The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 73

86. What is the role of the spleen in systemic mastocytosis? (Part Two)

  • The spleen is basically a big filter for the blood. In the previous post, I mentioned one of its functions: to catch certain types of infections in the blood that your immune system has a hard time fighting in other ways.  It does some other things, too. The spleen stores red blood cells and platelets so that your body has a backup supply in case of hemorrhage or trauma.
  • The spleen also looks for something else when it filters the blood: damaged or abnormal blood cells. Damaged or abnormal blood cells get caught in the spleen so that they don’t continue to circulate in the blood. The spleen then breaks down those bad cells and uses materials from them to help make new healthy cells.
  • If there are lots of abnormal cells, then the spleen gets swollen because it is holding many more cells than usual. This is why the spleen swells in diseases where the body has abnormal cells in the blood stream. How much the spleen swells is directly proportional to the amount of abnormal cells in the blood.
  • For example, in acute leukemias, there are tons of abnormal cells circulating in the bloodstream. The spleen catches as many as they can. Because there are a lot, the spleen swells very quickly. In chronic leukemias, there are still abnormal cells, but they are produced at a much slower rate over time. This means that the spleen has more time to break down the broken blood cells it catches before it catches more of them. In these scenarios, the spleen swells more slowly over a longer period of time.
  • You can apply this understanding directly to mastocytosis. Patients with indolent systemic mastocytosis have fewer mast cells than those with smoldering or aggressive systemic mastocytosis, or mast cell leukemia. The patients with indolent systemic mastocytosis make some abnormal mast cells. The spleen will catch the ones it sees and remove them from the bloodstream. But mast cells don’t live in the blood and they only pass through the bloodstream for a short time. So the spleen has time to break down some mast cells before it catches more.
  • When a patient with indolent systemic mastocytosis starts to produce higher numbers of mast cells, that’s when you see the spleen starting to swell. That’s why spleen swelling is a B finding for systemic mastocytosis – it is an indicator that the body is making more mast cells than before, and could be headed toward a more aggressive form.
  • The number getting filtered out by the spleen increases so the spleen swells. The more abnormal mast cells produced, the more the spleen swells.
  • Additionally, when the bone marrow is making lots of aberrant mast cells, they are introduced into the blood stream in much larger numbers than normal. This means that they are more likely to get caught in the spleen than in a person with indolent systemic mastocytosis.
  • In smoldering systemic mastocytosis, the body makes more mast cells than in indolent systemic mastocytosis, so it’s more common for the spleen to swell. In aggressive systemic mastocytosis, the bone marrow is producing a lot of mast cells and many of them are caught in the spleen over a short period of time. In mast cell leukemia, even more are made and caught, so the spleen becomes clogged up very quickly.
  • When the spleen is swollen from catching bad mast cells, the swelling causes it to break or damage other, healthy blood cells, too. This happens because the swelling of the spleen pinches the pathway for cells through the spleen so the other cells have to squeeze through, causing them to break. This is why patients with more advanced forms of systemic mastocytosis like smoldering systemic mastocytosis, aggressive systemic mastocytosis, and mast cell leukemia are more likely to have low blood cell counts than people with indolent systemic mastocytosis.
  • In addition to the risk of low blood cell counts, the swelling and dysfunction of the spleen can also contribute to portal hypertension. This is when there is high pressure in the blood vessel system that connects the GI tract, the pancreas, the spleen and the liver.
  • Portal hypertension is also a C finding for aggressive systemic mastocytosis. This means that a person who has this because of mastocytosis receives a diagnosis of aggressive systemic mastocytosis.
  • Portal hypertension can affect liver function and can cause fluid that should be in the liver to end up in the general abdominal space, a condition called ascites.
  • Splenic swelling often causes no symptoms. It is unusual for it to cause pain in the general area of the spleen. Left shoulder pain sometimes occurs if the spleen is very swollen.
  • The general rule of thumb is that the spleen has to be twice its normal size for it to be felt on a physical exam. The exact amount of swelling is usually measured by an ultrasound.
  • Spleen swelling does not usually require treatment. Generally, unless there is hypersplenism, it is not treated.
  • The treatment for hypersplenism is splenectomy, surgical removal of the spleen. The spleen is removed mainly for two reasons: to decrease portal hypertension, thereby reducing stress on the liver; and to prevent the spleen from rupturing, which can cause fatal hemorrhage.

This question was answered in two parts. Please see the previous post for more information.

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 and MCS

Mast cell disease and the spleen

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 72

86. What is the role of the spleen in systemic mastocytosis? (Part One)

  • The spleen is basically a big filter for the blood. It is supposed to catch certain types of infections in the blood that your immune system has a hard time fighting in other ways.
  • When the spleen is swollen but still functions pretty well, it is called splenomegaly.
  • Swelling of the spleen is not uncommon in systemic mastocytosis. Splenomegaly is most often seen in patients with smoldering systemic mastocytosis, aggressive systemic mastocytosis, and mast cell leukemia, but sometimes patients with indolent systemic mastocytosis have swelling of the spleen.
  • When the spleen swells, the pathway for the blood going through the filter gets pinched. Blood goes in but has to pass through a narrow exit route to get out of the spleen. The more swollen the spleen is, the narrower the pathway for the blood to get through the spleen. This means that cells can be damaged or broken open if the spleen is swollen.
  • How much this happens depends upon how swollen the spleen is. If it is only a little swollen, the change in blood cell counts can be minimal.
  • For systemic mastocytosis, a swollen spleen that works well (splenomegaly) is what is called a B finding. A B finding is a way to tell if a patient’s indolent systemic mastocytosis is moving to a more serious form, like smoldering systemic mastocytosis or aggressive systemic mastocytosis. If a patient has a B finding, they are monitored more closely to look for other clues that could mean the disease is progressing.
  • Please note that the B finding MUST be caused by the mastocytosis to count. For example, if an SM patient falls off their bike and injures their spleen, causing it to swell, this is not a B finding. If the mastocytosis didn’t cause the problem, it doesn’t count.
  • Mast cell patients who have a spleen that is swollen but works correctly don’t damage too many blood cells. This means blood counts are often normal in this situation. If blood cell counts are not normal, the spleen is not the cause.
  • Some patients with aggressive systemic mastocytosis and mast cell leukemia develop a condition called hypersplenism. Hypersplenism basically means the spleen is working way too hard. Hypersplenism is a C finding, a marker that indicates that a patient’s mastocytosis has become very aggressive. If a patient has a C finding, they are diagnosed with aggressive systemic mastocytosis (ASM).
  • Sometimes patients with mast cell leukemia have hypersplenism. However, there are stringent criteria for diagnosing mast cell leukemia. Just having a C finding isn’t enough for a diagnosis of mast cell leukemia, while just having a C finding IS enough for a diagnosis of aggressive systemic mastocytosis.
  • Having a C finding is not a defining feature of mast cell leukemia the way it is for aggressive systemic mastocytosis.
  • Some patients with systemic mastocytosis have another blood disorder that causes the bone marrow to make too many cells. This is cleverly named systemic mastocytosis with associated hematologic disorder (SM-AHD). People with SM-AHD can have any stage of systemic mastocytosis. If they have another blood disorder, they are categorized as having SM-AHD even if they have aggressive systemic mastocytosis or smoldering systemic mastocytosis. So a person with SM-AHD can have any type of systemic mastocytosis, including aggressive systemic mastocytosis.
  • Sometimes patients with systemic mastocytosis alongside another blood disorder (called SM-AHD) have hypersplenism. Here, the hypersplenism could be caused by one of two conditions: systemic mastocytosis, or the other blood disorder. If the mastocytosis causes the spleen issue, the patient gets a diagnosis of aggressive systemic mastocytosis just like any systemic mastocytosis patient. If the other blood disorder is what causes the hypersplenism, the patient does not get a diagnosis of aggressive systemic mastocytosis.
  • If the mastocytosis causes the spleen issue, then we know that this is a C finding, a marker for aggressive systemic mastocytosis. If the other blood disorder is what causes the hypersplenism, it is not a C finding and does not indicate aggressive systemic mastocytosis.
  • Please note that having a C finding is not a defining feature of SM-AHD the way it is for aggressive systemic mastocytosis.
  • Hypersplenism sometimes occurs in patients with SM-AHD. It could be caused by either the systemic mastocytosis or the other blood disorder. It can be trickier to figure out exactly what is causing the splenic issues.
  • If the mastocytosis causes the spleen issue, then we know that this is a C finding, a marker for aggressive systemic mastocytosis. If the other blood disorder is what causes the hypersplenism, it is not a C finding and does not indicate aggressive systemic mastocytosis.
  • Please note that having a C finding is not a defining feature of SM-AHD the way it is for aggressive systemic mastocytosis.
  • You can tell that a person has hypersplenism by looking at four things:
    1. Low counts of certain blood cells in the blood. Red blood cells, platelets, and some white blood cells can be low because of hypersplenism. The white blood cells that are low when a person is hypersplenic are eosinophils, neutrophils, and basophils. These cells all have granules full of chemicals like mast cells do.
    2. The bone marrow trying to make extra blood cells to make up for the ones that being destroyed by the spleen.
    3. Swelling of the spleen.
    4. The expectation that if the spleen is removed, the blood cell counts will go up and the bone marrow will start making normal amounts of blood cells again.

This question was answered in two parts. Please see the following post for more information.

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 and MCS

Mast cell disease and the spleen

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)

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 48

59. Is systemic mastocytosis a form of cancer? Why do some papers say the life expectancy for systemic mastocytosis patients is much shorter?

Systemic mastocytosis is a term that different people use in different ways, often without defining them for the audience. This can lead to some confusion.

In its broadest sense, systemic mastocytosis is actually a disease category rather than one specific diagnosis. The subtypes of systemic mastocytosis are indolent systemic mastocytosis (ISM), smoldering systemic mastocytosis (SSM), systemic mastocytosis with associated hematologic disease (SM-AHD), aggressive systemic mastocytosis (ASM), and mast cell leukemia (MCL).

When patients talk about systemic mastocytosis without specifying which diagnosis, they almost always mean indolent systemic mastocytosis (ISM), the most common form of SM. ISM is benign and has a normal life expectancy. But when providers and researchers talk about systemic mastocytosis, they usually mean the disease category that includes all of these diagnoses.

I just recently explained in another post what a neoplasm is. It is essentially when the body grows something that doesn’t belong there, like extra cells or a tumor. Cancers are neoplasms but not all neoplasms are cancerous. Indolent systemic mastocytosis is not cancerous. Even without taking drugs to kill off lots of mast cells, the prognosis is excellent with a normal life span. However, aggressive systemic mastocytosis and mast cell leukemia are considered cancerous. Without taking drugs to kill off mast cells, the body would be unable to cope with the huge number of mast cells and the damage they cause. Smoldering systemic mastocytosis is sort of a bridge between ISM, which is benign, and ASM, which is not.

If you are not aware that research papers usually use the term systemic mastocytosis to mean all forms of systemic mastocytosis and not just indolent systemic mastocytosis (ISM), it is easy to get confused and misunderstand what is being said. There was a paper published in 2009 that discussed expected survival for the various forms of systemic mastocytosis. It provides a very jarring statistic for patients who may not understand the context. This study found that many patients with systemic mastocytosis died 3-5 years after diagnosis.

Let’s pull this apart. We know there are five forms of SM: indolent SM, the most common form, which usually has a normal life span; smoldering SM, which usually has a shortened life span; aggressive SM, which can have a very shortened life span; mast cell leukemia, which has a very shortened life span; and SM with an associated hematologic disorder, which may have a shortened life span. When you average the life expectancies for a mixed group of patients with these various diagnoses, it shows that overall, SM patients are more likely to die 3-5 years after diagnosis when compared to healthy people of the same age.

Additionally, a lot of the patients in this study group were older and died of causes unrelated to systemic mastocytosis. However, because they were part of the study, their deaths of unrelated causes were still included in this data.

Let’s recap: in a research paper, the term systemic mastocytosis includes forms of SM that are malignant and can really shorten your life expectancy as well as forms that are benign and do not shorten your life expectancy. When you average the life expectancies of all of these forms together, it looks like patients are more likely to die 3-5 years after diagnosis. A bunch of other papers then used the data from this study in 2009 without explaining the details behind it. However, most patients with SM have normal life spans.

For more detailed information, please visit these 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 and MCS

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 43

52. Is it true that it can take up to six bone marrow biopsies to diagnose systemic mastocytosis?

Sort of. This has become sort of an urban legend in the mast cell community. I am partly to blame for this as I have offered this information up several times without explaining it, which is lazy on my part.

Systemic mastocytosis is diagnosed by biopsy. While a positive biopsy in any organ that’s not skin can be used to diagnose SM, bone marrow biopsies are overwhelmingly what is used to diagnose.

In 2004, a paper was published that discussed how well bone marrow biopsies worked for diagnosing SM in a group of 23 patients. These patients had bilateral bone marrow biopsies taken, so each patient had one on each side. In 19 of those patients, both of the biopsies showed mastocytosis. In 4 of those patients, only one of their two biopsies was positive. 4/23 is 17%, which is roughly 1/6. Based upon this figure, it means that theoretically, in a patient who has SM, they could have five negative biopsies before getting a positive biopsy.

It’s important to two things in mind when you think about this 1/6 thing. Firstly, this is a very small patient group. Things that you see in a small group don’t always translate to what really happens in larger groups. Another thing is that the criteria they used in 2004 to diagnose SM are not the same as the criteria we use now. It’s possible that with changes in diagnostic criteria that this 1/6 number is no longer accurate.

In reality, I have never met a person who needed six bone marrow biopsies to get a positive biopsy for SM. But I do know a few who needed two or three. It’s not impossible that it could take six to get a positive biopsy but it’s unlikely.

However, it’s also important to realize that every expert acknowledges that you can have a negative biopsy while having SM. The reason for this is that you can’t tell by looking whether or not a biopsy site will give you a positive biopsy for SM. You have to just hope that the mast cells are clustered where they stick the needle. Mast cells don’t cluster evenly throughout your bone marrow when you have SM. If you get a biopsy site where the mast cells didn’t happen to cluster, you are out of luck. For this reason, some doctors advocate getting bilateral bone marrow biopsies (two at once) to increase the chances of catching a positive biopsy.

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.

 

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)