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 2

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

3. What causes mast cell disease?

  • The cause of mast cell disease is not yet definitively known.
  • As mentioned yesterday, when the body makes too many copies of a broken cell, those cells are called ‘clonal’ cells. In clonal forms of mast cell disease, the bone marrow makes too many mast cells. Those mast cells also don’t work correctly. Examples of clonal mast cell diseases are systemic mastocytosis and cutaneous mastocytosis.
  • Patients with systemic mastocytosis often have a specific genetic mutation called the CKIT D816V mutation. About 80-90% of systemic mastocytosis patients have this mutation. This mutation is in mast cells and it tells the mast cells to stay alive WAY longer than they should. And mast cells already live for months or years, a very long time for cells to live in the body. So patients with this mutation can end up with way too many broken mast cells.
  • Despite the fact that we know that many patients have this mutation, we do not say that this mutation CAUSES the disease. The reason for this is that sometimes, mast cell patients don’t have the mutation when they get sick but they develop it later. Sometimes, mast cell patients have the mutation and then lose it later. So we are still looking for something that causes the disease.
  • Patients with non-clonal mast cell disease do not have a single major mutation like the CKIT D816V mutation. This makes it harder to diagnose. Researchers have found that many times, patients with MCAS DO have mutations similar to the ones systemic mastocytosis patients do. But the MCAS patients often have different mutations from each other. That’s why it’s not helpful yet for diagnosis.
  • Despite the fact that the mutations described here are not considered to be heritable, there is more and more evidence that mast cell disease can happen to many people in the same family. See the next question for more details.

4. Is mast cell disease heritable?

  • Mast cell disease often affects multiple members of the same family. Importantly, patients often have a different type of mast cell disease than their relatives. This implies that mast cell disease is more of a spectrum rather than several different diseases.
  • A survey found that 74% of mast cell patients interviewed reported at least one first degree relative that had mast cell disease. This same study found that 46% of those patients had mast cell disease that affected more than just their skin. This is called systemic disease.
  • The CKIT D816V mutation is the mutation most strongly associated with clonal mast cell disease. The CKIT D816V mutation is NOT heritable.
  • There are very rare instances of other heritable mutations in families that have mast cell disease. The significance of this is not clear.

5. Can mast cell disease be cured?

  • Generally speaking, there is no cure for mast cell disease.
  • Children who present with cutaneous mastocytosis sometimes grow out of their disease. Their lesions disappear. Their mast cell symptoms affecting the rest of the body may disappear. We do not know why this happens. It has been heavily researched with long term follow up of children with childhood mastocytosis (at least one paper followed them for 20 years).
  • Children with true systemic mastocytosis do not grow out of their disease.
  • There is not yet data on children with MCAS. Anecdotally, they do not seem to grow out of their disease like kids with cutaneous mastocytosis can. Importantly, this is just what it looks like to me. Again, there is no data.
  • People with adult onset mast cell disease have lifelong disease.
  • There is one notable exception to this scenario. There are reports of curing mast cell disease following hematopoietic stem cell transplant/bone marrow transplant.
  • Transplantation is EXTREMELY dangerous. The transplant is MUCH, MUCH more dangerous than mast cell disease. Many people do not survive the protocol necessary to prepare for transplant. Many die from complications, or from a disease they acquired after their transplant.
  • Rarely, people may have malignant forms of mast cell disease, aggressive systemic mastocytosis (ASM) or mast cell leukemia (MCL). A few patients with these diseases have tried transplants after everything else failed. While some did see improvement after transplant, no one has survived more than a few years.
  • Conversely, sometimes people with mast cell disease have these transplants for other reasons, like having another blood cancer or bone marrow disease that requires transplant. In this group of people, some see drastic improvement of their mast cell disease. Some see a full remission of mast cell disease. Some do not get any improvement. These findings are pretty recent so it’s hard to be more specific.

For more detailed reading, please visit these posts:

The Provider Primer Series: Introduction to Mast Cells

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)

Mast cell disease in families

Heritable mutations in mastocytosis