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Posted by on May 10, 2013 in The Basics |

What is Mastocytosis?

What is Mastocytosis?

Do you have any questions about mastocytosis? Then please head for the “Why Is It All So Confusing?” forum and we'll try and help.

A Comprehensive Video Summary

Let's get  started with this comprehensive video summary (7:23)  from the Mayo clinic.

As there is so much information in the video summary, we've also included a transcript at the bottom of this post, after our own brief introductory overview. It would be useful for you to read the transcript once at your own pace, and then proceed with the posts in this site, as we will be clarifying many of the concepts talked about in the video.

If this is your first encounter with mastocytosis, the amount of information contained in the video transcript may overwhelm you a bit. Once again, don't worry, throughout this site, we intend to take you through the detail bit-by-bit.

Pierre Noel, M.D., hematologist at Mayo Clinic in Arizona, discusses the diagnosis and treatment of systemic mastocytosis or mast cell disease.

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Let’s Summarise The “Comprehensive Video Summary”

Mastocytosis is a disease that is characterized by abnormal growth and accumulation of white blood cells called mast cells in

  1. the skin,
  2. in internal organs, or
  3. in both skin and internal organs.

Therefore, mastocytosis is a disorder caused by the presence of too many mast cells (overabundant, superfluous mast cells) in a person's body. Both children and adults can develop mastocytosis.

A mast cell is a type of blood cell made in the bone marrow that is involved in allergic reactions as well as fighting parasitic infections. In a mastocytosis patient, in addition to being overabundant, these mast cells cells may also be misshapen or malformed, further contributing to their dysfunction.

Mast cells, sitting next to all major organs, contain packets (or granules) of chemicals, including histamine, which are released outside the mast cell when the body feels it is under attack by germs.  This chemical release is a normal reaction of our immune system if indeed we are under attack.

As the released chemicals are a bit of a toxic affair, our body is usually very good at releasing those chemicals only in the case of an obvious attack, and the amount of chemicals released is in proportion to the perceived attack.  However, in mastocytosis patients, the release of those chemicals can happen for no real reason, even when there is no attack. And if there is an attack, the release is also out-of-proportion and too many chemicals are spilled out.

That would be bad enough if you had the right number of mast cells, but paired with the fact that mastocytosis patients have an over-abundance of mast cells, it is easy to understand why their bodies behave as if they were under constant, incessant and  massive attack.

This chemical release can lead to symptoms such as flushes, indigestion (dyspepsia), abdominal pain, muscle/bone pain, changes in blood pressure (usually a fall known as hypotension), generalised fatigue and in extreme cases, anaphylactic shock, which can be fatal.

The severity of the symptoms will depend on the site or organ affected and the extent to which the mast cells have built up in that organ, as well as how trigger-happy the mast cells are to release their chemically-loaded granules.

Mastocytosis  is a rare disorder. The true incidence of mastocytosis is unknown, but the available evidence suggests that it is a rare disease, with a prevalence of no more than 0.3 per 10,000, which qualifies it as an orphan disease.

In medical terms, mastocytosis is called a “myeloproliferative neoplasm characterized by infiltration of clonally derived mast cells in different tissues”. Quite a mouthful, but as you learn about the disease, you'll get used to these terms.

Mastocytosis has many forms, and we will learn the detail of these different forms in the “Diagnosis” section of this site. But, in broad terms, there are two general forms of mastocytosis: cutaneous and systemic.

Cutaneous Mastocytosis

Cutaneous mastocytosis is an increase of mast cells in the skin and accounts for about 90% of mastocytosis cases.

There are various sub-types of the cutaneous version, which we will discuss in another section of the site. But, by and large, Urticaria pigmentosa  is the most common version of Cutaneous Mastocytosis. It is characterized by tan or red-brown spots (lesions) on the skin. These spots generally appear first on the midsection of the body, and then can spread throughout the body. Symptoms such as nausea, vomiting, and diarrhea may also be present with urticaria pigmentosa.

If you are an adult, I am afraid you are stuck with those spots for life. However, if you are a child, there is a high likelihood that you'll get rid of it.

Cutaneous mastocytosis usually develops in early childhood. Most pediatric patients with CM have a benign and often self-limited clinical course. The disease often regresses spontaneously during puberty.

Systemic Mastocytosis

Systemic mastocytosis involves internal organs throughout the body, including the gastrointestinal tract, bone marrow, liver, spleen, and lymph nodes.

In 85% of people with systemic mastocytosis, the cutaneous mastocytosis sub-type of urticaria pigmentosa developed first.

The risk of developing systemic mastocytosis increases with age.

Depending on the number of mast cells in the different organ parts, it is classified as either indolent (slow-growing) or aggressive mastocytosis.

As the number of mast cells build up in an organ, symptoms of the disease may worsen. Currently, there is no known cure and no known cases of spontaneous remission.

Prognosis

The prognosis of mastocytosis depends on the specific classification of the disease.

In general, the prognosis of childhood mastocytosis is very good.

In adults, the prognosis for cutaneous mastocytosis and indolent mastocytosis is good. Occasionally, a patient with indolent mastocytosis progresses to a more severe classification, but this is unusual, especially if the diagnosis has been made for several years and the progression has not been rapid.

Most patients with indolent mastocytosis will have what is probably a normal life span. However, they should expect the quality and predictability of their life to be affected, sometimes significantly. No doctor will be able to tell you the measure of that your quality of life deterioration : while the symptom manifestation is generally broadly similar for a mastocytosis patient population, every patient is affected differently.

The prognosis for aggressive mastocytosis is guarded and relies on supportive care and response to cytoreductive therapy.

In spite of the generally good prognosis, managing anaphylaxis events is paramount, as these can, in extreme conditions,  be fatal.

Video Transcript

I'm Pierre Noel, I am an hematologist in the division of hematology / oncology at Mayo Scottsdale. I'd like to speak today with you about systemic mastocytosis.

Systemic mastocytosis is a rare disease and it's a disease involving myeloid cells which are part of the cells in the bone marrow.

The organ which is most frequently involved in mast cell disease is the skin. Over ninety percent of the patients with systemic mast cell disease have skin involvement.

How do you know if you have mast cell disease? Well, mast cells are cells which are present in our body, in different parts of our body, below our skin, gastrointestinal tract and bone marrow. Patients with systemic mast cell disease, for the large majority, approximately ninety-five percent, have a mutation in their mast cells, when we collect mast cells from the bone marrow. Over ninety-five percent of patients with systemic mast cell disease have a c-KIT mutation, which is a mutation we can analyze when we do a bone marrow biopsy, and this confirms the diagnosis of systemic mastocytosis, especially if it's done in conjunction with other tests.

Some of the other tests, when we look at the bone marrow, we look at the number of mast cells and the presence of mast cell aggregates. We require over fifteen mast cells as part of an aggregate and if we have a significant number of aggregates in conjunction with the presence of a mutation, we feel more comfortable in making a diagnosis of systemic mastocytosis.

Other factors, which are important, is something we can measure in the peripheral blood, which is called tryptase. Tryptase is, or the level of tryptase, correlates with the total mast cell burden in your body. So when we evaluate someone with systemic mastocytosis, we do a tryptase to try to evaluate how many mast cells are present.

The other thing we look at, when we look at mast cells, we look at what they look like morphologically, under a microscope and patients with systemic mastocytosis frequently have mast cells which have an unusual shape. Frequently, they have a spindle shape, and we look at the proportion of mast cells which have spindle shape.

Other organs which can be involved in systemic mastocytosis include the gastrointestinal tract, the spleen, the liver, the lymph nodes and when we evaluate patients in clinical we try to evaluate what organs are involved and the extent of the involvement. We stage patients with systemic mastocytosis based on their organ involvement, as well as the side-effects which occur from the systemic mastocytosis.

Some of these side effects can include fractures of bones, can include a spleen which is enlarged and kind of captures or traps a lot of the normal blood cells, it could be involvement of the liver which increases pressure on the liver and accumulation of fluid in the abdomen or it could be involvement of the gastrointestinal tract with problems of absorption and weight loss.

One other important thing in systemic mastocytosis is there's a proportion of patients who have a phenomenon called anaphylaxis and anaphylaxis is a severe allergic reaction which can occasionally result in death. Most patients do not die, but have problems breathing and problems with your blood pressure. This can occur following bee stings, snake bites, insect stings, but also, very commonly, it can be associated with medications. Apart from medications, symptoms of an anaphylaxis can occasionally occur in patients who do very strenuous exercise.

So, we see patients coming to us because they had an episode of hypotension with respiratory compromise and your physician thought about mast cell disease and did a tryptase and found that the tryptase was significantly increased, or someone had a severe reaction to an insect bite and that's a source of referral to an oncologist for evaluation for systemic mastocytosis.

What we do in patients with systemic mastocytosis, from a treatment standpoint, there are patients who have indolent systemic mastocytosis and these patients have an excellent prognosis and what we try to do is to minimize your symptoms and this minimization of symptoms can be done through the use of different forms of antihistamines, to block the histamine release from mast cells.

The other thing we do is, we give patients EpiPens, which are pens containing epinephrine, that they can use if they are unfortunate and have an anaphylactic reaction. They can react to this reaction by injecting, self-injecting or having a family member inject the epinephrine and help to resolve this episode of anaphylaxis.

The other thing we do with these patients is we evaluate them for osteoporosis because osteoporosis and fractures are complications which can be associated with systemic mastocytosis.

There are forms of systemic mastocytosis which are more aggressive. There is a sub-type called aggressive mastocytosis and the other one is mast-cell leukemia. These sub-types of mastocytosis need to be treated more aggressively and the standard of care for at these disorders has been to use alpha-interferon, as well as other chemotherapeutic drugs.

There's a small proportion of patients in which we do not have to c-KIT mutation and within that small sub-population  there are patients who are responsive to a drug called imatinib and we have used this with success in a small proportion of patients.

Mayo participates in investigational trials with different agents for patients to have aggressive systemic mastocytosis, and we are involved in Mayo in providing a complete evaluation of patients and offering them both the standard of care or in patients which fail the standard of care we evaluate their eligibility for investigational treatment.

Thank you very much for your attention.