The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 32

39. How are mast cell disease, Ehlers Danlos Syndrome and POTS connected? (Continued)

I’m answering this question in two parts because there is a lot of information to relay and it’s important that it is done clearly. This is the second part.

Mast cells are found throughout the body. There is no record of a person living without mast cells. They perform many essential functions. This is the reason why killing off all of a person’s mast cells is not a viable treatment for mast cell disease. While mast cells cause so many symptoms and problems for patients with mast cell disease, life is unsustainable without mast cells.

Let’s specifically consider just a few of the mast cell’s essential functions here and how they relate to POTS and EDS.

Mast cells help the body to regulate blood pressure and heart rate. Many of the mast cell’s chemicals do this so it happens in many different ways all stemming from mast cells. This means that when mast cells are not behaving appropriately, there are many ways in which this dysfunction can lead to not regulating blood pressure and heart rate correctly.

  • Histamine can affect blood pressure and heart rate differently depending upon how it acts on the body. If it uses the H1 receptors, it can cause low blood pressure. If it uses the H2 receptors, it elevates blood pressure. If it uses the H3 receptor, it can cause low blood pressure. When it does this at the H3 receptor, it’s because it tells the body not to release norepinephrine. Not releasing as much norepinephrine lowers heart rate and making the heart beat more weakly.
  • Prostaglandin D2 lowers blood pressure and causes fast heart beat. However, the molecule made by breaking down PGD2, called 9a,11b-PGF2 increases blood pressure.
  • Vasoactive intestinal peptide lowers blood pressure.
  • Heparin, chymase and tryptase can decrease blood pressure. They do this by helping to make a molecule called bradykinin. When this happens, a lot of fluid falls out of the blood stream and gets stuck in the tissues, causing swelling.
  • Thromboxane A2 increases blood pressure.
  • Many mast cell molecules affect the amount of angiotensin II. This molecule strongly drives the body toward high blood pressure. Some mast cell molecules that affect blood pressure this way include chymase and renin.

Another very essential function of mast cells is to make connective tissue. Mast cells help the body to shape itself correctly and to make tissue to heal wounds. When mast cells are not behaving appropriately, their dysfunction can interfere with making connective tissue and wound healing. It can cause wounds to heal very slowly or for there to be too much scar tissue. It can also cause the connective tissue to be too weak or too strong.

The interaction between POTS and mast cell disease

In POTS, the body is already predisposed toward not regulating blood pressure and heart rate correctly. When a person with POTS stands up, their body quickly causes the heart to beat very fast. When your body does this, it takes steps that cause mast cells to become activated. In turn, the mast cells release chemicals to try and regulate the heart rate. However, if you have mast cell disease, the mast cell may release the wrong chemicals, or too many chemicals, failing to regulate the heart rate. This in turn results in a situation where the body becomes very stressed. Stress activates mast cells, which results in more release of chemicals. Patients can very easily become trapped in a cycle where POTS and mast cell disease irritate each other.

POTS can be exacerbated by the use of medications that affect blood vessels. Medications that are vasodilators (that make the blood vessels bigger) are taken by many people, including mast cell patients. In some people, using medications that blocks the action of histamine or prostaglandins can help to improve symptoms of both POTS and mast cell disease. Conversely, some of the medications used to manage POTS, like beta blockers, can trigger mast cell reactions and raise the risk of anaphylaxis. However, some POTS treatments can also help alleviate mast cell symptoms, specifically the use of IV fluids.

A paper published in 2005 found that hyperadrenergic POTS was sometimes found in patients with mast cell activation disorders.

The interaction between EDS and POTS

POTS is a form of dysautonomia. Dysautonomia means dysfunction of the autonomic nervous system. This is the part of your nervous system that helps to control automatic functions like heart rate, blood pressure and digestion.

In EDS patients, the body does not make collagen correctly. Collagen is the most common connective tissue protein in the body. This can cause vascular laxity. Blood vessels change size depending upon how much blood they need to move through them. If they get larger, it is called vasodilation. When they get smaller, it is called vasoconstriction. When a person has vascular laxity, their vessels can get larger than they should and they can stay that way longer.

POTS is the most common form of orthostatic intolerance in HEDS. Orthostatic intolerance is when a patient has symptoms specifically as the result of standing up. All EDS patients have more autonomic symptoms than healthy people. Among patients with EDS, autonomic symptoms are more common and more severe in HEDS. 94% of HEDS patients have orthostatic symptoms, including lightheadedness, dizziness, palpitations, nausea, blurred vision, and anxiety. Dysautonomia is much worse in HEDS compared to CEDS and VEDS patients.

Patients with HEDS were found overall to have overactive sympathetic nervous systems. However, when their body needed to activate in response to regulate heart rate and blood pressure in response to changing position, their responses were not strong enough.

In EDS patients, the connective tissue does not support blood vessels enough. This makes the harder for the blood vessels to get the blood back to the right places when you stand up, exacerbating POTS.

The interaction between EDS and mast cell disease

Mast cells are involved in making and repairing connective tissue, which involves collagen. For this reason, there are many mast cells living in connective tissues. Mast cells are stimulated when the body is making or trying to make collagen. Because EDS causes the body to make collagen incorrectly, mast cells can become activated to try and make collagen and other connective tissue correctly. When mast cells in one place are activated a lot over a long time, they can activate other mast cells elsewhere, resulting in systemic symptoms.

The interactions among mast cell disease, POTS and EDS

It is undeniable that there is an association among mast cell disease, EDS and POTS. However, there is not much data published on this topic. There was a poster presented in 2015 that found some combination of EDS, POTS and MCAS in a group of 15 patients. This is a very small population and we need larger studies to understand incidence. There is ongoing work to tie this group of conditions to specific genetic markers. However, this also requires further investigation and more patients. In the absence of hard data, we are forced to use some early data and understanding of similar conditions to try and figure out exactly what happens. As more data comes out, this understanding may change.

This is very much a chicken and egg situation where it’s not clear exactly what begets what. EDS is a genetic disorder and considered primary. However, that does not necessarily mean POTS or mast cell disease is secondary in this scenario.

Regardless of which is the initiating condition, the relationship seems to be something like the following:

1. A patient has EDS. They make defective connective tissue. These defective tissues do not support the bodily organs and vessels properly.

2. A patient stands up. Blood quickly moves from the torso into the legs.

3. The blood vessels in the legs try become more narrow and more able to keep fluid in the bloodstream. However, in an EDS patient, the blood vessels are stretched out and not held in the right place because the connective tissue is too weak.

4. The blood vessels in the legs are not able to pump blood back to the heart quickly enough. The body interprets this as having low blood pressure.

5. The nervous system sends signals to increase heart rate to compensate for the “low” blood pressure.

6. The signals sent to increase heart rate activate mast cells.

7. Mast cells activate release mediators to try and regulate blood pressure and heart rate.

8. Mast cell mediators activate other mast cells, eventually affecting other parts of the body.

9. The molecules released by mast cells make blood vessels bigger and more leaky.

10. As fluid leaves the bloodstream and gets stuck in places where it can’t work (third spacing), blood pressure decreases and heart rate increases. This exacerbates POTS symptoms. The cycle repeats.

For more detailed reading, please visit these posts:

Cardiovascular manifestations of mast cell disease: Part 1 of 5

Cardiovascular manifestations of mast cell disease: Part 2 of 5

Cardiovascular manifestations of mast cell disease: Part 3 of 5

Cardiovascular manifestations of mast cell disease: Part 4 of 5

Cardiovascular manifestations of mast cell disease: Part 5 of 5

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part 1)

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part 2)

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part 3)

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part 4)

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part 5)

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 1

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 2

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 3

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 4

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 5

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 6

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 7

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Disease, Part 23

I answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

  1. Is mast cell activation the same as mast cell activation syndrome?
  • No.
  • This is the single most important clarification I make as an educator. It is crucial to understand that they aren’t the same thing, especially if you research mast cell activation syndrome online.
  • Mast cell activation is a normal and healthy process. Mast cell activation mostly means that they are ready to release chemicals in response to signals from inside the mast cell or from other cells. It is one of the major ways mast cells carry out their normal functions, like fighting infections, healing the body post trauma, and regulating the menstrual cycle.
  • Many things activate mast cells to tell mast cells to act in their normal functions. Bacteria, viruses, fungi, cancer cells, diarrhea, pain, surgery, physical or emotional stress, and many other things all activate mast cells normally. It is not surprising that these things activate mast cells because they should activate them.
  • Sometimes mast cells overreact to signals to activate, like in allergies and anaphylaxis.
  • The reason mast cell activation is a problem in mast cell disease is because mast cells respond way too strongly to activation signals. They release too many chemicals too often.
  • The other reason mast cell activation is also a problem in mast cell disease is because they become too easily activated.
  • Think of mast cells like houses. Like any house, they have doors. In healthy people, you need a lot of people knocking on the doors and windows at the same time to get the mast cell to open the doors and release chemicals. In mast cell patients, one person can knock a few times and all the doors open and release chemicals at once.

For more information, please visit this post:

The Provider Primer Series: Introduction to Mast Cells

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Disease, Part 22

I answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

  1. Does mast cell disease cause cognitive issues?
  • Yes.
  • The most common cognitive issue reported by mastocytosis patients is “brain fog”, a sort of difficulty in thinking and reacting normally.
  • Inability to focus, pay attention, find words, and keep things in short term memory are frequently reported by mast cell patients. Attentive deficit disorders are sometimes seen.
  • Aside from the effects of mast cell disease on your body, they also affect the lives of patients dramatically. 42% of mastocytosis patients in one study reported a high stress level. I would be willing to bet that across the entire population of mast cell patients, the number of people that feel a lot of stress is a lot higher than 42%. Many patients feel hopeless, guilty, or like a burden. While this is distinct from depression, a neurologic disorder, these feelings can make it hard for patients to focus or pay attention.
  • Mast cell disease can lower serotonin. Even where this is not the case, mast cells can greatly impact the way serotonin works in the body. Serotonin in a chemical that nerves and other cells use to talk to each other. It is also important in cognition. While this isn’t totally understood yet, it appears that increasing serotonin levels can improve memory and decrease impairment. It can also improve ability to learn things. Not enough serotonin was associated with memory and learning difficulties.
  • When mast cells are activated, your body thinks there is an emergency or an infection. It can activate a stress response. One of the things your body does during this response is release cortisol. Cortisol can further activate mast cells. It is also released by mast cells. Over time, more cortisol than normal can really fatigue the body. Long term stress response is associated with a lot of cognitive issues, including brain fog.
  • Mast cell disease is very disruptive to your sleep cycle. Personally, this is one of the hardest parts of the disease for me. Your body naturally starts releasing more histamine around 10pm, every night, for everyone. Mast cell patients often have worsened symptoms starting around then and continuing overnight.
  • Another mast cell mediator, prostaglandin D2 (PGD2), is the strongest known inducer of sleep in the body. Mast cell patients may have this in excess, making them even more tired.
  • Despite the common idea that histamine makes you drowsy, it actually keeps you awake. Many mast cell patients have insomnia because of the histamine release overnight. This translates to being exhausted during the day when histamine levels drop. Lack of sleep is a well documented cause of cognitive dysfunction.
  • Many mast cell patients have POTS or another form of dysautonomia. These conditions can prevent getting enough blood and oxygen to the brain.

For more information, please visit these posts:

Neuropsychiatric features of mast cell disease: Part 1 of 2

Neuropsychiatric features of mast cell disease: Part 2 of 2

MCAS: Neurologic and psychiatric symptoms

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 20

I answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

29. Why do I swell up when I have a reaction? Where does the fluid come from and where does it go?
• Your body feeds its cells by keeping blood circulating. The blood passes by cells. The cells pull nutrients, oxygen, and other things they want out of the blood. In return, the cells release their wastes into the bloodstream to carry them away to a place where they can be broken down.
• Mast cells make and release many chemicals. These chemicals are commonly called mediators because they mediate many reactions in the body that affect the body in many different ways.
• Mast cell mediators do many things. They can make blood vessels get looser or tighter to help control heart rate and blood pressure. Their ability to make blood vessels relax is the important point when considering swelling. When mast cells release certain mediators, the vessels relax and get a little wider.
• Vessels are made of a complicated network of cells and fibers. It’s like an afghan blanket: some parts of mostly solid and in other places, there are holes you can put your fingers through. When the vessels relax, those holes get larger so it’s easier for things to fall through the holes. In this case, what falls through the hole is fluid from the blood.
• Keep in mind that blood is a mixture of many things. For right now, let’s divide it into cells and everything else. Everything else is a liquid with some stuff dissolved in it.
• When the blood vessels relax, that liquid from the blood trickles out of the blood vessel and goes into the tissue. In some cases, if the blood vessels relax enough, cells actually fall out of the bloodstream and end up in tissue, too.
• The problem is that once you fall out of the bloodstream, you can’t just turn around and go right back in. That’s why swelling takes longer to subside than other symptoms, even with appropriate treatment.
• Everyone is familiar with the bloodstream. Less familiar is the lymphatic circulatory system. Lymphatic circulation is how your body moves things that fall out of the blood back to the bloodstream. This process is slower than processes that can release other symptoms and can sometimes take days.
• When you swell up, fluid falls out of your bloodstream and gets stuck in your tissues. The cells nearby will absorb some of the fluid and take up molecules they can use. However, if there is a lot of extra fluid there, the cells nearby cannot take up all of the fluid. Gradually, your lymphatic system sucks up that fluid and brings it back toward the heart so it can get back into the bloodstream.
• When you get hives (urticaria), it happens because fluid falls out of the bloodstream in a layer of tissue in the skin called the upper dermis.
• When you get angioedema, it happens because fluid falls out of the bloodstream in lower portions of tissue in the skin called the dermis, subcutaneous tissue, mucosa, and submucosa.
• The fact that the process for hives and angioedema is so similar and really distinguished only by which tissue layer they affect is the reason urticaria and angioedema so commonly occur together and are discussed together.

For more detailed reading, please visit the following posts:
Chronic urticaria and angioedema: Part 1
Chronic urticaria and angioedema: Part 2
Chronic urticaria and angioedema: Part 3
Chronic urticaria and angioedema: Part 4
Chronic urticaria and angioedema: Part 5
The Provider Primer Series: Management of mast cell mediator symptoms and release

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 18

I answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

27. Can mast cell patients travel? Can they fly?
• This is very individual and dependent upon your personal health situation, your ability to manage bad reactions on your own, where you live and where you want to travel. I have been fortunate enough to be able to travel widely through exhaustive preparation.
• You should always talk to your care team when you are thinking about travel. You must have a detailed understanding about how to recognize when you are headed for trouble, what you should do if you get into trouble, and when you should pursue emergency care.
Always carry rescue medications, your emergency protocol on provider letterhead, and a sheet listing your diagnoses, daily meds, rescue meds, and any special precautions. List over the counter medications as well.
• Make sure that all of your medications are legal in the country you are traveling to. Importantly, diphenhydramine (Benadryl) is illegal in some countries.
Get a fit to fly letter detailing what medications you need to bring onboard with you on letterhead from your doctor.
Call the airline directly to describe your needs. If you need to use medical equipment during the flight, tell them when you call and have the model number/ serial number ready.
• Also notify the airline if you need them to refrigerate medication for you.
• If standing is a trigger, or you have difficulty lifting luggage or carrying your bags with you, ask for a wheelchair to meet you at check-in and take you through the gate. It is my experience that when bringing a lot of medications through experience, it is easier to do this when you are in a wheelchair being escorted by airport personnel.
Identify safe foods at your destination. Many countries do not allow you to bring food in from another country. However, you can often bring solid food through the security to have on the plane.
• I premedicate heavily and many other mast cell patients who regularly fly also find that helpful. Speak with your providers about what protocol works best for you.
• Flying is unbelievably dehydrating. Hydrate well in the days before flying, the day of the flight, and while flying.
• Keep in mind that if the flight crew is uncomfortable with you flying, they can refuse to let you onboard. Emphasize that it is safe for you to to fly and that you have a fit to fly letter. If you are not able to manage a bad reaction alone, please do not fly alone.

For more detailed reading, please visit these posts:

How to travel with mast cell disease

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 16

I have answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

24. What is degranulation?
• Mast cells make chemicals inside them and often store them in pockets inside themselves. These pockets are called granules. When mast cells turn these pockets out so that the chemicals are dumped out of them into the body, that is called degranulation.
• There are several ways that mast cells release chemicals. These chemicals are commonly called mediators because they mediate many reactions in the body.
• Mast cells have to find certain building blocks from inside the body and whenever they find them, they use them to make mediators they need. Mast cells make some mediators whenever they have the opportunity and save them for later so they are there when they are needed. Often, the way mast cells save these mediators is by placing them inside granules. Mediators that are kept this way are called stored mediators.
• Mast cells have two options for getting those mediators out of their granules into the body. The first is to empty some of the granules entirely, just push everything out into the body at once. They can also release a little at a time. When mast cells are activated in response to an allergic or infectious process, overwhelmingly, they release the contents of a granule all at once.
Frequently, they empty many of the granules at the same time. This can cause an emergency response in your body and can impact your entire body. This is what happens during anaphylaxis but it happens during other processes too, like mast cell attacks, bad infections, or sudden trauma.
When mast cell patients say “I am degranulating”, it means they feel symptoms associated with mast cell mediator release. Histamine is stored in granules in large quantities so this is an offhand way of saying that they are feeling symptoms coming on.
• Mast cells have other ways of releasing mediators. They make some mediators only when they need to use them. These mediators are not stored but the building blocks they need are. A good example of this method is prostaglandin D2.
• Mast cells do not make prostaglandin D2 and stuff it inside granules. Instead, they keep the building blocks to make it inside of themselves. In this case, the building block they store is called arachidonic acid. When mast cells need to make prostaglandin D2, they use some of the arachidonic acid they have stored. But as soon as they use it to make prostaglandin D2, the mast cells secrete it right into the body. It is not stored in a granule.
• Mediators that are made with this kind of process are called “de novo” mediators. This means that the mediators are made “new” on demand when they are needed.

 

 

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 11

I have answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

19. How do other conditions affect mast cell disease?
Mast cell activity can affect literally every system in the body.
• Mast cells are found throughout the body and live in many tissues and organs in significant numbers.
• There are essentially three types of damaging mast cell activity:
Normal mast cells are getting bad signals from other cells and they do bad things. This is not mast cell disease because these mast cells are not broken. They are getting signals from other broken cells.
Abnormal mast cells do bad things and tell other nearby cells to do bad things. This is mast cell disease, specifically mast cell activation syndrome and sometimes monoclonal mast cell activation syndrome.
You make way too many mast cells, they are abnormal, they do bad things, and they tell other nearby cells to do bad things. This is mast cell disease, specifically all forms of mastocytosis (systemic, cutaneous, and mast cell leukemia), sometimes monoclonal mast cell activation syndrome and mast cell tumors (mastocytoma and mast cell sarcoma).
• Generally speaking, if you have mast cell disease, any other condition you have will irritate your mast cell disease. This can also work the other way around and mast cell disease can irritate your other conditions.
• Many conditions naturally trigger higher level mast cell activation.
• Any disease that causes your body to make a lot of cells very quickly is likely to trigger to mast cell activation. Cancers are mast cell activating. Non cancerous diseases where you make too many blood cells at once, like polycythemia vera or essential thrombocythemia, are are mast cell activating.
• Mast cells are usually found very close to tumors. Sometimes, they are found inside tumors. Mast cells are important for tumors to survive because they can make blood vessels to bring tumors the blood they need.
Diseases affecting the immune system are triggering to mast cells. In fact, many patients have mast cell activation syndrome caused by the immune disease irritating their mast cells so much. Many mast cell patients have autoimmune diseases like lupus or rheumatoid arthritis. Many patients also have deficiencies in their immune system. Because mast cells are immune cells, they are very responsive to signals from other immune cells. Mast cells think those cells need help from them to fight an infection or disease so they respond strongly to “help”.
Diseases that cause inflammation also trigger mast cells. This can happen whether the inflammation is local or not. Systemic inflammation is more irritating to mast cells since that kind of inflammation can find more mast cells throughout the body. Local inflammation can irritate mast cells nearby. It can also call mast cells from other parts of the body to that location.
• Mast cells are actively involved in fighting infections from viruses, bacteria, fungi, and parasites. This is the reason many mast cell patients find they are more reactive when they have even a minor illness, like a cold.
Any type of physical stress can activate mast cells. This can be something as simple as exercise or something more traumatic such as a car accident, a surgery, or childbirth. Even things that should be easy to recover from can activate mast cells, like a small cut, dehydration, or getting overheated. This also includes stress caused by another disease.
Emotional stress can activate mast cells, even if the big emotion is joy.
For more detailed reading, please visit this page:

Symptoms and effects of mast cell disease

 

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 6

I have answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

12. What do these blood and urine tests look for?

• There are a lot of tests ordered for mast cell disease. How they are interpreted can depend upon a lot of factors. Some of the tests are unreliable, a fact that will be addressed in detail later in this series. (And has been addressed in detail elsewhere on this blog). Please keep in mind when reading this post that I am being VERY general and assumed the test was performed correctly on a correctly stored sample.
• The most common test ordered for mast cell disease is serum tryptase. Tryptase is a molecule that mast cells release. While it has lots of functions in the body, and is especially important in healing wounds and tissue growth, the amount present in your body at a given moment should be low.
• Tryptase is special because mast cells release it in two ways. Firstly, they make and release a little bit steadily. This is not related to activation. Mast cells just normally release a little tryptase as they go about their work. So the idea is that if you have more mast cells than you should, and each of those mast cells releases a little tryptase all the time, that you will have a higher than normal serum tryptase.
• Patients with a clonal mast cell disease, in which they have too many broken mast cells, usually have elevated baseline tryptase. This means tryptase that is elevated at least two times when you are NOT having a big reaction or anaphylaxis.
• Mast cells also store lots of tryptase in their pockets. When the mast cell is activated and it empties out its pockets, lots of tryptase comes out at once. This is why tryptase can be higher after a reaction or anaphylaxis, because mast cells release a bunch at once.
• Patients with mast cell activation syndrome or cutaneous mastocytosis do not always have elevated tryptase even with a big reaction or anaphylaxis.
• Mast cells have huge amounts of histamine stored in their pockets inside their cells. Histamine has lots of functions inside the body and is required for normal body functions. In particular, it is important to our nervous system. Smaller amounts are released as a normal function of the body.
• A lot of histamine is released when mast cells are activated. The idea is that if your mast cells are more activated than they should be that your histamine level will be higher. However, the test recommended for us to consider the histamine level in mast cell patients is not for histamine. It is for n-methylhistamine. This is a molecule that is formed when the body breaks down histamine, which happens very quickly (within minutes of release). n-methylhistamine is more stable, which is why we look at it.
• The test for n-methylhistamine is most reliable when performed in a 24 hour urine sample. This is because the level in urine can fluctuate throughout the day.
• Mast cells make a lot of prostaglandin D2 (abbreviated PGD2). PGD2 is very important for cell communicating. It can carry a message from one cell to another, allowing cells to work together. Unlike histamine and tryptase, mast cells do not keep PGD2 stored in their pockets. They make it only when they need it and then release it.
• PGD2 is released in large amounts when mast cells are activated. However, because it is not stored in the pockets, it is not always elevated right away when you have a big activation event or anaphylaxis. Prostaglandin D2 is broken down quickly. While we do test directly for PGD2 for mast cell disease, we also test for 9a,11-PGF2, a molecule formed when PGD2 breaks down.
• The tests for PGD2 and 9a,11b-PGF2 are most reliable when performed in 24 hour urine samples. This is because the levels in urine can fluctuate throughout the day.
• Heparin is a blood thinning molecule that is stored in pockets inside mast cells. Mast cells are the only cells that release significant amounts of histamine. When the mast cell is activated and it releases histamine, the histamine comes out stuck to heparin. Heparin is broken down very quickly so it is hard to measure accurately.
• The test to assess heparin level actually looks for a molecule called anti-factor Xa that can interact with heparin. This test is performed in serum.
• Chromogranin A is released by mast cells. It is also released by a lot of other cells. The level of this molecule can be affected by many things, including common medications. It is sometimes tested for and considered a sign of mast cell disease if elevated when all other possible reasons can be excluded.
• Chromogranin A levels are most reliable in serum.

 

For more detailed reading, please visit these posts:

The Provider Primer Series: Management of mast cell mediator symptoms and release

The Provider Primer Series: Mast cell activation syndrome (MCAS)

The Provider Primer Series: Cutaneous Mastocytosis/ Mastocytosis in the Skin

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (ISM, SSM, ASM)

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (SM-AHD, MCL, MCS)

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 5

I have answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

10. How is mast cell disease diagnosed?
• There are several tests you need to definitively determine if you have mast cell disease and what kind you have.
The most well known test for mast cell disease is serum tryptase. This is a blood test. This is the test doctors are most likely to have heard of. Doctors may think that you can’t have mast cell disease if tryptase is normal. This is not true.
• If a patient has a tryptase over 20 ng/mL, the next step is usually a bone marrow biopsy. A tryptase over 20 ng/mL increases the likelihood that a patient has systemic mastocytosis. SM is most commonly confirmed by a bone marrow biopsy.
• You need a special stain in order to see mast cells in any biopsy. Stains that show mast cells include Giemsa Wright stain and toluidine blue. Your doctor should specify these stains.
• Several tests must be run on the bone marrow biopsy to look for clonal mast cell disease. Remember that in clonal diseases, the body makes too many broken cells.
• The shape of the mast cells in the biopsy is very important. If the mast cells are not shaped right, this can be a sign of mast cell disease.
• The number of mast cells grouped together in the body is also important. If 15 or more mast cells are all stuck together, this is called a cluster. When mast cells are clustered together like this, they can punch holes in the tissue and damage it a lot. This prevents the tissue from working right.
• Immunohistochemistry (IHC) is a way to find specific proteins that allow us to know what cells we are looking at in the biopsy. Often, these proteins are on the outside of the cells. Think of these are flags that a cell can wave. IHC can look for the specific flags a cell is waving so that we know for sure which cell is which. For mast cell disease, they want to look for CD117, CD25, and CD2. The CD117 flag is flown normally by all mast cells. CD25 and CD2 are special flags flown by mast cells if you have clonal mast cell disease.
• PCR is a way to look for genetic mutations. They need to look for a mutation in the mast cells in the bone marrow. The mutation is found at a specific place in the CKIT gene. This mutation is found in 80-90% of patients with systemic mastocytosis. It may also be found if patients have monoclonal mast cell activation syndrome.
• If a patient does not have a tryptase over 20 ng/mL, a bone marrow biopsy is often not ordered. There are other tests that can indicate mast cell disease.
• Urine collected over 24 hours can be tested for specific chemicals. In the case of mast cell disease, they are looking for chemicals that can be high if you have mast cell disease. These chemicals have very long, complicated names. I will explain in a later post exactly what they are and what they do. The most common ones are called n-methylhistamine, prostaglandin D2, 9a,11b-prostaglandin F2, and leukotriene E4. Anti-heparin Xa and chromogranin A are sometimes tested. They are much less reliable as indicators of mast cell disease than the others mentioned here.
• If a patient is suspected to have cutaneous mastocytosis, a skin biopsy is needed to confirm. As with bone marrow biopsies, your doctor should specify that they need to use toluidine blue or Giemsa Wright stain to be sure they see the mast cells.
• The skin biopsy should also receive the other tests I described above for bone marrow biopsy: the counting of mast cells and looking at the shape; looking for CD117, CD2, and CD25; and looking for the same mutation with PCR.
11. What kind of doctor diagnoses mast cell disease? Can any doctor order these tests?
Doctors from all different specialties may diagnose and manage mast cell disease. It depends upon the individual provider and where you are located. It could be a dermatologist, allergist, hematologist, pulmonologist, gastroenterologist, or another specialist.
• The serum tryptase is the easier to order and the most well known test. Many labs can run this test.
• The 24 hour urine tests are specialized. Some of them are run in only a few places and samples are usually shipped there. Most often, these samples are run at the Mayo Clinic. Many outpatient labs have no way to run those tests. You will need to speak with your doctor about how to get these tests. It is often easiest if they are run by a hospital lab but again, this depends upon the hospital.
• The PCR genetic test for this specific gene is run in more places than the urine tests but is still not very common. Again, it is often easiest if they are run by a hospital lab.
• A bone marrow biopsy is usually ordered by a hematologist or by another specialist that works commonly with hematologists. They are usually performed by hematology providers. Some testing can usually be performed in house (the counting of the cells and looking at the shape) while others may need to be sent out (the IHC testing).
• A skin biopsy is usually ordered by a dermatologist. Some testing can usually be performed in house (the counting of the cells and looking at the shape) while others may need to be sent out (the IHC testing).
For more detailed reading, please visit these posts:

The Provider Primer Series: Management of mast cell mediator symptoms and release

The Provider Primer Series: Mast cell activation syndrome (MCAS)

The Provider Primer Series: Cutaneous Mastocytosis/ Mastocytosis in the Skin

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (ISM, SSM, ASM)

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (SM-AHD, MCL, MCS)

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 3

I have answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

6. What symptoms does mast cell disease cause?

  • Mast cell disease can cause just about any symptom. Seriously.
  • Mast cell disease can cause symptoms in every system of the body. This is because mast cells are found in tissues throughout the body. They are intimately involved in lots of normal functions of the human body. When mast cells are not working correctly, lots of normal functions are not carried out correctly. When this happens, it causes symptoms. In short, mast cells can cause symptoms anywhere in the body because they were there already to help your body work right.
  • Skin symptoms can include flushing, rashes, hives (urticaria), itching, blistering, and swelling under the skin (angioedema).
  • GI symptoms include nausea, vomiting, diarrhea, constipation, problems with the GI not moving correctly in general (GI dysmotility), swelling of the GI tract, chest and abdominal pain, belching, bloating, discolored stool, excessive salivation, dry mouth, and trouble swallowing.
  • Cardiovascular symptoms include high or low blood pressure, fast or slow heart rate, irregular heartbeat, and poor circulation.
  • Neuropsychiatric symptoms include brain fog, difficulty concentrating, difficulty sleeping at night, excessive tiredness during the day, grogginess, anxiety, depression, tremors, numbness, weakness, burning and tingling (pins and needles), hearing loss, and auditory processing (difficulty understanding what was said to you).
  • Genitourinary symptoms include bladder pain, painful urination, painful intercourse/sexual activities, painful or irregular menstrual cycle (periods), and excessive or inadequate urination (too much or too little urine produced).
  • Respiratory symptoms include cough, excessive phlegm, wheezing, runny nose, sinus congestion, sneezing, and swelling of the airway.
  • General symptoms include fatigue, lack of stamina, difficulty exercising, itchy or watery eyes, and bruising easily.
  • There are some additional symptoms that I have observed in a large number of people that are not classically considered mast cell symptoms, but I now firmly believe them to be. One is fever. I think discoloration of the skin may be mast cell related for some people. Another is dystonia, involuntary muscle contraction, which can mimic appearance of a seizure. There are also different seizure-type episodes that may occur due to the nervous system being overactive. I am reluctant to call them pseudoseizures because that term specifically means they are caused as a result of mental illness. I have no evidence that these seizure-type episodes in mast cell patients occur due to mental illness. I personally refer to them as “mast cell derived seizures.” (For people who are wondering, I have been heavily researching this phenomenon and have some theories about why this happens. It’s not fleshed out enough yet to post but it’s on my think list.)
  • Having mast cell disease can make you more likely to have other conditions that cause symptoms.
  • I’m sure there are other symptoms I have forgotten to mention.

7. Why are skin and GI symptoms so common?

  • The skin has a lot of mast cells relative to other tissues. Your skin also comes into contact with lots of things in the environment. Think about the things your skin touches on a daily basis! It makes sense that it would get the exposure so skin symptoms can be common. Additionally, some of the chemicals mast cells release can cause fluid to become trapped in the skin. For these reasons, symptoms affecting the skin are pretty common.
  • The GI tract also has a lot of mast cells relative to other tissues. Your GI tract also comes in contact with lots of things in the environment. Let’s think about this for a minute. Your GI tract is essentially one long tube through your body. You put things from the environment in your GI tract at the top and they come back out the bottom of the tract. In a way, your GI tract is kind of like the outside of the inside of your body.
  • This is the analogy I learned in anatomy and physiology class to visualizing the GI tract as the outside of the inside of the body. Think of the body as a donut. (A low histamine, fully allergy friendly, requires no GI motility, wonderful donut.) Now think of the GI tract as the donut hole. You can put your finger through the hole in the middle of the donut. Only that center part of the donut will touch your finger. This is kind of like putting food throughout the GI tract. That food only touches a very small part of the body as it passes through.
  • Since what we put into our mouths (or other GI openings) is from the outside, your body has many mast cells in the GI tract to protect the body. Some of the chemicals mast cells release can cause fluid to become trapped in the layers of GI tissue. Some of the medications we take for mast cell disease can affect the GI tract. Some of them change how much acid we make in our stomachs. Some of them slow down the GI tract. A few of them speed it up or make the GI tract more fragile. For these reasons, symptoms affecting the GI tract are very common.

For more detailed reading, please visit these posts:

The Provider Primer Series: Management of mast cell mediator symptoms and release

The Provider Primer Series: Mast cell activation syndrome (MCAS)

The Provider Primer Series: Cutaneous Mastocytosis/ Mastocytosis in the Skin

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (ISM, SSM, ASM)

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (SM-AHD, MCL, MCS)