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June 2017

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 37

44. What is a myeloproliferative neoplasm? Is that what mast cell disease is?

First, let’s pull this term apart.

“Myelo” means marrow, like bone marrow. In this context, it refers to a specific group of blood cells that are made in the bone marrow. These cells are called myeloid or myelogenous cells. These cells all start as one kind of cell called a myeloid progenitor cell. Mast cells and eosinophils are myeloid cells. There are other myeloid cells, too.

“Proliferative” means making lots of cells quickly. In this case, it means making many cells too quickly. When too many cells are made too quickly, the cells are often not made correctly so they don’t work right.

“Myeloproliferative” means making too many myeloid cells very quickly, producing cells that often don’t work right.

“Neo” means new.

“Plasm” means the substance that makes up something living, like what makes up a cell or a tissue. “Plasm” is part of many words used in biology.

“Neoplasm” means the body growing new things, things that don’t belong there. For example, cancers are neoplasms. (Although not all neoplasms are cancers).

Myeloproliferative neoplasm means your body making too many myeloid cells that don’t work correctly.

Speaking generally, any condition where the body makes too many of these myeloid cells when they shouldn’t is a myeloproliferative neoplasm. This means all form of mastocytosis and mast cell tumors (mast cell sarcoma and mastocytoma) are myeloproliferative neoplasms.

However, when people ask if mast cell diseases are myeloproliferative neoplasms, they are usually asking about the WHO (World Health Organization) classification of mast cell disease, which is a little different.

The WHO puts out an exhaustive list of diseases for reference. They group similar diseases together under one category. This list is also revised periodically as new data becomes available or experts request it.

Under the 2008 WHO guidelines, mast cell diseases were classified as myeloproliferative neoplasms along with several other diseases. The other diseases also included in this category make too many myeloid cells too quickly, like essential thrombocythemia, in which the body makes too many platelets.

The mast cell diseases classified as myeloproliferative neoplasms were cutaneous mastocytosis: maculopapular cutaneous mastocytosis (MPCM), diffuse cutaneous mastocytosis (DCM), and solitary mastocytoma of the skin; systemic mastocytosis: indolent systemic mastocytosis (ISM), systemic mastocytosis with associated hematologic disease (SM-AHD), aggressive systemic mastocytosis (ASM), and mast cell leukemia (MCL); and mast cell sarcoma. Smoldering systemic mastocytosis (SSM) was mentioned as a provisional category rather than a formal category, meaning that the WHO did not agree that this diagnosis was different enough from ISM to warrant its own category. Neither monoclonal mast cell activation syndrome (MMAS) or mast cell activation syndrome (MCAS) were classified anywhere in the 2008 WHO Guidelines as they were not yet recognized by the WHO as diseases.

Last year, the WHO revised the classification of myeloproliferative neoplasms. It removed all forms of mast cell disease from the myeloproliferative neoplasm category and made a different category for mast cell diseases. This was done because the WHO recognized that mast cell diseases differed from the other myeloproliferative neoplasms in specific ways. They also recognized that mast cell activation syndrome has a ton in common with other mast cell diseases even though it’s not a neoplastic disease. (Mast cell activation syndrome is not from the body making too many mast cells).

So all mast cell diseases were put together. In the new category, the following mast cell diseases were included: cutaneous mastocytosis: maculopapular cutaneous mastocytosis (MPCM), diffuse cutaneous mastocytosis (DCM), and solitary mastocytoma of the skin; systemic mastocytosis: indolent systemic mastocytosis (ISM), systemic mastocytosis with associated clonal hematologic non-mast cell lineage disease (SM-AHNMD), aggressive systemic mastocytosis (ASM), and mast cell leukemia (MCL); mast cell sarcoma; monoclonal mast cell activation syndrome (MMAS); and mast cell activation syndrome (MCAS).

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 36

43. What is a rebound reaction?

Rebound is a term that gets used a lot in the mast cell community, often incorrectly. Rebound reactions occur when medication taken to suppress symptoms wears off. This phenomenon is easiest to see with the older H1 antihistamines like diphenhydramine (Benadryl). Benadryl is broken down pretty quickly by the body so it wears off in about 4-6 hours. In some situations, it can break down even faster.

When you take diphenhydramine, as soon as it’s in your body, the diphenhydramine looks for the molecules on the outsides of cells called histamine receptors. In order for histamine to affect your body, they have to find one of these histamine receptors and sit on it. If it can’t do that, the histamine is not able to cause symptoms or perform its normal function. The antihistamine finds those receptors and sits on top of it so that the histamine can’t fit in. This translates into fewer symptoms because the histamine is blocked.

How effective antihistamines are at finding those receptors and sitting on them differs from drug to drug. Some do this really quickly but others take a few hours to find the receptors. Some drugs can get knocked off the histamine receptors they sat on. Drugs like this are less effective antihistamines.

Diphenhydramine finds the histamine receptors very quickly and sticks to them very strongly. This is why it is such an effective antihistamine. Because it is such a strong antihistamine, when your body breaks it down, your symptoms can come back quickly and forcefully. This is called rebound. Your symptoms reappear because there’s no longer enough medication in your body to keep the histamine from working. (Please note that rebound reactions can also happen with other medications for other diseases in ways that do not affect histamine. I’m just being general here for the mast cell disease audience.)

Rebound reactions can be tricky to get out of because the natural response to take medication again to control the symptoms. However, when you do this, you may just be setting yourself up for another rebound reaction when this dose wears off. This is one of the reasons why many doctors prefer that their mast cell patients not take Benadryl frequently. When you are stuck in a rebound loop, it can cause a lot of inflammation and that can trigger your mast cells even more.

There are a few strategies to help decrease the likelihood of rebound reactions. One is to stagger medication dosing. If a couple of your medications can cause rebound, don’t take them at the same time if you can avoid it. Take one an hour or two after the other. Some patients find benefit in layering antihistamines. By taking multiple antihistamines, you can cover lots of histamine receptors. Sometimes, it covers enough that when your diphenhydramine wears off, your body doesn’t notice as much. This could lessen a rebound reaction or even prevent one in some circumstances. You could also take another strong medication to help control your mast cells in another way, like a steroid.

Following a major reaction or anaphylaxis, many providers opt to use a taper for diphenhydramine and steroids. This can help with rebound reactions. A patient doing this might take diphenhydramine every 4 hours for one day, then every 6 hours for two more days, then every 12 hours for two more days. By not stopping cold turkey, you can allow your body to adapt. Steroid tapers do the same thing. You want to give your body a chance to compensate for not having the medication around.

Not all medications cause rebound reactions. The second generation H1 antihistamines like cetirizine or loratadine do not normally cause rebound reactions.

One important point is that many people use the term “rebounding” when they actually mean a different thing called biphasic anaphylaxis. Rebounding specifically means the reappearance of symptoms because the medication controlling them has worn off. Biphasic anaphylaxis is when you have anaphylaxis again after having a first anaphylactic event, regardless of treatment. In this scenario, a person has anaphylaxis and takes medications to treat the anaphylaxis effectively. Sometime later on, the body has a second anaphylaxis event without being exposed again to a trigger. This is not tied to any specific treatment and is different than rebounding.

For more detailed reading, please visit these posts:

How to get out of a reaction cycle

Anaphylaxis and mast cell reactions

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 35

Author’s note: This is not medical advice. Any information found here should be used as a tool for discussions you have with a provider who knows you and your specific health situation.

42. How is anaphylaxis related to mast cell disease? How do I know when to use my epipen?

Anaphylaxis is a complication of mast cell disease. It is not an inherent part of mast cell disease or a symptom of mast cell disease. Many patients never experience it.

One study found that among mastocytosis patients, adult patients with SM are more likely to experience anaphylaxis than adults with CM or children with mastocytosis. But as many as half of adult patients and even more pediatric patients never have anaphylaxis. For MCAS, the number is reported as less frequent with incidence of anaphylaxis in one group around 17%. I personally think this number is very low and sampling error. It is my experience that MCAS patients are at least as likely to anaphylax as mastocytosis patients, if not more likely.

Even though lots of mast cell patients never experience it, it is important to be aware of the risk of anaphylaxis and take precautions. Mast cells are critical in the biology of anaphylaxis so having mast cells that are very reactive, or having more mast cells than usual, can lead to more severe anaphylaxis more often than someone in the general population might experience. All mast cell patients should carry two epipens at all time. They should also carry diphenhydramine (Benadryl, liquid preferred), and many also carry steroids to use in case of anaphylaxis.

One of the most common questions I am asked is when to use your epipen. The answer to this is complicated largely because so many symptoms of mast cell disease are also symptoms of anaphylaxis. It can be hard to figure out what is going on. I have written extensively about the difference between anaphylaxis and mast cell reactions before so I recommend you read those posts also if you have not already.

The answer to when you should use your epipen is pretty much always that you should ask your doctor or provider. This answer is true and is always right. It is important that someone who knows your health situation well weighs in.

But there’s another answer we can give to this question: that you should use you epipen when it will save your life.

There are various charts and scales that people and groups use to categorize the severity of anaphylaxis. These are not useful for mast cell disease. Do not use them. They are meaningless for us.

The purpose of those charts is to allow people to figure out when a bad anaphylaxis episode is on the way. It allows people to estimate by symptoms when they should use their epipen and call 911. The charts are saying, if you have these three symptoms, you could be heading for anaphylaxis, use your epipen. But for mast cell patients, you can have those three symptoms for a variety of reasons that are not anaphylaxis. It could be mast cell reaction or just regular symptoms. So mast cell patients can’t really predict anaphylaxis in the way described in the charts. These charts just do not work for us.

So when should mast cell patients use an epipen? Generally, the answer is that they should use it when they have trouble breathing or a significant drop in blood pressure. If you are looking for independent markers for when to use an epipen and not symptoms, this lines up with a pulse ox of below 91, or systolic blood pressure below 90 (for adults), or a 30% drop in blood pressure from baseline (for children or adults). Speaking abstractly, in mast cell patients, trouble breathing and significant drop in blood pressure are usually considered as signs of anaphylaxis that warrant use of an epipen. Additionally, if the patient has a set of symptoms that they know will lead to trouble breathing or low blood pressure, their provider will direct them to use an epipen as soon as those symptoms start.

Again, when you use an epipen is a discussion that you must have with your provider. Mast cell patients should all carry two epipens on them at all time and whatever else they use for rescue meds, usually liquid diphenhydramine, and sometimes other medications.

For more detailed reading, please visit these posts:

The definition of anaphylaxis

Anaphylaxis and mast cell reactions

Treatment of anaphylaxis

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 34

41. Can my mast cell disease go away? Will it ever not be a problem?

There are several common questions that basically all distill down to these sentiments. I’m going to answer them all here.

I have previously answered the question “Can mast cell disease be cured?” in this series but I think this question is a little different. When people ask if mast cell disease can go away, they mean can it become no longer a problem even if it’s not cured. That’s what I’m answering here.

This answer is very complicated so I’m just going to give my thoughts let’s about all sides of this situation.

Yes, it is possible for mast cell disease to be controlled enough to no longer be a problem in your life. But there are a lot of caveats.

The most common presentation of mast cell disease in cutaneous mastocytosis (mastocytosis in the skin) in children. In about 2/3 of cases, children “grow out of” their mast cell disease. Specifically, this means that they lose their skin lesions and have no obvious mast cell symptoms by their late teenage/early adult years. We don’t know why this happens.

However, there are instances where a person who grew out of their childhood CM have mast cell issues later in life. We have a greater understanding of mast cell diseases now and we know that you can have a whole host of mast cell issues without having skin lesions. So it’s not as clean cut as was previously thought.

For more serious forms of systemic mastocytosis, it is possible that with treatment, the disease can be “knocked down” to a less serious category. For example, a patient with aggressive systemic mastocytosis who does chemo may find that it helped enough that their diagnosis is now smoldering systemic mastocytosis. Or a patient with SSM has a big drop in the number of mast cells zooming around after taking interferon and now they have indolent systemic mastocytosis. While symptom severity doesn’t necessarily change when a patient has a less serious diagnosis, that does sometimes happen.

With the exception of childhood cutaneous mastocytosis, all other forms of mastocytosis are considered lifelong ventures. This includes all forms of adult onset cutaneous mastocytosis and all forms of systemic mastocytosis for children or adults. However, there are instances of patients with SM where bone marrow transplant seems to cure their disease. We need to continue to follow mast cell patients who have had bone marrow transplants to see how many of them have recurrence of mast cell disease.

Mast cell activation syndrome is often secondary to some other condition. Basically, one disease irritates your body so much that your mast cells flip out in response to the disease. The disease that caused the mast cell problem is called the primary condition. In these instances, mast cell activation syndrome is sometimes considered to be dependent upon the primary condition. This means that some doctors and researchers feel that if you control the primary condition, the mast cell activation syndrome will go away.

This sentiment seems straightforward but is actually pretty complex. Let’s pull it apart. Let’s say your primary condition is lupus. You are a patient with lupus. The lupus irritates your body so much that your mast cells just go bananas. Now you are a patient with lupus who has secondary MCAS. The lupus in this instance caused the MCAS. But what does that mean? Does that mean that without the lupus, you would never have had MCAS? Or does it mean that you would eventually have had MCAS secondary to something else? This is the topic of a lot of debate. (I personally am of the belief that MCAS is genetic and therefore you were always going to develop it at some point.) So it’s not clear yet whether a primary condition really “causes” MCAS or just wakes it up.

However, what is not disputed at all is that any type of inflammation can trigger mast cell activation and symptoms. So if you are a lupus patient, and your lupus is going crazy, that’s going to really bug your mast cells. If you are able to control your lupus, it will decrease the inflammation, which will calm your mast cells. But calming your mast cells isn’t really the same thing as your mast cell disease going away. Not having symptoms is not the same thing as being cured.

Another thing to consider is that even if the lupus is what triggered your MCAS, once your MCAS is triggered, it’s going to be triggered by everything. You can very easy get locked into a cycle where the lupus irritates your MCAS, which irritates your lupus, and around you go. So in a situation like this, where the mast cell activation is really out of control, it sometimes doesn’t matter what the primary condition is, and controlling the primary condition might not help.

Many patients with mast cell disease have their symptoms controlled enough to live pretty normal lives. Some mast cell patients don’t have really symptoms at all, even without medications. In a small group of MCAS patients, after a year of treatment with antihistamines and mast cell stabilizers, about 1/3 had complete resolution of symptoms and another 1/3 had one only symptom that was a problem. 

However, it’s important to remember that this is not having debilitating symptoms is not the same as not having mast cell disease. These patients are still predisposed towards mast cell activation and should take mast cell precautions for things like surgery or dental work. Many patients stay on antihistamines and/or a mast cell stabilizer even with good symptom control because it affords some protection from bad reactions and anaphylaxis. Patients should only stop regular medication with the supervision and direction of a provider who knows them. Additionally, trialing things like foods you reacted to, or starting an exercise program, require provider input.

You should also keep in mind that mast cell disease can be very erratic. It doesn’t always follow a trend so symptoms steadily improving does not guarantee that symptoms will stay well controlled. So while mast cell disease can be managed enough to not be a problem, there is always the possibility that it will show up again. Once you have a mast cell diagnosis, you are always going to be looking over your shoulder.



I forget sometimes that this life is extraordinary. Being sick just becomes incorporated into your life. It is impossible to survive if you are upset about it every day. It just becomes part of your routine and you learn to live with it.

I had a new IV line placed last week. My port has been accessed continuously in the same spot for three years. My skin is indurated and paper thin over the access site. I accidentally tore the needle out last month and that further irritated the skin. Since I was likely weeks away from being able to literally see the port through the hole in my chest, we opted to place a temporary IV line for me to use so I could deaccess the port to heal the skin. They put in a midline last week and deaccessed my port.

I had a PICC line for a while before I had my port. The PA who placed it was pretty terrified of my mast cells. She had been warned by the infusion nurses at the hospital. The placement itself was uneventful but I will never forget having to reassure her. It was the first time I saw a provider scared of my disease. The following day, a home IV nurse came to change the dressing and check the site. She was also scared. She asked me to hold my epipens while she changed it in case of anaphylaxis. I reassured her, too.

While I am grateful to have IV access because it keeps me out of the hospital, I had forgotten what a royal pain the ass it is to have a line in your arm. The port is easier is so many ways. I can access it and deaccess it at will. I can change the dressing myself. I can get it wet. I don’t have to deal with my pump constantly squawking that the line is occluded because I bent my arm. Blood doesn’t back up in the port line. I don’t have to constantly lock the line with heparin. I forgot the way IV Benadryl burns when it’s pushed into a smaller blood vessel. The midline is temporary but obnoxious after years of having a port.

Having the midline has brought back a lot of memories for me from around the time I got the PICC placed. One of the strategies social workers recommend for adapting to a medical device or deformity or disease is to give it a name. I named my PICC because I had to convince myself that I could learn to live with it. I named my ostomy, too. I don’t bother naming things anymore. Because it has become routine.

Sunday night, I ended up in the ER after sudden onset severe GI pain. This pain is high in the tract and much more severe than what I have experienced before, both in intensity and in duration. I went to the hospital because the pain was so bad that I honestly thought I had ruptured something. It was the kind of pain that makes you think you are dying. I was literally screaming in pain.

I spent the next day in the hospital where my screaming pain was interrupted only by intense vomiting from the pain meds. We have no idea what is causing the pain. I am not convinced that it is mast cell related. I came home last night because the hospital couldn’t do anything for me that I couldn’t do at home. The nausea and pain were still there. So I left with no answers and a lot of pain.

One of my nurses yesterday was really horrified when I told him all the things I do on a daily basis to manage my disease. He in particular was horrified that I needed so much medication and was still left with debilitating symptoms. It is only in seeing this awe reflected in the eyes of people who see so much suffering that I remember how sick I am.

Today was the longest day of the year. In many pagan traditions, the summer solstice is the day when the land of the living and the land of the dead overlap. It is a day for seeing ghosts of those who have gone before us and specters of who we used to be. A day when the past whispers to you as you walk past.

I have spent all day reading through my journals from when I had my PICC line placed. I have thought about all the ways my life has changed. In many ways it has gotten better. But it definitely changed me. There is a before and after in my identity as a chronically ill person. That timeline splits along the line extending from that date.

What’s funny is that while so many things have gotten worse in that time, a lot of things have gotten better. I am much happier. I am much less scared. I am much more independent. I am much more in control of my disease and my life.

I no longer have to convince myself everyday that I can make it through the day with a central line that everyone can see. Because it is just part of my life and it’s no longer extraordinary.

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 33

40. What is mastocytosis of childhood? Is mast cell disease different for children than adults?

Cutaneous mastocytosis in children is the most common form of mastocytosis. True systemic mastocytosis, in which the WHO criteria are met, is very rare in children.

In many ways, mastocytosis in children has huge differences from mastocytosis in adults. The exact reason for this is unclear. Because of how different the disease path can be for children, doctors and researchers sometimes refer it as mastocytosis of childhood. However, there is not officially a distinct diagnostic category.

Unlike in adults, mastocytosis in children is sometimes both benign and transient. Many kids have symptoms that either stay the same or improve as they get older. Many kids grow out of their mastocytosis. About 2/3 of children with cutaneous mastocytosis have no evidence of disease (no skin lesions or symptoms) by their late teen years or early adulthood. Many other children have improvement of symptoms and signs without completing growing out of their condition.

Children with mastocytosis often have some unusual things in their bone marrow biopsies. They often have clusters of mast cells and eosinophils with other cells in their bone marrow. However, the mast cells in those clusters are often normal mast cells and do not have the same markers we see in adults. Many of these children have more mast cells in their bone marrow biopsies than adults with mastocytosis. However, unless the biopsy shows true SM, it does not affect prognosis for the children. Children may have unusual things in their bone marrow biopsies but still go on to grow out of it.

The exception is if the child has true SM. Children with true SM do not grow out of their disease.

Children with mastocytosis often have symptoms that affect multiple organ systems, not just their skin. Abdominal pain and bone pain are often reported. Systemic symptoms do not tell us whether or not the child has SM or whether or not they will grow out of their disease.

An NIH study that included 105 children with mastocytosis found that children with normal baseline tryptase tests had negative bone marrow biopsies. It also found that a tryptase level elevated after anaphylaxis or a bad reaction did not signify that the child had SM. However, they did find that all children with SM had internal organ swelling. Most children with SM were positive for the CKIT D816V mutation.

There are no studies yet on the differences between adults and children with MCAS. There are enough anecdotal findings to suggest that children with MCAS do not grow out of their disease the way children with CM sometimes do.

For more detailed reading, please visit these posts:

Childhood mastocytosis: Update

Progression of mast cell diseases (Part 5)

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 Diseases, Part 31

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

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.

Let’s talk about what EDS and POTS are first.

Ehlers Danlos Syndrome (EDS) is a connective tissue disease. It can be, and often is, inherited. About 1 in 5000 people have some form of EDS.

There are several subtypes of EDS. The ones you hear about most are called classical, vascular, and hypermobility. The different forms of EDS used to be distinguished by numbers (like Type I, Type II, etc) but now they use descriptive terms instead. Types I and II EDS are now called classical EDS (cEDS); type IV EDS is now called vascular EDS (vEDS); and type III EDS is now called hypermobility type (hEDS or htEDS). There are also other rare variants of EDS.

Each of these subtypes has distinguishing features that make them unique from the other forms of EDS. All forms of EDS cause major systemic dysfunction of connective tissue, the pieces of you that hold your body together and keep everything in the right place. Generally, in EDS patients, their connective tissues tear easily and heal slowly. They usually (but do not always) show hypermobility in their joints (being double jointed or overly flexibility). Skin that is very stretchy or that heals very poorly is common.

Because you have connective tissues holding your whole body together, EDS can affect your entire body. All patients are at risk for symptoms that specifically impact their joints, muscles and bones. VEDS can significantly affect life span because it increases the risk of an aneurysm or a blood vessel bursting. HEDS patients often have cardiovascular, GI, and neurologic symptoms. CEDS patients often display the trademark skin stretchiness and many have extraordinary difficulties in healing incisions and wounds. Of course, many EDS patients have other symptoms, and there is a lot of symptom overlap among these forms. I am just generalizing here.

There is no cure and treatment is largely about managing symptoms and complications. EDS is usually diagnosed by a geneticist. There are genetic markers for most forms of EDS that can be found with genetic testing. However, the most common form of EDS, hypermobility type EDS (hEDS), does not have a known genetic marker. For this reason, geneticists often assess how hypermobile a patient is and then uses that to support the diagnosis of hEDS.

Postural orthostatic tachycardia syndrome (POTS) is a form of orthostatic intolerance, which means symptoms and problems caused specifically by standing up. POTS patients have a big jump in heart rate when they stand up (increase of 30 beats per minute or heart rate over 120 beats/minute in adults) that is not due to a drop in blood pressure. POTS is a form of dysautonomia, an umbrella term that covers several conditions in which the body is not able to control some of the body’s automatic functions like heart rate and blood pressure. (For those wondering, automatic is not a typo, and I did not mean to write autonomic, which is related here.)

There are multiple types of POTS. I’m just going to cover neuropathic POTS and hyperadrenergic POTS as they are the most applicable here. POTS can be a primary or secondary condition. It can cause very severely disabling symptoms and effects. It can cause a huge array of symptoms, including dizziness; fainting; exhaustion; inability to exercise; nausea; vomiting; major GI disturbances (both diarrhea and constipation); inappropriate sweating; chest pain; coldness, numbness, pain and weakness of extremities; and anxiety. Some patients are unable to stand up at all.

Neuropathic POTS, the most frequently described, is thought to be the result of the veins in the legs not being able to pump blood effectively. When you stand up from a sitting position or laying down, a lot of blood that was in your torso quickly moves into your legs. This happens to everyone. In most people, the veins in your legs are able to tighten and squeeze effectively to pump that blood out of the legs and get it back to your heart. In neuropathic POTS, your veins don’t seem to be able to do this as well so the blood gets stuck in your legs. Your body interprets this as having low blood pressure even though you have enough blood and it’s just not where your body expects it. In response to the “low blood pressure”, your heart starts beating very fast to try and get enough oxygenated blood to every place in your body that needs it.

Hyperadrenergic POTS is less common but relatively more common in mast cell patients. In this form, the body makes too much adrenaline (and often other similar molecules like noradrenaline). These molecules work together to cause the nervous system to tell the heart to beat way too fast in response to standing up and that blood moving into your legs. In patients with hyperadrenergic POTS, blood pressure is often increased while the heart rate is also increased instead of being normal or low as in neuropathic POTS.

The second part of this question (question 39) will be up in a day or two. Sorry for the length but I don’t think there’s a way to answer this question both clearly and with brevity.

The perfect medicine

I do not have a metaphorical list of things to do in life. I have a literal, physical list. I started it when I was 15 years old. I remember the noise the pen made on the notebook paper. (It’s hard to remember that I was once able to hear such noises). I remember carefully tearing the pages along the perforated edges of my spiral notebook. I folded it up and tucked it inside my journal.

In its first iteration, the list had over 100 things on it. Some of them were emotional (“fall in love with someone who loves me back”), some academic (“get a doctorate”), some simple (“paint my bedroom purple”), some about specific skills (“learn how to shoot a bow and arrow”), and others about experiences (“see the pyramids at Giza”, “swim in all four oceans”). One of them was to go to a Mayan temple. It was specifically written as “Go to Chichen Itza or a Mayan temple site.”

In the years that have followed, I have done many of the things on my list. I also periodically add to it. There are some things I will never do because they were linked to a specific timepoint or situation I never found myself in. I don’t mind. The list is a map, not an itinerary. It is the compass pointing to the true north of my life. It doesn’t mind if I sail around the bottom of the world to get there.

I have been in Mexico since last Sunday. It has been a very challenging week. There were major problems with my reservations and transportation and the staff have been frustratingly rude about correcting their mistakes. I have had some misadventures with my port and that was scary. (Fortunately, I have been on antibiotics for several days now and the port does not seem to be infected.) It was not exactly the relaxing week I was hoping for but I don’t think I’ve had a relaxing week in years so at least it wasn’t unfamiliar.

Yesterday, I got to watch a very dear friend get married on a beautiful beach covered by a warm, sweet wind as the sun went down. I got to watch my sister officiate the wedding and we were all excited to think that the next wedding we all attend will be my sister’s wedding next April. And today, after almost 20 years, I went to Coba, a large Mayan temple complex an hour from the resort I am staying at.

I was so excited to be able to do this. I was also scared. My life is an exercise in adjusting expectations. I have been let down so many times by this failing vessel my soul occupies. I would be crushed if I travelled all this way and couldn’t get to Coba.

My heart has been broken so many times by this body and the life it has imposed upon me. So many times I have felt like tiny pieces of me have been chiseled away along the lines of all these tiny spiderwebbing fractures. And most days I can cope with that and most days I like my life. But this was too important to me and I felt so vulnerable and so exposed. I was really scared that I would come so close and somehow miss this opportunity.

The weather was not cooperative. It rained a spectacular amount today. It took much longer than expected to get there because we had to drive slowly. It was the kind of rain that laughs at umbrellas and boots and ponchos. We were all completely soaked in a matter of seconds. But we were there. For an hour and a half, my family and I sloshed through mud puddles and negotiated the additional slipperiness of steps worn smooth and uneven long ago. My sister and her fiance got bicycles to ride to the biggest temple. My mom and I took a rickshaw to meet them there.

And then suddenly, emerging through the dense lush green of the jungle, there it was. We turned a corner and despite the special futility that is seeing things through wet glasses, I could see it. The largest pyramid, the one I had seen in so many books. The one I saw in an encyclopedia in seventh grade and never forget.

Cardio exercise is hairy for me under the absolute best circumstances and I avoid it as fiercely as I avoid undercooked egg whites. But I had made it so far and couldn’t leave without trying. I pushed down my fear and started climbing. It was wet and slick and hot. I kept my eyes on the steps and climbed, one hand on the rope strung down from the top, the other on the steps. If I turned around, if I looked at how high I was, if I thought about how easy it would be to fall, I would never have made it. I kept my head down and kept my eyes on the step immediately in before me. I moved forward and I didn’t look back. And almost 20 years after writing the entry in my list of things to do, I climbed to the very top of a Mayan pyramid.

One of my sister’s best friends is Buddhist. She was also in Mexico this week for the wedding. Last night, we chatted about living a good life with chronic illness. (She is a diabetic.) She told me that one of the leaders of her sect of Buddhism believes that for everything that can ail the body, there is a perfect medicine to cure it. Nothing can be done that cannot be undone with something somewhere in this world. Maybe it takes forever to find it. Maybe we never find it. But it is there nonetheless, waiting for us.

Maybe all those crystal slivers of my heart that I have lost were not really lost but scattered. Maybe this is the perfect medicine. To cross things off my list, to go to these places. To live your dreams when you are never even sure you will live until tomorrow.

To believe things will get better and that your life is good. That this life has value and so do you.

To move forward. And don’t look back.



The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 30

38. What is the difference between the forms of cutaneous mastocytosis?

Cutaneous mastocytosis is a form of mast cell disease in which way too many mast cells are found only in the skin and not in other organs. Over 80% of patients with mastocytosis have mastocytosis in their skin.

Patients who have systemic mastocytosis have too many mast cells in organs that are not in the skin. However, many of them also have too many mast cells in their skin. These patients are said to have “systemic mastocytosis with mastocytosis in the skin (MIS).” This terminology distinguishes these patients from those who only have too many mast cells in the skin.

There are three categories of cutaneous mastocytosis:

Maculopapular cutaneous mastocytosis (MPCM):
Previously called urticaria pigmentosa (UP). Many patients and providers still use the term UP and the term MPCM is more commonly found in research work.
This is the most common form of cutaneous mastocytosis.
UP causes lesions on the skin, often called “spots” or “masto spots”. In adults, these spots are usually little red/brown lesions. Sometimes a small amount of skin is affected. Other times, a lot of the skin becomes covered in spots.
In adults, UP spots are usually permanent. Some people who need chemo find that the chemo makes some of their UP spots disappear.
In children, UP spots are often larger. The shape and number of spots may change as they get older.
In children, UP spots sometimes resolve over time and disappear.
There is a type of UP called telangiectasia macularis eruptiva perstans (TMEP). This used to be a separate diagnosis from UP but we now know that it is just a kind of UP that looks different from the common red/brown spots.
In TMEP, little blood vessels growth very close to the skin and look like little red or brown spots.

Diffuse cutaneous mastocytosis (DCM):
DCM almost exclusively starts in childhood.
DCM does not cause spots. Instead, it causes overall redness and thickening of skin. It can also cause blistering. The blisters and wounds sometimes bleed.

Solitary cutaneous mastocytoma:
The third form of cutaneous mastocytosis is a little misleading in classification. This form is called solitary cutaneous mastocytoma.                                                                      This is a benign mast cell tumor that grows on the skin.                                         Mastocytomas can grow elsewhere in the body. When they do, they are not considered a form of cutaneous mastocytosis.
While the term is “solitary cutaneous mastocytoma”, some people do have multiple mastocytomas on their skin.