The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 66

80. When is chemotherapy necessary for mast cell disease?

  • For mastocytosis patients, chemotherapy is used for patients with systemic mastocytosis in whom the disease is malignant (aggressive systemic mastocytosis or mast cell leukemia) or seems to be progressing towards a cancerous form of the disease (smoldering systemic mastocytosis). There are very clear cut guidelines for this. Interferon and chemotherapy are used when a patient has smoldering mastocytosis with increasing mast cell counts; aggressive systemic mastocytosis; or mast cell leukemia, in order to kill off mast cells to slow disease progression and extend a patient’s lifespan.
  • A patient who already meets the criteria for systemic mastocytosis, who has two or more B findings, is considered to have smoldering systemic mastocytosis. SSM is a transition state between indolent SM, which has a normal lifespan, and malignant forms of mast cell disease, including ASM and MCL.
  • Having two or more of the following gets you a diagnosis of SSM: mast cell aggregates that take up 30% or more of cells in a bone marrow biopsy, and/or serum tryptase over 200 ng/mL; bone marrow with too many cells in it overall, without evidence of MDS or a myeloproliferative neoplastic disease; or organ swelling that has not yet affected organ function (swelling of the liver without ascites, spleen swelling enough that it can felt by palpation, lymph nodes swollen to 2 cm or larger).
  • Patients with SSM are watched to see if their body is making lots of mast cells quickly, or if their organs are feeling the strain of too many mast cells. One of the way they check this is to see how quickly their tryptase level increases. If their provider feels that their disease is progressing, they receive chemo or interferon to try and knock the disease down enough that they don’t reach the criteria for ASM.
  • Patients are diagnosed with ASM if they meet the criteria for SM and any of the following criteria: the body not making enough blood cells, cytopenia (absolute neutrophil count below 1000/ul, hemoglobin below 10g/dl, or platelets below 100000/ul); swelling of the liver along with free fluid in the abdomen (ascites), elevated liver enzymes, or portal hypertension; swelling of the spleen along with decreased blood cells due to damage in the spleen, excessive production of blood cells by the bone marrow to compensate, and likely resolution if the spleen is removed; malabsorption in the GI tract causing low protein in the blood (albumin) and weight loss; and severe bone dysfunction, causing a series of bone breaks and large osteolytic lesions from mastocytosis.
  • ASM patients are put on chemotherapy or interferon, usually continuously, unless there is evidence that they have killed off enough mast cells to have a less dangerous disease category.
  • Mast cell leukemia patients are on chemotherapy continuously.
  • There is no described use for chemo in cutaneous mastocytosis.
  • There are situations where patients with other disease categories (ISM, MMAS, MCAS) are put on chemo drugs to try and manage symptoms or shock episodes after all other therapies have failed. While this has been mentioned in literature, there have been no studies on it.
  • Chemo drugs should be used as a last resort. They can have significant side effects and complications that cannot always be remedied by stopping the treatment.
  • Please note that while newer, targeted chemos have become more common, they are in fact chemotherapy and carry significant risks despite being more tailored, including the potential for organ damage or failure.

For additional reading, please visit the following posts:

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

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

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

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 59

73. Can mast cell disease cause organ damage?

  • Yes.
  • The term organ damage is tricky because people use it to mean a lot of things while providers and researchers often use it to mean one very specific thing. For providers and researchers, the term “organ damage” usually means a change in the organ that affects its structure, like it becomes misshapen or deformed in some way. Structural changes like this are often irreversible. This damage to the organ’s shape and structure usually affects how the organ works, called organ function.
  • When patients and laypeople talk about organ damage, they usually mean a change in the way the organ functions, even if the structure is not changed at all. This is different in a very important way: changes in an organ that do not affect its permanent structure can sometimes be reversible.
  • Both cutaneous and systemic mastocytosis cause organ damage in a way that damages the organ’s structure. When too many mast cells burrow into the tissue of an organ, it has to push other things out of the way. When you have mastocytosis, the mast cells like to stick together and form a big clump in the tissue. This punches holes in the tissue, affecting the organ’s structure and shape. This is called dense infiltration. It is one of the criteria for systemic mastocytosis and also happens in cutaneous mastocytosis.
  • In patients with mastocytosis, those mast cells clumping together cause a lot of the organ damage. This means that people who have the most mast cells usually have the worst organ damage. Patients with malignant forms of mast cell disease, like mast cell leukemia or aggressive systemic mastocytosis, often have organs that are riddled with TONS of mast cells.
  • Mast cells don’t live in the blood so when your body makes way too many mast cells, those mast cells will dive into whatever organ they can to get out of the bloodstream. This causes damage to the structure that you can see with scans or in biopsies.  People with mast cell leukemia and aggressive systemic mastocytosis suffer so much damage to the shape and function of their organs that the organs can totally stop working, called organ failure.
  • One of the key differences researchers and providers see between mastocytosis and mast cell activation syndrome is that mast cells don’t cause THIS TYPE of structural damage in mast cell activation syndrome patients.
  • We know this because in biopsies, they do not have mast cells clumped together to punch holes in the tissue. Sometimes they have lots of mast cells, but it is much less damaging to the tissue if they aren’t clumped together. Think of it like poking something with finger versus punching with your fist.
  • In MCAS, mast cells do not cause structural damage to organs IN THIS WAY. However, many people with MCAS do have structural damage to their organs. Many of them also have organs that do not function correctly even if the organs look normal.
  • Even if you don’t have mast cells punching holes in all your organs, they can still do a lot of damage. This is because mast cells cause lots of inflammation, which can stress out your organs. Over time, your organs can be damaged by the mast cells releasing too many mediators. While this is not always dangerous, it is certainly painful and frustrating.
  • Many MCAS and mastocytosis patients have a lot of damage to their GI tracts from years of vomiting, obstructions, diarrhea or constipation. Hives and mastocytosis spots can damage your skin, causing discoloration, scarring or sensitivity. Muscles can become weaker over time because of mast cell inflammation. Swelling can stretch out your skin and connective tissues. Nerves can be damaged significantly, affecting organ function. Bones can become brittle and break, or can become too dense because the body is making new bone when it shouldn’t.
  • All of these effects on organ function can be caused by mast cells. Major changes in organ function can also cause secondary conditions to arise.
  • Mast cell patients are also at an increased risk for anaphylaxis which can cause changes in organ function or organ damage.
  • Patients who have trouble breathing or low blood pressure may not be getting enough oxygen to their whole body. That can cause lasting damage if it goes on long enough.

For more detailed reading, please visit the following posts:

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 55

69. What routine monitoring should mast cell patients receive?

There are not yet routine testing recommendations for MCAS patients, but there are some for mastocytosis patients. Many doctors use the mastocytosis recommendations to monitor their MCAS patients in the absence of specific MCAS guidelines.

Mastocytosis patients should monitor tryptase level annually. In mastocytosis patients, tryptase level is often a good marker for how many mast cells are in the body (although this is not always true.) If a patient’s tryptase is increasing over time, the provider will need to check other things to see if their disease is moving to a more serious disease category.

DEXA scans measure bone density. Osteoporosis is a common complication of systemic mastocytosis. Patients should receive regular osteoporosis screening, even if they are young.

Mastocytosis patients usually receive routine bloodwork annually that includes a complete blood count (CBC), which counts the amount of blood cells a person has; and a metabolic panel, which looks at how well the liver and kidneys are working.

Repeat biopsies are usually only done if the result will change treatment in some way. Most patients with systemic mastocytosis are diagnosed based upon bone marrow biopsies. These don’t usually need to be repeated unless tryptase level increases sharply or there are unusual results in routine blood count testing. Increasing tryptase can indicate that the body is making more mast cells much faster, which is sometimes linked to a more serious disease category. Unusual blood cell counts can indicate not just too many abnormal mast cells, but also other bone marrow conditions sometimes seen in mast cell patients, like myelofibrosis and essential thrombocythemia.

Patients with cutaneous mastocytosis are diagnosed by skin biopsy. There is not usually a need to repeat a skin biopsy for patients with CM.

Patients with systemic mastocytosis are usually diagnosed by bone marrow biopsy but can also be diagnosed as a result of a positive biopsy in any organ that is not the skin. A person can be diagnosed with SM via a GI biopsy.

GI biopsies are a little different than bone marrow biopsies in that there are sometimes reasons to repeat them. GI biopsies may be repeated to see if the general inflammation in the GI tract is improved or worsened. The provider may also be interested in whether or not the amount of mast cells in the GI tract has decreased. The result of GI biopsies often change treatment options so it is not unusual to repeat them. However, unlike bone marrow biopsies, repeated GI biopsies do not tell the provider if the mastocytosis is moving toward a more serious disease category or not.

MCAS patients are diagnosed based upon positive tests for molecules that indicate mast cells are overly active, like n-methylhistamine, and D2- or 9a,11b-F2 prostaglandins. Once the patient is diagnosed, there’s not a clear rationale for repeating these tests, although some providers do for their own information. Some providers like to check prostaglandin levels to see if treatment to stop mast cells from making prostaglandins (like use of aspirin or other NSAIDs) is helping.

However, it is important to understand that the level of mast cell mediators is not associated with symptoms. A person who has a normal level of 9a,11b-F2 prostaglandin may have the same symptoms as a person above the normal level, who may have the same symptoms as a person who has three times the normal level. For this reason, many providers consider these mediator tests to be less about the numerical value of the test and more about whether it’s normal or high, period.

For more detailed reading, please visit the following post:
The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 5
The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 6
The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 7
The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 8
The Provider Primer Series: Diagnostic criteria of systemic mastocytosis and all sub variants
The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (ISM, SSM, ASM)
The Provider Primer Series: Mediator testing
The Provider Primer Series: Mast cell activation syndrome (MCAS)

MastAttack position on Mast Cell Activation Syndrome

In the unlikely event that it is unclear where MastAttack stands on mast cell activation syndrome:

MCAS is a serious, debilitating disease that directly causes an array of symptoms that often interfere with the daily living activities of patients who have it.

MCAS increases the risk of anaphylaxis, a potentially fatal, severe allergic reaction.

MCAS patients require careful management of their condition to stay healthy and safe. Overwhelmingly, this requires medication. There is nothing wrong with needing medical management of MCAS. You are not doing anything wrong by taking medications prescribed by a knowledgeable provider.

MCAS patients are more likely to have other disabling conditions, such as gastroparesis, Ehlers Danlos Syndrome, Postural Orthostatic Tachycardia Syndrome, and various autoimmune disorders and immunodeficiencies, among others.

Patients with MCAS sometimes need an extraordinary level of nutritional intervention to prevent malnutrition, starvation, and complications thereof.

Patients with MCAS sometimes require central intravenous lines to facilitate nutrition, use of IV fluids, and IV medications.

Patients with MCAS sometimes require GI tubes to facilitate nutrition and medication use in patients who are not able to take foods and medications orally.

Patients with MCAS often live complicated, stressful lives. Their experiences do not deserve to be mocked or minimized. They should under no circumstances attempt to manage their disease on their own without medical supervision without detailed conversations with their own care teams.

Patients with MCAS often repeatedly suffer the indignity of having their very state of health questioned and belittled by providers, family members, coworkers, and the public. This is especially an issue where it concerns medically complex children as unfamiliar providers may incorrectly assume that these children are receiving unnecessary medical interventions, sometimes resulting in removing the child. All of these situations can discourage MCAS patients from seeking care and can endanger them.

The idea that MCAS patients cannot die of complications of their mast cell disease and other diagnoses is ridiculous. I know MCAS patients who have died from anaphylaxis or from the inability to receive needed therapies without anaphylaxis and shock. We are fortunate as a community that these deaths are rare, but to insinuate that they do not happen is both incorrect and disrespectful.

The recent “controversy” about whether or not MCAS can be serious and disabling is shocking and has been difficult to watch. I do not often find myself truly stunned. While many patients are fortunate to be able to live safely while managing MCAS, we all know a number of MCAS patients who are not able to achieve stability, and who require aggressive medical and surgical management to stay alive. I cannot believe I have to say this.

MCAS patients are an integral part of the mast cell community. Please support them now.

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 47

  1. 58. What is mastocytic enterocolitis?

A high powered field (hpf) is what you see through a microscope when you use powerful magnifying lenses. With very few exceptions, high powered fields using the same lenses are the same size. Since they are the same size, you can directly compare results from various groups all over the world.

In 2006, a paper was published that coined the term “mastocytic enterocolitis”. The author described mastocytic enterocolitis as more than 20 mast cells per high powered field. This paper was about people with severe chronic diarrhea that did not improve with treatment. The author found that healthy people had about 13 mast cells/hpf while people with severe chronic diarrhea had about 20 mast cells/hpf. The author felt that the extra mast cells were responsible for the diarrhea and inflammation so they called the extra mast cells in the colon and the small intestine “mastocytic enterocolitis”. Enterocolitis is the term for inflammation in the small intestine and colon.

The author felt that 20 mast cells/hpf was the cutoff between a normal amount of mast cells in the GI tract and an abnormal amount. Under 20 was considered normal while 20 and above was considered abnormal. However, there have been a number of papers since that look at how many mast cells are present in the GI tract for patients with different conditions as well as healthy people. There are several conditions that can cause you to have 20 or more mast cells/hpf. (I wrote an exhaustive series on this in 2015-2016. Links are below.)

Additionally, in some situations, people have over 20 mast cells/hpf without having any symptoms. Sometimes healthy people without any GI conditions have over 20 mast cells/hpf. For this reason, there is not agreement about how many mast cells in the GI tract is too many. (If you’re looking for my opinion, I think the number for what is too many is around 25-30/hpf. This is just my opinion.)

In the last several years, some doctors have begun linking mastocytic enterocolitis to mast cell disease. This makes sense because we know that in those people, mast cell inflammation drives GI symptoms and damage. Mast cell patients certainly have a lot of inflammation in the GI tract so having extra mast cells there makes sense. Some experts think that mastocytic enterocolitis is a sign of mast cell activation syndrome and that patients with mastocytic enterocolitis all have mast cell activation syndrome.

Mastocytic enterocolitis is absolutely a real phenomenon. In these people, mast cells cause a lot of GI symptoms and damage the GI tract. Experts have not all agreed upon whether or not everyone with mastocytic enterocolitis has mast cell disease. Also, there are some researchers that feel that mastocytic enterocolitis is actually its own mast cell disease rather than just a feature of another mast cell disease like mast cell activation syndrome.

Currently, mastocytic enterocolitis is not recognized by the WHO as its own disorder. However, that could certainly change. It was only last year that MCAS was recognized by the CDC even though it was routinely recognized by researchers and providers. (Author’s note: This was initially published stating that the WHO recognized MCAS, rather than the CDC. MCAS has not yet been recognized by the WHO. This is a whopper mistake on my part. Many thanks to the reader who saw this. Sorry!) I personally expect this to change in the next few years as more mast cell patients are diagnosed and mastocytic enterocolitis is better recognized. I think it is suggestive of mast cell disease but I also think providers need to eliminate other possible causes for the extra mast cells in the GI tract.

For more detailed information, please visit these posts:

Mast cells in the GI tract: How many is too many? (Part One)

Mast cells in the GI tract: How many is too many? (Part Two)

Mast cells in the GI tract: How many is too many? (Part Three)

Mast cells in the GI tract: How many is too many? (Part Four)

Mast cells in the GI tract: How many is too many? (Part Five)

Mast cells in the GI tract: How many is too many? (Part Six)

Mast cells in the GI tract: How many is too many? (Part Seven)

Mast cells in the GI tract: How many is too many? (Part Eight)

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 Diseases, Part 42

51. What is the difference between mast cell activation syndrome and histamine intolerance?

Histamine intolerance is not widely accepted by the mainstream medical establishment. I haven’t been able to find much about it in the way of peer reviewed literature. That said, it doesn’t seem ridiculous to me. It feels plausible, I just haven’t seen convincing evidence of that yet.

Histamine intolerance is when a patient has symptoms from ingesting something that has a lot of histamine in it, that causes the body to release histamine, or that interferes with the body’s ability to break down histamine. In histamine intolerance, the problem is what is being put into your body rather your body itself. The problem is external, not internal.

Mast cell activation syndrome is when a patient’s mast cells are fundamentally dysfunctional. The problem is internal, not external. There is no evidence at this point that patients with MCAS can’t break down histamine normally with enough time, there’s just so much of it that it takes longer.

Many patients with MCAS (and other mast cell diseases) often have symptoms when they ingest something that has a lot of histamine in it or that causes the body to release histamine. There are two theoretical ways in which ingestion of histamine can cause symptoms: either the histamine released/ingested makes it way to other parts of the body and causes symptoms there directly; or, the histamine released/ingested makes mast cells release more histamine.

Regardless of exactly what is happening, patients with MCAS and histamine intolerance can have identical symptoms to ingesting a trigger. Importantly, MCAS patients may have histamine symptoms from lots of other things, not just ingesting something.

Histamine intolerance is much more commonly discussed in holistic and alternative medicine groups, which is definitely not where my expertise is. If you are aware of some recent data on histamine intolerance, or if I have made a mistake in this post, please let me know so that I can correct it.

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 40

49. What is the relationship between FPIES and MCAS?

FPIES is food protein induced enterocolitis syndrome, a severe type of food allergy. It causes continuous vomiting and diarrhea upon ingestion of a trigger. FPIES reactions can cause dehydration and dangerous drop in blood pressure. I cannot emphasize enough that FPIES can be extremely serious and that the reactions can be life threatening if they are not managed properly.

FPIES almost exclusively affects children starting in infancy and resolves around the age of 5. The reasons for this are unknown. FPIES is a diagnosis of exclusion. There are no tests to identify FPIES.

An important point is that trigger avoidance is generally sufficient for management in children with FPIES. When the child is not being exposed to a trigger, they should not have lingering symptoms.

If a child with FPIES continues to have symptoms, the conventional thinking is often that there must be a trigger that has not yet been eliminated from their diet. In children with continuing symptoms, they frequently have more traditional allergy type symptoms than the profuse GI issues seen with FPIES exposures. This is where FPIES starts to overlap with MCAS. MCAS can cause the same reactions to foods seen in FPIES. MCAS can also cause daily symptoms even if food triggers are avoided. Increasingly, children who were initially diagnosed with FPIES are later diagnosed with MCAS.

There are a few possible scenarios here. Firstly, it is possible that the child has FPIES and has MCAS secondarily to the FPIES. It is also possible that the child was misdiagnosed with FPIES and had MCAS all along. It may also be that FPIES is some form of MCAS. They have a lot in common.

Because there is no test for FPIES, and it is very difficult to accurately perform mediator testing to look for mast cell disease in infants, it is hard to be definitive at that age anyway. In some cases, investigation of MCAS as a possible diagnosis for these children only occurs when they fail to “grow out of” FPIES around age 5. Having anaphylaxis also provides a clue towards MCAS as a potential diagnosis.

For more detailed reading, please visit these posts:

Food allergy series: FPIES (Part 1)

Food allergy series: FPIES (Part 2)

Food allergy series: Mast cell food reactions and the low histamine diet

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

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 38

45. Is mast cell disease autoimmune?

An autoimmune disease is the result of a patient’s immune system specifically targeting a normal, healthy part of their body. How particularly and precisely the immune system identifies part of the body to attack is very important to understanding my answer to this question.

Let’s look at some autoimmune diseases as examples.

Autoimmune thyroiditis (also called Hashimoto’s thyroiditis) is a prevalent autoimmune disease that targets the thyroid. The thyroid’s job is to make hormones that tell your body to do other things. These hormones are called thyroid hormones. When you have autoimmune thyroiditis, your immune system makes antibodies that target the thyroid and thyroid hormones. These are called autoantibodies. They target a normal part of body. There is no reason for the body to make these autoantibodies. They do not perform any healthy function for the body. The only function they serve is to attack part of the body.

When you have autoimmune thyroiditis, the immune system makes antibodies to things that are only found in the thyroid or made by the thyroid. (I’m being very general here.) Other autoimmune diseases target parts of the body that are found throughout the body so that the effects of the disease are more widespread. However, those diseases still target specific things.

Lupus is an autoimmune disease that affects many places in the body by precisely attacking things found throughout the body. The cells in your body all have DNA inside of them. This DNA has the genes to make proteins and other things your body needs. If the cell can’t use the DNA inside it correctly, it makes your body sick. This is exactly what happens in lupus. Lupus makes autoantibodies and attacks things inside your cells that your body needs to use the DNA. Because all of the cells in your body need to use their DNA, the things lupus attacks are found all over the body, not just one organ. But even though lupus attacks many organs and places throughout your body, it is still targeted to harm specific pieces of the body.

In autoimmune disease, the body makes specific things for the explicit purpose of damaging specific things.

Now let’s talk about mast cell disease.

Currently, mast cell diseases are not considered to be autoimmune by most – but not all – experts. (I’ll circle back to this.) When a person has mast cell disease, the fundamental issue is that they release tons of mast cell mediators at times when they shouldn’t, causing symptoms and damage to the body. But even though those chemicals can cause all kinds of problems, they are not targeted to attack specific structures. This is where the distinction is from autoimmune diseases. Mast cells release tons of histamine, but that histamine isn’t targeted to find a specific molecule inside of a liver cell. They release prostaglandin D2, but that PGD2 isn’t made for the particular purpose of attacking one particular thing inside of your thyroid.

Instead, the molecules released incorrectly by mast cells affect whatever cells are in its path. This is one of the reasons why there is such variability in symptoms and disease effects for mast cell patients. What parts of the body are affected the most is dependent upon a million things happening in the patient’s body. This is because the chemicals mast cells release are not targeted to any one place. They are just released by the mast cell and they go wherever they can before the body breaks them down.

I mentioned above that most experts did not consider mast cell diseases to be autoimmune, but not all of them. So let’s go back to that. Mastocytosis is not considered autoimmune but anyone as far as I am aware. There is absolutely no evidence that mastocytosis is autoimmune after decades of research. But MCAS is a newer entity and so there is less information on it due to less time spent researching it. There are still a lot of questions around MCAS and some experts think that whether or not it is autoimmune is one of them.

We know that at the very least that there is a connection between MCAS and autoimmune disease. Many MCAS patients have autoimmune disease, often more than one. We think MCAS occurs secondarily to the autoimmune disease in these patients. There’s also the fact that many MCAS patients are positive for ANA (antinuclear antibody), an autoantibody linked to lupus, even though they don’t have a diagnosed autoimmune disease that would cause that to be positive. Some people think that maybe MCAS is the autoimmune disease in that situation and that ANA is a marker indicating that MCAS is autoimmune. I have mentioned elsewhere that while we consider MCAS to usually be a secondary disease, there are some patients for whom we can’t find a primary disease. It is possible that MCAS is a primary condition in those people and that it is autoimmune.

You still need to keep in mind that even if we say that maybe the positive ANA shows that MCAS is autoimmune, there is still no evidence of any kind that indicates that mast cell mediators target a specific part of the body – a defining characteristic of autoimmune disease. That doesn’t mean there isn’t an autoantibody or some other mechanism for targeting precise structures in the body, just that we have no evidence of one existing right now.

Let’s recap: currently, most experts believe that mast cell diseases are not autoimmune because they do not target specific normal, healthy structures in the body. Mastocytosis is roundly agreed to not be autoimmune. There are some experts who feel that at least some cases of MCAS might be autoimmune. They feel this way because of the clear link between MCAS and other autoimmune diseases, as well as the fact that many MCAS patients are positive for an autoimmune marker, ANA, without evidence of an autoimmune disease that would explain that.

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.