can be ordered to help identify mast cell activation, but none of them are 100% accurateand all should be interpreted with care.

Treatment approaches are complex and individualized, and beyond the scope of a blog post. The take home point is if you have POTS or another form of dysautonomia and have some other symptoms that seem “allergic” like the ones that I mentioned above, you might want to ask your doctor about getting tested for MCAS. While any doctor can order the tests, an allergist or immunologist is the type of doctor that is most likely to be familiar with testing for MCAS.

Additional Resources
1. The presentation, diagnosis and treatment of mast cell activation syndrome.
2. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options.
3. Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders.

Dr. Andrew White is board certified in Internal Medicine and Allergy & Immunology. His practice at the Scripps Clinic in San Diego, California focuses on immune deficiencies and allergic disorders, including MCAS and mastocytosis. His research focus is on aspirin exacerbated respiratory disease.

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