The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 70

84. Is the problem for mast cell patients that they can’t break down histamine properly?

  • Not exactly. Mast cells that are overly activated will make and release more histamine but the activation comes before the histamine, not the other way around. There’s no evidence that indicates that in mast cell disease there is something wrong with the way the body breaks down histamine.
  • Histamine intolerance is not a well accepted diagnosis in the general medical establishment. Histamine intolerance is when patients react to foods and activities that contain or cause the production of histamine in the body. The general thinking on why this happens is that the body doesn’t make enough enzyme to break down the histamine at a normal rate. I have not seen convincing data that histamine intolerance is in fact due to the inability of the body to break down histamine fast enough. Regardless, I know a lot of people who feel better when they take DAO supplements or each DAO rich foods. DAO (diamine oxidase) is one of the enzymes your body uses to break down histamine.
  • Please keep in mind that histamine intolerance is a distinct phenomenon from mast cell disease. In mast cell disease, the problem is that the mast cells are too activated so they release excessive histamine into the body. In histamine intolerance, the mast cells are not overly activated, and the body can’t break down histamine fast enough. This means that even if a person with histamine intolerance makes a normal amount of histamine, their body can’t break it down at a normal rate.
  • It is theoretically possible to have both mast cell disease and histamine intolerance. There’s not a reliable way to test for histamine intolerance beyond symptoms, and there aren’t really robust diagnostic criteria. Some people with suspected mast cell disease test negative despite having mast cell symptoms and responding to treatment. This means that there’s no way to definitively know right now if a trigger causes a reaction because of histamine intolerance or a mast cell reaction beyond having a prior, firm diagnosis of mast cell disease.
  • There is something I find intriguing that may be linked to histamine intolerance. I mentioned diamine oxidase (DAO) above. It is one of enzymes your body uses to break down histamine. The other enzyme your body uses for this is called histamine n-methyltransferase. When this enzyme breaks down histamine, it produces n-methylhistamine.
  • N-methylhistamine is the most common breakdown product of histamine. It is also the molecule that we test for as part of the diagnostic workup for mast cell disease. The reason we test for n-methylhistamine instead of histamine is because histamine is broken down so quickly that n-methylhistamine stays in your body much longer than histamine. We use it as a surrogate marker for histamine since it’s easier to measure.
  • I know a lot of mast cell patients who have flagrant histamine symptoms that repeatedly have normal tests for n-methylhistamine both in blood tests and in 24-hour urine tests. There are a few reasons why this could be but I have started to wonder if the reason those tests come back normal is because your body doesn’t make enough of the enzyme that breaks down histamine in this way. As I said above, there is no real evidence to support this, just something I think about sometimes.

 

For additional reading, please visit the following posts:

The Provider Primer Series: Mediator testing

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 62

76. Is it true that allergic reactions can cause heart attacks?

  • Yes.
  • Kounis Syndrome is an acute coronary syndrome caused by activated mast cells releasing chemicals. It is sometimes referred to as “allergic heart attack.” In acute coronary syndrome, there is not enough blood being pumped into the heart. It is named for two of the large blood vessels supplying oxygen to the heart, the coronary arteries. When not enough blood is getting to the heart via the coronary arteries, it can damage heart muscle, sometimes permanently. Heart attack and angina are examples of acute coronary syndromes.
  • In Kounis Syndrome, mast cells become activated, releasing lots of chemicals. These chemicals can irritate the coronary artery, causing it to spasm. This spasm reduces the amount of blood getting to the heart. Sometimes, mast cell activation can trigger the formation of a clot. A clot can be the reason not enough blood is passing through the artery.
  • Several of the molecules released by mast cells can affect the cardiovascular system and contribute to causing Kounis Syndrome. Histamine and leukotrienes can cause the coronary artery to narrow. It can also activate platelets, helping a clot to form. Both tryptase and chymase can cause clots formed elsewhere to break off and get stuck in the coronary artery.
  • Mast cells also help regulate an important molecule called angiotensin II. Angiotensin II is a powerful regulator of blood pressure and can cause the coronary artery to narrow and tighten up.
  • People with Kounis Syndrome may have a history of coronary artery disease. Some patients have a stent in the coronary artery from a previous coronary issue. A stent is a tube that helps keep the blood vessel the right size so that the heart gets the blood it needs. However, many patients with Kounis Syndrome do not have any history of problems with their heart or blood vessels.
  • The symptoms of Kounis Syndrome sometimes look just like the symptoms of any other mast cell reaction or anaphylaxis, making it hard to know that a person is having Kounis Syndrome. Chest pain, irregular heart beat, the heart beating too fast or too slow, and palpitations are all common symptoms of Kounis Syndrome.
  • Another tricky thing about Kounis Syndrome is that it doesn’t always show up on the tests we use to look for heart attack or coronary issues. Because of this, doctors don’t always realize what is happening. Some people do have positive results to these tests, things like EKG, echocardiogram, chest x-ray, and bloodwork to look at levels at cardiac enzymes or troponin. Cardiac enzymes and troponins are often high in a person who is having a heart attack but are sometimes normal for patients with Kounis Syndrome.
  • In order to manage Kounis Syndrome, patients may need treatment for both the allergic reaction and the coronary syndrome.
  • Treatment for the allergic reaction is similar to anaphylaxis treatment: an H1 antihistamine like Benadryl, an H2 antihistamine like famotidine, a corticosteroid like methylprednisolone, IV fluids, and sometimes epinephrine, if that’s appropriate. Please note that epinephrine is not always appropriate for patients who have Kounis Syndrome because epinephrine can actually also cause the coronary artery to narrow.
  • Treatment for the cardiovascular aspect of Kounis Syndrome is very dependent upon symptoms and test results. Calcium channel blockers like verapamil, aspirin, and nitroglycerin are commonly used. Importantly, some of the common medications used to manage coronary syndrome are not safe for mast cell patients. These medications include beta blockers like metoprolol or atenolol, and, to a lesser extent, ACE inhibitors like lisinophil. These medications can interfere with epinephrine so epinephrine may not work if a patient needs it for anaphylaxis.
  • Anything that triggers mast cell activation can cause Kounis Syndrome, including emotional stress.

For additional information, please visit the following posts:
Kounis Syndrome: Subtypes and effects of mast cell mediators (Part 1 of 4)
Kounis Syndrome: Diagnosis (Part 2 of 4)
Kounis Syndrome: Treatment (Part 3 of 4)
Kounis Syndrome: Stress (Part 4 of 4)
Beta blockers and epinephrine
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
The Provider Primers Series: Medications that impact mast cell degranulation and anaphylaxis

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 57

71. What other diseases “look like” mast cell disease?

Mast cell diseases have many symptoms that are also commonly found in other disorders. This is one of the reasons why it is difficult to diagnose correctly. The following conditions have symptoms that can look like mast cell disease.

Neuroendocrine cells are specialized cells that help to pass signals from the nervous system to nearby cells, causing those cells to release hormones. There are many types of neuroendocrine tumors. Some conditions that look like mast cell disease are caused by these tumors. Symptoms from them are caused by the response of too much hormone.

Carcinoid syndrome is the result of a rare cancerous growth called carcinoid tumor. This tumor releases too much serotonin into the body. This can cause flushing, nausea, vomiting, diarrhea, difficulty breathing, and cardiovascular abnormalities such as abnormal heart rhythm. Mast cells also release serotonin but they release much less than carcinoid tumors.

VIPoma means vasoactive intestinal peptide –oma. When a word has –oma at the end, it means that it is a tumor. A VIPoma is a tumor that starts in the pancreas. It releases a chemical called vasoactive intestinal peptide. VIPoma can cause flushing, low blood pressure, and severe diarrhea leading to dehydration. A VIPoma can also abnormalities in the composition of the blood. Many patients have low potassium, high calcium, and high blood sugar.

Pheochromocytomas start as cells in the adrenal glands. They release excessive norepinephrine and epinephrine. They can cause headaches, heart palpitations, anxiety, and blood pressure abnormalities, among other things.

Zollinger-Ellison syndrome is a condition in which tumors release too much of a hormone called gastrin into the GI tract. This causes the stomach to make too much acid, damaging the stomach and affecting absorption.

Some blood cancers can cause mast cells to become overly activated. They may also cause an increase in tryptase, an important marker in diagnosing systemic mastocytosis.

Some other cancerous tumors like medullary thyroid carcinoma can cause mast cell type symptoms including flushing, diarrhea, and itching.

Most diseases with any allergic component can look like mast cell disease.

Eosinophilic gastrointestinal disease occurs when certain white blood cells called eosinophils become too reactive, causing inflammation to many triggers. Furthermore, people are more frequently being diagnosed with both EGID and mast cell disease.

Celiac disease is an autoimmune disease in which gluten causes an inflammatory reaction inside the body. The damage to the GI tract can be significant. Malabsorption is not unusual. Children with celiac disease may grow poorly. Bloating, diarrhea, ulceration, and abdominal pain are commonly reported.

FPIES (food protein induced enterocolitis syndrome) can cause episodes of vomiting, acidosis, low blood pressure and shock as a result of ingesting a food trigger.

Traditional (IgE) allergies can also look just like mast cell disease. They are usually distinguished by the fact that mast cell patients may react to a trigger whether or not their body specifically recognizes it as an allergen (does not make an IgE molecule to the trigger). Confusingly, it is possible to have both traditional IgE allergies and mast cell disease.

Postural orthostatic tachycardia syndrome (POTS) is commonly found in patients with mast cell disease. However, POTS itself can have similar symptoms to mast cell disease. Palpitations, blood pressure abnormalities, sweating, anxiety, nausea, and headaches are some symptoms both POTS and mast cell disease have. There are also other forms of dysautonomia which mimic the presentation of mast cell disease.

Achlorhydria is a condition in which the stomach does not produce enough acid to break down food properly. This can cause a lot of GI pain, malabsorption, anemia, and weight loss.

Hereditary angioedema and acquired angioedema are conditions that cause a person to swell, often severely. Swelling may affect the airway and can be fatal if the airway is not protected. Swelling within the abdomen can cause significant pain and GI symptoms like nausea and vomiting.

Gastroparesis is paralysis of the stomach. People with GP often experience serious GI pain, vomiting, nausea, diarrhea or constipation, bloating and swelling.

Inflammatory bowel diseases and irritable bowel syndrome can all cause GI symptoms identical to what mast cell patients experience.

This list is not exhaustive. There are many other diseases that can look similar to mast cell disease. These are the ones I have come across most commonly.

For more detailed reading, please visit the following posts:

Gastroparesis: Part 1
Gastroparesis: Treatment (part 2)
Gastroparesis: Diabetes and gastroparesis (Part 3)
Gastroparesis: Post-surgical gastroparesis (Part 4)
Gastroparesis: Less common causes (Part 5)
Gastroparesis: Autonomic nervous system and vagus nerve (Part 6)
Gastroparesis: Idiopathic gastroparesis (Part 7)

Food allergy series: Food related allergic disorders
Food allergy series: FPIES (part 1)
Food allergy series: FPIES (part 2)
Food allergy series: Eosinophilic colitis
Food allergy series: Eosinophilic gastrointestinal disease (part 1)
Food allergy series: Eosinophilic gastrointestinal disease (part 2)
Food allergy series: Eosinophilic gastrointestinal disease (part 3)
Food allergy series: Eosinophilic esophagitis (Part 1)
Food allergy series: Eosinophilic esophagitis (Part 2)
Food allergy series: Eosinophilic esophagitis (Part 3)

Angioedema: Part 1
Angioedema: Part 2
Angioedema: Part 3
Angioedema: Part 4

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 49

60. Is anaphylaxis the same as anaphylactic shock?

No. Anaphylaxis can result in anaphylactic shock but it often doesn’t. When talking about anaphylactic shock, people are referring to circulatory shock that was caused by anaphylaxis. Circulatory shock occurs when there is not enough blood to carry oxygen to all the tissues that need it. When the tissues don’t get enough oxygen, your organs stop working correctly.

Circulatory shock is usually caused by low blood pressure. Anaphylaxis commonly causes low blood pressure and that can cause shock. However, anaphylaxis does not always cause low blood pressure, and it does not always cause shock.

61. If a tryptase level over 10.9 ng/mL is high, why is one of the criteria for systemic mastocytosis a tryptase level of 20.0 ng/mL or higher?

Tryptase level is used in two ways in assessing mast cell patients: as a marker for activation, and as a marker for how many mast cells are in the body.

There are two primary methods of using tryptase to indicate mast cell activation.

The first way is to compare a tryptase level when a patient is reacting to a tryptase level when they are not reacting (baseline). Mast cells release more tryptase when they are activated. For mast cell patients, an increase of 20% + 2 ng/mL is considered evidence of mast cell activation. So if a patient has a baseline tryptase of 5 ng/mL when they are not reacting, anything 8 ng/mL (20% of 5 ng/mL is 1 ng/mL, then add 2 ng/mL = 8 ng/mL) or higher is considered evidence of activation.

The second way is to count anything over 10.9 ng/mL as evidence of activation.

When you are using tryptase as a measure of how many mast cells are in the body, the patient should not be reacting beyond their normal day to day symptoms. This is because you don’t want an increase in tryptase from activation to make the baseline level look higher than it is. Tryptase is used to measure how many mast cells are present because mast cells release some tryptase all the time, even when they aren’t activated.

Anything over 10.9 ng/mL is considered an elevation of tryptase. The reason that 20 ng/mL is the cutoff for the SM criterion is that patients are likely to have a positive bone marrow biopsy when the tryptase level is twice normal (21.8 ng/mL). They round the number down to 20 ng/mL because all tests have a margin of error. By rounding down to 20 ng/mL, they catch patients that might not have made the cutoff before because of an error in the test. This means that a patient who has a tryptase level of 20 ng/mL or higher is likely to have a bone marrow biopsy that will be positive for systemic mastocytosis.

For more detailed reading, please visit these posts:

Anaphylaxis and mast cell reactions

The Provider Primer Series: Mediator Testing

Patient questions: Everything you wanted to know about tryptase

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, part 8

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 45

54. How does mast cell disease affect clotting?

Heparin is a very potent blood thinner and inhibits the body’s ability to form clots.  Mast cells are full of heparin. Mast cells stores chemicals like heparin in little pouches inside them called granules. In the granules, histamine is stuck to heparin. This means that when mast cells open their granules and release histamine, heparin comes out with it. This can contribute to things like bruising or bleeding more than expected.

Mast cells release other chemicals that can affect clotting. Platelet activation factor and thromboxane A2 both encourage the body to make clots. Some chemicals that help to regulate when to make a clot can activate mast cells, like complement C3a and C5a.

55. How many people have mast cell disease?

It is hard to know exactly how many people have a rare disease because they are not reported if they are recognized and correctly diagnosed. As recognition and diagnosis improves, rare diseases are often found to be more prevalent than previously thought. The numbers below are current estimates.

Systemic mastocytosis is thought to affect around 0.3-13/100000 people. In one large study, indolent systemic mastocytosis (ISM) makes up 47% of cases. Aggressive systemic mastocytosis (ASM) has been described in various places as comprising 3-10%. Systemic mastocytosis with associated hematologic disease could count for as many of 40% of cases of SM. Mast cell leukemia is extremely rare and accounts for less than 1% of SM cases.

Systemic mastocytosis accounts for about 10% of total mastocytosis cases. This means that total mastocytosis cases come in at around 3-130/100000 people. The remaining 90% of mastocytosis cases are cutaneous with incidence roughly around 2.7-117/100000 people.

We do not have yet have a great grasp upon how many people have mast cell activation syndrome (MCAS) but from where I am sitting, it’s a lot and that number is likely to grow. We know that genetic studies have found mutations that might be linked to MCAS in up to 9% of the people in some groups. However, having a mutation is not the same thing as having a disease. As we learn more about MCAS, we will gain some clarity around how many people have it.

For more detailed reading, please visit the following posts:

Progression of mast cell diseases: Part 2

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

The Provider Primer Series: Natural history of SM-AHD, MCL and MCS

The Provider Primer Series: Cutaneous mastocytosis/Mastocytosis in the skin

 

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 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 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 4

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

8. Why are symptoms not the same for everyone?

  • Bodies are very complex. This sounds silly to say because of course bodies are complex, but the amount of work a body does on a second to second basis is staggering. All of your organs are working all the time. The way they are working depends on hormones, how recently you ate, if you are stressed out, what kind of environment you live in, if you have been or are pregnant, how old you are, if you are sexually active, where you are in your menstrual cycle, what medications you are on, and what things happened to you up to this point in your life. Not everyone’s body does the same things.
  • Mast cells are involved in regulating many processes at the same time that all of these things are happening. It is releasing chemicals to make these things happen and is receiving messages from other cells.
  • Mast cells are key cells in inflammation. Inflammation is when cells from the immune system tell the body that it is under attack. Some of those cells are white blood cels that were already present. Inflammation causes many white blood cells, including mast cells to go to the site of the inflammation. For example, if you break your arm, the cells near the broken bone will send messages that it needs help from immune cells. Those immune cells will then physically move to the place they were called to. Mast cells may move to the site of inflammation in this way.
  • When an area has been inflamed, sometimes white blood cells stick around even when the area is healed or healing. Mast cells can also do this. If an area is inflamed, you may end up with many mast cells in that spot where there had originally only been a few.
  • When an area has been inflamed, the immune cells nearby can be extra easy to activate for a while. They are “primed”. Primed cells are much more likely to start a new inflammatory episode, even for something tiny, because they are easier to activate. They remember that they previously had to call for help so their instinct is to do it again. In this way, old injuries may “act up” easily. This can keep nearby mast cells primed or even activated long term.
  • Mast cells have pockets called granules that store chemicals inside them. These chemicals are called mediators. They perform many of the mast cell’s normal functions.
  • Mast cells have different jobs in different places in the bodies. The mediators stored inside those pockets are not the same in all mast cells. They are full of the mediators that they need most to do specific jobs in that area. Mast cells can also make new mediators to do specific jobs. The mediators they make are also tailored to their specific jobs.
  • Some mediators are very specific and some are not. Think of this like sending an email. You can send an email to a particular person. This is specific. You can also send an email to an address used by many people, like an email account for several people who work in customer service. Any of them might see it and respond but you don’t know which one. This is nonspecific. Mast cell mediators might talk to just one type of cell or to several kinds of cells, either nearby or in other parts of the body. Which mediators are released can also depend on previous inflammation. Which mediators are released, where they are released, and how much is released also vary from person to person.

9. Why do symptoms change over time?

  • Symptoms can change over time for all of the reasons they are not the same from person to person.
  • It is also possible that symptoms can change due to progression of disease from one diagnostic category to another. For example, patients may suddenly notice their abdomen is swollen and hard. That could be because their liver is swollen and not working properly.
  • You CANNOT assume that the disease is progressing because symptoms change. Symptom change is NOT a marker for progression.
  • Mast cell disease is not inherently progressive. Many people never have a change in diagnosis.

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)